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

Surgical Treatment of Epilepsy

• Patient selection

• Diagnostic evaluation for surgical treatment

• Types of surgical treatment

• Outcomes of therapy: risk/benefit• Seizure freedom/cognitive function

Partial EpilepsyGoals of Therapy

• Render patient seizure-free

• Avoid neurological morbidity

• Improve quality of life

• Participating and productive member of society

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)

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)

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.

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.

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

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?

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)

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.

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.

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.

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.

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.

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

Wyllie E. The Treatment of Epilepsy: Principles and Practice. 4th ed. 2005.

Wyllie E. The Treatment of Epilepsy: Principles and Practice. 4th ed. 2005.

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

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

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

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

Long-term Intracranial Monitoring Subdural Grid Implantation

Functional Brain Monitoring

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.

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.

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.

Temporal LobectomyOperative Outcome

• Excellent outcome: 134 (77%)

• Seizure-free: 120 (69%)

• Operative complication: 2 (1%)

Radhakrishnan K, et al. Neurology. 1998.

Epilepsy SurgeryExtratemporal

• Non-lesional

• MRI is “normal”

• Limitations of ictal EEG

• Less favorable outcome

• Increased morbidity

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

Frontal LobectomyOperative Outcome

• 68 patients

• Excellent outcome: 59%• Abnormal MRI: 72%

• Normal MRI: 41%

Mosewich RK, et al. Epilepsia. 2000.

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

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.

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.

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.

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

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.

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

Technique of MST

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.

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.

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

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.

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.

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

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.

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

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.

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

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

RNS System

CT Scan Showing the Implanted Stimulator and Intracerebral Electrodes

Right-sided Seizure with No Stimulation

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

Responsive NeurostimulationEfficacy

Morrell MJ. Neurology. 2011.

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.

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.

SANTE Study Design

Anterior Nucleus of Thalamus Stimulation• Multi-center

• Prospective

• Randomized

• Double-blind

• Parallel design

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

• 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

Ablative Surgery

• Radio frequency ablation• Lesional ablation

• Gamma knife ablations• Lesional and MTLE ablation

• MRI guided laser ablation• Lesional and MTLE ablation

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

Typical Clinical Response

• Initial increase in auras with simultaneous decrease in focal seizures

• Headaches

• Radiological changes

One Year Post Radiosurgery

Two Years Post Radiosurgery

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.

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)

Laser Ablation for mTLEHeat Map

Wu C, et al. Epilepsia. 2019.

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.

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.

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.

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.

LITT Class 1 Outcome1 and 2 years

Wu C, et al. Epilepsia. 2019.

Predictive Power for Class 1 Outcome Location of Ablation

Wu C, et al. Epilepsia. 2019.

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).