Surgical Treatments For Epilepsy.14

REVIEW ARTICLE
Surgical Treatments
for Epilepsy

CONTINUUM AUDIO
INTERVIEW AVAILABLE
ONLINE
By George W. Culler IV, MD; Barbara C. Jobst, MD, Dr Med, FAAN
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ABSTRACT
PURPOSE OF REVIEW: More than 20 new antiseizure medications have been
approved by the US Food and Drug Administration (FDA) in the past
3 decades; however, outcomes in newly diagnosed epilepsy have not
improved, and epilepsy remains drug resistant in up to 40% of patients.
Evidence supports improved seizure outcomes and quality of life in those
who have undergone epilepsy surgery, but epilepsy surgery remains
underutilized. This article outlines indications for epilepsy surgery,
describes the presurgical workup, and summarizes current available
CITE AS:
surgical approaches.
CONTINUUM (MINNEAP MINN)
2022;28(2, EPILEPSY):536–558. RECENT FINDINGS: Class I evidence has demonstrated the superiority of
resective surgery compared to medical therapy for seizure control and
Address correspondence to
Dr George W. Culler, Geisel quality of life in patients with drug-resistant epilepsy. The use of minimally
School of Medicine at Dartmouth, invasive options, such as laser interstitial thermal therapy and stereotactic
Dartmouth-Hitchcock Medical
radiosurgery, are alternatives to resective surgery in well-selected
Center, One Medical Center
Dr, Lebanon, NH 03766, George. patients. Neuromodulation techniques, such as responsive
[email protected]. neurostimulation, deep brain stimulation, and vagus nerve stimulation,
RELATIONSHIP DISCLOSURE:
offer a suitable alternative, especially in those where resective surgery is
Dr Culler reports no disclosure. contraindicated or where patients prefer nonresective surgery. Although
Dr Jobst has received personal neuromodulation approaches reduce seizure frequency, they are less
compensation of $20,000 for
serving as an Associate Editor likely to be associated with seizure freedom than resective surgery.
on Neurology. The institution of
Dr Jobst has received research SUMMARY: Appropriate patients with drug-resistant epilepsy benefit from
support from the American
Epilepsy Society, the Centers epilepsy surgery. If two well-chosen and tolerated medication trials do not
for Disease Control and achieve seizure control, referral to a comprehensive epilepsy center for a
Prevention, the Department of
Defense, the Epilepsy
thorough presurgical workup and discussion of surgical options is
Foundation, Harvard Pilgrim appropriate. Mounting Class I evidence supports a significantly higher
Health Care, Inc, the National chance of stopping disabling seizures with surgery than with further
Institutes of Health, and
NeuroPace, Inc.
medication trials.
UNLABELED USE OF
PRODUCTS/INVESTIGATIONAL
USE DISCLOSURE:
INTRODUCTION
Drs Culler and Jobst discuss
E
the unlabeled/investigational pilepsy is considered drug resistant if at least two appropriately chosen
use of neurostimulation for the and used antiseizure medications have failed to control seizures.1
treatment of refractory
genetic/idiopathic
Despite the availability of many new antiseizure medications with
generalized epilepsy. differing mechanisms of action, outcomes in newly diagnosed epilepsy
have not improved, and the proportion of patients with drug-resistant
© 2022 American Academy epilepsy is up to 40%.2-4 Drug-resistant epilepsy is associated with high rates of
of Neurology. morbidity, including loss of independence, depression, neurologic impairment
536 APRIL 2022
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

(eg, memory loss), and worse quality of life. Additionally, patients with drug- KEY POINTS
resistant epilepsy have a mortality rate 5 to 10 times that of the general population
● Drug-resistant epilepsy is
secondary to sudden unexpected death in epilepsy (SUDEP), accidents, diagnosed when a person
and suicide.5 continues to have seizures
The efficacy of epilepsy surgery, including resective surgery and despite adequate trials of
neurostimulation, has been demonstrated in several Class I studies. Since 2001, two appropriately chosen
and well-tolerated
three randomized controlled trials comparing surgical to medical management
antiseizure medications.
have demonstrated resective surgical treatment is safe and effective for
drug-resistant epilepsy.6-8 Several randomized controlled trials and long-term ● One-third of patients with
open-label studies have also reported good seizure outcomes with the use of epilepsy have drug-resistant
neurostimulation (vagus nerve stimulation [VNS], responsive neurostimulation epilepsy. Drug-resistant
epilepsy is associated with
[RNS], and deep brain stimulation [DBS]) for drug-resistant epilepsy.9-11 higher rates of morbidity
Additionally, modern minimally invasive techniques, such as laser interstitial (eg, loss of independence,
thermal therapy (LITT) and stereotactic radiosurgery, are becoming popular depression, worse quality of
options in certain epilepsy centers. Overall, surgery may result in up to a 70% life) and mortality.
seizure freedom rate in carefully selected patients with drug-resistant epilepsy.12 ● Epilepsy surgery
evaluation is appropriate for
THE UNDERUTILIZATION OF EPILEPSY SURGERY anyone with focal disabling
Despite evidence supporting the efficacy of epilepsy surgery and practice seizures that continue to
occur despite treatment
parameters published by the American Academy of Neurology advising referral
with two appropriately
to an epilepsy center for surgical evaluation, epilepsy surgery remains chosen antiseizure
underutilized, with estimates of under 1% of eligible candidates referred for medications.
surgical evaluation.13 A 2020 study of children with epilepsy also concluded only
about 1% of children with a diagnostic code of drug-resistant epilepsy according ● Evaluation for surgery
begins at an established
to the International Classification of Diseases, Ninth Revision, Clinical Modification comprehensive epilepsy
(ICD-9-CM) received epilepsy surgical procedures.14 Although the center, where the diagnosis
above-mentioned studies have limitations, the low rates of epilepsy surgery are of epilepsy is confirmed.
likely multifactorial. Barriers include access issues (eg, lack of nearby epilepsy
program, transportation, lack of health insurance, inability to take time off
work), negative attitudes toward or fear of surgery, and lack of general education
or knowledge among referring providers and patients about epilepsy and
epilepsy surgery. TABLE 11-1 lists common misconceptions about epilepsy
surgery.
EPILEPSY SURGERY CANDIDATES

Evaluation for epilepsy surgery is appropriate for anyone with disabling seizures
that cause significant impairment in quality of life and continue to occur despite
treatment with two well-tolerated and appropriately chosen antiseizure
medications.15 Patients may have initially responded well to antiseizure
medications or have a history of prior remission but later become drug resistant
and thus suitable candidates for surgery.16
Referral to an established comprehensive epilepsy center for evaluation is
recommended, where video-EEG monitoring is usually performed. Video-EEG
helps to establish the diagnosis of epilepsy and rule out nonadherence to
antiseizure medications and pseudoresistance to antiseizure medications in
patients with nonepileptic seizures or those on the wrong antiseizure medication
for their syndrome.17
Surgical candidates with focal epilepsy may be broadly categorized into
several groups: patients with mesial temporal lobe epilepsy or neocortical
epilepsy, lesional epilepsy due to focal structural pathology (eg, low-grade
CONTINUUMJOURNAL.COM 537

SURGICAL TREATMENTS FOR EPILEPSY
glioma, cavernous malformation), or nonlesional focal epilepsy. In patients with

focal epilepsy, a presurgical evaluation for resective surgery should be
performed. If resective surgery is not an option, neurostimulation should be
considered as an alternative.
Other resective surgical alternatives, such as hemispherectomy or
hemispherotomy, may be appropriate for patients with severe epilepsy and
preexisting hemiparesis. Surgical options are limited for generalized epilepsies;

however, for drug-resistant epilepsies such as Lennox-Gastaut syndrome and
others, corpus callosotomy may offer palliation for disabling drop attacks or
rapidly generalizing seizures. Neuromodulation (eg, DBS, VNS) may also be

considered in those with generalized epilepsy who have disabling seizures.
PRESURGICAL EVALUATION
The goal of the presurgical evaluation in patients with drug-resistant epilepsy is
to best identify the cortical area that is generating seizures, which, when
removed by surgery, will result in seizure freedom. This is referred to as the
epileptogenic zone, which is a theoretical concept defined as the minimum
amount of cortex that must be resected to produce seizure freedom.18 To best
TABLE 11-1 Common Misconceptions About Epilepsy Surgerya
Misconception Fact
All drugs need to be tried Seizure freedom is unlikely after two drugs have failed
Bilateral EEG spikes are a contraindication to surgery Patients with unilateral-onset seizures usually have
bilateral spikes
Normal MRI is a contraindication to surgery Other techniques often detect a single epileptogenic zone
in patients with normal MRIs
Multiple or diffuse lesions on MRI are a The epileptogenic zone may involve only a part of the lesion
contraindication to surgery
Surgery is not possible if primary cortex is involved Essential functions can be localized and protected
Surgery will make memory worse if the patient has Poor memory usually will not get worse and could get better
an existing memory deficit
Chronic psychosis is a contraindication to surgery Outcome depends on the type of epilepsy and the type
of surgery
IQ less than 70 is a contraindication to surgery Outcome depends on the type of epilepsy and the type
of surgery
Patients with focal epilepsy and a focal lesion can have the Focal lesions can be incidental findings unrelated to
lesion removed without detailed presurgical evaluation the epilepsy; epileptogenicity of a lesion should always
be confirmed
Generalized epilepsy is a contraindication to surgery Appropriately selected patients with generalized epilepsy
may be candidates for deep brain stimulation, vagus nerve
stimulation, or potentially thalamic responsive
neurostimulation
EEG = electroencephalography; IQ = intelligence quotient; MRI = magnetic resonance imaging.

a
Modified with permission from Engel J Jr, Neurology.17 © 2016 American Academy of Neurology.
538 APRIL 2022

estimate the epileptogenic zone boundaries, a variety of different diagnostic tools
are used (TABLE 11-2).
The diagnosis of epilepsy begins with a comprehensive history that focuses on
describing seizure symptomatology, frequency, and epilepsy duration to
understand the epilepsy subtype and begin localization of the epileptogenic zone.
The hallmarks of the presurgical evaluation include continuous video-EEG
monitoring for interictal and ictal analysis to confirm the diagnosis of epilepsy
and correlate the patient’s reported symptomatology to aid in localization of the
seizure-onset zone.19,20 Antiseizure medications are often reduced to record
several seizures and ensure that the patient is having only one seizure type.
Modifications to a standard 10-20 electrode placement may include additional
Presurgical Investigative Tools and Their Significance TABLE 11-2
Presurgical investigations Significance

Seizure history and general medical history Characterizes typical seizure types and symptomatology by the patient and
their relatives which are later verified on video-EEG monitoring
Ascertains all relevant past history and epilepsy risk factors (eg, history of
prolonged febrile convulsions, meningoencephalitis, family history of
epilepsy, head trauma)
General medical and neurologic examination Identifies focal neurologic deficits, which suggest an underlying lesion or
diagnosis of a syndrome associated with epilepsy (ie, neurocutaneous
abnormalities in tuberous sclerosis complex or Sturge-Weber syndrome)
Video-EEG monitoring Confirms the diagnosis of epilepsy; interictal and ictal analysis provides
information regarding the lateralization and localization of the
Interictal EEG
epileptogenic zone
Ictal EEG
Seizure symptomatology
Neuropsychological assessment Provides preoperative baseline and predicts risk of cognitive decline with
surgery; helps identify and evaluate comorbid psychiatric disorders
MRI Identifies structural abnormalities associated with seizures (eg,

hippocampal sclerosis, focal cortical dysplasias)
Functional imaging (PET, SPECT) Provides ancillary information for epileptogenic zone localization:
Interictal focal hypometabolism on FDG-PET
Interictal hypoperfusion and ictal hyperperfusion on SPECT
PET and SPECT coregistered with MRI may aid in sensitivity of identifying an
epileptogenic lesion (PET-MRI, SISCOM)
Electrical and magnetic source imaging Provides ancillary electrical and magnetic source localization of interictal
(ESI, MSI); EEG-fMRI, HD-EEG epileptiform discharges
May be used for functional mapping
Functional mapping (fMRI, Wada test) Assesses language dominance, verbal memory dominance, and prediction
of postoperative decline
EEG = electroencephalography; ESI = electrical source imaging; FDG-PET = fludeoxyglucose positron emission tomography; MRI = magnetic
resonance imaging; MSI = magnetic source imaging; PET = positron emission tomography; SISCOM = subtraction ictal SPECT coregistered to MRI;
SPECT = single-photon emission computed tomography.

10-10 distanced scalp electrodes, sphenoidal electrodes, or subtemporal

electrodes to aid in localization.
High-resolution brain MRI with a dedicated epilepsy protocol is necessary to
detect a potential structural abnormality most likely responsible for seizures. In
patients with suspected temporal lobe epilepsy, three-dimensional T1-weighted,
T2-weighted, and fluid-attenuated inversion recovery (FLAIR) sequences with
thin coronal cuts through the hippocampus may detect subtle signal change,
atrophy, and/or loss of internal structure associated with mesial temporal
sclerosis and increase the likelihood of a favorable surgical outcome.21
Higher-resolution 3-Tesla (3T) or 7T MRI scanners improve the identification

of structural lesions by up to 20% compared with a 1.5T scanner.22 Careful
evaluation of the MRI by an expert neuroradiologist provides additional
sensitivity, with identification of lesions such as depth-of-the-sulcus dysplasia or
periventricular nodular heterotopias.23
Comprehensive neuropsychological testing is necessary both to localize
preoperative deficits that may correlate with the seizure-onset zone and to
FIGURE 11-1
Simplified proposed surgical algorithm for drug-resistant epilepsy.
EEG = electroencephalography; fMRI = functional magnetic resonance imaging; HD-EEG = high-density
electroencephalography; MEG = magnetoencephalography; MRI = magnetic resonance imaging; PET =
positron emission tomography; SPECT = single-photon emission computed tomography.
a
In some patients who receive intracranial evaluation, the epileptogenic zone is not fully delineated (ie,
the seizure-onset zone is not captured), and subsequent invasive evaluation is necessary before offering
surgical therapy.
b
Corpus callosotomy may be considered to reduce the frequency and severity of drop seizures, which
include generalized tonic-clonic, tonic, and atonic seizures.
c
Responsive neurostimulation of the centromedian nucleus of the thalamus has been considered a viable
therapeutic option for patients with drug-resistant focal and generalized epilepsy in some centers.
540 APRIL 2022

predict postoperative cognitive outcome and seizure control.24 For example, KEY POINTS
better preoperative verbal memory performance is a strong predictor of
● A presurgical evaluation is
postoperative memory decline following surgery of the dominant (left, in most necessary to identify the
cases) temporal lobe.25 cortical area that is
Positron emission tomography (PET) has proven valuable because a focal region generating seizures, which,
of hypometabolism may help confirm general epileptogenic zone location and when removed, will result in
seizure freedom; this is

predict favorable outcome with surgery when MRI is negative.26 Ictal single-
known as the epileptogenic
photon emission computed tomography (SPECT) might be useful when zone.
demonstrating a region of hyperperfusion, especially when subtracting interictal
SPECT imaging.27 When available, magnetoencephalography (MEG) and electrical ● Video-EEG monitoring
source imaging are other ancillary tools that may help localize a seizure focus. confirms the diagnosis of
epilepsy type by recording
To ensure a safe and optimal surgical outcome, identification of eloquent the patient’s habitual
cortex and its relation to the epileptogenic zone is necessary. Functional MRI seizures and correlates the
(fMRI) is helpful for language lateralization and identifying motor and sensory patient’s reported
areas. fMRI for lateralization of verbal and visuospatial memory is performed in symptomatology to aid in
localization.
some centers but is not entirely reliable.28 Developed by Dr Juhn Wada more
than 60 years ago, the intracarotid amobarbital procedure, or Wada test, is still ● Abnormalities on initial
used in some centers for language lateralization and to assess the risk of brain MRI may be missed.
postoperative amnesia with hippocampal resection.25,29 Careful inspection by an
expert neuroradiologist and
When these studies are concordant in localizing the seizure-onset zone to the
the use of higher-resolution
nondominant mesial temporal lobe or the respective lesion, resective surgery MRI scanners and positron
may sometimes be performed without further diagnostic workup (FIGURE 11-1). emission tomography (PET)
However, if presurgical studies are discordant or if doubt exists about the may identify subtle lesions
(eg, dysplasia).
seizure-onset zone, further diagnostic investigation with intracranial EEG is
necessary, including for patients who have lesions with poorly defined borders ● Neuropsychological
(eg, focal cortical dysplasia), dual pathology or multiple lesions, or a prior history testing and functional
of surgical failure. Intracranial EEG is also necessary when the seizure-onset zone imaging help predict
is close to eloquent cortex. postoperative deficits and
localize eloquent cortex.
INTRACRANIAL VIDEO-EEG MONITORING ● Resective surgery may be

Between 30% and 50% of epilepsy surgeries in tertiary epilepsy centers require possible without intracranial
intracranial EEG.30 The aim of intracranial EEG is twofold: (1) to record ictal and EEG studies if presurgical
findings (eg, ictal and
interictal electrographic data for epileptogenic zone delineation to support or
interictal EEG, seizure
disprove a hypothesis regarding the site of seizure onset from presurgical symptomatology, and MRI)
investigations and (2) to determine the location of eloquent cortex in relation to are concordant to the
the epileptogenic zone and define safety margins for surgery with the use of nondominant temporal lobe.
electrical stimulation for functional mapping.
● The goals of intracranial
Intracranial video-EEG monitoring is typically indicated for nonlesional focal EEG are twofold: (1) to
epilepsies or if presurgical evaluations are discordant. For example, intracranial further localize the
evaluation is necessary in temporal lobe epilepsy when atypical clinical features epileptogenic zone and
are present (eg, extratemporal symptomatology, when neuroimaging prove/disprove a hypothesis
and (2) to determine the
abnormalities disagree with suspected seizure-onset zones), when a high risk of location of eloquent cortex
postoperative cognitive decline is present (ie, dominant temporal lobe epilepsy), with electrical stimulation.
or to answer the question of whether the patient has bitemporal lobe epilepsy
(FIGURE 11-1). The use of intracranial EEG is illustrated in CASE 11-1 and CASE 11-2.
Two common approaches to intracranial EEG monitoring are (1) craniotomy
for implantation of subdural electrodes, including grid and strip electrodes with
or without depth electrodes, and (2) stereo-EEG with depth electrode placed
without craniotomy. A combination of stereotactic and subdural electrodes may
also be used.

CASE 11-1 A 39-year-old right-handed man with a history of drug-resistant epilepsy

since 1 year of age was referred to an epilepsy center. His seizures started
with an aura of a “funny feeling” that progressed to loss of awareness,
unresponsiveness, and frequent blinking with hand
automatisms. Despite being on appropriate doses of three antiseizure
medications, he still had one focal impaired awareness seizure per

month, with rare progression to bilateral tonic-clonic seizures. Six
antiseizure medications had previously failed to control his seizures.
A video-EEG showed right temporal sharp waves, and several of his

typical seizures were recorded with a right temporal onset. Over
2 decades, serial brain MRIs with dedicated epilepsy protocols had shown
a stable cystic left mesial temporal lobe mass and progressive right
hippocampal sclerosis and atrophy (FIGURE 11-2). An ictal single-photon
emission computed tomography (SPECT) scan performed during his
phase I evaluation showed increased uptake in the right anterior temporal
lobe during a typical seizure. A Wada test confirmed he was left
hemisphere dominant for language. Memory was intact on the left but
severely impaired on the right.
Since the patient continued to have intractable seizures and the
presurgical findings were concordant with right temporal lobe epilepsy
with the exception of bilateral temporal lobe lesions, stereo-EEG was
performed to confirm his seizures were arising only from the right
temporal lobe and not from the left temporal lobe. Stereo-EEG
electrodes were placed in bilateral amygdalae, hippocampi,
orbitofrontal, and insula, with additional subdural strip electrodes to
bilateral temporooccipital junctions (FIGURE 11-3).
Intracranial EEG recorded frequent epileptiform discharges arising
from the right hippocampus and amygdala. Ictal recording recorded six
of the patient’s habitual
seizures, which began with
high-frequency gamma
activity arising from the
right anterior hippocampus
and spread to the right
amygdala and posterior
hippocampus (FIGURE 11-4).
At the end of invasive EEG
monitoring, the stereo-EEG
electrodes were removed
and a right selective
amygdalohippocampectomy
was performed with laser
interstitial thermal therapy
(FIGURE 11-5). At his last FIGURE 11-2
follow-up, 2.5 years after Imaging of the patient in CASE 11-1. Coronal T2-
surgery, he remained seizure weighted, epilepsy protocol MRI shows right
free and very pleased with hippocampal atrophy (white arrow) and a left
perihippocampal cystic lesion (yellow arrow).
the surgery.
542 APRIL 2022

FIGURE 11-3
Imaging of the patient in CASE 11-1. Postoperative anteroposterior and lateral skull x-rays
show bilateral intracranial electrode placement.
FIGURE 11-4
EEG of the patient in CASE 11-1. Ictal EEG shows high-frequency gamma activity beginning in the
right anterior hippocampus (RAHCD1-3, arrows). Note: Only select channels are featured.
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FIGURE 11-5
Postoperative imaging of the patient in CASE 11-1. Axial (A) and coronal (B) contrast-enhanced
T1-weighted MRI demonstrates selective ablation of the right hippocampus and amygdala
(selective amygdalohippocampectomy) with laser interstitial thermal therapy, with contrast
enhancement seen within the ablation cavity (arrows).
COMMENT This case exemplifies the utility of stereo-EEG in clarifying the

epileptogenic zone, demonstrating that the left mesial temporal lobe mass
in this patient was not associated with the ictal onset of his habitual clinical
seizure. The use of stereo-EEG also confirmed a secondary hypothesis that
all the patient’s clinical seizures began from the right hippocampus, which
was concordant with all other presurgical evaluations. This enabled the
surgical epilepsy team to be more confident that removal of the right
mesial temporal lesion would render a good outcome and seizure freedom
for the patient.
Complications are typically low with stereo-EEG, with the most prevalent risk
being hemorrhage (1%) or infections (0.8%).31 In a direct comparison of 260
patients undergoing stereo-EEG and subdural electrode implantation at a single
institution, major iatrogenic events such as symptomatic hemorrhage or
infection were higher (7.2%) in patients receiving subdural evaluation than in
patients receiving stereo-EEG (0%, P=.003).32 Potential advantages and
disadvantages of each type of intracranial monitoring are summarized in TABLE 11-3.
EPILEPSY SURGERY
Three Class I randomized controlled trials have shown the effectiveness of
surgery compared to ongoing medical treatment in patients with drug-resistant
epilepsy, not only for seizure control but also for quality of life.6-8 Studies by
Wiebe and colleagues6 and Engel and colleagues7 established surgical efficacy in
adults with temporal lobe epilepsy, whereas Dwivedi and colleagues8 confirmed
similar success in the pediatric patient population. In addition to resective
544 APRIL 2022

surgery, surgical options include laser ablation and three US Food and Drug KEY POINTS
Administration (FDA)–approved neurostimulation devices. A simplified
● Only 30% to 50% of
proposed surgical algorithm is shown in FIGURE 11-1. epilepsy surgeries require
To measure seizure outcomes after surgery, the Engel Epilepsy Surgery intracranial EEG, which
Outcome Scale and the International League Against Epilepsy (ILAE) epilepsy includes the use of
surgery outcome classification are frequently used, both of which classify stereotactic electrodes,
subdural grid electrodes, or

postoperative seizures along a range from favorable (Engel class I/II or ILAE
a combination of the two to
outcome classification 1-3) to no worthwhile improvement or worsening seizures aid in delineation of the
(Engel class IV or ILAE outcome classification 5-6) (TABLE 11-4).33,34 epileptogenic zone.
The following sections explore the different types of surgical options in more
detail. A simplified summary of seizure freedom rates and indications for ● Three Class I randomized
controlled trials have shown
different surgical options is presented in TABLE 11-5.35-39 the effectiveness of
resective surgery compared
Resective Surgery to continued medical
Resection of the epileptogenic zone remains the gold standard for the best seizure treatment in adults and
children with drug-resistant
outcome in drug-resistant epilepsy compared to best medical therapy. The epilepsy.
following subsections review specific seizure outcomes in three common classes
of focal epilepsy: temporal lobe, extratemporal lobe, and lesional epilepsy. ● Different surgical options
are available for drug-
resistant epilepsy, including
TEMPORAL LOBE EPILEPSY. Temporal lobe epilepsy is the most common type of
resection, laser ablation,
focal epilepsy and is further divided into mesial and neocortical temporal lobe and neurostimulation, which
epilepsy depending on where seizures actually originate. The clinical syndromes can be tailored to the
of mesial and neocortical temporal lobe epilepsy often overlap, and specific patient.
distinguishing between the two may be difficult unless an obvious lesion is
● Verbal memory deficits
present. The effectiveness of surgery for temporal lobe epilepsy is well are the most consistent
established. In the first randomized study of continued medical treatment adverse effect following
compared to surgical treatment for patients with drug-resistant temporal lobe dominant (typically left)
epilepsy (n = 80), 58% of the patients treated surgically were free of seizures with temporal resections when
compared to nondominant
impaired awareness at 1 year compared to 8% treated medically ( P<.001).6 resection.
Quality-of-life ratings were significantly higher in the postsurgical group. In a
separate study of 38 patients with mesial temporal lobe epilepsy who underwent
surgery within 2 years of developing drug-resistant epilepsy, seizure freedom
was achieved in 73% of patients treated surgically after 2 years compared with
0% of the patients treated medically.7
The most common procedure for temporal lobe epilepsy is an anterior
temporal lobe resection, which includes the anterior temporal pole,
hippocampus, and amygdala.12 Because of the risk of verbal deficits when the
language-dominant (typically left) side is resected, the posterior extent of the
resection is further from the temporal pole on the right compared to the left.40
Selective amygdalohippocampectomy remains an alternative to anterior
temporal lobectomy if the epileptogenic zone is confined to the mesial temporal
structures (eg, hippocampal sclerosis) and appears to have efficacy similar to
anterior temporal lobectomy in regard to seizure, cognitive, and psychiatric
outcomes.41 If seizures are confirmed to arise from neocortical temporal regions
(eg, lateral or basal temporal cortex), a tailored resection sparing the
hippocampus can be performed.
In a systematic review of focal surgical resections, major neurologic
complications were noted to occur in 4% of patients undergoing temporal lobe
resections and were more common in pediatric patients than in adults.42 Verbal
memory deficits are the most consistent adverse effect following left temporal

CASE 11-2 A 50-year-old right-handed woman with a history of drug-resistant

epilepsy since 6 years of age was referred to an epilepsy center. Her
initial seizure symptomatology started with an aura of fear, causing her to
cry out before progressing to a bilateral tonic-clonic seizure. When she
was in her thirties, acute gastroenteritis prevented her from taking her
antiseizure medications, and she subsequently went into status

epilepticus and was in the intensive care unit for nearly 2 months.
Afterward, a new predominant seizure type emerged, described as drop
attacks without loss of consciousness. Her seizures began with a right-

sided somatosensory aura that progressed quickly to brief tonic-
myoclonic movements of the right hemibody, resulting in falls. Seizures
occurred daily, were often clustered, and were disabling despite
adequate doses of levetiracetam, carbamazepine, and gabapentin. By
the time she was referred for presurgical workup, she had persistent
right-sided weakness and was wheelchair dependent.
The patient’s video-EEG showed left frontal sharp waves, and habitual
seizures were captured that correlated with left hemispheric slowing
diffusely. Brain MRI with a dedicated epilepsy protocol was otherwise
nonlesional, with the exception of a mildly asymmetric, left smaller than
right, hippocampus. Fludeoxyglucose positron emission tomography
(FDG-PET) was unremarkable. Neuropsychological testing was notable for
impaired executive function and attention and impaired motor skills on the
right side.
The patient underwent intracranial EEG with broad coverage of the left
frontocentral region, including interhemispheric and left frontal grids, left
frontoparietal strip (1 x 8 contact), and a hippocampal depth electrode
(FIGURE 11-6). Intracranial video-EEG recorded several habitual focal seizures
correlating to seizure onset arising from the left mesial frontal lobe near the
leg motor cortex.
Because of the proximity of the seizure-onset zone to eloquent motor
cortex, the patient underwent implantation of a responsive neurostimulator
with subdural strips (FIGURE 11-7). The patient’s habitual seizures were recorded
via subdural strip electrodes. Electrocorticography of the patient’s seizures
recorded before turning on stimulation therapy and after
electrocorticography-triggered stimulation was turned on is shown
in FIGURE 11-8.
At her 2-year follow-up, the patient reported significantly decreased
seizure frequency, which was verified on chronic electrocorticography
recordings, and was able to walk independently.
546 APRIL 2022

FIGURE 11-6
Postoperative imaging of the patient in CASE 11-2. A, Three-dimensional reconstruction of a
T1-weighted MRI fused with CT for visualization of subdural grid and strip electrodes
placed over the left hemisphere. B, Sagittal postcontrast T1-weighted MRI shows
contacts from which the intracranial seizure onset was recorded (red circle). C, Axial
postcontrast T1-weighted MRI shows the one transoccipital hippocampal depth
electrode placement.
FIGURE 11-7
Postoperative imaging of the patient in CASE 11-2. A, Sagittal T1-weighted MRI with two 1 x 4
subdural strips placed over the leg motor cortex and supplementary sensorimotor area.
B, Sagittal T1-weighted MRI shows placement of responsive neurostimulation battery and
stimulator under the scalp anterior to strip electrodes. An additional strip electrode can be
seen which was placed over the convexity of left frontal lobe. C, Lateral skull x-ray shows
generator and strip electrodes. Two extra 1 x 4 subdural strips can be seen superior to the
interhemispheric strips placed over the convexity of left frontal lobe; however, these
electrodes were not connected to the stimulator.
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FIGURE 11-8
Electrocorticography of the patient in CASE 11-2. A, Long-episode recording of a typical
seizure, which is detected by the responsive neurostimulation (RNS) in blue tracing in the
top and bottom panels (time base expanded). In the middle panel, RNS provides
quantitative analysis of the seizure. B, RNS delivers stimulation at the onset of a typical
seizure (blue) and is shown to have stopped the seizure.
COMMENT This patient’s seizure symptomatology, EEG findings, and

neuropsychological testing results demonstrated a likely left frontal or
central lobule epilepsy involving highly eloquent primary somatosensory
and motor cortex. Brain MRI was nonlesional with the exception of a mildly
asymmetric, left smaller than right, hippocampus, which was of unclear
significance. Intracranial EEG with strip, grids, and hippocampal depth
electrode identified seizures arising from the left mesial frontal lobe. A
resection was not possible because of the proximity of the seizure focus to
the primary leg motor cortex, and the epilepsy surgical team placed a
responsive neurostimulator as a therapeutic means with excellent outcome.
resection when compared to right temporal resection.12 Visual field deficits, most
commonly a superior quadrantanopia due to injury to the inferior optic
radiations, comprise half of all permanent neurologic deficits but are generally
well tolerated.42
EXTRATEMPORAL LOBE EPILEPSY. Surgical resection of neocortical and

extratemporal epilepsies is more challenging because of the difficulty of defining
the boundaries of the epileptogenic zone and the concern for clinically functional
cortex (eg, primary motor, visual, and language areas). Frontal lobe surgery is
the next most common resection after temporal lobe surgery. In a meta-analysis
of nearly 1200 patients with frontal lobe epilepsy, resection resulted in a
seizure-free outcome in 45.1%; seizure-free outcome was higher in patients with
lesional epilepsy (61%) than in patients with nonlesional epilepsy (39%).12,43
548 APRIL 2022

Furthermore, in a systematic review and meta-analysis of studies evaluating all
epilepsy surgery outcomes, parietooccipital epilepsy surgery resulted in seizure
freedom for 46% of patients.44 Patients with nonlesional neocortical epilepsies
inevitably need intracranial EEG evaluation to better localize the epileptogenic
zone and delineate the bounds of eloquent cortex. Epileptogenic zones that
overlap with primary language areas (ie, the Broca and Wernicke areas), the
primary sensorimotor cortex, or the visual cortex cannot be safely resected

without a likely postoperative deficit. Factors associated with seizure-free
outcome in a 2015 systematic review are detailed in TABLE 11-6.
LESIONAL EPILEPSY. Lesional epilepsy, which is defined as having an unequivocal

MRI abnormality responsible for seizures, is associated with a better outcome than
nonlesional epilepsy. A meta-analysis including 2860 patients reported a 2.5 times
greater likelihood of a seizure-free outcome when a discrete lesion was resected
compared to no discrete lesion.45 Common pathologic entities responsible for
drug-resistant lesional epilepsy include hippocampal sclerosis, malformations of
cortical development, cavernous malformations, and low-grade tumors.
Malformations of cortical development are a common cause of drug-resistant
epilepsy and encompass a broad range of disorders, the most common of which is
focal cortical dysplasia. Identifying focal cortical dysplasia can be challenging
because dysplasia may be diffuse or multilobar, is commonly not seen on MRI
(or “MRI-negative”), and often is identified only on histopathology. In a subset
of patients, MRI identification of a transmantle sign or the use of FDG-PET in
MRI-negative cases helps to improve detection of subtle areas of cortical
thickening and depth-of-the-sulcus dysplasias, which subsequently helps with
surgical prognosis.46 In a retrospective series of patients with seizures due to
polymicrogyria or periventricular nodular heterotopia, the use of intracranial
Advantages and Disadvantages of Stereoelectroencephalography and Subdural TABLE 11-3

Grid Electrodes
Advantages Disadvantages
Stereo-EEG Maps three-dimensional epileptogenic networks, including Limited spatial sampling of electrical activity
easier sampling of spatially distinct and deep regions (eg, from tissue directly around each electrode
periventricular gray matter heterotopia, insular, depth-of-
Does not map spatially continuous coverage of
sulcus regions)
brain surface gyri
Easily samples bilateral hemispheres
Less feasible in young children (requires bone
No craniotomy, decreased perioperative pain, and shorter thickness > 2 mm)
recovery time
Lower rate of serious adverse events
Subdural grid More precise functional mapping when the epileptogenic Higher rates of serious adverse events
electrodes zone involves cortical regions adjacent to eloquent cortex
Sampling of insula is difficult and high risk
Craniotomy has been performed, and resection can occur
Sampling bilateral hemispheres is challenging
when electrodes come out
(ie, bilateral craniotomies)
Depth electrodes may be added to sample deep structures
Cannot sample gray matter in sulci (eg, depth-
of interest; however, the accuracy may be affected
of-sulcus lesions)
because of shifting of the brain after craniotomy

EEG helped to localize the epileptogenic zone and seizure freedom was reported
in 72% of patients with polymicrogyria and 76% of patients with periventricular
nodular heteropia.47,48
Cavernous malformations and arteriovenous malformations are the most
common vascular lesions found in patients with focal epilepsy. In a case series of
168 patients with symptomatic epilepsy attributed to cavernous malformations,
more than two-thirds of patients were seizure free at 3 years after surgery.49 In
this study, predictors for good outcome included mesiotemporal location, size
less than 1.5 cm, and the absence of secondarily generalized seizures. Typically,
surgery consists of lesionectomy plus resection of surrounding epileptogenic

cortex, often guided by intracranial monitoring or intraoperative
electrocorticography.
Low-grade slow-growing tumors are often associated with seizures.
Gangliogliomas and dysembryoplastic neuroepithelial tumors (DNETs) account
for the majority of tumors found in adults with epilepsy. In a 2017 multicenter
retrospective study of 339 patients with low-grade tumors who underwent
epilepsy surgery, 88% of patients with associated drug-resistant epilepsy became
seizure free.50 Younger age at surgery, a temporal resection site, and complete
tumor removal were predictors of a favorable seizure outcome in this cohort.
Laser Interstitial Thermal Therapy

Stereotactic ablation of seizure foci has become increasingly popular as a
minimally invasive surgical option for those with drug-resistant epilepsy. LITT is
performed with a fiberoptic laser probe using real-time MRI thermography to
TABLE 11-4 Engel and International League Against Epilepsy Classifications of

Postoperative Seizure Outcome
Engel Epilepsy Surgery Outcome Scale33

◆ Class I: free of disabling seizures (Ia); nondisabling focal aware seizures or auras only (Ib);
some disabling seizures after surgery but free of disabling seizures for ≥2 years (Ic);
convulsions with seizure medication withdrawal only (Id)
◆ Class II: initially seizure free (IIa) but had rare disabling seizures (IIb) in the past 2 years (IIc);
nocturnal seizures only (IId)
◆ Class III: worthwhile seizure reduction (IIIa); prolonged seizure-free periods last less than
2 years but >50% of follow-up period (IIIb)
◆ Class IV: no worthwhile improvement; significant seizure reduction (IVa); no change (IVb);
worsened seizures (IVc)
International League Against Epilepsy Classification34
◆ Class 1: completely seizure free (if since surgery, 1a); no auras
◆ Class 2: only auras; no other seizures
◆ Class 3: 1-3 seizure days per year; with or without auras
◆ Class 4: 4 seizure days per year to 50% reduction in baseline number of seizure days; with or
without auras
◆ Class 5: <50% reduction in baseline number of seizure days to 100% increase in baseline
number of seizure days; with or without auras
◆ Class 6: >100% increase in baseline number of seizure days; with or without auras
550 APRIL 2022

track the temperature of ablated tissue and visualize surrounding structures to be
protected. In a retrospective review of 58 consecutive patients undergoing
stereotactic laser amygdalohippocampectomy, 53.4% of patients were free of
disabling seizures (Engel class I).51 In this study, quality-of-life scores were
significantly improved. MRI-guided LITT has successfully been used for ablation
of epileptogenic lesions such as cavernous malformations, hypothalamic
hamartomas, and focal cortical dysplasia.52,53

In mostly small observational studies of patients with mesial temporal lobe
epilepsy, treatment with LITT appeared to result in less postoperative
neuropsychological decline specific to object naming and face recognition.54
Summary of Surgical Treatment Options and Reported Seizure Freedom TABLE 11-5
Rates
Surgical treatment in drug-resistant Seizure

epilepsy freedoma Indication
6,7
Continued medical treatment 0-8.0% Patients may decline surgical intervention or if the risk of adverse
effects of surgical treatments outweigh the potential benefits
Surgical resection12
Overall (median) 64.2%b Focal cortical resection may be considered in any patient with drug-
resistant epilepsy if the region causing seizures can be removed
All focal epilepsy 52-67%
with minimal risk of disabling neurologic or cognitive dysfunction
Temporal lobe epilepsy 58-76%
Extratemporal lobe epilepsy 34-56%
Frontal lobe epilepsy 45%
Laser ablation for mesial temporal 38-78% Minimally invasive option for patients who are good resective
lobe epilepsy35 candidates, especially those with mesial temporal lobe epilepsy or
epileptogenic lesions (ie, cavernous malformations) who are
resistant to open surgery; laser ablation does not preclude a
subsequent open surgery, if needed
Stereotactic radiotherapy for mesial 51-74% Minimally invasive option for patients who would be good
temporal lobe epilepsy36 candidates for anterior temporal lobectomy for mesial temporal
lobe epilepsy but are resistant to open surgery
Neuromodulationc
Vagus nerve stimulation37 8.3% Patients with focal drug-resistant epilepsy who undergo full surgical
evaluation and are deemed poor candidates for resective surgery;
Responsive neurostimulation38 29%
also an option for patients with multifocal epilepsy, generalized
39
Deep brain stimulation 16% epilepsy, or those who are opposed to resective surgery
Responsive neurostimulation is a safe and effective targeted
treatment option for seizures that arise from eloquent regions of
cortex and up to two suspected epileptogenic foci
Vagus nerve stimulation and deep brain stimulation are most often
used for patients who have poorly localized or multifocal epilepsy
a
Criteria vary among studies for definition of seizure remission.
b
Median seizure freedom rate among all studies.12
c
Seizure-free interval of at least 6 months at last follow-up.

Iatrogenic adverse events related to LITT are low and typically due to thermal
damage to surrounding structures. In a retrospective study of 57 patients who
underwent LITT for mesial temporal lobe epilepsy, lower rates of visual field
deficits and smaller deficits were seen than in patients who underwent historical
anterior temporal lobe resections.55 In another small series of 35 patients, one
patient developed a brain abscess.56
Randomized controlled trials comparing laser ablation to alternative therapies

have not been conducted; however, an open-label prospective study of LITT for
mesial temporal lobe epilepsy is ongoing.57 In nearly all cases, laser ablation
presents no barrier to subsequent open surgery, if needed, which may provide an

attractive alternative or first option for patients who are initially resistant to open
surgery. The use of LITT for the treatment of epilepsy is demonstrated in
CASE 11-1.
Stereotactic Radiosurgery
Stereotactic radiosurgery is a minimally invasive procedure performed with
radiation that has been considered as an alternative to open surgery for mesial
temporal lobe epilepsy. In the only prospective randomized trial of stereotactic
radiosurgery versus open temporal lobectomy (the ROSE [Radiosurgery or Open
Surgery for Epilepsy] trial), patients randomly assigned to the open temporal
lobectomy arm had an advantage in seizure remission over those treated with
TABLE 11-6 Factors Associated With Seizure-free Outcome After Resective Surgerya
Positive association
◆ Seizures without loss of awareness
◆ Complete resection of a lesion
◆ Febrile seizures in childhood
◆ Prolonged seizure freedom after surgery
Negative association
◆ Normal MRI
◆ Generalized tonic-clonic seizures
◆ Need for intracranial EEG (ie, stereo-EEG)
No association
◆ Sex
◆ Age
◆ Side of resection
Inconsistent association
◆ Duration of epilepsy
◆ Temporal versus extratemporal lobe epilepsy
◆ Pathology
EEG = electroencephalography; MRI = magnetic resonance imaging.

a
Modified with permission from Jobst BC, Cascino GD, JAMA.12 © 2015 American Medical Association.
552 APRIL 2022

stereotactic radiosurgery (78% compared to 52%), without a significant KEY POINTS
difference in verbal memory deficits.36 Adverse events related to stereotactic
● Visual field deficits, most
radiosurgery included transient cerebral edema and related symptoms after the commonly a superior
first year of treatment, which was expected. Long-term follow-up data are quadrantanopia, comprise
lacking. Stereotactic radiosurgery remains an alternative to anterior temporal half of all permanent
lobectomy at certain centers for patients reluctant to undergo open surgery. neurologic deficits after
temporal lobe resection and

are generally well tolerated.
HEMISPHERIC AND POORLY LOCALIZED EPILEPSY
Variations of surgical resection, such as corpus callosotomy, are reserved as a ● Surgery for lesional
means of palliation to reduce morbidity in patients with poorly localized or epilepsy, as defined by an
rapidly generalizing seizures that result in disabling drop attacks. The anterior unequivocal MRI
abnormality responsible for
two-thirds of the corpus callosum (partial callosotomy) are surgically divided; seizures, is associated with
however, sometimes a complete callosotomy is performed if seizures persist. In a better postoperative seizure
2019 systematic review of adults and children, approximately one-half of outcome than nonlesional
patients become free from debilitating drop attacks with either partial or epilepsy.
complete callosotomy.58 Hemispherectomy or functional hemispherotomy may ● The most common lesions
be used in select individual patients with catastrophic hemispheric epilepsy associated with seizures
syndromes, such as hemimegalencephaly, Sturge-Weber syndrome, large include malformations of
congenital hemiplegic strokes, and Rasmussen encephalitis. In a single-center cortical development, focal
cortical dysplasia,
retrospective review of patients undergoing hemispherectomy for epilepsy, 66%
cavernous and
(112 out of 170 patients) were reported to be seizure free at a median of 5.3 years.59 arteriovenous
malformations, and
NEUROMODULATION low-grade gliomas.
Three implantable neurostimulation therapies are now available for patients with
● Laser ablation and
drug-resistant epilepsy who undergo full surgical evaluation and are not stereotactic radiosurgery
candidates for resective surgery or prefer a less invasive approach as first-line are minimally invasive
surgical therapy. In most cases, these patients are not candidates for resective options available in some
surgery because of difficulty with localizing the seizure onset, multifocal seizure- centers for patients who are
candidates for resection but
onset zones, or an epileptogenic zone that overlaps with eloquent cortex. As a do not want a craniotomy.
class of therapy, neuromodulation demonstrates an initial seizure reduction that
improves over time. The following section explores the different ● Three implantable
neurostimulation options available for patients. neurostimulation therapies
are now available for
patients with drug-resistant
Responsive Neurostimulation epilepsy who undergo full
RNS is a closed-loop neurostimulation therapy that is triggered by early detection surgical evaluation and are
of epileptogenic activity. This is made possible by the stimulator’s ability to deemed poor candidates for
resective surgery.
continuously monitor intracranial EEG because of the implantation of two four-
contact depth or strip electrodes. EEG data can be downloaded and accessed by ● Responsive
the patient and physician to monitor therapy. The stimulator and battery are neurostimulation should be
placed under the patient’s scalp. RNS is a safe and effective treatment option, considered as a treatment
particularly for seizures that arise from eloquent regions of cortex and up to two option in those with seizures
that arise from eloquent
suspected epileptogenic foci. cortex and/or up to two
In the pivotal randomized controlled trial of RNS in adults with drug-resistant suspected seizure foci.
focal-onset seizures, a greater reduction in seizure frequency was seen in those
who received neurostimulation treatment (38%) than in the sham group (17%),
with no difference in adverse events.10 The 9-year prospective follow-up study of
this trial published in 2020 reported sustained and progressive improvement in
seizures over time, with greater than one-third of patients having a 90% or
greater reduction in seizure frequency.38 In a separate study of 126 patients with
focal neocortical epilepsy including seizures arising from eloquent cortex, a

median seizure reduction of 70% was seen in patients with frontal and parietal
seizure onsets, 58% in patients with temporal neocortical onset, and 51% in
patients with multilobar onsets.60 The successful use of RNS for epilepsy arising
from eloquent motor cortex is illustrated in CASE 11-2.
Significant improvement in overall quality of life and cognitive flexibility and
no deterioration in mood or neuropsychological function are reported with
RNS.61 Serious adverse events related to RNS include infection (4.1%) and
hemorrhage (2.7%) and are typically reported shortly after the surgical
procedure.38 The incidence of SUDEP has been reported as 2.8 per 1000 patient
stimulation years, which is lower than the published SUDEP rates in similar
epilepsy surgical candidates (9.3 per 1000 person-years).38
RNS demonstrates great flexibility in its use. Because of the ability to
continuously record intracranial EEG, carefully selected patients (eg, those with
mesial temporal lobe epilepsy) have been identified and achieved good outcomes
from a subsequent resection.62 Some centers will place RNS in addition to
performing a partial resection because the epileptogenic zone encompasses
eloquent cortex.63 A previous potential barrier, newer RNS models now allow for
the possibility of future 1.5T MRI if needed.
Deep Brain Stimulation

DBS is an open-loop deep brain stimulation that delivers continuous therapy to
the anterior nuclei of the thalamus. The DBS stimulator and battery are placed
under the skin in the upper chest. The mechanism by which DBS benefits
patients with epilepsy is still not well understood; however, animal models have
demonstrated that high-frequency stimulation of the anterior nucleus may raise
the cortical seizure threshold by causing inhibition of neuronal activity and/or
cortical desynchronization.64 Since resective surgery, laser ablation, and RNS
allow for targeted treatment of well-localized seizure-onset zones, DBS is
typically reserved as a treatment option for poorly localized epilepsy, patients
with multifocal or generalized epilepsy not amenable to the aforementioned
therapies, or those who are opposed to resective surgery.
In a pivotal study of drug-resistant focal epilepsy, bilateral stimulation of the
anterior nuclei of the thalamus was associated with a decrease in seizure
frequency of 29% during the study period and 56% at 2 years.11 The long-term
follow-up study showed sustained and improved efficacy, with 68% of patients
responding to DBS treatment at 5 years.39
Statistical improvements in quality-of-life measurements and low rates of
SUDEP (2.9 per 1000 patient stimulation years) are reported in long-term
follow-up studies.39 DBS is generally well tolerated, with low rates of adverse
events occurring around the time of device implantation limited to infection
(12.7%) and paresthesia (18.2%).11 Subjective worsening of memory and
depression was reported in the initial treatment group, but objective
neuropsychological testing showed no postoperative differences.11
Vagus Nerve Stimulation

VNS was initially developed as an open-loop stimulator; the device resembles
a cardiac pacemaker and delivers intermittent electrical impulses to the left
vagus nerve. The exact mechanisms of action on seizure reduction are
unknown. Hypotheses include changes in blood flow to different parts of the
brain, including the thalamus; desynchronization of hypersynchronized
554 APRIL 2022

cortical activity; or stimulating the release of neurotransmitters via afferent KEY POINTS
vagal projections to the brainstem and thalamus.65 Similar to DBS, VNS
● Deep brain stimulation
therapy is considered for those who are not candidates for or are opposed to and vagus nerve stimulation
resective surgery or have poorly localized multifocal epilepsy. Because of the are reserved as options for
limited surgical treatment options available for generalized epilepsy, VNS is poorly localized epilepsy or
also considered as a potential treatment option for drug-resistant multifocal epilepsy.
generalized epilepsy.37
● All three available
The initial multicenter randomized controlled trials showed mean seizure neurostimulation devices
reduction in the high-stimulation group of 25% compared to the 6% in the low-
are associated with seizure

stimulation (sham) group.66 Subsequent studies showed that response, as reduction, which improves
defined by greater than 50% reduction in seizure freedom, was seen in 23% to over time. Rates of adverse
events are low and typically
57% of patients.66,67 Similar to the above-mentioned neurostimulators, perioperative or related to
progressive increases in seizure control are seen with increasing duration stimulation, which can be
of implant.68 modified.
Additional quality-of-life measures independent of seizure outcomes have
been reported to improve over time in children and adults, although the exact
mechanism of this finding is unclear.69 Similar to other neurostimulation
therapies, the risk of SUDEP in VNS is lower (1.68 per 1000 patient stimulation
years) than published SUDEP rates in similar surgical candidates (3.7 per
1000 person-years). However, VNS has the lowest reported seizure-freedom
rates at last follow-up (<10%) of the three neurostimulation therapies. VNS
implantation is a relatively safe procedure, with the most common complications
being postoperative hematoma (1.9%), infection (2.6%), and vocal cord
paralysis (1.4%).70
Modern VNS systems are now customizable, with programming options that
include manual stimulation with a magnet swipe by a patient or caregiver at the
onset of a seizure or additional automatic stimulation delivery upon detection of
a predetermined tachycardia threshold (closed-loop stimulation). The latter
therapy is especially useful if patients experience an increase in heart rate with
their seizures.
CONCLUSION
Despite many new antiseizure medications with differing mechanisms of action
becoming available over the past several decades, rates of drug-resistant epilepsy
have not improved and remain up to 40% in patients with epilepsy. The
probability of achieving seizure freedom declines rapidly after two adequate
doses of antiseizure medication, and early referral for surgical therapy should
be considered.
Resective surgery has the highest rates of seizure freedom in temporal lobe
epilepsy, especially when localized to the mesial structures or when seizures arise
from a focal structural lesion. The use of minimally invasive options, such as laser
ablation and stereotactic radiosurgery, is an alternative to resective surgery in
well-selected patients.
As a class, neurostimulation has demonstrated sustained and progressive
improvements in efficacy over time. RNS is favored in patients with a high
preoperative risk of memory decline and an epileptogenic zone overlapping with
eloquent cortex. DBS and VNS are also good options for multifocal, generalized,
and poorly localized epilepsies. RNS, DBS, and VNS are also options for those
who are opposed to resective surgery.

Drug-resistant epilepsy causes irreversible psychological and social problems,

a lifetime of disability, and increased risk of death. Surgical therapy improves
seizure outcomes and quality of life in addition to decreasing morbidity and
mortality in patients with drug-resistant epilepsy.
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EPILEPSY SURGERY CANDIDATES

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glioma, cavernous malformation), or nonlesional focal epilepsy. In patients with

preexisting hemiparesis. Surgical options are limited for generalized epilepsies;

rapidly generalizing seizures. Neuromodulation (eg, DBS, VNS) may also be

TABLE 11-1 Common Misconceptions About Epilepsy Surgerya

EEG = electroencephalography; IQ = intelligence quotient; MRI = magnetic resonance imaging.

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Presurgical Investigative Tools and Their Significance TABLE 11-2

Presurgical investigations Significance

MRI Identifies structural abnormalities associated with seizures (eg,

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10-10 distanced scalp electrodes, sphenoidal electrodes, or subtemporal

Higher-resolution 3-Tesla (3T) or 7T MRI scanners improve the identification

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seizure freedom; this is

INTRACRANIAL VIDEO-EEG MONITORING ● Resective surgery may be

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CASE 11-1 A 39-year-old right-handed man with a history of drug-resistant epilepsy

medications, he still had one focal impaired awareness seizure per

A video-EEG showed right temporal sharp waves, and several of his

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COMMENT This case exemplifies the utility of stereo-EEG in clarifying the

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subdural grid electrodes, or

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CASE 11-2 A 50-year-old right-handed woman with a history of drug-resistant

antiseizure medications, and she subsequently went into status

attacks without loss of consciousness. Her seizures began with a right-

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COMMENT This patient’s seizure symptomatology, EEG findings, and

EXTRATEMPORAL LOBE EPILEPSY. Surgical resection of neocortical and

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primary sensorimotor cortex, or the visual cortex cannot be safely resected

LESIONAL EPILEPSY. Lesional epilepsy, which is defined as having an unequivocal

Advantages and Disadvantages of Stereoelectroencephalography and Subdural TABLE 11-3

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surgery consists of lesionectomy plus resection of surrounding epileptogenic

Laser Interstitial Thermal Therapy

TABLE 11-4 Engel and International League Against Epilepsy Classifications of

Engel Epilepsy Surgery Outcome Scale33

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hamartomas, and focal cortical dysplasia.52,53

neuropsychological decline specific to object naming and face recognition.54

Surgical treatment in drug-resistant Seizure

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Randomized controlled trials comparing laser ablation to alternative therapies