Principles of Neurosurgery,

edited by Robert G. Grossman. Rosenberg © 1991.

Published by Raven Press, Ltd., New York.

CHAPTER 15

The Epilepsies

Jerome Engel, Jr., Michel Levesque, Paul H. Crandall, D. Alan Shewmon,

Rebecca Rausch, and William Sutherling

Need for Surgical Treatment, 320
Etiology and Pathology, 320
Natural History, 321
Outpatient Evaluation, 322

Basic Evaluation, 322
EEG Evaluation, 323
Imaging Studies, 324

Neuropsychological Testing, 326
Indications for Further Evaluation, 326

Inpatient Evaluation, 328

Phase I (Extracranial EEG Telemetry), 329
Phase 2 (Intracranial EEG Telemetry), 334

Operative Procedures, 341

Electrocorticography, 341
Operative Techniques, 342

Special Considerations for the Developing Brain, 345

Intractability, 345
Timing of Surgery, 346
Identification of the Epileptogenic Zone, 346

Outcome, 347

Complications, 347
Seizures, 348
Psychosocial Adaptation, 350

Research Opportunities, 351
References, 353

The modern era of surgical treatment for epilepsy began
over one hundred years ago with the classic paper of
Horsley (1), but until recently very few patients with
medically intractable epileptic seizures were candidates
for this therapeutic intervention. The past decade has
witnessed a virtual explosion of interest in epilepsy sur-
gery. This is a result of the tremendous advances in neu-
rological diagnostic technology that have vastly im-
proved the localization of structural and functional

J. Engel, Jr: Departments of Neurology, Anatomy and Cell

Biology, and the Brain Research Institute, University of Califor-
nia, Reed Neurological Research Center, Los Angeles, Califor-
nia 90024-1769.

M. Levesque: Department of Surgery (Division of Neurosur-

gery), University of California, Los Angeles, California 90024-

6901.

P. H. Crandall: Departments of Neurology, Surgery (Divi-

sion of Neurosurgery), and the Brain Research Institute, Uni-
versity of California, Los Angeles, California 90024-6901.

D. A. Shewmon: Departments of Neurology and Pediatrics,

University of California, Los Angeles, California 90024-1752.

R. Rausch: Department of Psychiatry and Biobehavioral

Sciences, University of California, Reed Neurological Re-
search Center, Los Angeles, California 90024-1769.

W. Sutherling: Department of Neurology, University of Cali-

fornia, Reed Neurological Research Center, Los Angeles, Cali-
fornia 90024-1769.

abnormalities in the human brain, and of the greater

safety and efficacy of modern diagnostic and therapeutic
surgical procedures. Despite this, however, only a small
fraction of patients who might be candidates for epilepsy
surgery receive attention at epilepsy surgery centers. Al-
though it has been estimated that perhaps as many as
one quarter of a million people in the United States
alone might benefit from surgical intervention, perhaps
only four or five hundred a year receive this treatment
(2). This can be attributed in part to a lag in the dissemi-
nation of information to primary care physicians and
their patients concerning these new developments and
the indications for referral to epilepsy surgery centers,
and in part to the limited number of epilepsy surgery
facilities currently available. The latter results from a re-

luctance on the part of medical centers to commit the
personnel, space, and resources necessary for a dedicated
epilepsy surgery program at a time when reimbursement
for medical care involving expensive diagnostic and ther-
apeutic procedures is being questioned and reduced.
This chapter is intended to address the first problem di-
rectly, by describing the modern role of surgical inter-
vention in the treatment of epilepsy, with the hope that a
subsequent increased demand for epilepsy surgery will
indirectly help to resolve the second problem. The dis-
cussion is primarily concerned with localized resective

319

320 / CHAPTER 15

surgery for medically intractable partial epilepsy, but an

increasing number of patients with secondary general-

ized epilepsies are becoming candidates for large multi-
lobar resections as well as corpus callosum section, and
these procedures will also be briefly considered.

NEED FOR SURGICAL TREATMENT

The epilepsies afflict at least one million people in the

United States. These relatively common neurologic dis-
orders principally affect the lives of young people: over
75 percent of all epilepsy begins before the age of 15 (3).

According to the classifications of the International

League Against Epilepsy (4), epileptic seizures can be

divided into two categories: generalized seizures (those

that are generalized from the start and are associated
with bilaterally synchronous EEG changes), and partial
seizures (those in which ictal behavior and/or EEG alter-
ations indicate initial involvement of a restricted system

of neurons limited to a single hemisphere). Partial sei-

zures are further divided into simple (no impairment of
consciousness) and complex (impairment of conscious-
ness) subtypes.

In a 33-year-long study of 1,457 patients (5), a fairly

homogeneous white population in the northern United
States with recurrent seizures (either febrile or afebrile)
was identified, showing a mean annual incidence of
48.7/100,000 population. Prevalence for recurrent afe-

brile convulsions was approximately 6.7/1,000 popula-
tion. Sixty percent of the patients studied manifested
partial seizures, with higher incidence rates at the ex-
tremes of life.

In a French population of a more heterogeneous na-

ture, nearly 40 percent of 6,562 epileptics experienced
complex partial seizures (6). Complex partial seizures
are believed to be the single most common seizure type.
Anticonvulsant therapy is effective in only an estimated
35 to 50 percent of these patients (7). However, medi-
cally intractable partial seizures—and, in particular,
complex partial seizures—can often be successfully

treated with surgery. Furthermore, surgical intervention

may also benefit carefully selected patients with medi-
cally intractable generalized seizures that occur as symp-

toms of multifocal or diffuse cerebral disease processes.

More than 60 years after Horsley first described surgi-

cal therapy for partial epilepsy (1), the safety and efficacy

of surgical treatment was unequivocally demonstrated
for those patients in whom interictal EEG paroxysms
were highly unilateral and localized (8-10). Unfortu-
nately, the vast majority of patients were excluded be-
cause they were shown to have bilateral independent dis-
charges or widespread interictal abnormalities.
Regarding the application of surgical treatment in 1967,

Falconer wrote: "the selection of patients has been rigor-

ous, and we estimate that only about one in nine persons

referred for surgery fulfill [our] criteria" (11). The exces-

sive use of operating room time for intraoperative diag-

nostic studies, and the necessity for an integrated special-
ist team, resulted in surgical treatment becoming
underutilized in the 1960s, and only a handful of centers
treated significant numbers of patients.

Since the 1960s, a variety of diagnostic methods have

been developed that further enhance reliable localization
of epileptic foci (12). Our tools have been stereotactic
surgery (13,14), intracranial electrodes which provide for
artifact-free recordings during ictus (15-19), long-term
EEG monitoring (20-22), and techniques to localize ce-
rebral areas demonstrating focal functional deficit
(12,23). The principle objectives in this chapter are to
describe these diagnostic techniques, the surgical opera-

tions, and the results. Introduction of these new diagnos-
tic tests has resulted in identification of a progressively

larger population of patients with partial seizures who
could significantly benefit from surgical treatment with-
out incurring undue risks. In contrast to Falconer's expe-
rience, approximately 80 percent of patients evaluated
for surgery at UCLA eventually undergo a therapeutic
procedure. There is, therefore, an increasing need for
more facilities to provide this form of surgical therapy.

ETIOLOGY AND PATHOLOGY

-A distinction must be made between three terms that

are commonly used in reference to partial epilepsy: epi-
leptic focus, epileptogenic lesion, and epileptogenic re-

gion (24). An epileptic focus is an electrographic concept
that refers to the site of maximal EEG-recorded interictal
spike activity. An epileptogenic lesion is a structural con-
cept that refers to a discrete pathological substrate of par-
tial epilepsy. An epileptogenic region is a theoretical con-
cept that refers to the area of cerebral tissue that is
necessary and sufficient to generate recurrent partial sei-
zures. It is the epileptogenic region that needs to be iden-
tified by presurgical evaluation procedures and, ulti-
mately, resected in the surgical treatment of epilepsy.
The boundaries of the epileptogenic region, however,
can only be inferred from a variety of tests that define the
location and extent of functional and structural cerebral
abnormalities. The epileptic focus, epileptogenic lesion,

and epileptogenic region are not necessarily congruent
since interictal spikes may be secondarily generated
from multiple brain areas, and habitual seizures may

originate at a distance from documented structural le-

sions. Whereas EEG studies are essential to demonstrate
sites of interictal spike occurrence and ictal onset, these
data do not prove the location of the epileptogenic re-
gion. The pathological substrates of partial epilepsy may

be identified with structural imaging tests such as x-ray

computed tomography (XCT) and magnetic resonance

imaging (MRI), but the underlying defects are more of-
ten demonstrated in the surgical patient population only

by careful histological analysis of resected brain tissue.
These latter studies have helped to develop an under-

standing of the causes of human partial epilepsy (25,26).

THE EPILEPSIES / 321

Any localized injury to the cerebral cortex occurring

in utero or after birth can give rise to a partial seizure

disorder. Consequently, patients may have a history of

gestational or birth difficulties, head trauma, meningitis,
or other potential cerebral insults. More information
about the pathological anatomy underlying complex
partial seizures has been gained as a result of the tech-

nique of en bloc resection of the anterior temporal lobe
(see "Operative Procedures") (11,27-29), which allows

careful histologic evaluation of intact surgical speci-

mens. Most lesions encountered are in the medial tem-
poral structures (hippocampal pes, parahippocampal
gyrus, and amygdala), and their nature is usually not

suspected from routine diagnostic evaluation. Mesial
temporal sclerosis, the most common lesion found post-
mortem in patients with complex partial seizures (30), is

also the most common lesion found in resected temporal
lobe specimens (25,26,31-33).

Controversy exists concerning whether mesial tem-

poral sclerosis is a cause or an effect of recurrent epileptic
seizures. Patients with mesial temporal sclerosis have a
greater-than-expected incidence of prolonged febrile
convulsions in infancy and family history of epilepsy
(31), and prolonged seizures in animals can produce
changes in the hippocampus comparable to human me-
sial temporal sclerosis (34). Such observations have sug-

gested that there is a genetic predisposition to seizure
induction of this particular pattern of cell loss in the hip-
pocampus, and also to the subsequent appearance of re-
current complex partial seizures in association with the
lesion. The epileptogenicity of this pathological abnor-
mality has been inferred from the clinical knowledge
that seizures appear to originate within the sclerotic hip-
pocampal tissue (35), and that removal of a portion of
the temporal lobe containing mesial temporal sclerosis
usually results in resolution of the seizure disorder
(32,33). While patients who benefit from surgery occa-
sionally yield brain tissue that appears completely nor-
mal, quantitative cell counts of hippocampal specimens
from such individuals have revealed abnormal neuronal
loss suggesting a mild degree of hippocampal sclerosis

that is not recognized by routine pathological analysis

(36). It is currently believed that such cell loss leads to
axonal sprouting and synaptic reorganization, account-
ing for the development of chronic epileptic neuronal

activity (37-39).

Besides mesial temporal sclerosis and focal scarring

from trauma or infection, other pathologic changes com-
monly noted in surgically resected specimens from pa-
tients with partial epilepsy, who usually give no history
of any predisposing etiologic event, include glial tumors,
meningiomas, heterotopias, angiomas, cysts, and focal

cortical dysplasia (25,40,41).

A family history of epilepsy is not unusual in patients

with temporal lobe epilepsy (29,42). In contrast to the
family history of epilepsy found in hereditary primary
seizure disorders, where the seizure manifestations are

usually similar in all affected family members, the family
history of epilepsy in patients with complex partial sei-

zures is usually quite varied. Other family members may
have had chronic seizure disorders or isolated seizures
secondary to a variety of cerebral insults. This probably
indicates a genetically determined lowered threshold for
seizures, perhaps necessary for the development of un-
complicated partial epilepsy in response to a single focal

lesion.

Many of the diagnostic tests that will be discussed here

were developed under the assumption that epileptogenic
regions develop in, or adjacent to, areas of damaged

brain and should exhibit evidence of localized functional
deficit as well as epileptic excitability. If the site of epilep-
tic excitability, as measured by EEG-recorded interictal
spike activity and ictal onset, coincides with the site of
focal functional deficit, measured by a variety of tests to
be described later, the incidence of pathologic changes in
the resected specimen is high and surgical results are ex-
cellent (23,43,44). When partial epilepsy is treated by
resective surgery, careful pathologic evaluation of the
specimen is of clinical importance, as demonstration of a

structural lesion correlates with a good prognosis

(32,33,45). This information can be useful in preparing
the patient, family, and referring physician for the fu-
ture.

Unfortunately, the concept of a single isolated epilep-

togenic abnormality in patients with a medically intract-
able partial seizure disorder may be an oversimplifica-
tion of the problem. Multifocal abnormalities are often
encountered during the diagnostic evaluation, and pa-
tients frequently are only partially relieved of their epilep-
tic symptoms by surgery (46). Clearly a spectrum of epi-
leptic disorders ranges from simple partial seizure
phenomena due to a small well-defined epileptogenic le-

sion, through bilaterally independent and multifocal dis-
orders, to the so-called secondary generalized epilepsies

(47) in which the cerebral disturbances are so diffuse that
seizures appear to be generalized from the start (24). A
definitive determination of where an individual patient
may lie along this continuum can never be obtained

merely from pathologic evaluation of a resected tem-

poral lobe or other cortical specimens removed at sur-
gery. Additional lesions may still exist in the remaining
brain. Consequently, a clear picture has yet to emerge
concerning the pathophysiological basis of partial sei-
zure disorders that may or may not respond to surgical
intervention. Basic research programs at centers engaged
in the surgical treatment of epilepsy provide an impor-
tant opportunity to elucidate these issues, as will be dis-
cussed at the end of this chapter.

NATURAL HISTORY

A natural history of partial epilepsy is valuable as a

gauge against which to measure the efficacy of any thera-
peutic interventions (48). Strictly speaking, we are not

322 / CHAPTER 15

likely to get a true natural history, since all patients now
receive treatment. A series of articles from Oxford,
which followed 100 children with temporal lobe epilepsy
into adulthood, is the nearest approach to a natural his-
tory so far compiled (49,50-52). The subject patients

were taken from a larger unselected population of over

1000 children with seizures of all kinds. The collection of

the series began in 1948 and ceased in 1964. Patients
were followed until 1977. Clinical diagnosis was con-
firmed by two physicians, and an EEG demonstrated a
focal discharge in one or both temporal regions. Collec-
tion was strictly consecutive, and it was possible to trace
all of the patients in the series. Ninety-five patients were
divided into three outcome categories (five patients died

as children before the age of 15). Thirty-three patients

were able to support themselves socially and economi-
cally, were seizure-free, and were not receiving anticon-
vulsant medication. Thirty-two were also able to support
themselves socially and economically; however, they

were receiving anticonvulsants and were not necessarily

seizure-free. Thirty patients were not able to support
themselves and were considered to be totally dependent.

Eight risk factors were related to an adverse outcome:

(1) an IQ under 90; (2) seizure onset before 2.5 years of

age; (3) five or more severe grand mal attacks; (4) daily
temporal lobe attacks; (5) a left-sided EEG focus; (6) hy-
perkinetic syndrome; (7) catastrophic rage; and (8) the
necessity for special schooling. In the best group, 30 of

the 33 patients had three or fewer risk factors and 10 had
none. In the worst group, 25 of the 30 patients had four
or more risk factors. Nearly all patients in the best group
went into sustained remission before the age of 15; in

retrospect, some (if not most) of these probably had the

familial condition of benign epilepsy, with centrotem-

poral spikes (53), rather than temporal lobe epilepsy.

It is of particular interest here that a subset of patients

in this study who continued to have seizures ultimately
underwent surgical treatment. An investigation from
London of 666 patients with temporal lobe epilepsy (54)

also contained a subset of patients who had medically

intractable seizures and underwent surgical treatment.
Whereas in both studies patients with persistent seizures
generally experienced functional deterioration, this did
not occur when surgical resection successfully abolished
the habitual ictal events. Such evidence that psychoso-
cial. if not physiological, disability can be progressive has

been used as an argument for early surgical intervention
<55.56). These findings indicate the need for skilled re-

view of the medical and social status of children with
complex partial seizures. For those who can reach full
recovery, the withdrawal of drugs before the age of 15 is
of great importance. When seizures continue into adoles-

cence, full investigation with a view to possible neurosur-
gical treatment should be undertaken. Lindsay et al. (49)
concluded that "a major danger in caring for children
with temporal lobe epilepsy is delaying operation for re-
lief of seizures so long into adult life that social recovery
has become impossible."

OUTPATIENT EVALUATION

Because only patients with partial seizures can be con-

sidered candidates for localized surgical resection of an
epileptogenic region, it is important to obtain evidence
of a partial epileptic condition from history, neurologic
examination, and routine laboratory testing before sub-

jecting the patient to more exhaustive evaluation. How-

ever, some patients, usually children, with diffuse unilat-

eral or secondary generalized epileptic disturbances may

be candidates for larger multilobar resections, hemis-
pherectomy, or corpus callosum section.

Basic Evaluation

Description of Ictal Behavior

Usually the partial nature of a seizure can be ascer-

tained from a careful description of the behavioral event
given by a reliable observer. Therefore, the initial inter-
view with an epileptic patient should ideally include a
parent, spouse, or some other individual who has wit-
nessed the events in question. Subjective warnings noted
by the patient (auras) are an important indication of a
partial seizure disorder and may be useful in differentiat-
ing between partial and generalized epilepsy. Precise in-
formation regarding auras and initial clinical ictal events
can also have localizing value, although this is not as

reliable as was once believed (57,58).

Partial seizures accompanied by impairment of con-

sciousness (which may consist only of amnesia) are gener-
ally considered indicative of limbic system involvement.
The term complex partial is often used interchangeably
with limbic, psychomotor, or temporal lobe seizures.

However, it is very important to realize that complex

partial seizures can, and often do, result from extratem-
poral epileptogenic regions that invade temporal lobe
limbic structures only secondarily.

Some patients with complex partial seizures do not

experience or remember auras, and an accurate descrip-
tion of the behavioral ictal onset is sometimes unavail-
able or unreliable. Furthermore, partial seizures may not

always have a discrete focal or lateralized behavioral on-
set; ictal events that appear to be generalized at the start
can represent spread from a single epileptogenic region

located in a so-called silent area of the brain. Such sei-
zures include those that are secondarily generalized (par-
tial becoming tonic-clonic) according to the interna-

tional classification (4), as well as complex partial
seizures that begin with an alteration in consciousness

without warning and proceed to simple or complex auto-

matisms involving both sides of the body. These latter
ictal behaviors generally indicate a partial onset, even

though the behavioral manifestations are bilateral from
the start; however, brief events may be difficult to differ-
entiate from absences that occur with generalized seizure
disorders (47,59). Consequently, evidence to substan-

THE EPILEPSIES / 323

tiate the partial nature of an epileptic abnormality must
occasionally depend on EEG and imaging studies.

Patients often give a history of more than one type of

seizure. Most patients with partial seizures also have had

one or more secondarily generalized seizures. As a gen-

eral rule, the more different types of seizures a patient
has, the more likely she or he has multifocal or diffuse
cerebral disease and is not a good candidate for resective
surgery. However, careful evaluation of ictal events (as

described in the section on inpatient evaluation) may

reveal that what first appeared to be a variety of seizure
types may actually be a number of manifestations of the
same basic seizure, consistent with a single dominant
epileptogenic region.

Neurologic Examination

Even though patients with partial seizures who are be-

ing considered for surgical therapy usually do not demon-

strate focal deficits on neurologic examination, a careful
evaluation should always be performed. General physi-
cal findings, such as cafe au lait spots with axillary freck-

ling or evidence of hemiatrophy, may indicate heredi-

tary or congenital disorders associated with focal brain
lesions. The most common neurologic abnormalities
found in patients with complex partial seizures are mem-
ory disturbances, which often are revealed on specialized
testing, even when they have not been elicited by history.
Problems in remembering verbal material and asso-
ciated word-finding difficulties suggest an epileptogenic
region in the language-dominant hemisphere. More spe-
cific motor or sensory neurologic deficits usually imply
that the major pathologic changes are suprasylvian. For-
mal visual field testing is generally included in the
screening test battery, although visual field deficits are

not common in the absence of large mass lesions.

EEG Evaluation

Routine EEG

The most useful diagnostic tool in the evaluation of

the epileptic patient has traditionally been the EEG. For
the potential surgical candidate, routine outpatient EEG
studies are important to confirm the partial nature of the
epileptic disorder by demonstrating focal interictal spike
activity, as well as other focal intermittent or continuous
abnormalities. Preliminary localizing information may
also be obtained from the outpatient interictal EEG, but
differences of opinion exist concerning the relative value
of interictal electrophysiological phenomena for pur-

poses of localization, as compared with recordings of ic-
tal onset (12,19,60). Although good results can be ob-
tained in many cases with surgery performed entirely on
the basis of interictal scalp EEG localization, there is
general agreement that interictal epileptiform discharges
can be misleading in 10 to 20 percent of patients
(23,61,62). This is particularly true with complex partial

seizures of limbic origin. Interictal EEG spikes may be

more localizing with extratemporal neocortical foci, par-
ticularly if the interictal EEG spikes correspond with a
discrete structural lesion demonstrated on XCT or MRI.
Presently, inpatient ictal recordings are always also ob-
tained on all patients considered for surgery at UCLA
(see "Inpatient Evaluation").

There are a number of potential hazards to under-

stand and avoid when using routine interictal EEG stud-
ies to identify a partial seizure disorder and localize an
epileptogenic lesion. A number of normal EEG variants,
such as small sharp spikes, 14 and 6/sec positive spikes.

wicket spikes, the so-called psychomotor variant and
6/sec (larval or phantom) spike and wave phenomena
can be mistaken for pathologic spikes if their characteris-

tic features are not recognized (47). Abnormal spike dis-

charges, such as occipital spikes, periodic lateralized epi-
leptiform discharges, and sylvian spikes, may not be
associated with epilepsy or may not indicate the location
of a resectable epileptogenic region (47). Even epilepsy-

related pathologic interictal EEG spikes may tend to

shift location, particularly in children (61), and do not
always correlate reliably with the site of the epileptogenic
region (23,62,63). Bilateral independent temporal EEG

spikes are common in patients with complex partial sei-

zures who eventually do well with unilateral temporal
lobectomy (23,46), and the predominant EEG focus
may occasionally be contralateral to the primary epilep-
togenic region (23).

Special Electrodes

Basilar electrodes that are capable of recording epilep-

tiform activity originating from mesial aspects of the
temporal lobes are most commonly used in the EEG
evaluation of patients with complex partial seizures.
Electrodes placed on the earlobes, over the zygoma, or in
the true temporal (T1,T2) location are at least as effective
as nasopharyngeal electrodes in identifying interictal
spikes not seen with the routine 10-20 placement system
(64). Because nasopharyngeal electrodes are uncomfort-
able, unstable, near pharyngeal muscles that cause arti-
facts that may be impossible to differentiate from cere-

brally generated spikes, and are separated by wet mucous

membrane that makes lateralization difficult, their use is

discouraged. Sphenoidal electrodes provide a somewhat

higher yield than other basilar derivations and are quite
stable, so that their use is recommended for long-term
monitoring (65); however, this yield is not sufficiently
high to warrant their routine use in the outpatient EEG

laboratory. The use of several basilar derivations simulta-
neously may aid in defining an electrical field for interic-

tal spikes that has additional localizing value (66).

Small sharp spikes and 14 and 6/sec positive spikes

lack their characteristic appearance when recorded from
mesial temporal placements and cannot be easily differ-
entiated from pathologic spike phenomena, even by the
most experienced electroencephalographer, without ac-

324 / CHAPTER 15

cess to EEG patterns simultaneously derived from the
scalp (47). Therefore, basilar EEG studies should always

include an independent lateral temporal montage to

identify the surface electrical field of all medially re-
corded spikes (as in Fig. 4). These recordings should not
be done on an 8-channel EEG machine; such machines
do not allow sufficient independent surface monitoring
to analyze medially recorded phenomena properly. At
least 12, but preferably 16 or more, channels should be
used for these studies. A good general rule is to take seri-
ously only those mesial temporal spikes that have an
identifiable field over the appropriate temporal surface
not characteristic of 14 and 6/sec positive spikes, small
sharp spikes, or other normal variants. By using these

techniques properly, one can obtain positive recordings

from patients with suspected complex partial seizures
significantly more often than by routine EEG alone

(65,67).

Activation

Activation procedures such as hyperventilation, pho-

tic stimulation, and sleep are routinely used in the EEG
laboratory. Hyperventilation may provoke focal slow-
ing, spikes, and even partial seizures. Since photosensi-
tive epilepsy is almost always a primary generalized dis-
order, photic stimulation is much less likely to be useful

in the evaluation of partial seizures, except in the differ-

ential diagnosis between partial and generalized seizure
disorders. Sleep can also activate interictal EEG spike
discharges, particularly frontotemporal spikes associated
with complex partial seizures, but it is important to ig-

nore the normal and clinically insignificant sharp tran-

sients associated with sleep, and to be aware that interic-

tal EEG spikes activated by slow-wave sleep have less

localizing value than interictal spikes seen during wake-
fulness (68). As with basilar electrode placements, sleep
studies are useful for demonstrating the presence of a
focal epileptiform abnormality when the diagnosis of a
partial seizure disorder is not clear from history and ex-

amination and routine EEGs are equivocal; therefore,

the two techniques are often used together. However, if
the diagnosis is clear from other evidence, and the pa-
tient is scheduled to undergo an inpatient presurgical
evaluation, these procedures are not necessary.

Imaging Studies

Structural Imaging

Focal structural abnormalities may be demonstrated

with XCT or MRI, although this is not as common
among patients referred for surgical treatment of epi-

lepsy as has been reported for partial and secondarily
generalized epilepsies in general (69-75). When a well-

defined mass lesion is found, the surgical treatment is

often dictated more by the nature of this lesion than by
the epileptic seizures. Patients with obvious brain tu-
mors will not be considered further in this discussion of
surgery for epilepsy per se. With the advent of high-reso-
lution structural imaging, however, the clinical impor-
tance of many identified abnormalities is not always
clear. Defects seen on XCT and MRI can come and go
(76,77), and mesial temporal unidentified bright objects

(UBOs) consisting of nonspecific increases in intensity

on T2-weighted MRI image, unassociated with changes
on the Tl-weighted image, may have no structural corre-

late (78). Nonspecific structural defects such as small

cysts, areas of calcification, disgenetic disturbances, and
localized cerebral atrophy that are not in themselves an
indication for surgery help confirm the location of an
epileptogenic region identified by electrographic and
other functional means.

If the site of a demonstrated structural abnormality

correlates with the site of epileptiform EEG activity (see
"Inpatient Evaluation"), this is helpful in localizing re-

sectable epileptogenic tissue; however, one should bear

in mind that structural abnormalities may be totally
unrelated to the epileptogenic area (23). Consequently,
demonstration of a structural abnormality by itself
should not be considered sufficient evidence for localiza-

tion of the source of epileptic seizures.

Functional Imaging

The most important confirmatory test used at UCLA

is positron emission tomography (PET) with

18

F-fluoro-

deoxyglucose (FDG) (23,43,44,79-81). Many centers
have now demonstrated that the majority of patients
with partial epilepsy who are candidates for surgical
treatment have FDG-PET scans with characteristic meta-
bolic disturbances (82-85). This consists of a zone of
hypometabolism (Fig. 1), usually including the site of
ictal onset determined by surface and depth electrode
EEG telemetry, and the site of a structural lesion deter-

mined by microscopic evaluation of the resected speci-

men (43,80,81). Although temporal lobe hypometabo-

lism is encountered in 70 percent or more of patients
with medically refractory complex partial seizures of
mesial temporal origin, they are less commonly seen
when the epileptogenic region is neocortical (86). FDG-
PET may be particularly important in the presurgical
evaluation of infants and small children with severe uni-
lateral or secondary generalized epilepsy (87) where neu-
ronal plasticity allows larger resections than in the adult,

and chronic intracranial EEG recording is difficult to

perform. Many of these patients show unilateral hypo-
metabolic zones, even when structural imaging studies
are unremarkable. In this situation, FDG-PET also helps
to confirm that the contralateral hemisphere is function-

ing normally.

THE EPILEPSIES 323

FIG. 1. PET scan with FDG from a patient
with complex partial seizures of left mesial
temporal origin. This scan was performed on
a Siemens-CTI 831 tomograph with an in-
plane resolution of approximately 5 mm. Fif-
teen horizontal planes of section are ob-

tained simultaneously, and one or more sets
of pianes can then be reformatted into coro-
nal, sagittal, or other planes as desired. Note
that images front this tomograph show the
patient's left side on the right and the pa-
tient's right side on the left. The PET scan of
this patient demonstrates mild left temporal
hypometabolism, which can be seen on all
horizontal planes of section through the
temporal lobe shown in (A) and enlarged for
one section in (B). The hypometabolism can

also be appreciated in the coronal section

(C) and in sagittal section through the left
temporal lobe (D) when compared to the sag-

ittal section through the right temporal lobe

(E). (From reference 24, with permission.)

Ictal FDG-PET scans reveal areas of hyper- and hypo-

metabolism that correspond to the origin and/or spread
of epileptic discharge during the seizure (82,84,88). Such
ictal scans may be useful for elucidating the anatomic
substrates of specific ictal behaviors; however, because

regions involved in propagated activity cannot be distin-
guished from the site of seizure origin, these scans are not
as useful as interictal FDG-PET studies for localizing the
primary epileptogenic region.

Studies comparing FDG-PET with various EEG tests

have revealed basic differences (70,89). The FDG tech-
nique measures the average intensity, over time, of meta-
bolic activity in all cellular elements within each cerebral
structure scanned. The results are weighted according to

the energy requirements of individual elements without
regard to the specific function or orientation of these
elements, or to the temporal sequence of their activation.
The EEG, on the other hand, is a more dynamic tech-

nique influenced by the spatiotemporal relationships of
specific excitatory and inhibitory neuronal events within

these structures. The results are weighted according to
the degree of synchrony of these events and their spatial
orientation, without regard for the number of elements

actually involved. The FDG-PET technique reveals ana-
tomic localization better than EEG; the EEG is neces-
sary for the temporal sequencing of events. These tests
are complementary and together provide more func-
tional information about the epileptic abnormalities
under study than either test used alone.

Nonepileptogenic lesions can also be seen as a zone of

hypometabolism. Therefore, this FDG-PET defect per se
is not sufficient for identification of an epileptogenic
brain region and should be considered only as confirma-
tion of a focus demonstrated electrophysiologically. Al-

though the transformation of an interictal hypometabo-
lic zone into a hypermetabolic zone during ictus may be

326 / CHAPTER 15

pathognomonic of an epileptogenic region without EEG

evidence of epileptogenicity, focal hypermetabolism has

been reported in other conditions (90).

Single photon emission-computed tomography

(SPECT) is also being used to confirm the location of
epileptogenic regions. Interictal SPECT with tracers that
nonquantitatively measure cerebral perfusion provide
patterns that are similar to those of interictal FDG-PET
(91-94), although the reduced spatial resolution de-
creases the yield. In addition, a variety of biologically
active tracers does not exist, and radiation exposure to

the patient is greater than with FDG-PET. Ictal SPECT
is, however, more easily performed than ictal FDG-PET,
and can reveal patterns of hyper- and hypoperfusion that

may be useful for identifying the epileptogenic region

(93,95,96). However, as with ictal FDG-PET, it remains

difficult to differentiate the site of ictal origin from areas

of ictal'propagation. SPECT is currently more accessible
than PET since it does not require an on-site cyclotron;

but PET technology is becoming less complicated, and

more reasonably priced clinical systems are now being

made (97). Where PET is not available, SPECT remains

a useful alternative.

Neuropsychological Testing

Neuropsychological testing provides useful diagnostic

and prognostic information and is an important part of

the presurgical evaluation (98). The neuropsychological

evaluation is frequently used in combination with other
functional tests for confirmation of dysfunctional brain
areas (12,23,99). Prognostic uses of the neuropsychologi-
cal evaluation include information as to the probability
of seizure control following a focal resection (100,101),
prediction of the type and degree of cognitive loss follow-
ing surgical intervention (102,103), and the likelihood of
postoperative improvement in psychological and psy-

chosocial function (104,105).

A comprehensive neuropsychological evaluation

should assess a wide range of functions. The evaluation
should include measures of general brain integrity as
well as tests sensitive to dysfunction of the temporal lobe
and extratemporal areas. Psychological domains gener-
ally assessed are language, intelligence, attention, cogni-
tive-tracking, sensation, perception, motor skills, and
memory functioning, as well as personality and psycho-
social function (98,106).

The most reliable neuropsychological index of lateral-

ization of temporal lobe dysfunction is a selective mem-
ory deficit associated with one temporal lobe (107). The

memory deficit should exist independent of other neuro-

psychological deficiencies. Verbal memory tests such as

the delayed recall of logical prose and delayed recall of

newly learned unrelated word-pairs, both derived from

modified administration of the Wechsler Memory Scale
(108), have been found to be particularly sensitive to
dominant temporal lobe dysfunction. Nonverbal mem-
ory tests, such as the Rey-Osterrieth draw and recall test

and the delayed recall of the visual-reproduction subtest
of the WMS, are more sensitive to nondominant tem-
poral lobe functions. Interpretation of the neuropsycho-
logical profile is dependent upon knowledge of hemi-
spheric dominance for language, which is determined by

the intracarotid sodium amobarbital procedure (IAP).
This test is described in the section on inpatient evalua-
tion.

Indications for Further Evaluation

Positive Indications

Localized surgical resections are done to treat partial

seizures that appear to have a well-defined site of ictal

onset in a cortical area that can be removed without pro-

ducing additional unacceptable neurological deficits. Al-

though any epileptic disorder characterized by stereo-
typed partial seizures can be considered a positive
indication for further evaluation, in practice most pa-
tients who undergo inpatient evaluation for localized
surgical resections have complex partial seizures. PosiB
live indications for surgical treatments such as corpus

callosum section or large multilobar resection, including

hemispherectomy, are less well defined. Patients with sec-
ondary generalized epilepsies should be considered for
callosotomy when drop attacks are the most disabling
feature of their disorder.

Most complex partial seizures are limbic ictal events

that originate from one mesial temporal region, al-

though they also can occur as a result of epileptogenic

regions elsewhere that project to mesial temporal struc-
tures. The best surgical outcomes are obtained in pa-
tients with complex partial seizures of mesial temporal
origin who undergo anterior temporal lobectomy
(9,10,32,33,45,46,100,109-113). As a group, particu-

larly when the lesion is mesial temporal sclerosis, these

patients have a relatively high incidence of positive fam-

ily history for epilepsy, prolonged febrile convulsions in

infancy, and an onset of seizures in the first decade of life
(31). If an aura is present, it often has an epigastric or
other autonomic component, although a wide variety of
hallucinations and cognitive, affective, and psychosen-
sory symptoms may occur, followed by altered con-
sciousness, staring, automatic behavior, and postictal
confusion, with amnesia for the ictal event. Typically
these patients also experience auras without seizures.
Complex partial seizures may become secondarily gener-
alized, but this is a relatively infrequent occurrence.

THE EPILEPSIES / 327

(Other simple motor or special sensory seizures with pre-
served consciousness generally indicate extratemporal
onset, which is an indication for other types of focal cor-
tical excision). Neurologic examination may reveal a
moderate memory deficit and radiologic studies are
usually normal. The characteristic EEG pattern consists
of unilateral or, more commonly, bilateral independent
anterior temporal interictal spike foci. These features are

typical of "temporal lobe seizures"; however, such fea-
tures do not invariably distinguish an epileptogenic re-
gion within the temporal lobe from a primary site of
seizure generation elsewhere in the limbic system, or in
other cerebral areas that project to limbic structures.
Consequently, patients with such seizures are good can-

didates for presurgical evaluation, but conclusions re-

garding the actual location of the epileptogenic region
should not be made on this information alone.

While this profile characterizes an ideal surgical candi-

date, there is an infinite variety of manifestations of sur-
gically resectable epileptogenic regions. Each patient
presents a unique problem and must be dealt with inde-
pendently. It may be easier, therefore, to describe those
patients with partial epilepsy who, at this stage in the

outpatient work-up, are not candidates for further pre-
surgical evaluation.

Negative Indications

If pharmacologic management has not been adequate

to establish that the patient is medically intractable, sur-
gery is generally not considered until appropriate anti-
convulsants have been given a proper trial (42,55). Sur-
gery should also not be considered in patients with
seizures insufficiently severe to seriously disrupt the qual-
ity of life. Decisions regarding the severity of the seizure

disorder cannot be based on any uniform criteria, but

must take into account each patient's capabilities and
needs. For instance, a patient with a nondemanding oc-

cupation, who works alone with no set schedule, may
tolerate several seizures a day, while another with em-
ployment involving continued interaction with the pub-

lic or constant attention and quick judgment may be

unable to work with just a few seizures a year. In general,
patients with fewer than several seizures a month are not
considered for surgical therapy. Patients with severe

mental retardation are relatively poor candidates for lo-

calized resection, since this usually indicates diffuse cere-
bral damage and multifocal epilepsy. However, such sur-
gery may be justified occasionally if a reduction in
seizure frequency would significantly ease patient man-

agement at home or in an institution. While lower intel-

lectual scores have been correlated with poorer seizure

control following anterior temporal lobectomy (101),
there is no universal agreement concerning the degree of

mental impairment necessary before a patient should no
longer be considered a candidate for this procedure. Fur-

thermore, such patients may benefit from other surgical
interventions such as corpus callosum section or large
multilobar resections; in small children, the latter can
reverse a developmental delay. Chronic psychosis is of-
ten considered a relative contraindication to surgical
therapy, since this condition is rarely reversed when sei-
zures are abolished and patients remain incapacitated
(114). Less severe personality disturbances can improve
with abolition of habitual seizures (114), however, and
should not dissuade a decision to proceed with presurgi-
cal evaluation. When seizures are due to a known pro-
gressive cerebral degenerative process, localized surgical
intervention is usually inappropriate. Finally, patients
with medical contraindications to surgery should not be

considered further.

Common Misconceptions

Many good surgical candidates are never referred for

focal resective surgery as a result of misconceptions con-
cerning the indications for these procedures (12). Sur-

gery should be considered even if medication is shown to
be effective, when the necessary

7

dose required to control

seizures also causes unacceptable side-effects. This is a

particularly important concern in children, who do not
complain of overmedication and whose resultant poor
school performance or bad behavior may be erroneously
attributed to the epileptic disorder. Although patients
with progressive degenerative diseases are usually not
considered candidates for localized resection, progres-
sive symptoms may be due to increasing seizure fre-
quency, more severe seizures, drug effects, or psychoso-
cial factors, rather than to an underlying irreversible
progressive neuropathological process. Memory deficits
and specific cognitive impairment are not a contraindi-

1

cation to focal resective surgery since appropriate resec-1

tion does not necessarily increase these disabilities. In '
fact, memory often improves and IQ increases by an
average of 10 points following successful anterior tem-
poral lobectomy (101). Seizure-related reversible psy-
chotic symptoms, such as transient postical psychosis,
are not the same as chronic psychosis, and usually re-
solve postoperatively when seizures no longer occur.
There is no truth to the old belief that surgery is danger-
ous in the language-dominant hemisphere, since speech

areas now can easily be identified and avoided. Patients

with partial seizures that secondarily generalize, seizures
with multiple spread patterns from a single focus, "type
II" complex partial seizures (115), bilateral independent
or synchronous EEG spikes, and even occasional contra-

lateral ictal EEG onsets, usually have a single epilepto-

genic region that can be identified and resected with ben-

eficial results. Such patients, therefore, should not be

denied surgical consideration. Since patients with mesial
temporal sclerosis often have a family history of epilepsy
(31), this finding should not raise concern about a pri-

28 / CHAPTER 15

mary idiopathic epileptic disorder (116) that is not

treated surgically.

With increasing application of new diagnostic ap-

proaches (12), as well as improved safety of larger surgi-
cal resections and corpus callosum section, particularly
in children, more and more epileptic patients who would
not have been considered surgical candidates a few years
ago are now benefitting from surgical intervention. We
are rapidly reaching a point where almost any patient

with medically refractory epileptic seizures who appears

to have a partial or secondary generali/ed epileptic dis-

order deserves at least a preliminary evaluation at an

epilepsy surgery center.

INPATIENT EVALUATION

The approaches to presurgical evaluation are largely

dictated by the intended surgical procedure (2,117-119).
Figure 2 is a flow chart demonstrating the various proto-
cols for surgical treatment of epilepsy at UCLA. Al-
though this chapter is concerned primarily with localized

resective surgery, evaluation for large multilobar resec-
tions, hemispherectomy, and corpus callosum section

are also considered briefly. Patients who are candidates

for localized resection undergo an initial phase 1 inpa-
tient evaluation, which includes scalp and sphenoidal
EEC telemetry with video monitoring as well as addi-
tional confirmatory tests that do not require intracranial

procedures. If the epileptogenic region is not adequately

defined, patients may then go on to a phase 2 evaluation
with intracranial EEC telemetry and video monitoring.

If the epileptogenic region is suspected to be in limbic
structures, stereotactic depth electrode placement is
usually performed, often with subdural strips over se-
lected neocortical regions as well. When seizures are sus-
pected to originate in lateral neocortical regions and the

involved hemisphere is known, placement of subdural

grids is preferred. When there is doubt concerning which
intracranial recording procedure is most appropriate,
depth electrodes are used, since a second phase 2 with
subdural grids is always possible. When a craniotomy for
subdural grid placement is done initially, however, the
bone becomes too unstable to permit a second evalua-

tion with the UCLA orthogonal approach to stereotacti-
cally-implanted depth electrodes.

If the intended surgical procedure is a standardized

resection, such as anterior temporal lobectomy (26) or
amygdalohippocampectomy (120), the presurgical evalu-

FIG. 2. Flow chart illustrating the presurgical
evaluation scheme for epileptic patients at
UCLA. "Identification of extratemporal epilep-
togenic zones in patients who underwent
depth electrode evaluation may require a sec-
ond chronic intracranial procedure with sub-
dural grid electrodes. **Young children may
also be considered for hemispherectomy.
Also, some patients who do not already have

a severe hemiparesis may wish to undergo
surgery and accept this inevitable handicap.
(From reference 24, with permission.)

THE EPILEPSIES / 329

ation is designed to determine il" habitual seizures origi-

nate within the brain tissue to be resected, and if this

region also demonstrates focal functional deficits. When
the intended surgical procedure is a tailored resection
(121,122), the presurgical evaluation must not only
identify the site of seizure origin, but also the presumed
extent of the epileptogenic region and often the bound-
aries of adjacent primary cortical areas that cannot be

damaged. This latter situation, therefore, also requires

functional mapping procedures.

There arc several electrophysiological approaches to

the localization of the epileptogenic region in patients

with partial seizures who may be candidates for resective

surgical therapy (12). Some centers rely heavily on non-

invasive interictal EEG recording techniques, using rou-

tine scalp and basilar electrodes. These are usually sup-
plemented by intraoperative electrocorticography
(ECoG) (19,62,63), as described in the section on opera-
tive procedures. Others feel the epileptogenic region is

more reliably localized by inpatient recording of ictal

events using long-term video EEG monitoring (16), ei-

ther with scalp and sphenoidal electrodes (23), or with

intracranial (epi- and/or subdural) (17,18) or stereotacti-

cally implanted depth (13-15) electrodes. There is no

consensus on a single correct electrophysiological ap-
proach to the evaluation of the presurgical candidate
(12). Most now agree that ictal plus interictal data are
preferable to interictal data alone, and that chronic intra-

cranial recording is at least sometimes appropriate. Con-

siderable disagreement remains about when interictal
EEG and ECoG recordings are sufficient, and when

chronic intracranial recordings are necessary (19,123).

Because of the potential for false localization from elec-

trophysiological measures of epileptic excitability, it is

very important to use independent measures of func-
tional disturbance to confirm scalp and intracranial

EEG findings, and not to base decisions on only a few
tests. Consequently, the presurgical evaluation in most
centers now involves a variety of tests aimed at identify-
ing areas of abnormal l?rain structure and function (12).
The UCLA presurgical evaluation protocol utilizes ex-

tracranial and, as needed, various intracranial electro-

physiological approaches to localize epileptiform abnor-

malities. In addition, a variety of tests which measure

focal functional deficits are employed to confirm the lo-

cation of the epileptogenic region determined electro-

physiologically. This protocol, therefore, can be used to

illustrate most of the diagnostic procedures currently

available in epilepsy surgery centers.

Phase 1 (Extracranial EEG Telemetry)

Methods of Scalp and Sphenoidal EEG Telemetry

Patients determined by outpatient studies to be poten-

tial surgical candidates are initially admitted for approxi-
mately one to two weeks of scalp and sphenoidal EEG

telemetry with video monitoring. In some patients with
daily seizures, phase 1 EEG telemetry can actually be
achieved on an outpatient basis by recording in a teleme-
try unit located in the EEG laboratory for 8 hours a day.
Sphenoidal electrodes are 50-gauge, Teflon-coated, 15-
stranded stainless steel wires, which are bared at the tip.

These electrodes are inserted through a 22-gauge 1.5-

inch needle, as shown in Figure 3 (24). Wires have been

left in place for over six weeks without discomfort or

deterioration in recording characteristics.

During inpatient evaluation, the EEG is recorded con-

tinuously (24 hours a day) according to approved stan-
dards for long-term monitoring (20), transmitted via ra-

dio or cable telemetry, and stored on videotape (124).
Behavior is recorded by two video cameras and a micro-

phone, and data arc continuously stored on videotape.
Much of the patient's time is spent in quiet activities so

video recordings can be made, but ambulation and exer-
cise are possible without losing the EEG signal. As a rule,

FIG. 3. Illustration to show the placement of sphenoidal elec-

trodes. The needle is inserted approximately 1 inch anterior
to the tragus immediately under the zygomatic arch (black

dot on lateral view). The tip of the electrode should lie close to
the foramen ovale (basilar view). Inset shows how multi-
stranded Teflon-coated wire protrudes from the tip of the in-
sertion needle and is bent backward on the Teflon coating to
prevent breakage of wire strands. The inner lip of the needle
can also be beveled to further ensure that breakage of the
sphenoidal wire does not occur. (From reference 24, with per-
mission.)

330 / CHAPTER 15

only the ictal data are written out on paper for interpre-
tation. Seizures arc identified by continuous direct ob-

servation, or via video monitors. Patients can also signal
the occurrence of an aura with a call button. When sei-

zures occur, trained staff examine patients during the
events and their examinations are also recorded on the
videotape. In addition, subclinical electrographic ictal
EEG discharges may be captured by an automatic sei-
zure detector and by random searches. A time-code gen-

erator records clock time simultaneously on the video

image and on one channel of the EEG so that electrical
activity and behavior can be correlated exactly. Fifteen,

thirty, or more channels record EEG in common refer-
ence format so that seizures can then be played back in
any desired montage (125). Records are reviewed daily
by an electroencephalographer/neurologist and deriva-

tions may be changed if needed to better display any

abnormal activity observed.

The primary purpose of EEG telemetry with video

monitoring is to localize the site of onset of spontane-
ously occurring ictal EEG discharges, and to correlate

this with ictal behavioral changes. Anticonvulsant drugs
are cautiously tapered only if necessary, since this may

rarely precipitate atypical ictal events (126). Seizures are

occasionally activated by sleep deprivation, exercise, or

prolonged hyperventilation, when they do not occur

spontaneously.

Automatic spike detection programs are also available

for quantifying interictal spike frequencies at various lo-
cations (127). The site of maximum interictal spike oc-

currence, particularly those spikes recorded during

wakefulness (68,128) and REM sleep (129) correlates
well with the site of ictal onset.

Evaluation of Epileptiform Activity

Ictal EEG changes can be observed with scalp and

sphenoidal electrodes in most patients during complex

partial seizures, although isolated auras or other simple
partial seizures are only rarely accompanied by identifi-
able EEG abnormalities. Some examples of ictal onsets
recorded during scalp and sphenoidal EEG telemetry ap-
pear in Figure 4. The most easily recognized focal ictal
EEG onsets are localized to sphenoidal derivations, but

even these can be misleading due to propagated activity

from primary epileptogenic regions beyond the range of

recording electrodes (23,130). Two specific ictal onset
patterns shown in Figure 4 have equally reliable localiz-
ing value. Both depend upon the occurrence of rhythmic
activity of 5 Hz or faster, with phase reversal in one
sphenoidal electrode (130). When this pattern is the first
ictal change observed, or occurs after other changes that

are localized to the same sphenoidal electrode, it is re-

ferred to as an initial focal onset. When the pattern is
seen within 30 seconds after a diffuse ipsilateral, or gener-

alized ictal change, it is referred to as a delayed focal

onset. Since both initial and delayed focal patterns have
the same localizing value, we no longer consider it im-
portant to require that ictal EEG changes precede ictal

behavioral changes when analyzing scalp and sphenoi-
dal-recorded data. Both patterns are correct in identify-

ing the epileptogenic region demonstrated subsequently

by depth electrode evaluation in only about 85 percent
of patients, however. Consequently, confirmatory data
from other independent studies are also necessary.

When a consistent initial or delayed focal ictal EEG

onset is recorded from one sphenoidal electrode and a
preponderant interictal EEG spike focus is also identi-

fied in the same area, the patient may be considered for
surgery without intracranial evaluation if the criteria for
confirmatory evidence of focal functional deficit de-

scribed later are met. The number of seizures required to

conclude that ictal onsets are consistently focal is not

fixed and is determined in part by the nature of the pa-

tient's habitual seizures. If more than one habitual sei-
zure type has been reported, examples of each type

FIG. 4. Examples of EEG telemetry-recorded ictal onsets from four patients with complex partial sei-
zures. (A) Low-voltage 6 to 7 c.p.s. rhythmic activity appears at the right sphenoidal electrode (arrow) 5
sec before it is seen over the right temporal convexity. (B) Following a diffuse burst of muscle and eye
movement artifact, low-voltage 5 to 6 c.p.s. activity is recorded by the right sphenoidal electrode (arrow).

This becomes progressively slower and the amplitude increases; 5 sec later it is seen diffusely over the
right hemisphere. (C) Irregular, sharply contoured slow waves demonstrate phase reversal at the right
sphenoidal electrode (arrow) and are reflected as low-amplitude delta, without phase reversal, over the
right hemisphere. (D) In this lateralized but not localized ictal onset, voltage suppression and low-voltage
fast activity occur over the entire right hemisphere, although they are best seen at the right sphenoidal
electrode (arrow). This precedes by 3 sec the appearance of diffuse 3/sec spike and wave discharges,
which are also more prominent from the right frontotemporal and sphenoidal derivations. After 1 0 sec,
this latter activity evolves into high-voltage 7/sec sharp waves, which show phase reversal at the right
sphenoidal electrode and laterally at the right anterior to midtemporal region. The 5 to 7 c.p.s. patterns in

(A) and (B) illustrate an initial focal pattern and in (D) a delayed focal pattern, both of which correlate

highly with ipsilateral mesial temporal ictal onsets identified with depth electrode recording. The slower
focal rhythmic pattern in (C), however, has less localizing value. Calibration 1 sec, 100 nV. Note that
sensitivity is the same for A, B, C, and the first half of D but is decreased to half in D at the first calibration
mark. (From reference 99, with permission.)

332 / CHAPTER 15

should be recorded. It is most important to be certain
that the seizures captured on the telemetry unit are the
seizures causing the patient's problems at home. If neces-

sary, videotapes can be shown to family or friends for

verification. Additional tests are then performed during
phase 1 to obtain confirmatory evidence of dysfunction
at the site of ictal onset.

Evaluation of Focal Functional Deficits

FDG-PET and neuropsychological evaluations are

important confirmatory tests of focal functional deficit

that are performed on an outpatient basis and have al-
ready been described. Two other tests, thiopental activa-

tion and the intracarotid sodium amytal procedure
(IAP), require hospitalization and are usually done dur-
ing the phase 1 telemetry admission if ictal onsets are

focal.

Barbiturate narcosis is often used in order to activate

interictal EEG spike activity, although EEG spikes that
occur during slow-wave sleep have less localizing value
than those that occur during wakefulness (128). This test

is useful, however, because focal attenuation of barbitu-

rate-induced fast activity implies a functional deficit that
may indicate the site of the epileptogenic region
(45,131,132). We prefer to use intravenous thiopental
given at a rate of 25 mg every 30 seconds until adequate
fast activity is produced in the EEG (usually 200 to 300
mg). This drug is considerably more effective than seco-

barbital because it provides more control over the level

of consciousness, and the observation time is longer than
with the faster acting methohexital. In patients with
complex partial seizures, focal attenuation is most often
isolated to one sphenoidal electrode (Fig. 5); this finding

correlates well with the presence of a mesial temporal

lesion on that side, usually mesial temporal sclerosis
(45,131,132).

The intracarotid sodium amobarbital procedure was

originally done to lateralize hemispheric dominance for
language (133), and was later used to predict whether the
contralateral temporal lobe could support memory after
anterior temporal lobectomy (107). Further research has
shown that an induced transient global memory deficit,
following pharmacological ablation of one hemisphere,
correlates with the presence of an epileptogenic lesion in

the contralateral temporal lobe (134). In addition, patho-

logic shifting of language dominance from the left to the
right hemisphere generally indicates that the epilepto-
genic lesion is in the left temporal lobe (135).

Before the patient undergoes IAP, angiographic stud-

ies are recommended to provide information about the

perfusion pattern of the drug. These studies may also

identify arterial anomalies that would put the patient at
risk. Before injection of sodium amobarbital, baseline

measurements are made of the patient's language and

memory functions to serve as a comparison for drug-re-

lated behavior changes. Immediately prior to injection,
the patient is asked to count aloud while bilateral grip
strength is continuously assessed. Over a 4-second pe-
riod, 125 mg of sodium amobarbital in 10 cc of saline
solution is injected into one internal carotid artery via a

transfemoral cannula. Each hemisphere is infused sepa-

rately, with at least a 30-minute delay between injec-
tions. EEG is simultaneously recorded, and the neurolog-
ical status of the patient is continuously monitored. The
critical postinjection period for behavior assessment is
during the drug-induced marked unilateral EEG delta
slowing and hemiparesis. This period typically does not

last longer than 3 minutes. Within seconds after the dom-

inant hemisphere injection, cessation of counting occurs
and marked aphasia is immediately apparent, varying
from mutism to perseverative speech.

Initial aphasia testing is carried out in the first minute

after injection. The examination assesses expressive and
receptive language skills and includes naming, reading,

and responses to simple commands. Following this,
items to be remembered are presented. Memory for
these items is tested following return of EEG and behav-

ior to baseline, and at least 10 minutes postinjection.

The type of item presented should be appropriate for the
hemisphere being assessed. For instance, memory for
verbal material, either visually or aurally presented, is
not expected to be intact following a dominant hemi-

sphere injection. More detailed descriptions of the

IAP assessment procedure have been published else-
where (136).

Skull roentgenograms, XCT, MRI, and cerebral an-

giograms are also obtained during phase 1 if these studies
have not been carried out previously. Nonspecific struc-

tural abnormalities revealed by these studies provide

useful confirmatory information if their localization cor-
relates with the site of EEG-demonstrated epileptiform

activity, although these structural findings alone do not
necessarily indicate an epileptogenic lesion (23,74). As

noted earlier, the pathological correlates of high-inten-

sity areas in T2-weighted MRI scans remain unclear
and these abnormalities should be interpreted with cau-
tion (78).

Indications for Further Procedures

If a patient has a well-localized EEG-recorded ictal

onset (130), FDG-PET scans demonstrate a hypometa-

bolic zone in the same area, and there is no conflicting

localizing information from structural imaging, other
tests of focal functional deficit, or seizure semiology, a

standard anterior temporal lobectomy is recommended

FIG. 5. Simultaneous sphenoidal, nasopharyngeal, and temporal scalp recordings during thiopental
injection. Note attenuation of low-voltage fast activity recorded at the left sphenoidal electrode (channel!

3 and 4), but not at nasopharyngeal or scalp derivations. Calibration 1 sec, 100 yuV. Patient had menial
temporal sclerosis on left. (From reference 99, with permission.)

334 / CHAPTER 15

at UCLA without requiring phase 2 (243). Clear struc-
tural lesions on MRI and XCT can be substituted for
FDG-PET evidence of hypometabolism, but further

studies are necessary to determine when other tests of

focal functional deficit may serve this purpose.

When patients fail to meet the criteria for surgical re-

section after phase 1 evaluation, they may be considered
for phase 2 studies if seizures appear to be stereotyped
and the data collected during phase 1 allow a hypothesis
limiting possible epileptogenic regions to a few that can

be adequately explored with intracranial recording. If
the seizures are complex partial and a limbic onset is
suspected, depth electrodes are usually recommended. If
phase 1 has clearly lateralized the epileptogenic region to
one hemisphere and it appears to be in the lateral neo-
cortex, subdural grid electrodes are preferred.

When phase 1 evaluation indicates that seizures are

occurring from multiple sites, or no localizing hypothe-

sis can be derived, patients might still be considered for

large multilobar resections, hemispherectomy, or corpus
callosum section. These aggressive procedures are most
often justified in infants and small children in whom the
seizures are life-threatening or the likely cause of severe

developmental delay (137,138). Unilateral regions of hy-

pometabolism on FDG-PET that correlate with the pre-

dominance of interictal and/or ictal epileptiform EEG

discharges are the most important criteria for consider-

ing large resections in these patients (87,139), while drop

attacks as the major cause of disability are the primary
indication for callosotomy (140). Further work-up in
these patients may include spike-suppression tests (141),
and more specific psychological and psychosocial evalua-
tions. Patients undergoing hemispherectomy must ei-

ther have a useless contralateral hand or, in rare in-

stances, be willing to accept this deficit as an inevitable

consequence of the surgical procedure. Patients who in-
tend to undergo corpus callosum section must under-
stand that this is a palliative procedure that is unlikely to
abolish all ictal behaviors. There is some evidence that
patients with ipsilateral hand and language dominance

are at greater risk for disabling postoperative disconnec-

tion symptoms (142), but this is not considered an abso-

lute contraindication to callosotomy. Most centers
prefer to carry out partial callosotomy, commonly the
anterior two-thirds, which is usually effective without
causing a disconnection syndrome. If drop attacks per-

sist, the section can be completed later with minimal

symptoms of disconnection.

Phase 2 (Intracranial EEG Telemetry)

General Considerations

Due to the serious risk (but low incidence) of injury

from chronic intracranial electrode recording, only pa-

tients who appear very likely to benefit from surgical
treatment are selected for phase 2. For this group, when
phase 1 evaluation fails to localize a surgically resectable
epileptogenic lesion, intracranial recording offers a great
diagnostic advantage. With depth or subdural grid elec-
trodes, the ictal EEG recording is generally free of mus-
cle and movement artifacts, making it possible to ob-
serve exquisitely focal types of ictal onset and to follow
the spatiotemporal pattern of electrographic propaga-
tion. However, such focal onsets are observed only when
a recording electrode is at, or very close to, the primary
epileptogenic region. Since only a limited number of in-

tracranial electrodes can be safely placed, the number of
potential locations of the epileptogenic region should be

reasonably narrowed by the phase 1 evaluation before
these invasive procedures are contemplated.

EEG with stereotactically placed depth electrodes

(SEEG) is most frequently employed in patients with
complex partial seizures of presumed limbic origin when
(1) clear EEG lateralization of the ictal onset has not
been obtained; (2) EEG-recorded ictal onsets are well
lateralized but equally prominent in extratemporal and

temporal regions; (3) EEG-recorded ictal onsets are well

localized to one temporal lobe but confirmational evi-

dence of focal dysfunction or a structural lesion is miss-

ing or conflicting; (4) EEG-recorded ictal onsets are
clearly localized to one temporal lobe but other studies
and/or the clinical seizures (e.g., simple partial motor or
special sensory) suggest an extratemporal disturbance; or
(5) phase 1 evaluation suggests an epileptogenic region in
one temporal lobe that should be treated by a larger, or
more limited, resection than the standard anterior lobec-

tomy. In patients who may be candidates for selective
amygdalohippocampectomy or lateral temporal resec-
tion, depth electrodes are used to confirm that ictal on-
sets arise from the area of planned removal. .

Chronic recording with intracranial subdural grid

electrodes usually is utilized when (1) EEG and MRI
lateralization of the epileptogenic region has been ob-
tained and additional localization is necessary between
lobes or within a large area of cortex, and (2) localization
of essential cortex is necessary to avoid deficit during
resection of nearby seizure foci. The ability of subdural
grids to localize limbic ictal onsets is unknown. The rela-

tive advantages of grids versus depth electrodes is an area
of active investigation.

There are some general contraindications that relate

to the safety of intracranial electrode EEG recording
over a number of weeks. Patients who have serious multi-
ple illnesses or active infections that could lead to intra-
cranial infections, or who are otherwise poor surgical
risks (e.g., patients with diabetes mellitus who are prone
to infection) obviously should not undergo chronic intra-
cranial EEG. Also, certain skull defects (e.g., thinning of
the bone or a prior craniotomy) make depth electrodes
unstable and therefore unsafe. During phase 1 studies,

our patients are closely observed for emotional instabil-
ity, psychiatric disorders, or unusually violent ictal be-
havior, which would not allow them to tolerate phase 2.
Careful attention is devoted to ensuring that patients
and/or their parents have a full understanding of the
purposes and risks involved in these procedures as a
measure of obtaining full consent.

Methods of Electrode Implantation and Removal

Stereotactic Depth Electrode Implantation

Recent developments in neuroimaging have radically

changed the field of Stereotactic surgery. MRI now al-
lows direct visualization of brain structures in any plane.
By choosing specific pulse sequences, MRI can delineate
brain-CSF boundaries, grey and white matter junctions,
and even discrete pathological changes within deep cere-
bral regions. We now use a method of electrode implan-

tation based essentially on MRI guidance, Stereotactic

digital subtraction angiography (DSA), and Stereotactic
FDG-PET; these neuroimaging studies arc integrated in
a computerized image-analysis system that allows pre-

surgical planning of electrode implantation. This stereo-

tactic technique is made possible by an MRI-compatible
lightweight Stereotactic frame that is used for imaging
studies and intraoperative implantation, and for postop-
erative verification of electrode placement. The overall
principle remains to survey the limbic structures medial
to the temporal lobe from anterior to posterior, bilater-
ally and symmetrically (15). Additional extratemporal
structures are selected for implantation according to sei-
zure semiology, scalp EEGs, and/or hypometabolic ar-
eas on FDG-PET.

A modified Leksell Stereotactic frame (the OBT, Tipal

Instruments, Montreal, Canada) (143) is used for target
localization and electrode implantation (Fig. 6). It is con-
structed of electrically nonconducting material that is
compatible with CT, MRI, and DSA. With additional
modifications made at UCLA (144.145), Stereotactic
PET can also be obtained. Targets are reached from a
lateral orthogonal approach in a system of Cartesian co-
ordinates, where the X axis is along the anteroposterior
(sagittal) plane of the frame, the Y axis is along the infe-
rior to superior (coronal) plane, and the Z axis is in the

axial plane, extending positively to the right and nega-
tively to the left.

Four sets of Plexiglas® plates provide fiducial markers

on each side and top of the Stereotactic frame. Three
contain a Z-shaped channel filled with an appropriate
contrast material for each image modality and are tempo-
rarily attached to the Stereotactic frame. Aluminum tub-

ing is used during CT scanning, copper sulfate solution

(7 gm/1) is used for MRI studies, and for PET scans the

channels are filled with positron-emitting germanium

isotope. The plane of section is calculated from the loca-

THE EPILEPSIES / 335

>i!p; •

FIG. 6. The OBT (modified Leksell) frame used for intracere-
bral target localization and depth electrode implantation. Ste-

reotactic brain images obtained with magnetic resonance,

computerized tomography, digital angiography, and positron
emission tomography are artifact-free.

tion of the center arm of the Z-shaped marker in relation
to the two parallel end bars. For DSA studies, the fiducial

markers consist of four 1 -mm stainless steel disks placed

equidistantly at the four quadrants of the Plexiglas plates

located on either side of the head for a lateral view, or at
the front and back of the frame for an anteroposterior
view. Markers closest to the x-ray source will form a
larger rectangle on the x-ray film because of beam diver-
gence, and thus differentiate the side injected and pro-
vide data for computer analysis of depth of field.

The procedure per se is divided into three stages: (1)

Stereotactic imaging, (2) computerized image analysis,
and (3) Stereotactic implantation.

1. Stereotactic imaging. The Stereotactic frame is

placed on the patient's head using local anesthesia sup-

plemented with short-acting neuroleptics. Initially, the

frame is positioned over the head using auricular pins,

then five twist-drill holes are made in the outer table of
the skull at the front, back, and midline. Five MR-com-
patible carbon fiber pins are placed in the drilled holes

and secured to the frame. A memory ring is placed on

each pin at the outer portion of the frame to permit exact
repositioning of the frame for any future surgical proce-
dures. The patient is then brought to the MRI suite and
placed in a supine position, with the Stereotactic frame

anchored to a custom frame adaptor over the sliding ta-

ble of the MRI. Sagittal, coronal, and axial Stereotactic
MR images are obtained on a 0.3 Tesla unit. We use a
custom surface coil that fits closely around the frame to
increase the signal-to-noise ratio. Inversion-recovery se-
quences with a slice thickness of 4.9 mm and slice inter-
vals of 5.1 mm are obtained. Three excitations are used
in the coronal plane, and two in the axial and sagittal

•planes. A Stereotactic digital angiogram in both antero-

posterior and lateral projections is obtained using a stan-
dard femoral catheterization approach. Four-per-second

336

CHAPTER 15

arterial and venous phases are selected for further analy-
sis. Finally, a stereotactic FDG-PET is performed. A
frame adaptor allows fixation to the tomograph sliding
table. The patient is injected with 5 mCi of FDG, and 15
simultaneous axial planes with a center-to-center inter-

slice distance of 6.75 mm are obtained 40 minutes later.

Images are reconstructed by filtered backprojection to

an image with in-plane resolution of approximately 5 X

5 mm. The head-frame is then removed.

2. Computerized image analysis. All stereotactic digi-

tized imaging studies are analyzed after being transferred
to a central workstation. Image data such as size, slice

thickness and intervals, field of view, and orientation are

included. Surgical planning and selection of recording
sites are made at the central workstation using image-
analysis software. Selected images are retrieved from the
hard-disk memory and are simultaneously displayed in
separate windows (Fig. 7). Different planes from a single

FIG. 7. Multimodal stereotactic imaging system. Top: Different planes of different studies can be simulta-
neously displayed on the computerized workstation terminal. Bottom: Post-implantation MR, seen here
in the coronal plane, is used to verify accurate electrode placement. (From reference 145, with permis-
sion.)

THE EPILEPSIES / 337

modality or multimodal images can be displayed and
analyzed at the same time. A cursor system intercon-
nects the images and the X, Y, and Z coordinates of any

point within the stereotactic frame can be displayed. Ini-

tially, structures are selected on the sagittal MR; orthogo-
nal trajectories are simulated to sample both lateral tem-
poral neocortex and mesial temporal structures
(amygdala; anterior, mid, and posterior hippocampi;
and anterior, mid, and posterior parahippocampal gyri).
Labeled targets are automatically transposed to the coro-
nal and axial MR, and the Z coordinate, denning the

depth of implantation, is then determined. Next, phases

of the arterial and venous angiogram are selected and
trajectories are corrected within an avascular window.

Extratemporal targets are usually the orbito-frontal cor-

tex, the supplementary motor area, the anterior and pos-
terior cingulate gyri, or the occipital cortex. After com-
pletion of the target localization, a printout of all
coordinates is obtained.

3. Stereotactic implantation. Under general anesthe-

sia, at a subsequent surgical sitting, the stereotactic
frame is replaced over the patient's head using the pre-

measured skull-fixation pins and the position confirmed
with a portable skull x-ray. The frame is clamped to a

supportive device attached to a Mayfield holder. A modi-
fied side-carrier that slides on vertical side bars is posi-

tioned at the predetermined X and Y coordinates and
serves as a key landmark for measurement of electrode
length to reach the Z coordinate. The skin and skull are

penetrated from an orthogonal approach without

breaching the dura, which is carefully perforated with a
thin electrocautery, stopping at the subdural space. A
self-tapping MR-compatible titanium guide-screw is
then secured to the skull. The distance between the outer
portion of the screw and the side-carrier is translated into
a specific length for each electrode. Temporal electrodes
are multicontact rigid tubing with an outer diameter of

0.8 mm. The electrodes are constructed with MR-com-

patible nickel chromium and have a hollow center per-
mitting insertion of platinum alloy fine wire (40-micron
diameter) electrodes. Extratemporal electrodes are flexi-
ble nichrome fine wires (100-micron diameter) with
multicontact leads. Two reference electrodes are placed
in the galea. After placement, electrodes are bent toward
the vertex and embedded in a thin mold of acrylic poly-

mer. Additionally, stereotactic subdural strips of six or

eight platinum disc electrodes imbedded in silicone

(146) can be inserted over the convexity or the mesial
aspects of both hemispheres, when seizures are also sus-

pected of having a frontal or parietal lobe origin. This

can be accomplished by knowledge of the locations of

major draining veins from the stereotactic angiography.

Subdural strips are used as sentinel electrodes to sample

certain areas presumed to be involved in seizure onset

that are poorly sampled by the orthogonally placed
depth electrodes. The frame is removed postoperatively,

and the patient is transferred to the neurosurgical inten-
sive care unit for overnight observation. The patient is
sent to the telemetry unit when stable. Electrodes are
removed under local anesthesia after completion of the
monitoring period. Resective surgery is performed a few
months after removal of the electrodes to allow wound

healing and reduce the risk of infection.

Subdural Grid Implantation

This technique requires an initial craniotomy for the

insertion of multiple arrays of electrodes over the cortex

in the subdural space (18,147). Wide areas of lateral cor-

tex can be sampled as well as subtemporal, suboccipital,

orbito-frontal, mesial frontal, cingulate, mesial parietal.
or occipital areas. The grids are made of silicone and
contain up to 64 platinum discs, each with a diameter of

5 mm and a center-to-center interelectrode distance of

10 mm. After intraoperative definition of the sensorimo-

tor cortex with evoked responses, lateral coverage of the
central area, including peri-sylvian cortex, opercular
frontal, and superior temporal gyri, is obtained with a
single 64-contact grid. Additional grids are inserted to
sample specific lobes according to the desired presurgical
evaluation. Great care must be taken to avoid any tear or

displacement of major draining veins. The grids are tied
to each other to prevent movement or slippage. The con-

nectors are then tunneled under the skin through sepa-

rate incisions. An intracranial pressure monitor is also
placed to indicate significant postoperative cerebral
edema. The dura is closed in a water-tight fashion, and
the bone flap sutured in place. Corticosteroid administra-
tion and fluid restriction are used initially to allow ex-
pansion of the subdural space and accommodation of
the brain to the grids. Patients are then taken to the neu-
rosurgical intensive care unit before transfer to the telem-

etry ward for functional mapping and seizure monitor-
ing (18,148).

Depth Electrode Evaluations

During the first postoperative day, while the patient is

still in intensive care, prolonged direct SEEG (hardwire)
recordings are made to survey all depth electrode con-
tacts, as well as any subdural strip electrodes that may
have been inserted. Chain-linkage, common reference,

and bipolar recordings are obtained using a 21 -channel

EEG machine. Patients are then transferred to the telem-
etry unit for SEEG telemetry and video monitoring in
order to capture spontaneous seizures and perform other
studies. If indicated by the incidence of seizures during

phase 1 telemetry, anticonvulsant medications are
slowly tapered. During SEEG telemetry, ictal EEG and

behavioral data are gathered and seizures are detected as

described for phase 1. In addition, an automatic seizure

338 / CHAPTER 15

detector is used to identify ictal SEEG discharges that
might otherwise go unnoted (149,150). Subclinical elec-

trographic ictal events are also more commonly encoun-

tered with random searches during phase 2 than during
phase 1. Initial SEEG recordings are made using 30-
channel montages containing symmetrical derivations
from each hemisphere, including the most mesial and
most superficial contacts from temporal and extratem-
poral electrodes and any subdural strip electrodes. After
several typical episodes are recorded and the electrogra-
phic pattern is determined, montages may be changed to
define better the site of ictal onset. Even with 30 teleme-

try channels, not all depth electrode contacts can be sur-
veyed in the initial montage. Additional contacts may
need to be included later, as well as scalp and sphenoidal
derivations if needed to identify surface correlates. Focal

onsets are most clearly displayed by recording from the

bipolar tip of each depth electrode.

Mesial temporal EEG-recorded ictal onsets are called

focal (151) and considered to be localizing when they are

stereotyped; when only one or two electrode contacts are
involved initially; and when there is a clear progression
of the epileptic discharge, first to ipsilateral and then to
contralateral structures, which can be correlated tempo-
rally with the progression of behavioral ictal events (Fig.
8A-C). Often, however, the initial EEG changes are
more difficult to interpret, due to subtle focal onsets that
may be missed, or regional onsets (151) that initially in-
volve all, or most, depth contacts in one temporal lobe

simultaneously (Fig. 8D-F).

With our present knowledge, it is impossible to charac-

terize definitively and classify all SEEG-recorded ictal

phenomena. Although certain patterns may be corre-
lated with good or bad prognoses (152,153) and various
pathologic findings (154), there is much yet to be learned
about the neuronal events recorded by the ictal SEEG,
and the ultimate clinical significance of the abnormali-
ties revealed by this technique. Almost every patient we

FIG. 8. Segments of SEEG telemetry-recorded ictal onsets from six patients. These tracings represent
examples of progressively decreasing localizing value. (A) Very low-voltage fast activity begins (arrow) at
the left anterior hippocampal pes (LAH) and continues for 1 7 sec before it is barely seen in other areas.
(B) Low-voltage fast activity of much lower frequency than that seen in A begins (arrow) at the left
posterior hippocampal gyrus (LPG) and appears in all depth leads on the left after 5 sec. (C) 4 to 5/sec
sharp activity begins in the right middle hippocampal pes (RMH) (arrow) and 1 sec later is slightly re-
flected in all right depth electrodes. (D) Sharp activity begins with phase reversal in the left posterior
hippocampal pes (LPH) (arrow) and remains most prominent there, although it is reflected in all the other
depth electrodes. (E) Ictal rhythmic activity first appears in the left middle hippocampal gyrus (LMG) and
later spreads to other depth electrodes; this is preceded by a regional suppression (arrow) involving all
left temporal depth electrodes. (F) Ictal discharges begin with irregular regionally synchronous spike,
polyspike, and slow-wave bursts followed by a build-up of low-voltage fast activity, which is also synchro-
nous in both hippocampal pes and gyrus. (Note: R, right; L, left; AMYG, amygdala; A, anterior; M, middle;
P, posterior; H, hippocampal pes; G, hippocampal gyrus.) Calibration 1 sec. For each sample, the eight
channels not shown recorded from homologous contralateral depth sites, extratemporal, skull, and
sphenoidal derivations. (From reference 99, with permission.)

see appears to be unique, and each SEEG evaluation
seems to present a new set of confounding issues.

In general local onsets appear to indicate reliably that

the electrode contact is near the epileptogenic region,
while regional onsets tend to represent epileptiform activ-
ity propagated from a primary epileptogenic region dis-

tant from the available recording sites. Usually, how-
ever, this distant region is still within the same temporal
lobe. Consequently, a regional onset is not a poor prog-

nostic sign unless there is other evidence that this repre-

sents propagation from an extratemporal or contralat-
eral epileptogenic region. The finding of a regional onset,

however, should prompt more careful attention to this

possibility. The pattern of ictal propagation also pro-

vides clues to the site of seizure generation. In particular,

slow spread to contralateral limbic structures is typical of
mesial temporal seizures, while rapid contralateral
spread suggests a neocortical or extratemporal site of on-
set (153). Frontal depth or strip electrodes are useful not
only to rule out a frontal onset, but to demonstrate the

delayed ipsilateral frontal projection typical of mesial
temporal seizures (155). The differentiation between pri-
mary and propagated ictal discharges remains a prob-
lem, and sampling errors from the necessarily limited
electrode array can result in false localization.

In our experience, SEEG-recorded ictal data are still

the most reliable indicators of the location of the epilep-
togenic region, but confirmatory evidence of focal dys-
function is also sought during the phase 2 evaluation.
Additional functional information can be obtained by
studies that take advantage of the use of depth electrodes.
Whereas focal nonepileptiform abnormalities of base-
line rhythms are rarely seen during scalp EEG recordings
in our patients, there is often localized slowing or attenu-
ation of normal rhythmic activity recorded from intra-
cranial electrodes. Attenuation of normal SEEG-re-
cordcd faster rhythms is most reliably observed when the
placement of relatively equidistant multiple depth elec-

trodes is bilaterally symmetrical, and chain-linkage

montages are used (Fig. 9). Consistent attenuation of

THE EPILEPSIES / 339

normal rhythmic activity at most, or all, mesial temporal
depth electrodes on one side indicates a functional dis-
turbance that correlates well with the presence of a lesion
(23). Attenuation of barbiturate-induced fast activity in
one temporal lobe is much better revealed when intrave-
nous thiopental is given during SEEG recording than
during scalp and sphenoidal EEG, as described earlier.

Unilaterally attenuated SEEG-recorded thiopental-in-

duced fast activity also correlates well with the presence
of a lesion (23,132). Thiopental-induced interictal SEEG
spikes, like spontaneous spikes, are not reliably localiz-
ing when recorded from the temporal depth.

Electrical stimulation has been used extraoperatively

and intraoperatively to produce seizures as a means of
localizing a potential epileptogenic zone; however, local-
ization obtained from electrically induced events (as
with convulsant drug-induced seizures) may differ from
localization obtained from spontaneous events (156). De-
terminations of electrically induced afterdischarge
thresholds have been used to indicate the location of epi-
leptogenic tissue, but results are contradictory. At
UCLA, afterdischarge thresholds have been most consis-

tently elevated in the epileptogenic hippocampus, partic-

ularly when the lesion is hippocampal sclerosis (157),

while others have found a lowered afterdischarge thresh-
old to indicate epileptogenic brain tissue (158). Differ-
ences in stimulation parameters have been suggested as
one reason for these conflicting observations (158).

Intracarotid amobarbital testing is always done as the

last study of phase 2, even if this test was carried out
during phase 1, to be certain that no significant impair-

ment of memory function has been produced in the con-

tralateral temporal lobe as a result of electrode implanta-

tion and/or stimulation.

Subdural Grid Evaluations

From extensive experience with temporal limbic epi-

lepsy, we have learned that the highest degree of surgical

FIG. 9. Direct (hardwire) SEEG record-

ing demonstrates attenuation of nor-

mal rhythmic fast activity in the right
amygdala, hippocampal pes, and
gyrus. Abbreviations as in Figure 8,
except P, hippocampal pes. Calibra-
tion 1 sec, 1,000 /j.V. Patient had me-
sial temporal sclerosis on the right.
(From reference 99, with permission.)

340

CHAPTER 15

success is achieved when there is preoperative demonstra-
tion I MR. CT. SPECT, PET) of a pathological substrate,

proof of epileptogenesis in this same region, and com-

pleteness of the operation with postoperative pathology

found in the specimen. Similarly, in neocortical epi-
lepsy, it has long been known that surgical outcome is
best when a specific lesion can be demonstrated preoper-
atively. When extratemporal localization is obtained by
scalp EEG techniques alone, in the absence of a lesion, it
is too often incorrect. Furthermore, the absence of a
pathological substrate in the postoperative specimen will

correlate with a poor outcome.

Traditional methods elaborated by Penfield and his

colleagues utilized intraoperative electrocorticography
to identify interictal spiking discharges and direct bipo-
lar electrical stimulation of the brain to demonstrate the

epileptogenic cortex and functional regions acutely in

the operating room (159). Talairach and colleagues dem-
onstrated the irritative cortex, lesional cortex, and epilep-
tic cortex using depth electrodes (14). However, the num-

ber of electrodes that can be used is limited. These

regions can now be easily denned using implanted large
subdural grids. Since these electrodes cannot be moved

after implantation, a large array is necessary and sub-

dural strip electrodes are inadequate for this purpose.
The opportunity provided by implantation enlarges the
scope of the investigation. Children and adults who for
various reasons cannot tolerate a prolonged operative
procedure under local anesthesia can now be comfort-
ably evaluated (160,161).

In addition to localizing interictal and ictal epilepti-

form discharges using telemetry monitoring techniques

identical to those of depth electrode recordings, the ex-

tent of the functionally inactive region can be tested by
electrical stimulation, evoked potentials, and EEG back-
ground activity (Fig. 10). The functionally active cortical
area may be found to be displaced by the pathology. The
specific procedures of functional mapping using chronic

subdural electrode grids are dealt with in detail elsewhere

(18,148,162). Both cortical stimulation and event-re-

lated evoked potentials are utilized to localize essential

cortical regions. The parameters for cortical stimulation
are selected to avoid tissue damage. No simple rules exist
for safe parameters for functional mapping by cortical
stimulation. The specific parameters that are safe vary
with the specific electrode size and circuit, and must be
calculated by the physician performing the stimulations
(163). We define essential cortex as that tissue that must

be spared to avoid gross neurological deficit in sensori-

motor function and language. We assume that if careful

neurophysiologic assessment were performed, most, if
not all. brain tissue would be eloquent, and some measur-
able deficits would be identified after most focal exci-
sions of brain tissue. As is done with those patients who
undergo depth electrodes, the patient is informed that to

treat the seizure (a global positive deficit), he or she
usually must accept a selective deficit (a limited negative

deficit). Functional mapping is designed to localize cor-
tex that is essential to avoid deficits in activities of daily
living such as hand function and language. As many rele-
vant functions are tested at a site as feasible within the
time limitations and tolerance of the patient. Functional
mapping usually takes about a week to perform and re-
quires much patient cooperation. Not all patients are
capable of tolerating this procedure.

In the preceding era of epilepsy surgery, any interven-

tion into the primary cortices was generally avoided.
With increased confidence in cortical mapping, opera-
tions now often involve these primary cortical regions.
However, in our opinion it is not sufficient to remove
lesions alone; the resection must also include the epilep-
togenic cortex. The definition of epileptogenic cortex by
means of interictal epileptiform discharges and record-
ing of the ictal activity is still under development. In
some cases, focal ictal discharges have been quite limited
in extent and the subdural grid evaluations have allowed
less-than-lobar resection to be surgically successful and
with less than the expected morbidity.

Indications for Further Procedures

Unlike phase 1, where a specific protocol has been

established at UCLA for selection of surgical candidates,
the decision to carry out a resection after phase 2 is not
based on firm criteria. Ideally, all seizures should origi-
nate in one area of the brain and confirmatory tests
should reveal focal dysfunction in the same area. After
grid recording, tailored resections are determined pri-
marily by the pattern of ictal onset and early spread, and
designed to avoid essential cortical tissue. With SEEG
recording, a few complex partial seizures originating con-

tralateral to the presumed epileptogenic lesion (espe-

cially if these seizures are atypical and/or occur when
anticonvulsant medications have been significantly low-
ered) are not considered an absolute contraindication to
surgery, since patients with such findings often do well
postoperatively (126). In our experience, when SEEG-
recorded ictal onsets have been focal, there is rarely, if
ever, conflicting evidence of focal dysfunction elsewhere.
However, in some patients, a regional SEEG-recorded

ictal onset has been localized to one temporal lobe but
confirmatory tests suggest the focus may lie in part, or
entirely, outside the standard resection. In these cases,

particularly if functional mapping of primary cortex is

also necessary, a second phase 2 with subdural grid elec-

trodes or intraoperative corticography may be recom-

mended. When the time for ictal spread to contralateral.
or extratemporal structures is less than a second, or ictal
onsets are inconsistent or appear only after clinical signs

and symptoms, focal functional deficits are used to sug-

gest other epileptogenic regions that might justify a sec-
ond phase 2 procedure with subdural grids. When ictal
onsets are nonlocalizing, there is no confirmatory focal
dysfunction, and there is no additional evidence to sug-

THE EPILEPSIES / 341

FIG. 10. Focal seizure pattern from left frontal lobe. (A) Anteroposterior skull x-ray outline shows coro-
nal placement of electrodes over the left lateral convexity and shows the location of focal seizure onset

(heavy circles) in the lateral inferior frontal region. (B) Lateral skull x-ray outline shows that the zone of

seizure onset is near the speech cortex. Patient had simple partial seizure of forced thought and speech
arrest followed by complex partial seizure with ictal vocalization. (C) Electrographic seizure recording
shows focal onset of low-amplitude fast activity and sharp wave (arrows), followed by sustained high-
amplitude fast activity in the left lateral inferior frontal lobe near Broca's area. Previous depth electrode
evaluation documented seizure onset in the left lateral frontal lobe with subsequent spread to mesial
limbic structures after 1 5 to 20 seconds. Left frontal resection included most of the seizure zone,
extended up to Broca's area, and gave significant seizure reduction. Calibration 100 nV, 1 sec. (From
reference 148, with permission.)

gest specific alternatives to the areas already explored,

surgery cannot be recommended. Surgery is not per-

formed when SEEG-recorded seizures appear to origi-
nate with equal frequency from either side of the brain,
or when subdural grid-recorded seizures originate en-

tirely within primary cortex that can not be removed.

OPERATIVE PROCEDURES

Electrocorticography

In some centers intraoperative ECoG is performed

routinely under local anesthesia f62.63.120

the extent of resection is determined on the basis of in-

terictal ECoG findings. Since intraoperative ECoG re-
cordings are limited to the area of craniotomy, they can-

not be used to localize an epileptogenic region, but

rather are used to define better the limits of epileptogenic

tissue already localized by other techniques. This proce-

dure may be extremely helpful for certain neocortical

lesions; however, reliable localization of a limbic epilep-

togenic lesion on the basis of the complex interictal epi-
leptiform discharges encountered in the temporal lobe is

much more difficult, if not impossible (62). In fact, inter-

ictal spikes recorded from depth electrodes inserted at
surgery into the hippocampus and amygdala appear to

with QhcAn^f r»f r»athrvlrvmV ^Vionrroc u/Kila *»i-*i

342 CHAPTER 15

leptiform discharges are not readily recorded from these
structures when hippocampal sclerosis is present (45).

In addition to mapping the distribution of interictal

spike discharges and other spontaneous abnormal activ-

ity, imraoperative recording techniques are useful for de-
fining areas of cortical dysfunction demonstrated by lo-

calized attenuation of barbiturate fast activity induced
by intravenous thiopental. Evoked potential and stimula-
tion techniques are also used to identify primary motor,
sensory, and language cortex when suprasylvian resec-
tions are planned. Intraoperative cortical stimulation
can occasionally induce the habitual aura or behavioral
seizure; however, this should not be considered defini-
tive evidence that the stimulated site is the primary epi-
leptogenic region. Stimulation of distant, or even contra-
lateral, structures having afferent input into the primary

epileptogenic zone can induce an habitual seizure (45).

Nonetheless, valuable information can be determined
from intraoperative electrophysiological studies, and
ECoG procedures remain an important part of the surgi-

cal evaluation for some patients with partial epilepsy.

At UCLA, questions concerning older children and

adults that arise during phase 1 are usually answered by a

phase 2 evaluation in lieu of ECoG. When a standard en

bloc anterior temporal lobectomy is performed, it is

based on data acquired during presurgical evaluation;
intraoperative electrocorticography is rarely necessary.

Similarly, the presurgical evaluation for tailored resec-

tions usually involves chronic subdural grid recording to
delineate the epileptogenic region and extraoperative

functional mapping to identify essential primary cortex,

so that all necessary information for determining the lo-

cation and extent of the resection is derived prior to
operation. Intraoperative ECoG is commonly per-

formed for resections in infants and small children, how-

ever, where localization is obtained primarily with inter-
ictal and ictal scalp EEG recordings and FDG-PET, but
chronic intracranial evaluation is not done. Occasion-
ally, intraoperative ECoG is also useful in older children
and adults to resolve specific problems that arise during
phase 2 presurgical evaluation.

Operative Techniques

Temporal Lobe Resection

Temporal lobe resection is the most frequently per-

formed surgical procedure in the treatment of partial
epilepsies. Variations in techniques and extent of resec-
tion have been reviewed by Crandall (27). We will pre-
sent here four techniques of temporal resection.

Standard En Bloc Resection

The Falconer-Crandall resection (27,28) of the ante-

rior temporal lobe uses sharp dissection cleaving anatom-
ical structures of the temporal lobe (Fig. 11). This

method has the following advantages: it is performed

under general anesthesia; it allows fixation of the head
and the use of the surgical microscope; it permits quanti-
fication of the resection for interindividual analysis of
outcome; and it produces a surgical specimen suitable
for further neurophysiological and neuropathological

studies.

The patient is placed in a supine position with the

head at a 45-degree angle away from the side of surgery,
fixed using a three-pin head clamp. The vertex of the

head is tilted slightly downward. The head is slightly
higher than the chest with the table flexed. Steroids, anti-

5 c m

5 c m

FIG- 1 1 - Falconer en Woe anterior temporal lobectomy. (A) Arteries at risk are the anterior choroidal
artery and the posterior cerebral artery and its branches. The resection of lesser extent refers to the
nondominant lobe. (B) Coronal view of resection. (From reference 27, with permission.)

biotics, and diuretics are used. A bolster is placed under
the ipsilateral shoulder. A question-mark incision is
used, starting at the zygomatic arch a few millimeters
anterior to the ear, curved superiorly and posteriorly
above the ear, then directed toward the midline, curving
anteriorly 4 to 5 cm from the midline to end in the fron-
tal area within the hairline. A scalp flap is raised anteri-
orly until the frontal process of the zygoma is palpable.
To avoid injury to the frontalis branch of the facial

nerve, the skin is not elevated along the zygoma. The

temporalis muscle is incised longitudinally and reflected
anteriorly and posteriorly and held with fish-hooks. A
craniotomy is then created using a high-speed drill and
craniotome. Additional bone is removed from the lateral

wall of the middle fossa to obtain adequate exposure of

the anterior temporal area. Antibiotic-soaked sponges
are placed at the perimetry of the craniotomy, and gloves
are washed to remove blood and bone dust to prevent
"aseptic meningitis." The dura matter is incised in a U--

shaped curve hinged just above the location of the syl-

vian fissure.

The cortical incision is measured on the middle tem-

poral gyrus from the temporal tip at 6 cm on the non-

dominant and 4.5 to 5 cm on the dominant side. The

posterior incision is obliquely downward at about 45 de-
grees to spare the primary auditory cortex of the superior
temporal gyrus. This incision is continued anteriorly
within 5 mm from the sylvian fissure, paralleling the
curve of the sphenoid ridge until the floor of the middle
fossa is reached. The pia and bridging vessels are coagu-

lated with bipolar forceps and sharply incised with mi-
croscissors. Dissection is carried by subpial aspiration
along the anterior portion of the superior gyrus, preserv-
ing the arachnoid layer of the sylvian cistern and middle
cerebral artery branches. Cortex is progressively lifted

until the limen insulae is uncovered above the insula.

The posterior incision is deepened vertically with bipolar
coagulation and suction into the temporal stem and infe-
riorly until the floor of the middle fossa is reached. The
dissection is carried superiorly until the ependyma of the
temporal horn is opened, when a gush of cerebrospinal
fluid occurs. The surgical microscope is brought over the
surgical field, and self-retaining retractors are positioned
to elevate the lateral cortex. With microsurgical instru-
ments, the white matter over the roof of the temporal
horn is thinned anteriorly until the tip of the ventricle is
reached. This allows exposure of the lateral hump of the

glistening white hippocampus. The incision is carried
through the amygdala anteriorly until the original ante-
rior incision is reached. No incision is made medial to
the choroid plexus, as this is the location of the optic
tract. The tela choroidea and fimbria-fornix are de-

tached at the choroidal fissure with fine dissection. Great
care is taken to preserve branches from the anterior cho-

roidal artery running close to the optic tract and cerebral
peduncle. The hippocampus is transected in a coronal
direction 3 to 3.5 cm behind the tip of the pes hippo-

THE EPILEPSIES / 343

campi at the level of the lateral geniculate body. The
ambiens cistern is entered and small perforating vessels
(the Ammon's horn arteries) and arachnoid bridges are

sharply divided at the hippocampal sulcus. The posterior

cerebral artery, the anterior choroidal artery and the
third and fourth cranial nerves can be identified and are
preserved. The uncus is then lifted from its piai bed. leav-

ing the ambient cistern. The posterior transection

through the parahippocampal gyrus is continued until
the posterior incision has reached the floor of the middle
fossa. The specimen is removed en bloc and sent for
neuropathological and neurophysiological studies (Fig.

12). The surgical cavity is inspected and is completed.

Closure is accomplished in the usual fashion, with the
bone stitched back in place and the muscle and skin

closed in two layers.

Tailored Resection

In a tailored resection, the lateral or mesial extent of

temporal resection varies according to the presence of
interictal abnormalities on the ECoG. This type of resec-
tion is usually performed under local anesthesia to allow
cortical mapping of the sensorimotor area and speech

cortices, if operating on the dominant hemisphere. The

temporal structures are removed in two stages: a lateral

neocortical resection, followed by aspiration-suction of

the mesial structures. This technique has the advantage

of obtaining a cortical map of essential cortex as defined
by acute monopolor or bipolar stimulation, which may
facilitate resection of a larger neocortical area or presum-
ably reduce the severity of postoperative neuropsycholog-
ical deficits. The variability of temporal neocortical in-

terictal epileptiform activity during the ECoG, and the
difficulty in distinguishing primary from projected spike

activity in the frontal lobe remain problems for this tech-
nique.

FIG. 12. The hippocampus is detached by an incision along
the fimbria and through the amygdala. (From reference 99,

with permission.)

344 / CHAPTER 15

Amygdalohippocampectomy

With improvement in localizing seizure onset to dis-

crete areas of the temporal lobe in selected patients, Ya-

sargil introduced the transsylvian approach to resect the

mesial basal temporal lobe (120). Selective removal of

these structures using transventricular and transcortical

approaches was previously described by Niemeyer (165).

The goal is selective microscopic removal of the lateral
amygdala, the anterior hippocampus, and the parahip-
pocampal gyrus with preservation of the lateral temporal
structures. This procedure is reported to cause less func-

tional deficits with a similar outcome when compared to

standard lobectomies in selected patients (166). The
transsylvian approach is made through an interfascial
pterional craniotomy, placed slightly posteriorly, expos-
ing the anterior third of the superior temporal gyrus. The
inferior sylvian fissure is opened, and the lateral Ml seg-
ment of the middle cerebral artery is followed until the

basal surface of the superior temporal gyrus is reached,
between the origin of the temporo-polar and anterior
temporal arteries. The limen insulae is opened for a dis-
tance of 2 cm, and dissection is carried until the horn of

the ventricle is reached. The amygdala is dissected with a

microrongeur for histologic studies and the uncus is re-

moved subpially; the hippocampus is dissected circum-

ferentially, after identifying the posterior communicat-
ing artery, oculomotor nerve, optic tract, and anterior
choroidal artery. The overall mesial resection covers a
length of 4 cm, a width of 1.5 cm, and a depth of 2 cm.
This microsurgical procedure usually follows SEEG anal-

ysis of the patient's typical seizures.

Posterior Hippocampal Resection

Depth electrode recordings have been reported that

suggest that almost 20 percent of complex partial sei-
zures arise from the hippocampus beyond the posterior
limit of standard anterior temporal lobectomies (167).
Surgical access was modified by Spencer to resect docu-
mented epileptogenic posterior hippocampus through a
small resection of the temporal pole (168). The same

technique can be utilized when space-occupying lesions
are posteriorly placed within the hippocampus or hippo-
campal gyrus. Pathological demonstration of neuronal
loss and gliosis in the posterior hippocampal specimen is
correlated with a good surgical outcome.

Other Limited Resections

Selective corticectomies are performed in areas en-

compassing both interictal and ictal activity and may

occasionally involve portions of more than one lobe.

Neocortical resections following subdural grid evalua-
tions are usually performed at the time the subdural grid

is removed. Although this technique allows the bound-
aries of the resection to be determined preoperatively,

results of cortical stimulation can be confirmed with in-

traoperative bipolar stimulation under local anesthesia.
Many centers still perform neocortical resections using
intraoperative functional mapping alone (121). Exci-
sions of limited areas of sensorimotor cortex can be
made with minimal deficits, but dissections must respect
ascending arteries by skeletonizing these structures
(169). Care must also be taken not to extend the resec-
tion beyond the insula or deep into the white matter in
order to preserve long fiber tracts. Speech mapping al-

lows resection of peri-sylvian cortex in patients with evi-

dence of early ictal interference with speech. We prefer

to preserve Broca's area, even with evidence of ictal on-

set involving this region. Due to variability in the size
and location of Wernicke's area, functional mapping
permits more extensive dominant posterior temporal re-
section in some patients. Multiple subpial transections
of essential cortex, such as sensorimotor and language
areas, have been reported to interrupt seizure initiation
without inducing unacceptable neurological deficits

(170), but we have not yet had experience with this tech-
nique. Small resections within the occipital lobe can pre-

serve visual function with excellent control of the sei-
zure. Stereotactic ablations such as amygdalotomy and
Field of Forel-otomy are no longer recommended
(171,172).

Hemispherectomy

The initial technique of cerebral hemispherectomy,

described by Krynauw (173), involves resection of a
complete hemisphere, leaving in place the thalamus, ba-
sal ganglia, and brainstem on the ipsilateral side. After a
large hemicraniotomy and dural opening, distal
branches from the anterior cerebral, middle cerebral,
and posterior cerebral arteries are divided, leaving proxi-
mal vascularization to the basal ganglia intact. The cor-
pus callosum is divided completely, and the lateral ven-

tricle is entered. The caudate nucleus is identified, and a
plane of dissection is carried above the caudate from an-

terior to posterior down the atrium at the temporo-occi-

pital junction. The veins that drain into the sagittal sinus
and into the vein of Galen are taken. Following the lat-
eral ventricle into the temporal horn, the temporal lobe
is dissected in a fashion similar to the en bloc resection.
The insula is also taken. Because of complications ini-
tially described with this technique, including delayed

hemosiderosis and later hemorrhage and death, Ras-

mussen modified the complete hemispherectomy to a

subtotal hemispherectomy, leaving the disconnected

frontal and occipital poles in the surgical cavity
(174,175). The insula may or may not be removed ac-
cording to the intraoperative electrocorticogram. An ad-

THE EPILEPSIES / 345

ditional modification to prevent delayed bleeding con-

sists of plication of the dura, as described by Adams
(176). Other centers, such as UCLA, prefer to shunt the

surgical cavity into the peritoneal space, decreasing the

fibrinogen and blood products inside the surgical cavity

and preventing the formation of subdural membranes
(177). Multilobar resection may also be appropriate

when large parts of the cortex appear to be abnormal but

some ipsilateral areas can be spared (178).

Corpus Callosotomy

Most centers performing corpus callosotomy divide

the structure in two stages (179). Initially, the anterior
two-thirds is sectioned, including the genu, followed
later by posterior division of the splenium, if seizures
persist. The technique necessitates a vertex frontal crani-
otomy, usually over the nondominant hemisphere, ex-
posing the anterior interhemispheric fissure and preserv-

ing the large draining veins to the sagittal sinus. Vascular

anatomy is best defined presurgically with'a cerebral an-
giogram. Gentle lateral retraction of the frontal lobe al-
lows the identification of the cingulate gyrus and, inferi-

orly, of the pericallosal arteries. With magnification, the

white reflection of the corpus callosum can be easily seen

between the two pericallosal arteries. Care must be taken
not to confuse the callosomarginal artery with a perical-

losal artery and proceed with the dissection into the cin-

gulate gyrus. Division of the anterior two-thirds of the

corpus callosum is made with an ultrasonic aspirator

(CUSA) or with a small bore microsuction and fine bipo-
lar forceps. The ependyma of the roof of the third ventri-

cle can be identified and should be preserved to avoid a

possible ependymitis. The dissection is carried anteriorly
into the genu of the corpus callosum and stopped once
the rostrum is reached. Division of the anterior commis-

sure, fornix, or massa intermedia of the thalamus, as
originally described by Van Wagenen and Herren (com-
plete commissurotomy) (180), is no longer performed. If
seizures persist, a second stage callosotomy can be done,

extending the section into the splenium of the corpus
callosum.

SPECIAL CONSIDERATIONS FOR
THE DEVELOPING BRAIN

The obvious benefits of early intervention have made

pediatric epilepsy surgery an area of increasing interest
and rapid expansion. The approach to the surgical treat-
ment of intractable partial epilepsy in adults applies in
many respects equally to children with similar partial

epileptic disorders. Nevertheless, some uniquely pediat-
ric epileptic syndromes are also potentially treatable by

surgery. Moreover, considerations of brain development

and plasticity add a dimension to pediatric epilepsy sur-

gery that is not present with respect to adult patients
(137). In this section will be summarized the major ways
in which the approach to surgical management needs to
be adapted to the developing brain. The types of surgery
most commonly performed also differ: anterior tem-

poral lobectomy for complex partial seizures is the most

common form of epilepsy surgery in adults, whereas ex-

tratemporal excision, multilobar resection, hemispher-
ectomy, and corpus callosum section are the appropriate
treatments in a much higher proportion of pediatric

cases.

Intractability

The amount of time necessary to determine intracta-

bility is typically much shorter in pediatric than adult
surgical candidates. For the latter, it usually takes several
years to have exhausted all appropriate medical trials. In
contrast, there are far fewer antiepileptic drugs available
for use in young children, particularly infants; moreover,
because their seizures are typically much more frequent,
less time is required to determine whether a given change

in management has had any effect.

Certain etiologies of frequent seizures imply intracta-

bility almost by their very nature; for example, congeni-

tal brain malformations (181), Sturge-Weber syndrome

with early-onset seizures (182), or Rasmussen's encepha-

litis (183). If the seizures in such cases do not respond (or

respond only temporarily) to two or three of the most

appropriate antiepileptic drugs, it is extremely unlikely
that they will respond to any medical regimen or will
spontaneously remit. Cases of West syndrome unre-
sponsive to ACTH, prednisone, and/or selected antiepi-

leptic drugs like nitrazepam, are similarly unlikely to un-

dergo spontaneous remission, even though the infantile
spasms will change to some other seizure type as the
child grows (184). In rare cases, the unlikelihood of re-
mission can be determined even as early as the neonatal
period as, for example, with persistently unifocal, cryp-
togenic status epilepticus, which probably begins in utero
and, in our experience, has been uniformly due to focal
cortical dysplasia (87).

Most young children who are potential surgical candi-

dates have many seizures per week or even per day, and
there is little question regarding the designation of in-
tractable. Some children who have only occasional sei-
zures, however, might be considered potential surgical
candidates because of the deleterious effects of medica-
tions and interictal electrophysiological disturbances on
their development, particularly when there is a high like-
lihood of later breakthrough of more frequent seizures.
Drug toxicity is typically much more evident in adults

than in children. A child of average intelligence who is

toxic on antiepileptic medication is often mistakenly

considered to be dull (185). In other cases, side effects of

346

CHAPTER 15

medications can produce adverse personality changes
that seriously stress family dynamics and reduce the self-

esteem of the child (186). Thus, even though drug toxic-

ity per se may be readily reversible, some consequences
of its chronic presence could be permanent. To the ex-

tent that resective surgery could permit the elimination
or significant reduction of medication during these intel-
lectually and emotionally formative years, it might even-
tually be considered even if seizure frequency per se
might not be great enough to suggest a need for surgical
intervention.

Timing of Surgery

Considerations related to development and plasticity

render surgery more urgent in children than in adults,
given surgical candidacy. The extent to which frequent
seizures might damage the developing brain remains

highly controversial; nevertheless, there is considerable

evidence that molding of interneuronal connections is
profoundly influenced by local electrical activity (187),
interactions with other neurophysiological subsystems
(188), and dynamic interaction with the environment
(189). That repeated brief seizures do not cause neuronal

damage, in the pathologist's sense of hypoxic/ischemic
changes and neuronal loss, therefore in no way implies

that they are not harmful to the developing brain.

Frequent interictal epileptiform discharges might also

underlie the deleterious effects of what Penfield aptly
called nociferous cortex (190). These discharges are
known to cause transient disruption of cortical function-
ing not only at the site of the spike but at surrounding
and distant sites as well, through projected inhibitory
postsynaptic potentials (191) and antidromic "backfir-

ing" (192), both in experimental animals and in humans

(193). In the developing rabbit brain, interictal dis-
charges in the absence of seizures have been shown to
lead to cytoarchitectural changes in spatially distant but
functionally related areas (194). Such mechanisms could
contribute to the gradual intellectual and psychosocial
decline common in children with catastrophic epilepsy
(195), suggesting an argument for performing the sur-
gery as early in life as possible.

The extent to which antiepileptic drug toxicity can ad-

versely affect the developing brain directly, apart from

the secondary psychosocial consequences of their side
effects, has not been thoroughly studied. Although the
literature is conflicting, there are a sufficient number of
reports that suggest deleterious effects to warrant con-
cern (196-198) and to constitute a minor additional mo-
tive for favoring a potentially curative procedure over

the chronic administration of multiple, high-dose anti-
epileptic medications.

Although controversies continue over whether the

kindling phenomenon in animals is relevant to humans

(199,200), the risk of secondary epileptogenesis (201) re-
mains a concern for children with frequent recurrent sei-
zures. That this process is potentially reversible is sug-
gested by the fact that seizures and EEG spikes can often
disappear when children with bilateral or multifocal inde-
pendent epileptiform discharges, bilateral independent
ictal onsets, hypsarrhythmia or modified hypsarrhyth-
mia, or generalized slow spike waves undergo focal resec-

tion or hemispherectomy based on evidence of local-
ized or lateralized abnormalities on brain imaging
studies, EEG telemetry recorded ictal onsets, and/or
ECoG(137).

Experience with naturally occurring brain lesions and

with therapeutic hemispherectomy in humans indicates

that language functions will shift to the right hemisphere

following damage to the left early in life (202,203). Simi-
larly, children or adults with hemiplegia from early in-
fancy are typically able to walk quite well and can use the
paretic arm for gross, proximal movements and as a

helper for the normal arm (204,205), in marked contrast

to the dense hemiplegia following massive hemispheric
infarction in adulthood. Consequently, the earlier the
surgical intervention, the less the resultant deficit.

For all these reasons, the dynamic nature of neurode-

velopment and that of the epileptic process itself intro-
duce a particular urgency in the determination of medi-
cal intractability among children. There must be a
prudent compromise between letting sufficient time pass

to determine intractability and operating early enough to
maximize developmental potential through brain plastic-
ity. But once it becomes clinically evident that a young
child is suffering from one of the devastating epileptic
syndromes and that cortical resection offers a significant
chance of benefit, the earlier the operation is performed,
the better.

Identification of the Epileptogenic Zone

Some children with seizure disorders presently classi-

fied as secondary generalized epilepsies can benefit
greatly from resective surgery. Although the West and
Lennox-Gastaut syndromes, even those subclassified as
cryptogenic, have traditionally been thought to indicate
diffuse cerebral abnormalities (55), perhaps as many as a

third of the cases are actually due to focal or unilateral
pathology (206-209) and could respond favorably to fo-
cal resection or hemispherectomy (138,210). In such
cases, localization of the epileptogenic region is accom-
plished by the convergence, or at least noncontradiction,
of complementary types of evidence from structural
imaging studies, tests of epileptic excitability, and tests of

cortical dysfunction. Even when the ictal onsets are diffi-
cult to localize or lateralize and the epileptiform dis-

charges have a multifocal or widespread distribution, a
safely resectable lesion can be strongly suggested by dem-

onstration of a substantial focal functional deficit and a
structural lesion. In this instance, intraoperative ECoG
may be helpful for multilobar resections but is superflu-
ous if a complete hemispherectomy is planned (211).
Chronic intracranial electrode recordings are reserved
for those cases with lack of correspondence among the
various structural and functional parameters, or in
which the anticipated resection borders on essential
primary cortex, requiring careful functional map-

ping (161).

Indicators of focal cortical dysfunction are important

for two reasons: first, it is very likely that the epilepto-
genic region is anatomically identical to, or approxi-
mates, a zone of markedly dysfunctional cortex; and sec-

ond, the excision of such an area will not introduce a

significant new neurological deficit. Because the neuro-
logical examination in young children is much less local-
izing than in adults and large portions of cortex are as yet
clinically silent, it is important to assess cortical function
in as many other ways as possible, including interictal
EEG (with particular attention to nonepileptiform ab-
normalities), sodium thiopental activation, median
nerve somatosensory and visual evoked potentials, intra-
carotid amobarbital injection (Wada test) for older chil-

dren in whom the lateralization of memory and lan-
guage can be tested, and local cerebral metabolic
patterns on interictal FDG-PET scan. If hemispherec-
tomy is contemplated, these tests are also important for
determining the relative functional integrity of the other
hemisphere.

Of all these tests, the most useful in this group of pa-

tients is by far the FDG-PET scan, which can reveal well-
demarcated areas of marked dysfunction, even in the
context of normal CT and MRI studies (87,139,208).
These focal FDG-PET abnormalities have corresponded
closely with areas of dysfunction defined subsequently
by intraoperative electrocorticography (211) and with
focal cortical dysplasia on pathological examination of

resected tissue. FDG-PET and intraoperative electrocor-
ticography are now Used to guide multilobar resections
in small children with catastrophic secondary general-
ized epilepsies, particularly infantile spasms, even when
epileptiform abnormalities are not localizing (208). Sur-
gical resection in these children not only abolishes epilep-

tic seizures, but reverses developmental delay, which is

the most pressing criterion for considering surgical inter-
vention in this situation.

OUTCOME

Complications

A detailed analysis of surgical complications following

diagnostic or therapeutic procedures in major centers
performing epilepsy surgery has been made by Van

Buren (212) and will be briefly reviewed in this section.

THE EPILEPSIES / 347

Complications of Diagnostic Procedures

Invasive monitoring by stereotactic depth electrode

implantation carries a mortality rate of approximately 1
percent and a morbidity rate of approximately 4 percent

(212). No major complications have yet occurred using
magnetic resonance guidance associated with stereotac-
tic angiography (145). Transient hemiparesis has been
described with cerebral angiography, but the risk of ma-

jor complications, such as permanent neurological defi-

cit or death, is reported to be only 0.1 to 0.3 percent
(213). The use of stereotactic angiography has decreased
the number of hemorrhagic complications of depth elec-
trode implantations in most centers. Infectious compli-

cations of chronic depth electrode recording are reported
to vary between 1 and 5 percent. These consist of cere-

bral abscesses or meningitis and are more likely to occur
with increasing duration of the recording period. The

value of prophylactic antibiotics has not been estab-

lished. Electrodes should be disposable, to prevent any

possibility of transmission of slow virus such as Creutz-

feldt-Jacob disease (214).

Epidural grid recording as described by Goldring and

Gregorie did not produce any mortality in 100 patients

(215). They did report one scalp infection and one case
of aseptic necrosis of the bone flap in this series. Sub-
dural grid implantation for chronic recording can pro-
duce a transient rise in intracranial pressure (ICP), pre-
sumably from cerebral edema, in the first 48 hours. We
now use ICP monitoring concomitantly with steroids for

the first three days after electrode implantation. Acute or

delayed hemorrahgic complications occur in 0.5 percent
of cases. Placement of subdural strips is also associated
with hemorrhagic complications in 0.5 percent of cases
(212). Foreign body reaction to the grid has also been
described (212), and we have seen acute granulomatous
meningitis in a few patients of our series. Decreasing
intraoperative manipulation with the subdural grid and
copiously irrigating the subarachnoid space before im-
plantation appear to prevent this reaction.

Complications ofResective Procedures

Localized Cortical Resection

Aseptic meningitis presenting with fever and neck ri-

gidity is reported to occur in approximately 15 percent of
patients who undergo cortical resection (212). Cerebro-
spinal fluid studies show an increase in white blood cells

and protein and a decrease in glucose. Repeated cultures

remain negative. This complication improves without

treatment in 2-3 weeks.

In all series of anterior temporal lobectomy the mortal-

ity rate is extremely low. Minor side effects are frequent,
however. Most frequent is a superior quadrantanopsia
opposite to the side of surgery. Fortunately, this usually

348 / CHAPTER 15

remains unnoticed by the patient. Complete homony-
mous hemianopsia can occur due either to an optic tract
injury or an infarct of the optic radiations or occipital
cortex following injury to the posterior cerebral

branches. This complication is rare in most series. Tran-
sient oculomotor or trochlear nerve palsy is also de-
scribed following temporal resection and may take a few
weeks to improve completely. Transient or permanent
hemiparesis can be caused by prolonged retraction or
vasospasm of the middle cerebral artery ("manipulation
hemiplegia") or by injury to the anterior choroidal artery
supplying the internal capsule or cerebral peduncle.
Complications from resections of the dominant hemi-
sphere include speech difficulty, dysnomia, and dyspha-
sia. These are, however, transient and occur in approxi-
mately 5 percent of cases. Severe memory deficit has also
been described rarely in all series; at-risk patients may be

identified with the intracarotid amobarbital test,

Extratemporal resections may produce neurological

deficits functionally related to the site of cortical re-
moval. No attempt to describe these in detail will be

made here, but the reader may wish to consult Van

Buren's chapter (212).

Hemispherectomy

A complete hemispherectomy initially carried a high

operative mortality rate, reaching 6.6 percent, and was
also associated with serious complications late in the

postoperative course (174,175). The complications con-

r

sisted of delayed superficial cerebral hemosiderosis lead-

ing to subdural membrane formation causing late hemor-
rhagic catastrophes. This was attributed to repeated
minor trauma to the remaining hemisphere moving
freely in the cranial space, or to residual blood products
leading to subdural membrane formation. Modification
of the complete hemispherectomy, as discussed by Ras-

mussen, was intended to decrease the amount of move-

ment within the cranial space (174,175). Adams at-

tempted to decrease the subdural space by plication of

the dura (176), but this can cause a rapid rise in intracra-

nial pressure because of the decreased reabsorption ca-

pacity of the arachnoid villi. Acute hydrocephalus is also
a major complication, attributed to granular ependymi-
tis blocking the ventricular system. Additionally, the ab-
sorption capacity of the remaining hemisphere may be

decreased, creating a degree of nonobstructive hydro-

cephalus. Shunting of the surgical cavity to the perito-
neal space appears to decrease the amount of hydroceph-
alus and subdural membrane formation by decreasing

the amount of fibrinogen and blood breakdown prod-

ucts (177).

Corpus Callosotomy

Besides surgical complications such as infection or

frontal lobe infarction from venous thrombosis, neuro-

psychological complications following callosotomy are
frequent (140) and will be described only briefly here.

Transient mutism or decrease in speech spontaneity

may occur after an anterior or a complete section of the
corpus callosum. This may be due in part to intraopera-
tive retraction over the supplementary motor area. In
some patients with mixed cerebral dominance, callosot-
omy produced permanent speech and language dysfunc-

tion (142). A posterior section of the corpus callosum
produces a sensory disconnection syndrome that is best
demonstrated by tachitoscopic studies. Postoperative
worsening of seizures in a patient with a frontal focus has

been described (216).

Seizures

Variations in surgical approaches from one center to

another have complicated attempts to make general
statements about results. However, sufficient data have
been accumulated from a large number of centers to
draw some conclusions regarding the efficacy of anterior
temporal lobectomy. In 1975, Jensen reviewed 2,282

'published cases of temporal lobectomy and reported an

interseries range of 27.8 to 61.8 percent of patients who

became seizure-free (110). Data shown in Table 1 were

obtained 10 years later from 44 epilepsy surgery centers

(46). The results for anterior temporal lobectomy were
similar to those reported by Jensen, while extratcmporal

resections were somewhat less beneficial. The best re-

sults following extratemporal surgery were obtained with

hemispherectomy and large multilobar resections, al-

though neurological deficits inevitably occur. Corpus
callosum section appears to be largely a palliative, rather
than curative, procedure. As mentioned previously,
there is evidence to suggest that surgical results for ante-

rior temporal lobectomy are better if mesial temporal

structures are routinely removed (26,113). On the other
hand, memory impairment may be more common when

lobectomy includes the hippocampal pes.

Postoperative results with respect to epileptic seizures

comprise the most important category of data for deter-
mining the therapeutic usefulness of presurgical evalua-

tion protocols and operative techniques, yet these results
are the most difficult to define and quantify. Data are
reported inconsistently in the literature. For instance,

patients are usually considered seizure-free even if auras
continue, yet persistent auras suggest that the primary
epileptogenic region was not completely removed and
only the spread has been prevented. For analysis of out-
come in terms of the patient's ability to conduct a nor-

mal life, postoperative auras are usually inconsequential;

however, in the context of attempts to understand the
mechanisms of epilepsy and its resolution, this is an im-

iportant consideration. Also, the term seizure-free does

not necessarily mean free of seizures since surgery be-
cause, from a practical point of view, a patient who has

had a few seizures in the first year or two after surgery

THE EPILEPSIES / 349

TABLE 1. Survey results: outcome with respect to epileptic seizures"

Classification

Total Patients
Total Centers
Number Seizure-free

Percent (Range)

Number Improved

Percent

Number not Improved

Percent (Range)

Hemispherectomy

88

1 7

68

77.3(0-100)

1 6
18.2

4

4.5 (0-33)

Anterior

temporal lobectomy

2,336

40

1,296

55.5 (26-80)

648

27.7

392

16.8(6-29)

Extratemporal

resection

825

32

356

43.2 (0-73)

229

27.8

240

29.1 (17-89)

Corpus callosum

section

197

16

10

5.0 {0-1 3)

140

47

23 9 (10-38

!

From reference 46, with permission.

and then becomes seizure-free is just as well-off. Al-

though some studies have lumped seizure-free and al-

most seizure-free patients together, in most cases there is
a considerable difference between the two in terms of

social rehabilitation.

The outcome classification scheme suggested by the

International League Against Epilepsy is shown in Table
2. The seizure-free and rare seizure categories are rela-

tively straightforward. However, when deciding whether

or not to perform an operation on a particular patient,

the probability of worthwhile improvement rather than
complete cure is usually the determining factor. There-
fore, in order to evaluate the literature on a specific pro-

cedure or the track record of a particular center, it is the

definition of this borderline group that should be most
carefully considered. Unfortunately, criteria for differen-
tiating patients with worthwhile improvement who con-
tinue to have some seizures from those who do not bene-

_______TABLE 2. Outcome classification"_______

Class 1 : Seizure-free"

A. Completely seizure-free since surgery

B. Aura only since surgery
C. Some seizures after sugery, but seizure-free for at

least two years

D. Atypical generalized convulsion with antiepileptic drug

withdrawal only

Class 2: Rare seizures (almost seizure-free)

A. Initially seizure-free but has rare seizures now

B. Rare seizures since surgery

C. More than rare seizures after surgery, but rare

seizures for at least two years

D. Nocturnal seizures only, which cause no disability

Class 3: Worthwhile improvement

A. Worthwhile seizure reduction

B. Prolonged seizure-free intervals amounting to greater

than half the follow-up period, but not less than two

years

Class 4: No worthwhile improvement

A. Significant seizure reduction
B. No appreciable change
C. Seizures worse_____________________

" From reference 46, with permission.

6

Excludes early postoperative seizures (first few weeks).

fit from surgery are virtually impossible to define in a

standardized, quantitative fashion and often must be de-

termined independently for each individual.

Another problem derives from the fact that patients

may change, with respect to seizures, at any time. Since

this appears to be more common during the first few
years, some investigators feel it is necessary to wait five
years after surgery before drawing any conclusions re-
garding surgical results. Our experience, and that of

others (32,46,112), suggest that changes occurring after

two years are not much more clinically significant than
those after five, and that two years is an adequate follow-
up time for assessing results. Patients should be cau-
tioned, however, that one or two seizures in the first two
years following surgery do not necessarily mean they will
not ultimately become seizure-free, nor does the absence
of seizures during the first two years guarantee that sei-

zures will never return (Figs. 13 and 14). Because out-

come status can change from year to year, in order to

compare groups of patients with different follow-up pe-
riods it is preferable to use year-by-year outcome data
(Fig. 15).

Outcome statistics for surgical treatment of epilepsy

reflect selection philosophy as much as, if not more than. ,
accuracy of selection criteria. If only the best candidates J
for surgery were chosen, most centers would maintain
close to a 100-percent success rate. However, surgery is
often offered to patients whose diagnostic evaluation in-

dicates a higher probability of a poor outcome, because
nothing else can be done and maybe it will help. These

calculated risks probably account for the 10 to 20 per-
cent of patients who do not benefit from surgery in al-
most every series. An important measure of effective-

ness, therefore, would be obtained from knowledge of

the number of patients denied surgery who might have

benefited from this procedure. Absolute data are impossi-
ble to derive, but some information is available to indi-
cate that there is improvement in this area. For instance,
in 1967 only 11 percent of patients evaluated in Fal-
coner's series were selected for surgery (11), while approx-
imately 80 percent of all patients who undergo the

UCLA inpatient evaluation receive surgery.

FIG. 13. Year-by-year outcome classifications for patients

who were classified as seizure-free for one year (A) and two
years (B) after surgery. Outcome classifications are defined in

Table 2. (From reference 46, with permission.)

FIG. 14. Year-by-year outcome classifications for patients

who were classified as having rare seizures (A) and many

seizures (B) during the first postoperative year. The latter pa-
tients are those who were classified as Class 3 and Class 4.
Outcome classifications are defined in Table 2. (From refer-

ence 46, with permission.)

Psychosocial Adaptation

Behavioral changes associated with temporal lobe sur-

gery for epilepsy are related to psychosocial factors, as
well as to relief from seizures. It is generally agreed that
personality traits are more likely to improve after success-

ful surgery than are psychoses. Depression during the
first year following surgical treatment has been reported,

but is usually transient (217,218). While long-term de-

pression may be no more prominent postoperatively
than preoperatively, the reported 5 percent incidence per

mean five years of follow-up (114) stresses the need for
more intensive studies. The published effects of surgical

intervention on psychoses have been consistent. Surgical

treatment, while helping the epilepsy, does not improve

a chronic psychotic condition, which is usually the ma-

jor handicap for the patient (114). This is not the case for

rare ictal or postictal transient psychoses that usually re-
solve when the epilepsy is cured (219).

The extent of control of seizures is a significant factor

underlying improvement in social status following surgi-

cal treatment for epilepsy (105). We found that patients
tend to be slightly more dependent upon others two

months after the operation regardless of outcome, appar-

ently due to recovery from the recent surgery (101). But
by one year after surgery, patients whose seizure fre-
quencies are significantly reduced show the expected
gains in social independence when compared to their
preoperative social level. This is reflected by the percent-
age of patients who become employed or receive educa-
tional retraining. Similar social changes are not seen in
patients whose seizures are not controlled by surgery.

At one year after surgery, interpersonal relationships

also improve for the seizure-controlled patients. This im-
provement seems to be largely attributable to increased
non-family interactions, apparently associated with

newly developed social independence. The family rela-

tionships of patients are more resistant to change; in

some cases, interpersonal family relationships have even

THE EPILEPSIES / 351

——— New Series — — — Old Series

FIG. 15. Year-by-year outcome classification for all patients
operated on at UCLA between 1961 and 1985, divided into
those operated on before 1977 (broken line) and after 1977
(solid line), when the new presurgical evaluation protocol was
introduced. This graph demonstrates that after 1977 the per-
centage of patients who were seizure-free at the end of each
postsurgical year was higher, and the percentage of patients
who were not improved was lower. Outcome classifications
are defined in Table 2. (From reference 46, with permission.)

deteriorated following seizure control. For instance, di-
vorce appears to be more common in patients who have
become seizure-free. In this situation, the marital rela-
tionship apparently has required the patient to maintain
a dependent role (101). In selected cases, family counsel-
ing has proved beneficial.

Postoperative psychosocial adaptation improves in

most patients who experience relief from, or reduction
in, epileptic seizures. Risk factors for a poor psychosocial
outcome include inadequate family support, operation

after the age of 30, and evidence of an addictive personal-
ity (104).

Patients with improved seizure control show higher

scores on intelligence tests as early as one to two months
after surgery, and scores continue to increase for at least
one year. An average 10 point increase in IQ scores in the

first year is of particular significance, since all patients

are maintained during this time on preoperative anti-

convulsant medication levels. Intellectual changes seen

at this time, therefore, cannot be attributed to reduction
of medication levels, but probably reflect a general im-

provement in adaptive abilities heretofore depressed by

an active epileptic focus. Increases in intellectual scores
were not found postoperatively in patients whose sei-
zures were not controlled, nor in evaluated but un-
operated epileptic patients tested at comparable pe-
riods (101).

Selective memory deficits have been well documented

following surgical excision of either the left or right tem-
poral lobe. Difficulties in learning verbal material, pre-

sented either aurally or visually, have been associated

with the language-dominant temporal lobe. Difficulties
in learning material not easily verbalized have been asso-
ciated with the nondominant, temporal lobe (220,221).
The degree of memory deficit has been related to the
extent of hippocampus removed (107), and to the extent
of intactness of the opposite hippocampus (103). Recent
evidence indicates that these selective learning deficien-

cies occur whether or not the seizures were controlled by

the surgery (101). However, patients whose seizures are
surgically controlled, while demonstrating the selective
memory deficit associated with temporal lobe removal,
may concurrently show an increase in memory skills
normally associated with the contralateral intact tem-
poral lobe (101,222). This phenomenon is undoubtedly

related to the same process responsible for postoperative

increases in intellectual skills.

In Western societies a deficiency in verbal memory,

which is associated with dominant temporal lobe resec-
tion, is usually a greater handicap than a deficit in non-
verbal memory, associated with nondominant temporal
lobe resection. The potential effects of induced memory
deficits on the lifestyles of surgical candidates should be
carefully considered prior to surgery. It is possible that
for certain patients in selected occupations an induced
verbal memory deficit may be more devastating than an

uncontrolled seizure disorder. In our experience, the life-
styles of most patients considered for language-domi-
nant temporal lobe resection have not been heavily de-
pendent upon strong verbal memory skills. This may be

due to the fact that these patients already have subtle

verbal learning deficiencies (107). Nevertheless, selective
memory disturbances are usually enhanced by surgical
excision of the temporal lobe, particularly when seizures
continue, and the consequences of this potential handi-

cap should be considered.

RESEARCH OPPORTUNITIES

Quite apart from the clinical success of surgical ther-

apy for individual epileptic patients, and the value of

data collection for improving the efficacy of these proce-
dures, it is appropriate to discuss the importance of this
work to the more general problem of understanding epi-
lepsy. In the classical tradition of Hughlings Jackson

(223), and Penfield and Jasper (159), much of our knowl-
edge of the functional anatomy of the human brain has

352 / CHAPTER 15

been derived from studies of epileptic patients. Centers
engaged in the surgical treatment of epilepsy have
unique access to correlative behavioral, neurophysiologi-
cal, neuroanatomical, neuropathological, and neuro-
chemical information from epileptic patients that pro-
vides an extraordinary opportunity to investigate basic

mechanisms of epileptogenesis and normal brain func-

tion in humans (224). Because most basic research
carried out on epilepsy has employed animal models, the
relationships, if any, between the wide variety of experi-
mental epilepsies (225) and the human epilepsies (226)
are for the most part unknown. The fact that therapeutic
advances have generally come from studies utilizing ex-
perimental animal models has important clinical signifi-
cance. For example, the failure of antiepileptic pharma-

ceutical agents to control certain forms of complex

partial seizures may be directly related to the possibility
that this human disorder involves mechanisms signifi-
cantly different from those responsible for seizures in the

animal models used for developing antiepileptic drugs.

A limited amount of data from studies in humans sug-

gests that some aspects of the more popular laboratory
models of epilepsy are common to human epileptogene-

sis. The paroxysmal depolarization shift and afterhyper-

polarization recorded intracellularly from a wide variety
of experimental epileptic foci produce a burst of neuro-
nal firing followed by inhibition, which correlate with

the EEG spike and slow wave respectively (227). Extra-
cellular recordings from the human epileptic hippocam-

pus have demonstrated similar relationships between

unit firing and EEG waves (228), although the percent-

age of bursting neurons in the human epileptogenic re-
gion appears to be considerably smaller than in experi-
mental neocortical penicillin foci. Golgi stains of cortex
from chronic alumina foci have demonstrated neurons
with shrunken dendrites denuded of dendritic spines
(229). Similar cells have been found in resected temporal
lobe specimens taken from patients with complex partial
seizures (230). Although it is not yet known whether

these anatomically abnormal neurons are responsible for

the epileptic activity, a result of the epileptic activity, or
totally unrelated, their existence has figured prominently
in some theories of epileptogenesis (231,232). Morpho-
logical and electrophysiological data obtained from rats
with kainic acid-induced seizures suggest that loss of
principal neurons in the hilar area of the hippocampus
results in sprouting of granule cell mossy fiber axons
back onto their own dendrites, creating recurrent excit-
atory circuits (39). Similar morphological changes have

now been identified in the human epileptogenic hippo-

campus (37,38).

Differences between human complex partial seizures

and animal models have also been demonstrated by the

evaluation of surgical candidates. The most important
difference is that the majority of patients studied with
implanted depth electrodes do not appear to have a sin-

gle discrete epileptic focus, as is the case with artificially

created experimental lesions, but rather there are many
areas capable of independently initiating interictal, and
at times ictal, epileptiform discharges (233). These mul-

tifocal abnormalities may be the result of functional
changes such as those that occur with secondary epilep-
togenesis (234) or kindling (235), or of structural damage
induced by frequent seizures (34). It is not yet clear
whether the multifocal abnormalities observed in pa-
tients under evaluation for surgery represent features
common to all forms of secondary partial seizure dis-
orders in humans, or whether these findings are peculiar

to those patients whose seizures are medically intractable

and sufficiently severe to be considered for surgical ther-
apy. Evidence from primate models, however, suggests

that bilateral foci may be necessary before complex par-
tial seizures can become manifest (236). It is important
to realize that, in patients who are surgical candidates,
the object is to locate and excise the epileptogenic region
most responsible for initiating the patient's habitual sei-
zures, with the understanding that other distant areas of
epileptogenic tissue may very likely remain. This ex-
plains the variable results of surgery for epilepsy: why

many patients are seizure-free but continue to have

auras whereas others are improved although they have
occasional seizures.

Since many experimental animal models of epilepsy

result from interventions that disrupt GABA-mediated
inhibition, similar disinhibition has been suggested to
underlie human epileptogenesis. Morphological stud-
ies, however, suggest there is no preferential loss of
GABA-containing inhibitory interneurons or inhibitory
terminals on principal neurons of sclerotic epileptogenic
human hippocampus (237). Furthermore, electrophysio-
logical studies in human partial epilepsy, as well

as chronic animal models, now suggest that certain

inhibitory mechanisms may be enhanced interictally
(238), and in some cases could contribute to the appear-

ance of hypersynchronous ictal epileptiform discharges

(238,239). Since depth electrode recordings have identi-
fied at least two types of ictal onset in human partial
epilepsy, one with low-voltage fast activity and the other
with high-amplitude repetitive spikes (232), the transi-

tion to ictus in human partial epilepsy may involve more

than one mechanism, one perhaps requiring disinhibi-
tion, while the other involves hypersynchronization as a

result of enhanced excitatory and inhibitory mecha-
nisms similar to that proposed for petit mal type ab-
sences (239).

Another important difference between human and ex-

perimental epilepsy is illustrated by the variety of pat-
terns of regional metabolism seen with ictal FDG-PET

in human partial epilepsy (88) compared to the stereo-

typed 2DG autoradiographic patterns seen in animals
with experimental seizures induced by cortical penicillin
(240,241) and amygdaloid kindling (242). Whereas the

THE EPILEPSIES

353

preferential spread of ictal discharge from the epileptic

focus in these experimental models appears to be dic-
tated by the site of the primary focus and the technique
involved, propagation of ictal discharge in humans so far
appears to be unique to each individual patient.

Undoubtedly, there are common basic mechanisms of

epileptogenesis underlying both human and experimen-
tal seizure disorders. Much of our improved understand-
ing of the fundamental neurobiology of epilepsy, derived
over the past few decades from animal models, may even-
tually lead to new diagnostic and therapeutic approaches
in humans. However, it is of primary importance to

learn which experimental models of epilepsy resemble

which types of human seizure disorders, so that these

models can be used effectively and new models can be

developed where none yet exist. The research opportuni-
ties provided by programs that perform resective surgical
therapy for partial epilepsy should make it possible to
validate and extend basic animal research. The contin-
ued growth of interest in surgical resection as a viable
therapeutic alternative for medically intractable partial
epilepsy has implications beyond the benefit to those few
individual patients who may be selected for this inter-

vention. The data accumulated as a result of these proce-

dures may provide important insights into the basic neu-
ronal mechanisms of the human epilepsies and
eventually lead to new concepts of therapy and preven-

tion applicable to much larger populations of patients.

ACKNOWLEDGMENTS

Original research reported by the authors was sup-

ported in part by grants NS-02808, NS-15654, NS-
20806, and NS-00678 from the National Institutes of
Health, and by contract DE-AC03-76-SF00012 from the
Department of Energy.

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