Functional Neurosurgery: Epilepsy Surgery · 2015-11-12 · Epilepsy Surgery: History • Frederic and Erma Gibbs working with Percival Bailey (U. of Illinois 1947) – Temporal lobectomy

Functional Neurosurgery:Epilepsy Surgery

Functional Neurosurgery:Epilepsy Surgery

Kim J. Burchiel, M.D., F.A.C.S.Department of Neurological Surgery

Oregon Health and Science University

Kim J. Burchiel, M.D., F.A.C.S.Department of Neurological Surgery

Oregon Health and Science University

Epilepsy SurgeryEpilepsy Surgery

• 2 million in US have epilepsy• 400,000-600,000 medically intractable

– 25% candidates for epilepsy surgery• 1500 epilepsy surgery procedures done

in US per year• Cost of epilepsy surgery << lifetime

disability from epilepsy

• 2 million in US have epilepsy• 400,000-600,000 medically intractable

– 25% candidates for epilepsy surgery• 1500 epilepsy surgery procedures done

in US per year• Cost of epilepsy surgery << lifetime

disability from epilepsy


• J.E. Engle, M.D., Ph.D. (UCLA)– “In all of modern medicine, few generally

accepted therapeutic interventions are as underutilized as surgical treatment for epileptic seizures.”

• J.E. Engle, M.D., Ph.D. (UCLA)– “In all of modern medicine, few generally

accepted therapeutic interventions are as underutilized as surgical treatment for epileptic seizures.”

Epilepsy Surgery: HistoryEpilepsy Surgery: History

• Dr Benjamin Dudley– Trephinated 5 patients for focal motor seizures

(Transylvania Univ - Kentucky 1818-1827)• All 5 lived• 3 became seizure-free

• Hughings Jackson – Convinces Sir Victor Horsley to operate on 3

patients with post-traumatic seizures (National Hospital - London 1886)

• 2 became seizure-free

• Dr Benjamin Dudley– Trephinated 5 patients for focal motor seizures

(Transylvania Univ - Kentucky 1818-1827)• All 5 lived• 3 became seizure-free

• Hughings Jackson – Convinces Sir Victor Horsley to operate on 3

patients with post-traumatic seizures (National Hospital - London 1886)

• 2 became seizure-free

Epilepsy Surgery: HistoryEpilepsy Surgery: History

• Frederic and Erma Gibbs working with Percival Bailey (U. of Illinois 1947)– Temporal lobectomy

• Clinical localization

• Herbert Jasper and Wilder Penfield (Montreal Neurological Institute)– Temporal lobectomy

• Visible pathology– Epilepsy and the Functional Anatomy of the

Human Brain

• Frederic and Erma Gibbs working with Percival Bailey (U. of Illinois 1947)– Temporal lobectomy

• Clinical localization

• Herbert Jasper and Wilder Penfield (Montreal Neurological Institute)– Temporal lobectomy

• Visible pathology– Epilepsy and the Functional Anatomy of the

Human Brain

Epilepsy Surgery?

Medically Refractory Seizures

MRI

Video EEGWada TestNeuropsych

PETSPECT

Temporal LobectomyTemporal Lobectomy

Mesial Temporal SclerosisMesial Temporal Sclerosis

Mesial Temporal SclerosisMesial Temporal Sclerosis

Engel’s Classification System for Postoperative Seizure

Outcome

Engel’s Classification System for Postoperative Seizure

Outcome

• Class I: Free of disabling seizures• Class II: Rare disabling seizures• Class III Worthwhile improvement (>90%

seizure reduction)• Class IV No worthwhile improvement (< 90%

reduction or not improved)

• Class I: Free of disabling seizures• Class II: Rare disabling seizures• Class III Worthwhile improvement (>90%

seizure reduction)• Class IV No worthwhile improvement (< 90%

reduction or not improved)

Wiebe et al NEJM 2001Wiebe et al NEJM 2001

• 80 patients– Uncontrolled seizures

• > monthly• “strong temporal lobe semiology”• > one year• >2 drugs – Inc. DPH, CBZ, VPA

• 80 patients– Uncontrolled seizures

• > monthly• “strong temporal lobe semiology”• > one year• >2 drugs – Inc. DPH, CBZ, VPA

– Excluded patients• Brain lesions requiring urgent surgery• Progressive CNS disorders• Active psychosis• Pseudoseizures• FSIQ < 70• Previous epilepsy surgery• Focal extra-temporal EEG spikes/slowing • MRI evidence extra-temporal epileptogenic lesion• Bilateral temporal lobe pathology

– Excluded patients• Brain lesions requiring urgent surgery• Progressive CNS disorders• Active psychosis• Pseudoseizures• FSIQ < 70• Previous epilepsy surgery• Focal extra-temporal EEG spikes/slowing • MRI evidence extra-temporal epileptogenic lesion• Bilateral temporal lobe pathology


• Randomized controlled trial– Mesial temporal lobe surgery (n=40)– Antiepileptic drug therapy (n=40)

• Evaluated by two blinded neurologists– Record review only

• Randomized controlled trial– Mesial temporal lobe surgery (n=40)– Antiepileptic drug therapy (n=40)

• Evaluated by two blinded neurologists– Record review only


• Primary outcome measure– Freedom from seizures impairing

awareness (Engle class I)• Complex partial or generalized

• Primary outcome measure– Freedom from seizures impairing

awareness (Engle class I)• Complex partial or generalized


• Four patients assigned to surgery did not undergo surgery (intent to treat paradigm)– 1: declined surgery, 2: data inconsistent, 1:

no seizures during monitoring• Six patients had subdural electrode

recording

• Four patients assigned to surgery did not undergo surgery (intent to treat paradigm)– 1: declined surgery, 2: data inconsistent, 1:

no seizures during monitoring• Six patients had subdural electrode

recording


• Surgical morbidity– 1 thalamic infarct (sens loss in thigh)– 1 infection– 2 decline in verbal memory

• Asymptomatic VF deficits in 22 (55%)– Superior quadrantanopsia

• No surgical mortality– 1 death in medical arm (sudden, unexplained)

• Surgical morbidity– 1 thalamic infarct (sens loss in thigh)– 1 infection– 2 decline in verbal memory

• Asymptomatic VF deficits in 22 (55%)– Superior quadrantanopsia

• No surgical mortality– 1 death in medical arm (sudden, unexplained)


• Primary outcome (Engle class I)– Surgical group – 58%

• 64% in group actually having surgery– Medical group – 8%

• Quality of life– Significantly higher in surgical group

• Employment and school attendance– Strong trend in data favoring surgery

• Primary outcome (Engle class I)– Surgical group – 58%

• 64% in group actually having surgery– Medical group – 8%

• Quality of life– Significantly higher in surgical group

• Employment and school attendance– Strong trend in data favoring surgery





• Engle editorial– “Even if referrals for surgery for epilepsy

increase, successful outcomes with respect to seizures may not have a maximal beneficial effect on patients’ lives until referring physicians stop considering intervention for seizures a last resort.”

• Engle editorial– “Even if referrals for surgery for epilepsy

increase, successful outcomes with respect to seizures may not have a maximal beneficial effect on patients’ lives until referring physicians stop considering intervention for seizures a last resort.”


• What is it?• How effective is it?• Is it better or worse than Anterior Temporal

Lobectomy?– Seizure outcome– Neuropsychological outcome– Other

• When should its use be considered?

• What is it?• How effective is it?• Is it better or worse than Anterior Temporal

Lobectomy?– Seizure outcome– Neuropsychological outcome– Other

• When should its use be considered?

AmygdalohippocampectomyAmygdalohippocampectomy


Why Should AH be Considered?

Why Should AH be Considered?

• Preserve temporal neocortex in well-defined cases of mesial TL epilepsy

• Preserve neuropsychological functionfollowing epilepsy surgery– Avoid deficits– Maximize improvements

• Seizure free outcome must be comparable

• Preserve temporal neocortex in well-defined cases of mesial TL epilepsy

• Preserve neuropsychological functionfollowing epilepsy surgery– Avoid deficits– Maximize improvements

• Seizure free outcome must be comparable

Amygdalohippocampectomy: Surgical Approaches

Amygdalohippocampectomy: Surgical Approaches

• Transcortical• Trans-sylvian• Subtemporal

• Transcortical• Trans-sylvian• Subtemporal

Selective Amygdalohippocampectomy

Selective Amygdalohippocampectomy

Anterior Temporal LobectomyAnterior Temporal Lobectomy

• What it is• How effective it is• When its use should be considered• Potential Advantages over Anterior

Temporal Lobectomy

• What it is• How effective it is• When its use should be considered• Potential Advantages over Anterior

Temporal Lobectomy



Does Smaller = Better?ATL v AH


• What we want:– Large– Randomized– Contemporary– Single Center– Well defined selection criteria and pathology– Comprehensive standardized neuropsychological

battery and outcome measurements

• What we want:– Large– Randomized– Contemporary– Single Center– Well defined selection criteria and pathology– Comprehensive standardized neuropsychological

battery and outcome measurements

• What we have– Variable size– Non-randomized– Non-contemporary– Various inclusion criteria– Varied neuropsychological assessments at

variable time points

• What we have– Variable size– Non-randomized– Non-contemporary– Various inclusion criteria– Varied neuropsychological assessments at

variable time points



AH vs ATL: Seizure outcomeAH vs ATL: Seizure outcome

• N=74 consecutive, non-lesional cases– 37 AH– 37 ATL

• One year followup• Single center• Similar demographics, MRI features

• N=74 consecutive, non-lesional cases– 37 AH– 37 ATL

• One year followup• Single center• Similar demographics, MRI features

Arruda et al Ann Neurol 1996;40:446-50Arruda et al Ann Neurol 1996;40:446-50

Outcome by Procedure and Imaging Findings

Outcome by Procedure and Imaging Findings

% Seizure Free% Seizure FreeArruda et al Ann Neurol 1996;40:446-50Arruda et al Ann Neurol 1996;40:446-50

AH vs ATL: Seizure OutcomeAH vs ATL: Seizure Outcome

• Total N=321– AH = 138– ATL = 98– Lateral neocortical = 58– Lesion + Hippocampus = 27

• Retrospective• Non-randomized• Non-contemporary• Mean follow-up 38 months

• Total N=321– AH = 138– ATL = 98– Lateral neocortical = 58– Lesion + Hippocampus = 27

• Retrospective• Non-randomized• Non-contemporary• Mean follow-up 38 months

Clusmann J Neurosurg 2002; 97:1131-41Clusmann J Neurosurg 2002; 97:1131-41

AH vs. ATL: ResultsAH vs. ATL: Results

• Overall Outcome– 71% Class I– 11% Class II – 82% “satisfactory”

• Predictive factors– Clear MRI lesion– No history of status– MRI suggesting ganglioglioma or DNET– Concordant lateralized memory deficit– Absence of Dysplasia

• Overall Outcome– 71% Class I– 11% Class II – 82% “satisfactory”

• Predictive factors– Clear MRI lesion– No history of status– MRI suggesting ganglioglioma or DNET– Concordant lateralized memory deficit– Absence of Dysplasia


“Satisfactory” Outcome by Procedure

“Satisfactory” Outcome by Procedure

%

NS NS


AH vs ATL: Seizure outcomeAH vs ATL: Seizure outcome

• N= 161 (80 ATL, 81 AH)• Single Center• Single Pathology (HS)• Non-randomized• Non-contemporary• Mean followup 5.8 years

• N= 161 (80 ATL, 81 AH)• Single Center• Single Pathology (HS)• Non-randomized• Non-contemporary• Mean followup 5.8 years

Paglioli et al J Neurosurg 2006;104:70-78Paglioli et al J Neurosurg 2006;104:70-78

Outcome by Surgical Procedure

Outcome by Surgical Procedure

Paglioli et al J Neurosurg 2006;104:70-78Paglioli et al J Neurosurg 2006;104:70-78

Visual FunctionVisual Function

• Risk of contralateral quadrantanopsia• VFD 10% from center

– 7% ATL– 28% AH

• VFD 40% from center– 74% ATL– 78% AH

• Risk of contralateral quadrantanopsia• VFD 10% from center

– 7% ATL– 28% AH

• VFD 40% from center– 74% ATL– 78% AH

Egan et al Neurology 55:1818-22, 2000

Should AH Result in Better Postoperative Cognitive Function?


Perforant Path

Mossy FibersSchaffer Collaterals

Alveolar Path



• Less tissue is resected• Anterior Temporal Neocortex has a role in

– Language• Ojemann J Neurosurg 71:316-326, 1989• Hamberger et al.

– Neurology 56:56-61, 2001– Neurology 60:1478-83, 2003– Brain 128:2742-9, 2005

– Memory• Bayley et al Neuron 46:799-810

• Commissural pathways may connect operated side neocortex to opposite hipppocampus

• Less tissue is resected• Anterior Temporal Neocortex has a role in

– Language• Ojemann J Neurosurg 71:316-326, 1989• Hamberger et al.

– Neurology 56:56-61, 2001– Neurology 60:1478-83, 2003– Brain 128:2742-9, 2005

– Memory• Bayley et al Neuron 46:799-810

• Commissural pathways may connect operated side neocortex to opposite hipppocampus

Should AH Result in Better Postoperative Cognitive

Function?

Should AH Result in Better Postoperative Cognitive

Function?

• Disconnection of temporal neocortex• Preserved temporal neocortex is

hypometabolic– “Is amygdalohippocampectomy really selective in

medial temporal lobe epilepsy?” (Dupont et al Epilepsia 42:731-40, 2001)

• Disconnection of temporal neocortex• Preserved temporal neocortex is

hypometabolic– “Is amygdalohippocampectomy really selective in

medial temporal lobe epilepsy?” (Dupont et al Epilepsia 42:731-40, 2001)

AH vs. ATL: Cognitive Outcomes are Equivalent

AH vs. ATL: Cognitive Outcomes are Equivalent

• Montreal (ATL) n=23• Zurich (AH) n=25• Dublin (neocortical resection) n=23• Administered Verbal and Visuospatial

memory tests postoperatively (vs. controls)• Conclusion: Performance varied by side of

surgery not procedure

• Montreal (ATL) n=23• Zurich (AH) n=25• Dublin (neocortical resection) n=23• Administered Verbal and Visuospatial

memory tests postoperatively (vs. controls)• Conclusion: Performance varied by side of

surgery not procedure

Jones-Gotman Neuropsychologia 1997;35:963-73

Cognitive Outcomes Not Equivalent: Are the Data

Convincing?

Cognitive Outcomes Not Equivalent: Are the Data

Convincing?• Non-randomized, non-contemporary• N=49

– 17 ATL, 32 AH• Seizure free outcomes equivalent• IQ: Both groups gained 6-7 points postop.• Memory

– ATL: worsened non-verbal memory with R ATL– ATL: much worsened verbal memory with L ATL– AH: better memory following R AH– AH: smaller decrease in VM following L AH

• Non-randomized, non-contemporary• N=49

– 17 ATL, 32 AH• Seizure free outcomes equivalent• IQ: Both groups gained 6-7 points postop.• Memory

– ATL: worsened non-verbal memory with R ATL– ATL: much worsened verbal memory with L ATL– AH: better memory following R AH– AH: smaller decrease in VM following L AH

Morino ‘06

Neuropsychological OutcomesNeuropsychological Outcomes

• Paglioli et al (n=161 AH vs. ATL)– Many neuropsychological outcomes similar– With left sided surgery:

• 29% AH patients had improved verbal memory• 8% ATL patients had improved verbal memory• p=.05

• Clusmann et al (n=321, mostly AH and ATL)– Outcomes in AH superior for

• Verbal Memory• Attention• Total Neuropsychological performance

• Paglioli et al (n=161 AH vs. ATL)– Many neuropsychological outcomes similar– With left sided surgery:

• 29% AH patients had improved verbal memory• 8% ATL patients had improved verbal memory• p=.05

• Clusmann et al (n=321, mostly AH and ATL)– Outcomes in AH superior for

• Verbal Memory• Attention• Total Neuropsychological performance

ATL vs. AH: Effects on Verbal Memory by AgeATL vs. AH: Effects on Verbal Memory by Age

Selective Amygdalo-HippocampectomySelective Amygdalo-Hippocampectomy

Anterior TemporalLobectomy

Anterior TemporalLobectomy

ControlsControlsControls ControlsControlsControls

Pre-opPrePre--opop Pre-opPrePre--opop

Post-opPostPost--opopPost-opPostPost--opop

Helmstaedter et al 2002, 2003Helmstaedter et al 2002, 2003

AgeAge AgeAge

P<0.01P<0.01

Ver

bal M

emor

yV

erba

l Mem

ory

Does AH Result in Better Postoperative Cognitive

Function?

Does AH Result in Better Postoperative Cognitive

Function?• Yes

– Paglioli ’06– Morino ‘06– Gleissner ’02, ’04– Hori ’03, ‘07– Clusmann ’02– Pauli ‘99– Helmstaedter ‘96, ’97, ‘02– Wieser ’91 ‘98

• Yes– Paglioli ’06– Morino ‘06– Gleissner ’02, ’04– Hori ’03, ‘07– Clusmann ’02– Pauli ‘99– Helmstaedter ‘96, ’97, ‘02– Wieser ’91 ‘98

• No/Maybe/Equivocal– Jones-Gotman ’97– Wolf ‘93– Goldstein ’93

• No/Maybe/Equivocal– Jones-Gotman ’97– Wolf ‘93– Goldstein ’93

What can guide optimal selection of candidates for

AH?

What can guide optimal selection of candidates for

AH?

• Imaging• Electrophysiology• Clinical Factors• Alternative Imaging Techniques

• Imaging• Electrophysiology• Clinical Factors• Alternative Imaging Techniques

Factors Predictive of AH Failure

Factors Predictive of AH Failure

Abosch ‘02Abosch ‘02

%

Is Type of AH Important?Is Type of AH Important?

• Transcortical vs Transsylvian AH– Transsylvian: avoids neocortical resection but

transects ~20% of anterior temporal stem of superior temporal gyrus and risks vascular injury

– Transcortical: dissect lateral temporal neocortexand traverse WM

• N=140• Randomized• No time, selection, center bias

• Transcortical vs Transsylvian AH– Transsylvian: avoids neocortical resection but

transects ~20% of anterior temporal stem of superior temporal gyrus and risks vascular injury

– Transcortical: dissect lateral temporal neocortexand traverse WM

• N=140• Randomized• No time, selection, center bias

Lutz ‘04Lutz ‘04

Is Type of AH important?Is Type of AH important?

Lutz ‘04Lutz ‘04

Amygdalohippocampectomy: The OHSU Experience

Amygdalohippocampectomy: The OHSU Experience

• 68 consecutive patients with well-defined medial temporal lobe epilepsy and with at least 1 year follow-up

• Most had radiological evidence of mesial temporal sclerosis

• Ages 15-56

• 68 consecutive patients with well-defined medial temporal lobe epilepsy and with at least 1 year follow-up

• Most had radiological evidence of mesial temporal sclerosis

• Ages 15-56

Preoperative MRIPreoperative MRI




How small can it go?How small can it go?


Amygdalohippocampectomy: Surgical Outcome OHSU

Amygdalohippocampectomy: Surgical Outcome OHSU

%

Engel ClassificationEngel Classification

ConclusionsConclusions• Temporal lobe surgery superior to continued BMT for

medically-intractable Temporal Lobe Epilepsy (Class I evidence).

• Outcome of Amygdalohippocampectomy (AH) equivalent and Anterior Temporal Lobectomy (ATL) are equivalent (Class II)

• AH may be superior to ATL– Cognitive outcome (Class III)

• Transcortical AH may be superior to transsylvian AH– Language function (Class III)

• Temporal lobe surgery superior to continued BMT for medically-intractable Temporal Lobe Epilepsy (Class I evidence).

• Outcome of Amygdalohippocampectomy (AH) equivalent and Anterior Temporal Lobectomy (ATL) are equivalent (Class II)

• AH may be superior to ATL– Cognitive outcome (Class III)

• Transcortical AH may be superior to transsylvian AH– Language function (Class III)

Documents

Functional Neurosurgery: Epilepsy Surgery · 2015-11-12 · Epilepsy Surgery: History • Frederic and Erma Gibbs working with Percival Bailey (U. of Illinois 1947) – Temporal lobectomy