Developing practice recommendations for endovascular ... · Embolus Removal in Cerebral Ischemia...
Transcript of Developing practice recommendations for endovascular ... · Embolus Removal in Cerebral Ischemia...
Developing practice recommendations forendovascular revascularization for acuteischemic stroke
Marc A Lazzaro MDRoberta L Novakovic
MDAndrei V Alexandrov
MDZiad Darkhabani MDRandall C Edgell MDJoey English MDDonald Frei MDDara G Jamieson MDVallabh Janardhan MDNazli Janjua MDRashid M Janjua MDIrene Katzan MDPooja Khatri MDJawad F Kirmani MDDavid S Liebeskind
MDItalo Linfante MDThanh N Nguyen MDJeffrey L Saver MDLori Shutter MDAndrew Xavier MDDileep Yavagal MDOsama O Zaidat MD
ABSTRACT
Guidelines have been established for the management of acute ischemic stroke however spe-cific recommendations for endovascular revascularization therapy are lacking Burgeoning inves-tigation of endovascular revascularization therapies for acute ischemic stroke rapid devicedevelopment and a diverse training background of the providers performing the procedures un-derscore the need for practice recommendations This review provides a concise summary of theSociety of Vascular and Interventional Neurology endovascular acute ischemic stroke roundtablemeeting This document was developed to review current clinical efficacy of pharmacologic andmechanical revascularization therapy selection criteria periprocedure management and endo-vascular time metrics and to highlight current practice patterns It therefore provides an outlinefor the future development of multisociety guidelines and recommendations to improve patientselection procedural management and organizational strategies for revascularization therapiesin acute ischemic stroke Neurologyreg 201279 (Suppl 1)S243ndashS255
GLOSSARYACT activated clotting time AHA American Heart Association AIS acute ischemic stroke ASA American StrokeAssociation ASPECTS Alberta Stroke Program Early CT score CI confidence interval ECASS European CooperativeAcute Stroke Study III ED emergency department EMS emergency medical services ERT endovascular revascular-ization therapy FDA US Food and Drug Administration IA intra-arterial ICH intracranial hemorrhage IMS Interven-tional Management of Stroke J-MUSIC Japan Multicenter Stroke Investigatorsrsquo Collaboration MCA middle cerebralartery MELT MCA-Embolism Local fibrinolytic intervention Trial MERCI Mechanical Embolus Removal in CerebralIschemia MR CLEAN Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in theNetherlands MR RESCUE MR and Recanalization of Stroke Clots Using Embolectomy mRS modified Rankin ScaleNIHSS NIH Stroke Scale NINDS National Institute of Neurological Disorders and Stroke OR odds ratio PROACT Prolyse in Acute Cerebral Thromboembolism rtPA recombinant tissue plasminogen activator sICH symptomatic ICHSYNTHESIS EXP Intra-Arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke THERAPY Assess the Penum-bra System in the Treatment of Acute Stroke VBO vertebrobasilar occlusion
In an effort to improve outcome in patients with acute ischemic stroke (AIS) recent initiativeshave outlined the best medical management and developed protocols to facilitate timely iden-tification and administration of the US Food and Drug Administration (FDA)ndashapproved IVrecombinant tissue plasminogen activator (rtPA) to eligible patients12
Restoration of blood flow after AIS is associated with improved outcome and reducedmortality34 A meta-analysis including over 2000 patients in 53 studies confirmed a strongcorrelation between recanalization and good functional outcome at 3 months in comparisonwith nonrecanalization (odds ratio [OR] 443 95 confidence interval [CI] 332ndash591)4
Intra-arterial (IA) thrombolysis has not received FDA approval but randomized trials andseveral case series have led to endorsements by multiple associations for select patients5ndash9
Endovascular revascularization therapy (ERT) currently has a Class Ib recommendation for IAthrombolysis for select patients and a Level IIb recommendation for mechanical thrombus
From the Medical College of WisconsinFroedtert Hospital (MAL ZD OOZ) Milwaukee WI University of Texas Southwestern MedicalCenter at Dallas (RLN) Dallas University of Alabama (AVA) Birmingham St Louis University (RCE) St Louis MO University ofCalifornia San Francisco (JE) San Francisco Radiology Imaging Associates (DF) Denver CO Weill Cornell Medical College (DGJ) New YorkNY Texas Stroke Institute (VJ) Dallas Asia Pacific Comprehensive Stroke Institute (NJ) Pahoa HI Wake Forest Baptist Health (RMJ)Winston-Salem NC Cleveland Clinic Foundation (IK) Cleveland OH University of Cincinnati (PK LS) Cincinnati OH New JerseyNeuroscience Institute (JFK) JFK Medical Center Edison University of California Los Angeles (DSL JLS) Los Angeles Baptist MedicalCenter (IL) Miami FL Boston University Medical Center (TNJ) Boston MA Wayne State University (AX) Detroit MI and University ofMiami (DY) Miami FL
Go to Neurologyorg for full disclosures Disclosures deemed relevant by the authors if any are provided at the end of this article
Correspondence amp reprintrequests to Dr NovakovicRobinNovakovicUTSouthwesternedu
copy 2012 American Academy of Neurology S243
extraction in the American Heart Association(AHA) guidelines1ndash9 Two device familieshave FDA approval for ERT the Merci Re-triever (Concentric Medical Inc MountainView CA) and the Penumbra Aspiration Sys-tem (Penumbra Inc Alameda CA) andmultiple new devices are rapidly approachingFDA approval and market availability1011 Es-tablished guidelines and recommendationsare available for the early treatment of adultswith AIS1 and for the development of com-prehensive stroke centers7 and training stan-dards for endovascular ischemic stroketreatment9 However guidelines for ERT forAIS are lacking Ongoing clinical trials andthe brisk pace of emerging technologies havefostered enthusiasm for endovascular therapyfor AIS resulting in the need for developmentof practice recommendations
This outline was developed by a panel ofphysicians with a range of expertise in neuro-interventional procedures vascular neurol-ogy neurocritical care neurosurgery andneuroradiology In many instances definitiveclinical trialndashbased data are lacking and prac-tices are discussed on the basis of pathophysi-ologic rationale and expert opinion not onthe basis of randomized clinical trials
SAFETY AND EFFICACY OF ENDOVASCULARREVASCULARIZATION THERAPY FOR ACUTEISCHEMIC STROKE Endovascular treatment op-tions for intracerebral revascularization have evolvedconsiderably over the past decade Several trials eval-uating the various therapies are summarized in table1 The Prolyse in Acute Cerebral Thromboembolism(PROACT) and PROACT II studies evaluated theuse of IA thrombolysis with prourokinase in middlecerebral artery (MCA) occlusions56 The initial phase2 trial demonstrated higher recanalization rates withprourokinase5 The phase 3 trial PROACT II dem-onstrated the effectiveness of IA thrombolysis withprourokinase in patients with an MCA occlusiontreated within 6 hours from symptom onset6 A min-imum requirement NIH Stroke Scale (NIHSS) scoreof 4 except for isolated aphasia or hemianopia wasrequired for enrollment Patients treated with prou-rokinase had a higher rate of recanalization (66 vs18 p 0001) and were more likely to have agood outcome (modified Rankin Scale [mRS] scoreof 0ndash2 at 90 days 40 vs 25 p 004) despite ahigher rate of symptomatic intracranial hemor-rhage (sICH) (10 vs 2 p 006) The MCA-
Embolism Local fibrinolytic intervention Trial(MELT) was a similarly designed trial comparingurokinase to placebo in patients with MCA occlu-sions which was terminated early because of the ap-proval of the IV administration of rtPA in Japan12
Although the MELT findings are underpowered theresults are consistent with those of the PROACT tri-als suggesting higher recanalization rates (74) withIA thrombolysis12 A meta-analysis of these 3 trialsand 2 additional smaller trials combined 395 ran-domized patients and showed that IA thrombolysisincreased the odds of both nondisabled outcome(mRS score 0ndash1 OR 25 95 CI 133ndash314 p
0001) and nondependent outcome (mRS score 0ndash2OR 14 95 CI 131ndash351 p 0003)13 A case-control analysis from Japanrsquos Multicenter Stroke In-vestigatorsrsquo Collaboration (J-MUSIC) compared 91patients with an acute cardioembolic stroke treatedwith IA urokinase within 45 hours of symptom on-set to a matched control group that did not receiveIA therapy The analysis showed that a favorable out-come (mRS score of 0 ndash2) was more frequentlyobserved in the urokinase group (505 vs 341p 00124) and there was no difference in mortal-ity rate14 Although confirmatory trials required forFDA approval of IA therapy have not been per-formed these randomized trials and numerous caseseries support the use of IA thrombolysis in selectpatients who are ineligible for IV thrombolysis
Mechanical devices for ERT have evolved as ameans of achieving faster rates of recanalization inmedium- to large-vessel occlusions The MechanicalEmbolus Removal in Cerebral Ischemia (MERCI)and Multi-MERCI were prospective single-armmulticenter trials designed to test the efficacy andsafety of a corkscrew thrombectomy device in thetreatment of medium- to large-vessel occlusions (an-terior and posterior circulation) within 8 hours ofsymptom onset10 A combined analysis of the 2 stud-ies demonstrated a successful recanalization rate (de-fined as Thrombolysis in Myocardial Infarction 2 or3 score) of 646 with good clinical outcome (mRSscore of 0ndash2) in 324 despite an sICH rate of78 in the first study and 98 in the second15
The Penumbra Pivotal Stroke Trial provided registrydata on a novel aspiration-thrombectomy device thePenumbra system used within 8 hours for large-artery cerebrovascular occlusion11 A quarter of thepatients achieved an mRS score of less than or equalto 2 at 90 days Different techniques for measuringrecanalization preclude a direct comparison betweenthe rates achieved with MERCI and Penumbra butboth exceed the natural history rate16
Randomized trials are ongoing such as the LocalVersus Systemic Thrombolysis for Acute Ischemic
S244 Neurology 79 (Suppl 1) September 25 2012
Stroke (SYNTHESIS EXP) and the MulticenterRandomized Clinical trial of Endovascular treatmentfor Acute ischemic stroke in the Netherlands (MRCLEAN) comparing endovascular recanalization vsstandard medical treatment alone (including IV rtPAor supportive care alone)1718 The NIH-funded Me-chanical Retrieval and Recanalization of Stroke ClotsUsing Embolectomy (MR RESCUE) trial is compar-ing the effectiveness of endovascular therapy within 8hours of symptom onset and standard medical careto standard medical treatment alone19 Several trialsare testing bridging therapies combining early ad-ministration of IV rtPA with the endovascular ap-proach including the Interventional Management ofStroke III (IMS III) and Assess the Penumbra Systemin the Treatment of Acute Stroke (THERAPY) tri-als20 In the United States the ongoing IMS a ran-domized multicenter trial will enroll 900 subjectswith AIS within 3 hours of symptom onset to com-pare combined IV and IA rtPA to IV rtPA alone21
Alternative revascularization methods continue toevolve and have included acute intracranial stent im-plantation22 and temporary endovascular bypass andthrombectomy with a retrievable stent2324 Initialopen series reports with stent retrievers suggest po-tentially higher recanalization rates and shorter pro-cedure times
PATIENT SELECTION FOR ENDOVASCULARREVASCULARIZATION THERAPY IN ACUTEISCHEMIC STROKE Designing a decision algo-rithm for patient selection for ERT in AIS is hin-dered by variable enrollment criteria in the trialscited previously The presented outline for the devel-opment of a decision algorithm is based on findingsfrom available randomized controlled trials and ex-trapolated from criteria from recent and ongoingclinical trials (figure) This is an example of one pos-sible algorithm and further investigation is necessaryprior to clinical use
Outside of clinical trials IV therapy remains first-line treatment for eligible patients presenting withclinical symptoms of AIS Through a systematic re-view of the literature the American Stroke Associa-tion (ASA) guidelines outline the best medicalmanagement as well as protocols to facilitate timelyadministration of IV rtPA to patients eligible forthrombolysis1 For patients with moderate to severedeficits and minimal or no early ischemic changes onbrain imaging therapy triage is largely governed bytime from symptom onset There is strong evidencefrom multiple clinical trials to support the use of IVrtPA within 3 hours22526 Current FDA approvalexists for patients presenting up to 3 hours fromsymptom onset and a science advisory from theASAAHA has recommended expanding the time
Tab
le1
Dat
afr
omse
lect
edtr
ials
ofen
dov
ascu
lar
reva
scul
ariz
atio
nth
erap
yfo
rac
ute
isch
emic
stro
ke
PR
OA
CT
5P
RO
AC
TII
6E
MS
56IM
SI55
IMS
II40
ME
RC
I10M
ELT
12M
ulti
-ME
RC
I29P
enum
bra
PS
T11
Sol
itai
reA
Bp
ilot
stud
y24
Yea
r1
99
81
99
91
99
92
00
42
00
72
00
52
00
72
00
82
00
92
01
0
Inte
rven
tion
Pro
UK
IV
hepa
rin
vsIV
hepa
rin
pl
aceb
o(IA
salin
ein
fusi
on)
Pro
UK
IV
hepa
rin
vsIV
hepa
rin
IVtP
Aor
IVpl
aceb
ofo
llow
edby
IAtP
AIV
IA
tPA
IV
hepa
rin
IV
IAtP
A
IVhe
pari
nw
ith
orw
itho
utE
kos
Mer
ciX
6R
etri
ever
IV
hepa
rin
UK
vsco
ntro
lL5
Ret
riev
er
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enum
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aspi
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stem
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rin
Sol
itai
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echa
nica
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rom
bect
omy
Enr
ollm
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tim
eh
6
6
3
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8
Des
ign
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Sin
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ety
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Sin
gle
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ospe
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ingl
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asib
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No
ofp
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40
18
03
58
08
11
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11
41
64
12
52
0
Rec
anal
izat
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rate
of
trea
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tco
ntro
l5
81
46
61
85
51
05
66
0(T
ICI
TIM
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)4
67
45
76
9w
ith
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29
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Occ
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onsi
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Mea
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71
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71
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81
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91
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9
SIC
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15
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97
89
29
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12
10
mR
S0
ndash2at
90
day
s
oftr
eatm
ent
cont
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30
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(mR
S0
ndash1at
90
days
)4
02
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62
84
91
36
25
45
Abb
revi
atio
nsA
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an
teri
orce
rebr
alar
tery
adj
tx
adju
ncti
veth
erap
yA
ICA
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Cer
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hem
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kin
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Neurology 79 (Suppl 1) September 25 2012 S245
window to 45 hours in a subgroup of patients onthe basis of results of the European CooperativeAcute Stroke Study III (ECASS III)2527
Patients presenting after 45 hours are not eligiblefor systemic thrombolysis however data exist ascited previously for the consideration of IA fibrino-lytic administration up to 6 hours from symptomonset in patients with a large- to medium-vessel oc-clusion61228 For patients in whom endovasculartherapy can be initiated within 8 hours from symp-tom onset 2 mechanical revascularization devicefamilies have demonstrated safe and feasible rates ofrecanalization in single-arm prospective trials101129
The optimal device for mechanical revascularizationhas not been identified and the rapid growth of de-vice technology will likely continue to challenge rig-orous clinical evaluation
Vertebrobasilar artery occlusion (VBO) has an in-variably poor outcome if recanalization is notachieved early The recent literature shows that mor-tality with acute VBO treated with nonthrombolyticdrugs is 80 to 90 although lower rates of 42 to60 can be achieved with IA therapy283031 Successof recanalization and neurologic status before treat-ment are independent predictors of a favorable out-come after IA therapy3031 Multiple studies failed toestablish a time window that would definitively ex-
clude patients from IA therapy30 One study found asignificantly better clinical outcome in patients withacute VBO treated within 6 hours after symptomonset than in patients treated after 6 hours (favorableoutcome of 36 vs 7 mortality of 52 vs 70p 0005)28 Other studies demonstrated trends to-ward better outcome with shorter duration of symp-toms and no significant association between time totreatment and clinical outcome3031 When patients arein a coma or have had prolonged symptoms additionalimaging such as MRI with diffusion and perfusion orCT perfusion might help in identifying those who arelikely to benefit from intervention However the cur-rent application of CT perfusion results to the posteriorcirculation may be limited
The trials that shape the current decision patternshave been largely based on time from symptom on-set Data are lacking on the efficacy of ERT beyond12 hours from symptom onset in patients with poste-rior circulation occlusion and beyond 8 hours in an-terior circulation occlusion1011293132 Given the poornatural history of VBO revascularization has beenconsidered beyond 12 hours from symptom onsetEnthusiasm continues for a perfusion imagingndashbaseddecision algorithm although rigorous data to sup-port this approach are lacking33 Further study ofperfusion imaging may assist with selection of pa-
Figure Possible decision algorithm for revascularization therapies in acute ischemic stroke
S246 Neurology 79 (Suppl 1) September 25 2012
tients who would benefit from revascularization be-yond 8 hours34
At the very least noncontrast head CT ordiffusion- and susceptibility-weighted MRI are re-quired to exclude hemorrhage and identify early isch-
emic changes that could pose increased hemorrhagicrisk following revascularization Larger regions ofwell-defined hypoattenuation (CT) or hyperintensity(MRI) indicating infarcted tissue may carry a consid-erably higher risk of hemorrhage following revascu-larization Careful consideration may be needed forpatients with CT hypodensity or MRI hyperintensityin greater than 13 of the MCA territory or withprominent sulcal effacement35 Alternative standard-ized scoring systems may include the Alberta StrokeProgram Early CT Score (ASPECTS)36
Future studies may show that for patients whoreceive IV rtPA and have a clinical presentation sug-gestive of a large-vessel occlusion early considerationof ERT may be important The limited efficacy of IVrtPA in large vessel occlusions is demonstrated byrecanalization rates as low as 30 in the proximalMCA and 6 in the terminal internal carotid artery(ICA)37 Urgent noninvasive vascular imaging canidentify patients with a large-vessel occlusion Theinterval from a decision to pursue IA intervention toreaching the clot can be long with time required toobtain consent transport and prepare the patient andnegotiate tortuous anatomy Accordingly an efficientstrategy may be to activate the neurointerventional teamwhen a large-vessel occlusion is suspected without delayin IV rtPA initiation If dramatic clinical improvementoccurs patients can be rerouted to repeat noninvasivevessel assessment One retrospective study has shownthat in those patients with a contraindication to IV rtPAor whose IV therapy fails the use of ERT within thefirst 3 hours after stroke symptom onset has a low sICHrate of 5338
Patients with fluctuating deficits or continuedmild deficits (NIHSS score 4) following rapid im-provement from presentation carry a risk of harbor-ing a large-vessel occlusion with tenuous collateralsupply Failure of collateral supply could lead toacute deterioration therefore emergent noninvasiveangiography to identify vessel occlusions amenable toERT may be considered To date no randomizedclinical trial has compared the natural history ofmedical treatment alone to early recanalization withERT in this subset of patients
For patients in whom ERT is considered inclu-sion and exclusion criteria will be needed Based onthe existing clinical trials and guidelines a frame-work for the future development of criteria can beoutlined (table 2)
SELECTION OF ENDOVASCULAR REVASCU-LARIZATION THERAPY TECHNIQUE The heter-ogeneity of AIS characteristics including thrombuscomposition occlusion location thrombus volumeburden and collateral perfusion may demand tai-
Table 2 Possible selection criteria for acute ischemic stroke endovascularrevascularization therapy
Inclusion criteria for ERT
Neurologic deficit attributable to a medium- to large-vessel occlusion
IA chemical thrombolysis can be initiated within 6 h of symptom onset
Mechanical thrombectomy treatment can be initiated within window of 8 h from time of onsetfor anterior circulation strokes
ERT can be initiated within window of 12 h from time of onset for posterior circulationstrokes
Treatment beyond 6ndash8 h may be guided by advanced imaging results (DWI MRI PWI CTP)when available
Potentially disabling neurologic deficit
Persistent or worsening neurological deficits following IV rtPA administration
Exclusion criteria for ERT
Arterial stenosis precluding safe access
Suspicion of aortic dissection
Uncontrolled hypertension defined as systolic blood pressure 185 mm Hg or diastolicblood pressure 110 mm Hg that cannot be reasonably treated with antihypertensivemedication
Platelet count 30000
Use of warfarin anticoagulation with INR 30
Known bleeding diathesis
Deficits attributable to glucose 50 mgdL
Seizure at onset if residual deficits are due to a postictal state rather than ischemia
Imaging findings
Significant mass effect with midline shift
Intracranial hemorrhage (ICH SAH subdural or epidural hematoma)
Subacute infarct on head CTMRI that occupies 13 of the MCA territory or 100 cc ofbrain tissue
CNS lesion with high likelihood of hemorrhage should be excluded from IA pharmacologicthrombolysis (brain tumor abscess vascular malformation aneurysm contusion)
May consider IA thrombolysis in patients with small unruptured aneurysms or benigntumors with low vascularity
Relative contraindications for ERT therapy
Intracranial or spinal surgery head trauma or stroke in separate vascular territory within 3months
History of ICH
Terminal illness with short life expectancy or severe comorbid illness
Pregnancy
Risk vs benefit of clinical symptoms and ability to shield patient must be considered
Known subacute bacterial endocarditis with or without mycotic aneurysm and stroke
Special consideration may be needed for patients on dabigatran
Relative contraindications for adjunctive ERT following IV rtPA
Glucose 400 mgdL based on increased ICH risk
Ongoing hemodialysis or peritoneal dialysis due to possibly increased ICH risk
Abbreviations CTP CT perfusion DWI MRI diffusion-weighted MRI ERT endovascu-lar revascularization therapy IA intra-arterial ICH intracerebral hemorrhage INR
international normalized ratio MCA middle cerebral artery NIHSS NIH Stroke ScalertPA recombinant tissue plasminogen activator SAH subarachnoid hemorrhage
Neurology 79 (Suppl 1) September 25 2012 S247
lored interventions For example greater efficacy andsafety may be demonstrated in distal vessel revascu-larization by use of IA fibrinolytic therapy vs a me-chanical device that may be more difficult to deliverAlternatively in large proximal vessel occlusionsgreater benefit may be achieved with mechanicalthrombectomy Furthermore carotid occlusion atthe origin of the ICA may be better treated with bal-loon angioplasty and stent implantation
Pharmacologic thrombolysis Local IA thrombolysisefficacy was demonstrated in PROACT II6 This ledto an AHA Class I level of evidence B recommenda-tion that IA thrombolysis is an option for the treat-ment of selected patients who have AIS under 6hours duration due to occlusions of the MCA andwho are not otherwise candidates for IV rtPA1 Al-though variability in study designs prohibits direct com-parison of the data theoretically there may be a higherrisk of intracerebral hemorrhage (ICH) with chemicalIA thrombolysis than with mechanical revasculariza-tion However increased ICH was not substantiated ina multicenter study39
Microcatheter position during thrombolytic infu-sion may also theoretically affect recanalization ratesThe microcatheter position varies among the studiesin some instances it is placed distal to the thrombuswithin the thrombus or proximal to the thrombusSome operators will use multiple locations to infusertPA throughout the thrombus The maximum safedose for IA rtPA is not known however if we extrap-olate from large clinical trial experience then a max-
imum dose of 22 mg as in the IMS trials may be areasonable initial limit2140
Bridging therapies Bridging therapy trials evaluatingthe combined approach have shown better recanali-zation rates for medium- to large-vessel occlusionsHowever they have shown only trends toward betteroutcomes in comparison with the IV rtPAndashtreatedsubjects in the National Institute of NeurologicalDisorders and Stroke (NINDS) rtPA Stroke Study ora database registry4041 Potential benefit of bridgingtherapy increases when the target population is lim-ited to IV rtPA nonresponders (40 IV-IA patientsreached functional independence at 3 months vs149 of recipients of only IV rtPA among the non-responders [p 0012]) This benefit came at thecost of a higher morbidity associated with the bridg-ing therapy (OR 214 95 CI 058 ndash783 forsICH)42 The early Emergency Management ofStroke Bridging TrialIMS trials used a protocol of06 mgkg IV rtPA with up to an additional maxi-mum of 22 mg IA rtPA which in most patients al-lowed for the total dose to remain below the NINDSmaximum amount of 90 mg (table 3) Howevernewer bridging studies and the amended IMS III areusing full-dose IV rtPA in the combined IV-IA treat-ment arm2021
Mechanical revascularization Mechanical techniquesfor ERT including thrombectomy clot retrievaland thromboaspiration have shown comparable orslightly higher recanalization rates than IA thrombol-
Table 3 Intra-arterial thrombolytic dosing and methods from selected trials
Trial PROACT5 PROACT II6 MELT12 IMS I55 IMS II40 IMS III21
Agent ProUK ProUK UK rtPA rtPA rtPA
Max dose Two-tier dose6 mg and 12 mg
9 mg 600000 IU IV rtPA 06 mgkg 60mg maxIA rtPA 22 mg
IV rtPA 06 mgkg60 mg maxIA rtPA 22 mg
IV rtPA 06 mgkg 60 mgmaxpossibly IA rtPA 22 mg
Median dose mg 6 and 12 9 mdash mdash 12 mdash
Infusion duration h 2 2 2 2 2 2
Infusion location At proximal one-thirdof thrombus
At proximal one-thirdof thrombus
Distal tothrombus
2 mg distal to thrombusthen 2 mg intothrombus then infusion
At site of thrombuswith or withoutEkos ultrasoundcatheter
1 mg distal and 1 mgproximal then 20 mg overmaximum of 2 h
Mechanical disruption Prohibited Prohibited Only withguidewire
Only with guidewire ormicrocatheter
Only with guidewireor microcatheter
Merci device Ekos orpenumbra device with IArtPA infusion ormicrocatheter IA rtPAinfusion
Intraproceduralsystemic thrombo-prophylaxis
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 5000IU bolus
Heparin 2000 IU bolusand 450 IUh infusion
Heparin 2000 IUbolus and 450 IUhinfusion
Heparin 2000 IU bolus and450 IUh infusion until theend of the procedure
Adjunctiveantithrombotic agents
Prohibited in first24 h
Prohibited in first24 h
Prohibited infirst 24 h
Prohibited in first 24 h Prohibited in first24 h
Prohibited in first 24 h
Abbreviations IA intra-arterial IMS Interventional Management of Stroke trial IU international units MELT Middle cerebral artery Embolism LocalFibrinolytic intervention Trial PROACT Prolyse in Acute Cerebral Thromboembolism trial rtPA IV recombinant tissue plasminogen activator UK
urokinase
S248 Neurology 79 (Suppl 1) September 25 2012
ysis alone (table 1) Newer devices such as the Soli-taire FR retrievable stent (eV3 Irvine CA) haveshown even higher recanalization rates (84ndash90)2324 In appropriately selected patients me-chanical revascularization may theoretically have alower risk of hemorrhagic complications given theabsence or reduced need for a thrombolytic agent Inpatients who are considered for ERT after full-doseIV rtPA a mechanical approach might be favorableLimitations of mechanical revascularization includedevice failure deliverability to distal locations andembolization
Multimodal revascularization Given the heterogene-ity of vessel occlusion etiology in AIS a combinationof multiple techniques may afford the highest successfor revascularization Small series suggest that multi-modal therapies including IA thrombolysis and stentimplantation lead to higher recanalization rates39
Future studies may find mechanical thrombectomyto be more successful in proximal large-vessel occlu-sions whereas local IA thrombolysis would be pre-ferred in distal small-vessel occlusions Also stentimplantation may be most effective for in situ intra-cranial atherosclerosis with supervening thrombosisbut retrieval and aspiration techniques may be moreeffective for thromboemboli occlusive in relativelynormal recipient arteries4
Posterior circulation modality selection The besttreatment modality for patients with VBO remainspoorly defined A large prospective observationalregistry and a separate systematic analysis of pub-lished case series analyzed a total of 1012 patientsboth studies did not support unequivocal superiorityof IA therapy vs IV thrombolysis3243 However theheterogeneity of the data between the patients withinthe groups analyzed limits interpretation of the clini-cal conclusions Early recanalization is an importantprognostic factor for good clinical outcome as suchhigher and safer rates of recanalization are beingachieved with newer therapeutic strategies utilizingmechanical embolectomy devices retrievable stentsangioplasty with or without stenting use of glyco-protein IIbIIIa inhibitors and combinationsthereof2328304445
TARGET TIME INTERVALS AND TRIAGE ANDTRANSFER STRATEGIES Time to revasculariza-tion is an independent predictor of good outcome inpatients with AIS4647 Randomized trials of IV rtPAhave demonstrated the greatest benefit in subjectstreated within 90 minutes of symptom onset225 Re-canalization rates with ERT are higher than with IVrtPA alone although the delay to treatment may at-tenuate the benefit This illustrates the importance ofestablishing benchmark door-to-revascularization
Tab
le4
Tre
atm
ent
tim
esin
sele
cted
stud
ies
inm
inut
es
Tri
alP
RO
AC
T5
PR
OA
CT
II6
IMS
I55IM
SII
I21E
MS
56M
ELT
12R
EC
AN
ALI
SE
41P
enum
bra
PS
T11
Mul
tiM
ER
CI29
M
ER
CI10
Wol
feet
al50
Doc
rocq
etal
54C
osta
lat
etal
43M
iley
etal
53S
uare
zet
al51
Mat
tle
etal
49F
lahe
rty
etal
52
No
ofsu
bje
cts
40
12
16
25
00
35
56
50
12
53
05
96
13
50
91
54
57
44
Tre
atm
ent
IApr
oUK
orpl
aceb
oIA
proU
KIV
-IA
rtP
AIV
aor
IV
IAb
IV-I
Aa
orIA
rtP
Ab
IAU
KIV
-IA
orIV
-IA
Trt
PA
IAT
IV
rtP
AIA
TIV
-IA
aor
IArt
PA
bIA
UK
IV-R
Sor
RS
alon
eIV
-IA
Tor
IAT
IAU
KIA
TU
KIV
IA
rtP
A
Tim
e-to
-doo
r1
14
Tim
e-to
-CT
MR
Isc
anm
ean
(med
ian)
Ons
et1
05
Ons
et1
62
(14
5)
Doo
r5
9(3
4)
Imag
ing
-to-
GP
16
1(1
53
)8
1(6
5)
CT
scan
-to-
mic
roca
thet
er1
74
Tim
e-to
-ER
Tin
itia
tion
oran
gio
gra
mor
GP
SO
(33
0)
SO
(31
8)
SO
21
7(2
12
)
SO
12
37
25
52
IV-b
olus
toG
P8
74
SO
a(1
98
)Oslash
b(1
80
)Oslash
SO
22
7S
O1
32
SO
25
8pound
SO
(25
8)
SO
a1
51
b2
61
SO
32
4(3
30
)S
O3
21
Doo
r(1
30
)S
O2
44
SO
(22
6)
GP
-to-
max
TIM
IT
ICI
54
(48
)
SO
-to-
max
TIM
IT
ICI
a(3
78
)b(
34
2)
(22
0)
37
7(3
27
)
Abb
revi
atio
nsE
MS
E
mer
genc
yM
anag
emen
tof
Str
oke
ER
T
endo
vasc
ular
reva
scul
ariz
atio
ntr
eatm
ent
GP
gr
oin
punc
ture
IA
in
tra-
arte
rial
IA
T
intr
a-ar
teri
alth
erap
y(in
clud
esth
rom
boly
sis
and
mec
hani
cal
tech
niqu
es)
IMS
In
terv
enti
onal
Man
agem
ento
fStr
oke
tria
lM
ELT
M
iddl
ece
rebr
alar
tery
Em
bolis
mLo
calF
ibri
noly
tic
inte
rven
tion
Tria
lM
ER
CI
Mec
hani
calE
mbo
lus
Rem
oval
inC
ereb
ralI
sche
mia
PR
OA
CT
P
roly
sein
Acu
teC
ereb
ralT
hrom
boem
bolis
mtr
ial
PS
T
Piv
otal
Str
oke
Tria
lR
EC
AN
ALI
SE
R
Eca
nalis
atio
nus
ing
Com
bine
din
trav
enou
sA
ltep
lase
and
Neu
roin
terv
enti
onal
Alg
orit
hmfo
racu
teIs
chem
icS
trok
ER
S
retr
ieva
ble
sten
trt
PA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
O
sym
ptom
onse
tTI
CI
thro
mbo
lysi
sin
cere
bral
infa
rcti
onT
IMI
thro
mbo
lysi
sin
myo
card
iali
nfar
ctio
nU
K
urok
inas
e
Neurology 79 (Suppl 1) September 25 2012 S249
times The Brain Attack Coalition has recommendedthat IV rtPA be administered within 60 minutesfrom arrival to the emergency department (ED) foreligible patients48 The established time intervals tar-get a multidisciplinary goal Each component of theprocessmdashED physicians ancillary staff laboratoryand radiology services neurology team and radiol-ogy staffmdashis essential for the time goal As suchERT time intervals should integrate into the existingmodel beginning with patient arrival to the EDSeparate time intervals can be established for patientstransferred from another institution and patientswho receive adjunctive ERT following IV rtPA ther-apy Because vascular anatomy can add unpredictabledelays in procedural times the endpoint should re-flect the last modifiable variable Therefore ERTtime intervals should reflect door-to-puncture (morepredictable) puncture-to-clot and clot-to-closegoals A clot-to-close time of 120 minutes as de-scribed in IMS III may be warranted to establishprocedural termination times More variables in-cluding anatomy evidence of persistent penumbraand ERT method may be used in the future to mod-ify time benchmarks
In the limited case series discussing time intervalsto ERT there is variability in which interval is uti-lized (table 4)56111215414349 ndash56 Randomized trialsshow feasibility in achieving time intervals of approx-imately 4 to 5 hours from stroke onset to IA rtPAadministration655 In PROACT II median timefrom stroke onset to randomization and IA rtPA ad-ministration was 282 minutes whereas the IMSstudy demonstrated an interval of 231 minutes fromstroke onset to IA rtPA administration655 Timefrom CT scan to microcatheter placement in thecerebrovasculature had a mean time of 174 60minutes in 91 patients undergoing ERT for AISdemonstrating wide variability and a need for timestandards53 Transferred patients whose laboratorytests and CT scan have already been completed maystill have a door-to-puncture time of up to 60 min-utes57 Further study is needed to identify barriers torapid access to endovascular therapy
Currently the American College of Cardiologyand the AHA recommend that door-to-balloon timein ST segment elevation myocardial infarctionshould be within 90 minutes A similar future pro-posal could be made for ERT in AIS with a goaldoor-to-puncture time of 90 minutes (table 5) Thiswould include activation of the stroke team technol-ogists and nurses Adjunctive time benchmarks canbe developed including puncture-to-clot and clot-to-close goals This target is more difficult to achievefor cerebral than cardiac revascularization as strokepatients require more time-consuming neurologic
Tab
le5
Ben
chm
ark
tim
esfo
rre
vasc
ular
izat
ion
ther
apie
san
dp
ossi
ble
inte
rval
sfo
rE
RT
Am
eric
anC
olle
geof
Car
diol
ogy6
7A
SA
AH
AA
ISG
uide
lines
forI
Vrt
-PA
68
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rE
RT
pres
enti
ngto
ED
ldquoP
rim
ary
ER
TTi
merdquo
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rRes
cue
ER
Tfo
llow
ing
IVfa
ilure
ldquoIV
-Fai
lure
toR
escu
eE
RTrdquo
Pro
pose
dgo
als
forA
ISpa
tien
tstr
ansf
erre
dfr
omou
tsid
eho
spit
alfo
rER
TldquoD
rip-
and-
Shi
pto
ER
Trdquo
Doo
r-to
-bal
loon
tim
e9
0m
inD
oor-
to-n
eedl
eti
me
60
min
Doo
r-to
-gro
inpu
nctu
reti
me
90
min
Nee
dle
-to-
gro
inp
unct
ure
tim
e6
0m
inD
oora -t
o-G
roin
Pun
ctur
eti
me
60
min
ST
EM
Icon
firm
ed
card
iolo
gis
tno
tifi
ed
10
min
Doo
rto
ED
10
min
Doo
rto
ED
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
0m
in)
ER
Tte
amis
noti
fied
asso
onas
larg
eto
med
ium
vess
eloc
clus
ion
issu
spec
ted
(ie
N
IHS
Sh
yper
dens
eM
CA
onC
T)in
elig
ible
pati
ents
10
min
afte
rth
eel
igib
ility
CT
scan
and
befo
reIV
bolu
s
Tran
sfer
from
outs
ide
hosp
ital
init
iate
dan
gio
suit
eac
tiva
ted
team
acti
vate
d
Pri
orto
arri
val
ED
stab
ilize
sp
atie
nta
ctiv
ates
cath
lab
30
min
Str
oke
team
acti
vati
on1
5m
inS
trok
ean
dE
RT
team
sac
tiva
tion
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
5m
in)
Rec
eivi
ngho
spit
alar
riva
lR
apid
hist
ory
and
exam
rev
iew
ofre
ferr
ing
hosp
ital
film
s
15
min
Cat
hla
ban
din
terv
enti
onal
ist
read
y
60
min
CT
scan
init
iate
d2
5m
inC
Tsc
anin
itia
ted
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(2
5m
in)
Ang
iosu
ite
acti
vate
dte
amon
stan
dby
cons
ider
noni
nvas
ive
vasc
ular
imag
ing
25
min
afte
rth
eel
igib
ility
CT
scan
and
afte
rIV
bolu
sin
itia
tion
Anc
illar
ybr
ain
imag
ing
(ie
CT
perf
usio
n)3
5m
in
Fin
alch
eck
and
wri
tten
cons
ent
70
min
CT
scan
inte
rpre
ted
elig
ibili
tyas
sess
ed4
5m
inC
Tsc
anin
terp
rete
del
igib
ility
asse
ssed
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(4
5m
in)
Rep
eat
NIH
SS
obt
ain
wri
tten
cons
ent
repe
atC
Tif
clin
ical
wor
seni
ng
45
min
afte
rth
eC
Tsc
anan
d3
0m
inaf
ter
the
IVrt
PA
bolu
s
Fin
alch
eck
wri
tten
cons
ent
pati
ent
prep
ped
45
min
Cat
hete
riza
tion
and
PC
Indashb
allo
onin
flat
ion
90
min
IVrt
PA
infu
sion
60
min
Gro
inpu
nctu
re9
0m
inG
roin
punc
ture
60
min
bG
roin
punc
ture
60
min
Abb
revi
atio
nsA
HA
A
mer
ican
Hea
rtA
ssoc
iati
onA
IS
acut
eis
chem
icst
roke
ang
io
angi
ogra
mA
SA
A
mer
ican
Str
oke
Ass
ocia
tion
ED
em
erge
ncy
depa
rtm
ent
ER
T
endo
vasc
ular
reva
scul
ariz
atio
nth
erap
yIA
intr
a-ar
teri
alM
CA
m
iddl
ece
rebr
alar
tery
NIH
SS
N
IHS
trok
eS
cale
PC
Ipe
rcut
aneo
usco
rona
ryin
terv
enti
onr
tPA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
TEM
IS
Tse
gmen
tele
vati
onm
yoca
rdia
linf
arct
ion
aF
rom
tim
eof
arri
valt
oac
cept
ing
hosp
ital
door
b
Tim
ew
illne
edto
bead
just
edto
allo
wfo
rad
diti
onal
imag
ing
ifcl
inic
alex
amin
atio
nw
orse
nsor
sym
ptom
ssu
gges
the
mor
rhag
ictr
ansf
orm
atio
n
S250 Neurology 79 (Suppl 1) September 25 2012
evaluation and brain imaging before proceeding tothe angiography laboratory
Achieving a 90-minute door-to-puncture timewould likely require the neurointerventionalist toplay an integral part in the stroke team because thedecisions on treatment strategy may evolve as the pa-tient proceeds through the AIS protocol and IV rtPAevaluation pathway The ERT protocol should inte-grate into the IV rtPA pathway For interhospitaltransfers the completed imaging and laboratorystudies as well as additional lead time may reduce thetarget time interval to 60 minutes for door-to-puncture However significant delay in hospitaltransfer may warrant repeat neuroimaging when thepatient arrives at the recipient institution Bench-mark times will need to be established for IV nonre-sponders with special consideration for additionaldelay when clinical deterioration following IV rtPArequires a repeat brain imaging prior to ERT
Triage and transfer strategies The considerable de-cline in efficacy of revascularization therapies ataround 6 to 8 hours from symptom onset demandswell-organized triage and transfer strategies46 Emer-gency department reorganization has been an area offocus to improve early identification of stroke pa-tients Tracking door-to-thrombolysis times posi-tioning a CTMRI scanner within the departmentand having emergency medical services (EMS) send aprehospital notification are steps that have improvedthrombolysis access58 However given the limitedavailability of Comprehensive Stroke Center infra-structure few centers in a given geographic regionwill have capabilities for providing comprehensivestroke care and 247 ERT This will lead to a highproportion of patients eligible for ERT arriving byinterhospital transfer Transfer delay has been shownto be a major factor limiting the use of ERT in strokepatients accounting for an estimated odds of treat-ment decrease by 25 for every minute of transfertime59 To avoid transfer delay regional protocols fortriage of AIS patients by EMS personnel to desig-nated stroke centers has become a focus of prehospi-tal stroke triage policy60
Alternative strategies include initiation of IVthrombolytic in a referring hospital prior to transferldquodrip-and-shiprdquo followed by further management atthe accepting hospital which may include ERT Adescribed model of ldquodrip ship and retrieverdquo usedfull-dose IV rtPA (09 mgkg) followed by ERT withmechanical thrombectomy and thrombo-aspirationsuggesting feasibility in basilar artery occlusion61
Different models may evolve where the patient re-ceives ERT in an outside hospital and is transferredfor further care at a comprehensive stroke centerwhere neurosurgery neurocritical care and vascular
neurology expertise are available known as ldquoretrieve-and-shiprdquo Pay-for-performance measures similar tothose for acute myocardial infarction could help fa-cilitate transfer of appropriate patients from primaryto comprehensive stroke centers (the hub-and-spokemodel)
GENERAL PREPROCEDURAL AND INTRAPROCE-DURAL MANAGEMENT Anesthesia and monitoringThe type of anesthesia for ERT has been a topic ofcontroversy with recent reports suggesting worseoutcome with use of general endotracheal anesthesiapossibly due to treatment delays and complicationsfrom intubation6263 Alternatively conscious seda-tion may pose a different set of risks related to patientcooperation especially in those with severe aphasiaor neglect which may negatively influence time torevascularization and procedural success Further-more ancillary monitoring requiring invasive arterialaccess for blood pressure monitoring and central IVaccess may also be of limited value and add delay toinitiation of therapy Further study is needed to eval-uate sedation methods for ERT Sedation methodsmay currently vary among centers
Thromboprophylaxis with systemic anticoagulationArterial catheterization carries a risk of thromboem-bolism often requiring systemic anticoagulationRandomized clinical trials of ERT report variableprotocols for thromboprophylaxis including bolusIV heparin infusion of 2000 to 5000 units atprocedure onset followed by continuous infusionsof approximately 500 units of IV heparin per hourfor the procedure duration621 Alternatively acti-vated clotting time (ACT) values can be obtainedwith heparin boluses to maintain an ACT at atherapeutic goal Limited data exist on the safetyof heparin anticoagulation during ERT proce-dures A subgroup analysis of the MERCI trialshowed no association with hemorrhage or 90-daymortality and heparin use64 A reasonable ACTrange may be 250 to 300 seconds during ERT
Renal prophylaxis Patients with AIS may also havechronic renal impairment which may worsen withcontrast administered during angiography Inter-ventions designed to prevent contrast-induced ne-phropathy have not been rigorously studiedReasonable prophylaxis strategies include hydra-tion with isotonic saline Recent data have notprovided strong support for the administration ofN-acetylcysteine65 The use of sodium bicarbonateinfusion may be reasonable for patients with renalinsufficiency but it can be limited by the largevolume and time to acquire the solution from thepharmacy Periprocedural renal prophylaxis for
Neurology 79 (Suppl 1) September 25 2012 S251
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
httpnneurologyorgcontent7913_Supplement_1S243fullincluding high resolution figures can be found at
References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
Citations
ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
ehttpnneurologyorgcgicollectionall_cerebrovascular_disease_strokAll Cerebrovascular diseaseStrokefollowing collection(s) This article along with others on similar topics appears in the
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httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
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rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2012 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
extraction in the American Heart Association(AHA) guidelines1ndash9 Two device familieshave FDA approval for ERT the Merci Re-triever (Concentric Medical Inc MountainView CA) and the Penumbra Aspiration Sys-tem (Penumbra Inc Alameda CA) andmultiple new devices are rapidly approachingFDA approval and market availability1011 Es-tablished guidelines and recommendationsare available for the early treatment of adultswith AIS1 and for the development of com-prehensive stroke centers7 and training stan-dards for endovascular ischemic stroketreatment9 However guidelines for ERT forAIS are lacking Ongoing clinical trials andthe brisk pace of emerging technologies havefostered enthusiasm for endovascular therapyfor AIS resulting in the need for developmentof practice recommendations
This outline was developed by a panel ofphysicians with a range of expertise in neuro-interventional procedures vascular neurol-ogy neurocritical care neurosurgery andneuroradiology In many instances definitiveclinical trialndashbased data are lacking and prac-tices are discussed on the basis of pathophysi-ologic rationale and expert opinion not onthe basis of randomized clinical trials
SAFETY AND EFFICACY OF ENDOVASCULARREVASCULARIZATION THERAPY FOR ACUTEISCHEMIC STROKE Endovascular treatment op-tions for intracerebral revascularization have evolvedconsiderably over the past decade Several trials eval-uating the various therapies are summarized in table1 The Prolyse in Acute Cerebral Thromboembolism(PROACT) and PROACT II studies evaluated theuse of IA thrombolysis with prourokinase in middlecerebral artery (MCA) occlusions56 The initial phase2 trial demonstrated higher recanalization rates withprourokinase5 The phase 3 trial PROACT II dem-onstrated the effectiveness of IA thrombolysis withprourokinase in patients with an MCA occlusiontreated within 6 hours from symptom onset6 A min-imum requirement NIH Stroke Scale (NIHSS) scoreof 4 except for isolated aphasia or hemianopia wasrequired for enrollment Patients treated with prou-rokinase had a higher rate of recanalization (66 vs18 p 0001) and were more likely to have agood outcome (modified Rankin Scale [mRS] scoreof 0ndash2 at 90 days 40 vs 25 p 004) despite ahigher rate of symptomatic intracranial hemor-rhage (sICH) (10 vs 2 p 006) The MCA-
Embolism Local fibrinolytic intervention Trial(MELT) was a similarly designed trial comparingurokinase to placebo in patients with MCA occlu-sions which was terminated early because of the ap-proval of the IV administration of rtPA in Japan12
Although the MELT findings are underpowered theresults are consistent with those of the PROACT tri-als suggesting higher recanalization rates (74) withIA thrombolysis12 A meta-analysis of these 3 trialsand 2 additional smaller trials combined 395 ran-domized patients and showed that IA thrombolysisincreased the odds of both nondisabled outcome(mRS score 0ndash1 OR 25 95 CI 133ndash314 p
0001) and nondependent outcome (mRS score 0ndash2OR 14 95 CI 131ndash351 p 0003)13 A case-control analysis from Japanrsquos Multicenter Stroke In-vestigatorsrsquo Collaboration (J-MUSIC) compared 91patients with an acute cardioembolic stroke treatedwith IA urokinase within 45 hours of symptom on-set to a matched control group that did not receiveIA therapy The analysis showed that a favorable out-come (mRS score of 0 ndash2) was more frequentlyobserved in the urokinase group (505 vs 341p 00124) and there was no difference in mortal-ity rate14 Although confirmatory trials required forFDA approval of IA therapy have not been per-formed these randomized trials and numerous caseseries support the use of IA thrombolysis in selectpatients who are ineligible for IV thrombolysis
Mechanical devices for ERT have evolved as ameans of achieving faster rates of recanalization inmedium- to large-vessel occlusions The MechanicalEmbolus Removal in Cerebral Ischemia (MERCI)and Multi-MERCI were prospective single-armmulticenter trials designed to test the efficacy andsafety of a corkscrew thrombectomy device in thetreatment of medium- to large-vessel occlusions (an-terior and posterior circulation) within 8 hours ofsymptom onset10 A combined analysis of the 2 stud-ies demonstrated a successful recanalization rate (de-fined as Thrombolysis in Myocardial Infarction 2 or3 score) of 646 with good clinical outcome (mRSscore of 0ndash2) in 324 despite an sICH rate of78 in the first study and 98 in the second15
The Penumbra Pivotal Stroke Trial provided registrydata on a novel aspiration-thrombectomy device thePenumbra system used within 8 hours for large-artery cerebrovascular occlusion11 A quarter of thepatients achieved an mRS score of less than or equalto 2 at 90 days Different techniques for measuringrecanalization preclude a direct comparison betweenthe rates achieved with MERCI and Penumbra butboth exceed the natural history rate16
Randomized trials are ongoing such as the LocalVersus Systemic Thrombolysis for Acute Ischemic
S244 Neurology 79 (Suppl 1) September 25 2012
Stroke (SYNTHESIS EXP) and the MulticenterRandomized Clinical trial of Endovascular treatmentfor Acute ischemic stroke in the Netherlands (MRCLEAN) comparing endovascular recanalization vsstandard medical treatment alone (including IV rtPAor supportive care alone)1718 The NIH-funded Me-chanical Retrieval and Recanalization of Stroke ClotsUsing Embolectomy (MR RESCUE) trial is compar-ing the effectiveness of endovascular therapy within 8hours of symptom onset and standard medical careto standard medical treatment alone19 Several trialsare testing bridging therapies combining early ad-ministration of IV rtPA with the endovascular ap-proach including the Interventional Management ofStroke III (IMS III) and Assess the Penumbra Systemin the Treatment of Acute Stroke (THERAPY) tri-als20 In the United States the ongoing IMS a ran-domized multicenter trial will enroll 900 subjectswith AIS within 3 hours of symptom onset to com-pare combined IV and IA rtPA to IV rtPA alone21
Alternative revascularization methods continue toevolve and have included acute intracranial stent im-plantation22 and temporary endovascular bypass andthrombectomy with a retrievable stent2324 Initialopen series reports with stent retrievers suggest po-tentially higher recanalization rates and shorter pro-cedure times
PATIENT SELECTION FOR ENDOVASCULARREVASCULARIZATION THERAPY IN ACUTEISCHEMIC STROKE Designing a decision algo-rithm for patient selection for ERT in AIS is hin-dered by variable enrollment criteria in the trialscited previously The presented outline for the devel-opment of a decision algorithm is based on findingsfrom available randomized controlled trials and ex-trapolated from criteria from recent and ongoingclinical trials (figure) This is an example of one pos-sible algorithm and further investigation is necessaryprior to clinical use
Outside of clinical trials IV therapy remains first-line treatment for eligible patients presenting withclinical symptoms of AIS Through a systematic re-view of the literature the American Stroke Associa-tion (ASA) guidelines outline the best medicalmanagement as well as protocols to facilitate timelyadministration of IV rtPA to patients eligible forthrombolysis1 For patients with moderate to severedeficits and minimal or no early ischemic changes onbrain imaging therapy triage is largely governed bytime from symptom onset There is strong evidencefrom multiple clinical trials to support the use of IVrtPA within 3 hours22526 Current FDA approvalexists for patients presenting up to 3 hours fromsymptom onset and a science advisory from theASAAHA has recommended expanding the time
Tab
le1
Dat
afr
omse
lect
edtr
ials
ofen
dov
ascu
lar
reva
scul
ariz
atio
nth
erap
yfo
rac
ute
isch
emic
stro
ke
PR
OA
CT
5P
RO
AC
TII
6E
MS
56IM
SI55
IMS
II40
ME
RC
I10M
ELT
12M
ulti
-ME
RC
I29P
enum
bra
PS
T11
Sol
itai
reA
Bp
ilot
stud
y24
Yea
r1
99
81
99
91
99
92
00
42
00
72
00
52
00
72
00
82
00
92
01
0
Inte
rven
tion
Pro
UK
IV
hepa
rin
vsIV
hepa
rin
pl
aceb
o(IA
salin
ein
fusi
on)
Pro
UK
IV
hepa
rin
vsIV
hepa
rin
IVtP
Aor
IVpl
aceb
ofo
llow
edby
IAtP
AIV
IA
tPA
IV
hepa
rin
IV
IAtP
A
IVhe
pari
nw
ith
orw
itho
utE
kos
Mer
ciX
6R
etri
ever
IV
hepa
rin
UK
vsco
ntro
lL5
Ret
riev
er
IVhe
pari
nP
enum
bra
aspi
rati
onsy
stem
IV
hepa
rin
Sol
itai
reA
Bm
echa
nica
lth
rom
bect
omy
Enr
ollm
ent
tim
eh
6
6
3
3
3
8
6
8
8
8
Des
ign
RC
TP
hase
IIR
CT
Pha
seIII
RC
TP
hase
IS
ingl
ear
ms
afet
yan
dfe
asib
ility
Sin
gle
arm
saf
ety
and
feas
ibili
tyS
ingl
ear
m
Pro
spec
tive
RC
TS
ingl
ear
m
pros
pect
ive
Sin
gle
arm
pr
ospe
ctiv
eS
ingl
ear
ms
afet
yan
dfe
asib
ility
No
ofp
atie
nts
40
18
03
58
08
11
51
11
41
64
12
52
0
Rec
anal
izat
ion
rate
of
trea
tmen
tco
ntro
l5
81
46
61
85
51
05
66
0(T
ICI
TIM
I2ndash3
)4
67
45
76
9w
ith
adjt
x8
29
0
Occ
lusi
onsi
teM
CA
MC
AC
CA
IC
AM
CA
BA
ICA
MC
AV
AB
A
SC
AP
CA
AC
A
AIC
AP
ICA
ICA
MC
AV
AB
A
SC
AP
CA
AC
A
AIC
AP
ICA
ICA
MC
A
VA
BA
M
CA
ICA
MC
A
VA
BA
IC
AM
CA
VA
BA
IC
AM
CA
Mea
nN
IHS
S
trea
tmen
tco
ntro
l1
71
91
71
71
61
11
81
92
01
41
41
91
81
9
SIC
H
oftr
eatm
ent
cont
rol
15
71
09
21
18
56
69
97
89
29
81
12
10
mR
S0
ndash2at
90
day
s
oftr
eatm
ent
cont
rol
30
21
(mR
S0
ndash1at
90
days
)4
02
54
76
74
34
62
84
91
36
25
45
Abb
revi
atio
nsA
CA
an
teri
orce
rebr
alar
tery
adj
tx
adju
ncti
veth
erap
yA
ICA
an
teri
orin
feri
orce
rebe
llara
rter
yB
A
basi
lara
rter
yC
CA
co
mm
onca
roti
dar
tery
EM
S
Em
erge
ncy
Man
agem
ent
ofS
trok
eB
ridg
ing
Tria
lIA
in
tra-
arte
rial
IC
A
intr
acra
nial
inte
rnal
caro
tid
arte
ryI
MS
In
terv
enti
onal
Man
agem
ent
ofS
trok
etr
ial
MC
A
mid
dle
cere
bral
arte
ryM
ELT
M
iddl
ece
rebr
alar
tery
Em
bolis
mLo
cal
Fib
rino
lyti
cin
terv
enti
onTr
ial
ME
RC
IM
echa
nica
lEm
bolu
sR
emov
alin
Cer
ebra
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hem
iam
RS
m
odif
ied
Ran
kin
Sca
leN
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S
NIH
Str
oke
Sca
leP
CA
po
ster
ior
cere
bral
arte
ryP
ICA
po
ster
ior
infe
rior
cere
bella
rar
tery
PR
OA
CT
P
roly
sein
Acu
teC
ereb
ralT
hrom
boem
bolis
mtr
ial
PS
T
Piv
otal
Str
oke
Tria
lR
CT
ra
ndom
ized
cont
rolle
dtr
ial
SC
A
supe
rior
cere
bella
rar
tery
SIC
H
sym
ptom
atic
intr
acra
nial
hem
orrh
age
TIC
Ith
rom
boly
sis
ince
rebr
alin
farc
tion
TIM
Ith
rom
boly
sis
inm
yoca
rdia
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tPA
ti
ssue
plas
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intr
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vert
ebra
lart
ery
Neurology 79 (Suppl 1) September 25 2012 S245
window to 45 hours in a subgroup of patients onthe basis of results of the European CooperativeAcute Stroke Study III (ECASS III)2527
Patients presenting after 45 hours are not eligiblefor systemic thrombolysis however data exist ascited previously for the consideration of IA fibrino-lytic administration up to 6 hours from symptomonset in patients with a large- to medium-vessel oc-clusion61228 For patients in whom endovasculartherapy can be initiated within 8 hours from symp-tom onset 2 mechanical revascularization devicefamilies have demonstrated safe and feasible rates ofrecanalization in single-arm prospective trials101129
The optimal device for mechanical revascularizationhas not been identified and the rapid growth of de-vice technology will likely continue to challenge rig-orous clinical evaluation
Vertebrobasilar artery occlusion (VBO) has an in-variably poor outcome if recanalization is notachieved early The recent literature shows that mor-tality with acute VBO treated with nonthrombolyticdrugs is 80 to 90 although lower rates of 42 to60 can be achieved with IA therapy283031 Successof recanalization and neurologic status before treat-ment are independent predictors of a favorable out-come after IA therapy3031 Multiple studies failed toestablish a time window that would definitively ex-
clude patients from IA therapy30 One study found asignificantly better clinical outcome in patients withacute VBO treated within 6 hours after symptomonset than in patients treated after 6 hours (favorableoutcome of 36 vs 7 mortality of 52 vs 70p 0005)28 Other studies demonstrated trends to-ward better outcome with shorter duration of symp-toms and no significant association between time totreatment and clinical outcome3031 When patients arein a coma or have had prolonged symptoms additionalimaging such as MRI with diffusion and perfusion orCT perfusion might help in identifying those who arelikely to benefit from intervention However the cur-rent application of CT perfusion results to the posteriorcirculation may be limited
The trials that shape the current decision patternshave been largely based on time from symptom on-set Data are lacking on the efficacy of ERT beyond12 hours from symptom onset in patients with poste-rior circulation occlusion and beyond 8 hours in an-terior circulation occlusion1011293132 Given the poornatural history of VBO revascularization has beenconsidered beyond 12 hours from symptom onsetEnthusiasm continues for a perfusion imagingndashbaseddecision algorithm although rigorous data to sup-port this approach are lacking33 Further study ofperfusion imaging may assist with selection of pa-
Figure Possible decision algorithm for revascularization therapies in acute ischemic stroke
S246 Neurology 79 (Suppl 1) September 25 2012
tients who would benefit from revascularization be-yond 8 hours34
At the very least noncontrast head CT ordiffusion- and susceptibility-weighted MRI are re-quired to exclude hemorrhage and identify early isch-
emic changes that could pose increased hemorrhagicrisk following revascularization Larger regions ofwell-defined hypoattenuation (CT) or hyperintensity(MRI) indicating infarcted tissue may carry a consid-erably higher risk of hemorrhage following revascu-larization Careful consideration may be needed forpatients with CT hypodensity or MRI hyperintensityin greater than 13 of the MCA territory or withprominent sulcal effacement35 Alternative standard-ized scoring systems may include the Alberta StrokeProgram Early CT Score (ASPECTS)36
Future studies may show that for patients whoreceive IV rtPA and have a clinical presentation sug-gestive of a large-vessel occlusion early considerationof ERT may be important The limited efficacy of IVrtPA in large vessel occlusions is demonstrated byrecanalization rates as low as 30 in the proximalMCA and 6 in the terminal internal carotid artery(ICA)37 Urgent noninvasive vascular imaging canidentify patients with a large-vessel occlusion Theinterval from a decision to pursue IA intervention toreaching the clot can be long with time required toobtain consent transport and prepare the patient andnegotiate tortuous anatomy Accordingly an efficientstrategy may be to activate the neurointerventional teamwhen a large-vessel occlusion is suspected without delayin IV rtPA initiation If dramatic clinical improvementoccurs patients can be rerouted to repeat noninvasivevessel assessment One retrospective study has shownthat in those patients with a contraindication to IV rtPAor whose IV therapy fails the use of ERT within thefirst 3 hours after stroke symptom onset has a low sICHrate of 5338
Patients with fluctuating deficits or continuedmild deficits (NIHSS score 4) following rapid im-provement from presentation carry a risk of harbor-ing a large-vessel occlusion with tenuous collateralsupply Failure of collateral supply could lead toacute deterioration therefore emergent noninvasiveangiography to identify vessel occlusions amenable toERT may be considered To date no randomizedclinical trial has compared the natural history ofmedical treatment alone to early recanalization withERT in this subset of patients
For patients in whom ERT is considered inclu-sion and exclusion criteria will be needed Based onthe existing clinical trials and guidelines a frame-work for the future development of criteria can beoutlined (table 2)
SELECTION OF ENDOVASCULAR REVASCU-LARIZATION THERAPY TECHNIQUE The heter-ogeneity of AIS characteristics including thrombuscomposition occlusion location thrombus volumeburden and collateral perfusion may demand tai-
Table 2 Possible selection criteria for acute ischemic stroke endovascularrevascularization therapy
Inclusion criteria for ERT
Neurologic deficit attributable to a medium- to large-vessel occlusion
IA chemical thrombolysis can be initiated within 6 h of symptom onset
Mechanical thrombectomy treatment can be initiated within window of 8 h from time of onsetfor anterior circulation strokes
ERT can be initiated within window of 12 h from time of onset for posterior circulationstrokes
Treatment beyond 6ndash8 h may be guided by advanced imaging results (DWI MRI PWI CTP)when available
Potentially disabling neurologic deficit
Persistent or worsening neurological deficits following IV rtPA administration
Exclusion criteria for ERT
Arterial stenosis precluding safe access
Suspicion of aortic dissection
Uncontrolled hypertension defined as systolic blood pressure 185 mm Hg or diastolicblood pressure 110 mm Hg that cannot be reasonably treated with antihypertensivemedication
Platelet count 30000
Use of warfarin anticoagulation with INR 30
Known bleeding diathesis
Deficits attributable to glucose 50 mgdL
Seizure at onset if residual deficits are due to a postictal state rather than ischemia
Imaging findings
Significant mass effect with midline shift
Intracranial hemorrhage (ICH SAH subdural or epidural hematoma)
Subacute infarct on head CTMRI that occupies 13 of the MCA territory or 100 cc ofbrain tissue
CNS lesion with high likelihood of hemorrhage should be excluded from IA pharmacologicthrombolysis (brain tumor abscess vascular malformation aneurysm contusion)
May consider IA thrombolysis in patients with small unruptured aneurysms or benigntumors with low vascularity
Relative contraindications for ERT therapy
Intracranial or spinal surgery head trauma or stroke in separate vascular territory within 3months
History of ICH
Terminal illness with short life expectancy or severe comorbid illness
Pregnancy
Risk vs benefit of clinical symptoms and ability to shield patient must be considered
Known subacute bacterial endocarditis with or without mycotic aneurysm and stroke
Special consideration may be needed for patients on dabigatran
Relative contraindications for adjunctive ERT following IV rtPA
Glucose 400 mgdL based on increased ICH risk
Ongoing hemodialysis or peritoneal dialysis due to possibly increased ICH risk
Abbreviations CTP CT perfusion DWI MRI diffusion-weighted MRI ERT endovascu-lar revascularization therapy IA intra-arterial ICH intracerebral hemorrhage INR
international normalized ratio MCA middle cerebral artery NIHSS NIH Stroke ScalertPA recombinant tissue plasminogen activator SAH subarachnoid hemorrhage
Neurology 79 (Suppl 1) September 25 2012 S247
lored interventions For example greater efficacy andsafety may be demonstrated in distal vessel revascu-larization by use of IA fibrinolytic therapy vs a me-chanical device that may be more difficult to deliverAlternatively in large proximal vessel occlusionsgreater benefit may be achieved with mechanicalthrombectomy Furthermore carotid occlusion atthe origin of the ICA may be better treated with bal-loon angioplasty and stent implantation
Pharmacologic thrombolysis Local IA thrombolysisefficacy was demonstrated in PROACT II6 This ledto an AHA Class I level of evidence B recommenda-tion that IA thrombolysis is an option for the treat-ment of selected patients who have AIS under 6hours duration due to occlusions of the MCA andwho are not otherwise candidates for IV rtPA1 Al-though variability in study designs prohibits direct com-parison of the data theoretically there may be a higherrisk of intracerebral hemorrhage (ICH) with chemicalIA thrombolysis than with mechanical revasculariza-tion However increased ICH was not substantiated ina multicenter study39
Microcatheter position during thrombolytic infu-sion may also theoretically affect recanalization ratesThe microcatheter position varies among the studiesin some instances it is placed distal to the thrombuswithin the thrombus or proximal to the thrombusSome operators will use multiple locations to infusertPA throughout the thrombus The maximum safedose for IA rtPA is not known however if we extrap-olate from large clinical trial experience then a max-
imum dose of 22 mg as in the IMS trials may be areasonable initial limit2140
Bridging therapies Bridging therapy trials evaluatingthe combined approach have shown better recanali-zation rates for medium- to large-vessel occlusionsHowever they have shown only trends toward betteroutcomes in comparison with the IV rtPAndashtreatedsubjects in the National Institute of NeurologicalDisorders and Stroke (NINDS) rtPA Stroke Study ora database registry4041 Potential benefit of bridgingtherapy increases when the target population is lim-ited to IV rtPA nonresponders (40 IV-IA patientsreached functional independence at 3 months vs149 of recipients of only IV rtPA among the non-responders [p 0012]) This benefit came at thecost of a higher morbidity associated with the bridg-ing therapy (OR 214 95 CI 058 ndash783 forsICH)42 The early Emergency Management ofStroke Bridging TrialIMS trials used a protocol of06 mgkg IV rtPA with up to an additional maxi-mum of 22 mg IA rtPA which in most patients al-lowed for the total dose to remain below the NINDSmaximum amount of 90 mg (table 3) Howevernewer bridging studies and the amended IMS III areusing full-dose IV rtPA in the combined IV-IA treat-ment arm2021
Mechanical revascularization Mechanical techniquesfor ERT including thrombectomy clot retrievaland thromboaspiration have shown comparable orslightly higher recanalization rates than IA thrombol-
Table 3 Intra-arterial thrombolytic dosing and methods from selected trials
Trial PROACT5 PROACT II6 MELT12 IMS I55 IMS II40 IMS III21
Agent ProUK ProUK UK rtPA rtPA rtPA
Max dose Two-tier dose6 mg and 12 mg
9 mg 600000 IU IV rtPA 06 mgkg 60mg maxIA rtPA 22 mg
IV rtPA 06 mgkg60 mg maxIA rtPA 22 mg
IV rtPA 06 mgkg 60 mgmaxpossibly IA rtPA 22 mg
Median dose mg 6 and 12 9 mdash mdash 12 mdash
Infusion duration h 2 2 2 2 2 2
Infusion location At proximal one-thirdof thrombus
At proximal one-thirdof thrombus
Distal tothrombus
2 mg distal to thrombusthen 2 mg intothrombus then infusion
At site of thrombuswith or withoutEkos ultrasoundcatheter
1 mg distal and 1 mgproximal then 20 mg overmaximum of 2 h
Mechanical disruption Prohibited Prohibited Only withguidewire
Only with guidewire ormicrocatheter
Only with guidewireor microcatheter
Merci device Ekos orpenumbra device with IArtPA infusion ormicrocatheter IA rtPAinfusion
Intraproceduralsystemic thrombo-prophylaxis
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 5000IU bolus
Heparin 2000 IU bolusand 450 IUh infusion
Heparin 2000 IUbolus and 450 IUhinfusion
Heparin 2000 IU bolus and450 IUh infusion until theend of the procedure
Adjunctiveantithrombotic agents
Prohibited in first24 h
Prohibited in first24 h
Prohibited infirst 24 h
Prohibited in first 24 h Prohibited in first24 h
Prohibited in first 24 h
Abbreviations IA intra-arterial IMS Interventional Management of Stroke trial IU international units MELT Middle cerebral artery Embolism LocalFibrinolytic intervention Trial PROACT Prolyse in Acute Cerebral Thromboembolism trial rtPA IV recombinant tissue plasminogen activator UK
urokinase
S248 Neurology 79 (Suppl 1) September 25 2012
ysis alone (table 1) Newer devices such as the Soli-taire FR retrievable stent (eV3 Irvine CA) haveshown even higher recanalization rates (84ndash90)2324 In appropriately selected patients me-chanical revascularization may theoretically have alower risk of hemorrhagic complications given theabsence or reduced need for a thrombolytic agent Inpatients who are considered for ERT after full-doseIV rtPA a mechanical approach might be favorableLimitations of mechanical revascularization includedevice failure deliverability to distal locations andembolization
Multimodal revascularization Given the heterogene-ity of vessel occlusion etiology in AIS a combinationof multiple techniques may afford the highest successfor revascularization Small series suggest that multi-modal therapies including IA thrombolysis and stentimplantation lead to higher recanalization rates39
Future studies may find mechanical thrombectomyto be more successful in proximal large-vessel occlu-sions whereas local IA thrombolysis would be pre-ferred in distal small-vessel occlusions Also stentimplantation may be most effective for in situ intra-cranial atherosclerosis with supervening thrombosisbut retrieval and aspiration techniques may be moreeffective for thromboemboli occlusive in relativelynormal recipient arteries4
Posterior circulation modality selection The besttreatment modality for patients with VBO remainspoorly defined A large prospective observationalregistry and a separate systematic analysis of pub-lished case series analyzed a total of 1012 patientsboth studies did not support unequivocal superiorityof IA therapy vs IV thrombolysis3243 However theheterogeneity of the data between the patients withinthe groups analyzed limits interpretation of the clini-cal conclusions Early recanalization is an importantprognostic factor for good clinical outcome as suchhigher and safer rates of recanalization are beingachieved with newer therapeutic strategies utilizingmechanical embolectomy devices retrievable stentsangioplasty with or without stenting use of glyco-protein IIbIIIa inhibitors and combinationsthereof2328304445
TARGET TIME INTERVALS AND TRIAGE ANDTRANSFER STRATEGIES Time to revasculariza-tion is an independent predictor of good outcome inpatients with AIS4647 Randomized trials of IV rtPAhave demonstrated the greatest benefit in subjectstreated within 90 minutes of symptom onset225 Re-canalization rates with ERT are higher than with IVrtPA alone although the delay to treatment may at-tenuate the benefit This illustrates the importance ofestablishing benchmark door-to-revascularization
Tab
le4
Tre
atm
ent
tim
esin
sele
cted
stud
ies
inm
inut
es
Tri
alP
RO
AC
T5
PR
OA
CT
II6
IMS
I55IM
SII
I21E
MS
56M
ELT
12R
EC
AN
ALI
SE
41P
enum
bra
PS
T11
Mul
tiM
ER
CI29
M
ER
CI10
Wol
feet
al50
Doc
rocq
etal
54C
osta
lat
etal
43M
iley
etal
53S
uare
zet
al51
Mat
tle
etal
49F
lahe
rty
etal
52
No
ofsu
bje
cts
40
12
16
25
00
35
56
50
12
53
05
96
13
50
91
54
57
44
Tre
atm
ent
IApr
oUK
orpl
aceb
oIA
proU
KIV
-IA
rtP
AIV
aor
IV
IAb
IV-I
Aa
orIA
rtP
Ab
IAU
KIV
-IA
orIV
-IA
Trt
PA
IAT
IV
rtP
AIA
TIV
-IA
aor
IArt
PA
bIA
UK
IV-R
Sor
RS
alon
eIV
-IA
Tor
IAT
IAU
KIA
TU
KIV
IA
rtP
A
Tim
e-to
-doo
r1
14
Tim
e-to
-CT
MR
Isc
anm
ean
(med
ian)
Ons
et1
05
Ons
et1
62
(14
5)
Doo
r5
9(3
4)
Imag
ing
-to-
GP
16
1(1
53
)8
1(6
5)
CT
scan
-to-
mic
roca
thet
er1
74
Tim
e-to
-ER
Tin
itia
tion
oran
gio
gra
mor
GP
SO
(33
0)
SO
(31
8)
SO
21
7(2
12
)
SO
12
37
25
52
IV-b
olus
toG
P8
74
SO
a(1
98
)Oslash
b(1
80
)Oslash
SO
22
7S
O1
32
SO
25
8pound
SO
(25
8)
SO
a1
51
b2
61
SO
32
4(3
30
)S
O3
21
Doo
r(1
30
)S
O2
44
SO
(22
6)
GP
-to-
max
TIM
IT
ICI
54
(48
)
SO
-to-
max
TIM
IT
ICI
a(3
78
)b(
34
2)
(22
0)
37
7(3
27
)
Abb
revi
atio
nsE
MS
E
mer
genc
yM
anag
emen
tof
Str
oke
ER
T
endo
vasc
ular
reva
scul
ariz
atio
ntr
eatm
ent
GP
gr
oin
punc
ture
IA
in
tra-
arte
rial
IA
T
intr
a-ar
teri
alth
erap
y(in
clud
esth
rom
boly
sis
and
mec
hani
cal
tech
niqu
es)
IMS
In
terv
enti
onal
Man
agem
ento
fStr
oke
tria
lM
ELT
M
iddl
ece
rebr
alar
tery
Em
bolis
mLo
calF
ibri
noly
tic
inte
rven
tion
Tria
lM
ER
CI
Mec
hani
calE
mbo
lus
Rem
oval
inC
ereb
ralI
sche
mia
PR
OA
CT
P
roly
sein
Acu
teC
ereb
ralT
hrom
boem
bolis
mtr
ial
PS
T
Piv
otal
Str
oke
Tria
lR
EC
AN
ALI
SE
R
Eca
nalis
atio
nus
ing
Com
bine
din
trav
enou
sA
ltep
lase
and
Neu
roin
terv
enti
onal
Alg
orit
hmfo
racu
teIs
chem
icS
trok
ER
S
retr
ieva
ble
sten
trt
PA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
O
sym
ptom
onse
tTI
CI
thro
mbo
lysi
sin
cere
bral
infa
rcti
onT
IMI
thro
mbo
lysi
sin
myo
card
iali
nfar
ctio
nU
K
urok
inas
e
Neurology 79 (Suppl 1) September 25 2012 S249
times The Brain Attack Coalition has recommendedthat IV rtPA be administered within 60 minutesfrom arrival to the emergency department (ED) foreligible patients48 The established time intervals tar-get a multidisciplinary goal Each component of theprocessmdashED physicians ancillary staff laboratoryand radiology services neurology team and radiol-ogy staffmdashis essential for the time goal As suchERT time intervals should integrate into the existingmodel beginning with patient arrival to the EDSeparate time intervals can be established for patientstransferred from another institution and patientswho receive adjunctive ERT following IV rtPA ther-apy Because vascular anatomy can add unpredictabledelays in procedural times the endpoint should re-flect the last modifiable variable Therefore ERTtime intervals should reflect door-to-puncture (morepredictable) puncture-to-clot and clot-to-closegoals A clot-to-close time of 120 minutes as de-scribed in IMS III may be warranted to establishprocedural termination times More variables in-cluding anatomy evidence of persistent penumbraand ERT method may be used in the future to mod-ify time benchmarks
In the limited case series discussing time intervalsto ERT there is variability in which interval is uti-lized (table 4)56111215414349 ndash56 Randomized trialsshow feasibility in achieving time intervals of approx-imately 4 to 5 hours from stroke onset to IA rtPAadministration655 In PROACT II median timefrom stroke onset to randomization and IA rtPA ad-ministration was 282 minutes whereas the IMSstudy demonstrated an interval of 231 minutes fromstroke onset to IA rtPA administration655 Timefrom CT scan to microcatheter placement in thecerebrovasculature had a mean time of 174 60minutes in 91 patients undergoing ERT for AISdemonstrating wide variability and a need for timestandards53 Transferred patients whose laboratorytests and CT scan have already been completed maystill have a door-to-puncture time of up to 60 min-utes57 Further study is needed to identify barriers torapid access to endovascular therapy
Currently the American College of Cardiologyand the AHA recommend that door-to-balloon timein ST segment elevation myocardial infarctionshould be within 90 minutes A similar future pro-posal could be made for ERT in AIS with a goaldoor-to-puncture time of 90 minutes (table 5) Thiswould include activation of the stroke team technol-ogists and nurses Adjunctive time benchmarks canbe developed including puncture-to-clot and clot-to-close goals This target is more difficult to achievefor cerebral than cardiac revascularization as strokepatients require more time-consuming neurologic
Tab
le5
Ben
chm
ark
tim
esfo
rre
vasc
ular
izat
ion
ther
apie
san
dp
ossi
ble
inte
rval
sfo
rE
RT
Am
eric
anC
olle
geof
Car
diol
ogy6
7A
SA
AH
AA
ISG
uide
lines
forI
Vrt
-PA
68
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rE
RT
pres
enti
ngto
ED
ldquoP
rim
ary
ER
TTi
merdquo
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rRes
cue
ER
Tfo
llow
ing
IVfa
ilure
ldquoIV
-Fai
lure
toR
escu
eE
RTrdquo
Pro
pose
dgo
als
forA
ISpa
tien
tstr
ansf
erre
dfr
omou
tsid
eho
spit
alfo
rER
TldquoD
rip-
and-
Shi
pto
ER
Trdquo
Doo
r-to
-bal
loon
tim
e9
0m
inD
oor-
to-n
eedl
eti
me
60
min
Doo
r-to
-gro
inpu
nctu
reti
me
90
min
Nee
dle
-to-
gro
inp
unct
ure
tim
e6
0m
inD
oora -t
o-G
roin
Pun
ctur
eti
me
60
min
ST
EM
Icon
firm
ed
card
iolo
gis
tno
tifi
ed
10
min
Doo
rto
ED
10
min
Doo
rto
ED
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
0m
in)
ER
Tte
amis
noti
fied
asso
onas
larg
eto
med
ium
vess
eloc
clus
ion
issu
spec
ted
(ie
N
IHS
Sh
yper
dens
eM
CA
onC
T)in
elig
ible
pati
ents
10
min
afte
rth
eel
igib
ility
CT
scan
and
befo
reIV
bolu
s
Tran
sfer
from
outs
ide
hosp
ital
init
iate
dan
gio
suit
eac
tiva
ted
team
acti
vate
d
Pri
orto
arri
val
ED
stab
ilize
sp
atie
nta
ctiv
ates
cath
lab
30
min
Str
oke
team
acti
vati
on1
5m
inS
trok
ean
dE
RT
team
sac
tiva
tion
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
5m
in)
Rec
eivi
ngho
spit
alar
riva
lR
apid
hist
ory
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igib
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S250 Neurology 79 (Suppl 1) September 25 2012
evaluation and brain imaging before proceeding tothe angiography laboratory
Achieving a 90-minute door-to-puncture timewould likely require the neurointerventionalist toplay an integral part in the stroke team because thedecisions on treatment strategy may evolve as the pa-tient proceeds through the AIS protocol and IV rtPAevaluation pathway The ERT protocol should inte-grate into the IV rtPA pathway For interhospitaltransfers the completed imaging and laboratorystudies as well as additional lead time may reduce thetarget time interval to 60 minutes for door-to-puncture However significant delay in hospitaltransfer may warrant repeat neuroimaging when thepatient arrives at the recipient institution Bench-mark times will need to be established for IV nonre-sponders with special consideration for additionaldelay when clinical deterioration following IV rtPArequires a repeat brain imaging prior to ERT
Triage and transfer strategies The considerable de-cline in efficacy of revascularization therapies ataround 6 to 8 hours from symptom onset demandswell-organized triage and transfer strategies46 Emer-gency department reorganization has been an area offocus to improve early identification of stroke pa-tients Tracking door-to-thrombolysis times posi-tioning a CTMRI scanner within the departmentand having emergency medical services (EMS) send aprehospital notification are steps that have improvedthrombolysis access58 However given the limitedavailability of Comprehensive Stroke Center infra-structure few centers in a given geographic regionwill have capabilities for providing comprehensivestroke care and 247 ERT This will lead to a highproportion of patients eligible for ERT arriving byinterhospital transfer Transfer delay has been shownto be a major factor limiting the use of ERT in strokepatients accounting for an estimated odds of treat-ment decrease by 25 for every minute of transfertime59 To avoid transfer delay regional protocols fortriage of AIS patients by EMS personnel to desig-nated stroke centers has become a focus of prehospi-tal stroke triage policy60
Alternative strategies include initiation of IVthrombolytic in a referring hospital prior to transferldquodrip-and-shiprdquo followed by further management atthe accepting hospital which may include ERT Adescribed model of ldquodrip ship and retrieverdquo usedfull-dose IV rtPA (09 mgkg) followed by ERT withmechanical thrombectomy and thrombo-aspirationsuggesting feasibility in basilar artery occlusion61
Different models may evolve where the patient re-ceives ERT in an outside hospital and is transferredfor further care at a comprehensive stroke centerwhere neurosurgery neurocritical care and vascular
neurology expertise are available known as ldquoretrieve-and-shiprdquo Pay-for-performance measures similar tothose for acute myocardial infarction could help fa-cilitate transfer of appropriate patients from primaryto comprehensive stroke centers (the hub-and-spokemodel)
GENERAL PREPROCEDURAL AND INTRAPROCE-DURAL MANAGEMENT Anesthesia and monitoringThe type of anesthesia for ERT has been a topic ofcontroversy with recent reports suggesting worseoutcome with use of general endotracheal anesthesiapossibly due to treatment delays and complicationsfrom intubation6263 Alternatively conscious seda-tion may pose a different set of risks related to patientcooperation especially in those with severe aphasiaor neglect which may negatively influence time torevascularization and procedural success Further-more ancillary monitoring requiring invasive arterialaccess for blood pressure monitoring and central IVaccess may also be of limited value and add delay toinitiation of therapy Further study is needed to eval-uate sedation methods for ERT Sedation methodsmay currently vary among centers
Thromboprophylaxis with systemic anticoagulationArterial catheterization carries a risk of thromboem-bolism often requiring systemic anticoagulationRandomized clinical trials of ERT report variableprotocols for thromboprophylaxis including bolusIV heparin infusion of 2000 to 5000 units atprocedure onset followed by continuous infusionsof approximately 500 units of IV heparin per hourfor the procedure duration621 Alternatively acti-vated clotting time (ACT) values can be obtainedwith heparin boluses to maintain an ACT at atherapeutic goal Limited data exist on the safetyof heparin anticoagulation during ERT proce-dures A subgroup analysis of the MERCI trialshowed no association with hemorrhage or 90-daymortality and heparin use64 A reasonable ACTrange may be 250 to 300 seconds during ERT
Renal prophylaxis Patients with AIS may also havechronic renal impairment which may worsen withcontrast administered during angiography Inter-ventions designed to prevent contrast-induced ne-phropathy have not been rigorously studiedReasonable prophylaxis strategies include hydra-tion with isotonic saline Recent data have notprovided strong support for the administration ofN-acetylcysteine65 The use of sodium bicarbonateinfusion may be reasonable for patients with renalinsufficiency but it can be limited by the largevolume and time to acquire the solution from thepharmacy Periprocedural renal prophylaxis for
Neurology 79 (Suppl 1) September 25 2012 S251
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
httpnneurologyorgcontent7913_Supplement_1S243fullincluding high resolution figures can be found at
References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
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ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
ehttpnneurologyorgcgicollectionall_cerebrovascular_disease_strokAll Cerebrovascular diseaseStrokefollowing collection(s) This article along with others on similar topics appears in the
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httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
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reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
Stroke (SYNTHESIS EXP) and the MulticenterRandomized Clinical trial of Endovascular treatmentfor Acute ischemic stroke in the Netherlands (MRCLEAN) comparing endovascular recanalization vsstandard medical treatment alone (including IV rtPAor supportive care alone)1718 The NIH-funded Me-chanical Retrieval and Recanalization of Stroke ClotsUsing Embolectomy (MR RESCUE) trial is compar-ing the effectiveness of endovascular therapy within 8hours of symptom onset and standard medical careto standard medical treatment alone19 Several trialsare testing bridging therapies combining early ad-ministration of IV rtPA with the endovascular ap-proach including the Interventional Management ofStroke III (IMS III) and Assess the Penumbra Systemin the Treatment of Acute Stroke (THERAPY) tri-als20 In the United States the ongoing IMS a ran-domized multicenter trial will enroll 900 subjectswith AIS within 3 hours of symptom onset to com-pare combined IV and IA rtPA to IV rtPA alone21
Alternative revascularization methods continue toevolve and have included acute intracranial stent im-plantation22 and temporary endovascular bypass andthrombectomy with a retrievable stent2324 Initialopen series reports with stent retrievers suggest po-tentially higher recanalization rates and shorter pro-cedure times
PATIENT SELECTION FOR ENDOVASCULARREVASCULARIZATION THERAPY IN ACUTEISCHEMIC STROKE Designing a decision algo-rithm for patient selection for ERT in AIS is hin-dered by variable enrollment criteria in the trialscited previously The presented outline for the devel-opment of a decision algorithm is based on findingsfrom available randomized controlled trials and ex-trapolated from criteria from recent and ongoingclinical trials (figure) This is an example of one pos-sible algorithm and further investigation is necessaryprior to clinical use
Outside of clinical trials IV therapy remains first-line treatment for eligible patients presenting withclinical symptoms of AIS Through a systematic re-view of the literature the American Stroke Associa-tion (ASA) guidelines outline the best medicalmanagement as well as protocols to facilitate timelyadministration of IV rtPA to patients eligible forthrombolysis1 For patients with moderate to severedeficits and minimal or no early ischemic changes onbrain imaging therapy triage is largely governed bytime from symptom onset There is strong evidencefrom multiple clinical trials to support the use of IVrtPA within 3 hours22526 Current FDA approvalexists for patients presenting up to 3 hours fromsymptom onset and a science advisory from theASAAHA has recommended expanding the time
Tab
le1
Dat
afr
omse
lect
edtr
ials
ofen
dov
ascu
lar
reva
scul
ariz
atio
nth
erap
yfo
rac
ute
isch
emic
stro
ke
PR
OA
CT
5P
RO
AC
TII
6E
MS
56IM
SI55
IMS
II40
ME
RC
I10M
ELT
12M
ulti
-ME
RC
I29P
enum
bra
PS
T11
Sol
itai
reA
Bp
ilot
stud
y24
Yea
r1
99
81
99
91
99
92
00
42
00
72
00
52
00
72
00
82
00
92
01
0
Inte
rven
tion
Pro
UK
IV
hepa
rin
vsIV
hepa
rin
pl
aceb
o(IA
salin
ein
fusi
on)
Pro
UK
IV
hepa
rin
vsIV
hepa
rin
IVtP
Aor
IVpl
aceb
ofo
llow
edby
IAtP
AIV
IA
tPA
IV
hepa
rin
IV
IAtP
A
IVhe
pari
nw
ith
orw
itho
utE
kos
Mer
ciX
6R
etri
ever
IV
hepa
rin
UK
vsco
ntro
lL5
Ret
riev
er
IVhe
pari
nP
enum
bra
aspi
rati
onsy
stem
IV
hepa
rin
Sol
itai
reA
Bm
echa
nica
lth
rom
bect
omy
Enr
ollm
ent
tim
eh
6
6
3
3
3
8
6
8
8
8
Des
ign
RC
TP
hase
IIR
CT
Pha
seIII
RC
TP
hase
IS
ingl
ear
ms
afet
yan
dfe
asib
ility
Sin
gle
arm
saf
ety
and
feas
ibili
tyS
ingl
ear
m
Pro
spec
tive
RC
TS
ingl
ear
m
pros
pect
ive
Sin
gle
arm
pr
ospe
ctiv
eS
ingl
ear
ms
afet
yan
dfe
asib
ility
No
ofp
atie
nts
40
18
03
58
08
11
51
11
41
64
12
52
0
Rec
anal
izat
ion
rate
of
trea
tmen
tco
ntro
l5
81
46
61
85
51
05
66
0(T
ICI
TIM
I2ndash3
)4
67
45
76
9w
ith
adjt
x8
29
0
Occ
lusi
onsi
teM
CA
MC
AC
CA
IC
AM
CA
BA
ICA
MC
AV
AB
A
SC
AP
CA
AC
A
AIC
AP
ICA
ICA
MC
AV
AB
A
SC
AP
CA
AC
A
AIC
AP
ICA
ICA
MC
A
VA
BA
M
CA
ICA
MC
A
VA
BA
IC
AM
CA
VA
BA
IC
AM
CA
Mea
nN
IHS
S
trea
tmen
tco
ntro
l1
71
91
71
71
61
11
81
92
01
41
41
91
81
9
SIC
H
oftr
eatm
ent
cont
rol
15
71
09
21
18
56
69
97
89
29
81
12
10
mR
S0
ndash2at
90
day
s
oftr
eatm
ent
cont
rol
30
21
(mR
S0
ndash1at
90
days
)4
02
54
76
74
34
62
84
91
36
25
45
Abb
revi
atio
nsA
CA
an
teri
orce
rebr
alar
tery
adj
tx
adju
ncti
veth
erap
yA
ICA
an
teri
orin
feri
orce
rebe
llara
rter
yB
A
basi
lara
rter
yC
CA
co
mm
onca
roti
dar
tery
EM
S
Em
erge
ncy
Man
agem
ent
ofS
trok
eB
ridg
ing
Tria
lIA
in
tra-
arte
rial
IC
A
intr
acra
nial
inte
rnal
caro
tid
arte
ryI
MS
In
terv
enti
onal
Man
agem
ent
ofS
trok
etr
ial
MC
A
mid
dle
cere
bral
arte
ryM
ELT
M
iddl
ece
rebr
alar
tery
Em
bolis
mLo
cal
Fib
rino
lyti
cin
terv
enti
onTr
ial
ME
RC
IM
echa
nica
lEm
bolu
sR
emov
alin
Cer
ebra
lIsc
hem
iam
RS
m
odif
ied
Ran
kin
Sca
leN
IHS
S
NIH
Str
oke
Sca
leP
CA
po
ster
ior
cere
bral
arte
ryP
ICA
po
ster
ior
infe
rior
cere
bella
rar
tery
PR
OA
CT
P
roly
sein
Acu
teC
ereb
ralT
hrom
boem
bolis
mtr
ial
PS
T
Piv
otal
Str
oke
Tria
lR
CT
ra
ndom
ized
cont
rolle
dtr
ial
SC
A
supe
rior
cere
bella
rar
tery
SIC
H
sym
ptom
atic
intr
acra
nial
hem
orrh
age
TIC
Ith
rom
boly
sis
ince
rebr
alin
farc
tion
TIM
Ith
rom
boly
sis
inm
yoca
rdia
linf
arct
ion
tPA
ti
ssue
plas
min
ogen
acti
vato
rU
K
urok
inas
eV
A
intr
acra
nial
vert
ebra
lart
ery
Neurology 79 (Suppl 1) September 25 2012 S245
window to 45 hours in a subgroup of patients onthe basis of results of the European CooperativeAcute Stroke Study III (ECASS III)2527
Patients presenting after 45 hours are not eligiblefor systemic thrombolysis however data exist ascited previously for the consideration of IA fibrino-lytic administration up to 6 hours from symptomonset in patients with a large- to medium-vessel oc-clusion61228 For patients in whom endovasculartherapy can be initiated within 8 hours from symp-tom onset 2 mechanical revascularization devicefamilies have demonstrated safe and feasible rates ofrecanalization in single-arm prospective trials101129
The optimal device for mechanical revascularizationhas not been identified and the rapid growth of de-vice technology will likely continue to challenge rig-orous clinical evaluation
Vertebrobasilar artery occlusion (VBO) has an in-variably poor outcome if recanalization is notachieved early The recent literature shows that mor-tality with acute VBO treated with nonthrombolyticdrugs is 80 to 90 although lower rates of 42 to60 can be achieved with IA therapy283031 Successof recanalization and neurologic status before treat-ment are independent predictors of a favorable out-come after IA therapy3031 Multiple studies failed toestablish a time window that would definitively ex-
clude patients from IA therapy30 One study found asignificantly better clinical outcome in patients withacute VBO treated within 6 hours after symptomonset than in patients treated after 6 hours (favorableoutcome of 36 vs 7 mortality of 52 vs 70p 0005)28 Other studies demonstrated trends to-ward better outcome with shorter duration of symp-toms and no significant association between time totreatment and clinical outcome3031 When patients arein a coma or have had prolonged symptoms additionalimaging such as MRI with diffusion and perfusion orCT perfusion might help in identifying those who arelikely to benefit from intervention However the cur-rent application of CT perfusion results to the posteriorcirculation may be limited
The trials that shape the current decision patternshave been largely based on time from symptom on-set Data are lacking on the efficacy of ERT beyond12 hours from symptom onset in patients with poste-rior circulation occlusion and beyond 8 hours in an-terior circulation occlusion1011293132 Given the poornatural history of VBO revascularization has beenconsidered beyond 12 hours from symptom onsetEnthusiasm continues for a perfusion imagingndashbaseddecision algorithm although rigorous data to sup-port this approach are lacking33 Further study ofperfusion imaging may assist with selection of pa-
Figure Possible decision algorithm for revascularization therapies in acute ischemic stroke
S246 Neurology 79 (Suppl 1) September 25 2012
tients who would benefit from revascularization be-yond 8 hours34
At the very least noncontrast head CT ordiffusion- and susceptibility-weighted MRI are re-quired to exclude hemorrhage and identify early isch-
emic changes that could pose increased hemorrhagicrisk following revascularization Larger regions ofwell-defined hypoattenuation (CT) or hyperintensity(MRI) indicating infarcted tissue may carry a consid-erably higher risk of hemorrhage following revascu-larization Careful consideration may be needed forpatients with CT hypodensity or MRI hyperintensityin greater than 13 of the MCA territory or withprominent sulcal effacement35 Alternative standard-ized scoring systems may include the Alberta StrokeProgram Early CT Score (ASPECTS)36
Future studies may show that for patients whoreceive IV rtPA and have a clinical presentation sug-gestive of a large-vessel occlusion early considerationof ERT may be important The limited efficacy of IVrtPA in large vessel occlusions is demonstrated byrecanalization rates as low as 30 in the proximalMCA and 6 in the terminal internal carotid artery(ICA)37 Urgent noninvasive vascular imaging canidentify patients with a large-vessel occlusion Theinterval from a decision to pursue IA intervention toreaching the clot can be long with time required toobtain consent transport and prepare the patient andnegotiate tortuous anatomy Accordingly an efficientstrategy may be to activate the neurointerventional teamwhen a large-vessel occlusion is suspected without delayin IV rtPA initiation If dramatic clinical improvementoccurs patients can be rerouted to repeat noninvasivevessel assessment One retrospective study has shownthat in those patients with a contraindication to IV rtPAor whose IV therapy fails the use of ERT within thefirst 3 hours after stroke symptom onset has a low sICHrate of 5338
Patients with fluctuating deficits or continuedmild deficits (NIHSS score 4) following rapid im-provement from presentation carry a risk of harbor-ing a large-vessel occlusion with tenuous collateralsupply Failure of collateral supply could lead toacute deterioration therefore emergent noninvasiveangiography to identify vessel occlusions amenable toERT may be considered To date no randomizedclinical trial has compared the natural history ofmedical treatment alone to early recanalization withERT in this subset of patients
For patients in whom ERT is considered inclu-sion and exclusion criteria will be needed Based onthe existing clinical trials and guidelines a frame-work for the future development of criteria can beoutlined (table 2)
SELECTION OF ENDOVASCULAR REVASCU-LARIZATION THERAPY TECHNIQUE The heter-ogeneity of AIS characteristics including thrombuscomposition occlusion location thrombus volumeburden and collateral perfusion may demand tai-
Table 2 Possible selection criteria for acute ischemic stroke endovascularrevascularization therapy
Inclusion criteria for ERT
Neurologic deficit attributable to a medium- to large-vessel occlusion
IA chemical thrombolysis can be initiated within 6 h of symptom onset
Mechanical thrombectomy treatment can be initiated within window of 8 h from time of onsetfor anterior circulation strokes
ERT can be initiated within window of 12 h from time of onset for posterior circulationstrokes
Treatment beyond 6ndash8 h may be guided by advanced imaging results (DWI MRI PWI CTP)when available
Potentially disabling neurologic deficit
Persistent or worsening neurological deficits following IV rtPA administration
Exclusion criteria for ERT
Arterial stenosis precluding safe access
Suspicion of aortic dissection
Uncontrolled hypertension defined as systolic blood pressure 185 mm Hg or diastolicblood pressure 110 mm Hg that cannot be reasonably treated with antihypertensivemedication
Platelet count 30000
Use of warfarin anticoagulation with INR 30
Known bleeding diathesis
Deficits attributable to glucose 50 mgdL
Seizure at onset if residual deficits are due to a postictal state rather than ischemia
Imaging findings
Significant mass effect with midline shift
Intracranial hemorrhage (ICH SAH subdural or epidural hematoma)
Subacute infarct on head CTMRI that occupies 13 of the MCA territory or 100 cc ofbrain tissue
CNS lesion with high likelihood of hemorrhage should be excluded from IA pharmacologicthrombolysis (brain tumor abscess vascular malformation aneurysm contusion)
May consider IA thrombolysis in patients with small unruptured aneurysms or benigntumors with low vascularity
Relative contraindications for ERT therapy
Intracranial or spinal surgery head trauma or stroke in separate vascular territory within 3months
History of ICH
Terminal illness with short life expectancy or severe comorbid illness
Pregnancy
Risk vs benefit of clinical symptoms and ability to shield patient must be considered
Known subacute bacterial endocarditis with or without mycotic aneurysm and stroke
Special consideration may be needed for patients on dabigatran
Relative contraindications for adjunctive ERT following IV rtPA
Glucose 400 mgdL based on increased ICH risk
Ongoing hemodialysis or peritoneal dialysis due to possibly increased ICH risk
Abbreviations CTP CT perfusion DWI MRI diffusion-weighted MRI ERT endovascu-lar revascularization therapy IA intra-arterial ICH intracerebral hemorrhage INR
international normalized ratio MCA middle cerebral artery NIHSS NIH Stroke ScalertPA recombinant tissue plasminogen activator SAH subarachnoid hemorrhage
Neurology 79 (Suppl 1) September 25 2012 S247
lored interventions For example greater efficacy andsafety may be demonstrated in distal vessel revascu-larization by use of IA fibrinolytic therapy vs a me-chanical device that may be more difficult to deliverAlternatively in large proximal vessel occlusionsgreater benefit may be achieved with mechanicalthrombectomy Furthermore carotid occlusion atthe origin of the ICA may be better treated with bal-loon angioplasty and stent implantation
Pharmacologic thrombolysis Local IA thrombolysisefficacy was demonstrated in PROACT II6 This ledto an AHA Class I level of evidence B recommenda-tion that IA thrombolysis is an option for the treat-ment of selected patients who have AIS under 6hours duration due to occlusions of the MCA andwho are not otherwise candidates for IV rtPA1 Al-though variability in study designs prohibits direct com-parison of the data theoretically there may be a higherrisk of intracerebral hemorrhage (ICH) with chemicalIA thrombolysis than with mechanical revasculariza-tion However increased ICH was not substantiated ina multicenter study39
Microcatheter position during thrombolytic infu-sion may also theoretically affect recanalization ratesThe microcatheter position varies among the studiesin some instances it is placed distal to the thrombuswithin the thrombus or proximal to the thrombusSome operators will use multiple locations to infusertPA throughout the thrombus The maximum safedose for IA rtPA is not known however if we extrap-olate from large clinical trial experience then a max-
imum dose of 22 mg as in the IMS trials may be areasonable initial limit2140
Bridging therapies Bridging therapy trials evaluatingthe combined approach have shown better recanali-zation rates for medium- to large-vessel occlusionsHowever they have shown only trends toward betteroutcomes in comparison with the IV rtPAndashtreatedsubjects in the National Institute of NeurologicalDisorders and Stroke (NINDS) rtPA Stroke Study ora database registry4041 Potential benefit of bridgingtherapy increases when the target population is lim-ited to IV rtPA nonresponders (40 IV-IA patientsreached functional independence at 3 months vs149 of recipients of only IV rtPA among the non-responders [p 0012]) This benefit came at thecost of a higher morbidity associated with the bridg-ing therapy (OR 214 95 CI 058 ndash783 forsICH)42 The early Emergency Management ofStroke Bridging TrialIMS trials used a protocol of06 mgkg IV rtPA with up to an additional maxi-mum of 22 mg IA rtPA which in most patients al-lowed for the total dose to remain below the NINDSmaximum amount of 90 mg (table 3) Howevernewer bridging studies and the amended IMS III areusing full-dose IV rtPA in the combined IV-IA treat-ment arm2021
Mechanical revascularization Mechanical techniquesfor ERT including thrombectomy clot retrievaland thromboaspiration have shown comparable orslightly higher recanalization rates than IA thrombol-
Table 3 Intra-arterial thrombolytic dosing and methods from selected trials
Trial PROACT5 PROACT II6 MELT12 IMS I55 IMS II40 IMS III21
Agent ProUK ProUK UK rtPA rtPA rtPA
Max dose Two-tier dose6 mg and 12 mg
9 mg 600000 IU IV rtPA 06 mgkg 60mg maxIA rtPA 22 mg
IV rtPA 06 mgkg60 mg maxIA rtPA 22 mg
IV rtPA 06 mgkg 60 mgmaxpossibly IA rtPA 22 mg
Median dose mg 6 and 12 9 mdash mdash 12 mdash
Infusion duration h 2 2 2 2 2 2
Infusion location At proximal one-thirdof thrombus
At proximal one-thirdof thrombus
Distal tothrombus
2 mg distal to thrombusthen 2 mg intothrombus then infusion
At site of thrombuswith or withoutEkos ultrasoundcatheter
1 mg distal and 1 mgproximal then 20 mg overmaximum of 2 h
Mechanical disruption Prohibited Prohibited Only withguidewire
Only with guidewire ormicrocatheter
Only with guidewireor microcatheter
Merci device Ekos orpenumbra device with IArtPA infusion ormicrocatheter IA rtPAinfusion
Intraproceduralsystemic thrombo-prophylaxis
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 5000IU bolus
Heparin 2000 IU bolusand 450 IUh infusion
Heparin 2000 IUbolus and 450 IUhinfusion
Heparin 2000 IU bolus and450 IUh infusion until theend of the procedure
Adjunctiveantithrombotic agents
Prohibited in first24 h
Prohibited in first24 h
Prohibited infirst 24 h
Prohibited in first 24 h Prohibited in first24 h
Prohibited in first 24 h
Abbreviations IA intra-arterial IMS Interventional Management of Stroke trial IU international units MELT Middle cerebral artery Embolism LocalFibrinolytic intervention Trial PROACT Prolyse in Acute Cerebral Thromboembolism trial rtPA IV recombinant tissue plasminogen activator UK
urokinase
S248 Neurology 79 (Suppl 1) September 25 2012
ysis alone (table 1) Newer devices such as the Soli-taire FR retrievable stent (eV3 Irvine CA) haveshown even higher recanalization rates (84ndash90)2324 In appropriately selected patients me-chanical revascularization may theoretically have alower risk of hemorrhagic complications given theabsence or reduced need for a thrombolytic agent Inpatients who are considered for ERT after full-doseIV rtPA a mechanical approach might be favorableLimitations of mechanical revascularization includedevice failure deliverability to distal locations andembolization
Multimodal revascularization Given the heterogene-ity of vessel occlusion etiology in AIS a combinationof multiple techniques may afford the highest successfor revascularization Small series suggest that multi-modal therapies including IA thrombolysis and stentimplantation lead to higher recanalization rates39
Future studies may find mechanical thrombectomyto be more successful in proximal large-vessel occlu-sions whereas local IA thrombolysis would be pre-ferred in distal small-vessel occlusions Also stentimplantation may be most effective for in situ intra-cranial atherosclerosis with supervening thrombosisbut retrieval and aspiration techniques may be moreeffective for thromboemboli occlusive in relativelynormal recipient arteries4
Posterior circulation modality selection The besttreatment modality for patients with VBO remainspoorly defined A large prospective observationalregistry and a separate systematic analysis of pub-lished case series analyzed a total of 1012 patientsboth studies did not support unequivocal superiorityof IA therapy vs IV thrombolysis3243 However theheterogeneity of the data between the patients withinthe groups analyzed limits interpretation of the clini-cal conclusions Early recanalization is an importantprognostic factor for good clinical outcome as suchhigher and safer rates of recanalization are beingachieved with newer therapeutic strategies utilizingmechanical embolectomy devices retrievable stentsangioplasty with or without stenting use of glyco-protein IIbIIIa inhibitors and combinationsthereof2328304445
TARGET TIME INTERVALS AND TRIAGE ANDTRANSFER STRATEGIES Time to revasculariza-tion is an independent predictor of good outcome inpatients with AIS4647 Randomized trials of IV rtPAhave demonstrated the greatest benefit in subjectstreated within 90 minutes of symptom onset225 Re-canalization rates with ERT are higher than with IVrtPA alone although the delay to treatment may at-tenuate the benefit This illustrates the importance ofestablishing benchmark door-to-revascularization
Tab
le4
Tre
atm
ent
tim
esin
sele
cted
stud
ies
inm
inut
es
Tri
alP
RO
AC
T5
PR
OA
CT
II6
IMS
I55IM
SII
I21E
MS
56M
ELT
12R
EC
AN
ALI
SE
41P
enum
bra
PS
T11
Mul
tiM
ER
CI29
M
ER
CI10
Wol
feet
al50
Doc
rocq
etal
54C
osta
lat
etal
43M
iley
etal
53S
uare
zet
al51
Mat
tle
etal
49F
lahe
rty
etal
52
No
ofsu
bje
cts
40
12
16
25
00
35
56
50
12
53
05
96
13
50
91
54
57
44
Tre
atm
ent
IApr
oUK
orpl
aceb
oIA
proU
KIV
-IA
rtP
AIV
aor
IV
IAb
IV-I
Aa
orIA
rtP
Ab
IAU
KIV
-IA
orIV
-IA
Trt
PA
IAT
IV
rtP
AIA
TIV
-IA
aor
IArt
PA
bIA
UK
IV-R
Sor
RS
alon
eIV
-IA
Tor
IAT
IAU
KIA
TU
KIV
IA
rtP
A
Tim
e-to
-doo
r1
14
Tim
e-to
-CT
MR
Isc
anm
ean
(med
ian)
Ons
et1
05
Ons
et1
62
(14
5)
Doo
r5
9(3
4)
Imag
ing
-to-
GP
16
1(1
53
)8
1(6
5)
CT
scan
-to-
mic
roca
thet
er1
74
Tim
e-to
-ER
Tin
itia
tion
oran
gio
gra
mor
GP
SO
(33
0)
SO
(31
8)
SO
21
7(2
12
)
SO
12
37
25
52
IV-b
olus
toG
P8
74
SO
a(1
98
)Oslash
b(1
80
)Oslash
SO
22
7S
O1
32
SO
25
8pound
SO
(25
8)
SO
a1
51
b2
61
SO
32
4(3
30
)S
O3
21
Doo
r(1
30
)S
O2
44
SO
(22
6)
GP
-to-
max
TIM
IT
ICI
54
(48
)
SO
-to-
max
TIM
IT
ICI
a(3
78
)b(
34
2)
(22
0)
37
7(3
27
)
Abb
revi
atio
nsE
MS
E
mer
genc
yM
anag
emen
tof
Str
oke
ER
T
endo
vasc
ular
reva
scul
ariz
atio
ntr
eatm
ent
GP
gr
oin
punc
ture
IA
in
tra-
arte
rial
IA
T
intr
a-ar
teri
alth
erap
y(in
clud
esth
rom
boly
sis
and
mec
hani
cal
tech
niqu
es)
IMS
In
terv
enti
onal
Man
agem
ento
fStr
oke
tria
lM
ELT
M
iddl
ece
rebr
alar
tery
Em
bolis
mLo
calF
ibri
noly
tic
inte
rven
tion
Tria
lM
ER
CI
Mec
hani
calE
mbo
lus
Rem
oval
inC
ereb
ralI
sche
mia
PR
OA
CT
P
roly
sein
Acu
teC
ereb
ralT
hrom
boem
bolis
mtr
ial
PS
T
Piv
otal
Str
oke
Tria
lR
EC
AN
ALI
SE
R
Eca
nalis
atio
nus
ing
Com
bine
din
trav
enou
sA
ltep
lase
and
Neu
roin
terv
enti
onal
Alg
orit
hmfo
racu
teIs
chem
icS
trok
ER
S
retr
ieva
ble
sten
trt
PA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
O
sym
ptom
onse
tTI
CI
thro
mbo
lysi
sin
cere
bral
infa
rcti
onT
IMI
thro
mbo
lysi
sin
myo
card
iali
nfar
ctio
nU
K
urok
inas
e
Neurology 79 (Suppl 1) September 25 2012 S249
times The Brain Attack Coalition has recommendedthat IV rtPA be administered within 60 minutesfrom arrival to the emergency department (ED) foreligible patients48 The established time intervals tar-get a multidisciplinary goal Each component of theprocessmdashED physicians ancillary staff laboratoryand radiology services neurology team and radiol-ogy staffmdashis essential for the time goal As suchERT time intervals should integrate into the existingmodel beginning with patient arrival to the EDSeparate time intervals can be established for patientstransferred from another institution and patientswho receive adjunctive ERT following IV rtPA ther-apy Because vascular anatomy can add unpredictabledelays in procedural times the endpoint should re-flect the last modifiable variable Therefore ERTtime intervals should reflect door-to-puncture (morepredictable) puncture-to-clot and clot-to-closegoals A clot-to-close time of 120 minutes as de-scribed in IMS III may be warranted to establishprocedural termination times More variables in-cluding anatomy evidence of persistent penumbraand ERT method may be used in the future to mod-ify time benchmarks
In the limited case series discussing time intervalsto ERT there is variability in which interval is uti-lized (table 4)56111215414349 ndash56 Randomized trialsshow feasibility in achieving time intervals of approx-imately 4 to 5 hours from stroke onset to IA rtPAadministration655 In PROACT II median timefrom stroke onset to randomization and IA rtPA ad-ministration was 282 minutes whereas the IMSstudy demonstrated an interval of 231 minutes fromstroke onset to IA rtPA administration655 Timefrom CT scan to microcatheter placement in thecerebrovasculature had a mean time of 174 60minutes in 91 patients undergoing ERT for AISdemonstrating wide variability and a need for timestandards53 Transferred patients whose laboratorytests and CT scan have already been completed maystill have a door-to-puncture time of up to 60 min-utes57 Further study is needed to identify barriers torapid access to endovascular therapy
Currently the American College of Cardiologyand the AHA recommend that door-to-balloon timein ST segment elevation myocardial infarctionshould be within 90 minutes A similar future pro-posal could be made for ERT in AIS with a goaldoor-to-puncture time of 90 minutes (table 5) Thiswould include activation of the stroke team technol-ogists and nurses Adjunctive time benchmarks canbe developed including puncture-to-clot and clot-to-close goals This target is more difficult to achievefor cerebral than cardiac revascularization as strokepatients require more time-consuming neurologic
Tab
le5
Ben
chm
ark
tim
esfo
rre
vasc
ular
izat
ion
ther
apie
san
dp
ossi
ble
inte
rval
sfo
rE
RT
Am
eric
anC
olle
geof
Car
diol
ogy6
7A
SA
AH
AA
ISG
uide
lines
forI
Vrt
-PA
68
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rE
RT
pres
enti
ngto
ED
ldquoP
rim
ary
ER
TTi
merdquo
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rRes
cue
ER
Tfo
llow
ing
IVfa
ilure
ldquoIV
-Fai
lure
toR
escu
eE
RTrdquo
Pro
pose
dgo
als
forA
ISpa
tien
tstr
ansf
erre
dfr
omou
tsid
eho
spit
alfo
rER
TldquoD
rip-
and-
Shi
pto
ER
Trdquo
Doo
r-to
-bal
loon
tim
e9
0m
inD
oor-
to-n
eedl
eti
me
60
min
Doo
r-to
-gro
inpu
nctu
reti
me
90
min
Nee
dle
-to-
gro
inp
unct
ure
tim
e6
0m
inD
oora -t
o-G
roin
Pun
ctur
eti
me
60
min
ST
EM
Icon
firm
ed
card
iolo
gis
tno
tifi
ed
10
min
Doo
rto
ED
10
min
Doo
rto
ED
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
0m
in)
ER
Tte
amis
noti
fied
asso
onas
larg
eto
med
ium
vess
eloc
clus
ion
issu
spec
ted
(ie
N
IHS
Sh
yper
dens
eM
CA
onC
T)in
elig
ible
pati
ents
10
min
afte
rth
eel
igib
ility
CT
scan
and
befo
reIV
bolu
s
Tran
sfer
from
outs
ide
hosp
ital
init
iate
dan
gio
suit
eac
tiva
ted
team
acti
vate
d
Pri
orto
arri
val
ED
stab
ilize
sp
atie
nta
ctiv
ates
cath
lab
30
min
Str
oke
team
acti
vati
on1
5m
inS
trok
ean
dE
RT
team
sac
tiva
tion
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
5m
in)
Rec
eivi
ngho
spit
alar
riva
lR
apid
hist
ory
and
exam
rev
iew
ofre
ferr
ing
hosp
ital
film
s
15
min
Cat
hla
ban
din
terv
enti
onal
ist
read
y
60
min
CT
scan
init
iate
d2
5m
inC
Tsc
anin
itia
ted
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(2
5m
in)
Ang
iosu
ite
acti
vate
dte
amon
stan
dby
cons
ider
noni
nvas
ive
vasc
ular
imag
ing
25
min
afte
rth
eel
igib
ility
CT
scan
and
afte
rIV
bolu
sin
itia
tion
Anc
illar
ybr
ain
imag
ing
(ie
CT
perf
usio
n)3
5m
in
Fin
alch
eck
and
wri
tten
cons
ent
70
min
CT
scan
inte
rpre
ted
elig
ibili
tyas
sess
ed4
5m
inC
Tsc
anin
terp
rete
del
igib
ility
asse
ssed
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(4
5m
in)
Rep
eat
NIH
SS
obt
ain
wri
tten
cons
ent
repe
atC
Tif
clin
ical
wor
seni
ng
45
min
afte
rth
eC
Tsc
anan
d3
0m
inaf
ter
the
IVrt
PA
bolu
s
Fin
alch
eck
wri
tten
cons
ent
pati
ent
prep
ped
45
min
Cat
hete
riza
tion
and
PC
Indashb
allo
onin
flat
ion
90
min
IVrt
PA
infu
sion
60
min
Gro
inpu
nctu
re9
0m
inG
roin
punc
ture
60
min
bG
roin
punc
ture
60
min
Abb
revi
atio
nsA
HA
A
mer
ican
Hea
rtA
ssoc
iati
onA
IS
acut
eis
chem
icst
roke
ang
io
angi
ogra
mA
SA
A
mer
ican
Str
oke
Ass
ocia
tion
ED
em
erge
ncy
depa
rtm
ent
ER
T
endo
vasc
ular
reva
scul
ariz
atio
nth
erap
yIA
intr
a-ar
teri
alM
CA
m
iddl
ece
rebr
alar
tery
NIH
SS
N
IHS
trok
eS
cale
PC
Ipe
rcut
aneo
usco
rona
ryin
terv
enti
onr
tPA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
TEM
IS
Tse
gmen
tele
vati
onm
yoca
rdia
linf
arct
ion
aF
rom
tim
eof
arri
valt
oac
cept
ing
hosp
ital
door
b
Tim
ew
illne
edto
bead
just
edto
allo
wfo
rad
diti
onal
imag
ing
ifcl
inic
alex
amin
atio
nw
orse
nsor
sym
ptom
ssu
gges
the
mor
rhag
ictr
ansf
orm
atio
n
S250 Neurology 79 (Suppl 1) September 25 2012
evaluation and brain imaging before proceeding tothe angiography laboratory
Achieving a 90-minute door-to-puncture timewould likely require the neurointerventionalist toplay an integral part in the stroke team because thedecisions on treatment strategy may evolve as the pa-tient proceeds through the AIS protocol and IV rtPAevaluation pathway The ERT protocol should inte-grate into the IV rtPA pathway For interhospitaltransfers the completed imaging and laboratorystudies as well as additional lead time may reduce thetarget time interval to 60 minutes for door-to-puncture However significant delay in hospitaltransfer may warrant repeat neuroimaging when thepatient arrives at the recipient institution Bench-mark times will need to be established for IV nonre-sponders with special consideration for additionaldelay when clinical deterioration following IV rtPArequires a repeat brain imaging prior to ERT
Triage and transfer strategies The considerable de-cline in efficacy of revascularization therapies ataround 6 to 8 hours from symptom onset demandswell-organized triage and transfer strategies46 Emer-gency department reorganization has been an area offocus to improve early identification of stroke pa-tients Tracking door-to-thrombolysis times posi-tioning a CTMRI scanner within the departmentand having emergency medical services (EMS) send aprehospital notification are steps that have improvedthrombolysis access58 However given the limitedavailability of Comprehensive Stroke Center infra-structure few centers in a given geographic regionwill have capabilities for providing comprehensivestroke care and 247 ERT This will lead to a highproportion of patients eligible for ERT arriving byinterhospital transfer Transfer delay has been shownto be a major factor limiting the use of ERT in strokepatients accounting for an estimated odds of treat-ment decrease by 25 for every minute of transfertime59 To avoid transfer delay regional protocols fortriage of AIS patients by EMS personnel to desig-nated stroke centers has become a focus of prehospi-tal stroke triage policy60
Alternative strategies include initiation of IVthrombolytic in a referring hospital prior to transferldquodrip-and-shiprdquo followed by further management atthe accepting hospital which may include ERT Adescribed model of ldquodrip ship and retrieverdquo usedfull-dose IV rtPA (09 mgkg) followed by ERT withmechanical thrombectomy and thrombo-aspirationsuggesting feasibility in basilar artery occlusion61
Different models may evolve where the patient re-ceives ERT in an outside hospital and is transferredfor further care at a comprehensive stroke centerwhere neurosurgery neurocritical care and vascular
neurology expertise are available known as ldquoretrieve-and-shiprdquo Pay-for-performance measures similar tothose for acute myocardial infarction could help fa-cilitate transfer of appropriate patients from primaryto comprehensive stroke centers (the hub-and-spokemodel)
GENERAL PREPROCEDURAL AND INTRAPROCE-DURAL MANAGEMENT Anesthesia and monitoringThe type of anesthesia for ERT has been a topic ofcontroversy with recent reports suggesting worseoutcome with use of general endotracheal anesthesiapossibly due to treatment delays and complicationsfrom intubation6263 Alternatively conscious seda-tion may pose a different set of risks related to patientcooperation especially in those with severe aphasiaor neglect which may negatively influence time torevascularization and procedural success Further-more ancillary monitoring requiring invasive arterialaccess for blood pressure monitoring and central IVaccess may also be of limited value and add delay toinitiation of therapy Further study is needed to eval-uate sedation methods for ERT Sedation methodsmay currently vary among centers
Thromboprophylaxis with systemic anticoagulationArterial catheterization carries a risk of thromboem-bolism often requiring systemic anticoagulationRandomized clinical trials of ERT report variableprotocols for thromboprophylaxis including bolusIV heparin infusion of 2000 to 5000 units atprocedure onset followed by continuous infusionsof approximately 500 units of IV heparin per hourfor the procedure duration621 Alternatively acti-vated clotting time (ACT) values can be obtainedwith heparin boluses to maintain an ACT at atherapeutic goal Limited data exist on the safetyof heparin anticoagulation during ERT proce-dures A subgroup analysis of the MERCI trialshowed no association with hemorrhage or 90-daymortality and heparin use64 A reasonable ACTrange may be 250 to 300 seconds during ERT
Renal prophylaxis Patients with AIS may also havechronic renal impairment which may worsen withcontrast administered during angiography Inter-ventions designed to prevent contrast-induced ne-phropathy have not been rigorously studiedReasonable prophylaxis strategies include hydra-tion with isotonic saline Recent data have notprovided strong support for the administration ofN-acetylcysteine65 The use of sodium bicarbonateinfusion may be reasonable for patients with renalinsufficiency but it can be limited by the largevolume and time to acquire the solution from thepharmacy Periprocedural renal prophylaxis for
Neurology 79 (Suppl 1) September 25 2012 S251
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
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References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
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ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
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reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
window to 45 hours in a subgroup of patients onthe basis of results of the European CooperativeAcute Stroke Study III (ECASS III)2527
Patients presenting after 45 hours are not eligiblefor systemic thrombolysis however data exist ascited previously for the consideration of IA fibrino-lytic administration up to 6 hours from symptomonset in patients with a large- to medium-vessel oc-clusion61228 For patients in whom endovasculartherapy can be initiated within 8 hours from symp-tom onset 2 mechanical revascularization devicefamilies have demonstrated safe and feasible rates ofrecanalization in single-arm prospective trials101129
The optimal device for mechanical revascularizationhas not been identified and the rapid growth of de-vice technology will likely continue to challenge rig-orous clinical evaluation
Vertebrobasilar artery occlusion (VBO) has an in-variably poor outcome if recanalization is notachieved early The recent literature shows that mor-tality with acute VBO treated with nonthrombolyticdrugs is 80 to 90 although lower rates of 42 to60 can be achieved with IA therapy283031 Successof recanalization and neurologic status before treat-ment are independent predictors of a favorable out-come after IA therapy3031 Multiple studies failed toestablish a time window that would definitively ex-
clude patients from IA therapy30 One study found asignificantly better clinical outcome in patients withacute VBO treated within 6 hours after symptomonset than in patients treated after 6 hours (favorableoutcome of 36 vs 7 mortality of 52 vs 70p 0005)28 Other studies demonstrated trends to-ward better outcome with shorter duration of symp-toms and no significant association between time totreatment and clinical outcome3031 When patients arein a coma or have had prolonged symptoms additionalimaging such as MRI with diffusion and perfusion orCT perfusion might help in identifying those who arelikely to benefit from intervention However the cur-rent application of CT perfusion results to the posteriorcirculation may be limited
The trials that shape the current decision patternshave been largely based on time from symptom on-set Data are lacking on the efficacy of ERT beyond12 hours from symptom onset in patients with poste-rior circulation occlusion and beyond 8 hours in an-terior circulation occlusion1011293132 Given the poornatural history of VBO revascularization has beenconsidered beyond 12 hours from symptom onsetEnthusiasm continues for a perfusion imagingndashbaseddecision algorithm although rigorous data to sup-port this approach are lacking33 Further study ofperfusion imaging may assist with selection of pa-
Figure Possible decision algorithm for revascularization therapies in acute ischemic stroke
S246 Neurology 79 (Suppl 1) September 25 2012
tients who would benefit from revascularization be-yond 8 hours34
At the very least noncontrast head CT ordiffusion- and susceptibility-weighted MRI are re-quired to exclude hemorrhage and identify early isch-
emic changes that could pose increased hemorrhagicrisk following revascularization Larger regions ofwell-defined hypoattenuation (CT) or hyperintensity(MRI) indicating infarcted tissue may carry a consid-erably higher risk of hemorrhage following revascu-larization Careful consideration may be needed forpatients with CT hypodensity or MRI hyperintensityin greater than 13 of the MCA territory or withprominent sulcal effacement35 Alternative standard-ized scoring systems may include the Alberta StrokeProgram Early CT Score (ASPECTS)36
Future studies may show that for patients whoreceive IV rtPA and have a clinical presentation sug-gestive of a large-vessel occlusion early considerationof ERT may be important The limited efficacy of IVrtPA in large vessel occlusions is demonstrated byrecanalization rates as low as 30 in the proximalMCA and 6 in the terminal internal carotid artery(ICA)37 Urgent noninvasive vascular imaging canidentify patients with a large-vessel occlusion Theinterval from a decision to pursue IA intervention toreaching the clot can be long with time required toobtain consent transport and prepare the patient andnegotiate tortuous anatomy Accordingly an efficientstrategy may be to activate the neurointerventional teamwhen a large-vessel occlusion is suspected without delayin IV rtPA initiation If dramatic clinical improvementoccurs patients can be rerouted to repeat noninvasivevessel assessment One retrospective study has shownthat in those patients with a contraindication to IV rtPAor whose IV therapy fails the use of ERT within thefirst 3 hours after stroke symptom onset has a low sICHrate of 5338
Patients with fluctuating deficits or continuedmild deficits (NIHSS score 4) following rapid im-provement from presentation carry a risk of harbor-ing a large-vessel occlusion with tenuous collateralsupply Failure of collateral supply could lead toacute deterioration therefore emergent noninvasiveangiography to identify vessel occlusions amenable toERT may be considered To date no randomizedclinical trial has compared the natural history ofmedical treatment alone to early recanalization withERT in this subset of patients
For patients in whom ERT is considered inclu-sion and exclusion criteria will be needed Based onthe existing clinical trials and guidelines a frame-work for the future development of criteria can beoutlined (table 2)
SELECTION OF ENDOVASCULAR REVASCU-LARIZATION THERAPY TECHNIQUE The heter-ogeneity of AIS characteristics including thrombuscomposition occlusion location thrombus volumeburden and collateral perfusion may demand tai-
Table 2 Possible selection criteria for acute ischemic stroke endovascularrevascularization therapy
Inclusion criteria for ERT
Neurologic deficit attributable to a medium- to large-vessel occlusion
IA chemical thrombolysis can be initiated within 6 h of symptom onset
Mechanical thrombectomy treatment can be initiated within window of 8 h from time of onsetfor anterior circulation strokes
ERT can be initiated within window of 12 h from time of onset for posterior circulationstrokes
Treatment beyond 6ndash8 h may be guided by advanced imaging results (DWI MRI PWI CTP)when available
Potentially disabling neurologic deficit
Persistent or worsening neurological deficits following IV rtPA administration
Exclusion criteria for ERT
Arterial stenosis precluding safe access
Suspicion of aortic dissection
Uncontrolled hypertension defined as systolic blood pressure 185 mm Hg or diastolicblood pressure 110 mm Hg that cannot be reasonably treated with antihypertensivemedication
Platelet count 30000
Use of warfarin anticoagulation with INR 30
Known bleeding diathesis
Deficits attributable to glucose 50 mgdL
Seizure at onset if residual deficits are due to a postictal state rather than ischemia
Imaging findings
Significant mass effect with midline shift
Intracranial hemorrhage (ICH SAH subdural or epidural hematoma)
Subacute infarct on head CTMRI that occupies 13 of the MCA territory or 100 cc ofbrain tissue
CNS lesion with high likelihood of hemorrhage should be excluded from IA pharmacologicthrombolysis (brain tumor abscess vascular malformation aneurysm contusion)
May consider IA thrombolysis in patients with small unruptured aneurysms or benigntumors with low vascularity
Relative contraindications for ERT therapy
Intracranial or spinal surgery head trauma or stroke in separate vascular territory within 3months
History of ICH
Terminal illness with short life expectancy or severe comorbid illness
Pregnancy
Risk vs benefit of clinical symptoms and ability to shield patient must be considered
Known subacute bacterial endocarditis with or without mycotic aneurysm and stroke
Special consideration may be needed for patients on dabigatran
Relative contraindications for adjunctive ERT following IV rtPA
Glucose 400 mgdL based on increased ICH risk
Ongoing hemodialysis or peritoneal dialysis due to possibly increased ICH risk
Abbreviations CTP CT perfusion DWI MRI diffusion-weighted MRI ERT endovascu-lar revascularization therapy IA intra-arterial ICH intracerebral hemorrhage INR
international normalized ratio MCA middle cerebral artery NIHSS NIH Stroke ScalertPA recombinant tissue plasminogen activator SAH subarachnoid hemorrhage
Neurology 79 (Suppl 1) September 25 2012 S247
lored interventions For example greater efficacy andsafety may be demonstrated in distal vessel revascu-larization by use of IA fibrinolytic therapy vs a me-chanical device that may be more difficult to deliverAlternatively in large proximal vessel occlusionsgreater benefit may be achieved with mechanicalthrombectomy Furthermore carotid occlusion atthe origin of the ICA may be better treated with bal-loon angioplasty and stent implantation
Pharmacologic thrombolysis Local IA thrombolysisefficacy was demonstrated in PROACT II6 This ledto an AHA Class I level of evidence B recommenda-tion that IA thrombolysis is an option for the treat-ment of selected patients who have AIS under 6hours duration due to occlusions of the MCA andwho are not otherwise candidates for IV rtPA1 Al-though variability in study designs prohibits direct com-parison of the data theoretically there may be a higherrisk of intracerebral hemorrhage (ICH) with chemicalIA thrombolysis than with mechanical revasculariza-tion However increased ICH was not substantiated ina multicenter study39
Microcatheter position during thrombolytic infu-sion may also theoretically affect recanalization ratesThe microcatheter position varies among the studiesin some instances it is placed distal to the thrombuswithin the thrombus or proximal to the thrombusSome operators will use multiple locations to infusertPA throughout the thrombus The maximum safedose for IA rtPA is not known however if we extrap-olate from large clinical trial experience then a max-
imum dose of 22 mg as in the IMS trials may be areasonable initial limit2140
Bridging therapies Bridging therapy trials evaluatingthe combined approach have shown better recanali-zation rates for medium- to large-vessel occlusionsHowever they have shown only trends toward betteroutcomes in comparison with the IV rtPAndashtreatedsubjects in the National Institute of NeurologicalDisorders and Stroke (NINDS) rtPA Stroke Study ora database registry4041 Potential benefit of bridgingtherapy increases when the target population is lim-ited to IV rtPA nonresponders (40 IV-IA patientsreached functional independence at 3 months vs149 of recipients of only IV rtPA among the non-responders [p 0012]) This benefit came at thecost of a higher morbidity associated with the bridg-ing therapy (OR 214 95 CI 058 ndash783 forsICH)42 The early Emergency Management ofStroke Bridging TrialIMS trials used a protocol of06 mgkg IV rtPA with up to an additional maxi-mum of 22 mg IA rtPA which in most patients al-lowed for the total dose to remain below the NINDSmaximum amount of 90 mg (table 3) Howevernewer bridging studies and the amended IMS III areusing full-dose IV rtPA in the combined IV-IA treat-ment arm2021
Mechanical revascularization Mechanical techniquesfor ERT including thrombectomy clot retrievaland thromboaspiration have shown comparable orslightly higher recanalization rates than IA thrombol-
Table 3 Intra-arterial thrombolytic dosing and methods from selected trials
Trial PROACT5 PROACT II6 MELT12 IMS I55 IMS II40 IMS III21
Agent ProUK ProUK UK rtPA rtPA rtPA
Max dose Two-tier dose6 mg and 12 mg
9 mg 600000 IU IV rtPA 06 mgkg 60mg maxIA rtPA 22 mg
IV rtPA 06 mgkg60 mg maxIA rtPA 22 mg
IV rtPA 06 mgkg 60 mgmaxpossibly IA rtPA 22 mg
Median dose mg 6 and 12 9 mdash mdash 12 mdash
Infusion duration h 2 2 2 2 2 2
Infusion location At proximal one-thirdof thrombus
At proximal one-thirdof thrombus
Distal tothrombus
2 mg distal to thrombusthen 2 mg intothrombus then infusion
At site of thrombuswith or withoutEkos ultrasoundcatheter
1 mg distal and 1 mgproximal then 20 mg overmaximum of 2 h
Mechanical disruption Prohibited Prohibited Only withguidewire
Only with guidewire ormicrocatheter
Only with guidewireor microcatheter
Merci device Ekos orpenumbra device with IArtPA infusion ormicrocatheter IA rtPAinfusion
Intraproceduralsystemic thrombo-prophylaxis
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 5000IU bolus
Heparin 2000 IU bolusand 450 IUh infusion
Heparin 2000 IUbolus and 450 IUhinfusion
Heparin 2000 IU bolus and450 IUh infusion until theend of the procedure
Adjunctiveantithrombotic agents
Prohibited in first24 h
Prohibited in first24 h
Prohibited infirst 24 h
Prohibited in first 24 h Prohibited in first24 h
Prohibited in first 24 h
Abbreviations IA intra-arterial IMS Interventional Management of Stroke trial IU international units MELT Middle cerebral artery Embolism LocalFibrinolytic intervention Trial PROACT Prolyse in Acute Cerebral Thromboembolism trial rtPA IV recombinant tissue plasminogen activator UK
urokinase
S248 Neurology 79 (Suppl 1) September 25 2012
ysis alone (table 1) Newer devices such as the Soli-taire FR retrievable stent (eV3 Irvine CA) haveshown even higher recanalization rates (84ndash90)2324 In appropriately selected patients me-chanical revascularization may theoretically have alower risk of hemorrhagic complications given theabsence or reduced need for a thrombolytic agent Inpatients who are considered for ERT after full-doseIV rtPA a mechanical approach might be favorableLimitations of mechanical revascularization includedevice failure deliverability to distal locations andembolization
Multimodal revascularization Given the heterogene-ity of vessel occlusion etiology in AIS a combinationof multiple techniques may afford the highest successfor revascularization Small series suggest that multi-modal therapies including IA thrombolysis and stentimplantation lead to higher recanalization rates39
Future studies may find mechanical thrombectomyto be more successful in proximal large-vessel occlu-sions whereas local IA thrombolysis would be pre-ferred in distal small-vessel occlusions Also stentimplantation may be most effective for in situ intra-cranial atherosclerosis with supervening thrombosisbut retrieval and aspiration techniques may be moreeffective for thromboemboli occlusive in relativelynormal recipient arteries4
Posterior circulation modality selection The besttreatment modality for patients with VBO remainspoorly defined A large prospective observationalregistry and a separate systematic analysis of pub-lished case series analyzed a total of 1012 patientsboth studies did not support unequivocal superiorityof IA therapy vs IV thrombolysis3243 However theheterogeneity of the data between the patients withinthe groups analyzed limits interpretation of the clini-cal conclusions Early recanalization is an importantprognostic factor for good clinical outcome as suchhigher and safer rates of recanalization are beingachieved with newer therapeutic strategies utilizingmechanical embolectomy devices retrievable stentsangioplasty with or without stenting use of glyco-protein IIbIIIa inhibitors and combinationsthereof2328304445
TARGET TIME INTERVALS AND TRIAGE ANDTRANSFER STRATEGIES Time to revasculariza-tion is an independent predictor of good outcome inpatients with AIS4647 Randomized trials of IV rtPAhave demonstrated the greatest benefit in subjectstreated within 90 minutes of symptom onset225 Re-canalization rates with ERT are higher than with IVrtPA alone although the delay to treatment may at-tenuate the benefit This illustrates the importance ofestablishing benchmark door-to-revascularization
Tab
le4
Tre
atm
ent
tim
esin
sele
cted
stud
ies
inm
inut
es
Tri
alP
RO
AC
T5
PR
OA
CT
II6
IMS
I55IM
SII
I21E
MS
56M
ELT
12R
EC
AN
ALI
SE
41P
enum
bra
PS
T11
Mul
tiM
ER
CI29
M
ER
CI10
Wol
feet
al50
Doc
rocq
etal
54C
osta
lat
etal
43M
iley
etal
53S
uare
zet
al51
Mat
tle
etal
49F
lahe
rty
etal
52
No
ofsu
bje
cts
40
12
16
25
00
35
56
50
12
53
05
96
13
50
91
54
57
44
Tre
atm
ent
IApr
oUK
orpl
aceb
oIA
proU
KIV
-IA
rtP
AIV
aor
IV
IAb
IV-I
Aa
orIA
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Ab
IAU
KIV
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UK
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Sor
RS
alon
eIV
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Tor
IAT
IAU
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TU
KIV
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A
Tim
e-to
-doo
r1
14
Tim
e-to
-CT
MR
Isc
anm
ean
(med
ian)
Ons
et1
05
Ons
et1
62
(14
5)
Doo
r5
9(3
4)
Imag
ing
-to-
GP
16
1(1
53
)8
1(6
5)
CT
scan
-to-
mic
roca
thet
er1
74
Tim
e-to
-ER
Tin
itia
tion
oran
gio
gra
mor
GP
SO
(33
0)
SO
(31
8)
SO
21
7(2
12
)
SO
12
37
25
52
IV-b
olus
toG
P8
74
SO
a(1
98
)Oslash
b(1
80
)Oslash
SO
22
7S
O1
32
SO
25
8pound
SO
(25
8)
SO
a1
51
b2
61
SO
32
4(3
30
)S
O3
21
Doo
r(1
30
)S
O2
44
SO
(22
6)
GP
-to-
max
TIM
IT
ICI
54
(48
)
SO
-to-
max
TIM
IT
ICI
a(3
78
)b(
34
2)
(22
0)
37
7(3
27
)
Abb
revi
atio
nsE
MS
E
mer
genc
yM
anag
emen
tof
Str
oke
ER
T
endo
vasc
ular
reva
scul
ariz
atio
ntr
eatm
ent
GP
gr
oin
punc
ture
IA
in
tra-
arte
rial
IA
T
intr
a-ar
teri
alth
erap
y(in
clud
esth
rom
boly
sis
and
mec
hani
cal
tech
niqu
es)
IMS
In
terv
enti
onal
Man
agem
ento
fStr
oke
tria
lM
ELT
M
iddl
ece
rebr
alar
tery
Em
bolis
mLo
calF
ibri
noly
tic
inte
rven
tion
Tria
lM
ER
CI
Mec
hani
calE
mbo
lus
Rem
oval
inC
ereb
ralI
sche
mia
PR
OA
CT
P
roly
sein
Acu
teC
ereb
ralT
hrom
boem
bolis
mtr
ial
PS
T
Piv
otal
Str
oke
Tria
lR
EC
AN
ALI
SE
R
Eca
nalis
atio
nus
ing
Com
bine
din
trav
enou
sA
ltep
lase
and
Neu
roin
terv
enti
onal
Alg
orit
hmfo
racu
teIs
chem
icS
trok
ER
S
retr
ieva
ble
sten
trt
PA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
O
sym
ptom
onse
tTI
CI
thro
mbo
lysi
sin
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bral
infa
rcti
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thro
mbo
lysi
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myo
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iali
nfar
ctio
nU
K
urok
inas
e
Neurology 79 (Suppl 1) September 25 2012 S249
times The Brain Attack Coalition has recommendedthat IV rtPA be administered within 60 minutesfrom arrival to the emergency department (ED) foreligible patients48 The established time intervals tar-get a multidisciplinary goal Each component of theprocessmdashED physicians ancillary staff laboratoryand radiology services neurology team and radiol-ogy staffmdashis essential for the time goal As suchERT time intervals should integrate into the existingmodel beginning with patient arrival to the EDSeparate time intervals can be established for patientstransferred from another institution and patientswho receive adjunctive ERT following IV rtPA ther-apy Because vascular anatomy can add unpredictabledelays in procedural times the endpoint should re-flect the last modifiable variable Therefore ERTtime intervals should reflect door-to-puncture (morepredictable) puncture-to-clot and clot-to-closegoals A clot-to-close time of 120 minutes as de-scribed in IMS III may be warranted to establishprocedural termination times More variables in-cluding anatomy evidence of persistent penumbraand ERT method may be used in the future to mod-ify time benchmarks
In the limited case series discussing time intervalsto ERT there is variability in which interval is uti-lized (table 4)56111215414349 ndash56 Randomized trialsshow feasibility in achieving time intervals of approx-imately 4 to 5 hours from stroke onset to IA rtPAadministration655 In PROACT II median timefrom stroke onset to randomization and IA rtPA ad-ministration was 282 minutes whereas the IMSstudy demonstrated an interval of 231 minutes fromstroke onset to IA rtPA administration655 Timefrom CT scan to microcatheter placement in thecerebrovasculature had a mean time of 174 60minutes in 91 patients undergoing ERT for AISdemonstrating wide variability and a need for timestandards53 Transferred patients whose laboratorytests and CT scan have already been completed maystill have a door-to-puncture time of up to 60 min-utes57 Further study is needed to identify barriers torapid access to endovascular therapy
Currently the American College of Cardiologyand the AHA recommend that door-to-balloon timein ST segment elevation myocardial infarctionshould be within 90 minutes A similar future pro-posal could be made for ERT in AIS with a goaldoor-to-puncture time of 90 minutes (table 5) Thiswould include activation of the stroke team technol-ogists and nurses Adjunctive time benchmarks canbe developed including puncture-to-clot and clot-to-close goals This target is more difficult to achievefor cerebral than cardiac revascularization as strokepatients require more time-consuming neurologic
Tab
le5
Ben
chm
ark
tim
esfo
rre
vasc
ular
izat
ion
ther
apie
san
dp
ossi
ble
inte
rval
sfo
rE
RT
Am
eric
anC
olle
geof
Car
diol
ogy6
7A
SA
AH
AA
ISG
uide
lines
forI
Vrt
-PA
68
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rE
RT
pres
enti
ngto
ED
ldquoP
rim
ary
ER
TTi
merdquo
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rRes
cue
ER
Tfo
llow
ing
IVfa
ilure
ldquoIV
-Fai
lure
toR
escu
eE
RTrdquo
Pro
pose
dgo
als
forA
ISpa
tien
tstr
ansf
erre
dfr
omou
tsid
eho
spit
alfo
rER
TldquoD
rip-
and-
Shi
pto
ER
Trdquo
Doo
r-to
-bal
loon
tim
e9
0m
inD
oor-
to-n
eedl
eti
me
60
min
Doo
r-to
-gro
inpu
nctu
reti
me
90
min
Nee
dle
-to-
gro
inp
unct
ure
tim
e6
0m
inD
oora -t
o-G
roin
Pun
ctur
eti
me
60
min
ST
EM
Icon
firm
ed
card
iolo
gis
tno
tifi
ed
10
min
Doo
rto
ED
10
min
Doo
rto
ED
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
0m
in)
ER
Tte
amis
noti
fied
asso
onas
larg
eto
med
ium
vess
eloc
clus
ion
issu
spec
ted
(ie
N
IHS
Sh
yper
dens
eM
CA
onC
T)in
elig
ible
pati
ents
10
min
afte
rth
eel
igib
ility
CT
scan
and
befo
reIV
bolu
s
Tran
sfer
from
outs
ide
hosp
ital
init
iate
dan
gio
suit
eac
tiva
ted
team
acti
vate
d
Pri
orto
arri
val
ED
stab
ilize
sp
atie
nta
ctiv
ates
cath
lab
30
min
Str
oke
team
acti
vati
on1
5m
inS
trok
ean
dE
RT
team
sac
tiva
tion
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
5m
in)
Rec
eivi
ngho
spit
alar
riva
lR
apid
hist
ory
and
exam
rev
iew
ofre
ferr
ing
hosp
ital
film
s
15
min
Cat
hla
ban
din
terv
enti
onal
ist
read
y
60
min
CT
scan
init
iate
d2
5m
inC
Tsc
anin
itia
ted
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(2
5m
in)
Ang
iosu
ite
acti
vate
dte
amon
stan
dby
cons
ider
noni
nvas
ive
vasc
ular
imag
ing
25
min
afte
rth
eel
igib
ility
CT
scan
and
afte
rIV
bolu
sin
itia
tion
Anc
illar
ybr
ain
imag
ing
(ie
CT
perf
usio
n)3
5m
in
Fin
alch
eck
and
wri
tten
cons
ent
70
min
CT
scan
inte
rpre
ted
elig
ibili
tyas
sess
ed4
5m
inC
Tsc
anin
terp
rete
del
igib
ility
asse
ssed
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(4
5m
in)
Rep
eat
NIH
SS
obt
ain
wri
tten
cons
ent
repe
atC
Tif
clin
ical
wor
seni
ng
45
min
afte
rth
eC
Tsc
anan
d3
0m
inaf
ter
the
IVrt
PA
bolu
s
Fin
alch
eck
wri
tten
cons
ent
pati
ent
prep
ped
45
min
Cat
hete
riza
tion
and
PC
Indashb
allo
onin
flat
ion
90
min
IVrt
PA
infu
sion
60
min
Gro
inpu
nctu
re9
0m
inG
roin
punc
ture
60
min
bG
roin
punc
ture
60
min
Abb
revi
atio
nsA
HA
A
mer
ican
Hea
rtA
ssoc
iati
onA
IS
acut
eis
chem
icst
roke
ang
io
angi
ogra
mA
SA
A
mer
ican
Str
oke
Ass
ocia
tion
ED
em
erge
ncy
depa
rtm
ent
ER
T
endo
vasc
ular
reva
scul
ariz
atio
nth
erap
yIA
intr
a-ar
teri
alM
CA
m
iddl
ece
rebr
alar
tery
NIH
SS
N
IHS
trok
eS
cale
PC
Ipe
rcut
aneo
usco
rona
ryin
terv
enti
onr
tPA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
TEM
IS
Tse
gmen
tele
vati
onm
yoca
rdia
linf
arct
ion
aF
rom
tim
eof
arri
valt
oac
cept
ing
hosp
ital
door
b
Tim
ew
illne
edto
bead
just
edto
allo
wfo
rad
diti
onal
imag
ing
ifcl
inic
alex
amin
atio
nw
orse
nsor
sym
ptom
ssu
gges
the
mor
rhag
ictr
ansf
orm
atio
n
S250 Neurology 79 (Suppl 1) September 25 2012
evaluation and brain imaging before proceeding tothe angiography laboratory
Achieving a 90-minute door-to-puncture timewould likely require the neurointerventionalist toplay an integral part in the stroke team because thedecisions on treatment strategy may evolve as the pa-tient proceeds through the AIS protocol and IV rtPAevaluation pathway The ERT protocol should inte-grate into the IV rtPA pathway For interhospitaltransfers the completed imaging and laboratorystudies as well as additional lead time may reduce thetarget time interval to 60 minutes for door-to-puncture However significant delay in hospitaltransfer may warrant repeat neuroimaging when thepatient arrives at the recipient institution Bench-mark times will need to be established for IV nonre-sponders with special consideration for additionaldelay when clinical deterioration following IV rtPArequires a repeat brain imaging prior to ERT
Triage and transfer strategies The considerable de-cline in efficacy of revascularization therapies ataround 6 to 8 hours from symptom onset demandswell-organized triage and transfer strategies46 Emer-gency department reorganization has been an area offocus to improve early identification of stroke pa-tients Tracking door-to-thrombolysis times posi-tioning a CTMRI scanner within the departmentand having emergency medical services (EMS) send aprehospital notification are steps that have improvedthrombolysis access58 However given the limitedavailability of Comprehensive Stroke Center infra-structure few centers in a given geographic regionwill have capabilities for providing comprehensivestroke care and 247 ERT This will lead to a highproportion of patients eligible for ERT arriving byinterhospital transfer Transfer delay has been shownto be a major factor limiting the use of ERT in strokepatients accounting for an estimated odds of treat-ment decrease by 25 for every minute of transfertime59 To avoid transfer delay regional protocols fortriage of AIS patients by EMS personnel to desig-nated stroke centers has become a focus of prehospi-tal stroke triage policy60
Alternative strategies include initiation of IVthrombolytic in a referring hospital prior to transferldquodrip-and-shiprdquo followed by further management atthe accepting hospital which may include ERT Adescribed model of ldquodrip ship and retrieverdquo usedfull-dose IV rtPA (09 mgkg) followed by ERT withmechanical thrombectomy and thrombo-aspirationsuggesting feasibility in basilar artery occlusion61
Different models may evolve where the patient re-ceives ERT in an outside hospital and is transferredfor further care at a comprehensive stroke centerwhere neurosurgery neurocritical care and vascular
neurology expertise are available known as ldquoretrieve-and-shiprdquo Pay-for-performance measures similar tothose for acute myocardial infarction could help fa-cilitate transfer of appropriate patients from primaryto comprehensive stroke centers (the hub-and-spokemodel)
GENERAL PREPROCEDURAL AND INTRAPROCE-DURAL MANAGEMENT Anesthesia and monitoringThe type of anesthesia for ERT has been a topic ofcontroversy with recent reports suggesting worseoutcome with use of general endotracheal anesthesiapossibly due to treatment delays and complicationsfrom intubation6263 Alternatively conscious seda-tion may pose a different set of risks related to patientcooperation especially in those with severe aphasiaor neglect which may negatively influence time torevascularization and procedural success Further-more ancillary monitoring requiring invasive arterialaccess for blood pressure monitoring and central IVaccess may also be of limited value and add delay toinitiation of therapy Further study is needed to eval-uate sedation methods for ERT Sedation methodsmay currently vary among centers
Thromboprophylaxis with systemic anticoagulationArterial catheterization carries a risk of thromboem-bolism often requiring systemic anticoagulationRandomized clinical trials of ERT report variableprotocols for thromboprophylaxis including bolusIV heparin infusion of 2000 to 5000 units atprocedure onset followed by continuous infusionsof approximately 500 units of IV heparin per hourfor the procedure duration621 Alternatively acti-vated clotting time (ACT) values can be obtainedwith heparin boluses to maintain an ACT at atherapeutic goal Limited data exist on the safetyof heparin anticoagulation during ERT proce-dures A subgroup analysis of the MERCI trialshowed no association with hemorrhage or 90-daymortality and heparin use64 A reasonable ACTrange may be 250 to 300 seconds during ERT
Renal prophylaxis Patients with AIS may also havechronic renal impairment which may worsen withcontrast administered during angiography Inter-ventions designed to prevent contrast-induced ne-phropathy have not been rigorously studiedReasonable prophylaxis strategies include hydra-tion with isotonic saline Recent data have notprovided strong support for the administration ofN-acetylcysteine65 The use of sodium bicarbonateinfusion may be reasonable for patients with renalinsufficiency but it can be limited by the largevolume and time to acquire the solution from thepharmacy Periprocedural renal prophylaxis for
Neurology 79 (Suppl 1) September 25 2012 S251
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
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References
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reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
tients who would benefit from revascularization be-yond 8 hours34
At the very least noncontrast head CT ordiffusion- and susceptibility-weighted MRI are re-quired to exclude hemorrhage and identify early isch-
emic changes that could pose increased hemorrhagicrisk following revascularization Larger regions ofwell-defined hypoattenuation (CT) or hyperintensity(MRI) indicating infarcted tissue may carry a consid-erably higher risk of hemorrhage following revascu-larization Careful consideration may be needed forpatients with CT hypodensity or MRI hyperintensityin greater than 13 of the MCA territory or withprominent sulcal effacement35 Alternative standard-ized scoring systems may include the Alberta StrokeProgram Early CT Score (ASPECTS)36
Future studies may show that for patients whoreceive IV rtPA and have a clinical presentation sug-gestive of a large-vessel occlusion early considerationof ERT may be important The limited efficacy of IVrtPA in large vessel occlusions is demonstrated byrecanalization rates as low as 30 in the proximalMCA and 6 in the terminal internal carotid artery(ICA)37 Urgent noninvasive vascular imaging canidentify patients with a large-vessel occlusion Theinterval from a decision to pursue IA intervention toreaching the clot can be long with time required toobtain consent transport and prepare the patient andnegotiate tortuous anatomy Accordingly an efficientstrategy may be to activate the neurointerventional teamwhen a large-vessel occlusion is suspected without delayin IV rtPA initiation If dramatic clinical improvementoccurs patients can be rerouted to repeat noninvasivevessel assessment One retrospective study has shownthat in those patients with a contraindication to IV rtPAor whose IV therapy fails the use of ERT within thefirst 3 hours after stroke symptom onset has a low sICHrate of 5338
Patients with fluctuating deficits or continuedmild deficits (NIHSS score 4) following rapid im-provement from presentation carry a risk of harbor-ing a large-vessel occlusion with tenuous collateralsupply Failure of collateral supply could lead toacute deterioration therefore emergent noninvasiveangiography to identify vessel occlusions amenable toERT may be considered To date no randomizedclinical trial has compared the natural history ofmedical treatment alone to early recanalization withERT in this subset of patients
For patients in whom ERT is considered inclu-sion and exclusion criteria will be needed Based onthe existing clinical trials and guidelines a frame-work for the future development of criteria can beoutlined (table 2)
SELECTION OF ENDOVASCULAR REVASCU-LARIZATION THERAPY TECHNIQUE The heter-ogeneity of AIS characteristics including thrombuscomposition occlusion location thrombus volumeburden and collateral perfusion may demand tai-
Table 2 Possible selection criteria for acute ischemic stroke endovascularrevascularization therapy
Inclusion criteria for ERT
Neurologic deficit attributable to a medium- to large-vessel occlusion
IA chemical thrombolysis can be initiated within 6 h of symptom onset
Mechanical thrombectomy treatment can be initiated within window of 8 h from time of onsetfor anterior circulation strokes
ERT can be initiated within window of 12 h from time of onset for posterior circulationstrokes
Treatment beyond 6ndash8 h may be guided by advanced imaging results (DWI MRI PWI CTP)when available
Potentially disabling neurologic deficit
Persistent or worsening neurological deficits following IV rtPA administration
Exclusion criteria for ERT
Arterial stenosis precluding safe access
Suspicion of aortic dissection
Uncontrolled hypertension defined as systolic blood pressure 185 mm Hg or diastolicblood pressure 110 mm Hg that cannot be reasonably treated with antihypertensivemedication
Platelet count 30000
Use of warfarin anticoagulation with INR 30
Known bleeding diathesis
Deficits attributable to glucose 50 mgdL
Seizure at onset if residual deficits are due to a postictal state rather than ischemia
Imaging findings
Significant mass effect with midline shift
Intracranial hemorrhage (ICH SAH subdural or epidural hematoma)
Subacute infarct on head CTMRI that occupies 13 of the MCA territory or 100 cc ofbrain tissue
CNS lesion with high likelihood of hemorrhage should be excluded from IA pharmacologicthrombolysis (brain tumor abscess vascular malformation aneurysm contusion)
May consider IA thrombolysis in patients with small unruptured aneurysms or benigntumors with low vascularity
Relative contraindications for ERT therapy
Intracranial or spinal surgery head trauma or stroke in separate vascular territory within 3months
History of ICH
Terminal illness with short life expectancy or severe comorbid illness
Pregnancy
Risk vs benefit of clinical symptoms and ability to shield patient must be considered
Known subacute bacterial endocarditis with or without mycotic aneurysm and stroke
Special consideration may be needed for patients on dabigatran
Relative contraindications for adjunctive ERT following IV rtPA
Glucose 400 mgdL based on increased ICH risk
Ongoing hemodialysis or peritoneal dialysis due to possibly increased ICH risk
Abbreviations CTP CT perfusion DWI MRI diffusion-weighted MRI ERT endovascu-lar revascularization therapy IA intra-arterial ICH intracerebral hemorrhage INR
international normalized ratio MCA middle cerebral artery NIHSS NIH Stroke ScalertPA recombinant tissue plasminogen activator SAH subarachnoid hemorrhage
Neurology 79 (Suppl 1) September 25 2012 S247
lored interventions For example greater efficacy andsafety may be demonstrated in distal vessel revascu-larization by use of IA fibrinolytic therapy vs a me-chanical device that may be more difficult to deliverAlternatively in large proximal vessel occlusionsgreater benefit may be achieved with mechanicalthrombectomy Furthermore carotid occlusion atthe origin of the ICA may be better treated with bal-loon angioplasty and stent implantation
Pharmacologic thrombolysis Local IA thrombolysisefficacy was demonstrated in PROACT II6 This ledto an AHA Class I level of evidence B recommenda-tion that IA thrombolysis is an option for the treat-ment of selected patients who have AIS under 6hours duration due to occlusions of the MCA andwho are not otherwise candidates for IV rtPA1 Al-though variability in study designs prohibits direct com-parison of the data theoretically there may be a higherrisk of intracerebral hemorrhage (ICH) with chemicalIA thrombolysis than with mechanical revasculariza-tion However increased ICH was not substantiated ina multicenter study39
Microcatheter position during thrombolytic infu-sion may also theoretically affect recanalization ratesThe microcatheter position varies among the studiesin some instances it is placed distal to the thrombuswithin the thrombus or proximal to the thrombusSome operators will use multiple locations to infusertPA throughout the thrombus The maximum safedose for IA rtPA is not known however if we extrap-olate from large clinical trial experience then a max-
imum dose of 22 mg as in the IMS trials may be areasonable initial limit2140
Bridging therapies Bridging therapy trials evaluatingthe combined approach have shown better recanali-zation rates for medium- to large-vessel occlusionsHowever they have shown only trends toward betteroutcomes in comparison with the IV rtPAndashtreatedsubjects in the National Institute of NeurologicalDisorders and Stroke (NINDS) rtPA Stroke Study ora database registry4041 Potential benefit of bridgingtherapy increases when the target population is lim-ited to IV rtPA nonresponders (40 IV-IA patientsreached functional independence at 3 months vs149 of recipients of only IV rtPA among the non-responders [p 0012]) This benefit came at thecost of a higher morbidity associated with the bridg-ing therapy (OR 214 95 CI 058 ndash783 forsICH)42 The early Emergency Management ofStroke Bridging TrialIMS trials used a protocol of06 mgkg IV rtPA with up to an additional maxi-mum of 22 mg IA rtPA which in most patients al-lowed for the total dose to remain below the NINDSmaximum amount of 90 mg (table 3) Howevernewer bridging studies and the amended IMS III areusing full-dose IV rtPA in the combined IV-IA treat-ment arm2021
Mechanical revascularization Mechanical techniquesfor ERT including thrombectomy clot retrievaland thromboaspiration have shown comparable orslightly higher recanalization rates than IA thrombol-
Table 3 Intra-arterial thrombolytic dosing and methods from selected trials
Trial PROACT5 PROACT II6 MELT12 IMS I55 IMS II40 IMS III21
Agent ProUK ProUK UK rtPA rtPA rtPA
Max dose Two-tier dose6 mg and 12 mg
9 mg 600000 IU IV rtPA 06 mgkg 60mg maxIA rtPA 22 mg
IV rtPA 06 mgkg60 mg maxIA rtPA 22 mg
IV rtPA 06 mgkg 60 mgmaxpossibly IA rtPA 22 mg
Median dose mg 6 and 12 9 mdash mdash 12 mdash
Infusion duration h 2 2 2 2 2 2
Infusion location At proximal one-thirdof thrombus
At proximal one-thirdof thrombus
Distal tothrombus
2 mg distal to thrombusthen 2 mg intothrombus then infusion
At site of thrombuswith or withoutEkos ultrasoundcatheter
1 mg distal and 1 mgproximal then 20 mg overmaximum of 2 h
Mechanical disruption Prohibited Prohibited Only withguidewire
Only with guidewire ormicrocatheter
Only with guidewireor microcatheter
Merci device Ekos orpenumbra device with IArtPA infusion ormicrocatheter IA rtPAinfusion
Intraproceduralsystemic thrombo-prophylaxis
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 5000IU bolus
Heparin 2000 IU bolusand 450 IUh infusion
Heparin 2000 IUbolus and 450 IUhinfusion
Heparin 2000 IU bolus and450 IUh infusion until theend of the procedure
Adjunctiveantithrombotic agents
Prohibited in first24 h
Prohibited in first24 h
Prohibited infirst 24 h
Prohibited in first 24 h Prohibited in first24 h
Prohibited in first 24 h
Abbreviations IA intra-arterial IMS Interventional Management of Stroke trial IU international units MELT Middle cerebral artery Embolism LocalFibrinolytic intervention Trial PROACT Prolyse in Acute Cerebral Thromboembolism trial rtPA IV recombinant tissue plasminogen activator UK
urokinase
S248 Neurology 79 (Suppl 1) September 25 2012
ysis alone (table 1) Newer devices such as the Soli-taire FR retrievable stent (eV3 Irvine CA) haveshown even higher recanalization rates (84ndash90)2324 In appropriately selected patients me-chanical revascularization may theoretically have alower risk of hemorrhagic complications given theabsence or reduced need for a thrombolytic agent Inpatients who are considered for ERT after full-doseIV rtPA a mechanical approach might be favorableLimitations of mechanical revascularization includedevice failure deliverability to distal locations andembolization
Multimodal revascularization Given the heterogene-ity of vessel occlusion etiology in AIS a combinationof multiple techniques may afford the highest successfor revascularization Small series suggest that multi-modal therapies including IA thrombolysis and stentimplantation lead to higher recanalization rates39
Future studies may find mechanical thrombectomyto be more successful in proximal large-vessel occlu-sions whereas local IA thrombolysis would be pre-ferred in distal small-vessel occlusions Also stentimplantation may be most effective for in situ intra-cranial atherosclerosis with supervening thrombosisbut retrieval and aspiration techniques may be moreeffective for thromboemboli occlusive in relativelynormal recipient arteries4
Posterior circulation modality selection The besttreatment modality for patients with VBO remainspoorly defined A large prospective observationalregistry and a separate systematic analysis of pub-lished case series analyzed a total of 1012 patientsboth studies did not support unequivocal superiorityof IA therapy vs IV thrombolysis3243 However theheterogeneity of the data between the patients withinthe groups analyzed limits interpretation of the clini-cal conclusions Early recanalization is an importantprognostic factor for good clinical outcome as suchhigher and safer rates of recanalization are beingachieved with newer therapeutic strategies utilizingmechanical embolectomy devices retrievable stentsangioplasty with or without stenting use of glyco-protein IIbIIIa inhibitors and combinationsthereof2328304445
TARGET TIME INTERVALS AND TRIAGE ANDTRANSFER STRATEGIES Time to revasculariza-tion is an independent predictor of good outcome inpatients with AIS4647 Randomized trials of IV rtPAhave demonstrated the greatest benefit in subjectstreated within 90 minutes of symptom onset225 Re-canalization rates with ERT are higher than with IVrtPA alone although the delay to treatment may at-tenuate the benefit This illustrates the importance ofestablishing benchmark door-to-revascularization
Tab
le4
Tre
atm
ent
tim
esin
sele
cted
stud
ies
inm
inut
es
Tri
alP
RO
AC
T5
PR
OA
CT
II6
IMS
I55IM
SII
I21E
MS
56M
ELT
12R
EC
AN
ALI
SE
41P
enum
bra
PS
T11
Mul
tiM
ER
CI29
M
ER
CI10
Wol
feet
al50
Doc
rocq
etal
54C
osta
lat
etal
43M
iley
etal
53S
uare
zet
al51
Mat
tle
etal
49F
lahe
rty
etal
52
No
ofsu
bje
cts
40
12
16
25
00
35
56
50
12
53
05
96
13
50
91
54
57
44
Tre
atm
ent
IApr
oUK
orpl
aceb
oIA
proU
KIV
-IA
rtP
AIV
aor
IV
IAb
IV-I
Aa
orIA
rtP
Ab
IAU
KIV
-IA
orIV
-IA
Trt
PA
IAT
IV
rtP
AIA
TIV
-IA
aor
IArt
PA
bIA
UK
IV-R
Sor
RS
alon
eIV
-IA
Tor
IAT
IAU
KIA
TU
KIV
IA
rtP
A
Tim
e-to
-doo
r1
14
Tim
e-to
-CT
MR
Isc
anm
ean
(med
ian)
Ons
et1
05
Ons
et1
62
(14
5)
Doo
r5
9(3
4)
Imag
ing
-to-
GP
16
1(1
53
)8
1(6
5)
CT
scan
-to-
mic
roca
thet
er1
74
Tim
e-to
-ER
Tin
itia
tion
oran
gio
gra
mor
GP
SO
(33
0)
SO
(31
8)
SO
21
7(2
12
)
SO
12
37
25
52
IV-b
olus
toG
P8
74
SO
a(1
98
)Oslash
b(1
80
)Oslash
SO
22
7S
O1
32
SO
25
8pound
SO
(25
8)
SO
a1
51
b2
61
SO
32
4(3
30
)S
O3
21
Doo
r(1
30
)S
O2
44
SO
(22
6)
GP
-to-
max
TIM
IT
ICI
54
(48
)
SO
-to-
max
TIM
IT
ICI
a(3
78
)b(
34
2)
(22
0)
37
7(3
27
)
Abb
revi
atio
nsE
MS
E
mer
genc
yM
anag
emen
tof
Str
oke
ER
T
endo
vasc
ular
reva
scul
ariz
atio
ntr
eatm
ent
GP
gr
oin
punc
ture
IA
in
tra-
arte
rial
IA
T
intr
a-ar
teri
alth
erap
y(in
clud
esth
rom
boly
sis
and
mec
hani
cal
tech
niqu
es)
IMS
In
terv
enti
onal
Man
agem
ento
fStr
oke
tria
lM
ELT
M
iddl
ece
rebr
alar
tery
Em
bolis
mLo
calF
ibri
noly
tic
inte
rven
tion
Tria
lM
ER
CI
Mec
hani
calE
mbo
lus
Rem
oval
inC
ereb
ralI
sche
mia
PR
OA
CT
P
roly
sein
Acu
teC
ereb
ralT
hrom
boem
bolis
mtr
ial
PS
T
Piv
otal
Str
oke
Tria
lR
EC
AN
ALI
SE
R
Eca
nalis
atio
nus
ing
Com
bine
din
trav
enou
sA
ltep
lase
and
Neu
roin
terv
enti
onal
Alg
orit
hmfo
racu
teIs
chem
icS
trok
ER
S
retr
ieva
ble
sten
trt
PA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
O
sym
ptom
onse
tTI
CI
thro
mbo
lysi
sin
cere
bral
infa
rcti
onT
IMI
thro
mbo
lysi
sin
myo
card
iali
nfar
ctio
nU
K
urok
inas
e
Neurology 79 (Suppl 1) September 25 2012 S249
times The Brain Attack Coalition has recommendedthat IV rtPA be administered within 60 minutesfrom arrival to the emergency department (ED) foreligible patients48 The established time intervals tar-get a multidisciplinary goal Each component of theprocessmdashED physicians ancillary staff laboratoryand radiology services neurology team and radiol-ogy staffmdashis essential for the time goal As suchERT time intervals should integrate into the existingmodel beginning with patient arrival to the EDSeparate time intervals can be established for patientstransferred from another institution and patientswho receive adjunctive ERT following IV rtPA ther-apy Because vascular anatomy can add unpredictabledelays in procedural times the endpoint should re-flect the last modifiable variable Therefore ERTtime intervals should reflect door-to-puncture (morepredictable) puncture-to-clot and clot-to-closegoals A clot-to-close time of 120 minutes as de-scribed in IMS III may be warranted to establishprocedural termination times More variables in-cluding anatomy evidence of persistent penumbraand ERT method may be used in the future to mod-ify time benchmarks
In the limited case series discussing time intervalsto ERT there is variability in which interval is uti-lized (table 4)56111215414349 ndash56 Randomized trialsshow feasibility in achieving time intervals of approx-imately 4 to 5 hours from stroke onset to IA rtPAadministration655 In PROACT II median timefrom stroke onset to randomization and IA rtPA ad-ministration was 282 minutes whereas the IMSstudy demonstrated an interval of 231 minutes fromstroke onset to IA rtPA administration655 Timefrom CT scan to microcatheter placement in thecerebrovasculature had a mean time of 174 60minutes in 91 patients undergoing ERT for AISdemonstrating wide variability and a need for timestandards53 Transferred patients whose laboratorytests and CT scan have already been completed maystill have a door-to-puncture time of up to 60 min-utes57 Further study is needed to identify barriers torapid access to endovascular therapy
Currently the American College of Cardiologyand the AHA recommend that door-to-balloon timein ST segment elevation myocardial infarctionshould be within 90 minutes A similar future pro-posal could be made for ERT in AIS with a goaldoor-to-puncture time of 90 minutes (table 5) Thiswould include activation of the stroke team technol-ogists and nurses Adjunctive time benchmarks canbe developed including puncture-to-clot and clot-to-close goals This target is more difficult to achievefor cerebral than cardiac revascularization as strokepatients require more time-consuming neurologic
Tab
le5
Ben
chm
ark
tim
esfo
rre
vasc
ular
izat
ion
ther
apie
san
dp
ossi
ble
inte
rval
sfo
rE
RT
Am
eric
anC
olle
geof
Car
diol
ogy6
7A
SA
AH
AA
ISG
uide
lines
forI
Vrt
-PA
68
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rE
RT
pres
enti
ngto
ED
ldquoP
rim
ary
ER
TTi
merdquo
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rRes
cue
ER
Tfo
llow
ing
IVfa
ilure
ldquoIV
-Fai
lure
toR
escu
eE
RTrdquo
Pro
pose
dgo
als
forA
ISpa
tien
tstr
ansf
erre
dfr
omou
tsid
eho
spit
alfo
rER
TldquoD
rip-
and-
Shi
pto
ER
Trdquo
Doo
r-to
-bal
loon
tim
e9
0m
inD
oor-
to-n
eedl
eti
me
60
min
Doo
r-to
-gro
inpu
nctu
reti
me
90
min
Nee
dle
-to-
gro
inp
unct
ure
tim
e6
0m
inD
oora -t
o-G
roin
Pun
ctur
eti
me
60
min
ST
EM
Icon
firm
ed
card
iolo
gis
tno
tifi
ed
10
min
Doo
rto
ED
10
min
Doo
rto
ED
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
0m
in)
ER
Tte
amis
noti
fied
asso
onas
larg
eto
med
ium
vess
eloc
clus
ion
issu
spec
ted
(ie
N
IHS
Sh
yper
dens
eM
CA
onC
T)in
elig
ible
pati
ents
10
min
afte
rth
eel
igib
ility
CT
scan
and
befo
reIV
bolu
s
Tran
sfer
from
outs
ide
hosp
ital
init
iate
dan
gio
suit
eac
tiva
ted
team
acti
vate
d
Pri
orto
arri
val
ED
stab
ilize
sp
atie
nta
ctiv
ates
cath
lab
30
min
Str
oke
team
acti
vati
on1
5m
inS
trok
ean
dE
RT
team
sac
tiva
tion
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
5m
in)
Rec
eivi
ngho
spit
alar
riva
lR
apid
hist
ory
and
exam
rev
iew
ofre
ferr
ing
hosp
ital
film
s
15
min
Cat
hla
ban
din
terv
enti
onal
ist
read
y
60
min
CT
scan
init
iate
d2
5m
inC
Tsc
anin
itia
ted
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(2
5m
in)
Ang
iosu
ite
acti
vate
dte
amon
stan
dby
cons
ider
noni
nvas
ive
vasc
ular
imag
ing
25
min
afte
rth
eel
igib
ility
CT
scan
and
afte
rIV
bolu
sin
itia
tion
Anc
illar
ybr
ain
imag
ing
(ie
CT
perf
usio
n)3
5m
in
Fin
alch
eck
and
wri
tten
cons
ent
70
min
CT
scan
inte
rpre
ted
elig
ibili
tyas
sess
ed4
5m
inC
Tsc
anin
terp
rete
del
igib
ility
asse
ssed
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(4
5m
in)
Rep
eat
NIH
SS
obt
ain
wri
tten
cons
ent
repe
atC
Tif
clin
ical
wor
seni
ng
45
min
afte
rth
eC
Tsc
anan
d3
0m
inaf
ter
the
IVrt
PA
bolu
s
Fin
alch
eck
wri
tten
cons
ent
pati
ent
prep
ped
45
min
Cat
hete
riza
tion
and
PC
Indashb
allo
onin
flat
ion
90
min
IVrt
PA
infu
sion
60
min
Gro
inpu
nctu
re9
0m
inG
roin
punc
ture
60
min
bG
roin
punc
ture
60
min
Abb
revi
atio
nsA
HA
A
mer
ican
Hea
rtA
ssoc
iati
onA
IS
acut
eis
chem
icst
roke
ang
io
angi
ogra
mA
SA
A
mer
ican
Str
oke
Ass
ocia
tion
ED
em
erge
ncy
depa
rtm
ent
ER
T
endo
vasc
ular
reva
scul
ariz
atio
nth
erap
yIA
intr
a-ar
teri
alM
CA
m
iddl
ece
rebr
alar
tery
NIH
SS
N
IHS
trok
eS
cale
PC
Ipe
rcut
aneo
usco
rona
ryin
terv
enti
onr
tPA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
TEM
IS
Tse
gmen
tele
vati
onm
yoca
rdia
linf
arct
ion
aF
rom
tim
eof
arri
valt
oac
cept
ing
hosp
ital
door
b
Tim
ew
illne
edto
bead
just
edto
allo
wfo
rad
diti
onal
imag
ing
ifcl
inic
alex
amin
atio
nw
orse
nsor
sym
ptom
ssu
gges
the
mor
rhag
ictr
ansf
orm
atio
n
S250 Neurology 79 (Suppl 1) September 25 2012
evaluation and brain imaging before proceeding tothe angiography laboratory
Achieving a 90-minute door-to-puncture timewould likely require the neurointerventionalist toplay an integral part in the stroke team because thedecisions on treatment strategy may evolve as the pa-tient proceeds through the AIS protocol and IV rtPAevaluation pathway The ERT protocol should inte-grate into the IV rtPA pathway For interhospitaltransfers the completed imaging and laboratorystudies as well as additional lead time may reduce thetarget time interval to 60 minutes for door-to-puncture However significant delay in hospitaltransfer may warrant repeat neuroimaging when thepatient arrives at the recipient institution Bench-mark times will need to be established for IV nonre-sponders with special consideration for additionaldelay when clinical deterioration following IV rtPArequires a repeat brain imaging prior to ERT
Triage and transfer strategies The considerable de-cline in efficacy of revascularization therapies ataround 6 to 8 hours from symptom onset demandswell-organized triage and transfer strategies46 Emer-gency department reorganization has been an area offocus to improve early identification of stroke pa-tients Tracking door-to-thrombolysis times posi-tioning a CTMRI scanner within the departmentand having emergency medical services (EMS) send aprehospital notification are steps that have improvedthrombolysis access58 However given the limitedavailability of Comprehensive Stroke Center infra-structure few centers in a given geographic regionwill have capabilities for providing comprehensivestroke care and 247 ERT This will lead to a highproportion of patients eligible for ERT arriving byinterhospital transfer Transfer delay has been shownto be a major factor limiting the use of ERT in strokepatients accounting for an estimated odds of treat-ment decrease by 25 for every minute of transfertime59 To avoid transfer delay regional protocols fortriage of AIS patients by EMS personnel to desig-nated stroke centers has become a focus of prehospi-tal stroke triage policy60
Alternative strategies include initiation of IVthrombolytic in a referring hospital prior to transferldquodrip-and-shiprdquo followed by further management atthe accepting hospital which may include ERT Adescribed model of ldquodrip ship and retrieverdquo usedfull-dose IV rtPA (09 mgkg) followed by ERT withmechanical thrombectomy and thrombo-aspirationsuggesting feasibility in basilar artery occlusion61
Different models may evolve where the patient re-ceives ERT in an outside hospital and is transferredfor further care at a comprehensive stroke centerwhere neurosurgery neurocritical care and vascular
neurology expertise are available known as ldquoretrieve-and-shiprdquo Pay-for-performance measures similar tothose for acute myocardial infarction could help fa-cilitate transfer of appropriate patients from primaryto comprehensive stroke centers (the hub-and-spokemodel)
GENERAL PREPROCEDURAL AND INTRAPROCE-DURAL MANAGEMENT Anesthesia and monitoringThe type of anesthesia for ERT has been a topic ofcontroversy with recent reports suggesting worseoutcome with use of general endotracheal anesthesiapossibly due to treatment delays and complicationsfrom intubation6263 Alternatively conscious seda-tion may pose a different set of risks related to patientcooperation especially in those with severe aphasiaor neglect which may negatively influence time torevascularization and procedural success Further-more ancillary monitoring requiring invasive arterialaccess for blood pressure monitoring and central IVaccess may also be of limited value and add delay toinitiation of therapy Further study is needed to eval-uate sedation methods for ERT Sedation methodsmay currently vary among centers
Thromboprophylaxis with systemic anticoagulationArterial catheterization carries a risk of thromboem-bolism often requiring systemic anticoagulationRandomized clinical trials of ERT report variableprotocols for thromboprophylaxis including bolusIV heparin infusion of 2000 to 5000 units atprocedure onset followed by continuous infusionsof approximately 500 units of IV heparin per hourfor the procedure duration621 Alternatively acti-vated clotting time (ACT) values can be obtainedwith heparin boluses to maintain an ACT at atherapeutic goal Limited data exist on the safetyof heparin anticoagulation during ERT proce-dures A subgroup analysis of the MERCI trialshowed no association with hemorrhage or 90-daymortality and heparin use64 A reasonable ACTrange may be 250 to 300 seconds during ERT
Renal prophylaxis Patients with AIS may also havechronic renal impairment which may worsen withcontrast administered during angiography Inter-ventions designed to prevent contrast-induced ne-phropathy have not been rigorously studiedReasonable prophylaxis strategies include hydra-tion with isotonic saline Recent data have notprovided strong support for the administration ofN-acetylcysteine65 The use of sodium bicarbonateinfusion may be reasonable for patients with renalinsufficiency but it can be limited by the largevolume and time to acquire the solution from thepharmacy Periprocedural renal prophylaxis for
Neurology 79 (Suppl 1) September 25 2012 S251
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
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References
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reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
lored interventions For example greater efficacy andsafety may be demonstrated in distal vessel revascu-larization by use of IA fibrinolytic therapy vs a me-chanical device that may be more difficult to deliverAlternatively in large proximal vessel occlusionsgreater benefit may be achieved with mechanicalthrombectomy Furthermore carotid occlusion atthe origin of the ICA may be better treated with bal-loon angioplasty and stent implantation
Pharmacologic thrombolysis Local IA thrombolysisefficacy was demonstrated in PROACT II6 This ledto an AHA Class I level of evidence B recommenda-tion that IA thrombolysis is an option for the treat-ment of selected patients who have AIS under 6hours duration due to occlusions of the MCA andwho are not otherwise candidates for IV rtPA1 Al-though variability in study designs prohibits direct com-parison of the data theoretically there may be a higherrisk of intracerebral hemorrhage (ICH) with chemicalIA thrombolysis than with mechanical revasculariza-tion However increased ICH was not substantiated ina multicenter study39
Microcatheter position during thrombolytic infu-sion may also theoretically affect recanalization ratesThe microcatheter position varies among the studiesin some instances it is placed distal to the thrombuswithin the thrombus or proximal to the thrombusSome operators will use multiple locations to infusertPA throughout the thrombus The maximum safedose for IA rtPA is not known however if we extrap-olate from large clinical trial experience then a max-
imum dose of 22 mg as in the IMS trials may be areasonable initial limit2140
Bridging therapies Bridging therapy trials evaluatingthe combined approach have shown better recanali-zation rates for medium- to large-vessel occlusionsHowever they have shown only trends toward betteroutcomes in comparison with the IV rtPAndashtreatedsubjects in the National Institute of NeurologicalDisorders and Stroke (NINDS) rtPA Stroke Study ora database registry4041 Potential benefit of bridgingtherapy increases when the target population is lim-ited to IV rtPA nonresponders (40 IV-IA patientsreached functional independence at 3 months vs149 of recipients of only IV rtPA among the non-responders [p 0012]) This benefit came at thecost of a higher morbidity associated with the bridg-ing therapy (OR 214 95 CI 058 ndash783 forsICH)42 The early Emergency Management ofStroke Bridging TrialIMS trials used a protocol of06 mgkg IV rtPA with up to an additional maxi-mum of 22 mg IA rtPA which in most patients al-lowed for the total dose to remain below the NINDSmaximum amount of 90 mg (table 3) Howevernewer bridging studies and the amended IMS III areusing full-dose IV rtPA in the combined IV-IA treat-ment arm2021
Mechanical revascularization Mechanical techniquesfor ERT including thrombectomy clot retrievaland thromboaspiration have shown comparable orslightly higher recanalization rates than IA thrombol-
Table 3 Intra-arterial thrombolytic dosing and methods from selected trials
Trial PROACT5 PROACT II6 MELT12 IMS I55 IMS II40 IMS III21
Agent ProUK ProUK UK rtPA rtPA rtPA
Max dose Two-tier dose6 mg and 12 mg
9 mg 600000 IU IV rtPA 06 mgkg 60mg maxIA rtPA 22 mg
IV rtPA 06 mgkg60 mg maxIA rtPA 22 mg
IV rtPA 06 mgkg 60 mgmaxpossibly IA rtPA 22 mg
Median dose mg 6 and 12 9 mdash mdash 12 mdash
Infusion duration h 2 2 2 2 2 2
Infusion location At proximal one-thirdof thrombus
At proximal one-thirdof thrombus
Distal tothrombus
2 mg distal to thrombusthen 2 mg intothrombus then infusion
At site of thrombuswith or withoutEkos ultrasoundcatheter
1 mg distal and 1 mgproximal then 20 mg overmaximum of 2 h
Mechanical disruption Prohibited Prohibited Only withguidewire
Only with guidewire ormicrocatheter
Only with guidewireor microcatheter
Merci device Ekos orpenumbra device with IArtPA infusion ormicrocatheter IA rtPAinfusion
Intraproceduralsystemic thrombo-prophylaxis
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 2000 IUbolus and 500 IUhinfusionfor 4 h
Heparin 5000IU bolus
Heparin 2000 IU bolusand 450 IUh infusion
Heparin 2000 IUbolus and 450 IUhinfusion
Heparin 2000 IU bolus and450 IUh infusion until theend of the procedure
Adjunctiveantithrombotic agents
Prohibited in first24 h
Prohibited in first24 h
Prohibited infirst 24 h
Prohibited in first 24 h Prohibited in first24 h
Prohibited in first 24 h
Abbreviations IA intra-arterial IMS Interventional Management of Stroke trial IU international units MELT Middle cerebral artery Embolism LocalFibrinolytic intervention Trial PROACT Prolyse in Acute Cerebral Thromboembolism trial rtPA IV recombinant tissue plasminogen activator UK
urokinase
S248 Neurology 79 (Suppl 1) September 25 2012
ysis alone (table 1) Newer devices such as the Soli-taire FR retrievable stent (eV3 Irvine CA) haveshown even higher recanalization rates (84ndash90)2324 In appropriately selected patients me-chanical revascularization may theoretically have alower risk of hemorrhagic complications given theabsence or reduced need for a thrombolytic agent Inpatients who are considered for ERT after full-doseIV rtPA a mechanical approach might be favorableLimitations of mechanical revascularization includedevice failure deliverability to distal locations andembolization
Multimodal revascularization Given the heterogene-ity of vessel occlusion etiology in AIS a combinationof multiple techniques may afford the highest successfor revascularization Small series suggest that multi-modal therapies including IA thrombolysis and stentimplantation lead to higher recanalization rates39
Future studies may find mechanical thrombectomyto be more successful in proximal large-vessel occlu-sions whereas local IA thrombolysis would be pre-ferred in distal small-vessel occlusions Also stentimplantation may be most effective for in situ intra-cranial atherosclerosis with supervening thrombosisbut retrieval and aspiration techniques may be moreeffective for thromboemboli occlusive in relativelynormal recipient arteries4
Posterior circulation modality selection The besttreatment modality for patients with VBO remainspoorly defined A large prospective observationalregistry and a separate systematic analysis of pub-lished case series analyzed a total of 1012 patientsboth studies did not support unequivocal superiorityof IA therapy vs IV thrombolysis3243 However theheterogeneity of the data between the patients withinthe groups analyzed limits interpretation of the clini-cal conclusions Early recanalization is an importantprognostic factor for good clinical outcome as suchhigher and safer rates of recanalization are beingachieved with newer therapeutic strategies utilizingmechanical embolectomy devices retrievable stentsangioplasty with or without stenting use of glyco-protein IIbIIIa inhibitors and combinationsthereof2328304445
TARGET TIME INTERVALS AND TRIAGE ANDTRANSFER STRATEGIES Time to revasculariza-tion is an independent predictor of good outcome inpatients with AIS4647 Randomized trials of IV rtPAhave demonstrated the greatest benefit in subjectstreated within 90 minutes of symptom onset225 Re-canalization rates with ERT are higher than with IVrtPA alone although the delay to treatment may at-tenuate the benefit This illustrates the importance ofestablishing benchmark door-to-revascularization
Tab
le4
Tre
atm
ent
tim
esin
sele
cted
stud
ies
inm
inut
es
Tri
alP
RO
AC
T5
PR
OA
CT
II6
IMS
I55IM
SII
I21E
MS
56M
ELT
12R
EC
AN
ALI
SE
41P
enum
bra
PS
T11
Mul
tiM
ER
CI29
M
ER
CI10
Wol
feet
al50
Doc
rocq
etal
54C
osta
lat
etal
43M
iley
etal
53S
uare
zet
al51
Mat
tle
etal
49F
lahe
rty
etal
52
No
ofsu
bje
cts
40
12
16
25
00
35
56
50
12
53
05
96
13
50
91
54
57
44
Tre
atm
ent
IApr
oUK
orpl
aceb
oIA
proU
KIV
-IA
rtP
AIV
aor
IV
IAb
IV-I
Aa
orIA
rtP
Ab
IAU
KIV
-IA
orIV
-IA
Trt
PA
IAT
IV
rtP
AIA
TIV
-IA
aor
IArt
PA
bIA
UK
IV-R
Sor
RS
alon
eIV
-IA
Tor
IAT
IAU
KIA
TU
KIV
IA
rtP
A
Tim
e-to
-doo
r1
14
Tim
e-to
-CT
MR
Isc
anm
ean
(med
ian)
Ons
et1
05
Ons
et1
62
(14
5)
Doo
r5
9(3
4)
Imag
ing
-to-
GP
16
1(1
53
)8
1(6
5)
CT
scan
-to-
mic
roca
thet
er1
74
Tim
e-to
-ER
Tin
itia
tion
oran
gio
gra
mor
GP
SO
(33
0)
SO
(31
8)
SO
21
7(2
12
)
SO
12
37
25
52
IV-b
olus
toG
P8
74
SO
a(1
98
)Oslash
b(1
80
)Oslash
SO
22
7S
O1
32
SO
25
8pound
SO
(25
8)
SO
a1
51
b2
61
SO
32
4(3
30
)S
O3
21
Doo
r(1
30
)S
O2
44
SO
(22
6)
GP
-to-
max
TIM
IT
ICI
54
(48
)
SO
-to-
max
TIM
IT
ICI
a(3
78
)b(
34
2)
(22
0)
37
7(3
27
)
Abb
revi
atio
nsE
MS
E
mer
genc
yM
anag
emen
tof
Str
oke
ER
T
endo
vasc
ular
reva
scul
ariz
atio
ntr
eatm
ent
GP
gr
oin
punc
ture
IA
in
tra-
arte
rial
IA
T
intr
a-ar
teri
alth
erap
y(in
clud
esth
rom
boly
sis
and
mec
hani
cal
tech
niqu
es)
IMS
In
terv
enti
onal
Man
agem
ento
fStr
oke
tria
lM
ELT
M
iddl
ece
rebr
alar
tery
Em
bolis
mLo
calF
ibri
noly
tic
inte
rven
tion
Tria
lM
ER
CI
Mec
hani
calE
mbo
lus
Rem
oval
inC
ereb
ralI
sche
mia
PR
OA
CT
P
roly
sein
Acu
teC
ereb
ralT
hrom
boem
bolis
mtr
ial
PS
T
Piv
otal
Str
oke
Tria
lR
EC
AN
ALI
SE
R
Eca
nalis
atio
nus
ing
Com
bine
din
trav
enou
sA
ltep
lase
and
Neu
roin
terv
enti
onal
Alg
orit
hmfo
racu
teIs
chem
icS
trok
ER
S
retr
ieva
ble
sten
trt
PA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
O
sym
ptom
onse
tTI
CI
thro
mbo
lysi
sin
cere
bral
infa
rcti
onT
IMI
thro
mbo
lysi
sin
myo
card
iali
nfar
ctio
nU
K
urok
inas
e
Neurology 79 (Suppl 1) September 25 2012 S249
times The Brain Attack Coalition has recommendedthat IV rtPA be administered within 60 minutesfrom arrival to the emergency department (ED) foreligible patients48 The established time intervals tar-get a multidisciplinary goal Each component of theprocessmdashED physicians ancillary staff laboratoryand radiology services neurology team and radiol-ogy staffmdashis essential for the time goal As suchERT time intervals should integrate into the existingmodel beginning with patient arrival to the EDSeparate time intervals can be established for patientstransferred from another institution and patientswho receive adjunctive ERT following IV rtPA ther-apy Because vascular anatomy can add unpredictabledelays in procedural times the endpoint should re-flect the last modifiable variable Therefore ERTtime intervals should reflect door-to-puncture (morepredictable) puncture-to-clot and clot-to-closegoals A clot-to-close time of 120 minutes as de-scribed in IMS III may be warranted to establishprocedural termination times More variables in-cluding anatomy evidence of persistent penumbraand ERT method may be used in the future to mod-ify time benchmarks
In the limited case series discussing time intervalsto ERT there is variability in which interval is uti-lized (table 4)56111215414349 ndash56 Randomized trialsshow feasibility in achieving time intervals of approx-imately 4 to 5 hours from stroke onset to IA rtPAadministration655 In PROACT II median timefrom stroke onset to randomization and IA rtPA ad-ministration was 282 minutes whereas the IMSstudy demonstrated an interval of 231 minutes fromstroke onset to IA rtPA administration655 Timefrom CT scan to microcatheter placement in thecerebrovasculature had a mean time of 174 60minutes in 91 patients undergoing ERT for AISdemonstrating wide variability and a need for timestandards53 Transferred patients whose laboratorytests and CT scan have already been completed maystill have a door-to-puncture time of up to 60 min-utes57 Further study is needed to identify barriers torapid access to endovascular therapy
Currently the American College of Cardiologyand the AHA recommend that door-to-balloon timein ST segment elevation myocardial infarctionshould be within 90 minutes A similar future pro-posal could be made for ERT in AIS with a goaldoor-to-puncture time of 90 minutes (table 5) Thiswould include activation of the stroke team technol-ogists and nurses Adjunctive time benchmarks canbe developed including puncture-to-clot and clot-to-close goals This target is more difficult to achievefor cerebral than cardiac revascularization as strokepatients require more time-consuming neurologic
Tab
le5
Ben
chm
ark
tim
esfo
rre
vasc
ular
izat
ion
ther
apie
san
dp
ossi
ble
inte
rval
sfo
rE
RT
Am
eric
anC
olle
geof
Car
diol
ogy6
7A
SA
AH
AA
ISG
uide
lines
forI
Vrt
-PA
68
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rE
RT
pres
enti
ngto
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S250 Neurology 79 (Suppl 1) September 25 2012
evaluation and brain imaging before proceeding tothe angiography laboratory
Achieving a 90-minute door-to-puncture timewould likely require the neurointerventionalist toplay an integral part in the stroke team because thedecisions on treatment strategy may evolve as the pa-tient proceeds through the AIS protocol and IV rtPAevaluation pathway The ERT protocol should inte-grate into the IV rtPA pathway For interhospitaltransfers the completed imaging and laboratorystudies as well as additional lead time may reduce thetarget time interval to 60 minutes for door-to-puncture However significant delay in hospitaltransfer may warrant repeat neuroimaging when thepatient arrives at the recipient institution Bench-mark times will need to be established for IV nonre-sponders with special consideration for additionaldelay when clinical deterioration following IV rtPArequires a repeat brain imaging prior to ERT
Triage and transfer strategies The considerable de-cline in efficacy of revascularization therapies ataround 6 to 8 hours from symptom onset demandswell-organized triage and transfer strategies46 Emer-gency department reorganization has been an area offocus to improve early identification of stroke pa-tients Tracking door-to-thrombolysis times posi-tioning a CTMRI scanner within the departmentand having emergency medical services (EMS) send aprehospital notification are steps that have improvedthrombolysis access58 However given the limitedavailability of Comprehensive Stroke Center infra-structure few centers in a given geographic regionwill have capabilities for providing comprehensivestroke care and 247 ERT This will lead to a highproportion of patients eligible for ERT arriving byinterhospital transfer Transfer delay has been shownto be a major factor limiting the use of ERT in strokepatients accounting for an estimated odds of treat-ment decrease by 25 for every minute of transfertime59 To avoid transfer delay regional protocols fortriage of AIS patients by EMS personnel to desig-nated stroke centers has become a focus of prehospi-tal stroke triage policy60
Alternative strategies include initiation of IVthrombolytic in a referring hospital prior to transferldquodrip-and-shiprdquo followed by further management atthe accepting hospital which may include ERT Adescribed model of ldquodrip ship and retrieverdquo usedfull-dose IV rtPA (09 mgkg) followed by ERT withmechanical thrombectomy and thrombo-aspirationsuggesting feasibility in basilar artery occlusion61
Different models may evolve where the patient re-ceives ERT in an outside hospital and is transferredfor further care at a comprehensive stroke centerwhere neurosurgery neurocritical care and vascular
neurology expertise are available known as ldquoretrieve-and-shiprdquo Pay-for-performance measures similar tothose for acute myocardial infarction could help fa-cilitate transfer of appropriate patients from primaryto comprehensive stroke centers (the hub-and-spokemodel)
GENERAL PREPROCEDURAL AND INTRAPROCE-DURAL MANAGEMENT Anesthesia and monitoringThe type of anesthesia for ERT has been a topic ofcontroversy with recent reports suggesting worseoutcome with use of general endotracheal anesthesiapossibly due to treatment delays and complicationsfrom intubation6263 Alternatively conscious seda-tion may pose a different set of risks related to patientcooperation especially in those with severe aphasiaor neglect which may negatively influence time torevascularization and procedural success Further-more ancillary monitoring requiring invasive arterialaccess for blood pressure monitoring and central IVaccess may also be of limited value and add delay toinitiation of therapy Further study is needed to eval-uate sedation methods for ERT Sedation methodsmay currently vary among centers
Thromboprophylaxis with systemic anticoagulationArterial catheterization carries a risk of thromboem-bolism often requiring systemic anticoagulationRandomized clinical trials of ERT report variableprotocols for thromboprophylaxis including bolusIV heparin infusion of 2000 to 5000 units atprocedure onset followed by continuous infusionsof approximately 500 units of IV heparin per hourfor the procedure duration621 Alternatively acti-vated clotting time (ACT) values can be obtainedwith heparin boluses to maintain an ACT at atherapeutic goal Limited data exist on the safetyof heparin anticoagulation during ERT proce-dures A subgroup analysis of the MERCI trialshowed no association with hemorrhage or 90-daymortality and heparin use64 A reasonable ACTrange may be 250 to 300 seconds during ERT
Renal prophylaxis Patients with AIS may also havechronic renal impairment which may worsen withcontrast administered during angiography Inter-ventions designed to prevent contrast-induced ne-phropathy have not been rigorously studiedReasonable prophylaxis strategies include hydra-tion with isotonic saline Recent data have notprovided strong support for the administration ofN-acetylcysteine65 The use of sodium bicarbonateinfusion may be reasonable for patients with renalinsufficiency but it can be limited by the largevolume and time to acquire the solution from thepharmacy Periprocedural renal prophylaxis for
Neurology 79 (Suppl 1) September 25 2012 S251
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
httpnneurologyorgcontent7913_Supplement_1S243fullincluding high resolution figures can be found at
References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
Citations
ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
ehttpnneurologyorgcgicollectionall_cerebrovascular_disease_strokAll Cerebrovascular diseaseStrokefollowing collection(s) This article along with others on similar topics appears in the
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httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
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rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2012 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
ysis alone (table 1) Newer devices such as the Soli-taire FR retrievable stent (eV3 Irvine CA) haveshown even higher recanalization rates (84ndash90)2324 In appropriately selected patients me-chanical revascularization may theoretically have alower risk of hemorrhagic complications given theabsence or reduced need for a thrombolytic agent Inpatients who are considered for ERT after full-doseIV rtPA a mechanical approach might be favorableLimitations of mechanical revascularization includedevice failure deliverability to distal locations andembolization
Multimodal revascularization Given the heterogene-ity of vessel occlusion etiology in AIS a combinationof multiple techniques may afford the highest successfor revascularization Small series suggest that multi-modal therapies including IA thrombolysis and stentimplantation lead to higher recanalization rates39
Future studies may find mechanical thrombectomyto be more successful in proximal large-vessel occlu-sions whereas local IA thrombolysis would be pre-ferred in distal small-vessel occlusions Also stentimplantation may be most effective for in situ intra-cranial atherosclerosis with supervening thrombosisbut retrieval and aspiration techniques may be moreeffective for thromboemboli occlusive in relativelynormal recipient arteries4
Posterior circulation modality selection The besttreatment modality for patients with VBO remainspoorly defined A large prospective observationalregistry and a separate systematic analysis of pub-lished case series analyzed a total of 1012 patientsboth studies did not support unequivocal superiorityof IA therapy vs IV thrombolysis3243 However theheterogeneity of the data between the patients withinthe groups analyzed limits interpretation of the clini-cal conclusions Early recanalization is an importantprognostic factor for good clinical outcome as suchhigher and safer rates of recanalization are beingachieved with newer therapeutic strategies utilizingmechanical embolectomy devices retrievable stentsangioplasty with or without stenting use of glyco-protein IIbIIIa inhibitors and combinationsthereof2328304445
TARGET TIME INTERVALS AND TRIAGE ANDTRANSFER STRATEGIES Time to revasculariza-tion is an independent predictor of good outcome inpatients with AIS4647 Randomized trials of IV rtPAhave demonstrated the greatest benefit in subjectstreated within 90 minutes of symptom onset225 Re-canalization rates with ERT are higher than with IVrtPA alone although the delay to treatment may at-tenuate the benefit This illustrates the importance ofestablishing benchmark door-to-revascularization
Tab
le4
Tre
atm
ent
tim
esin
sele
cted
stud
ies
inm
inut
es
Tri
alP
RO
AC
T5
PR
OA
CT
II6
IMS
I55IM
SII
I21E
MS
56M
ELT
12R
EC
AN
ALI
SE
41P
enum
bra
PS
T11
Mul
tiM
ER
CI29
M
ER
CI10
Wol
feet
al50
Doc
rocq
etal
54C
osta
lat
etal
43M
iley
etal
53S
uare
zet
al51
Mat
tle
etal
49F
lahe
rty
etal
52
No
ofsu
bje
cts
40
12
16
25
00
35
56
50
12
53
05
96
13
50
91
54
57
44
Tre
atm
ent
IApr
oUK
orpl
aceb
oIA
proU
KIV
-IA
rtP
AIV
aor
IV
IAb
IV-I
Aa
orIA
rtP
Ab
IAU
KIV
-IA
orIV
-IA
Trt
PA
IAT
IV
rtP
AIA
TIV
-IA
aor
IArt
PA
bIA
UK
IV-R
Sor
RS
alon
eIV
-IA
Tor
IAT
IAU
KIA
TU
KIV
IA
rtP
A
Tim
e-to
-doo
r1
14
Tim
e-to
-CT
MR
Isc
anm
ean
(med
ian)
Ons
et1
05
Ons
et1
62
(14
5)
Doo
r5
9(3
4)
Imag
ing
-to-
GP
16
1(1
53
)8
1(6
5)
CT
scan
-to-
mic
roca
thet
er1
74
Tim
e-to
-ER
Tin
itia
tion
oran
gio
gra
mor
GP
SO
(33
0)
SO
(31
8)
SO
21
7(2
12
)
SO
12
37
25
52
IV-b
olus
toG
P8
74
SO
a(1
98
)Oslash
b(1
80
)Oslash
SO
22
7S
O1
32
SO
25
8pound
SO
(25
8)
SO
a1
51
b2
61
SO
32
4(3
30
)S
O3
21
Doo
r(1
30
)S
O2
44
SO
(22
6)
GP
-to-
max
TIM
IT
ICI
54
(48
)
SO
-to-
max
TIM
IT
ICI
a(3
78
)b(
34
2)
(22
0)
37
7(3
27
)
Abb
revi
atio
nsE
MS
E
mer
genc
yM
anag
emen
tof
Str
oke
ER
T
endo
vasc
ular
reva
scul
ariz
atio
ntr
eatm
ent
GP
gr
oin
punc
ture
IA
in
tra-
arte
rial
IA
T
intr
a-ar
teri
alth
erap
y(in
clud
esth
rom
boly
sis
and
mec
hani
cal
tech
niqu
es)
IMS
In
terv
enti
onal
Man
agem
ento
fStr
oke
tria
lM
ELT
M
iddl
ece
rebr
alar
tery
Em
bolis
mLo
calF
ibri
noly
tic
inte
rven
tion
Tria
lM
ER
CI
Mec
hani
calE
mbo
lus
Rem
oval
inC
ereb
ralI
sche
mia
PR
OA
CT
P
roly
sein
Acu
teC
ereb
ralT
hrom
boem
bolis
mtr
ial
PS
T
Piv
otal
Str
oke
Tria
lR
EC
AN
ALI
SE
R
Eca
nalis
atio
nus
ing
Com
bine
din
trav
enou
sA
ltep
lase
and
Neu
roin
terv
enti
onal
Alg
orit
hmfo
racu
teIs
chem
icS
trok
ER
S
retr
ieva
ble
sten
trt
PA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
O
sym
ptom
onse
tTI
CI
thro
mbo
lysi
sin
cere
bral
infa
rcti
onT
IMI
thro
mbo
lysi
sin
myo
card
iali
nfar
ctio
nU
K
urok
inas
e
Neurology 79 (Suppl 1) September 25 2012 S249
times The Brain Attack Coalition has recommendedthat IV rtPA be administered within 60 minutesfrom arrival to the emergency department (ED) foreligible patients48 The established time intervals tar-get a multidisciplinary goal Each component of theprocessmdashED physicians ancillary staff laboratoryand radiology services neurology team and radiol-ogy staffmdashis essential for the time goal As suchERT time intervals should integrate into the existingmodel beginning with patient arrival to the EDSeparate time intervals can be established for patientstransferred from another institution and patientswho receive adjunctive ERT following IV rtPA ther-apy Because vascular anatomy can add unpredictabledelays in procedural times the endpoint should re-flect the last modifiable variable Therefore ERTtime intervals should reflect door-to-puncture (morepredictable) puncture-to-clot and clot-to-closegoals A clot-to-close time of 120 minutes as de-scribed in IMS III may be warranted to establishprocedural termination times More variables in-cluding anatomy evidence of persistent penumbraand ERT method may be used in the future to mod-ify time benchmarks
In the limited case series discussing time intervalsto ERT there is variability in which interval is uti-lized (table 4)56111215414349 ndash56 Randomized trialsshow feasibility in achieving time intervals of approx-imately 4 to 5 hours from stroke onset to IA rtPAadministration655 In PROACT II median timefrom stroke onset to randomization and IA rtPA ad-ministration was 282 minutes whereas the IMSstudy demonstrated an interval of 231 minutes fromstroke onset to IA rtPA administration655 Timefrom CT scan to microcatheter placement in thecerebrovasculature had a mean time of 174 60minutes in 91 patients undergoing ERT for AISdemonstrating wide variability and a need for timestandards53 Transferred patients whose laboratorytests and CT scan have already been completed maystill have a door-to-puncture time of up to 60 min-utes57 Further study is needed to identify barriers torapid access to endovascular therapy
Currently the American College of Cardiologyand the AHA recommend that door-to-balloon timein ST segment elevation myocardial infarctionshould be within 90 minutes A similar future pro-posal could be made for ERT in AIS with a goaldoor-to-puncture time of 90 minutes (table 5) Thiswould include activation of the stroke team technol-ogists and nurses Adjunctive time benchmarks canbe developed including puncture-to-clot and clot-to-close goals This target is more difficult to achievefor cerebral than cardiac revascularization as strokepatients require more time-consuming neurologic
Tab
le5
Ben
chm
ark
tim
esfo
rre
vasc
ular
izat
ion
ther
apie
san
dp
ossi
ble
inte
rval
sfo
rE
RT
Am
eric
anC
olle
geof
Car
diol
ogy6
7A
SA
AH
AA
ISG
uide
lines
forI
Vrt
-PA
68
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rE
RT
pres
enti
ngto
ED
ldquoP
rim
ary
ER
TTi
merdquo
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rRes
cue
ER
Tfo
llow
ing
IVfa
ilure
ldquoIV
-Fai
lure
toR
escu
eE
RTrdquo
Pro
pose
dgo
als
forA
ISpa
tien
tstr
ansf
erre
dfr
omou
tsid
eho
spit
alfo
rER
TldquoD
rip-
and-
Shi
pto
ER
Trdquo
Doo
r-to
-bal
loon
tim
e9
0m
inD
oor-
to-n
eedl
eti
me
60
min
Doo
r-to
-gro
inpu
nctu
reti
me
90
min
Nee
dle
-to-
gro
inp
unct
ure
tim
e6
0m
inD
oora -t
o-G
roin
Pun
ctur
eti
me
60
min
ST
EM
Icon
firm
ed
card
iolo
gis
tno
tifi
ed
10
min
Doo
rto
ED
10
min
Doo
rto
ED
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
0m
in)
ER
Tte
amis
noti
fied
asso
onas
larg
eto
med
ium
vess
eloc
clus
ion
issu
spec
ted
(ie
N
IHS
Sh
yper
dens
eM
CA
onC
T)in
elig
ible
pati
ents
10
min
afte
rth
eel
igib
ility
CT
scan
and
befo
reIV
bolu
s
Tran
sfer
from
outs
ide
hosp
ital
init
iate
dan
gio
suit
eac
tiva
ted
team
acti
vate
d
Pri
orto
arri
val
ED
stab
ilize
sp
atie
nta
ctiv
ates
cath
lab
30
min
Str
oke
team
acti
vati
on1
5m
inS
trok
ean
dE
RT
team
sac
tiva
tion
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
5m
in)
Rec
eivi
ngho
spit
alar
riva
lR
apid
hist
ory
and
exam
rev
iew
ofre
ferr
ing
hosp
ital
film
s
15
min
Cat
hla
ban
din
terv
enti
onal
ist
read
y
60
min
CT
scan
init
iate
d2
5m
inC
Tsc
anin
itia
ted
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(2
5m
in)
Ang
iosu
ite
acti
vate
dte
amon
stan
dby
cons
ider
noni
nvas
ive
vasc
ular
imag
ing
25
min
afte
rth
eel
igib
ility
CT
scan
and
afte
rIV
bolu
sin
itia
tion
Anc
illar
ybr
ain
imag
ing
(ie
CT
perf
usio
n)3
5m
in
Fin
alch
eck
and
wri
tten
cons
ent
70
min
CT
scan
inte
rpre
ted
elig
ibili
tyas
sess
ed4
5m
inC
Tsc
anin
terp
rete
del
igib
ility
asse
ssed
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(4
5m
in)
Rep
eat
NIH
SS
obt
ain
wri
tten
cons
ent
repe
atC
Tif
clin
ical
wor
seni
ng
45
min
afte
rth
eC
Tsc
anan
d3
0m
inaf
ter
the
IVrt
PA
bolu
s
Fin
alch
eck
wri
tten
cons
ent
pati
ent
prep
ped
45
min
Cat
hete
riza
tion
and
PC
Indashb
allo
onin
flat
ion
90
min
IVrt
PA
infu
sion
60
min
Gro
inpu
nctu
re9
0m
inG
roin
punc
ture
60
min
bG
roin
punc
ture
60
min
Abb
revi
atio
nsA
HA
A
mer
ican
Hea
rtA
ssoc
iati
onA
IS
acut
eis
chem
icst
roke
ang
io
angi
ogra
mA
SA
A
mer
ican
Str
oke
Ass
ocia
tion
ED
em
erge
ncy
depa
rtm
ent
ER
T
endo
vasc
ular
reva
scul
ariz
atio
nth
erap
yIA
intr
a-ar
teri
alM
CA
m
iddl
ece
rebr
alar
tery
NIH
SS
N
IHS
trok
eS
cale
PC
Ipe
rcut
aneo
usco
rona
ryin
terv
enti
onr
tPA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
TEM
IS
Tse
gmen
tele
vati
onm
yoca
rdia
linf
arct
ion
aF
rom
tim
eof
arri
valt
oac
cept
ing
hosp
ital
door
b
Tim
ew
illne
edto
bead
just
edto
allo
wfo
rad
diti
onal
imag
ing
ifcl
inic
alex
amin
atio
nw
orse
nsor
sym
ptom
ssu
gges
the
mor
rhag
ictr
ansf
orm
atio
n
S250 Neurology 79 (Suppl 1) September 25 2012
evaluation and brain imaging before proceeding tothe angiography laboratory
Achieving a 90-minute door-to-puncture timewould likely require the neurointerventionalist toplay an integral part in the stroke team because thedecisions on treatment strategy may evolve as the pa-tient proceeds through the AIS protocol and IV rtPAevaluation pathway The ERT protocol should inte-grate into the IV rtPA pathway For interhospitaltransfers the completed imaging and laboratorystudies as well as additional lead time may reduce thetarget time interval to 60 minutes for door-to-puncture However significant delay in hospitaltransfer may warrant repeat neuroimaging when thepatient arrives at the recipient institution Bench-mark times will need to be established for IV nonre-sponders with special consideration for additionaldelay when clinical deterioration following IV rtPArequires a repeat brain imaging prior to ERT
Triage and transfer strategies The considerable de-cline in efficacy of revascularization therapies ataround 6 to 8 hours from symptom onset demandswell-organized triage and transfer strategies46 Emer-gency department reorganization has been an area offocus to improve early identification of stroke pa-tients Tracking door-to-thrombolysis times posi-tioning a CTMRI scanner within the departmentand having emergency medical services (EMS) send aprehospital notification are steps that have improvedthrombolysis access58 However given the limitedavailability of Comprehensive Stroke Center infra-structure few centers in a given geographic regionwill have capabilities for providing comprehensivestroke care and 247 ERT This will lead to a highproportion of patients eligible for ERT arriving byinterhospital transfer Transfer delay has been shownto be a major factor limiting the use of ERT in strokepatients accounting for an estimated odds of treat-ment decrease by 25 for every minute of transfertime59 To avoid transfer delay regional protocols fortriage of AIS patients by EMS personnel to desig-nated stroke centers has become a focus of prehospi-tal stroke triage policy60
Alternative strategies include initiation of IVthrombolytic in a referring hospital prior to transferldquodrip-and-shiprdquo followed by further management atthe accepting hospital which may include ERT Adescribed model of ldquodrip ship and retrieverdquo usedfull-dose IV rtPA (09 mgkg) followed by ERT withmechanical thrombectomy and thrombo-aspirationsuggesting feasibility in basilar artery occlusion61
Different models may evolve where the patient re-ceives ERT in an outside hospital and is transferredfor further care at a comprehensive stroke centerwhere neurosurgery neurocritical care and vascular
neurology expertise are available known as ldquoretrieve-and-shiprdquo Pay-for-performance measures similar tothose for acute myocardial infarction could help fa-cilitate transfer of appropriate patients from primaryto comprehensive stroke centers (the hub-and-spokemodel)
GENERAL PREPROCEDURAL AND INTRAPROCE-DURAL MANAGEMENT Anesthesia and monitoringThe type of anesthesia for ERT has been a topic ofcontroversy with recent reports suggesting worseoutcome with use of general endotracheal anesthesiapossibly due to treatment delays and complicationsfrom intubation6263 Alternatively conscious seda-tion may pose a different set of risks related to patientcooperation especially in those with severe aphasiaor neglect which may negatively influence time torevascularization and procedural success Further-more ancillary monitoring requiring invasive arterialaccess for blood pressure monitoring and central IVaccess may also be of limited value and add delay toinitiation of therapy Further study is needed to eval-uate sedation methods for ERT Sedation methodsmay currently vary among centers
Thromboprophylaxis with systemic anticoagulationArterial catheterization carries a risk of thromboem-bolism often requiring systemic anticoagulationRandomized clinical trials of ERT report variableprotocols for thromboprophylaxis including bolusIV heparin infusion of 2000 to 5000 units atprocedure onset followed by continuous infusionsof approximately 500 units of IV heparin per hourfor the procedure duration621 Alternatively acti-vated clotting time (ACT) values can be obtainedwith heparin boluses to maintain an ACT at atherapeutic goal Limited data exist on the safetyof heparin anticoagulation during ERT proce-dures A subgroup analysis of the MERCI trialshowed no association with hemorrhage or 90-daymortality and heparin use64 A reasonable ACTrange may be 250 to 300 seconds during ERT
Renal prophylaxis Patients with AIS may also havechronic renal impairment which may worsen withcontrast administered during angiography Inter-ventions designed to prevent contrast-induced ne-phropathy have not been rigorously studiedReasonable prophylaxis strategies include hydra-tion with isotonic saline Recent data have notprovided strong support for the administration ofN-acetylcysteine65 The use of sodium bicarbonateinfusion may be reasonable for patients with renalinsufficiency but it can be limited by the largevolume and time to acquire the solution from thepharmacy Periprocedural renal prophylaxis for
Neurology 79 (Suppl 1) September 25 2012 S251
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
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References
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rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2012 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
times The Brain Attack Coalition has recommendedthat IV rtPA be administered within 60 minutesfrom arrival to the emergency department (ED) foreligible patients48 The established time intervals tar-get a multidisciplinary goal Each component of theprocessmdashED physicians ancillary staff laboratoryand radiology services neurology team and radiol-ogy staffmdashis essential for the time goal As suchERT time intervals should integrate into the existingmodel beginning with patient arrival to the EDSeparate time intervals can be established for patientstransferred from another institution and patientswho receive adjunctive ERT following IV rtPA ther-apy Because vascular anatomy can add unpredictabledelays in procedural times the endpoint should re-flect the last modifiable variable Therefore ERTtime intervals should reflect door-to-puncture (morepredictable) puncture-to-clot and clot-to-closegoals A clot-to-close time of 120 minutes as de-scribed in IMS III may be warranted to establishprocedural termination times More variables in-cluding anatomy evidence of persistent penumbraand ERT method may be used in the future to mod-ify time benchmarks
In the limited case series discussing time intervalsto ERT there is variability in which interval is uti-lized (table 4)56111215414349 ndash56 Randomized trialsshow feasibility in achieving time intervals of approx-imately 4 to 5 hours from stroke onset to IA rtPAadministration655 In PROACT II median timefrom stroke onset to randomization and IA rtPA ad-ministration was 282 minutes whereas the IMSstudy demonstrated an interval of 231 minutes fromstroke onset to IA rtPA administration655 Timefrom CT scan to microcatheter placement in thecerebrovasculature had a mean time of 174 60minutes in 91 patients undergoing ERT for AISdemonstrating wide variability and a need for timestandards53 Transferred patients whose laboratorytests and CT scan have already been completed maystill have a door-to-puncture time of up to 60 min-utes57 Further study is needed to identify barriers torapid access to endovascular therapy
Currently the American College of Cardiologyand the AHA recommend that door-to-balloon timein ST segment elevation myocardial infarctionshould be within 90 minutes A similar future pro-posal could be made for ERT in AIS with a goaldoor-to-puncture time of 90 minutes (table 5) Thiswould include activation of the stroke team technol-ogists and nurses Adjunctive time benchmarks canbe developed including puncture-to-clot and clot-to-close goals This target is more difficult to achievefor cerebral than cardiac revascularization as strokepatients require more time-consuming neurologic
Tab
le5
Ben
chm
ark
tim
esfo
rre
vasc
ular
izat
ion
ther
apie
san
dp
ossi
ble
inte
rval
sfo
rE
RT
Am
eric
anC
olle
geof
Car
diol
ogy6
7A
SA
AH
AA
ISG
uide
lines
forI
Vrt
-PA
68
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rE
RT
pres
enti
ngto
ED
ldquoP
rim
ary
ER
TTi
merdquo
Pro
pose
dgo
als
forA
ISpa
tien
tsel
igib
lefo
rRes
cue
ER
Tfo
llow
ing
IVfa
ilure
ldquoIV
-Fai
lure
toR
escu
eE
RTrdquo
Pro
pose
dgo
als
forA
ISpa
tien
tstr
ansf
erre
dfr
omou
tsid
eho
spit
alfo
rER
TldquoD
rip-
and-
Shi
pto
ER
Trdquo
Doo
r-to
-bal
loon
tim
e9
0m
inD
oor-
to-n
eedl
eti
me
60
min
Doo
r-to
-gro
inpu
nctu
reti
me
90
min
Nee
dle
-to-
gro
inp
unct
ure
tim
e6
0m
inD
oora -t
o-G
roin
Pun
ctur
eti
me
60
min
ST
EM
Icon
firm
ed
card
iolo
gis
tno
tifi
ed
10
min
Doo
rto
ED
10
min
Doo
rto
ED
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
0m
in)
ER
Tte
amis
noti
fied
asso
onas
larg
eto
med
ium
vess
eloc
clus
ion
issu
spec
ted
(ie
N
IHS
Sh
yper
dens
eM
CA
onC
T)in
elig
ible
pati
ents
10
min
afte
rth
eel
igib
ility
CT
scan
and
befo
reIV
bolu
s
Tran
sfer
from
outs
ide
hosp
ital
init
iate
dan
gio
suit
eac
tiva
ted
team
acti
vate
d
Pri
orto
arri
val
ED
stab
ilize
sp
atie
nta
ctiv
ates
cath
lab
30
min
Str
oke
team
acti
vati
on1
5m
inS
trok
ean
dE
RT
team
sac
tiva
tion
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(1
5m
in)
Rec
eivi
ngho
spit
alar
riva
lR
apid
hist
ory
and
exam
rev
iew
ofre
ferr
ing
hosp
ital
film
s
15
min
Cat
hla
ban
din
terv
enti
onal
ist
read
y
60
min
CT
scan
init
iate
d2
5m
inC
Tsc
anin
itia
ted
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(2
5m
in)
Ang
iosu
ite
acti
vate
dte
amon
stan
dby
cons
ider
noni
nvas
ive
vasc
ular
imag
ing
25
min
afte
rth
eel
igib
ility
CT
scan
and
afte
rIV
bolu
sin
itia
tion
Anc
illar
ybr
ain
imag
ing
(ie
CT
perf
usio
n)3
5m
in
Fin
alch
eck
and
wri
tten
cons
ent
70
min
CT
scan
inte
rpre
ted
elig
ibili
tyas
sess
ed4
5m
inC
Tsc
anin
terp
rete
del
igib
ility
asse
ssed
Inpa
ralle
lwit
hIV
rtP
Apa
thw
ay(4
5m
in)
Rep
eat
NIH
SS
obt
ain
wri
tten
cons
ent
repe
atC
Tif
clin
ical
wor
seni
ng
45
min
afte
rth
eC
Tsc
anan
d3
0m
inaf
ter
the
IVrt
PA
bolu
s
Fin
alch
eck
wri
tten
cons
ent
pati
ent
prep
ped
45
min
Cat
hete
riza
tion
and
PC
Indashb
allo
onin
flat
ion
90
min
IVrt
PA
infu
sion
60
min
Gro
inpu
nctu
re9
0m
inG
roin
punc
ture
60
min
bG
roin
punc
ture
60
min
Abb
revi
atio
nsA
HA
A
mer
ican
Hea
rtA
ssoc
iati
onA
IS
acut
eis
chem
icst
roke
ang
io
angi
ogra
mA
SA
A
mer
ican
Str
oke
Ass
ocia
tion
ED
em
erge
ncy
depa
rtm
ent
ER
T
endo
vasc
ular
reva
scul
ariz
atio
nth
erap
yIA
intr
a-ar
teri
alM
CA
m
iddl
ece
rebr
alar
tery
NIH
SS
N
IHS
trok
eS
cale
PC
Ipe
rcut
aneo
usco
rona
ryin
terv
enti
onr
tPA
re
com
bina
ntti
ssue
plas
min
ogen
acti
vato
rS
TEM
IS
Tse
gmen
tele
vati
onm
yoca
rdia
linf
arct
ion
aF
rom
tim
eof
arri
valt
oac
cept
ing
hosp
ital
door
b
Tim
ew
illne
edto
bead
just
edto
allo
wfo
rad
diti
onal
imag
ing
ifcl
inic
alex
amin
atio
nw
orse
nsor
sym
ptom
ssu
gges
the
mor
rhag
ictr
ansf
orm
atio
n
S250 Neurology 79 (Suppl 1) September 25 2012
evaluation and brain imaging before proceeding tothe angiography laboratory
Achieving a 90-minute door-to-puncture timewould likely require the neurointerventionalist toplay an integral part in the stroke team because thedecisions on treatment strategy may evolve as the pa-tient proceeds through the AIS protocol and IV rtPAevaluation pathway The ERT protocol should inte-grate into the IV rtPA pathway For interhospitaltransfers the completed imaging and laboratorystudies as well as additional lead time may reduce thetarget time interval to 60 minutes for door-to-puncture However significant delay in hospitaltransfer may warrant repeat neuroimaging when thepatient arrives at the recipient institution Bench-mark times will need to be established for IV nonre-sponders with special consideration for additionaldelay when clinical deterioration following IV rtPArequires a repeat brain imaging prior to ERT
Triage and transfer strategies The considerable de-cline in efficacy of revascularization therapies ataround 6 to 8 hours from symptom onset demandswell-organized triage and transfer strategies46 Emer-gency department reorganization has been an area offocus to improve early identification of stroke pa-tients Tracking door-to-thrombolysis times posi-tioning a CTMRI scanner within the departmentand having emergency medical services (EMS) send aprehospital notification are steps that have improvedthrombolysis access58 However given the limitedavailability of Comprehensive Stroke Center infra-structure few centers in a given geographic regionwill have capabilities for providing comprehensivestroke care and 247 ERT This will lead to a highproportion of patients eligible for ERT arriving byinterhospital transfer Transfer delay has been shownto be a major factor limiting the use of ERT in strokepatients accounting for an estimated odds of treat-ment decrease by 25 for every minute of transfertime59 To avoid transfer delay regional protocols fortriage of AIS patients by EMS personnel to desig-nated stroke centers has become a focus of prehospi-tal stroke triage policy60
Alternative strategies include initiation of IVthrombolytic in a referring hospital prior to transferldquodrip-and-shiprdquo followed by further management atthe accepting hospital which may include ERT Adescribed model of ldquodrip ship and retrieverdquo usedfull-dose IV rtPA (09 mgkg) followed by ERT withmechanical thrombectomy and thrombo-aspirationsuggesting feasibility in basilar artery occlusion61
Different models may evolve where the patient re-ceives ERT in an outside hospital and is transferredfor further care at a comprehensive stroke centerwhere neurosurgery neurocritical care and vascular
neurology expertise are available known as ldquoretrieve-and-shiprdquo Pay-for-performance measures similar tothose for acute myocardial infarction could help fa-cilitate transfer of appropriate patients from primaryto comprehensive stroke centers (the hub-and-spokemodel)
GENERAL PREPROCEDURAL AND INTRAPROCE-DURAL MANAGEMENT Anesthesia and monitoringThe type of anesthesia for ERT has been a topic ofcontroversy with recent reports suggesting worseoutcome with use of general endotracheal anesthesiapossibly due to treatment delays and complicationsfrom intubation6263 Alternatively conscious seda-tion may pose a different set of risks related to patientcooperation especially in those with severe aphasiaor neglect which may negatively influence time torevascularization and procedural success Further-more ancillary monitoring requiring invasive arterialaccess for blood pressure monitoring and central IVaccess may also be of limited value and add delay toinitiation of therapy Further study is needed to eval-uate sedation methods for ERT Sedation methodsmay currently vary among centers
Thromboprophylaxis with systemic anticoagulationArterial catheterization carries a risk of thromboem-bolism often requiring systemic anticoagulationRandomized clinical trials of ERT report variableprotocols for thromboprophylaxis including bolusIV heparin infusion of 2000 to 5000 units atprocedure onset followed by continuous infusionsof approximately 500 units of IV heparin per hourfor the procedure duration621 Alternatively acti-vated clotting time (ACT) values can be obtainedwith heparin boluses to maintain an ACT at atherapeutic goal Limited data exist on the safetyof heparin anticoagulation during ERT proce-dures A subgroup analysis of the MERCI trialshowed no association with hemorrhage or 90-daymortality and heparin use64 A reasonable ACTrange may be 250 to 300 seconds during ERT
Renal prophylaxis Patients with AIS may also havechronic renal impairment which may worsen withcontrast administered during angiography Inter-ventions designed to prevent contrast-induced ne-phropathy have not been rigorously studiedReasonable prophylaxis strategies include hydra-tion with isotonic saline Recent data have notprovided strong support for the administration ofN-acetylcysteine65 The use of sodium bicarbonateinfusion may be reasonable for patients with renalinsufficiency but it can be limited by the largevolume and time to acquire the solution from thepharmacy Periprocedural renal prophylaxis for
Neurology 79 (Suppl 1) September 25 2012 S251
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
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References
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reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
evaluation and brain imaging before proceeding tothe angiography laboratory
Achieving a 90-minute door-to-puncture timewould likely require the neurointerventionalist toplay an integral part in the stroke team because thedecisions on treatment strategy may evolve as the pa-tient proceeds through the AIS protocol and IV rtPAevaluation pathway The ERT protocol should inte-grate into the IV rtPA pathway For interhospitaltransfers the completed imaging and laboratorystudies as well as additional lead time may reduce thetarget time interval to 60 minutes for door-to-puncture However significant delay in hospitaltransfer may warrant repeat neuroimaging when thepatient arrives at the recipient institution Bench-mark times will need to be established for IV nonre-sponders with special consideration for additionaldelay when clinical deterioration following IV rtPArequires a repeat brain imaging prior to ERT
Triage and transfer strategies The considerable de-cline in efficacy of revascularization therapies ataround 6 to 8 hours from symptom onset demandswell-organized triage and transfer strategies46 Emer-gency department reorganization has been an area offocus to improve early identification of stroke pa-tients Tracking door-to-thrombolysis times posi-tioning a CTMRI scanner within the departmentand having emergency medical services (EMS) send aprehospital notification are steps that have improvedthrombolysis access58 However given the limitedavailability of Comprehensive Stroke Center infra-structure few centers in a given geographic regionwill have capabilities for providing comprehensivestroke care and 247 ERT This will lead to a highproportion of patients eligible for ERT arriving byinterhospital transfer Transfer delay has been shownto be a major factor limiting the use of ERT in strokepatients accounting for an estimated odds of treat-ment decrease by 25 for every minute of transfertime59 To avoid transfer delay regional protocols fortriage of AIS patients by EMS personnel to desig-nated stroke centers has become a focus of prehospi-tal stroke triage policy60
Alternative strategies include initiation of IVthrombolytic in a referring hospital prior to transferldquodrip-and-shiprdquo followed by further management atthe accepting hospital which may include ERT Adescribed model of ldquodrip ship and retrieverdquo usedfull-dose IV rtPA (09 mgkg) followed by ERT withmechanical thrombectomy and thrombo-aspirationsuggesting feasibility in basilar artery occlusion61
Different models may evolve where the patient re-ceives ERT in an outside hospital and is transferredfor further care at a comprehensive stroke centerwhere neurosurgery neurocritical care and vascular
neurology expertise are available known as ldquoretrieve-and-shiprdquo Pay-for-performance measures similar tothose for acute myocardial infarction could help fa-cilitate transfer of appropriate patients from primaryto comprehensive stroke centers (the hub-and-spokemodel)
GENERAL PREPROCEDURAL AND INTRAPROCE-DURAL MANAGEMENT Anesthesia and monitoringThe type of anesthesia for ERT has been a topic ofcontroversy with recent reports suggesting worseoutcome with use of general endotracheal anesthesiapossibly due to treatment delays and complicationsfrom intubation6263 Alternatively conscious seda-tion may pose a different set of risks related to patientcooperation especially in those with severe aphasiaor neglect which may negatively influence time torevascularization and procedural success Further-more ancillary monitoring requiring invasive arterialaccess for blood pressure monitoring and central IVaccess may also be of limited value and add delay toinitiation of therapy Further study is needed to eval-uate sedation methods for ERT Sedation methodsmay currently vary among centers
Thromboprophylaxis with systemic anticoagulationArterial catheterization carries a risk of thromboem-bolism often requiring systemic anticoagulationRandomized clinical trials of ERT report variableprotocols for thromboprophylaxis including bolusIV heparin infusion of 2000 to 5000 units atprocedure onset followed by continuous infusionsof approximately 500 units of IV heparin per hourfor the procedure duration621 Alternatively acti-vated clotting time (ACT) values can be obtainedwith heparin boluses to maintain an ACT at atherapeutic goal Limited data exist on the safetyof heparin anticoagulation during ERT proce-dures A subgroup analysis of the MERCI trialshowed no association with hemorrhage or 90-daymortality and heparin use64 A reasonable ACTrange may be 250 to 300 seconds during ERT
Renal prophylaxis Patients with AIS may also havechronic renal impairment which may worsen withcontrast administered during angiography Inter-ventions designed to prevent contrast-induced ne-phropathy have not been rigorously studiedReasonable prophylaxis strategies include hydra-tion with isotonic saline Recent data have notprovided strong support for the administration ofN-acetylcysteine65 The use of sodium bicarbonateinfusion may be reasonable for patients with renalinsufficiency but it can be limited by the largevolume and time to acquire the solution from thepharmacy Periprocedural renal prophylaxis for
Neurology 79 (Suppl 1) September 25 2012 S251
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
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for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
httpnneurologyorgcontent7913_Supplement_1S243fullincluding high resolution figures can be found at
References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
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ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
ehttpnneurologyorgcgicollectionall_cerebrovascular_disease_strokAll Cerebrovascular diseaseStrokefollowing collection(s) This article along with others on similar topics appears in the
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httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
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rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2012 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
ERT in select AIS patients is an important area inneed of further investigation
POSTPROCEDURAL MANAGEMENT ImagingPatients may benefit from postprocedural imagingincluding noncontrast head CT or susceptibility-weighted MRI within 16 to 32 hours from ERTGiven the associated risk of hemorrhagic complica-tions with revascularization therapy urgent head CTor MRI may be needed for clinical deterioration inthe postprocedure period Intraprocedure imaging isalso possible in many angiography suites and can of-fer rapid diagnostic information
Neuromonitoring Intensive care unit monitoringwith staff trained in neurologic patient care may beimportant for postprocedure neuromonitoring in-cluding frequent neurologic examination assessmentsby nursing staff experienced and trained in neurovas-cular diseases Intensive monitoring would also in-clude surveillance for groin-access complications andthe appropriate management Stroke severity andoutcome scales may be important in performancemonitoring
Blood pressure management Patients in whom revas-cularization was successful may be at risk of reperfu-sion hemorrhage thereby warranting aggressiveblood pressure control Common practice has fol-lowed a protocol similar to that for post IV rtPAadministration with vigilant blood pressure monitor-ing for at least the first 24 hours Blood pressure ismeasured every 15 minutes for 2 hours then every30 minutes for 6 hours and every hour for 18hours Goal blood pressure is targeted to remainbelow 180105 mm Hg Bolus dosing of labetololor continuous infusion of nicardipine has beenused to achieve target blood pressure Adjustmentsin blood pressure parameters may be necessary toachieve clinical stability
Antithrombotic regimen Postprocedure antithrom-botic regimen will likely follow a similar pathway tothat in general AIS management Antithromboticsare usually avoided in the first 24 hours following IVand IA administration of a thrombolytic agent Cer-tain procedures may present exceptions such as pa-tients receiving stent implantation in which therespective preferred regimen will need to be imple-mented This may include loading doses of 325 to650 mg of aspirin (orally or rectally) and 300 to 600mg of clopidogrel with subsequent dual antiplatelettherapy with daily aspirin (325 mg) and clopidogrel(75 mg) for 4 to 12 weeks followed by indefinitesingle-antiplatelet therapy with aspirin 325 mg dailyor tailored to the underlying etiology A potentialhazard of dual antiplatelet therapy for acute stent im-
plantation in a patient with a recent large stroke in-cludes hemorrhage
Glycemia management Hyperglycemia may be asso-ciated with an increased risk of hemorrhagic transfor-mation of the cerebral infarction66 An appropriateglycemic-control regimen will likely be modeled afterexisting management strategies developed for AIS
Statin therapy Comprehensive management strate-gies for patients with AIS who undergo ERT willlikely also adopt statin therapy regimens modeled af-ter those developed for AIS patients in general
CLINICAL OUTCOME MEASUREMENTS Moni-toring clinical outcomes following ERT is importantfor quality metrics Thresholds and benchmarks foracceptable stroke severityndashweighted sICH and mor-tality rates need to be established The proportion ofpatients completing 90-day clinical follow-up (fromthose who are eligible) needs to be established Simi-larly consensus on rates of 90-day good functionalmRS outcome (score of 0ndash2) following ERT needsto be established
DISCUSSION This outline can be used as a frame-work for the development of future practice recom-mendations and as an interim tool that the practicingneurovascular specialist can use to assess the rapidlyevolving management strategies This evolving fieldis marked by ongoing intense investigation of varioustherapies for acute revascularization which will de-mand frequent reevaluation and modification ofthese strategies
AUTHOR CONTRIBUTIONSAll authors participated in the design and revision of the manuscript Dr
Lazzaro draftingrevising the manuscript study concept or design analy-
sis or interpretation of data Dr Novakovic draftingrevising the manu-
script acquisition of data statistical analysis study supervision Dr
Alexandrov draftingrevising the manuscript discussion of review con-
tent Dr Darkhabani draftingrevising the manuscript acquisition of
data Dr Edgell draftingrevising the manuscript Dr English drafting
revising the manuscript analysis or interpretation of data Dr Frei draft-
ingrevising the manuscript Dr Jamieson draftingrevising the
manuscript Dr Janardhan draftingrevising the manuscript study con-
cept or design analysis or interpretation of data development of stroke
algorithms and figures for acute ischemic stroke endovascular therapy Dr
N Janjua draftingrevising the manuscript Dr RM Janjua drafting
revising the manuscript Dr Katzan draftingrevising the manuscript Dr
Khatri study concept or design Dr Kirmani study concept or design
study supervision Dr Liebeskind draftingrevising the manuscript anal-
ysis or interpretation of data acquisition of data Dr Linfante drafting
revising the manuscript study concept or design analysis or
interpretation of data study supervision Dr Nguyen draftingrevising
the manuscript Dr Saver draftingrevising the manuscript study con-
cept or design analysis or interpretation of data Dr Shutter drafting
revising the manuscript Dr Xavier draftingrevising the manuscript Dr
Yavagal draftingrevising the manuscript Dr Zaidat draftingrevising
the manuscript study concept or design contribution of vital reagents
toolspatients acquisition of data statistical analysis study supervision
S252 Neurology 79 (Suppl 1) September 25 2012
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
httpnneurologyorgcontent7913_Supplement_1S243fullincluding high resolution figures can be found at
References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
Citations
ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
ehttpnneurologyorgcgicollectionall_cerebrovascular_disease_strokAll Cerebrovascular diseaseStrokefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpnneurologyorgsubscribersadvertiseInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2012 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
DISCLOSUREDr Lazzaro reports no disclosures Dr Novakovic performs endovascular
treatments for acute ischemic strokes (has not used a retrievable stent) Dr
Alexandrov serves as an Associate Editor for Frontiers in Interventional
Neurology has a patent for Therapeutic Methods and Apparatus for Use of
Sonication to Enhance Perfusion of Tissue has received publishing royalties
for Cerebrovascular Ultrasound in Stroke Prevention and Treatment (first
and second editions) has served as a consultant for Cerevast Therapeutics
spends 60 effort on clinical stroke service at Comprehensive Stroke
Center UAB Hospital monitoring endovascular procedures and evaluat-
ing success of recanalization with imaging has received research support
from Cerevast Therapeutics Inc has received research support from
NINDS has received compensation from Cerevast Therapeutics Inc
and has received license fee payments from Therapeutic Methods and Ap-
paratus for Use of Sonication to Enhance Perfusion of Tissue Dr Darkha-
bani reports no disclosures Dr Edgell serves as an Associate Editor
Frontiers in Interventional Neurology Dr English has served on the scien-
tific advisory board of Concentric Medical Inc Clinical Events Commit-
tee serves on the editorial boards of Neurohospitalist and The Stroke
Interventionalist and serves as Medical Scientific Advisor for Silk Road
Medical Dr Frei has served as a consultant to Penumbra Inc Dr Ja-
mieson has served as a consultant to Bayer and Boerhinger-Ingelheim
served on the speakers bureau for Boehringer-Ingelheim and Merck
served on the scientific advisory board for Bayer and on the Adjudication
Committee for ARRIVE trial and serves as an Assistant Editor for Neurol-
ogy Alert Dr Janardhan reports no disclosures Dr N Janjua serves on
the scientific advisory board for LundbeckDSMB and Neurointerven-
tions receives research support from NIHNINDS and holds stock or
stock options or board of directors compensation for Neurointerventions
Dr RM Janjua reports no disclosures Dr Katzan has served as consul-
tant to Pzifer and Genentech served as a speaker for and received com-
pensation from Cardionet serves on the Real World Advisory Board for
Pfizer has received research funding from Novartis Inc Hoffman-La
Roche Ltd and Takeda Pharmaceuticals and has received research fund-
ing from Ohio Department of Health Dr Khatri is on the Executive
Committee of the IMS III Trial is Neurology PI of the Penumbra
THERAPY Trial and has received research support from Genentech
Inc for survey implementation served on the editorial boards of Frontiers
in Endovascular and Interventional Neurology has received research sup-
port from the NIHNINDS and has served as an expert witness for stroke
cases over the last 2 years Dr Kirmani served on the advisory board for
Otsuka Pharmaceuticals served as an Associate Editor for Frontiers in
Clinical Trials in Neurology received publishing royalties from the Taylor
and Francis Group for The Stroke Center Handbook receives research sup-
port from Penumbra Inc and Genentech Inc received research support
from NIHNINDS and has served as expert witness for stroke cases Dr
Liebeskind served as a consultant for Concentric Medical and CoAxia and
receives research support from NIH Dr Linfante served as a consultant
for Codman Neurovascular and Stryker holds stock options in Surpass
Limited serves on the Scientific Advisory Board for Codman Neurovas-
cular serves on the editorial boards for Stroke and Journal of Neurointer-
ventional Surgery and serves on the speakers bureau for Codman Dr
Nguyen serves as Associate Editor of Frontiers in Vascular and Interven-
tional Neurology and Editor of SVIN newsletter The Core performs intra-
arterial stroke procedures and serves as a consultant for Penumbra Dr
Saver serves on the editorial boards of Stroke Reviews in Neurologic Dis-
ease Journal of Neuroimaging and Journal of Stroke and Cerebrovascular
Diseases is an employee of the University of California (UC) which holds
a patent on retriever devices for stroke serves on scientific advisory
boards for which the UC Regents receive payments for CoAxia Inc
Concentric Medical Talecris Biotherapeutics Ferrer AGA Medical Cor-
poration BrainsGate PhotoThera Ev3 and Sygnis Bioscience GmbH amp
Co KG is an unpaid site investigator in multicenter clinical trials spon-
sored by AGA Medical Corporation Lundbeck Inc and Ev3 for which
the UC Regents received payments based on clinical trial contracts for the
number of subjects enrolled is an unpaid site investigator in the NIH
IRIS CLEAR IMS 3 SAMMPRIS and VERITAS multicenter clinical
trials for which the UC Regents receive payments based on clinical trial
contracts for the number of subjects enrolled receives research support
from the NIH and NINDS receives research support from the AHA and
performs acute stroke care (35) Dr Shutter serves on the scientific
advisory board for Neuren Pharmaceuticals receives funding for travel or
speaker honoraria from Codman JampJ and NIH serves as a consultant for
Cincinnati Bengals receives research support from Department of De-
fense and NIH (NINDS) receives research support from the Mayfield
Education and Research Fund and holds stock options in UCB Pharma
Dr Xavier receives research support from Concentric Medical and from
Medical University of South CarolinaNIH study Dr Yavagal received
an honorarium from Penumbra Inc for consultation and speaking serves
as an Associate Editor for Frontiers in Endovascular Neurology and serves
as a consultant to Penumbra Inc Codman Neurovascular Micrus Inc
Genentech and Boston Scientific Dr Zaidat serves on the scientific advi-
sory board for Talecris served on the adjudication committee for Stryker
received speaker honoraria from Stryker served on the editorial board of
Frontiers in Neurology (Endovascular amp Interventional Neurology Sec-
tion) serves as Editor of The Journal of Neurointerventional Surgery and
serves as Associate Editor and is a member of the Editorial Board of Jour-
nal of Stroke amp Cerebrovascular Diseases served as a consultant for Stryker
Neurovascular Codman Neurovascular and Microvention Inc and has
received research support from Society of Vascular amp Interventional Neu-
rology (SVIN) for this educational activity Go to Neurologyorg for full
disclosures
Received December 10 2011 Accepted in final form February 23 2012
REFERENCES1 Adams HP Jr del Zoppo G Alberts MJ et al Guidelines
for the early management of adults with ischemic stroke aguideline from the American Heart AssociationAmericanStroke Association Stroke Council Clinical CardiologyCouncil Cardiovascular Radiology and InterventionCouncil and the Atherosclerotic Peripheral Vascular Dis-ease and Quality of Care Outcomes in Research Interdisci-plinary Working Groups Stroke 2007381655ndash1711
2 The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group Tissue plasminogen ac-tivator for acute ischemic stroke N Engl J Med 19953331581ndash1587
3 Zaidat OO Suarez JI Sunshine JL et al Thrombolytictherapy of acute ischemic stroke correlation of angio-graphic recanalization with clinical outcome AJNR Am JNeuroradiol 200526880ndash884
4 Rha JH Saver JL The impact of recanalization on ischemicstroke outcome a meta-analysis Stroke 200738967ndash973
5 del Zoppo GJ Higashida RT Furlan AJ Pessin MS Row-ley HA Gent M PROACT a phase II randomized trial ofrecombinant pro-urokinase by direct arterial delivery inacute middle cerebral artery stroke PROACT Investiga-tors Prolyse in Acute Cerebral Thromboembolism Stroke1998294ndash11
6 Furlan A Higashida R Wechsler L et al Intra-arterialprourokinase for acute ischemic stroke the PROACT IIstudy a randomized controlled trial Prolyse in Acute Ce-rebral Thromboembolism JAMA 19992822003ndash2011
7 Alberts MJ Latchaw RE Selman WR et al Recommenda-tions for comprehensive stroke centers a consensus statementfrom the Brain Attack Coalition Stroke 2005361597ndash1616
8 Leifer D Bravata DM Connors JJ 3rd et al Metrics formeasuring quality of care in comprehensive stroke centersdetailed follow-up to Brain Attack Coalition comprehensivestroke center recommendations a statement for healthcareprofessionals from the American Heart AssociationAmericanStroke Association Stroke 201142849ndash877
9 Meyers PM Schumacher HC Higashida RT et al Indica-tions for the performance of intracranial endovascular neu-
Neurology 79 (Suppl 1) September 25 2012 S253
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
httpnneurologyorgcontent7913_Supplement_1S243fullincluding high resolution figures can be found at
References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
Citations
ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
ehttpnneurologyorgcgicollectionall_cerebrovascular_disease_strokAll Cerebrovascular diseaseStrokefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpnneurologyorgsubscribersadvertiseInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2012 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
rointerventional procedures a scientific statement from
the American Heart Association Council on Cardiovascu-
lar Radiology and Intervention Stroke Council Council
on Cardiovascular Surgery and Anesthesia Interdisciplin-
ary Council on Peripheral Vascular Disease and Interdisci-
plinary Council on Quality of Care and Outcomes
Research Circulation 20091192235ndash2249
10 Smith WS Sung G Starkman S et al Safety and efficacy
of mechanical embolectomy in acute ischemic stroke re-
sults of the MERCI trial Stroke 2005361432ndash1438
11 The penumbra pivotal stroke trial safety and effectiveness
of a new generation of mechanical devices for clot removal
in intracranial large vessel occlusive disease Stroke 2009
402761ndash2768
12 Ogawa A Mori E Minematsu K et al Randomized trial
of intraarterial infusion of urokinase within 6 hours of
middle cerebral artery stroke the Middle Cerebral Artery
Embolism Local Fibrinolytic Intervention Trial (MELT)
Japan Stroke 2007382633ndash2639
13 Lee M Hong KS Saver JL Efficacy of intra-arterial fibri-
nolysis for acute ischemic stroke meta-analysis of random-
ized controlled trials Stroke 201041932ndash937
14 Inoue T Kimura K Minematsu K Yamaguchi T A case-
control analysis of intra-arterial urokinase thrombolysis in
acute cardioembolic stroke Cerebrovasc Dis 200519225ndash
228
15 Nogueira RG Liebeskind DS Sung G Duckwiler G Smith
WS Predictors of good clinical outcomes mortality and suc-
cessful revascularization in patients with acute ischemic stroke
undergoing thrombectomy pooled analysis of the Mechani-
cal Embolus Removal in Cerebral Ischemia (MERCI) and
Multi MERCI Trials Stroke 2009403777ndash3783
16 Saver JL Liebeskind DS Nogueira RG Jahan R Need to
clarify Thrombolysis In Myocardial Ischemia (TIMI) scale
scoring method in the Penumbra Pivotal Stroke Trial
Stroke 201041e115ndashe116
17 Intra-arterial Versus Systemic Thrombolysis for Acute
Ischemic Stroke SYNTHESIS EXP Available at stroke-
centerorg Accessed November 26 2011
18 MR CLEAN a multicenter randomized clinical trial of endo-
vascular treatment for acute ischemic stroke in the Nether-
lands 2011 Available at wwwtrialregisternltrialregadmin
rctviewaspTC1804 Accessed November 26 2011
19 Mechanical Retrieval and Recanalization of Stroke Clots
Using Embolectomy MR RESCUE Available at clinical-
trialsgovct2showNCT00389467 Accessed November
26 2011
20 Assess the Penumbra System in the Treatment of Acute
Stroke (THERAPY) Available at clinicaltrialsgovct2
showNCT01429350 Accessed November 26 2011
21 The Interventional Management of Stroke (IMS) trials
Available at httpwwwstrokecenterorgtrialstrialDe-
tailaspxtid747 Accessed August 26 2011
22 Zaidat OO Wolfe T Hussain SI et al Interventional
acute ischemic stroke therapy with intracranial self-
expanding stent Stroke 2008392392ndash2395
23 Roth C Papanagiotou P Behnke S et al Stent-assisted
mechanical recanalization for treatment of acute intracere-
bral artery occlusions Stroke 2010412559ndash2567
24 Castano C Dorado L Guerrero C et al Mechanical
thrombectomy with the Solitaire AB device in large artery
occlusions of the anterior circulation a pilot study Stroke
2010411836ndash1840
25 Hacke W Kaste M Bluhmki E et al Thrombolysis withalteplase 3 to 45 hours after acute ischemic stroke N EnglJ Med 20083591317ndash1329
26 Clark WM Wissman S Albers GW Jhamandas JH Mad-den KP Hamilton S Recombinant tissue-type plasmino-gen activator (alteplase) for ischemic stroke 3 to 5 hoursafter symptom onset the ATLANTIS study a randomizedcontrolled trial Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke JAMA 19992822019ndash2026
27 Del Zoppo GJ Saver JL Jauch EC Adams HP Jr Expan-sion of the time window for treatment of acute ischemicstroke with intravenous tissue plasminogen activator a sci-ence advisory from the American Heart AssociationAmer-ican Stroke Association Stroke 2009402945ndash2948
28 Eckert B Kucinski T Pfeiffer G Groden C Zeumer HEndovascular therapy of acute vertebrobasilar occlusionearly treatment onset as the most important factor Cere-brovasc Dis 20021442ndash50
29 Smith WS Sung G Saver J et al Mechanical thrombec-tomy for acute ischemic stroke final results of the MultiMERCI trial Stroke 2008391205ndash1212
30 Schulte-Altedorneburg G Hamann GF Mull M et alOutcome of acute vertebrobasilar occlusions treated withintra-arterial fibrinolysis in 180 patients AJNR Am J Neu-roradiol 2006272042ndash2047
31 Arnold M Nedeltchev K Schroth G et al Clinical andradiological predictors of recanalisation and outcome of 40patients with acute basilar artery occlusion treated withintra-arterial thrombolysis J Neurol Neurosurg Psychiatry200475857ndash862
32 Schonewille WJ Wijman CA Michel P et al Treatmentand outcomes of acute basilar artery occlusion in the Basi-lar Artery International Cooperation Study (BASICS) aprospective registry study Lancet Neurol 20098724 ndash730
33 Mishra NK Albers GW Davis SM et al Mismatch-baseddelayed thrombolysis a meta-analysis Stroke 201041e25ndashe33
34 Jovin TG Liebeskind DS Gupta R et al Imaging-basedendovascular therapy for acute ischemic stroke due toproximal intracranial anterior circulation occlusion treatedbeyond 8 hours from time last seen well retrospective mul-ticenter analysis of 237 consecutive patients Stroke 2011422206ndash2211
35 Hacke W Kaste M Fieschi C et al Intravenous throm-bolysis with recombinant tissue plasminogen activator foracute hemispheric stroke the European Cooperative AcuteStroke Study (ECASS) JAMA 19952741017ndash1125
36 Pexman JH Barber PA Hill MD et al Use of the AlbertaStroke Program Early CT Score (ASPECTS) for assessingCT scans in patients with acute stroke AJNR Am J Neu-roradiol 2001221534ndash1542
37 Saqqur M Uchino K Demchuk AM et al Site of arterialocclusion identified by transcranial Doppler predicts theresponse to intravenous thrombolysis for stroke Stroke200738948ndash954
38 Mathews MS Sharma J Snyder KV et al Safety effective-ness and practicality of endovascular therapy within thefirst 3 hours of acute ischemic stroke onset Neurosurgery200965860ndash865 2009
39 Gupta R Tayal AH Levy EI et al Intra-arterial throm-bolysis or stent placement during endovascular treatmentfor acute ischemic stroke leads to the highest recanalization
S254 Neurology 79 (Suppl 1) September 25 2012
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
httpnneurologyorgcontent7913_Supplement_1S243fullincluding high resolution figures can be found at
References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
Citations
ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
ehttpnneurologyorgcgicollectionall_cerebrovascular_disease_strokAll Cerebrovascular diseaseStrokefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpnneurologyorgsubscribersadvertiseInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2012 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
rate results of a multicenter retrospective study Neurosur-gery 2011681618ndash1623
40 The Interventional Management of Stroke (IMS) II studyStroke 2007382127ndash2135
41 Mazighi M Serfaty JM Labreuche J et al Comparison ofintravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and con-firmed arterial occlusion (RECANALISE study) aprospective cohort study Lancet Neurol 20098802ndash809
42 Rubiera M Ribo M Pagola J et al Bridging intravenous-intra-arterial rescue strategy increases recanalization andthe likelihood of a good outcome in nonresponder intrave-nous tissue plasminogen activator-treated patients a case-control study Stroke 201142993ndash997
43 Costalat V Machi P Lobotesis K et al Rescue combinedand stand-alone thrombectomy in the management oflarge vessel occlusion stroke using the solitaire device aprospective 50-patient single-center study timing safetyand efficacy Stroke 2011421929ndash1935
44 Eckert B Koch C Thomalla G et al Aggressive therapywith intravenous abciximab and intra-arterial rtPA and ad-ditional PTAstenting improves clinical outcome in acutevertebrobasilar occlusion combined local fibrinolysis andintravenous abciximab in acute vertebrobasilar stroketreatment (FAST) results of a multicenter study Stroke2005361160ndash1165
45 Pfefferkorn T Mayer TE Opherk C et al Staged escala-tion therapy in acute basilar artery occlusion intravenousthrombolysis and on-demand consecutive endovascularmechanical thrombectomy preliminary experience in 16patients Stroke 2008391496ndash1500
46 Khatri P Abruzzo T Yeatts SD Nichols C Broderick JPTomsick TA Good clinical outcome after ischemic strokewith successful revascularization is time-dependent Neu-rology 2009731066ndash1072
47 Nogueira RG Smith WS Sung G et al Effect of time toreperfusion on clinical outcome of anterior circulation strokestreated with thrombectomy pooled analysis of the MERCIand Multi MERCI trials Stroke Epub 2011 Sept 15
48 NINDS Proceedings of a National Symposium on RapidIdentification and Treatment of Acute Stroke NationalInstitute of Neurological Disorders and Stroke 2011Available at httpwwwnindsnihgovnews_and_eventsproceedingsstroke_proceedingsexecsumhtm AccessedSeptember 15 2011
49 Mattle HP Arnold M Georgiadis D et al Comparison ofintraarterial and intravenous thrombolysis for ischemicstroke with hyperdense middle cerebral artery sign Stroke200839379ndash383
50 Wolfe T Suarez JI Tarr RW et al Comparison of com-bined venous and arterial thrombolysis with primary arte-rial therapy using recombinant tissue plasminogenactivator in acute ischemic stroke J Stroke CerebrovascDis 200817121ndash128
51 Suarez JI Sunshine JL Tarr R et al Predictors of clinicalimprovement angiographic recanalization and intracra-nial hemorrhage after intra-arterial thrombolysis for acuteischemic stroke Stroke 1999302094ndash2100
52 Flaherty ML Woo D Kissela B et al Combined IV andintra-arterial thrombolysis for acute ischemic stroke Neu-rology 200564386ndash388
53 Miley JT Memon MZ Hussein HM et al A multicenteranalysis of ldquotime to microcatheterrdquo for endovascular therapyin acute ischemic stroke J Neuroimaging 201121159ndash64
54 Ducrocq X Bracard S Taillandier L et al Comparison of
intravenous and intra-arterial urokinase thrombolysis for
acute ischaemic stroke J Neuroradiol 20053226ndash32
55 Combined intravenous and intra-arterial recanalization for
acute ischemic stroke the Interventional Management of
Stroke Study Stroke 200435904ndash911
56 Lewandowski CA Frankel M Tomsick TA et al Com-
bined intravenous and intra-arterial r-TPA versus intra-
arterial therapy of acute ischemic stroke Emergency
Management of Stroke (EMS) Bridging Trial Stroke
1999302598ndash2605
57 Lazzaro MA LV Mohammad Y Chen M Lopes DK
Prabhakaran S Weekend effect is not observed in time to
angiography for transferred acute ischemic stroke patients
Cerebrovasc Diseases 201029(suppl 2)329
58 Lindsberg PJ Happola O Kallela M Valanne L Kuisma
M Kaste M Door to thrombolysis ER reorganization and
reduced delays to acute stroke treatment Neurology 2006
67334ndash336
59 Prabhakaran S Ward E John S et al Transfer delay is a
major factor limiting the use of intra-arterial treatment in
acute ischemic stroke Stroke 2011421626ndash1630
60 Crocco TJ Grotta JC Jauch EC et al EMS management
of acute strokendashprehospital triage (resource document to
NAEMSP position statement) Prehosp Emerg Care 2007
11313ndash317
61 Pfefferkorn T Holtmannspotter M Schmidt C et al
Drip ship and retrieve cooperative recanalization therapy
in acute basilar artery occlusion Stroke 201041722ndash726
62 Abou-Chebl A Lin R Hussain MS et al Conscious seda-
tion versus general anesthesia during endovascular therapy
for acute anterior circulation stroke preliminary results
from a retrospective multicenter study Stroke 201041
1175ndash1179
63 Gupta R Local is better than general anesthesia during
endovascular acute stroke interventions Stroke 201041
2718ndash2719
64 Nahab F Walker GA Dion JE Smith WS Safety of
periprocedural heparin in acute ischemic stroke endovas-
cular therapy the Multi MERCI trial J Stroke Cerebro-
vasc Dis Epub 2011 June 1
65 Acetylcysteine for prevention of renal outcomes in patients
undergoing coronary and peripheral vascular angiography
main results from the randomized Acetylcysteine for
Contrast-Induced Nephropathy Trial (ACT) Circulation
20111241250ndash1259
66 Kase CS Furlan AJ Wechsler LR et al Cerebral hemor-
rhage after intra-arterial thrombolysis for ischemic stroke
the PROACT II trial Neurology 2001571603ndash1610
67 Antman EM Anbe DT Armstrong PW et al ACCAHA
guidelines for the management of patients with ST-
elevation myocardial infarction a report of the American
College of CardiologyAmerican Heart Association Task
Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients with
Acute Myocardial Infarction) J Am Coll Cardiol 200444
E1ndashE211
68 Fonarow GC Smith EE Saver JL et al Improving door-
to-needle times in acute ischemic stroke the design and
rationale for the American Heart AssociationAmerican
Stroke Associationrsquos target stroke initiative Stroke 2011
422983ndash2989
Neurology 79 (Suppl 1) September 25 2012 S255
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
httpnneurologyorgcontent7913_Supplement_1S243fullincluding high resolution figures can be found at
References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
Citations
ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
ehttpnneurologyorgcgicollectionall_cerebrovascular_disease_strokAll Cerebrovascular diseaseStrokefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpnneurologyorgsubscribersadvertiseInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2012 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
DOI 101212WNL0b013e31826959fc201279S243-S255 Neurology
Marc A Lazzaro Roberta L Novakovic Andrei V Alexandrov et al ischemic stroke
Developing practice recommendations for endovascular revascularization for acute
This information is current as of September 24 2012
ServicesUpdated Information amp
httpnneurologyorgcontent7913_Supplement_1S243fullincluding high resolution figures can be found at
References
1httpnneurologyorgcontent7913_Supplement_1S243fullref-list-This article cites 60 articles 41 of which you can access for free at
Citations
ticleshttpnneurologyorgcontent7913_Supplement_1S243fullotherarThis article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
ehttpnneurologyorgcgicollectionall_cerebrovascular_disease_strokAll Cerebrovascular diseaseStrokefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpnneurologyorgsubscribersadvertiseInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2012 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology