Treatment of Refractory Epilepsyd2qrtshcpf0x30.cloudfront.net/nodes/58/Treatment...Treatment of...
Transcript of Treatment of Refractory Epilepsyd2qrtshcpf0x30.cloudfront.net/nodes/58/Treatment...Treatment of...
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Treatment of Refractory EpilepsyPre-surgical Evaluation, Surgical Options, and Neurostimulation
Michael C. Smith, MDDirector, Rush Epilepsy Center
Professor and Senior Attending NeurologistRush University Medical Center
Chicago, Illinois
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Surgical Treatment of Epilepsy
• Patient selection
• Diagnostic evaluation for surgical treatment
• Types of surgical treatment
• Outcomes of therapy: risk/benefit• Seizure freedom/cognitive function
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Partial EpilepsyGoals of Therapy
• Render patient seizure-free
• Avoid neurological morbidity
• Improve quality of life
• Participating and productive member of society
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Focal EpilepsyTreatment
• “Old” drugs (CBZ, PB, PHT, VPA)
• “New” drugs (FBM, GBP, LAC, LEV, LTG, OXC, PGB, TGB, TPM, VGB, ZNS, CLO, PER, PRP, EZO, ECZ, ESL, BRV)
• Electrical stimulation (VNS, RNS, DBS)
• Diet (Ketogenic, Atkins, Low-Glycemic Index)
• Epilepsy surgery (ablative/resective/ disconnection)
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Response to AED Therapy5-Year Follow-Up
• 525 newly diagnosed patients
• 470 AED-naïve
• 55 AED-experienced
• 63% seizure-free for 1 year
• AED-naïve: 64%• 60% after first or second
monotherapy trial
• AED-experienced: 56%
• Most withdrawals or change of treatment were due to intolerable side effects
Kwan P, et al. N Engl J Med. 2000.
47%
13%
1% 3%0
20
40
60
80
100
First Second Third 2 drugs
AED-Naïve Patients
Monotherapy Trial
Re
spo
nse
to
AED
(%
pat
ien
ts)
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EpilepsyEfficacy of Treatment
• 63% were seizure-free the last year
• Only 11% who failed the first AED became seizure-free
• About 30%–40% will have a difficult-to-control seizure disorder
• 0% seizure-free on ≥3 AEDs
Brodie MJ, et al. Neurology. 2012.
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Definition of Intractable Epilepsy
Some variability in published definitions, but there are three main components:
1. Absence of response to 2 AEDs tolerated at reasonable doses
2. Minimal frequency (1 seizure/m) or lack of seizure remission of 6–12 months
3. Duration of epilepsy of 1–10 years of uncontrolled seizures
Berg AT, et al. Epilepsia. 2006; Berg AT. Neurol Clin. 2009; Kwan P, et al. Epilepsia. 2009.
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Medically Intractable Surgical EvaluationMy Criteria
• Failed two or more drugs to maximally tolerated dose (VPA, DPH, CBZ, LTG, LEV, TOP, ZNG). Different MOA
• Failure due to lack of efficacy, not intolerance
• Add adjunctive AED or combination (LEV-LTG, VPA-LTG) with synergistic MOAs
• Unable to achieve complete seizure control within 2 years
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Evaluation of the Medically Intractable PatientQuestions
• Does the patient have epilepsy?
• Need to record with EEG the events in question?• Nonepileptic event
• Psychiatric or medical etiology
• Are the AEDs that have been used appropriate for the seizure type?
• Have adequate blood levels been tolerated and documented to prove that seizures are medically intractable due to lack of efficacy, not tolerability?
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Surgical Decision Making
• Focal resections • First choice in appropriate candidates? Ablation?
• Importance of early intervention
• Palliative surgery (successful outcome does not always mean “cure”)• Vagus nerve stimulation (VNS)
• Corpus callosum division (CCD)
• Multiple subpial transection (MST)
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Epilepsy SurgeryComparative Study
• N Engl J Med, August 2, 2001
• Randomized controlled study
• 80 patients with TLE
• London, Ontario, Canada
• Surgery effective (P<0.001)
• QOL favors surgery (P<0.001)
Wiebe S, et al. N Engl J Med. 2001.
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NEJM Editorial
• Few accepted therapeutic interventions are as underutilized as surgical treatment of epilepsy
• Two million patients suffer with epilepsy in the United States
• 400,000 to 600,000 not controlled with AEDs
• 1990 survey: 1500 therapeutic surgical interventions
• Seizure-free rate: 70%–90% with surgical therapy
• Quality of life for patients with epilepsy treated surgically is related to the reoccurrence of seizures
• QOL—higher employment/school attendance in surgical group
Engel J. N Engl J Med. 2001.
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Practice ParametersTLE Surgery
• Epilepsy: chronic neurologic disorder affects 0.5%–1% of world’s population
• In the United States and other industrial nations with many AEDs available, 30%–40% of patients not adequately controlled
• WHO survey: disability from epilepsy accounts for ~1% of global burden of disease as measured by disability-adjusted life years (DALYs)
• This ranks third behind affective disorder and alcohol dependence among neurologic disorders. Comparable to worldwide burden due to lung and breast cancer
Engel J, et al. Epilepsia. 2003.
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Practice ParametersTLE Surgery
• Surgical procedures for treatment of epilepsy• 1985: ~500 year
• 1990: ~1500 year
• 2003: ~3000 year
• Estimated that there are 100,000–200,000 potential surgical candidates in the United States
• Early intervention may prevent or reverse the psychosocial sequelae of continued seizures in children
Engel J, et al. Epilepsia. 2003.
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Practice ParametersTLE Surgery
• Surgical efficacy compared to results from randomized clinical trials of AEDs
• Same patients with intractable partial epilepsy
• Responder rate (50% reduction of seizure frequency) of 50% is a good response
• Few patients rendered seizure-free
• Best results• VGB 6000 mg/d: 54% RR
• Most AEDs lower RR
• Vagal nerve stimulator: 30%–50% RR at 1 year
Engel J, et al. Epilepsia. 2003.
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Temporal Lobectomy Presurgical Evaluation
• Routine EEG
• MRI-head
• Seizure protocol/volumetrics
• Long-term EEG monitoring to record seizures
• Neuropsychological testing
• Sodium amobarbital study—functional MRI
• Other: MEG, fMRI, SISCOM, PET, intracranial EEG recording/stimulation
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Wyllie E. The Treatment of Epilepsy: Principles and Practice. 4th ed. 2005.
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Wyllie E. The Treatment of Epilepsy: Principles and Practice. 4th ed. 2005.
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Imaging in EpilepsySurgically Remediable Syndromes
• Lesional epilepsy: tumor, vascular anomaly, malformation of cortical development• Structural MRI
• Medial temporal lobe epilepsy: mesial temporal sclerosis• Structural MRI, PET
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Wieshmann UC. J Neurol Neurosurg Psychiatry. 2003.
CT vs MRI
CT
• Neonate <2 years
• Acute insult
• MRI incompatible
• Acute hemorrhage
• Ca+2
MRI• Focal seizure any age
• Focal fixed deficit
• Loss of prior control
• Resolution/details
• Axis variable
• T2 2D GRE for Ca+2 or hemosiderin
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von Oertzen J, et al. J Neurol Neurosurg Psychiatry. 2002.
Standard MRI vs Epilepsy ProtocolSurgical Patients (N=90)
Specificity %
Sensitivity %
Non-expert reader 22 —
Expert reader, standard MRI 40 —
Epilepsy protocol 89 >90
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Multiple Normal 1.5T MRIs Prior to High-resolution 3T MRI
• Cortical malformation
• Left • 3T MRI high-resolution 3D
structural scan
• Right• 3T MRI high-resolution
Cubic FLAIR
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Long-term Intracranial Monitoring Subdural Grid Implantation
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Functional Brain Monitoring
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Surgery
• Mesial temporal lobe epilepsy
• Frontal lobe epilepsy
• Lesional focal epilepsy• Focal encephalomalacia
• Tumor
• Vascular malformation
• Congenital developmental anomaly
• Neocortical cryptogenic epilepsy
Engel J, et al. Epilepsia. 2003; Wiebe S, et al. New Engl J Med. 2001; Zimmerman R, et al. Mayo Clin Proc. 2003; Treiman DM. Neuropsych Dis and Treat. 2010; Asadi-Pooya AA, et al. Epilepsy Behav. 2008.
Epilepsies That May Benefit Available Interventions
• Resection of the seizure focus
• Multiple subpial transection when seizure focus is in eloquent cortex
• Destruction of seizure focus by gamma knife/RF/laser*
• Corpus callosotomy
*Gamma knife, RF, and laser ablation are not FDA approved.
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Randomized, Controlled Trial of Surgery for TLE
• 80 patients randomly assigned for either surgery (40 patients) or AED therapy (40 patients) for 1 year
• Out of 40 patients, 4 refused surgery; of the remaining 36 patients, 6 required invasive pre-surgical investigation
• Results: percentage of patients free of seizures that impair awareness• 58% randomized to surgery
• 8% randomized to AED therapy
• 64% actually had surgery
• P<0.001
Wiebe S, et al. N Engl J Med. 2001.
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Temporal LobectomyEfficacy
• Long-term operative outcome (5 years)
• 62 of 89 patients (70%) seizure-free
• 18 of 89 patients (20%) significantly improved
Sperling MR, et al. JAMA. 1996.
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Temporal LobectomyOperative Outcome
• Excellent outcome: 134 (77%)
• Seizure-free: 120 (69%)
• Operative complication: 2 (1%)
Radhakrishnan K, et al. Neurology. 1998.
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Epilepsy SurgeryExtratemporal
• Non-lesional
• MRI is “normal”
• Limitations of ictal EEG
• Less favorable outcome
• Increased morbidity
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32
258
LP1…6RP1…6
1
LA1…4RA1…4
17
9
Open circles: midline electrodesFilled circles: surface electrodes
EEGSeizure onsetSeizure onsetInterictal discharge P16, P31, P32
SSEPHandFoot
CORTICAL STIMULATIONP6-P8 Left thumb tingling, twitchP16-P1 Left hand flexionP23-P1 head turn leftP24-P1 Left hand clonic flexionP31-P1 head turn leftP32-P1 left hand flexionP31-P32 all limbs extended (like a seizure)RP1-P1 left leg extensionRP2-P1 all limbs extendedRP1-RP2 all limbs extendedRP3-RP4 head turn leftLP1-LP2 Right foot inversion
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Frontal LobectomyOperative Outcome
• 68 patients
• Excellent outcome: 59%• Abnormal MRI: 72%
• Normal MRI: 41%
Mosewich RK, et al. Epilepsia. 2000.
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Long-term Seizure-free Rates Vary According to Surgery Type
Téllez-Zenteno JF, et al. Brain. 2005.
66%
61%59%
46% 46%
35% 34%
27%
16%
0%
10%
20%
30%
40%
50%
60%
70%
TL HEMI TL+EXTRA PAR OCCI CALLO* EXTRA TL FRONT MST
% p
atie
nts
Seizure-free rates(defined by the authors; follow-up ≥5 years;
results pooled if >2 studies)
TL, temporal lobe; HEMI, hemispherectomy; TL+EXTRA, grouped temporal and extratemporal lobe; PAR, parietal lobe; OCCI, occipital lobe; CALLO, callosotomy—freedom from drop attacks; EXTRA TL, grouped extratemporal lobe; FRONT, frontal lobe; MST, multiple subpial transections.
N 3895
N169
N2334
N82
N35
N99
N169
N486
N74
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Longer-term Follow-up and AED Drug Withdrawal
• 50 consecutive patients with MTS
• Mean F/U=5.8 years
• 82% seizure free at 1 year
• 76% seizure free at 2 years
• 64% seizure free at 5 years
• No further recurrence beyond 5 years
• 29% of recurrence associated with withdrawal of meds
Lowe AJ, et al. Epilepsia. 2004.
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Quality of Life Outcome
• Multicenter study: 396 cases
• Compared to pre-op baseline, at 3 months QOL, anxiety, depression improved (P<0.0001)
• QOL was highly correlated with seizure outcome
Spencer SS, et al. Neurology. 2003.
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Cost-Effectiveness
• 200 patients, intention-to-treat analysis projected over 35 years
• By year 8, surgery was more cost-effective in direct costs than medical treatment
• This does not take into account the effect on QOL and indirect costs
Wiebe S, et al. J Epilepsy. 1995.
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Corpus Callosum Division
• Corpus callosum division is a palliative procedure to improve the seizure control of patients with medically intractable epilepsy who have no localizable, single surgically resectable lesion
• Developed by Van Waganen in Rochester, New York, in 1939, refined by Wilson at Dartmouth in the 1970s, and others to the present
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Corpus Callosum DivisionPatient Outcomes
• 60%–100% of patients with drop seizures (as a primary indication) achieve a 50% or greater reduction in seizures
• 21%–67% of those with tonic-clonic seizures (as a primary indication) have a >50% reduction
• Seizure-free rates range from 2%–5%
Fuiks KS, et al. J Neurosurg. 1991; Wilson DH, et al. Neurology. 1982.
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Indications for Multiple Subpial Transection (MST)
• MST may be used alone or more commonly with cortical resection
• MST is used when the epileptogenic zone originates in or overlaps eloquent cortex where a resection is precluded due to the expected functional loss
• Eloquent cortex includes primary sensorimotor cortex and speech cortex
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Technique of MST
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Efficacy of MSTWorldwide
Significant Improvement
No Worthwhile Improvement
Neurologic Complications
Author, Year No. of
PatientsOnly MST
MST & RES
MST Only
MST & RES
No. of Patients
Type (No. of Patients)
Shimizu, et al. 1991. 12 12 — 0 0 0 —
Sawhney, et al. 1995. 21 8 12 1 0 0 —
Zonghui. 1995. 50 32a — 18a — 0 —
Wyler, et al. 1995. 6 6 — 0 — 1 Mild motor (1)
Hufnagel, et al. 1997. 22 4 15 2 1 7Mild speech deficits (2); mild motor deficits (3); overt speech deficits (2)
Pacia. 1997. 21 3 18 0 1 9Mild dysnomia (7); moderate dysphasia (1); loss of proprioception in hand (1)
Rougier, et al. 1934. 7 2 0 5 0 0
Patil, et al. 1997. 19 4 13 1 1 0
Rush Epilepsy Center 10 25 56 7 12 17Permanent (7); transient (8); sensorimotor (13)
TOTAL 258 96 114 34 15 34
aIn this study, it was not clear whether MST alone versus MST-resection was performed.
MST, multiple subpial transection; RES, resection.
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Neurostimulation for Epilepsy
• Responsive neurostimulation (RNS) • FDA approval (2014)
• Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) Trial• FDA approval (2018)
• Vagal nerve stimulation (VNS)• FDA approved for adjunctive treatment of epilepsy
(recently approved for patients ≥4 years old)
FDA Product Information.
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Open-Loop Neurostimulation
Stimulation delivered continuously or on a clock cycle
Examples: VNS and DBS
Stimulation is delivered only in response to detected
Epileptiform activity
Example: RNS
stim
stim
stim
stim
stimstim
stim
stim
Detection Stimulation
Closed-Loop Neurostimulation
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VNS Approved Indication
• In 1997, the U.S. Food and Drug Administration (FDA) approved vagus nerve stimulation (VNS) as adjunctive therapy for reducing the frequency of seizures in patients >12 years of age with partial onset seizures refractory to antiepileptic medications.
• In 2017, the FDA expanded its use as adjunctive therapy for patients ≥4 years of age with partial onset seizures that are refractory to antiepileptic medications.
FDA Product Information.
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VNS Parameters
Parameter Units Range Typical
*Output Current Milliamps (mA) 0–3.5 1.5
Signal Frequency Hertz (Hz) 1–30 20–30
*Pulse Width Microseconds (µs) 130–1,000 250–500
*Signal On-time Seconds (sec) 7–60 30
Signal Off-time Minutes (min) 0.2–180 5
*Independent, on-demand magnet mode parameters also available.
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Duty Cycle Calculation
Note: ON times should not exceed OFF times
OFF TIME (minutes)
ON TIME (seconds)
0.2 0.3 0.5 0.8 1.1 1.8 3 5 10
7 58 44 30 20 15 10 6 4 2
14 69 56 41 29 23 15 9 6 3
21 76 64 49 36 29 19 12 8 4
30 81 71 57 44 35 25 16 10 5
60 89 82 71 59 51 38 27 18 10
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VNS Therapy Works via Several Pathways
Changes in EEG
VNS Therapy
Neurotransmitter Expression
Cerebral Blood Flow
Norepinephrine1,2,7
GABA3,5,6
Serotonin4,5
Aspartate4,5
Desynchronization EEG rhythms9,10
Thalamus8,11
Cortex8,11
Anti-convulsive effect
1Roosevelt RW, et al. Brain Res. 2006; 2Hassert DL, et al. Behav Neurosci. 2004; 3Woodbury DM, Woodbury JW. Epilepsia. 1990; 4Hammond BM, et al. Brain Res. 1992; 5Ben-Menachem E, et al. Epilepsy Res. 1995;
6Marrosu F, et al. Epilepsy Res. 2003; 7Krahl SE, et al. Epilepsia. 1998; 8Henry TR, et al. Epilepsia. 2004; 9Wang H, Zylka MJ. J Neurosci. 2009; 10Koo B, et al. J Clin Neurophysiol. 2001; 11Vonck K, et al. Seizure. 2008.
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Seizure Cessation during Automatic Stimulation Was Observed in AspireSR Clinical Trials
Data on File, Cyberonics, Inc. Houston TX.
>60% of seizures treated
(N=46) ended during
automatic stimulation
For seizures that ended
during stimulation
(N=28), the closer
stimulation was to
seizure onset, the shorter
the seizure duration
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VNS in EpilepsyUpdated AAN Guidelines
Morris GL, et al. Neurology. 2013.
Recommendation Level
VNS may be considered as adjunctive treatment for children with partial or generalized epilepsy
C
VNS may be considered in patients with Lennox-Gastaut syndrome (LGS) C
In adult patients receiving VNS for epilepsy, improvement in mood may be an additional benefit
C
VNS may be considered progressively effective in patients over multiple years of exposure
C
Optimal VNS settings are still unknown, and evidence is insufficient to support the recommendation for the use of standard stimulation vs rapid stimulation to reduce seizure occurrence
U
Other: Extra vigilance in monitoring for site infection should be undertaken in children.C—Possibly effective, ineffective, or harmful (or possibly useful/predictive or not useful/predictive) for the given
condition in the specified populationU—Data inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven.
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Clinical UseVNS
• Maximize current load? Fast cycle/regular • Stimulation intensity (2–3 mA)
• On time (30 sec)
• Off time (1.8 min)
• Delay in maximal benefit 12–18 months
• Decrease SE by decreasing stimulation frequency from 30 Hz to 20 Hz
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Clinical ImpactVNS
• Rush Series over 450 patients
• At 6 months ~35% responder rate
• At 1 year ~46% responder rate
• Postictal state decreased in the majority
• Severity of seizures improved in the majority
• Mood improved in the majority
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RNS System
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CT Scan Showing the Implanted Stimulator and Intracerebral Electrodes
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Right-sided Seizure with No Stimulation
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Response to 2.5 mA
Response to 4.5 mA
Electrographic seizure that progressed to clinical CPS then GTC
Electrographic and clinical response to therapeutic stimulation
Left-sided seizure detected by subdural electrodes
Comparison of the ictal EEG response to increased therapeutic stimulation from 2.5 to 4.5 mA
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Responsive NeurostimulationEfficacy
Morrell MJ. Neurology. 2011.
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RNS System
Clinical Trial Efficacy Results• 29% responder rate for treatment group (N=95) at 4
months (27% in sham group)
• Responder rates for total seizures increased during the open label period from • 29% at 4 months (N=95)
• to 44% at 12 months (N=181)
• to 55% at 24 months (N=174)
• 14.5% had at least one 6-month seizure-free period
• Improves quality of life
Morrell MJ, et al. Epilepsia. 2008; Morrell MJ, et al. Neurology. 2011;Heck CM, et al. Epilepsia. 2014; Bergey GK. Neurology. 2015.
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RNS System
Temporal Lobe Epilepsy Clinical Trial Efficacy Results
• N=93 with MTLE• 68 bilateral, 17 left, 8 right
• 37% mean reduction in seizures vs 21% in control group (P=0.01)• Both groups showed decrease in seizures after
implantation
Salanova V, et al. Neurology. 2010; Morrell MJ. Neurology. 2011.
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SANTE Study Design
Anterior Nucleus of Thalamus Stimulation• Multi-center
• Prospective
• Randomized
• Double-blind
• Parallel design
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SANTE TrialResults
0
25
50
75
100
End Implant Double Blind Open Label Long Term
20.9
14.5
21.2
40.4 41
56
Control
Stimulation
Me
dia
n %
Se
izu
re R
ed
uct
ion
P=0.038
P=0.002
Fisher R, et al. Epilepsia. 2010.
(N=110) (N=81)(N=108) (N=99)
Effectiveness dependent on region of seizure onset. Temporal lobe onset P=0.025
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• 110 patients implanted
• The primary objective was met: stimulation reduced seizures
• Improvement over time: 68% reduction by 3 years
• No stimulation related deaths
• No symptomatic hemorrhages (some seen on imaging)
• Results submitted for FDA approval—initially denied
• Now given FDA approval and used clinically in the United States
Fisher R, et al. Epilepsia. 2010; FDA Product Information.
SANTE Trial Conclusions
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Ablative Surgery
• Radio frequency ablation• Lesional ablation
• Gamma knife ablations• Lesional and MTLE ablation
• MRI guided laser ablation• Lesional and MTLE ablation
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Radiosurgical Treatment
• Conformal radiation directed at temporal portion of the amygdala, the anterior 2 cm of the hippocampus and adjacent parahippocampal gyrus
• Total volume within 50% isodose line between 5.5 and 7.5 cc
• Treatment isocenters: 2–6
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Typical Clinical Response
• Initial increase in auras with simultaneous decrease in focal seizures
• Headaches
• Radiological changes
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One Year Post Radiosurgery
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Two Years Post Radiosurgery
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Gamma Knife Ablation for MTLE
• European prospective study1
• 21 patients treated 24 Gy (1 died MI)
• At 2 years: 65% seizure free
• 9/20 (44%) visual field cut, no neuropsych deterioration
• U.S. prospective study2
• 30 patients randomized high-dose 24 Gy (13 patients) vs low-dose 20 Gy (17 patients)
• At 36 months• Seizure-free: 77% high-dose vs 59% low-dose
• Visual field deficit: 61% high-dose vs 41% low-dose
• Verbal memory: improves 12%, worsens 15%
1Regis J, et al. Epilepsia. 2004; 2Barbaro N, et al. Ann Neurol. 2009.
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Potential Risk of Radiosurgery for Epilepsy
• Risk of ongoing seizures while waiting for radiosurgical effect—2 to 3 years (including sudden death from epilepsy)
• Neuropsychological deficits• Language/Memory
• Visual field defects• Quadrantanopsia (relatively likely)
• Homonymous hemianopsia (in Europe with >8 cc volume)
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Laser Ablation for mTLEHeat Map
Wu C, et al. Epilepsia. 2019.
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MRI Guided Laser Ablation
• Using stereotactic frame MRI, guided laser is placed in the amygdala and a series of MRI-guided laser ablations in amygdala/hippocampus
• 13 patients (9 with MTS), 15 procedures: f/u 1–25 months• 7/13 (54%) seizure-free Engel class IA, B, or D
• 2/13 (15%) Class IVB; 3/13 (23%) Class IIIA, 1 recent
• Failures occurred early; 2 went on to resection
• Mean volume of ablation 60%—did not correlate: outcome
• 1 small occipital subdural hemorrhage; 1 homonymous hemianopsia
• Neuropsych: no worsening, improved naming/object 6 m
• Small series, needs longer follow up? Late failures
Willie JT, et al. Neurosurgery. 2014.
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MRI-guided Laser Ablation
• Using stereotactic frame, MRI-guided laser is placed in the amygdala and a series of MRI-guided laser ablations in amygdala/hippocampus
• 41 patients TLE, +/- MTS underwent SLAH
• 5/41 (12%) did not maintain seizure freedom
• Repeat ablation amygdala, entorhinal cortex, parahippocampal gyrus with 1–3 trajectories
• 5/5 seizure free; however, mean follow-up only 6 mo
• ? Long-term efficacy
Willie JT, et al. Neurosurgery. 2015.
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MRI-guided Laser Ablation
• Using stereotactic frame, MRI-guided laser is placed in the amygdala and a MRI-guided laser ablation in amygdala/hippocampus
• 23 patients TLE, +/- MTS underwent laser ablation
• 65% Engel Class 1 (free of disabling seizures ) at 1-year F/U
• Sparing of the mesial head of hippocampus was correlated with persistent disabling seizures (P=0.01)
• Laterally trajectory showed trend for poor outcome (P=0.08)
• ? Long-term efficacy
Jermakowicz W, et al. Epilepsia. 2017.
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Laser Interstitial Thermal Therapy (LITT)Trial Multicenter—234 mTLE patients
At last follow-up of at least 1 year:• 58% achieved Engel I outcomes• 76.9% achieved either Engel I or Engel II outcomes• MRI–MST did not affect outcome• Presence of history of GTC decreased outcome• Complications: 5.1% visual, 4.3% psychiatric, 1.3%
post-op hemorrhage
Ablation location was correlated with Class I outcome: anterior, medial, and inferior temporal lobe ablations, which involved greater amygdalar volume = better outcomes.
Wu C, et al. Epilepsia. 2019.
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LITT Class 1 Outcome1 and 2 years
Wu C, et al. Epilepsia. 2019.
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Predictive Power for Class 1 Outcome Location of Ablation
Wu C, et al. Epilepsia. 2019.
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Conclusions
• Surgical treatment of epilepsy is effective and cost-effective in the appropriate patient.
• Evidence-based data suggests that surgery is more effective than best medical care for TLE.
• Radiosurgery/laser ablation appear effective in TLE, but are not FDA approved—longer follow-up needed.
• Thalamic stimulation for multifocal epilepsy is effective, and now has FDA approval (2018).
• Vagal nerve stimulation is FDA approved as adjunct treatment and in Lennox-Gastaut syndrome (LGS), may be progressively more effective over time.
• Responsive neurostimulation is effective in multifocal epilepsy and has FDA approval (2014).