Surgical Treatment of Epilepsy in Adults

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Surgical treatment of epilepsy in adults

Author: Gregory D Cascino, MD
Section Editor: Paul Garcia, MD
Deputy Editor: John F Dashe, MD, PhD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2020. | This topic last updated: Sep 27, 2019.
INTRODUCTION
Epilepsy is one of the most common chronic neurologic disorders, and approximately 20 to 30 percent of
patients with epilepsy will have medically and socially disabling seizure disorders. Such patients are at
increased risk for serious morbidity and mortality, including cognitive disorders, depression, physical trauma,
and sudden death in epilepsy. The goals of treatment for individuals with drug-resistant epilepsy are to render
the patient seizure free, avoid treatment-related adverse effects, and allow the individual to become a
participating and productive member of society.
Most individuals who will respond favorably to antiseizure drugs are successfully managed within the first two
years of treatment. Patients who do not respond favorably to two antiseizure drugs used appropriately are
likely to have drug-resistant epilepsy and should be investigated for surgery and other alternative forms of
treatment.
Surgical therapy is an important and underutilized treatment in patients with drug-resistant focal epilepsy.
Surgical procedures for epilepsy range from focal resection of the epileptogenic cortex (antero-mesial temporal
lobe and other focal cortical resections) to interventions that remove or isolate the cortex of a grossly diseased
hemisphere (functional hemispherectomy, anterior corpus callosotomy, multiple subpial transections). The
latter procedures are most often performed in children and are not discussed further here. In general, only
complete resection of the epileptogenic brain region offers the chance of long-term seizure freedom.
This topic will discuss the surgical treatment of drug-resistant focal epilepsy in adults utilizing focal cortical
resection. Epilepsy surgery in children and other aspects of epilepsy management and treatment in adults are
discussed separately. (See "Overview of the management of epilepsy in adults" and "Evaluation and
management of drug-resistant epilepsy" and "Seizures and epilepsy in children: Refractory seizures and
prognosis", section on 'Epilepsy surgery'.)
SURGICAL CANDIDATES
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Focal cortical resection is a consideration in patients with drug-resistant focal epilepsy if the seizures emanate
from a region that can be removed with minimal risk of disabling neurologic or cognitive dysfunction.
The localization of seizure onset, underlying surgical pathology, and seizure type(s) are important
determinants of surgical candidacy and outcomes. The most favorable candidates are those with magnetic
resonance imaging (MRI)-identified lesions that represent both the pathologic process underlying the
epileptogenic brain tissue and the location of seizure onset. Such MRI findings, together with concordant
electroencephalography (EEG) data, are pivotal in selecting operative candidates and determining the strategy
for the surgical procedure. (See 'Surgical evaluation' below.)
In adults, there are three major types of seizure disorders that may be remedied with focal cortical resective
surgery:
Patients with mesial temporal lobe epilepsy with localization of the epileptogenic zone in the amygdala
and hippocampus are the most common candidates for effective surgical therapy. As discussed below,
substantial observational data and a single completed randomized trial support the superiority of surgical
therapy compared with continued antiseizure medication for patients with drug-resistant temporal lobe
epilepsy. (See 'Mesial temporal lobe epilepsy' below.)
Patients with lesional epilepsy due to focal structural pathology, such as a low-grade glial tumor,
cavernous malformation, or malformation of cortical development (MCD) with medically refractory
seizures, may also be good surgical candidates. There are important differences in the likelihood of
surgical success depending on the specific pathologic finding, however. For example, operative outcomes
are distinctly less favorable in individuals with focal cortical dysplasia and other MCDs. (See 'Lesional
epilepsy' below.)
Patients with drug-resistant focal epilepsy and a normal brain MRI are more challenging, but some of
these patients are nonetheless good surgical candidates. Localization of the epileptic brain tissue in these
patients often requires long-term intracranial EEG monitoring in addition to functional and metabolic brain
imaging. (See 'Neocortical epilepsy with normal brain MRI' below.)
Patients who are usually not surgical candidates for focal cortical resection include individuals with bilateral or
multifocal seizure onset, those with significant medical comorbidities that preclude the surgery, and patients
with generalized-onset epilepsy. Patients in whom the site of seizure onset and initial seizure propagation is
intimately associated with functional cortex may also not be appropriate candidates for resective surgery.
SURGICAL EVALUATION
The goals of the surgical evaluation are to identify the epileptogenic zone, determine the extent to which it can
be resected, and avoid operative morbidity, especially injury to eloquent cortex. Standard components of the
surgical evaluation are discussed below.

In general, decisions about the potential effectiveness of focal cortical resection rely most heavily on the
concordance of clinical seizure semiology, ictal and interictal scalp electroencephalography (EEG) findings,
and structural magnetic resonance imaging (MRI). Positron emission tomography (PET), single-photon
emission computed tomography (SPECT), and magnetoencephalography (MEG) typically play a confirmative
role in cases of questionable structural lesions or in patients with multiple lesions or a normal MRI.
Neuropsychologic testing and functional localization techniques are used to help localize the epileptogenic
zone and determine the safety of the proposed procedure, for example by estimating cognitive reserve in the
contralateral hemisphere.
Clinical evaluation — A comprehensive evaluation is essential in patients with drug-resistant epilepsy.

Patients should be referred to neurologists who have subspecialty expertise in epilepsy and are based at a
comprehensive epilepsy center that has the necessary multidisciplinary resources and personnel. (See
"Evaluation and management of drug-resistant epilepsy".)
The history and neurologic examination are critical to confirm the diagnosis and characterize seizure
semiology and clinical localization. Particular emphasis should be placed on the presence of multiple or
differing seizure semiologies, which may raise concern for multiple epileptogenic zones.
Comorbid psychiatric disease (eg, anxiety or depression) is common in patients with drug-resistant epilepsy
and has been associated with worse postsurgical seizure outcomes. While the presence of a psychiatric
disorder does not preclude surgery, presurgical psychiatric evaluation and psychosocial assessment are
advised in order to mitigate potential complications postoperatively [1]. (See 'Psychologic sequelae' below.)
At most epilepsy centers, each patient's diagnostic evaluation is discussed at a surgical epilepsy consensus
conference prior to epilepsy surgery in order to discuss the surgical treatment plan, as well as to review
potential alternative treatment options.
Neuropsychologic testing — Neuropsychologic studies are performed to evaluate the presence of verbal or
nonverbal learning and memory deficits. The rationale for these studies as part of a presurgical epilepsy
evaluation is fourfold [2]:
To determine preoperative cognitive performance as a baseline that can be compared with a

postoperative examination
To identify and quantify ictal and postictal deficits as an aid to seizure characterization, lateralization, and
localization
To provide evidence-based predictions of cognitive risk associated with the proposed surgery
To provide comprehensive preoperative counseling, including neuropsychologic education of the patient

and family
Neuropsychologic studies may be of highest diagnostic yield in individuals with temporal lobe epilepsy.

Intellectual disability has traditionally been a relative contraindication to temporal lobectomy because it implies
bilateral and potentially diffuse rather than focal brain pathology. In some studies, low intelligence quotient (IQ)
has been associated with lower postoperative seizure remission rates and increased risk of postoperative
cognitive sequelae. However, intellectual disability may not be an independent predictor of surgical outcome,
and some patients may still benefit from epilepsy surgery.
Routine and video-EEG — Routine EEG recording with standard activating procedure and long-term scalp-
recorded video-EEG monitoring are essential to confirm and localize the site of seizure onset in individuals
with focal epilepsy. Additional scalp-recorded EEG electrodes, including anterior or inferior temporal
electrodes, are often placed to increase the diagnostic yield of the neurophysiologic studies. (See
"Electroencephalography (EEG) in the diagnosis of seizures and epilepsy", section on 'Special electrode
placement'.)
Interictal and ictal EEG patterns are utilized for surgical localization. Using computer-assisted video-EEG in an
inpatient epilepsy monitoring unit, habitual seizures are recorded to determine the correlation between ictal
semiology and EEG findings. The peri-ictal neurologic examination provides an additional functional
assessment that can assist in lateralizing and localizing the epileptogenic zone.
High-resolution brain MRI — All patients undergoing surgical evaluation should have a high-resolution brain
MRI with sequences optimized for visualization of the hippocampus and gray-white matter junction. The MRI
should include coronal or oblique-coronal T1- and T2-weighted and fluid-attenuated inversion recovery
(FLAIR) sequences. Postcontrast T1-weighted images are not useful in patients with mesial temporal sclerosis
but should be included in the evaluation of suspected tumors or vascular anomalies. High field strength (3-
Tesla) MRI is preferred for maximal sensitivity. (See "Neuroimaging in the evaluation of seizures and epilepsy",
section on 'Epilepsy protocol for MRI'.)
In patients with temporal lobe epilepsy associated with hippocampal sclerosis (also called mesial temporal
sclerosis), the most common imaging alteration is hippocampal atrophy with a signal intensity change that
reflects gliosis (image 1 and image 2) [3]. FLAIR sequences increase the sensitivity of MRI to indicate a signal
change [4]. Loss of internal structure of the hippocampus may also be seen. An MRI finding of mesial temporal
lobe sclerosis is predictive of better seizure and neurocognitive outcomes following surgery [5,6].
High-resolution structural MRI also has a high diagnostic yield in patients with tumors or vascular
malformations. The latter are often best visualized on gradient-echo sequences, which are sensitive for blood
products. Typical imaging features of tumors and vascular malformations are discussed elsewhere. (See
"Overview of the clinical features and diagnosis of brain tumors in adults", section on 'Neuroimaging features'
and "Brain arteriovenous malformations", section on 'Diagnosis' and "Vascular malformations of the central
nervous system", section on 'Neuroimaging'.)
In patients with focal cortical dysplasia, MRI findings may be subtle and include mild cortical thickening, a
prominent deep sulcus, a cortical signal intensity change, blurring of the gray-white junction, or aberrant
cortical architecture (image 3). Thin-section 3D volumetric MRI and reformatted 1.5 mm 3D spoiled gradient
echo (SPGR) sequences are particularly useful, since it is difficult to resolve volume-averaged normal cortical

infolding from true abnormalities if the spatial resolution of the images is coarser than 1.5 mm. Higher field
strength (eg, 3-Tesla) also aids in detecting cortical dysplasia.
Advanced MRI techniques — Quantitative MRI techniques have limited diagnostic value over and above
visual inspection but may provide useful prognostic information. MRI-based volumetric studies of the
hippocampal formation can objectively determine the degree of hippocampal volume loss in patients with
mesial temporal sclerosis using a standardized protocol; results are compared with age-matched normal
controls to assign abnormal values. A unilateral reduction in hippocampal volume is a reliable indicator of the
epileptogenic temporal lobe in patients with medically refractory focal epilepsy [7]. Patients with bilateral
hippocampal atrophy or hippocampal atrophy contralateral to the site of seizure onset are more likely to
experience adverse cognitive outcomes following temporal lobe surgery [5].
FDG-PET — Measurement of interictal cerebral glucose metabolism using [18F]-2-deoxyglucose PET (FDG-
PET) is a sensitive functional neuroimaging technique in patients with temporal lobe epilepsy. Unilateral
temporal lobe hypometabolism on FDG-PET (image 4) correlates strongly with the temporal lobe of seizure
origin and is predictive of seizure freedom following epilepsy surgery, independent of structural MRI findings
[6,8]. FDG-PET can also be clinically useful in patients with extratemporal regions of seizure onset. This
includes individuals with focal cortical dysplasia who may have an unremarkable MRI study. (See
"Neuroimaging in the evaluation of seizures and epilepsy", section on 'Positron emission tomography'.)
FDG-PET and MRI coregistration increases the diagnostic yield of preoperative imaging and may improve
surgical outcome in patients with negative MRI studies and focal cortical dysplasia. In such patients, FDG-
PET/MRI demonstrates a hypometabolic zone indicative of the site of focal cortical dysplasia and the region of
seizure onset. This modality is highly sensitive in detecting focal cortical dysplasia type II (Taylor-type) in
patients with a normal brain MRI, and it may improve outcomes. (See 'Efficacy' below.)
Ictal SPECT — Ictal SPECT studies are used to map increased cerebral blood flow during seizures to assist in
localizing the epileptogenic zone (image 5). While not technically feasible at all institutions due to logistic
constraints of ictal tracer injection, SPECT is particularly useful in patients with a conflicting noninvasive
epilepsy evaluation with regard to localization of the epileptic brain tissue. SPECT findings can also influence
the diagnostic strategy for placement of intracranial EEG electrodes. (See 'Seizure localization' below.)
SPECT studies involve cerebral blood flow imaging using radiopharmaceuticals, most often either technetium-
99m-hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-bicisate, that have a rapid first-pass brain
extraction with maximum uptake being achieved within 30 to 60 seconds of an intravenous injection. (See
"Neuroimaging in the evaluation of seizures and epilepsy", section on 'Single-photon emission computed
tomography'.)
Subtraction ictal SPECT coregistered to MRI (SISCOM) is a modification of the ictal SPECT technique that
superimposes ictal and interictal SPECT images and brain MRI (image 5). SISCOM has been used in patients
with normal MRI studies, those with multifocal EEG or MRI abnormalities, and individuals with intractable
epilepsy who are being considered for reoperation. In a series of 51 patients undergoing surgical evaluation,
SISCOM had a significantly higher rate of localization (88 versus 39 percent), better interobserver agreement,

and better predictive value for surgical outcome compared with visual inspection of interictal and ictal images
[9].
Some of the limitations of visual inspection may be overcome by statistic parametric mapping methods, which
permit better localization of the focal hyperperfusion abnormality concordant with the epileptogenic zone in
patients with both temporal lobe and extratemporal epilepsy [10].
Speech and language localization — In selected patients, eloquent cortex involved with speech and
language function must be well defined before temporal lobe and frontal lobe resections in order to minimize
operative morbidity. The standard method for determining critical areas of functional cortex is intraoperative
electrical cortical stimulation. If necessary, this can be carried out intraoperatively in awake patients, or
extraoperatively using implanted subdural electrodes for long-term intracranial EEG monitoring.
Preoperatively, functional MRI and the intracarotid amobarbital procedure (also called the Wada test) are two
methods used to assess language localization and predict postoperative language and memory outcomes.
Functional MRI is generally preferred over intracarotid amobarbital given its superior safety profile [11].
Functional MRI is a noninvasive neuroimaging technique that is capable of language localization as well
as lateralization of language processes. In many epilepsy centers, this has largely replaced intracarotid
amobarbital procedures. Functional MRI can also be used to assess sensory and motor eloquent cortices
and as an alternative or adjunct to the Wada test in predicting neurocognitive sequelae after surgery [12-
20]. (See "Neuroimaging in the evaluation of seizures and epilepsy", section on 'Functional magnetic
resonance imaging'.)
Numerous studies have estimated the validity of functional MRI as an alternative to the Wada test and
have found an overall discordance rate of approximately 15 percent [11,21,22]. Discordance rates may be
slightly higher in patients with extratemporal foci and larger lesions. In one study that measured language
outcomes after anterior temporal lobectomy in patients with discordant functional MRI and Wada testing
preoperatively, functional MRI provided a more accurate prediction of language outcome in 7 of 10 cases
[23].
However, some patients cannot complete functional MRI, or have inconclusive results, and still require
preoperative Wada testing [20]. Most centers use Wada tests only for patients with temporal lobe epilepsy
at significant risk for cognitive decline (eg, left temporal lobe epilepsy with normal MRI, bilateral
hippocampal atrophy, or bitemporal seizures).
Intracarotid amobarbital administration is an invasive procedure that has been used for many years in
surgical candidates to determine the language-dominant hemisphere as well as assess the risk of
postoperative memory decline after temporal lobectomy [24-26]. Amobarbital or another anesthetic is
injected into the internal carotid artery, temporarily suppressing function on that side while language and
memory tests are performed. Neuropsychologic testing after intracarotid injection of amobarbital allows for
assessment of language and memory function in each hemisphere independently. While complications
are reported in up to 11 percent of patients, serious adverse events (stroke, carotid dissection, localized
bleeding, and infection) occur in less than 1 percent [27,28].
Other anesthetic agents such as pentobarbital, etomidate, methohexital, and propofol have been
investigated as alternatives to amobarbital, which has not been consistently available. In general, these
agents appear to be well tolerated and produce results similar to amobarbital for presurgical testing [29-
32]. Etomidate has been associated with adrenal insufficiency when used in critically ill patients [33]. In
one study, propofol was associated with a higher risk of significant side effects, especially in older patients
[34].
Lack of test standardization and selection bias limit our understanding of the reliability of the Wada test as
a predictive tool.
Invasive EEG monitoring — In selected cases, invasive intracranial EEG monitoring is required for
localization of the epileptogenic zone before a resection can be performed. Invasive monitoring is primarily
used when noninvasive techniques fail to localize the area of seizure onset or if other tests have discordant
results. Although use of intracranial electrodes in mesial temporal lobe epilepsy has diminished over time,
invasive monitoring continues to be used commonly in patients with neocortical focal epilepsy, particularly
those with a normal MRI or bilateral seizure foci. (See 'Seizure localization' below.)
SURGICALLY REMEDIABLE EPILEPTIC SYNDROMES
Mesial temporal lobe epilepsy — Mesial temporal lobe epilepsy is the most frequently encountered surgically
remediable epileptic syndrome in adults. Patients typically experience focal dyscognitive seizures, also known
as complex partial seizures, with or without aura or tonic-clonic seizures. The most common pathologic
substrate associated with temporal lobe epilepsy is hippocampal sclerosis (mesial temporal sclerosis), which is
characterized by selected focal neuronal loss and gliosis in the hippocampus, predominantly affecting CA1,
CA3, and the dentate granule cell layer. Hippocampal sclerosis is the most commonly encountered
histopathologic diagnosis at the time of epilepsy surgery in adults and accounts for approximately 45 percent
of all resections [35]. (See "Localization-related (focal) epilepsy: Causes and clinical features", section on
'Seizure semiology'.)
Patients with mesial temporal lobe epilepsy due to tumors or other structural lesions in the temporal lobe are
discussed below in the context of lesional epilepsy surgery (see 'Lesional epilepsy' below), and those with
extrahippocampal temporal lobe epilepsy and a normal brain magnetic resonance imaging (MRI) are
discussed in the context of neocortical epilepsy with normal brain MRI. (See 'Neocortical epilepsy with normal
brain MRI' below.)
Surgical techniques — The most common surgical procedure for mesial temporal epilepsy is resection of
the anterior temporal pole, hippocampus, and part of the amygdala. The posterior extent of the anterior
temporal resection is measured to minimize risk to the visual radiations and language cortex (4.0 to 4.5 cm
back from the temporal pole on the dominant side, and 5.0 to 5.5 cm on the nondominant side). Cortical
resection may also be tailored based on language mapping and intraoperative electrocorticography, as
language areas in the temporal cortex are variable.

Selective amygdalohippocampectomy has been explored as an alternative to anterior temporal lobectomy that
spares the temporal lobe neocortex. Seizure control rates might be similar with a selective approach, but
potential differences in neurocognitive outcomes have not been well studied [36]. There are conflicting results
regarding the effectiveness of the specific operative strategies to achieve seizure freedom in individuals with
mesial temporal lobe epilepsy. A 2018 meta-analysis noted that the only direct evidence comparing surgical
efficacy of selective amygdalohippocampectomy with anterior temporal lobectomy comes from observational
studies and is therefore is of low quality [36]. Importantly, most individuals experience a significant reduction in
seizure frequency with either operative approach.
Other minimally invasive or noninvasive approaches are under investigation [37-40]. The role of radiosurgery
and laser thermal ablation in mesial temporal lobe epilepsy related to mesial temporal sclerosis is not yet clear.
Efficacy — Patients with temporal lobe epilepsy and localization of the epileptogenic zone to the amygdala
and hippocampus are extremely good candidates for resective surgery, which is associated with superior
outcomes compared with continued medical management.
This was demonstrated by a randomized, controlled trial involving 80 patients with temporal lobe epilepsy
whose seizures were poorly controlled with medical therapy [41]. Approximately three-quarters of the patients
had magnetic resonance imaging (MRI) findings consistent with hippocampal sclerosis, 10 to 15 percent had
structural lesions such as tumors or vascular malformations, and approximately 15 percent had normal MRI
scans. Patients were randomly assigned to surgery or continued antiseizure drug treatment. At one year, the
cumulative proportion of patients who were free of seizures that impaired awareness was significantly greater
in the surgery group than the medical group (58 versus 8 percent). Quality-of-life ratings were also higher in
the postsurgical group.
A second randomized, controlled study was initiated to evaluate the efficacy of early surgery versus continued
medical management in patients who had failed two antiseizure drug trials, but the trial was stopped early
because of slow enrollment [42,43]. After two years of follow-up, seizure remission occurred in 11 of 15
patients assigned to surgical treatment and none of 23 patients assigned to medical management. Quality-of-
life measures were not different between the assigned treatment groups. However, an on-treatment analysis
that included seven patients in the medical group who underwent surgery during follow-up found a significant
benefit for surgery on quality of life.
Based on these and other observational studies, the most important preoperative predictors of seizure
freedom after anterior temporal lobe resection for mesial temporal lobe epilepsy include [6,44-52]:
Presence of a focal brain lesion on MRI
Presence of unilateral mesial temporal sclerosis in the temporal lobe of seizure origin
Presence of a localized temporal lobe positron emission tomography (PET) abnormality, even if brain MRI
is normal

Electroencephalography (EEG) data showing concordant location of ictal onset and interictal epileptiform
discharges
Shorter preoperative seizure duration
Postoperatively, the strongest predictor of long-term seizure control is freedom from seizures in the first year
after surgery, particularly generalized seizures or focal seizures with altered or impaired awareness [44,45,53-
56]. The presence of interictal epileptiform discharges on an EEG performed within the first few years after
surgery has been associated with an approximately threefold higher risk of recurrent seizures [57,58].
Taken together, patients with MRI scans showing hippocampal sclerosis who undergo anterior temporal
lobectomy for intractable epilepsy have the most favorable seizure outcomes, with approximately 65 to 75
percent of patients remaining continuously seizure free or having only auras up to 10 years after surgery [59-
61]. An additional 10 to 15 percent of patients will have seizures postoperatively but eventually achieve
terminal remission. In highly selected series limited to patients most likely to do well with surgery (ie, positive
MRI findings, pathologically proven hippocampal sclerosis, concordant EEG findings, no dual pathology or
discordant preoperative data), long-term rates of seizure freedom as high as 90 percent have been reported
[62].
The surgical outcome of patients with a localized temporal lobe PET abnormality and a normal MRI may be
equivalent to individuals with MRI-identified unilateral hippocampal sclerosis. Seventy-six percent of patients in
one series with temporal lobe PET hypometabolism and a normal MRI were seizure free following surgery [8].
For patients with mesial temporal lobe epilepsy and a normal brain MRI, rates of seizure freedom after anterior
temporal lobectomy range from 50 to 60 percent. Most (70 to 87 percent) achieve at least a 75 percent
reduction in seizure frequency [63-68]. In a series of 87 patients with a normal MRI undergoing anterior
temporal lobectomy, 55 percent had an excellent operative outcome, defined as seizure free or auras only [69].
Neocortical epilepsy with normal brain MRI — The surgical management of focal seizures of neocortical
origin (ie, extrahippocampal) can be challenging because of difficulty defining the boundaries of the
epileptogenic zone that must be resected for seizure freedom. There are also increased concerns regarding
clinically functional cortex.
The clinical manifestations of neocortical epilepsy depend on the area of cortex involved. Seizures arising from
functional cortex can be localized based on neurologic symptoms that occur at seizure onset or during the
postictal state. Compared with mesial temporal lobe seizures, lateral temporal neocortical seizures are more
likely to manifest as experiential auras and less likely to manifest as epigastric auras and contralateral
dystonia. Frontal lobe seizures tend to be shorter and more frequent than temporal lobe seizures, with
manifestations varying from motionless staring to violent automatisms. Frontal lobe seizures are often confined
to sleep. Parietal and occipital seizures typically have complex sensory symptoms such as visual
hallucinations of objects or scenes. (See "Localization-related (focal) epilepsy: Causes and clinical features",
section on 'Neocortical epilepsy'.)

Despite these general principles, extrahippocampal focal seizures often have varied clinical semiology and can
be difficult to localize with scalp-recorded ictal EEG studies. In addition, ictal behaviors may relate to seizure
propagation and provide few clues regarding the site of actual seizure onset. Another challenge to clinical
localization in neocortical epilepsy is that seizures may be tonic-clonic without a clinically recognized focal
seizure, or the focal seizure may be very brief or subtle, such as a brief stare with arrest of activity or
hypermotor activity.
Seizure localization — In order to adequately localize seizures and tailor resections to spare eloquent
cortex, the surgical evaluation in patients with neocortical epilepsy often includes functional or metabolic
imaging and long-term intracranial EEG monitoring.
Before invasive EEG recordings, patients usually undergo functional neuroimaging to include PET and/or ictal
single-photon emission computed tomography (SPECT) in an attempt to better localize the epileptogenic zone
and direct intracranial electrode placement. The diagnostic yield of PET and SPECT in patients with
neocortical epilepsy depends on multiple factors, including the underlying pathology, localization of the
epileptogenic zone, and the specific neuroimaging technique. PET or SPECT studies may permit an anterior
temporal lobe resection in patients with unilateral temporal lobe scalp-recorded seizures and negative brain
MRI scans. Individuals with extratemporal seizures and normal brain MRIs almost invariably require
intracranial EEG recordings or functional mapping for surgical localization, or both.
The strategy for intracranial EEG recordings often includes a combination of subdural strips or grids of
electrodes and depth electrodes. Depth electrodes are implanted stereotactically by a neurosurgical team
using brain imaging for localization. In two retrospective series of more than 400 patients, the major
complication rate of invasive monitoring was 7 to 9 percent; the majority of these complications were either
intracranial hemorrhage or infection [70,71]. Use of subdural electrodes may pose higher risk than use of
depth electrodes [71-73].
Stereoelectroencephalography (SEEG) is another invasive technique that is being increasingly used to

evaluate patients with nonlesional drug-resistant focal epilepsy being considered for surgical treatment [74-77].
SEEG may be preferred in individuals with epileptogenic zones that are difficult to evaluate with subdural grid
recordings, such as the insula, the depth of sulci, and mesial regions of cerebral cortex. In selected patients
being considered for focal cortical resection, the effectiveness and safety of SEEG compares favorably with
other methodologies for intracranial EEG recording [74,75,78], with a pooled complication rate of 1.3 percent
across multiple studies [79].
In some cases, patients who undergo a full surgical evaluation for nonlesional epilepsy, including intracranial
EEG monitoring, are deemed poor candidates for surgery [80]. Common reasons include difficulty localizing
seizure onset, multifocal seizures, overlap with functional cerebral cortex, or morbidity associated with chronic
intracranial EEG recordings.
Efficacy — Even with an appropriate comprehensive presurgical evaluation, seizure outcomes tend to be
less favorable in patients with neocortical epilepsy and normal MRI scans compared with those with mesial

temporal lobe epilepsy due to hippocampal sclerosis or a structural lesion. Patients with extratemporal
seizures do even less well.
Surgical procedures used for patients with neocortical nonlesional epilepsy include topectomy (ie, removal of
cortex while sparing underlying white matter) and lobar and multilobar cortical resections. Rates of seizure
freedom after such procedures range from 30 to 55 percent based on small, mostly single-center observational
studies [80-84]. Predictors of better outcome include the presence of a localizing PET or SPECT study, high
concordance of the noninvasive presurgical evaluation, the presence of an aura, and complete resection of
areas of ictal onset [84].
Lesional epilepsy — Patients with intractable focal epilepsy due to focal brain lesions require a
comprehensive epilepsy evaluation to establish the relationship between the pathologic findings and the
epileptogenic zone. Common pathologic entities responsible for medically refractory lesional epilepsy include
low-grade tumors, cavernous hemangiomas, and focal cortical dysplasia.
Primary brain tumors — The incidence of seizures among patients with primary brain tumors is related to
tumor type and grade and cortical localization. Low-grade, slowly growing tumors are most commonly
associated with a chronic seizure disorder. Gangliogliomas and dysembryoplastic neuroepithelial tumors
(DNET) together account for approximately three-quarters of all tumors found in adults undergoing epilepsy
surgery [35]. Other examples include pilocytic astrocytoma, gangliocytoma, pleomorphic xanthoastrocytoma,
and oligodendroglioma.
Imaging features common to all these tumors include typically small size, location at or near a cortical surface,
sharply defined borders, little or no surrounding edema, and, with the exception of pilocytic astrocytoma, little
or no contrast enhancement. In a series of 133 patients from one institution who underwent operations for
extratemporal epilepsy, tumors were identified in 28 percent of cases. These included, in order of decreasing
frequency, astrocytoma, ganglioglioma, DNET, glioneuronal hamartoma, oligodendroglioma, and
oligoastrocytoma [85]. Roughly the same proportion of patients have tumors in series of patients undergoing
surgery for temporal lobe epilepsy [41,86,87].
Seizure outcome in patients undergoing surgical treatment for intractable focal epilepsy due to a primary brain
neoplasm is typically very good. Most individuals become seizure free or nearly seizure free [88,89]. Although
complete tumor resection is the goal, tumors associated with functional cortex (eg, perirolandic lesions) may
require a subtotal excision to avoid a postoperative neurologic deficit.
Some studies have suggested that DNETs are associated with higher seizure relapse rates compared with
other epileptogenic tumors [59,90]. A review of 29 relevant studies found seizure-freedom rates ranging from
58 to 100 percent (median 86 percent) with a median follow-up of four years [91]. The median age at the time
of surgery was 18 years. Among 12 studies that reported rates of antiseizure drug discontinuation,
approximately half of seizure-free patients were off all antiseizure drugs. The most commonly identified
predictors of seizure freedom were younger age at the time of surgery, shorter duration of epilepsy, and
complete resection. In a separate study that included 79 patients with DNET with long-term follow-up, the rate
of long-term seizure freedom was 42 percent at 10 years after surgery [59].

Vascular malformations — Cavernous malformations and arteriovenous malformations are the most
common vascular lesions found in patients with focal epilepsy. Venous angiomas and telangiectasias are often
incidental findings in patients with seizure disorders and are not typically causative lesions. Seizures are a
common presenting feature of cavernous malformation.
Resection typically leads to complete seizure control or significant improvement. In a case series of 168
patients with symptomatic epilepsy attributed to cavernous malformations, more than two-thirds of patients
were seizure free at three years after surgery [92]. Predictors for good outcome included mesiotemporal
location, size <1.5 cm, and the absence of secondarily generalized seizures. In another study, 87 percent of 56
patients undergoing resection of a supratentorial cavernous malformation were seizure free following surgical
treatment [93].
Malformations of cortical development — Malformations of cortical development (MCDs) are an

important etiology for drug-resistant focal epilepsy. Among various diffuse and focal MCDs, focal cortical
dysplasias are the most common surgically remediable lesions in adults. Before widespread availability of MRI,
many culprit lesions were only diagnosed at the time of postmortem examination. Even with high-resolution
structural MRI, some patients with so-called MRI-negative focal epilepsy have evidence of focal cortical
dysplasia at the time of surgery.
Not uncommonly, focal cortical dysplasias have extratemporal locations and are associated with focal seizures
that are difficult to localize with scalp-recorded EEG. [18F]-2-deoxyglucose PET (FDG-PET)/MRI may be very
useful in the surgical evaluation of such patients. (See 'FDG-PET' above.)
The International League Against Epilepsy has developed a three-tier classification of focal cortical dysplasias
[94].
Focal cortical dysplasia type I involves radial or tangential dyslamination of the neocortex. MRI studies in
these patients may be normal or show very subtle blurring of the grey-white matter junction or thinning of
the cerebral cortex.
Focal cortical dysplasia type II exhibits dysmorphic neurons with or without balloon cells. MRI studies may
be normal or show blurring of the grey-white matter junction, a fluid-attenuated inversion recovery (FLAIR)
signal intensity alteration, a transmantle sign, or increased cortical thickness. Abnormal cortical gyration or
sulcation pattern may also be evident.
Focal cortical dysplasia type III is associated with dual pathology that may include hippocampal sclerosis,
tumor, or vascular lesions.
Importantly, the diagnostic yield of MRI is dependent on the specific pathologic alterations [94]. A normal MRI
study in a patient with a drug-resistant focal epilepsy does not exclude the diagnosis of focal cortical dysplasia.
Not uncommonly, MCDs associated with intractable epilepsy are extratemporal and multilobar lesions.
Efficacy — Epilepsy surgery is less effective in patients with focal cortical dysplasia than in patients with
other lesional pathology (eg, tumors or cavernous malformations). Challenging issues in these patients include

the difficulty identifying areas of focal cortical dysplasia using MRI, the presence of extratemporal neocortical
lesions, and multilobar pathology.
One center reported that 57 percent of 166 patients with focal cortical dysplasia followed for two years or
longer after surgery were seizure free [95]. Success rates may be higher in patients with a specific form of
focal cortical dysplasia type II in which dysplastic features are maximal at the bottom of the sulcus (referred to
as a transmantle sign on MRI) [96,97].
FDG-PET/MRI may improve the surgical outcome in patients with focal cortical dysplasia type II associated
with balloon cells (Taylor-type focal cortical dysplasia) [98]. In a study that included 23 patients who underwent
SEEG and epilepsy surgery, and who had pathologically verified focal cortical dysplasia type II, MRI was
negative in 13 patients and showed subtle alterations in 10 patients. FDG-PET/MRI revealed a hypometabolic
zone in 22 of 23 patients. Twenty of the 23 patients (87 percent) became seizure free following surgery.
Temporal encephaloceles — Temporal encephaloceles are a relatively rare cause of drug-resistant focal
epilepsy but are increasingly reported in surgical series of temporal lobe epilepsy, which likely represents
increased awareness and advances in neuroimaging rather than a true increase in incidence. Detection of
encephaloceles is facilitated by thin-slice 3D MRI sequences and skull base computed tomography (CT)
(image 6). Their presence may be related to current or prior raised intracranial pressure, based on associated
imaging findings and higher prevalence in obese patients [99].
Anteroinferior/basal temporal encephaloceles, rather than posterior and lateral defects, are most commonly
implicated in temporal lobe epilepsy. It remains unclear whether temporal encephaloceles represent a singular
epileptogenic focus that can be removed via a lesionectomy sparing the medial structures or are a part of an
extensive epileptogenic network requiring treatment with anterior temporal lobectomy and
amygdalohippocampectomy.
The surgical approach to encephaloceles can vary. Extratemporal cases usually undergo lesionectomy
exclusively, whereas two-thirds of temporal encephalocele cases undergo anterior temporal lobectomy and
amygdalohippocampectomy [100].
SURGICAL COMPLICATIONS
The morbidity and mortality associated with temporal lobe resection for epilepsy treatment are low. In the
Nationwide Inpatient Sample hospital discharge database, anterior temporal lobe resections for epilepsy
performed between 1988 and 2003 were associated with a 10.8 percent overall morbidity and no mortality
[101].
Cognitive sequelae — Epilepsy surgery poses some risk to cognitive function. Approximately one-fourth to
one-third of patients develop some degree of memory loss [102,103]. Left temporal lobe resections can result
in decrements in verbal memory [102,104-107], while spatial memory and learning may be affected by right-
sided surgery [108].

In a six-year follow-up study of 85 patients who had serial examinations over six years, cognition continued to
decline for two years following left temporal lobe resection, but it then stabilized over the next four years
[109,110]. After right temporal lobe resections, cognitive scores initially improved but returned to preoperative
baseline two years after surgery. Another cohort study of patients who had temporal lobe resections reported
stable cognitive function for 2 to 10 years after temporal lobe resection [111]. Patients with higher presurgical
abilities are at greater risk for memory decline following temporal lobectomy compared with those with lower
presurgical scores [102,112-114].
In at least one comparative study, children appeared to recover lost cognitive function more quickly and more
completely than adults, presumably reflecting greater neuronal plasticity [110,115]. Older age and lower
baseline verbal intelligence quotient (IQ) have also been identified as risk factors in some groups [103].
The possibility of cognitive impairment after surgery needs to be balanced against the potential for control of
seizures, as this may be more important for functional outcomes. In one study of 138 patients undergoing
epilepsy surgery, health-related quality of life (HRQOL) improved in all patients with seizure remission,
regardless of neurocognitive sequelae [116]. However, in individuals without seizure remission, memory
decline after surgery was associated with reduced HRQOL, which remained stable in the absence of this
complication.
A preliminary, nonrandomized study in 112 patients after temporal lobectomy suggests that postoperative
cognitive rehabilitation may be helpful in ameliorating some of these deficits, particularly a decline in verbal
memory [117].
Visual field defects — Additional neurologic sequelae of temporal lobe surgery include visual field defects
(VFDs), which are usually limited to a superior quadrant and may be detectable only by formal testing. VFDs
are mainly due to injury to the inferior optic radiations (Meyer loop), which course anteriorly in the temporal
lobe. In a systematic review of 76 studies that included data on over 1000 patients who underwent temporal
lobe epilepsy surgery, the incidence of superior quadrantanopsia was 18 percent and the incidence of major
field defects (homonymous hemianopsia) was 2 percent [118].
Risk may be higher for left-sided resections. In a prospective case series of 105 patients undergoing anterior
temporal lobectomy, 16 had a new postoperative VFD; 12 of these occurred following a left-sided resection
[119]. Risk may also vary according to the type of resection that is performed. In one retrospective study of 276
patients who underwent mesial temporal lobe epilepsy surgery, rates of homonymous scotoma within the
central 20 degrees ranged from 56 percent after anterior temporal lobectomy to 21 percent after selective
subtemporal amygdalohippocampectomy [120].
Some of the variability in rates of VFD may be related to significant interindividual variation in the anterior
extent of Meyer loop, which is incompletely predicted preoperatively by current neuroimaging techniques [121-
125]. Limited data suggest that use of intraoperative magnetic resonance imaging (MRI) with display of optic
radiation tractography during surgery, where available, may help to minimize risk [126].
VFDs can improve somewhat from the initial postoperative defect, and driving restrictions based upon this
deficit should be reevaluated up to one to two years later [127]. (See "Homonymous hemianopia".)
Psychologic sequelae — Psychiatric problems, including depression and psychosocial adjustment difficulties,
are not uncommon after epilepsy surgery. Risk factors include a personal or family history of psychiatric
disease, poor family and psychosocial support, and certain personality traits [1,128,129]. Presurgical
psychiatric evaluation and psychosocial assessment and comprehensive, long-term postsurgical
neuropsychologic follow-up are advised in order to mitigate these complications [1,2].
Others — Other neurologic deficits (aphasia, cranial nerve palsy, hemiparesis) occur in 6 percent and are
permanent in only half of these cases [130,131]. Death associated with epilepsy surgery is extremely rare (1 in
700) [131].
ANTISEIZURE DRUG MANAGEMENT AFTER SURGERY
As discussed above, seizure control within the first year after surgery also predicts more favorable longer-term
seizure outcomes [44,53-56]. Long remissions can occur after a relapse; however, these remissions are
associated with a poorer outcome than an equivalent period of complete seizure remission immediately
following surgery. Similarly, some patients will relapse after an extended period of remission, but these patients
usually do not become medically intractable. Patients who develop recurrent intractability are usually
identifiable within several months after surgery.
Patients and families understandably hope that antiseizure drugs can be tapered and withdrawn after surgery.
The rationale for reducing antiseizure drugs includes avoidance of drug interactions and dose-related adverse
effects, as well as concerns regarding teratogenesis. Patients often believe that medication is unnecessary if
they have had "successful" surgery, and thus perceive continued use of antiseizure drugs as an unwanted
reminder of a disease process that is no longer an active issue for them.
There are no prospective, randomized data evaluating discontinuation of antiseizure drugs following epilepsy
surgery. A review of six retrospective studies including 611 children and adults followed for one to six years
postoperatively noted the following [132]:
The mean seizure recurrence rate was 34 percent after planned discontinuation of antiseizure drugs in
patients who were seizure free after epilepsy surgery (most often temporal lobe surgery).
The seizure recurrence rate increased during years one to three of follow-up.
More than 90 percent of adults who had recurrent seizures regained control with reinstitution of previous
antiseizure drug therapy.
The incidence of recurrent seizures was not affected by the duration of postoperative antiseizure drug
treatment, suggesting that there is no value to treating for a specified period of time before attempting to
stop therapy.
No factors were identified that predicted the risk of relapse after tapering antiseizure drugs, despite
looking at factors such as duration of epilepsy, age at onset of epilepsy, and preoperative magnetic

resonance imaging (MRI). However, it is not clear whether any of these factors would be predictive of
relapse in a prospective, randomized study.
There are compelling reasons for patients to be considered for antiseizure drug taper and withdrawal following
epilepsy surgery. These include antiseizure drug adverse effects, potential drug interactions, cost of therapy,
and pregnancy-related considerations. Such factors are weighed against the risk of recurrent seizures, which
may affect legal driving status. In practice, most individuals are not considered for antiseizure drug withdrawal
unless they are seizure free for at least one year following surgery. Those with auras or seizure activity
following surgery should probably remain on antiseizure drug therapy unless they are seizure free for two to
five years.
There is controversy regarding the utility of electroencephalography (EEG) postoperatively to predict the
likelihood of seizure recurrence with drug discontinuation. The emergence of epileptiform activity during the
drug taper may be associated with an increased risk of seizure activity. We typically determine an antiseizure
drug level and perform an EEG prior to antiseizure drug taper and withdrawal. When the decision is made to
taper, an antiseizure drug is usually withdrawn over several weeks. Long tapering schedules (eg, a year or
longer) have not been shown to be beneficial.
Most, but not all, individuals who have seizure activity associated with antiseizure drug termination will become
seizure free again with reinstitution of medical treatment. Even if all antiseizure drugs cannot be tapered, many
patients are successfully tapered to antiseizure drug monotherapy, which may minimize adverse effects, cost
of therapy, and potential drug interactions. The goal of surgery remains to render the patient seizure free, with
or without continued antiseizure drug treatment [133].
TRENDS IN EPILEPSY SURGERY
Despite a large and growing body of evidence supporting the benefit of epilepsy surgery in carefully selected
patients with drug refractory epilepsy, surgery remains underutilized [134-139]. A population-based study
utilizing the United States Nationwide Inpatient Sample found that there were 6653 resective surgeries from
1990 to 2008, and there was no growth trend over this time period [134]. By contrast, a similar study
examining pediatric epilepsy surgery trends in the United States found that rates of epilepsy surgery
incrementally rose from 1997 to 2009 [140].
At the same time, there is evidence that the patient population undergoing surgical treatment at large epilepsy
centers has changed. In several studies, the absolute number of anterior temporal lobe resections, as well as
the percentage of epilepsy surgeries comprising anterior temporal resections, has decreased over time [141-
143]. The reasons for decreased utilization of the most common operative procedure for epilepsy are not clear.
At many epilepsy centers, an increasing number of patients referred for consideration of surgery have negative
magnetic resonance imaging (MRI) studies, multifocal seizures, or indeterminate outpatient diagnostic
evaluations [144].

SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world
are provided separately. (See "Society guideline links: Seizures and epilepsy in adults".)
SUMMARY AND RECOMMENDATIONS
Patients with drug-resistant focal epilepsy should be referred to a comprehensive epilepsy center to
confirm the diagnosis, categorize the epilepsy syndrome, and evaluate all possible treatment options,
including surgery. (See "Evaluation and management of drug-resistant epilepsy".)
Surgical evaluation is recommended for patients with refractory focal seizures (Grade 1A). The most
favorable candidates are those with magnetic resonance imaging (MRI)-identified lesions that correlate
with the electrophysiologic localization of seizure onset. (See 'Surgical candidates' above.)
The goals of the surgical evaluation are to identify the epileptogenic zone fully and avoid operative
morbidity associated with a focal cortical resection. Standard components of the surgical evaluation
include detailed neurologic history and examination, neuropsychologic testing, routine
electroencephalography (EEG) recordings with standard activating procedures, inpatient long-term video-
EEG monitoring in an epilepsy monitoring unit, high-resolution brain MRI, and functional and metabolic
imaging using positron emission tomography (PET) and/or single-photon emission computed tomography
(SPECT). Preoperative formal speech and language testing and visual field examinations are also
performed in selected patients. (See 'Surgical evaluation' above.)
In adult patients, mesial temporal lobe epilepsy secondary to mesial temporal sclerosis is the most
frequently encountered surgically remediable epileptic syndrome. The most common surgical procedure is
an anterior temporal resection in which the temporal pole is removed along with the hippocampus and part
of the amygdala. The best surgical candidates are those patients with focal, unilateral brain lesions (eg,
mesial temporal sclerosis, tumor, or vascular malformation) that correlate with focal-onset seizures
localizing to the ipsilateral temporal lobe. (See 'Mesial temporal lobe epilepsy' above.)
Patients with focal seizures of neocortical origin and normal brain MRI scans may also be candidates for
epilepsy surgery, but management is often more challenging because of difficulty lateralizing and
localizing the epileptogenic zone, difficulty defining the extent of brain tissue that must be resected for
seizure freedom, and concerns regarding functional cortex. (See 'Neocortical epilepsy with normal brain
MRI' above.)
Low-grade primary brain tumors, vascular malformations, and malformations of cortical development
(MCDs) are other causes of refractory focal epilepsy. Resection of the epileptogenic brain region often
results in improved seizure control. Outcomes are typically better for patients with tumors and vascular
malformations than for patients with focal cortical dysplasia. (See 'Lesional epilepsy' above.)

Epilepsy surgery is associated with low rates of morbidity and mortality when performed at specialized
centers. The most common adverse effects related to epilepsy surgery are cognitive impairment and
visual field defects (VFDs). (See 'Surgical complications' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
Topic 91820 Version 31.0

Note the decreased volume and abnormal increased T2 signal of the

hippocampus (arrow) and atrophy of the left temporal lobe, including the white
matter.
MRI: magnetic resonance imaging.
Graphic 77659 Version 4.0

FLAIR sequence of the same patient; because FLAIR nulls CSF signal, abnormal
signal intensity in the hippocampus (arrow) is relatively more apparent.
MRI: magnetic resonance imaging; FLAIR: fluid-attenuated inversion recovery; MTS:

mesial temporal sclerosis; CSF: cerebrospinal fluid.

Short TI Inversion Recovery (STIR) coronal oblique MR image, showing focal

dysplasia in the left parahippocampal gyrus (arrow 1) and occipitotemporal
gyrus (arrow 2). Cortical thickening, increased signal in the subcortical white
matter, and blurring of the gray-white margin are appreciable in these two
regions.
MRI: magnetic resonance imaging.

An interictal PET scan after intravenous injection of Fluorine-18-fluoro-2-deoxy-D-glucose

(FDG), showing left temporal hypometabolism, medial more than lateral (see boxed area),
but extending to the insula and possibly to the parietal region.
PET: positron emission tomography.

Coronal SISCOM image showing a region of hyperperfusion in the left inferior frontal lobe (arrow). Patient has
drug-resistant focal epilepsy of left superior temporal lobe origin. Brain MRI was normal. (Note: The left
cerebral hemisphere is on the right side of the figure).
MRI: magnetic resonance image; SISCOM: subtraction ictal SPECT co-registered to MRI; SPECT: single photon
emission computed tomography.

Coronal T2-weighted FLAIR (A) and turbo-spin-echo (B) sequences showing a small encephalocele with gliosis arising from the left
temporal lobe through the floor of the left middle cranial fossa (arrows).
MRI: magnetic resonance imaging; FLAIR: fluid-attenuated inversion recovery.

Surgical Treatment of Epilepsy in Adults - UpToDate

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Clinical evaluation — A comprehensive evaluation is essential in patients with drug-resistant epilepsy.

To determine preoperative cognitive performance as a baseline that can be compared with a

To provide comprehensive preoperative counseling, including neuropsychologic education of the patient

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SURGICALLY REMEDIABLE EPILEPTIC SYNDROMES

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Presence of a focal brain lesion on MRI

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Shorter preoperative seizure duration

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Stereoelectroencephalography (SEEG) is another invasive technique that is being increasingly used to

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Malformations of cortical development — Malformations of cortical development (MCDs) are an

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ANTISEIZURE DRUG MANAGEMENT AFTER SURGERY

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TRENDS IN EPILEPSY SURGERY

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SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

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Topic 91820 Version 31.0

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Note the decreased volume and abnormal increased T2 signal of the

MRI: magnetic resonance imaging.

Graphic 77659 Version 4.0

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MRI: magnetic resonance imaging; FLAIR: fluid-attenuated inversion recovery; MTS:

Graphic 69972 Version 3.0

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Short TI Inversion Recovery (STIR) coronal oblique MR image, showing focal

MRI: magnetic resonance imaging.

Graphic 65171 Version 4.0

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An interictal PET scan after intravenous injection of Fluorine-18-fluoro-2-deoxy-D-glucose

PET: positron emission tomography.

Graphic 75459 Version 5.0

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Graphic 97084 Version 2.0

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MRI: magnetic resonance imaging; FLAIR: fluid-attenuated inversion recovery.

Graphic 116536 Version 1.0

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