Progress continues to be made indeveloping stroke services in Wales, but it isslower and less comprehensive than is ourvision.

The “Stroke Services Improvement Plan”has completed its work programme, butthe Welsh Stroke Alliance, which wasdeveloped as its clinical reference body, isto continue to advise the Stroke DeliveryGroup of the Welsh Assembly Government.

The £2.25m recurrent funding for acutestroke services has been fully implementedthroughout Wales, and that has enabledmost Health Boards to meet the AOFtargets for Stroke and to radically improvethe service to patients.

Many of the improvements in service aredue to the skills, initiative and flexibility ofour Stroke Teams, but additional funding isessential for certain gains to be achieved.

We among others have developed and aredelivering 9-5 Thrombolysis for acutestroke by innovation without any additionalfunding, but 24/7 delivery throughoutWales is a different matter…..

The Health Wellbeing and LocalGovernment committee of the NationalAssembly of Wales has completed aninquiry into Stroke Services in Wales, towhich I and many others contributed, andtheir report is eagerly awaited and shouldhelp to keep Stroke as a priority.

Health Boards have all submitted theirAction Plans for 2009-2015, with a view todeveloping “world class” stroke services bythat date.

Having initially concentrated on acuteservices, perceived as the basic essential,work is on-going on improving prevention,rehabilitation and longer term care. This issupported by the learning sets of All WalesStroke Improvement Collaborative and thedevelopment and use of “Intelligenttargets” to allow on-going monitoring ofcare delivery. Most of these targets aresimplistic process rather than outcomemeasures, and without clerical support canimpinge on clinical time.

The National Sentinel Stroke Audits allowus to benchmark our progress, and if theydemonstrate progress may encouragefurther investment. The 2009Organisational Audit is perhaps too early,but shows some improvement.

Onward and upward…

Dr Richard Dewar MD FRCPConsultant Physician and Stroke Specialist

Editorial

welsh stroke bulletinHysbysiad Trawiad yr Ymenydd Cymru

March 2010Volume 21

ContentsChallenges in implementing thrombolysis for acuteischaemic stroke in clinical practice

Stroke Research Group Update: Accrual to Welsh sites

4th UK Stroke Forum 2009 at Glasgow: More than 90medical centers in UK are thrombolysing ischaemicstroke patients

A curious constellation of deficits

Arteriovenous Malformations and Hemorrhagic Stroke

Pick of the Papers: June to December 2009

Welsh Association of StrokePhysicians (WASP)Dr. Anne Freeman - ChairmanDr. Mushtaq Wani - Vice ChairmanDr Tom Hughes - Secretary

EditorDr. Taj HasanCaerphilly District Miners HospitalCaerphilly

Editorial boardDr Chris HudsonSingleton HospitalSwansea

Dr Dick DewarRoyal Glamorgan HospitalLlantrisant

Dr Pradeep KhannaNevill Hall HospitalAbergavenny

Dr V AdhiyamanGlan Clwyd Hospital, Rhyl

Dr Abhaya GuptaCarmarthen General Hospital Carmarthen

Now published

Bi-annually

We would like to thank Sanofi Aventis and Bristol Myers Squibb for their continued support

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National Sentinel Stroke Audit 2009 Organisational Audit Report

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Challenges in implementing thrombolysisfor acute ischaemic stroke in clinicalpracticeSHAKEEL AHMAD, MARIA FITZPATRICK, JOZEF JAROSZ*, LALIT KALRA

DEPARTMENT OF STROKE MEDICINE, KING’S COLLEGE LONDON SCHOOL OF MEDICINE, LONDON*DEPARTMENT OF NEURORADIOLOGY, KING’S COLLEGE HOSPITAL, LONDON

ABSTRACT

Background: Less than 1% stroke patients inEngland were thrombolysed, partly because of lack ofrapid triage and scanning procedures. Weinvestigated efficiency of hospital processes in 50consecutively thrombolysed patients in a Londonhospital.

Methods: A care pathway was used for thrombolysisup to 6 hours after stroke onset. Perfusion CTscanning (PCT) was undertaken in 25 (50%) patients.Data were collected on baseline characteristics andthe times of stroke onset, presentation, imaging andtreatment. Outcome was measured by measuring theNational Institute of Health Stroke Scale (NIHSS)score, mortality, intracranial haemorrhage (ICH) andRankin score at 1, 7, 30 and 90 days..

Results: The median time from stroke onset topresentation was 0:51min, arrival to scan 1h:07minand scan to treatment 0:30min. The median “door toneedle” time was 1h:51min. Although 45 (90%)patients were in hospital within 2 hours of strokeonset, only 28 (56%) were thrombolysed within 3hours. There were no difference in the medianchange in NIHSS score (7 v 6), mortality (7/28 v4/22) or ICH (2/28 v 3/22) between 0-3 and 3-6hour groups. PCT did not delay treatment and wasassociated with a trend towards lower mortality (0/10v 3/12) and comparable ICH rate (1/10 v 2/12) inpatients treated after 3 hours.

Conclusions: Thrombolysis in routine clinicalpractice is feasible and safe in local hospitals butrequires implementing robust processes for rapidassessment for eligibility. PCT does not delaytreatment and may be helpful in refining thrombolysisdecisions.

INTRODUCTION

The introduction of thrombolytic therapy hasrevolutionised the management of acute stroke patients.There are no doubts that thrombolysis is, indeed, apowerful intervention which significantly reduces deathor dependency (OR 0.66, 95% CI 0.53 to 0.83) with nosignificant increase in adverse effects (OR 1.13, 95% CI0.86 to 1.48) for ischaemic stroke patients treated within3 hours of onset.1 Unfortunately, the trial benefits ofthrombolysis do not translate fully into clinicaleffectiveness in mainstream practice; studies have shownthat only 25-33% of patients present to hospitals within3 hours of stroke onset,2,3 and only 5-11% of allischaemic stroke patients are thromblysed even inspecialist centres in USA and Europe.3-7 The situation isworse in England and Wales, where thrombolysis hasnot been implemented widely and remains a cause fornational concern.8

The emphasis for improving the uptake of thrombolysishas been on increasing public awareness of strokesymptoms and encouraging early presentation tohospitals that have facilities to thrombolyse strokepatients.4,5,9 However, this may not be the onlyproblem; a UK-wide study has shown that nearly 33% ofacute stroke patients present to hospitals within 3 hoursand 50% within 6 hours of symptom onset, but there areconsiderable delays in assessment processes afterarriving at hospitals.2 These can be attributed to lowpriority given to stroke by the emergency departments,10

delays in accessing neuro-imaging11 and delays inalerting treating physicians.6,12 Despite concerns thataccess to specialist stroke care may hinderthrombolysis,8 little attention has been devoted todefining resources or processes required to facilitatethrombolytic practice once these patients present tohospitals.

2

3

A major requirement for thrombolysis is that treatmenttakes place within a 3 hour time window.13 This objectivemay be compromised significantly even in patients whopresent early to hospitals, if assessment and referralprocesses after arrival at hospital are not optimised.14

There is also an issue about patients who may presentbeyond the three hour time window but have CT scanswhich show no or limited signs of early infarction andmeet other criteria for intervention. A modest treatmentbenefit for death or dependence (OR 0.84, 95% CI 0.75to 0.95) has been demonstrated in those treated up to 6hours but there is also an increased risk of intracranialhaemorrhage (OR 4.34, 95% CI 3.14 to 5.99).1

Penumbral imaging techniques have shown that asignificant amount of threatened brain tissue is stillsalvageable beyond 3 hours in many patients,15-17 andthe benefit/risk ratio for thrombolysis up to 6 hours couldbe altered favourably by adopting a diagnostic approachthat allows clinicians to individualise treatment decisions.17

These issues were investigated by analysing data collectedin 50 thrombolysed stroke patients to assess the timetaken to perform various processes associated withthrombolysis after presentation to hospital and the role ofperfusion computed tomography (PCT) imaging ininforming thrombolysis decisions.

METHODS

Analysis of prospectively collected data was undertaken infirst 50 thrombolysed patients at an inner city teachinghospital (King’s College Hospital, London) serving apopulation of 225,000 residents. A nurse-led fast tracksystem was in place in the Accident and Emergencydepartment to expedite the management of stroke patientspotentially eligible for thrombolysis.18 A nurse confirmedthe diagnosis of stroke using the ‘Face Arm SpeechTest’,19 ascertained the time of symptom onset from thepatient or relative and alerted the “on call” specialistregistrar, who had a stroke or a neurology background.The nurse also undertook baseline observations(temperature, respiratory rate, blood pressure, glucose,oxygen saturation, ECG and GCS), establishedintravenous access, and sent blood samples (FBC, U&E,glucose and clotting) to the laboratory. An urgent non-enhanced CT scan was requested. The time of strokeonset, presentation to hospital, nurse assessment and scanrequest were recorded.

The patient was reviewed by the specialist registrar prior toscanning to establish diagnosis, exclude stroke mimics,assess stroke severity and level of impairments as well asascertain eligibility for thrombolysis. A non-enhanced CTscan was undertaken using Lightspeed 16 GE MedicalSystems CT scanner and processed by ADW 4.1.

Images were reformatted as 10mm axial slices andreviewed with window settings of 40/35 Hounsfield units.The scans were assessed by a consultant neuro-radiologistor a trained stroke physician for the presence ofhaemorrhage, hyperdensity of major arteries, gyralswelling and cortical hypodensity. A decision to proceed toperfusion scanning was undertaken on clinical groundswhilst the patient was still in the scanner suite. PCT wasundertaken using 50ml of iodinated contrast (Iohexol 300)injected via an antecubital vein using a Medrad pumpinjector at 4 ml/sec. Two slices 10mm apart were acquired5 seconds after the injection through the level of the basalganglia, representing parts of the territories of the anterior,middle and posterior cerebral arteries. CT images wereprocessed and analysed using Functool 2.6.6.i software(GE Healthcare, UK). Maps of Cerebral Blood Flow (CBF),Cerebral Blood Volume (CBV) and Mean Transit time(MTT) were produced and analysed for areas ofabnormality at the time of the scan. PCT data were usedto inform the decision making process for thrombolysis.The times that the CT scan was undertaken and thefindings finally reported were recorded.

Thrombolysis was administered in A&E, 0.9mg/Kg of tPAwas used with an upper limit of 90mg per patient. A bolusof 10% of the total dose was given followed by a 60minute intravenous infusion of the remaining dose. Thetime treatment was commenced was recorded. Patientswere transferred to the acute stroke unit and monitored ona high dependency bed for heart rate, blood pressure,temperature, oxygen saturation, blood glucose,neurological status and signs of internal or superficialbleeding. Optimal physiological homeostasis wasmaintained. CT scan were repeated 24 hours afterthrombolysis or earlier if there was any neurologicaldeterioration.

National Institute of Health Stroke Score (NIHSS) wasmeasured on admission, 24 hours and 1 week. Mortalitywas recorded at 1 week, 4 weeks and 3 months. Themodified Rankin score was measured at 3 months. Thefrequency of intra- and extracranial haemorrhagic eventsand deaths related to haemorrhage were recorded.Intracranial haemorrhagic events were classified as HItypes I and II and PH types I and II.20

Descriptive data are presented using means or medians asappropriate. Data for age, blood cholesterol, bloodglucose, systolic and diastolic BP were normally distributedand analysed using the t test. Data for process times, NIHscores and modified Rankin score showed a non-parametric distribution and were analysed using theMann-Whitney test. Category data for mortality,haemorrhagic complications and proportions wereanalysed using the Chi squared and the Fisher exact testwhen counts were low.

4

RESULTS

The mean age of the 50 thrombolysed patients was 69.7(SD 14.4) years and 33 (66%) were male. Of these, 25(50%) were known hypertensive, 7 (14%) were diabetic,25 (50%) were smokers, 13 (26%) hadhypercholesterolaemia, 15 (30%) were in atrial fibrillationand 10 (20%) had a previous stroke. On presentation,they had mean blood pressure of 143/76 (SD 22/17)mm Hg, mean blood glucose was 7.2 (SD 3.0) and theirmean cholesterol was 4.6 (SD 0.9). Later investigationsfor stroke aetiology showed that strokes due to cardiacemboli in 18 (36%) patients (atrial fibrillation or patentforamen ovale), carotid artery disease in 19 (38%)patients (atherosclerosis or dissection) and undeterminedor multiple causes in 13 (26%) patients.

The median time from onset to arrival of thrombolysedpatients was 51 minutes (IQR 0h:37min to 1h:19min). Ofthese, 27 (54%) patients arrived within 1 hour, 18 (36%)patients between 1-2 hours, 3 (6%) patients between 2-3hours and 2 (4%) between 3 and 6 hours. The medianinterval between arrival and scan was 1h:07min (IQR0h:46min to 1h:36min). Only 7 (14%) patients werescanned within 30 minutes of arrival and a further 15(30%) patients were scanned between 30-60 minutes. Themedian scan to treatment time was 30 minutes (IQR 19 to47 minutes). The arrival to treatment or “door to needle”time was 1h:51min (IQR 1h:26min to 2h:15min). Only 2(4%) patients were thrombolysed within 45 minutes ofarrival. The median onset to treatment time was 2h:47min(IQR 2h:15min to 3h:20min). 25 (50%) patients had aPCT prior to thrombolysis. There were no differences in thetime between arrival to scanning and scanning totreatment between patients who were thrombolysed afterperfusion scanning and those thrombolysed withoutperfusion scans (Table 1).

Of the 50 patients, 28 (56%) were thrombolysed within 0-3 hours and 22 (44%) within 3-6 hours (Table 2). Ofthose thrombolysed beyond 3 hours, 14 (28%) werethrombolysed between 3-4 hours, 4 (8%) between 4 to 5hours and 4 (8%) between 5-6 hours. Although the strokeseverity of patients thrombolysed in 3-6 hours was lessthen those thrombolysed within 3 hours (Baseline NIH 9 v14), this was not statistically significant. There were asignificant difference in the duration of the onset to arrivalin A&E between the two groups (0h:42min v 1h:10min;p=0.005), and there were further delays in assessmentfor thrombolysis after arrival in patients who werethrombolysed beyond 3 hours (0h:47min v 1h:30min; p=0.0001). However, there was no difference in the durationfrom imaging to treatment between the 0-3 and 3-6 hourtime groups. Outcome was comparable between the twogroups with the median change in NIH score at 1 weekbeing (-7 v –6; p=0.497). The rate of ICH and mortality

were comparable between the two groups. (Table 2)

Of the 22 patients who underwent thrombolysis between3-6 hours, PCT prior to thrombolysis was undertaken in10 patients (Table 3). There were no significantdifferences from onset to arrival and arrival to scanningtimes or treatment between the two groups. There was atrend towards better outcomes for patients in whom PCThas been used to guide thrombolysis decisions with lessmortality, equivalent intracranial haemorrhage rates,greater improvement on NIH scores both at 24 hours and1 week and lower Rankin scores at 3 months, but thesedid not achieve statistical significance (Table3).

DISCUSSION

These data shows that routine thrombolysis for acutestroke patients is feasible, safe and can be implementedin mainstream clinical practice in England and Wales. Itsuggests that additional imaging modalities such asperfusion CT imaging can be used to refine thrombolysisdecisions as they do not cause significant delays but mayhave the potential to improve the effectiveness ofthrombolysis. The study also showed that one of the mostimportant barriers to early thrombolysis in clinical practicewas the time taken from presentation to hospital andimaging for eligibility for thrombolysis, even when agreedprotocols were in place, suggesting that this aspect of theprocess needs specific attention if thrombolysis is to besuccessfully implemented in clinical practice.

The most important conclusion of the National AuditOffice report on Stroke Care was that an efficient andeffective emergency response to stroke was generallylacking in England.8 The low rate of thrombolysis inEngland (below 1%) was attributed partly to a lack ofpublic awareness and partly to the fact that AmbulanceTrusts, Accident and Emergency departments and specialiststroke teams did not routinely provide an effective,integrated response that included rapid triage and accessto scanning.8 The lack of rapid triage rather than access toscanning was demonstrated by our data, which showedthat the time taken to assess eligibility for thrombolysisafter presentation to hospital may exceed the time betweenstroke onset and presentation in a significant proportion ofpatients, resulting in their treatment being undertakenoutside the 3 hour time window.

The provision of round the clock emergency response forstroke patients is resource intensive and requires 24 houravailability of staff trained in thrombolysis.7,9,21 Lack ofresources and staff has been identified as a major causefor in-hospital delays universally,3,14,22 but may beparticularly important in England and Wales because ofthe cost constraints within the NHS, changes in medicalstaff working patterns and limited opportunities for

5

specialist training in stroke care.23 An average districtgeneral hospital in England serves a population of250,000 and may treat about 500 acute stroke patients ayear. Even if a 24 hour specialist service locally couldachieve a 5-10% thrombolysis rate, there will issues ofacquiring sufficient expertise, training specialists,maintaining systems efficiency and cost-effectiveness ofthe service at individual centres. An alternative would beto adopt a regional approach based on either a networkof local hospitals or a stroke centre to deliver consistenthigh quality, safe, effective and cost-effective thrombolysisservices.9,24

A major issue facing hospitals that offer thrombolysis istreatment of patients outside the 3 hour time window.Although treatment only within a randomised controlledtrial is recommended currently,25 evidence from othercentres suggests that the therapeutic time window can beextended beyond 3 hours by carefully selecting patientson the basis of further perfusion imaging to provide aphysiological 'tissue clock',15-17 This approach to extendthe therapeutic window has been used successfully inseveral small studies and a recent randomised clinicaltrial.26 In contrast to MRI techniques for perfusionimaging used in these studies, Perfusion ComputedTomography (PCT) is widely available, fast and can beperformed immediately after unenhanced CT. 27 PCTdeficits correlate with MRI perfusion deficits, clinicalneurological scores, and final infarct volumes.27-29 In thisstudy, PCT was an important adjunct to non-enhanced CTscans in selecting patients for thrombolysis, did not addsignificantly to time taken for assessment of eligibility andmay have improved outcomes. However, there isconsiderable debate on imaging the “penumbra” and therole of such imaging in aiding thrombolysis decisions,which merit further investigation.30

The interpretations of data presented are limited by therelatively small numbers of thrombolysed patientsincluded in analysis and the fact that it represents practiceat a single centre. However, there are not many examplesof thrombolytic practice in the UK and the paper identifiesan important barrier to implementing effectivethrombolysis which is likely to be common to most centrespreparing to introduce thrombolysis. It can be argued thatthe long duration between patient presentation andscanning is a local issue and reflects poor coordination ofan appropriate response in a specific hospital. Many ofthe delays in specialist assessment could be attributed to24 hour availability of staff trained in thrombolysis, bothbecause of the lack of such trained individuals as well asthe allocation of adequate resources to run thethrombolysis service, issues that are common to manyhospitals. Despite being one of the largest series reportedfrom England, the small number of subjects may have

masked important differences in outcome betweenpatients thrombolysed between 0-3 and 3-6 hours.Similarly, the trend towards better outcome in patientsthrombolysed after PCT may have been diluted withinclusion of more patients. The reporting of PCT imageswas not masked to patients’ clinical condition and theremay be further bias due to the semi-quantitative nature ofPCT images and slices chosen to generate these images.Nevertheless, the data presented suggests thatthrombolysis for stroke can be safely implemented inroutine hospital practice in England and Wales but thereare significant resource, training and organisational issueswithin hospitals which need to be addressed to achievethe good clinical outcomes and financial savingshighlighted in the National Audit Office report.

KEY POINTS

• Thrombolysis in routine clinical practice is feasible andsafe in local hospitals

• Successful implementation of thrombolysis in routine clinical practice in England is dependent on developing efficient processes for rapid assessment of patients after they present to hospitals

• PCT does not delay treatment and may be helpful in refining thrombolysis decisions

REFERENCES

1. Wardlaw JM, Zoppo G, Yamaguchi T, Berge E. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2003;(3):CD000213.

2. Harraf F, Sharma AK, Brown MM, Lees KR, Vass RI, Kalra L. A multicentre observational study of presentation and early assessment of acute stroke. BMJ. 2002;325:17-21.

3. California Acute Stroke Pilot Registry (CASPR) Investigators. Prioritizing interventions to improve rates of thrombolysis for ischemic stroke. Neurology. 2005;64(4):654-9.

4. Lacy C, Suh D, Bueno M, Kostis J, for the STROKE Collaborative Study Group. Delay in presentation and evaluation for acute stroke: Stroke Time Registry for Outcomes Knowledge and Epidemiology (STROKE). Stroke. 2001;32:63–69.

5. Schroeder E, Rosamond W, Morris D, Evenson K, HinnA. Determinants of emergency medical services use in a population with stroke symptoms: the Second Delay in Accessing Stroke Healthcare (DASH II) Study. Stroke.2000;31:2591–2596.

6. Morris DL, Rosamond W, Madden K, Schultz C, Hamilton S. Prehospital and emergency department delays after acute stroke. The Genentech Stroke Presentation Survey. Stroke 2000;31:2585

7. Weir NU, Buchan AM. A study of the workload and effectiveness of a comprehensive acute stroke service.J Neurol Neurosurg Psychiatry. 2005;76(6):863-5.

8. National Audit Office. Reducing Brain Damage: Faster access to better stroke care. The Stationery Office, 2006 London

9. Alberts MJ, Latchaw RE, Selman WR, Shephard T, Hadley MN, Brass LM, Koroshetz W, Marler JR, BoossJ, Zorowitz RD, Croft JB, Magnis E, Mulligan D, Jagoda A, O'Connor R, Cawley CM, Connors JJ, Rose-DeRenzy JA, Emr M, Warren M, Walker MD; Brain Attack Coalition. Recommendations for comprehensive stroke centers: a consensus statementfrom the Brain Attack Coalition. Stroke. 2005 Jul;36(7):1597-616.

10. Ravindrane A, Croft-Baker J, Jarrett D, Severs MP. Causes of delay in hospital assessment after stroke. Age Ageing 2000; 29:57

11. Lin CS, Tsai J, Woo P, Chang H. Prehospital delay and emergency department management of ischaemic stroke patients in Taiwan, R.O.C. Prehosp Emerg Care 1999; 3:194-200

12. Wester P, Radberg J, Lundgren B, Peltonen M. Factorsassociated with delayed admission to hospital and in-hospital delays in acute stroke and TIA: a prospective, multicentre study. Stroke 1999; 30:40-8

13. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, HamiltonS; ATLANTIS Trials Investigators; ECASS Trials Investigators; NINDS rt-PA Study Group Investigators.Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004;363:768-74.

14. Ruland S, Gorelick PB, Schneck M, Kim D, Moore CG, Leurgans S. Acute stroke care in Illinois: a statewide assessment of diagnostic and treatment capabilities. Stroke. 2002 May;33(5):1334-9.

15. Ringleb PA, Schellinger PD, Schranz C, Hacke W. Thrombolytic therapy within 3 to 6 hours after onset of ischemic stroke: useful or harmful? Stroke. 2002;33(5):1437-41.

16. Kent DM, Ruthazer R, Selker HP. Are some patients likely to benefit from recombinant tissue-type

plasminogen activator for acute ischemic stroke even beyond 3 hours from symptom onset? Stroke. 2003 ;34(2):464-7.

17. Davis SM, Donnan GA, Butcher KS, Parsons M. Selection of thrombolytic therapy beyond 3 h using magnetic resonance imaging. Curr Opin Neurol. 2005;18(1):47-52.

18. Fitzpatrick M, Birns J. Thrombolysis for acute ischaemic stroke and the role of the nurse. Br J Nurs.2004;13(20):1170-4.

19. Harbison J, Hossain O, Jenkinson D, Davis J, Louw SJ, Ford GA. Diagnostic accuracy of stroke referrals from primary care, emergency room physicians, and ambulance staff using the face arm speech test. Stroke. 2003;34(1):71-6.

20. Wolpert S, Bruchmann H, Greenlee R, et al. Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. AJNR Am J Neuroradiol. 1993; 14:3-13

21. Klijn CJ, Hankey GJ; American Stroke Association and European Stroke Initiative. Management of acuteischaemic stroke: new guidelines from the American Stroke Association and European Stroke Initiative. Lancet Neurol. 2003;2(11):698-701.

22. Kwan J, Hand P, Sandercock P. A systematic review of barriers to delivery of thrombolysis for acute stroke. Age Ageing. 2004 Mar;33(2):116-21.

23. Jenkinson D, Ford GA. Research and development instroke services. BMJ. 2006 Feb 11;332(7537):318.

24. Brainin M, Olsen TS, Chamorro A, Diener HC, Ferro J, Hennerici MG, Langhorne P, Sivenius J; EUSI Executive Committee; EUSI Writing Committee. Organization of stroke care: education, referral, emergency management and imaging, stroke units and rehabilitation. European Stroke Initiative. Cerebrovasc Dis. 2004;17 Suppl 2:1-14.

25. Intercollegiate Stroke Working Party. National clinical guidelines for stroke 2nd edition. Clinical Effectiveness & Evaluation Unit, Royal College Of Physicians, 2004 London

26. Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR, Soehngen M, Warach S; DIAS Study Group.The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke. 2005;36(1):66-73.

27. Meuli RA. Imaging viable brain tissue with CT scan during acute stroke.

Cerebrovasc Dis. 2004;17 Suppl 3:28-34.

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27. Meuli RA. Imaging viable brain tissue with CT scan during acute stroke.

Cerebrovasc Dis. 2004;17 Suppl 3:28-34.

28. Bisdas S, Donnerstag F, Ahl B, Bohrer I, Weissenborn K, Becker H. Comparison of perfusion computed tomography with diffusion-weighted magnetic resonance imaging in hyperacute ischemic stroke. J Comput Assist Tomogr. 2004;28(6):747-55.

29. Schramm P, Schellinger PD, Klotz E, Kallenberg K, Fiebach JB, Kulkens S, Heiland S, Knauth M, Sartor K. Comparison of perfusion computed tomography

and computed tomography angiography source images with perfusion-weighted imaging and diffusion-weighted imaging in patients with acute stroke of less than 6 hours' duration. Stroke. 2004;35(7):1652-8.

30. Schellinger PD, Fiebach JB, Hacke W. Imaging-baseddecision making in thrombolytic therapy for ischemic stroke: present status. Stroke. 2003; 34: 575–583.

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Table 1: Comparison of median process times between patients with & without PCT

Time given in 00hours:00 minutes format. IQR: Interquartile range; PCT: Perfusion Computed Tomography

Onset-Arrival (IQR)

Arrival-Scan (IQR)

Scan-Treatment (IQR)

Arrival-Treatment (IQR)

Onset-Treatment (IQR)

PCT(n=25)

1:00 (0:42-1:20)

1:05 (0:45-1:37)

0:29 (0:19-0:45)

1:48 (1:06-2:10)

2:35 (2:15-3:10)

No PCT(n=25)

0:46 (0:37-1:19)

1:13 (0:47-1:35)

0:30 (0:19-1:00)

1:58 (1:40-2:20)

3:00 (2:15-3:35)

P value

0.674

0.711

0.496

0.107

0.263

8

Table 2: A comparison of baseline characteristics, outcomes and process duration between patients thrombolysedbetween 0-3 hours and 3-6 hours.

Mean and (SD) given unless specified otherwise. SBP: Systolic blood pressure; DBP: Diastolic blood pressure; NIHSS:National Institute of Health Stroke Scale; mRS: Modified Rankin Score. Times given as 00hours:00 minutes.

Mean Age (years)

Male Gender (%)

Mean SBP (mm Hg)

Mean DBP (mm Hg)

Mean Blood Glucose (mmols/l)

Mean NIHSS score at baseline

Mean NIHSS score at 24 hr

Mean NIHSS score 1 week

Mean change NIHSS score (0 to 24 hr)

Mean change NIHSS score (0 to 1 wk)

Median mRS at 3 month

Intracranial Haemorrhage (%)

Mortality at 3 months (%)

Median Onset-Arrival time (IQR)

Median Arrival-Scan time IQR

Median Scan-Treatment time (IQR)

Median Arrival-Treatment time (IQR)

Median Onset-Treatment time (IQR)

0-3 hours (n=28)

72.2(15.7)

17 (61%)

141.3 (24.3)

77.8 (18.3)

7.3 (3.2)

14 (9-17)

9 (6-14)

7 (1-10)

-3 (-6 to –1)

-7 (-8 to –5)

3 (1-5)

2 (7.1%)

7 (25%)

0:42 (0:29-1:00)

0:47 (0:34-1:20)

0:26 (0:16-0:48)

1:32 (1:04-1:52)

2:19 (1:57-2:35)

3-6 hours(n=22)

66.8 (12.1)

16 (73%)

146 (20.7)

72.2 (15.5)

7.2 (2.7)

9 (7-16)

5 (7-16)

2 (1-8)

-5 (-6 to –1)

-6 (-7 to –4)

2 (1-4)

3 (13.6%)

4 (18%)

1:10 (0:49-1:46)

1:30 (1:04-1:56)

0:32 (0:20-0:47)

2:11 (1:53-2:54)

3:30 (3:10-4:33)

P value

0.181

0.549

0.47

0.25

0.91

0.116

0.181

0.496

0.715

0.497

0.601

0.362

0.597

0.005

0.0001

0.473

0.0001

0.0001

9

Table 3: A comparison of baseline characteristics, outcomes and process duration between patients thrombolysed withand without PCT scanning in the 3-6 hours time window.

Mean and (SD) given unless specified otherwise. SBP: Systolic blood pressure; DBP: Diastolic blood pressure; NIHSS:National Institute of Health Stroke Scale; mRS: Modified Rankin Score. Times given as 00hours:00 minutes.

Mean Age (years)

Male Gender (%)

Mean SBP (mm Hg)

Mean DBP (mm Hg)

Mean Blood Glucose (mmols/l)

Mean NIHSS score at baseline

Mean NIHSS score at 24 hr

Mean NIHSS score 1 week

Mean change NIHSS score (0 to 24 hr)

Mean change NIHSS score (0 to 1 wk)

Median mRS at 3 month

Intracranial Haemorrhage (%)

Mortality at 3 months (%)

Median Onset-Arrival time (IQR)

Median Arrival-Scan time IQR

Median Scan-Treatment time (IQR)

Median Arrival-Treatment time (IQR)

Median Onset-Treatment time (IQR)

PCT(n=10)

68.6 (15.3)

7 (70%)

151.8 (16.4)

74 (15.8)

7.5 (2.9)

8 (7-11)

2 (2-9)

1 (1-4)

-5.5 (-6 to –2)

-6.5 (-9 to -5)

1.5 (1-3)

1

0

1:05 (0:46-1:18)

1:40 (1:23-1:56)

0:38 (0:30-0:47)

2:13 (2:01-2:43)

3:20 (3:08-4:13)

No PCT(n=12)

66.9 (13.4)

9 (75%)

141.3 (23.4)

70.8 (15.7)

6.9 (2.6)

9 (8-21)

7 (3-20)

3 (2-11)

-3.5 (-6 to -1)

-5 (-7 to –3)

2.5 (2-6)

2

4

1:17 (0:55-2:09)

1:19 (1:00-1:54)

0:25 (0:18-0:55)

2:06 (1:51-2:55)

3:40 (3:16-4:36)

P value

0.855

0.523

0.335

0.610

0.607

0.422

0.247

0.261

0.345

0.201

0.129

0.612

0.258

0.382

0.310

0.602

0.754

0.554

10

Stroke Research Group Update: Accrual to Welsh sitesDR ALLISON COOPER

Study Acronym/Short Title

AVERT

CADISS

ENOS

LoTS Care

HPS2-THRIVE

IST3

Modified Rankin Study

SOS

Stroke INF

Stroke Survivors Needs Survey

SRN007 (TRA2P-TIMI 50)

Study Site

Royal Gwent Hospital

Nevill Hall Hospital

UHW

Royal Gwent Hospital

Ysbyty Gwynedd Hospital

Cardiff Royal Infirmary

Singleton

Royal Gwent Hospital

UHW

UHW

Nevill Hall Hospital

Withybush

Royal Glamorgan Hospital

Bronglais Hospital

Nevill Hall Hospital

Royal Glamorgan Hospital

Royal Gwent Hospital

UHW

Morriston

Singleton

Princess of Wales

Newtown Medical Practice

St Thomas Surgery, Pembrokeshire

Bryngwyn Surgery, Newport

Overton Surgery, Wrexham

UHW

Royal Gwent Hospital

Status

Open

Open

In set up

In set up

Open

Open

Open

Open

Open

Open

In set up

In set up

Open

Open

Open

In set up

Open

Open

Open

Open

Open

Open

In set up

In set up

In set up

Open

Open

This stroke research update focuses on Wales’ growing involvement in NIHR Stroke Research Network (NIHR SRN)adopted studies. Welsh sites are now involved in numerous NIHR SRN studies (see table 1).

Table 1: Current studies open and in set up at Welsh sites (as of Dec 2009)

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Table 2: Total accrual from 2007 to Dec 2010 (year ends 31-Mar-2010)

Overall Accrual

2007/2008

2008/2009

2009/2010

Apr

5

1

14

May

5

6

12

Jun

4

4

15

Jul

6

13

12

Aug

5

7

11

Sep

9

11

14

Oct

12

10

27

Nov

6

5

38

Dec

7

11

20

Jan

5

13

Feb

4

4

Mar

5

11

Total

73

96

163

ENOS, IST3, SOS, Stroke INF and Modified Rankin Scale Study are Acute Stroke studies; HPS2-THRIVE, TRA2P-TIMI50 and CADISS are Prevention studies; AVERT is a Rehabilitation study and LoTS Care and the Stroke SurvivorsNeeds Survey are within Primary Care. Details for all the studies shown can be found on the NIHR CRN portfoliodatabase http://public.ukcrn.org.uk/search/

Accrual to NIHR SRN adopted studies by sites within Wales has increased steadily from 2007 (see table 2). In thefirst 9 months of the 2009/2010 year accrual has already exceeded last years total. Two sites in particular are doingwell with their recruitment. Cardiff Royal Infirmary recruited the first patient in the UK to the LoTS Care trial andremains the highest recruiter to date. Morriston Hospital was the top recruiter to the Stroke INF trial in November2009.

In addition to the studies currently open and recruiting this year, there are two newly opened studies (SOS andAVERT) on 4 sites in total that will begin recruiting imminently. Two existing studies (IST-3 and Stroke Survivors NeedsSurvey) are in the process of being set up at several further sites. The addition of these new study sites will furtherincrease the Wales accrual total this year.

The portfolio has broadened so that studies in Wales now cover 4 clinical studies groups (CSG) - Acute, Prevention,Rehabilitation and Primary Care.

More hospitals across Wales are now involved in stroke studies. In addition to the established sites in Cardiff,Newport, Swansea and Aberystwyth, studies are now open or being set up in Bridgend, Bangor, Llantrisant,Abergavenny and Haverfordwest as well as in 4 general practices.

CRC Cymru Research Professional Network support for stroke studies in Wales has grown since 2008 throughcollaboration with the Stroke Research Portfolio Development Fellow (SRPDF) Dr Allison Cooper. The three networksin South East Wales, South West Wales and North Wales all have research support staff identified to specificallysupport stroke studies in their areas and work closely with the SRPDF to assess the feasibility of studies in Wales,identify suitable sites, obtain the necessary approvals and ensure good recruitment to studies. This support ensuresthat accrual rates will continue to improve this year and in subsequent years.

Please contact Dr Allison Cooper, OPAN Stroke Research Portfolio Development Fellow onallison.cooper@swansea.ac.uk or on 07717 576108 if you would like to discuss participating in any NIHR SRNportfolio studies or for any further information on the content of this update or the work of the OPAN StrokeResearch Group.

4th UK Stroke Forum 2009 at Glasgow: More than 90 medical centers in UK arethrombolysing ischaemic stroke patientsDR AMER JAFAR ASSOCIATE SPECIALIST IN STROKE MEDICINE ST WOOLOS HOSPITAL, NEWPORT

For the fourth year running the British Association ofStroke Physicians (BASP) and Stroke Associationmanaged to put a comprehensive programme for theStroke Forum UK. It is a good platform for the strokephysicians and stroke allied health professionals to meetand discuss the latest developments in the field of acuteand post acute stroke care. The Stroke Forum was heldin Glasgow (Scotland) from 1st to 3rd December 2009.

There were hundreds of delegates attending theconference which was organized in the beautifulwaterfront area. They came from all over the country todiscuss stroke care and share ideas and experiences.The BASP training session was chaired by DrChristopher Price and the learning objectives of thissession were to:

• Understand a safe practice during thrombolytic therapy for acute stroke

• Recognise situations and approaches to investigation of patients with rarer causes of stroke

• Appreciate the variable presentations of neurological migraine and the role of investigations

• Recognise features of dizziness which do not indicate vascular disease and require further investigation

• Raise awareness about the current training programme for Stroke Medicine

The highlights of the first day included an updateprovided by Professor Kennedy Lees from the Universityof Glasgow about the Safe Implementation ofThrombolysis in Stroke Monitoring Study (SITS-MOST).The aim of the SITS-MOST is to assess the safety andefficacy of intravenous alteplase as a thrombolytictherapy within the first 3 hours of the onset of acuteischaemic stroke. It was reported that 6483 patientswere recruited from 285 centres (50% with very littleprevious experience in stroke thrombolysis) in 14countries between 2002 and 2006 for this prospective,

longitudinal and observational study.

Professor Lees mentioned that there are 93 centers inthe UK that are participating in thrombolysing strokepatients but in comparison with the rest of Europe thedoor to needle time is slightly longer for the UKhospitals. Professor Lees concluded that although theprocess currently is moving in the right direction, we inthe UK are still thrombolysing more severely affectedstroke patients than the rest of the European colleagues.

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Professor Garry Ford discussed the issue ofthrombolysing patients over the age of 80 years. Theissue of whether to offer thrombolysis to patients abovethe age of 80 remains unclear and is one of theuncertainties that is being examined by the ThirdInternational Stroke Trial (IST-3). He mentioned that,based on the current data, the mortality rate for above80 years old patients is higher than those below 80(31% v 14%). He informed the gathering that currently aresearch grant is available for the Hyperacute Phase ofthe Pathway for at least 8 stroke units in the UK in orderto enhance the thrombolysis service.

NURSES STROKE FORUM

On the first day of the UK Stroke Forum there was asession for the Nurses and Allied Health Professionals. Itwas a lively session and a number of important areaswere covered including the rationale for food and fluidneeds following a stroke (Dr Anne Rowat) and the issueof PEG feeding from the patient/carer perspectives (DrAilsa Brotherton).

Another important area that was discussed in one of thesessions was on the subject of Life after Stroke. Thesession highlighted the key issues contributing to theexperience of life after stroke; explored the currentevidence on programmes designed to support life afterstroke using examples from four different programmesof research and practice development; and outlined thekey gaps in the current provision and the potentialbarriers to participation after stroke, incorporating thestroke survivor’s perspective.

STROKE REHABILITATION

The Forum paid attention to the issue of StrokeRehabilitation this year. Dr Kate Radford from theUniversity of Central Lancashire talked about thevocational rehabilitation for stroke patients and therewas another lecture on “getting out of the house” by DrPip Logan.

Professor Julie Bernhardt from Australia presented to theForum the latest research results regarding the timing ofstarting rehabilitation after stroke. She spoke about anew model for rehabilitating stroke patients. She is themain investigator of the AVERT trail (A Very EarlyRehabilitation Trial for Stroke) that is examining themodel of early rehabilitation. She believes that it is apragmatic trial which investigates the benefit of earlyrehabilitation to stroke patients on a 5 days a weekbasis. It is an international multi-center trial with fewcentres in England and Wales participating in recruitingpatients for it.

The model combines the acute care with rehabilitationenabling the rehabilitation team to start rehabilitation ofa stroke patient whilst the patient is still in the acutesetting. She mentioned that the advice for the cliniciansis to let the rehabilitation team provide the interventionto stroke patients as soon as it is clinically possible andonce the patients are haemodynamically stable.

AND FINALLY...

The second day of the Forum was devoted to the BASPtrainees and included a session on the abstractpresentation to describe the findings of their researchactivities. There were several interesting topics includinga presentation about the inflammatory markers andoutcome following stroke; the reliability of the ModifiedRankin Scale; and the need for intensive cardiacmonitoring following a TIA.

The Forum hosted many high quality presentationsincluding new ideas for a better stroke care and a TIAservice in various parts of the UK. There was anexcellent opportunity to discuss ideas and share theexperience between the delegates. The Forum alsoremembered the important role the Paramedics play inthe provision of TIA and Stroke care with a presentationabout extending the role of Paramedics in the earlymanagement of TIA and stroke by David Davis from theSouth East Coast Ambulance Service. We came awayfrom the conference feeling very optimistic about thefuture of stroke care in the UK.

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14

A curious constellation of deficitsROB POWELL AND TOM HUGHESDEPARTMENT OF NEUROLOGYUNIVERSITY HOSPITAL OF WALES, CARDIFF

CASE HISTORY

A 66 year old woman presented after her husband wasunable to rouse her from sleep one Sunday morning.She had been well the previous evening and had nothad any warning symptoms preceding this. Over the nextfew hours she continued to be sleepy. She opened hereyes to verbal commands, but remained rather vagueand disorientated, and had difficulty forming sentences.She then improved over the course of the day and wasdischarged after a brief admission to hospital duringwhich a CT head was reported as normal.

Over the course of the next 5 days her husband reportedthat she was not herself. She had clear word findingdifficulties, more pronounced when speaking Englishrather than her native Dutch. She was unsteady on herfeet and tended to veer to the right when walking. Shecontinued to sleep for long periods of time andcomplained that she had difficulty reading the paper.

On examination she was in sinus rhythm, wasnormotensive with normal heart sounds and no carotidbruits. She was orientated, but sleepy. She had evidenceof a subtle expressive dysphasia with mild word findingdifficulties. Her memory was grossly intact. Her eyemovements were abnormal, characterised by limitationof downgaze and marked slowing of vertical saccades.She had a mild gait ataxia, but no peripheral ataxia. Shehad no motor weakness, sensory loss or pyramidal signsin her limbs.

A CT head (Figure 1) revealed a small low density areain the medial aspect of the left thalamus consistent withan infarct. Routine blood tests were normal, glucose 5.1mmol/L, cholesterol 4.9 mmol/L. Carotid Dopplers werenormal. The chest X-ray and 12- lead ECG were normaland a transthroacic echocardiogram is awaited. Shehad no known cardiovascular risk factors and had notcomplained of any neck pain. She was started on aspirin300mg for 2 weeks, reducing after to 75mg,Dipyridamole 200mg bd (to be taken for two years) andSimvastatin 40mg daily. Since then she has graduallyimproved, but three months on she still has word findingdifficulty when in company and needs to have a sleep inthe afternoon.

DISCUSSION

Our patient suffered a left paramedian thalamic infarct,the mechanism of which has not yet been identified.The thalamus is situated between the midbrain andforebrain, is multi-functional, and acts as a relaybetween subcortical structures and the cerebral cortex.Although comprised of a large number of differentnuclei it can be divided into four functional components(Figure 2). The anterior nuclei are involved in languagefunction, the lateral nuclei in motor and sensoryfunction, and the posterior (pulvinar) nuclei projectpredominantly to visual cortex. The medial nuclei arebelieved to be responsible for arousal and vigilance,but also play a role in memory function due to theirconnections with the limbic system1.

The thalamus derives its blood supply entirely from theposterior circulation. The medial thalamic nuclei aresupplied by the paramedian artery. In a relativelycommon anatomical variant both paramedian thalamicarteries arise from the same side, either as a singletrunk or as two separate closely related vessels 2.Obstruction of the single trunk or of the two closelyrelated vessels will result in bilateral paramedianthalamic infarction1.

The midbrain is supplied by the paramedianmesencephalic arteries and may be affected in thissyndrome if the arteries arise from a common trunkwith the paramedian thalamic arteries, resulting inproblems with eye movements and ataxia. The anteriorthalamus is supplied by the polar artery. However this isabsent in around 50% of individuals, in whom theparamedian thalamic artery supplies its territory1. If the polar artery is absent, dysphasia will be part ofthe syndrome of paramedian thalamic infarction, as we suspect to be the case in our patient.

In summary, we present a case of a paramedianthalamic infarction. This characteristic stroke syndromeis probably under-diagnosed, and is interesting in that it proves an exception to two widely held views that stroke is not a cause of loss of consciousness, and that posterior circulation strokes do not causedysphasia.

15

REFERENCES

1. Reilly M et al. Bilateral Paramedian Thalamic Infarction: A Distinct but Poorly Recognized Stroke Syndrome. QJM 1992;82(297):63-70

2. Percheron G. Les arteres du thalamus humain. II—arteres et territoires thalamiques paramedians de I'artere basilairecommunicante. Rev Neurol (Paris) 1976; 132: 304-324.

Figure 1: CT brain demonstrating a left thalamic infarct

Figure 2: Anatomy of the Thalamus

Polar artery

Internal carotid artery

Poterior communicatingartery

Thalamogeniculatearteries

Posterior choroidalarteries

Posterior cerebralartery

Lateral

Anterior

Posterior

Para-median

Thalamo-subthalamic arteries

Basilar artery

Arteriovenous Malformations andHemorrhagic StrokeDR M USMANSPECIALIST REGISTRAR IN GERIATRIC MEDICINECAERPHILLY DISTRICT MINER’S HOSPITAL, CAERPHILLY EMAIL: DRUSMAN_AKRAM@HOTMAIL.COM

INTRODUCTION

Arteriovenous malformation (AVM) is an uncommoncause of hemorrhagic stroke accounting for about 2% 1, 2 of all the strokes. A clear understanding of thediagnosis and treatment options is essential as AVMsare an important cause of intracranial hemorrhage inyoung adults. Although AVMs are uncommon theapparent incidence has increased in the last twodecades due to an earlier detection with imagingtechniques even if the patient is asymptomatic.

PATHOPHYSIOLOGY

The pathogenesis of AVMs constitutes a focal abnormalconglomeration of dilated arteries and veins with loss ofnormal vascular organization resulting in an abnormalarteriovenous shunting. The actual time of thedevelopment of AVMs and their triggering mechanismsare unclear. The involvement of the border zone sharedby the distal branches of the anterior, middle andposterior cerebral arteries3 might explain the time ofdevelopment in the late fetal period. The underlyingphysiological mechanism is bleeding in thesubarachnoid and the interventricular space, includingthe brain parenchyma. Neurological deficits andseizures are explained by the enlarging AVMs.

EPIDEMIOLOGY OF AVMS

No population based data is available on theprevalence of AVMs. There is also very little informationavailable on the prospective population based incidenceof bleeding from AVMs. The New York IslandsArteriovenous Malformation Study4 (a prospectivepopulation based survey) indicated the incidence of 1.34per 100,000 of the newly diagnosed AVMs. Theincidence of first ever hemorrhage was 0.51 per100,000 with the conclusion that nearly half of the AVMpatients suffered intracranial hemorrhage. Theoccurrence of AVMs is thought to be sporadic and fewerpatients with familial AVMs5 have been described.

No racial and sex predilection has been linked to theincidence of AVMs.

CLINICAL CHARACTERISTICS

The most common presentation of an arteriovenousmalformation is the intracerebral haemorrhage,3, 6

followed by the subarachnoid and intraventricularhaemorrhage. The clinical features include seizures andproblems resulting from the mass effect (from directcompression on the surrounding structures) and ischemicsteal (high flow through the AV malformation causinghypo perfusion of the adjacent tissues.

However, seizures are reported to be the initial symptomsin 16 to 53% of patients12 not caused by thehaemorrhage. Other clinical features such as headacheand focal neurological deficit occurred in 7 to 50% ofpatients.11

NATURAL HISTORY OF UNTREATEDARTERIOVENOUS MALFORMATION

The overall risk of hemorrhage from an untreated AVMis estimated to be about 2 to 4 %5, 6, per year. The AVMpresenting with an intracranial hemorrhage isconsidered to be a strong risk factor for thedevelopment of subsequent bleeding.3,5,6 Othermorphological risk factors for an AVM hemorrhageinclude a small sized AVM, an associated large arterialaneurysm, a deep venous drainage and the anatomicallocation particularly if deep within the brain (i.e. basalganglia, internal capsule and thalamus).

The effect of race and ethnic difference has also beenstudied in hemorrhagic AVMs. In a retrospective study8,the Hispanics had an increased risk of subsequenthemorrhage at 3.1% in comparison to a 2.1% risk ofbleeding in the Whites. The rising age also contributesto the AVM related hemorrhage. In a prospectiveColumbian AVM database9, an increasing age wassignificantly associated with hemorrhagic AVMs, alongwith the morphological characteristics outlined above.

16

17

Although a familial occurrence has also beendescribed, a systematic review10 did not find anysignificant familial association. In a Finish study11

involving a 24-year follow up, the annual incidence ofhemorrhage was 2 to 4% in AVMs that were deemeduntreatable.

IMAGING STUDIES

Arteriovenous malformation is usually identified with aComputed Tomography (CT) or Magnetic ResonanceImaging (MRI). A Catheter Angiography can provide adetailed visualization of the vascular structure. AMagnetic Resonance Angiography is quite useful indescribing the cerebral structures surrounding an AVM.It also helps in the detection of any associatedaneurysms, any obstruction as well as the pattern ofvenous flow through the AVMs. The Angiography(Figure 1) remains the gold standard investigation inidentifying the architecture of AVMs but is associatedwith the risk of stroke, arterial injury and a reaction tothe contrast medium.12 Super selective angiography isperformed via a flexible catheter into one of the maincerebral arteries to measure the feeding pressurewhich is a predictor for subsequent hemorrhage.

MANAGEMENT

The treatment of AVMs is best achieved by amultidisciplinary team approach including neurologists,neuroradiologists and neurosurgeons. The overalltreatment goal is the complete obliteration of the shuntthus reducing the risk of subsequent hemorrhage.

There are no randomized clinical trials available tocompare the invasive treatment versus the medicalmanagement alone in patients presenting with anunruptured AVMs. The intervention is considered incases where there is a high risk of hemorrhage (Figure2) and what treatments patients prefer. The Multi-center Unruptered Brain Arteriovenous MalformationTrail (ARUBA) with final results due for publication in2012 will provide us more information comparinginvasive measures versus medical management.

The invasive treatment methods include endovascularembolization, surgical resection or focal beamradiation alone or in combination. Surgical resection(Figure 3) results in immediate cure and the risksassociated with surgery are assessed with Spetzler-Martin Scale13 which is used to grade the AVMs (themaximum diameter, location and the presence orabsence of deep venous drainage) as the predictors ofsurgical outcome.13 The higher grade is associated

with increased surgical risk and the patients with grade1 to 3 are usually offered surgical resection afterembolization.

Radio-surgery is often indicated with lesion less than 3cm in diameter and located in an eloquent area wheresurgery is likely to cause a neurological deficit. Thecurative effect of radiotherapy takes approximately 1 to3 years for complete obliteration of AVM, during whichthere is a continuous risk of hemorrhage. In aprospective study14 of 500 patients (median follow upof 8 years) treated with radio-surgery, the risk ofhemorrhage was greatly reduced by 88%. The goal ofembolization is to block the high velocity arterial tovenous shunting, resulting in a reduction in the size ofthe AVM which improves the success rate of othermodes of treatment. It can also be used to relieveneurological symptoms caused by a large lesion.

Aneurysms are found in about 58% of AVMs and thetreatment depends upon their size and location. Thosepresenting in the feeding artery of AVM and more than7 mm in size are treated with the microsurgicalclipping or endovascular coiling. The selection oftreatment options in treating AVMs remains uncertaindue to the influence of many variables on the naturalhistory of AVMs, particularly the effect of size,association of aneurysms and the age at presentation.The guidelines published in 2001 on the managementoptions15 of treating AVMs, by the Stroke Council ofAmerican Stroke Association are based on the naturalhistory of AVMs and the risks associated with differentoptions. These recommendations are for AVMs ofgrades from 1 to 3.

CONCLUSION

Younger patients presenting with a hemorrhagic strokeneed to be investigated for the AVMs with a cerebralangiogram to assess the morphology and featuresassociated with an increased risk of hemorrhage. Nodata is available from the randomized clinical trials toguide us about the treatment options, includingsurgical resection, embolization, radio-surgery or thecombination of three options.

The choice of therapy depends upon the specificfeatures of the lesion, age of the patient, presence orabsence of bleeding, associated aneurysms andpattern of venous drainage. Given the complexity ofthe management options, patients with AVMs shouldbe managed in centers with expertise in various abovementioned treatment options aimed at a better clinicaloutcome.

18

Figure 1: Right internalcarotid artery angiogramshowing AVM with deepdraining vein and clippedaneurysm.

Figure 2: The axial T2 MRI withAVM nidus on the right andintraventricular haemorrhage. Thearrows demonstrate large drainingveins in the right lateral ventricleindicating a high risk of rebleeding.

Figure 3: Sagittal T1-weighted MRIshows artefacts from metal clips used inremoving the arteriovenous malformation(AVM) but no evidence of residualarteriovenous malformation.

REFERENCES

1. Perrat G, Nishioka H. Report on the cooperative study of intracranial Aneurysms and subarachnoid hemorrhages. Arteriovenous malformation: an Analysis of 545 cases of cranio-cerebral arteriovenous malformations and Fistulae reported tothe cooperative study. J Neurousurg 1966; 25:467-490.

2. Gross CR, Kas CR, Mohr JP, Cunningham SC, Baker WE. Stroke in south Alabama: incidence and diagnostic features – a population based study. Stroke 1984; 15:249-255.

3. Stapf C, Mohr JP, Sciacca RR, et al: Incident hemorrhage risk of brain Arteriovenous malformation located in the arterial border zones. Stroke 31: 2365- 2368, 2000.

4. C Stapf, H Mast, RR Sciacca, JP Mohr, et al: The NewYork Island AVM Study. Stroke 2003; 34:e29.

5. J van Beijnum, H B Der Worp, H M Schippers, O vanNieuwenhuizen, et al Familial Occurrence of Brain Arteriomalformations: A systematic Review. Journal ofNeurology, Neurosurgery, and Psychiatry 2007; 78:1213-1217.

6. ApSimon HT, Reef H, Phadke RV, Popovic EA. A population based study of Brain arteriovenous malformation: long term treatment outcomes. Stroke 2002; 33:2794- 2800.

7. Stapf C, Mast H, Sciacca RR, et al. Predictors of hemorrhage in patients with Untreated brain arteriovenous malformation. Neurology 2006; 66:1350-1355.

8. Helen Kim, Stephen Sidney, Charles E, et al. Racial/Ethnic Differences in Longitudinal Risk of Hemorrhage in Brain Arteriovenous MalformationPatients. Stroke: 2007; 38:2430-2437

9. C Staph, A. V. Khaw, R.R Sciacca, et al. Effect of Age on Clinical and Morphological Characteristics in Patients with Brain Arteriovenous Malformation. Stroke 2003; 34:2664-2669.

10. Familial Occurrence of Brain arterovenous malformation: a systemic review. Journal of neurology, Neurosurgery and psychiatry 2007; 78:1213-1217.

11. Ondra SL, Troup H, George ED. The Natural History of Symptomatic Arteriovenous malformationof the Brain: A 24 year follows up assessment. Neurosurg1990; 73:387-391.

12. Heiseman, JE, Dean BL, Hodak JA et al. Neurologiccomplications of Cerebral angiography. AJNR Am JNeuroradiol 1994; 15:1401-1407

13. Spetzler RF, Martin NA. A proposed grading system for arteriovenous Malformation. J Neurosurg.1986; 65:476-483.

14. Maruyama K, Kawahara N, Shin M, et al. The risk of hemorrhage after radio surgery for cerebral arteriovenous malformation. N Engl J Med: 2005; 352:146-153

15. Ogilvy CS, Stieg PE, Awad I, et al. AHA Scientific Statement: Recommendations for the management of intracranial arteriovenous Malformation. American Stroke Association. Stroke 2001; 32:1458-1471.

1 Schwamm, L H, Audebert H J, Amarenco P, et al. on behalf of the American Heart AssociationStroke Council; Council on Epidemiology andPrevention; Interdisciplinary Council on PeripheralVascular Disease; and the Council onCardiovascular Radiology and Intervention.Recommendations for the Implementation ofTelemedicine within Stroke Systems of Care: APolicy Statement From the American HeartAssociation. Stroke 2009; 40:2635-2660.

2. Schwamm L H, Holloway R G, Amarenco P, et al. on behalf of the American Heart AssociationStroke Council and the Interdisciplinary Council onPeripheral Vascular Disease. A Review of theEvidence for the Use of Telemedicine within StrokeSystems of Care: A Scientific Statement from theAmerican Heart Association/American StrokeAssociation. Stroke. 2009; 40:2616-2634.

3. Robert G. Hart and Lesly A. Pearce. CurrentStatus of Stroke Risk Stratification in Patients withAtrial Fibrillation. Stroke 2009; 40:2607-2610.

A review.

4. Controversies in Stroke:

Fiebach J B and Schellinger P D. MR MismatchIs Useful for Patient Selection for Thrombolysis: Yes.Stroke 2009; 40:2906-2907.

Schäbitz W-R. MR Mismatch Is Useful for Patient Selection for Thrombolysis: No. Stroke 2009; 40:2908-2909.

Stephen M. Davis and Geoffrey A. Donnan.MR Mismatch and Thrombolysis: Appealing but Validation Required. Stroke 2009; 40:2910.

5. del Zoppo G J, Saver J L, Jauch E C, et al. onbehalf of the American Heart Association StrokeCouncil. Expansion of the Time Window forTreatment of Acute Ischemic Stroke WithIntravenous Tissue Plasminogen Activator: AScience Advisory From the American HeartAssociation/American Stroke Association. Stroke2009; 40:2945-2948.

6. Summers D, Leonard A, Wentworth D, et al.on behalf of the American Heart AssociationCouncil on Cardiovascular Nursing and the StrokeCouncil. Comprehensive Overview of Nursing andInterdisciplinary Care of the Acute Ischemic StrokePatient: A Scientific Statement From the AmericanHeart Association. Stroke 2009; 40:2911-294.

7. Cucchiara B, Kasner S E, Tanne D, et al. forthe SAINT Investigators. Factors AssociatedWith Intracerebral Hemorrhage After ThrombolyticTherapy for Ischemic Stroke: Pooled Analysis ofPlacebo Data From the Stroke-Acute Ischemic NXYTreatment (SAINT) I and SAINT II Trials. Stroke2009; 40:3067-3072.

National Institutes of Health Stroke Scale, extensiveearly CT changes, baseline antiplatelet use(particularly double antiplatelet therapy) wasassociated with an increased risk of post–rtPAsymptomatic intracerebral hemorrhage. Of thesefactors, only National Institutes of Health StrokeScale was associated with clinical outcome.

8. Mitchell P H, Veith R C, Becker K J, et al.Brief Psychosocial–Behavioral Intervention WithAntidepressant Reduces Poststroke DepressionSignificantly More Than Usual Care WithAntidepressant: Living Well With Stroke:Randomized, Controlled Trial. Stroke 2009;40:3073-3078.

“One hundred one clinically depressed patientswith ischemic stroke within 4 months of indexstroke were randomly assigned to an 8-week briefpsychosocial–behavioral intervention plusantidepressant or usual care, includingantidepressant…. A brief psychosocial–behavioralintervention is highly effective in reducingdepression in both the short and long term.”

9. Amarenco P, Labreuche J, Lavallée P C, etal. Does ABCD2 Score Below 4 Allow More Timeto Evaluate Patients With a Transient IschemicAttack? Stroke 2009; 40:3091-3095.

“One in 5 patients with an ABCD2 score <4 hadhigh-risk disease requiring urgent treatmentdecision-making…”

Pick of the PapersJune to December 2009

SELECTED BY: DR HAMSARAJ SHETTY, UNIVERSITY HOSPITAL OF WALES, CARDIFF CF14 4XW

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10. Henry J.M. Barnett. Reflections on the CarotidArtery: 438 BC to 2009 AD: The Karolinska 2008Award Lecture in Stroke Research. Stroke 2009;40:3143-3148.

11. Pouwels S, Lalmohamed A, Leufkens B, etal. Risk of Hip/Femur Fracture After Stroke: APopulation-Based Case-Control Study. Stroke.2009;40:3281-3285.

“Stroke is associated with a 2.0-fold increase inthe risk of hip/femur fracture. The risk was highestamong patients younger than 71 years, females,and those whose stroke was more recent….”

12. Latchaw R E, Alberts M J, Lev M H, et al. onbehalf of the American Heart Association Councilon Cardiovascular Radiology and Intervention,Stroke Council, and the Interdisciplinary Councilon Peripheral Vascular Disease. Recommendationsfor Imaging of Acute Ischemic Stroke: A ScientificStatement From the American Heart Association.Stroke 2009; 40:3646-3678.

13. King A and Markus H S. Doppler EmbolicSignals in Cerebrovascular Disease and Predictionof Stroke Risk: A Systematic Review and Meta-Analysis. Stroke 2009; 40:3711-3717.

“Embolic signals predict stroke risk in acute stroke,symptomatic carotid stenosis, and postoperativelyafter carotid endarterectomy…”

14. Nogueira R G, Liebeskind D S, Sung G, etal. on Behalf of the MERCI; and Multi MERCIWriting Committee. Predictors of Good ClinicalOutcomes, Mortality, and SuccessfulRevascularization in Patients with Acute IschemicStroke Undergoing Thrombectomy: PooledAnalysis of the Mechanical Embolus Removal inCerebral Ischemia (MERCI) and Multi MERCI Trials.Stroke 2009; 40:3777-3783.

“Final recanalization status represents thestrongest predictor of clinical outcomes in patientsundergoing thrombectomy. The ability to removethe clot is negatively influenced by systolic bloodpressure on presentation…..”

15. Kesar T M, Perumal R, Reisman D S, et al. Functional Electrical Stimulation of AnklePlantarflexor and Dorsiflexor Muscles: Effects onPoststroke Gait. Stroke 2009; 40:3821-3827.

“…delivering FES to both the plantarflexor anddorsiflexor muscles can help to correct poststrokegait deficits at multiple joints (ankle and knee)during both the swing and stance phases of gait…”

16. Connolly SJ, Ezekowitz MD, Yusuf S, et al.Dabigatran versus Warfarin in Patients with AtrialFibrillation. N Engl J Med 361:1139- 1151.

“..dabigatran given at a dose of 110 mg wasassociated with rates of stroke and systemicembolism that were similar to those associated withwarfarin, as well as lower rates of majorhemorrhage. Dabigatran administered at a doseof 150 mg, as compared with warfarin, wasassociated with lower rates of stroke and systemicembolism but similar rates of major hemorrhage..”

17. Sun J C J,Michael J Davidson M J, Lamy A,Eikelboom JW. Antithrombotic management ofpatients with prosthetic heart valves: current evidenceand future trends. Lancet 2009; 374: 565-576.

A review.

18. Lafuente-Lafuente C, Mahé I, and Extramiana F. Management of atrial fibrillation. BMJ 2009;339:bBMJ 2009;339:b5216.

A review.

19. Strazzullo P, D’Elia L, Kandala N, and Cappuccio F P. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ 2009; 339:b4567.

20. Schürks M, Rist P M, Bigal M E, et al.Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ 2009;339:b3914.

“ Migraine is associated with a twofold increasedrisk of ischaemic stroke, which is only apparentamong people who have migraine with aura.…results also suggest a higher risk among womenand risk was further magnified for people withmigraine who were aged less than 45, smokers,and women who used oral contraceptives….”

Pick of the Papers June to December 2009

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21. Freynhagen R and Bennett M I. Diagnosis and management of neuropathic pain. BMJ 2009; 339: b3002

A review.

22. Salman R A , Labovitz D L, and Stapf C.Spontaneous intracerebral haemorrhage. BMJ 2009;339:b2586.

A review.

23. Boysen G, Krarup L-H, Zeng X, et al. for theExStroke Pilot Trial Group. ExStroke Pilot Trial ofthe effect of repeated instructions to improvephysical activity after ischaemic stroke: amultinational randomised controlled clinical trial.BMJ 2009; 339: b2810.

“..Repeated encouragement and verbal instructionin being physically active did not lead to asignificant increase in physical activity…”

24. Inzitari D, Pracucci G, Poggesi A, et al. onbehalf of the LADIS Study Group. Changes inwhite matter as determinant of global functionaldecline in older independent outpatients: threeyear follow-up of LADIS (leukoaraiosis anddisability) study cohort. BMJ 2009; 339: b2477.

“…in older adults who seek medical attention fornon-disabling complaints, severe age relatedchanges in white matter independently andstrongly predict rapid global functional decline…”

25. Terént A, Asplund K, Farahmand B, et al.Stroke unit care revisited: who benefits the most?A cohort study of 105 043 patients in Riks-Stroke,the Swedish Stroke Register. J NeurolNeurosurg Psychiatry 2009; 80:881-887.

“Stroke unit care was associated with better long-term survival in all subgroups, but youngerpatients, patients with intracerebral haemorrhageand patients who were unconscious had the bestrelative effect…”

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Pick of the Papers June to December 2009

9th Welsh StrokeConference

Friday 25th June 2010

Riverfront Centre, Newport

Themes to include acute stroke, stroke rehabilitation,thrombolysis training session, neuroprotection, etc

The Bhowmick Lecture will be delivered by Professor JeffSaver, Stroke Physician, UCLA, California

Call for Abstracts for posters now open. Abstracts to be received by April 30th Submission to allison.cooper@swansea.ac.uk

Best poster authors will be invited to give platform presentation during afternoon session

Poster themes: Science, Service and Clinical Cases of InterestInformation/guidance about posters from

allison.cooper@swansea.ac.uk and chris.burton@bangor.ac.uk

Bhowmick BursaryGuidance and application forms from hamsaraj.shetty@wales.nhs.uk

Information also can be found on the Welsh stroke intranet site at nww.stroke.wales.nhs.uk

Applications to be in by end of May

Information about conference and further details from welshstrokeconference@yahoo.co.uk