Principles of Neurosurgery, edited by Robert G. Grossman. Rosenberg © 1991. Published by Raven Press, Ltd., New York.
CHAPTER
15
The Epilepsies Jerome Engel, Jr., Miche l Levesque, Pa ul H. Crandall, Crand all, D. Alan Ala n Shewmon, Rebecca Rausch, and William Sutherling Need for Surgical Treatment, 320 Etiology and Pathology, 320 Natural History, 321 Outpatient Evaluation, 322 Basic 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 the Developing Develop ing Brain, 345 Intractability, 345 Tim ing in g 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 surgery. This is a result of the tre mendo us advances in neurological diagnostic technology that have vastly improved the localization of structural and functional
abnormalities in the human brain, and of the greater safety and efficacy ef ficacy of modern diagnostic and therapeutic surgical surgical procedures. Despite Despite this, however, only a small fraction of patients who might be candidates for epilepsy surgery receive attention at epilepsy surgery centers. Although 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 dissemidissemination 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 currentl y available. The latter results from a reluctance on the part of medical centers to commit the personnel, space, and resources necessary for a dedicated epilepsy epilepsy surgery surgery program at a time when reimbursement rei mbursement for medical care involving expensive diagnostic and therapeutic procedures is being questioned and reduced. This chapter is intended to address the first problem directly, by describing the modern role of surgical intervention in the treatment treat ment of epilepsy, epilepsy, with the hope that a subsequent increased demand for epilepsy surgery will indirectly help to resolve the second problem. The discussion is primarily concerned with localized resective
J. Engel, Jr: Departments of Neurology, Anatomy and Cell Biology, and the Brain Research Institu te, U nivers ity of California, Reed N eurological Research Center, Los Angeles, CaliforCalifornia 90024-1769. M. Levesque: Levesque: Department of Surgery (Division of Neurosurgery), University of California, Los Angeles, California 900246901.
P. H. Crandall: Departments of Neurology, Surgery (Division of Neurosurgery), and the Brain Research Institute, University of California, Los Angeles, California 90024-6901. D. A . Shew mon: D epartments of Neurol ogy and Pediatri Pediatrics, cs, University of California, Los Angeles, California 90024-1752. R. Rausch: Department of Psychiatry and Biobehavioral Sciences, University of California, Reed Neurological Research Center, Los Angeles, California 90024-1769. W. Sutherling: D epartment of Neurology, University of CaliCalifornia, Reed Neurological Research Center, Los Angeles, California 90024-1769.
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surgery for medically intractable partial epilepsy, but an
increasing number of patients with secondary generalized epilepsies are becoming candidates for large multilobar resections as well as corpus callosum section, and these procedures will also be briefly considered. NE NEED FOR SURGICAL TREATMENT
The epilepsies afflict at least one million people in the United States. These relatively common neurologic disorders 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 wh ich ictal behavior and/or EEG alteralterations 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) consciousness) and com plex ( impairm ent of consci consciousousness) 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 afebrile convulsions was approximately 6.7/1,000 population. Sixty percent of the patients studied manifested partial seizures, with higher incidence rates at the extremes of life. In a French population of a more heterogeneous nature, 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. Anticonv ulsant thera py is effective in only an estimate estimatedd 35 to 50 percent of these patients (7). However, medically 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 medically intractable generalize d seizures that that occur as symptoms of multifocal or diffuse cerebral disease processes. More than 60 years after Horsley first described surgical cal therapy for p artial artial 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). Unfortunately, the vast majority of patients were excluded because they were shown to h ave bilateral indepen dent disdischarges or widespread interictal abnormalities. Regarding the application of surgical surgical treatment treat ment in 1967, 1967, Falconer wrote: "the selection of patients has been rigorous, and w e estimate that only about one in nine persons referred for surgery fulfill [our] criteria" (11). The excessive use of operatin operatingg room time for intraoperative intraoperative diag-
nostic studies, and an d the necessity necessity for fo r an integrated speci specialalist team, resulted in surgical treatment becoming underu tilized in the 1960s, 1960s, and only a handf ul of centers treated significant numbers of patients. Since the 1960s, 1960s, a variety of diagnostic methods hav e been developed that fu rther enh ance reliable reliable localization of epileptic foci (12). Our tools have been stereotactic surgery (13, 14), intracran ial electrodes electrodes wh ich provide fo r artifact-free recordings during ictus (15-19), long-term EEG monitoring monitor ing (20-22), and techniques to localize cecerebral 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. Introd uctio n of these new diagnosdiagnostic tests has resulted in identification of a progressively larger population of patients with partial seizures who could could significantly significantly benef it from surgical surgical treatment without inc urring und ue risks. risks. In contrast contrast to Falconer's Falconer's experience, 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 com monl y used in reference to partial partial epilepsy: epilepsy: epileptic focus, epileptogenic lesion, and epileptogenic reelectrographic concept gion (24). A n epileptic focus is an electrographic that ref ers to the site of maxim al EEG-recorded interictal spike activity. A n epileptogenic lesion is a structu ral concept cept that t hat refers r efers to t o a discrete discrete pathological pathological substrate of p parartial epilepsy. A n epileptogenic region is a theoretical concept that refers to the area of cerebral tissue that is necessary and sufficient to generate recurrent partial seizures. It is the epileptogenic region region that needs to be identified by presurgical evaluation procedures and, ultimately, resecte resected d in the surgical treatment tr eatment of epile epileps psy. y. The boundaries of the epileptogenic region, however, can on ly be in ferred fro m a variety of tests 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 lesions. Whereas EEG EEG studies are essential essential to demonstrate sites of interictal spike occurrence and ictal onset, these data do not prove the location of the epileptogenic region. The pathological pathological substrates substrates of partial epilep epilepsy sy may ma y
be identified with structural imaging tests such as x-ray computed tomography (XCT) and magnetic resonance imaging imaging (M RI), bu t the underlying underlying defects are more often demonstrated in the surgical surgical patient popu lation only by careful histological analysis of resected brain tissue. These latter studies have helped to develop an under-
standing of the causes of hu ma n partial epilepsy epilepsy (25,26).
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surgery for medically intractable partial epilepsy, but an
increasing number of patients with secondary generalized epilepsies are becoming candidates for large multilobar resections as well as corpus callosum section, and these procedures will also be briefly considered. NE NEED FOR SURGICAL TREATMENT
The epilepsies afflict at least one million people in the United States. These relatively common neurologic disorders 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 wh ich ictal behavior and/or EEG alteralterations 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) consciousness) and com plex ( impairm ent of consci consciousousness) 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 afebrile convulsions was approximately 6.7/1,000 population. Sixty percent of the patients studied manifested partial seizures, with higher incidence rates at the extremes of life. In a French population of a more heterogeneous nature, 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. Anticonv ulsant thera py is effective in only an estimate estimatedd 35 to 50 percent of these patients (7). However, medically 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 medically intractable generalize d seizures that that occur as symptoms of multifocal or diffuse cerebral disease processes. More than 60 years after Horsley first described surgical cal therapy for p artial artial 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). Unfortunately, the vast majority of patients were excluded because they were shown to h ave bilateral indepen dent disdischarges or widespread interictal abnormalities. Regarding the application of surgical surgical treatment treat ment in 1967, 1967, Falconer wrote: "the selection of patients has been rigorous, and w e estimate that only about one in nine persons referred for surgery fulfill [our] criteria" (11). The excessive use of operatin operatingg room time for intraoperative intraoperative diag-
nostic studies, and an d the necessity necessity for fo r an integrated speci specialalist team, resulted in surgical treatment becoming underu tilized in the 1960s, 1960s, and only a handf ul of centers treated significant numbers of patients. Since the 1960s, 1960s, a variety of diagnostic methods hav e been developed that fu rther enh ance reliable reliable localization of epileptic foci (12). Our tools have been stereotactic surgery (13, 14), intracran ial electrodes electrodes wh ich provide fo r artifact-free recordings during ictus (15-19), long-term EEG monitoring monitor ing (20-22), and techniques to localize cecerebral 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. Introd uctio n of these new diagnosdiagnostic tests has resulted in identification of a progressively larger population of patients with partial seizures who could could significantly significantly benef it from surgical surgical treatment without inc urring und ue risks. risks. In contrast contrast to Falconer's Falconer's experience, 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 com monl y used in reference to partial partial epilepsy: epilepsy: epileptic focus, epileptogenic lesion, and epileptogenic reelectrographic concept gion (24). A n epileptic focus is an electrographic that ref ers to the site of maxim al EEG-recorded interictal spike activity. A n epileptogenic lesion is a structu ral concept cept that t hat refers r efers to t o a discrete discrete pathological pathological substrate of p parartial epilepsy. A n epileptogenic region is a theoretical concept that refers to the area of cerebral tissue that is necessary and sufficient to generate recurrent partial seizures. It is the epileptogenic region region that needs to be identified by presurgical evaluation procedures and, ultimately, resecte resected d in the surgical treatment tr eatment of epile epileps psy. y. The boundaries of the epileptogenic region, however, can on ly be in ferred fro m a variety of tests 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 lesions. Whereas EEG EEG studies are essential essential to demonstrate sites of interictal spike occurrence and ictal onset, these data do not prove the location of the epileptogenic region. The pathological pathological substrates substrates of partial epilep epilepsy sy may ma y
be identified with structural imaging tests such as x-ray computed tomography (XCT) and magnetic resonance imaging imaging (M RI), bu t the underlying underlying defects are more often demonstrated in the surgical surgical patient popu lation only by careful histological analysis of resected brain tissue. These latter studies have helped to develop an under-
standing of the causes of hu ma n partial epilepsy epilepsy (25,26).
T H E E P I L E P S IE IE S
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 gestatio gestational nal or birth difficulties, head trau ma, meningitis, or other potential cerebral insults. More information about the pathological anatomy underlying complex partial seizures has been gained as a result of the technique of en of en bloc resection of the anterior temporal lobe (see "Operative Procedures") (11,27-29), which allows careful histologic evaluation of intact surgical specimens. Most lesions encountered are in the medial temporal 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 postmortem in patients with comp lex partial seizures seizures (30), (30), is also the most common lesion fou nd in resected resected temporal lobe specimens (25,26,31-33). Controversy exists concerning whether mesial temporal sclerosis sclerosis is is a cause or an eff ect of recurre nt epileptic seizures. Patients with mesial temporal sclerosis have a greater-than-expected incidence of prolonged febrile convulsions in infancy and f ami ly history of epilepsy (31), and prolonged seizures in animals can produce changes changes in the hippocamp us comparable to to hu man mesial temporal sclerosis (34). Such observations have suggested that there is a genetic predisposition to seizure inductio n of this this pa rticular pattern of cell cell loss in the h ip-
pocampus, and also to the subsequent appearance of recurrent complex partial seizures in association with the lesion. The epileptogenicity of this pathological abnormality has been inferred from the clinical knowledge that seizures appear to originate with in the sclerotic sclerotic hippocampal 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 occasionally yield brain tissue that appears completely normal, 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
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usually similar in all affected family members, the family history of epilepsy in patients with complex partial seizures is is usually usually qu ite varied. varied. Other f amily m embers may have had chronic seizure disorders or isolated seizures secondary secondary to a variety of cerebral cerebral insults . T his p robably indicates indicates a genetically genetically determ ined lowered lowered th reshold for seizures, perhaps necessary for the development of uncomplicated partial epilepsy in response to a single focal lesion. M any of the diagnostic diagnostic tests tests tha t w ill be discus discusse sedd 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 site of epilepepileptic 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 described later, th e inciden ce of pathol ogic changes in the resected specimen is high and surgical results are excellent (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 future. Un for tu nate ly, the concept concept of a singl singlee isolat isolated ed epileptogenic abnormality in patients with a medically intractable partial seizure disorder may be an oversimplification of the problem. Multifocal abnormalities are often encountered during the diagnostic evaluation, and patients frequ ently are only partially relieved of the ir epilepepileptic symptoms by surgery surgery (46). Clearly a spectrum of epileptic disorders ranges from simple partial seizure phen omena due to a small w ell-defined epileptogenic epileptogenic lelesion, through bilaterally independent and multifocal dis-
orders, to the so-called secondary generalized epilepsies (47) in which the cerebral cerebral disturbances disturbances are so diffu se 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-
(36). It is currently believed that such cell loss leads to axonal sprouting and synaptic reorganization, accounting for the development of chronic epileptic neuronal activity (37-39). Besides mesial temporal sclerosis and focal scarring from traum a or infection, other pathologic pathologic changes comcommonly noted in surgically resected specimens from patients with partial epilepsy, who usually give no history of any predisposing predisposing etiologic etiologic event, inclu de glial tum ors, meningiomas, heterotopias, angiomas, cysts, and focal
poral lobe or other cortical specimens removed at surgery. Additional lesions may still exist in the remaining brain. Consequently, a clear picture has yet to emerge concerning the pathophysiological basis of partial seizure disorders that may or may not respond to surgical interven tion. Basic Basic research research p rograms at centers engaged engaged in the surgical treatment of epilepsy provide an important opportunity to elucidate these issues, as will be discussed at the end of this chapter.
cortical dysplasia (25,40,41). A fam ily history of epilepsy epilepsy is not unu sual 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
NATURAL HISTORY
A natural history of partial epilepsy is valuable as a gauge against against which to measure the eff icacy of any therapeutic interventions (48). Strictly speaking, we are not
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likely to get a true na tur al h istory, since all patients now receive treatment. A series of articles from Oxford, which followed 100 children wi th temp oral lobe epilepsy into adulthood, is the nearest approach to a natural history 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 confirmed by two physicians, and an EEG demonstrated a focal discharge in one or both temporal regions. Collection was strictly consecutive, a nd it was possible to trace all of the patients in the series. N inety-f ive 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 economically, were seizure-free, and were not receiving anticonvu lsant medication. Thirty-tw o 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) hyperkinetic 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 fo ur 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 centrotemporal 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 temp oral 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 psychosocial. 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 review 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 importan ce. W hen seizures continue into adolescence, full investigation with a view to possible neurosu rgical 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 relief of seizures so long into adu lt lif e th at social recovery has become impossible."
OUTPATIENT EVALUATION
Because only patients with partial seizures can be considered 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 rou tine laboratory testing before sub jec ting the p atient to more exhau stiv e e valuation. However, some patients, usually children, with diffuse unilateral or secondary generalized epileptic disturban ces may be candidates for larger multilobar resections, hemispherectomy, or corpus callosum section. Basic Evaluation
De scrip tio n of Ictal Behavior Usually the partial nature of a seizure can be ascertained from a caref ul description of the behavioral event given by a reliable observer. Therefore, the initial interview with an epileptic patient should ideally include a parent, spouse, or some other individual who has witnessed the events in question. Sub jective w arnings noted by the patient (auras) are an important indication of a partial seizure disorder and may be useful in differentiating between partial and generalized epilepsy. Precise information 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 consciousness (which may consist on ly of amnesia) are generally considered indicative of limbic system invol vem ent. 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 extratemporal epileptogenic regions that invade temporal lobe limbic structures only secondarily. Some patients with complex partial seizures do not experience or rem ember auras, and an accurate description of the behavioral ictal onset is sometimes unavailable or unreliable. Furtherm ore, partial seizures may not always have a discrete focal or lateralized behavioral onset; 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 seizures inclu de those th at are secondarily generalized (partial becoming tonic-clonic) according to the international classification (4), as well as complex partial seizures that begin with an alteration in consciousness witho ut warn ing and proceed to simple or complex automatisms 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 differentiate f rom absences that occur with generalized seizure disorders (47,59). Consequently, evidence to substan-
TH E EPILEPS IES
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 p artial seizures also have had one or more secondarily generalized seizures. As a general 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 n umb er of manifestations of the same basic seizure, consistent with a single dominant epileptogenic region. Neurologic Examination
Even thou gh patients with partial seizures who are being considered for surgical therap y usu ally do not dem onstrate focal deficits on neurologic examination, a careful evaluation should always be performed. General physical findings, such as cafe au lait spots with axillary freckling or evidence of hemiatrophy, may indicate hereditary or congenital disorders associated with focal brain lesions. The most comm on neurologic abnorm alities fou nd in patients with complex partial seizures are memory disturbances, which often are revealed on specialized testing, even w hen th ey hav e not been elicited by history. Problems in remembering verbal material and associated word-finding difficulties suggest an epileptogenic region in the language-dominant hemisphere. More specific motor or sensory neurologic deficits usually imply that the major pathologic changes are suprasylvian. Formal 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
Ro utine EEG The most useful diagnostic tool in the evaluation of the epileptic patient has tradition ally been the EEG. For the potential surgical candidate, routine ou tpatient EEG studies are imp ortant to confirm the p artial 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 purposes of localization, as co mpared wi th recordings of ictal onset (12,19,60). Although good results can be obtained in many cases with surgery performed entirely on the basis of interictal scalp EEG localization, there is general agreem ent that interictal epilep tiform discharges can be misleading in 10 to 20 percent of patients (23,61,62). This is particularly true w ith complex partial seizures of limbic origin. Interictal EEG spikes may be
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more localizing with extratemporal neocortical foci, particularly if the interictal EEG spikes correspond with a discrete structura l lesion demonstrated on XCT or M RI. Presently, inpatient ictal recordings are always also obtained on all patients considered for surgery at UCLA (see "Inpatient Evaluation"). There are a number of potential hazards to understand and avoid whe n using routine interictal EEG studies to identify a partial seizure disorder and localize an epileptogenic lesion. A n um ber 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 p athologic spikes if their characteristic features are not recognized (47). Abnormal spike discharges, such as occipital spikes, periodic lateralized epileptiform discharges, and sylvian spikes, may not be associated with epilepsy or may not indicate the location of a resectable epilep togenic region (47). Even epilepsyrelated pathologic interictal EEG spikes may tend to
shift location, particularly in children (61), and do not always correlate reliably w ith th e site of the epileptogenic region (23,62,63). Bilateral independent temporal EEG spikes are common in patients with complex partial seizures who eventually do well with unilateral temporal lobectomy (23,46), and the predominant EEG focus may occasionally be contralateral to the pri mar y epileptogenic region (23).
Special Electrodes Basilar electrodes that are capable of recording epileptiform 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 th e earlobes, over the zygo ma, or in th e 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 u ncom fortable, unstable, near ph aryngeal muscles that cause artifacts that may be impossible to differentiate from cere-
brally generated spikes, and are separated by wet mu cou s membran e that makes lateralization diff icu lt, the ir use is discouraged. Sph enoidal electrodes provide a somew hat 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 laborator y. Th e use of several basilar deriv ations simultaneously may aid in defining an electrical field for interictal spikes that has additional localizing value (66). Small sharp spikes and 14 and 6/sec positive spikes lack their characteristic appearance w hen recorded f rom mesial temporal p lacements and cannot be easily differentiated from pathologic spike phenomena, even by the most experienced electroencephalographer, w ithou t ac-
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cess to EEG patterns simultaneously derived from the scalp (47 ). Th erefore, basilar EEG studies should always include an independent lateral temporal montage to identify the surface electrical field of all medially recorded 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 rul e is to take seriously 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, photic stimulation, and sleep are routinely used in the EEG laboratory. Hyperventilation may provoke focal slowing, spikes, and even partial seizures. Since photosensitive epilepsy is almost always a primary generalized disorder, photic stimulation is much less likely to be usefu l in the evaluation of partial seizures, except in the differential 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 ignore the normal and clinically insignificant sharp transients associated with sleep, and to be aware that interictal EEG spikes activated by slow-wave sleep have less localizing value than interictal spikes seen du ring wakefulness (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 examination and routine EEGs are equivocal; therefore, the two techniques are ofte n used together. How ever, if the diagnosis is clear from other evidence, and the patient 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 epilepsy 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 tumors will not be considered further in this discussion of surgery for epilepsy per se. W ith the advent of high-resolution structural imaging, however, the clinical importance of many identified abnormalities is not always clear. D efects seen on XCT and M RI can come and go (76,77), and mesial temporal unidentified bright objects (UBOs) consisting of nonspecific increases in intensity on T2-weighted M R I image, unassociated with changes on the Tl-w eighted image, may hav e no structural correlate (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 localization of the source of epileptic seizures.
Functional Imagin g
The most important confirmatory test used at UCLA 18
is positron emission tomography (PET) with F-fluorodeoxyglucose (FDG) (23,43,44,79-81). Many centers
have now demonstrated that the majority of patients with partial epilepsy who are candidates for surgical treatm ent h ave FD G-PET scans with characteristic metabolic 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 determined by microscopic evaluation of the resected specimen (43,80,81). Although temporal lobe hypometabolism 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). FDGPET may be particularly important in the presurgical evaluation of infants and small children with severe unilateral or secondary generalized epilepsy (87) wh ere neuronal plasticity allows larger resections than in the adult, and chronic intracranial EEG recording is difficult to perform. Many of these patients show unilateral hypometabolic zones, even when structural imaging studies are unrema rkabl e. In this situation, FDG-PET also helps to conf irm that the contralateral hemisphere is functioning normally.
T HE EPILEPSIES
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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 inplane resolution of approximately 5 mm. Fifteen horizontal planes of section are obtained simultaneously, and one or more sets of pianes can then be reformatted into coronal, sagittal, or other planes as desired. Note that images front this tomograph show the patient's left side on the right and the patient'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 sagittal section through the right temporal lobe (E). (From reference 24, with permission.)
Ictal FDG-PET scans reveal areas of hyp er- and hypometabolism that correspond to the origin and/or spread of epileptic discharge du ring th e 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 distinguished f rom the site of seizure origin, these scans are not as us efu l as interictal FD G-PET studies for localizing the primary epileptogenic region. Studies comparing FDG-PET with various EEG tests have revealed basic differences (70,89). The FDG technique measures the average intensity, over time, of metabolic activity in all cellular elements w ithin 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 th e temp oral 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 neu rona l 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 techniq ue reveals anatomic localization better than EEG; the EEG is necessary for th e temp oral seq uencing of events. These tests are complementary and together provide more functional 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 sh ould be considered only as confirm ation of a focu s demonstrated electrophysiologically. Although the transform ation of an interictal hypometabolic zone into a hypermetabolic zone during ictus may be
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patho gnomon ic of an epileptogenic region withou t 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 pattern s that are similar to th ose of interictal FDG -PET (91-94), although the reduced spatial resolution decreases the yield. In addition, a variety of biologically active tracers does not exist, and radiation exposure to the p atient is greater than with FDG-PET. Ictal SPECT is, how ever, m ore easily perform ed than ictal FDG-PET, and can reveal patterns of hyper- and hyp operfu sion that may be useful for identifying the epileptogenic region (93,95,96). How ever, 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 requ ire 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 freq uently used in combination with other fun ctional tests for confirmation of dysfunctional brain areas (12 ,23 ,99). P rognostic uses of the neu ropsycholo gical evaluation include information as to the probability of seizure control following a focal resection (100,101), prediction of the typ e and degree of cognitive loss fol low ing surgical intervention (102,103), and the likelihood of postoperative improvement in psychological and psychosocial 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 dy sfu nction of the tempo ral lobe and extratemporal areas. Psychological domains generally assessed are langu age, intelligence, a ttention , cognitive-tracking, sensation, perception, motor skills, and memory functioning, as well as personality and psychosocial function (98,106). The most reliable neuropsychological index of lateralization of temporal lobe dysfu nction is a selective memory deficit associated with one temporal lobe (107). The memory deficit should exist independent of other neuropsychological 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 adm inistration of the W echsler Memory Scale (108), have been found to be particularly sensitive to dominant temporal lobe dysfunction. Nonverbal memory 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 temporal lobe functions. Interpretation of the neurop sychological profile is dependent upon knowledge of hemispheric dominan ce for language, which is determined by the intracarotid sodium amobarbital procedure (IAP). This test is described in the section on inpatient evaluation.
Indications for Further Evalua tion
Positive Ind ica tions
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 w ithou t producing additional unacceptable neurological deficits. Although any epileptic disorder characterized by stereotyped partial seizures can be considered a positive indication for further evaluation, in practice most patients 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 hemisph erectomy, are less well defined. Patients with secondary 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 structures. The best surgical outcomes are obtained in patients 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 inf anc y, and an onset of seizures in the first decade of life (31). If an aura is present, it often has an epigastric or other autonom ic component, alth ough a wide variety of hallucinations and cognitive, affective, and psychosensory symptoms may occur, followed by altered consciousness, 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 generalized, but this is a relatively infrequent occurrence.
THE EPILEPSIES
(Other simp le m otor or special sensory seizures with preserved consciousness generally indicate extratemporal onset, which is an indication for other types of focal cortical excision). Neurologic examination may reveal a moderate memory deficit and radiologic studies are usually normal. The characteristic EEG pattern consists of unilateral or, more com monly, bilateral independent anterior temporal interictal spike foci. These features are typical of "temporal lobe seizures"; however, such features do not invariably distinguish an epileptogenic region 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, p atients with such seizures are good candidates for presurgical evaluation, but conclusions regarding the actual location of the epileptogenic region should not be made on this information alone. While this profile characterizes an ideal surgical candidate, there is an inf inite variety of manifestations of surgically resectable epileptogenic regions. Each patient presents a un iqu e problem and must be dealt with independently. 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 presurgical evaluation. Negative Ind ica tio ns
If pharmacologic management has not been adequate to establish that the patient is medically intractable, sur-
gery is generally not considered until appropriate anticonvulsants have been given a proper trial (42,55). Surgery should also not be considered in patients with seizures insuf ficie ntly severe to seriously disrupt the qu ality 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 occupation, who works alone with no set schedule, may tolerate several seizures a day, while another with employment involving continued interaction with the public or constant attention and quick judgment may be unabl e to work with just a few seizures a year. In general, patients with few er than several seizures a month are not considered for surgical therapy. Patients with severe mental retardation are relatively poor candidates for localized resection, since this usually indicates diffuse cerebral damage and multifocal epilepsy. Howev er, such surgery may be justified occasionally if a reduction in seizure frequency would significantly ease patient management at home or in an institution. Wh ile lower intellectual 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-
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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 often considered a relative contraindication to surgical therapy, since this condition is rarely reversed when seizures 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 w ith presurgical evaluation. When seizures are due to a known progressive 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 concerning the indications for these procedures (12). Surgery should be considered even if medication is shown to be effectiv e, wh en the necessary7 dose req uired to control seizures also causes unacceptable side-effects. This is a particularly important concern in children, wh o do not complain of overmedication and whose resultant poor school perfo rmance 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, progressive symptoms may be due to increasing seizure frequency, more severe seizures, drug effects, or psychosocial 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 temporal lobectomy (101). Seizure-related reversible psychotic symptoms, such as transient postical psychosis,
are not the same as chronic psychosis, and usually resolve postoperatively when seizures no longer occur. There is no tr uth to the old belief that su rgery is dangerous 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 (11 5), bilateral indep endent or synchron ous EEG spikes, and even occasional contralateral ictal EEG onsets, usually have a single epileptogenic region that can be identified and resected with beneficial 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-
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mary idiopathic epileptic disorder (116) that is not treated surgically. With increasing application of new diagnostic approaches (12), as well as improved safety of larger surgical resections and corpus callosum section, particularly in children, more and more epileptic patients who w ould not h ave 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 wh o appears to have a partial or secondary generali/ed epileptic disorder deserves at least a preliminary evaluation at an
epilepsy surgery center. INPATIENT EVALUATION
The approaches to presurgical evaluation are largely dictated by the inten ded surgical procedure (2,11 7-1 19). Figure 2 is a flow chart demonstrating the various protocols for surgical treatment of epilepsy at UCLA. Althou gh this chap ter is concerned primarily w ith localized resective surgery, evaluation for large multilobar resections, hemispherectomy, and corpus callosum section are also considered briefly. Patients who are candidates
for localized resection undergo an initial phase 1 inpatient evaluation, which includes scalp and sphenoidal EEC telemetry with video monitoring as well as additional confirm atory tests that do not requ ire intracranial procedures. If the epileptogenic region is not adeq uately define d, 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 selected neocortical regions as well. When seizures are suspected to originate in lateral n eocortical regions and the involved hemisphere is known, placement of subdural grids is preferred. W hen 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. W hen a craniotomy for subdural grid placement is done initially, however, the bone becomes too unstable to permit a second evaluation with the UCLA orthogonal approach to stereotactically-implanted depth electrodes. If the intended surgical procedure is a standardized resection, such as anterior temporal lobectomy (26) or amygdalohip pocamp ectomy (120), the presurgical evalu-
FIG. 2. Flow chart illustrating the presurgical evaluation scheme for epileptic patients at UCLA. "Identification of extratemporal epileptogenic zones in patients who underwent depth electrode evaluation may require a second chronic intracranial procedure with subdural 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.)
T H E E P I L E P S IE S
ation is designed to determ ine il" habitual seizures originate 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 boundaries 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 no ninvasive interictal EEG recording techniques, using routine scalp and basilar electrodes. These are usually supplemented by intraoperative electrocorticography (ECoG) (1 9,62,63 ), as described in the section on operative procedures. Others feel the epileptogenic region is
more reliably localized by inpatient recording of ictal events using long-term video EEG monitoring (16), either with scalp and sphenoidal electrodes (23), or with intracranial (epi- and/or subd ural) (17 ,18) or stereotacti-
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tial surgical candidates are initially admitted for app roximately 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 telemetry unit located in the EEG laborato ry for 8 ho urs a day. Sphenoidal electrodes are 50-gauge, Teflon-coated, 15stranded stainless steel wires, which are bared at the tip.
These electrodes are inserted through a 22-gauge 1.5inch needle, as shown in Figure 3 ( 24). W ires 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 standards for long-term mo nitoring (20), transmitted via radio or cable telemetry, and stored on videotape (124). Beh avior is recorded by two v ideo cameras and a microphone, 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 exercise are possible w ith ou t losing the EEG signal. A s a rule,
cally implanted depth (13-15) electrodes. There is no consensus on a single correct electrophysiological approach to the evaluation of the presurgical candidate (12). Most now agree that ictal plus interictal data are preferable to interictal data alone , and tha t chronic intracranial recording is at least sometimes app ropriate. C onsiderable disagreement remains about when interictal EEG and ECoG recordings are sufficient, and when chronic intr acranial recordings are necessary (1 9,123). Because of the p otential f or false localization f rom electrophysiological measures of epileptic excitability, it is very important to use independent measures of functional 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 inv olves a variety of tests aimed at identifying areas of abnorma l l?rain structur e and fu nction (12). The UCLA presurgical evaluation protocol utilizes extracranial and, as needed, various intracranial electrophysiological approaches to localize epileptiform abnormalities. In addition, a variety of tests which measure focal functional deficits are employed to confirm the location of the epileptogenic region determined electrophysiologically. This protocol, therefore, can be used to illustrate most of the diagnostic procedures currently available in epilepsy surgery centers. Phase 1 (Extracranial EEG Telemetry)
Meth ods of Scalp and Sphenoidal EE G Telemetry
Patients determined by ou tpatient studies to be p oten-
FIG. 3. Illustration to show the placement of sphenoidal electrodes. 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 multistranded Teflon-coated wire protrudes from the tip of the insertion 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 permission.)
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only the ictal data are written out on paper for interpretation. Seizures arc identified by continuous direct observation, or via video monitors. Patients can also signal
the occurrence of an au ra w ith a call button. W hen seizures 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 seizure detector and by random searches. A time-code generator records clock time simultaneously on the video
image and on one channe l of the EEG so that electrical activity and behavior can be correlated exactly. Fifteen, thirty, or more channels record EEG in common reference format so that seizures can then be played back in any desired montage (125). Records are reviewed daily by an electroencephalographer/neurologist and derivations 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 spontaneously occurring ictal EEG discharges, and to correlate this with ictal behavioral changes. A nticonvulsan t 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. A utoma tic spike detection programs are also available for qu antif ying interictal spike frequ encies at various locations (127). The site of maximu m interictal spike occurrence, particularly those spikes recorded during wakefulness (68,128) and REM sleep (129) correlates well w ith t he site of ictal onset. Ev alua tion of Ep ileptiform Ac tivity
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 identifiable EEG abnormalities. Some examples of ictal onsets recorded during scalp and sphenoidal EEG telemetry appear 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 h ave eq ually reliable localizing value. Both depend upon the occurrence of rhythmic activity of 5 Hz or faster, with phase reversal in one sphenoidal electrode (130). W hen this p attern is the first ictal change observed, or occurs after other changes that
are localized to the same sphenoidal electrode, it is referred to as an initial focal onset. When the pattern is seen with in 30 seconds after a diffu se ipsilateral, or generalized 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 important to require that ictal EEG changes precede ictal behavioral changes when analyzing scalp and sphenoidal-recorded data. Both patterns are correct in identifying the epileptogenic region dem onstrated 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 identified in the same area, the patient may be considered for surgery without intracranial evaluation if the criteria for confirmatory evidence of focal functional deficit described later are met. The n um ber of seizures required to
conclude that ictal onsets are consistently focal is not fixed and is determined in part by the natu re of the patient's habitual seizures. If more than one habitual seizure type has been reported, examples of each type
FIG. 4. Examples of EEG telemetry-recorded ictal onsets from four patients with complex partial seizures. (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 10 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.)
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should be recorded. It is most important to be certain that the seizures captured on the telemetry unit are the seizures ca usin g the p atient's problems at home. If necessary, 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. Ev alua tion of Focal Functio nal D eficits
FDG-PET and neuropsychological evaluations are important confirmatory tests of focal functional deficit
that are performed on an outpatient basis and have already been described. Two othe r tests, thiope ntal activation and the intracarotid sodium amytal procedure (IAP), require hospitalization and are usually done during 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 h ave less localizing valu e than those that occur during wa kefu lness (128 ). This test is useful, however, because focal attenuation of barbiturate-induced fast activity implies a fu nctional 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 secobarbital because it provides more control over the level of consciousness, and th e observation tim e is longer than with the faster acting methohexital. In patients with complex partial seizures, focal attenuation is most often isolated to one sphe noidal electrode (Fig. 5); this find ing 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 fo r language (133), and was later used to predict whether th e contralateral temporal lobe could supp ort 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, pathologic shifting of language dominance from the left to the right hemisphere generally indicates that the epileptogenic lesion is in the left temporal lobe (135). Before the patient undergoes IAP, angiographic studies are recommended to provide inform ation abou t 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-related behavior changes. Immediately prior to injection, the patient is asked to count aloud while bilateral grip strength is continuously assessed. Over a 4-second period, 125 mg of sodium amobarbital in 10 cc of saline solution is injected into one internal carotid artery via a transfem oral cannula. Each hemisph ere is infused separately, with at least a 30-minute delay between injections. EEG is simul taneously recorded, and the neurological status of the pa tient is continuousl y 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 minu tes. With in seconds after the dominant 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 fo llow ing retu rn 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 hemisphere injection. More detailed descriptions of the IAP assessment procedure have been published elsewhere (136). Skull roentgenograms, XCT, MRI, and cerebral angiograms are also obtained during phase 1 if these studies hav e not been carried out previously. N onspecific structural abnormalities revealed by these studies provide useful confirmatory information if their localization correlates 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-intensity areas in T2-weighted MRI scans remain unclear and these abnormalities should be interpreted with caution (78).
In dica tio ns for Fur ther Pr oc ed ures If a patient has a well-localized EEG-recorded ictal onset (130), FDG-PET scans demonstrate a hypometabolic 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, 1 00 yuV. Patient had menial temporal sclerosis on left. (From reference 99, with permission.)
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at UCLA without requiring phase 2 (243). Clear structural 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 resection 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 neocortex, subdural grid electrodes are preferred. When phase 1 evaluation indicates that seizures are occurring from multiple sites, or no localizing hypothe-
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 reco rding offers a great diagnostic advantage. With depth or subdural grid electrodes, the ictal EEG recording is generally free of muscle and movement artifacts, making it possible to observe exquisitely focal types of ictal onset and to follow the spatiotemporal pattern of electrographic propagation. Ho wev er, 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 intracranial 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
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at UCLA without requiring phase 2 (243). Clear structural 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 resection 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 neocortex, 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 hypometabolism on FDG-PET that correlate with the predominance of interictal and/or ictal epileptiform EEG discharges are the most important criteria for consider-
ing large resections in these patients (87,13 9), w hile 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 evaluations. Patients undergoing hemispherectomy must ei-
ther have a useless contralateral hand or, in rare instances, be willing to accept this deficit as an inevitable consequence of the surgical procedure. Patients who intend to undergo corpus callosum section must understand 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 disconnection symptoms (142), but this is not considered an absolute 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 reco rding offers a great diagnostic advantage. With depth or subdural grid electrodes, the ictal EEG recording is generally free of muscle and movement artifacts, making it possible to observe exquisitely focal types of ictal onset and to follow the spatiotemporal pattern of electrographic propagation. Ho wev er, 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 intracranial 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 evidence of focal dysfunction or a structural lesion is missing 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 lobectomy. In patients who may be candidates for selective amygdalohippocampectomy or lateral temporal resection, depth electrodes are used to confirm that ictal onsets 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 obtained 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-
tiv e advantages of grids versu s 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 multiple illnesses or active infections that could lead to intracranial infections, or who are otherwise poor surgical risks (e.g., patients with diabetes mellitus who are prone to infection) obviously should not undergo chronic intracranial 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,
THE EPILEPSIES
our patients are closely observed for emotional instability, psychiatric disorders, or unusually violent ictal behavior, 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.
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Methods of Electrode Implantation and Removal
Stereotactic Depth Electrode Implantation Recent developments in neuroimaging have radically changed the field of Stereotactic surgery. MRI now allows direct visualization of brain structures in an y plane. By choosing specific pulse sequences, MRI can delineate brain-CSF boundaries, grey and white matter junction s, and even discrete pathological changes within deep cerebral regions. We now use a method of electrode implantation 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 p lanning of electrode impl antation. This stereotactic technique is made possible by an MRI-compatible lightweight Stereotactic frame that is used for imaging studies and intraoperative implantation, and for postoperative verification of electrode placement. The overall principle remains to survey the limbic structures medial to the temporal lobe from anterior to posterior, bilaterally and symmetrically (15). Additional extratemporal structures are selected for implantation according to seizure semiology, scalp EEGs, and/or hypometabolic areas on FDG-PET. A m odified Leksell Stereotactic fram e (the OBT, Tipal Instruments, Montreal, Canada) (14 3) is used for target localization and electrode implantation (Fig. 6). It is constructed 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 coordinates, where the X axis is along the anteroposterior (sagittal) plane of the f rame, the Y axis is along the inferior to superior (coronal) plane, and the Z axis is in the
axial plane, extending positively to the right and negatively to the left. Four sets of Plexiglas® plates provide fid ucia l mark ers 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 temporarily attached to the Stereotactic frame. Aluminum tubing is used during CT scanning, copper sulfate solution (7 gm/1) is used for MRI studies, and fo r PET scans the channels are filled with positron-emitting germanium isotope. The plane of section is calculated from the loca-
FIG. 6. The OBT (modified Leksell) frame used for intracerebral target localization and depth electrode implantation. Stereotactic 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 mark ers consist of fou r 1 -mm stainless steel disks placed equidistan tly at th e f ou r quadrants of the Plexiglas plates located on either side of the head for a lateral view, or at the front and back of the f rame f or an anteroposterior view. Markers closest to the x-ray source will form a larger rectangle on the x-ray film because of beam divergence, and thus differentiate the side injected and provide data for com puter 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 supplemented 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-compatible 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 f ram e to permit exact repositioning of the fram e f or any fu tur e surgical procedures. The patient is then brought to the MRI suite and placed in a supine position, with the Stereotactic frame
anchored to a custom f rame a daptor over the sliding table 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 sequences with a slice thickness of 4.9 mm and slice intervals 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 anteroposterior and lateral projections is obtained using a standard femoral catheterization approach. Four-per-second
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arterial and venous phases are selected for further analysis. 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 minu tes 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. Com puterized image analysis. All stereotactic digitized 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 imageanalysis software. Selected images are retrieved from the hard-disk memory and are simultaneously displayed in separate windows (Fig. 7). D ifferent planes fro m a single
FIG. 7. Multimodal stereotactic imaging system. Top: Different planes of different studies can be simultaneously 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 permission.)
T H E E P I L E P S IE S
modality or multimodal images can be displayed and analyzed at the same time. A cursor system interconnects the images an d the X, Y , an d Z coordinates of any point w ithin the stereotactic fram e can be displayed. Initially , structures are selected on the sagittal M R; orthogonal trajectories are simulated to samp le both lateral temporal neocortex and mesial temporal structures (amygdala; anterior, mid, and posterior hippocampi; and anterior, mid, and posterior parahipp ocampal gyri). Labeled targets are au tom atical ly transposed to the coronal 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 cortex, the supplementary motor area, the anterior and posterior cingulate gyri, or the occipital cortex. After completion 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 premeasured skull-fixation pins and the position confirmed with a portable skull x-ray. The frame is clamped to a supp ortive device attached to a M ayfield holder. A modified side-carrier that slides on vertical side bars is positioned 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. Th e distance between th e outer port ion of the screw and the side-carrier is translated into a specific length fo r each electrode. T emporal electrodes are multicontact rigid tubing with an outer diameter of 0.8 mm. The electrodes are constructed with MR-compatible nickel chromium and have a hollow center permitting insertion of platinum alloy fine w ire (40-micron diameter) electrodes. Extratemporal electrodes are flexible nichrome fine wires (100-micron diameter) with multicontact leads. Two reference electrodes are placed in the galea. Af ter placem ent, electrodes are bent toward the vertex and embedded in a thin mold of acrylic polymer. 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 h emispheres, when seizures are also suspected 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 samp le certain areas presumed to be involved in seizure onset that are poorly sampled by the orthogonally placed depth electrodes. The frame is removed postoperatively,
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and the p atient 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 mon itoring period. Resective surgery is perform ed 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 mu ltipl e a rrays of electrodes over the cortex in th e su bdural space (18 ,147). Wide areas of lateral cor-
tex can be sampled as well as subtemporal, subocc ipital, 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 . A fte r intraoperative def inition of the sensorimotor cortex wi th ev oked 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 samp le specific lobes according to the desired p resurgical eval uatio n. Great care mu st be taken to avoid an y tear or displacement of major d raining veins. The grids are tied to each other to prev ent mo vem ent or slippage. The connectors are then tunneled under the skin through separate 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 fl ap su tured in place. Corticosteroid admin istration and fluid restriction are used initially to allow expansion of the subdural space and accommodation of the brain to the grids. P atients are then taken to the neu rosurgical intensive care unit before transf er to the telemetry ward for functional mapping and seizure monitoring (18,148).
De pth Ele ctro de Eval uatio ns
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 contacts, 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 telemetry unit for SEEG telemetry and video monitoring in order to capture spontane ous seizures and pe rform oth er studies. If indicated by the incidence of seizures durin g 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
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CH APT ER 15
detector is used to identify ictal SEEG discharges that might otherwise go unno ted (149 ,150). Subclinical electrographic ictal events are also more comm only encou ntered with random searches during phase 2 than during phase 1. Initial SEEG recordings are made using 30channel montages containing symmetrical derivations from each hemisphere, including the most mesial and most superficial contacts from temporal and extratemporal electrodes and any subdural strip electrodes. After several typical episodes are recorded and the electrographic pattern is determined, montages may be changed to define better the site of ictal onset. Even with 30 telemetry 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 sp henoidal derivations if needed to iden tif y sur face 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
foca l (1 51 ) 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, w hich can be correlated temporally w ith the progression of behavioral ictal events (Fig. 8A-C). Often, however, the initial EEG changes are more dif ficu lt to interpret, due to subtle focal onsets that may be missed, or regional onsets (151) that initially involve all, or most, depth contacts in one temporal lobe simultaneously (Fig. 8D-F). With our present knowledge, it is impossible to characterize definitively and classify all SEEG-recorded ictal phenomena. Although certain patterns may be correlated 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 abnormalities revealed by this technique. Alm ost 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 17 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 reflected 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 synchronous 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.)
TH E EPILEPSIES
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, wh ile regional onsets tend to represent epilep tiform activity propagated from a primary epileptogenic region distant from the available recording sites. Usually, however, this distant region is still within the same temporal lobe. Consequently, a regional onset is not a poor prognostic sign unless there is other evidence that this represents propagation from an extratemporal or contralateral epileptogenic region. The f indi ng of a regional onset, however, should prompt more careful attention to this possibility. The pattern of ictal propagation also provides clues to the site of seizure generation. In p articular, slow spread to contralateral limbic structures is typical of mesial temporal seizures, while rapid contralateral spread suggests a neocortical or extratem pora l site of onset (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 primary and propagated ictal discharges remains a problem, 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 epileptogenic region, but confirmatory evidence of focal dysfunction 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 baseline rhy thm s are rarely seen dur ing scalp EEG recordings in our patients, there is often localized slowing or attenuation of normal rhythmic activity recorded from intracranial electrodes. Attenuation of normal SEEG-recordcd faster rh yth ms is most reliably observed when the placement of relatively equ idistant mu ltiple depth electrodes is bilaterally symmetrical, and chain-linkage montages are used (Fig. 9). Con sistent attenu ation of
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normal rhy thm ic activity at most, or all, mesial temporal depth electrodes on one side indicates a functional disturb ance t hat correlates well w ith th e presence of a lesion (23). Attenuation of barbiturate-induced fast activity in one temporal lobe is mu ch better revealed wh en intravenous thiopental is given during SEEG recording than during scalp and sphenoidal EEG, as described earlier. Unilaterally attenuated SEEG-recorded thiopental-induced fast activity also correlates well with the presence of a lesion (23,132). Thiopental-induced interictal SEEG spikes, like spontaneous spikes, are not reliably localizing 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; how ever, localization obtained from electrically induced events (as with convulsant drug-induced seizures) may differ from localization obtained from spontaneous events (156). Determinations of electrically induced afterdischarge thresholds hav e been used to indicate the location of epileptogenic tissue, but results are contradictory. At UCLA , afterdischarge thresholds have been most consistently elevated in the ep ileptogenic hippocamp us, particularly when the lesion is hippocampal sclerosis (157), while others have found a lowered afterdischarge threshold to indicate epileptogenic brain tissue (158). Differences 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 impairment of mem ory functi on h as been produced in the contralateral temporal lobe as a resu lt of electrode implantation and/or stimulation. Subdural Grid Evaluations
From extensive experience with temporal limbic epilepsy, we have learned that the highest degree of surgical
FIG. 9. Direct (hardwire) SEEG record-
ing demonstrates attenuation of normal rhythmic fast activity in the right amygdala, hippocampal pes, and gyrus. Abbreviations as in Figure 8, except P, hippocampal pes. Calibration 1 sec, 1,000 /j.V. Patienthadmesial temporal sclerosis on the right. (From reference 99, with permission.)
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success is achieved wh en there is preop erative demonstration I MR. CT. SPECT, PET) of a pathological substrate, proof of epileptogenesis in this same region, and com pl eten es s of the operation with postoperative pathology found in the specimen. Similarly, in neocortical epilepsy, it has long been known that surgical outcome is best w hen a specific lesion can be demonstrated preop eratively. W hen extratemporal localization is obtained by scalp EEG techniq ues 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 bipolar electrical stimulation of the brain to demonstrate the epileptogenic cortex and functional regions acutely in the operating room (159). Talairach and colleagues demonstrated the irritative cortex, lesional cortex, and epileptic 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 subdural 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 comfortably evaluated (160,161). In addition to localizing interictal and ictal epileptiform discharges using telemetry monitoring techniques identical to those of depth electrode recordings, the extent of the functionally inactive region can be tested by electrical stimulation, evoked potentials, and EEG background 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 subdu ral electrode grids are dealt with in detail elsewhere (18,148,162). Both cortical stimulation and event-related evoked potentials are utilized to localize essential cortical regions. The parameters for cortical stimulation are selected to avoid tissue damage. N o 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 sensorimotor function and language. W e assume that if careful neurophysiologic assessment were performed, most, if not all. brain tissue wou ld be eloquent, and some measurable deficits would be identified after most focal excisions of brain tissu e. A s is done with those p atients wh o 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 cortex that is essential to avoid deficits in activities of daily living such as hand function and language. As m any relevant functions are tested at a site as feasible within the time lim itations and tolerance of the patient. Functional mapping usually takes about a week to perform and requires much patient cooperation. Not all patients are capable of tolerating this procedure. In the preceding era of epilepsy surgery, any intervention into the primary cortices was generally avoided. With increased confidence in cortical mapping, operations 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 epileptogenic cortex. The definition of epileptogenic cortex by means of interictal epileptiform discharges and recording of the ictal activity is still under development. In some cases, focal ictal discharges have been qu ite limited in extent and the su bdural grid evaluations have allowed less-than-lobar resection to be surgically successful and with less than the expected morbidity. Indica tio ns for Furth er Proced ures
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 originate in one area of the brain and confirmatory tests should reveal focal dysfunction in the same area. After grid recording, tailored resections are determined primarily 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 (especially if these seizures are atypical and/or occur when anticonvulsant medications have been significantly lowered) are not considered an absolute contraindication to surgery, since patients with such findings often do well postoperatively (126). In our experience, when SEEGrecorded 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 electrodes or intraoperative corticography may be recommended. When the time for ictal spread to contralateral. or extratemporal structures is less than a second, or ictal onsets are inconsistent or appear only a fter clinical signs and symptoms, focal functional deficits are used to suggest other epileptogenic regions that might justify a second 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 EPILE PSIES
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FIG. 10. Focal seizure pattern from left frontal lobe. (A) Anteroposterior skull x-ray outline shows coronal 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 highamplitude 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 10 0 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 originate with equal frequency from either side of the brain, or when subdural grid-recorded seizures originate entirely within primary cortex that can not be removed. OPERATIVE PROCEDURES Electrocorticography
In some centers intraoperative ECoG is performed routinel under local anesthesia f62.63.120
the extent of resection is determined on the basis of interictal ECoG findings. Since intraoperative ECoG recordings are lim ited to th e area of craniotomy, they cannot be used to localize an epileptogenic region, but rather are used to define better the limits of epileptogenic
tissue already localized by oth er techniqu es. This procedure may be extremely helpful for certain neocortical lesions; how ever, reliable localization of a lim bic epileptogenic lesion on the basis of the complex interictal epileptif orm discharges encountered in th e temporal lobe is mu ch more diff icu lt, if not impossible (62). In fact, interictal spikes recorded from depth electrodes inserted at surgery into the hippocampus and amygdala appear to w i t hQ h c A n ^ f r» f r»athrvlrvm V ^Vionrroc
u /K il a *»i-*i
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CH APTER 15
leptiform discharges are no t 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 activity, imraoperative recording techniques are useful for defining areas of cortical dysfunction demonstrated by localized attenuation of barbiturate fast activity induced by intravenous thiopental. Evoked potential and stimulation techniques are also used to identify primary motor, sensory, and language cortex when suprasylvian resections are planned. Intraoperative cortical stimulation can occasionally induce the habitual aura or behavioral seizure; however, this should not be considered definitive evidence that the stimulated site is the primary epileptogenic region. Stimulation of distant, or even contralateral, 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-
ever, where localization is obtained primarily with interictal and ictal scalp EEG recordings and FDG-PET, but chronic intracranial evaluation is not done. Occasionally, 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 performed surgical procedure in the treatment of partial epilepsies. Variations in techniques and extent of resection have been reviewed by Crandall (2 7). W e will pre-
sent here four techniques of temporal resection.
Standard En Bloc Resection The Falconer-Crandall resection (27,28) of the ante-
cal evaluation f or some patients with partial epilepsy. At UCLA, questions concerning older children and adults that arise during phase 1 are usually answered by a
rior temporal lobe uses sharp dissection cleaving anatomical structures of the temporal lobe (Fig. 11). This
phase 2 evaluation in lieu of ECoG. W hen a standard en
method has the following advantages: it is performed
bloc anterior temporal lobectomy is performed, it is based on data acquired during presurgical evaluation;
under general anesthesia; it allows fixation of the head and the use of the surgical microscope; it permits quantification of the resection for interindividual analysis of outcome; and it produces a surgical specimen suitable for further neurophysiological and neuropathological
intraoperative electrocorticography is rarely necessary. Similarly, the presurgical evaluation for tailored resections 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 performed for resections in infan ts and small children, how-
studies. The patient is placed in a supine position with the head at a 45-degree angle away f rom 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-
5cm
5cm
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.)
TH E EPILEPSIES 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 su periorly and p osteriorly above the ear, then directed toward the midline, cur ving anteriorly 4 to 5 cm from the midline to end in the frontal area within the hairline. A scalp flap is raised anteriorly unt il the fron tal process of the zygom a is palpable. To avoid injury to the frontalis branch of the facial nerve, the skin is not elevated along the zygoma. The temp oralis muscle is incised lon gitu dina lly 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 p erimetry of the cra niotom y, and gloves are washed to remove blood and bone dust to prevent "aseptic meningitis." Th e dur a ma tter is incised in a U-shaped curve hinged just above the location of the sylvian fissure. The cortical incision is measured on the middle temporal 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 obl iqu ely dow nw ard at about 45 degrees to spare the p rimary a ud itor y 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 coagulated with bipolar forceps and sharply incised with microscissors. Dissection is carried by subpial aspiration along the anterior portion of the sup erior gyrus, preserving the arach noid layer of the sylv ian 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 temp oral stem and inferiorly until the floor of the middle fossa is reached. The dissection is carried superiorly unt il the ependyma of the temporal horn is opened, when a gush of cerebrospinal flu id occurs. The surgical microscope is brought over the surgical field, and self -retaining retractors are positioned to elevate the lateral cortex. With microsurgical instruments, the white matter over the roof of the temporal horn is thinned anteriorly unti l the tip of the ventricle is reached. This allows exposure of the lateral h um p of the glistening white hippocampus. The incision is carried through the amygdala anteriorly until the original anterior incision is reached. No incision is made m edial to the choroid plexus, as this is the location of the optic tract. The tela choroidea and fimbria-fornix are detached at the choroidal fissure w ith fi ne dissection. Great
care is taken to preserve branches fro m th e anterior choroidal artery ru nni ng 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-
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campi at the level of the lateral geniculate body. The
amb iens cistern is entered and small perfora ting vessels (the Ammon's horn arteries) and arachnoid bridges are sharply divided at the hippocamp al sulcus. The posterior cerebral artery, the anterior choroidal artery and the
third and f ou rth cranial nerv es can be identified and are preserved. The uncus is then lifted from its piai bed. leaving 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 abn orm alitie s on the ECoG. This type of resection is usuall y performed unde r local anesthesia to allow cortical mapping of the sensorimotor area and speech cortices, if operating on the dominant hemisphere. The
temporal stru ctures are removed in tw o stages: a lateral neocortical resection, follow ed by asp iration-suction of the mesial structures. This technique has th e advantage of obtaining a cortical ma p of essential cortex as define d by acute monopolor or bipolar stimulation, which may facilitate resection of a larger neocortical area or p resum ably reduce the severity of postoperative neuropsychological deficits. The variability of temporal neocortical interictal epileptiform activity during the ECoG, and the difficulty in distinguishing primary from projected spike
activity in the fron tal lobe remain problems for this technique.
FIG. 12. The hippocampus is detached by an incision along the fimbria and through the amygdala. (From reference 99, with permission.)
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CH APT ER 15
Am ygdalohi ppocamp ectomy
approaches was prev iously described by Niemeyer (165). The goal is selective microscopic removal of the lateral amygdala, the anterior hippocampus, and the parahippocamp al gyrus w ith preservation of the lateral temporal structures. This procedure is reported to cause less functional deficits with a similar outcome wh en compared to standard lobectomies in selected patients (166). The transsylvian approach is made through an interfascial pterional craniotomy, placed slightly posteriorly, exposing the anterior third of the superior temp oral gyrus. The inferior sylvian fissure is opened, and the lateral Ml segment 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 temp oral arteries. The lime n insu lae is opened for a distance of 2 cm , a nd dissection is carried un til the h orn of
is removed. Although this technique allows the boundaries of the resection to be determined preoperatively, results of cortical stimulation can be confirm ed w ith intraoperative bipolar stimulation under local anesthesia. Many centers still perform neocortical resections using intraoperative functional mapping alone (121). Excisions 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 resection beyond the insula or deep into the white matter in order to preserve long fiber tracts. Speech mapping allows resection of peri-sylvian cortex in p atients with evidence of early ictal interference with speech. We prefer to preserve B roca's area, even with evide nce of ictal onset involving this region. Due to variability in the size and location of Wernicke's area, functional mapping permits more extensive dominant posterior temporal resection 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 h ave not yet had experience with th is tech-
the v entricle is reached. The amygdala is dissected with a
nique. Small resections within the occipital lobe can pre-
microrongeur for histologic studies and the uncus is re-
serve visual function with excellent control of the seizure. Stereotactic ablations such as amygdalotomy and Field of Forel-otomy are no longer recommended (171,172).
With improvement in localizing seizure onset to discrete areas of the tem pora l lobe in selected patients, Y asargil introduced th e transsylv ian ap proach to resect the mesial basal temporal lobe (120). Selective removal of these structures using transventricular and transcortical
moved subpially; the hippocampus is dissected circum-
ferentially, after identifying the posterior communicating artery, oculomotor nerve, optic tract, and anterior choroidal artery. The overall mesial resection covers a length of 4 cm, a w idth of 1.5 cm, and a depth of 2 cm. This microsurgical procedure usually follow s SEEG analysis of the patient's typical seizures.
Posterior Hippocampal Resection Depth electrode recordings have been reported that suggest that almost 20 percent of complex partial seizures arise from the hippocampus beyond the posterior limit of standard anterior temporal lobectomies (167). Surgical access was modified by Spencer to resect documented 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 hippocampal gyrus. Pathological demonstration of neuronal loss and gliosis in the posterior hipp ocamp al specimen is correlated with a good surgical outcom e. Other Limited Resections
Hemisp herecto my The initial technique of cerebral hemispherectomy, described by Krynauw (173), involves resection of a complete hem isphere, leaving in place the thalamu s, basal 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, leav ing proximal vascularization to the basal ganglia intact. The corpus callosum is divided completely, and the lateral ventricle is entered. Th e caudate nucle us is identified , and a plane of dissection is carried above the caudate from anterior to posterior down the atrium at the temporo-occipital juncti on. The veins tha t drain into the sagittal sinus and into the vein of Galen are taken. Following the lateral 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 initially described with this technique, including delayed
hemosiderosis and later hemorrhage and death, RasSelective corticectomies are performed in areas en-
mussen modified the complete hemispherectomy to a
compassing both interictal and ictal activity and may occasionally involve portions of more than one lobe. Neocortical resections following subdural grid evaluations are usually p erformed at the time the su bdural grid
subtotal hemispherectomy, leaving the disconnected frontal and occipital poles in the surgical cavity (174,175). The insula may or may not be removed according to the intraoperative electrocorticogram. An ad-
THE EPILEP SIES
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ditional modification to prevent delayed bleeding consists 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
gery that is not present with respect to adult patients (137). In this section will be summarized the major ways in which the app roach to surgical managem ent needs to be adapted to the dev eloping br ain. The types of surgery most commonly performed also differ: anterior tem-
(177). Multilobar resection may also be appropriate
common form of epilepsy surgery in adults, whereas extratemporal excision, multilobar resection, hemispherectomy, and corpu s callosum section are the appropriate treatments in a much higher proportion of pediatric
wh en large p arts 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 techn ique necessitates a vertex fronta l craniotomy, usually over the nondominant hemisphere, exposing the anterior interhemisph eric fissure and p reserving the large draining veins to the sagittal sinus. Vascular anatomy is best defined presurgically w ith'a cerebral angiogram. Gentle lateral retraction of the frontal lobe allows the identification of the cingulate gyrus an d, inferiorly, of the pericallosal arteries. With magnification, the white reflection of the corpus callosum can be easily seen between th e two pericallosal arteries. Care mu st be taken not to conf use the callosomarginal artery with a pericallosal artery and proceed with the dissection into the cingulate gyrus. Division of the anterior two-thirds of the corpus callosum is made with an ultrasonic aspirator (CUSA ) or with a small bore microsuction an d fin e bipolar forceps. The e pendym a of the roof of the th ird ventricle can be identified and should be preserved to avoid a possible ep endymitis. The dissection is carried anteriorly into the genu of the corpus callosum and stopped once the rostrum is reached. Division of the an terior commissure, fornix, or massa intermedia of the thalamus, as originally described by Van W agenen and Herren (complete comm issurotom y) (180), is no longer perform ed. If
poral lobectomy for complex partial seizures is the most
cases. Intractability The amount of time necessary to determine intractability is typically much shorter in pediatric than adult surgical candidates. For the latter, it usually takes several years to hav e exhau sted all approp riate medical trials. In contrast, there are far fewer antiepileptic drugs available for use in you ng children, p articularly infants; moreover, because their seizures are typically much more frequent, less time is requ ired to determin e wh ether a given change in management has had any effect.
The obvious benefits of early intervention have made pediatric epilepsy surgery an area of increasing interest and rapid expansion. T he app roach to the surgical treatment of intractable partial epilepsy in adults applies in many respects equally to children with similar partial epileptic disorders. Nevertheless, some uniquely pediatric epileptic syndromes are also potentially treatable by surgery. M oreover, considerations of brain developm ent
Certain etiologies of frequent seizures imply intractability almost by their very nature; for examp le, congenital brain malformations (181), Sturge-Weber syndrome with early-onset seizures (182), or Rasmussen's encephalitis (183 ). If the seizures in such cases do not resp ond (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 unresponsive to ACTH, prednisone, and/or selected antiepileptic drugs like nitrazepam, are similarly unli kely to undergo 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 remission can be determined ev en as early as the neonatal period as, for example, with persistently unifocal, cryptogenic status epilepticus, wh ich probably begins in utero and, in our experience, has been uniformly due to focal cortical dysplasia (87 ). Most you ng children w ho are potential surgical candidates have many seizures per week or even per day, and there is little question regarding the designation of intractable. Some children who have only occasional seizures, however, might be considered potential surgical candidates because of the deleterious effects of medications and interictal electrophysiological disturbances on their developm ent, particula rly when there is a high likelihood 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
and plasticity add a dimension to pediatric epilepsy sur-
considered to be dull (185). In other cases, side effects of
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
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CHAPTER 15
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
(199,2 00), the risk of secondary epileptogenesis (20 1) remains a concern for children with f req uen t recurrent seizures. That this process is potentially reversible is suggested by the fact that seizures and EEG spikes can often disappear when children with bilateral or multifoca l independent epileptiform discharges, bilateral independent ictal onsets, hypsarrhythmia or modified hypsarrhythmia, or generalized slow spike waves u ndergo focal resection or hemispherectomy based on evidence of localized or lateralized abnormalities on brain imaging studies, EEG telemetry recorded ictal onsets, and/or ECoG(137). Experience with natural ly occurring brain lesions and with therapeutic hemispherectomy in hum ans indicates that language functions will shift to the right hemisphere following damage to the left early in life (202,203). Similarly, children or adults with hemiplegia from early infancy are typically able to walk quite well and can use the paretic arm for gross, proximal movements and as a
highly controversial; nevertheless, there is considerable
helper for the normal arm (204,205), in marked contrast
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 neu ronal
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 dy namic natu re of neurodevelopment and that of the epileptic process itself introduce a particular urgency in the determination of medical intractability among children. There must be a pru dent compromise between letting sufficien t time pass to determine intractability and operating early enough to maximize dev elopm ental potential throug h brain plasticity. 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 benef it, th e earlier the operation is performed, the better.
medications can produce adverse personality changes that seriously stress family dynamics and reduce the selfesteem of the child (186) . Thus, even th oug h drug toxicity per se may be readily reversible, some consequences of its chronic presence could be permanent. To the extent that resective surgery could permit the elimination or significant reduction of medication du ring these intellectually and emotionally formative years, it might eventually be considered even if seizure frequency per se might not be great enough to suggest a need for surgical intervention. Timing of Surgery
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 kno wn 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 "backfiring" (192), both in experimental animals and in huma ns
(193). In the developing rabbit brain, interictal discharges in the absence of seizures have been shown to lead to cytoarchitectural changes in sp atially distant but functi onall y 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 surgery as early in life as possible. The extent to wh ich antiepileptic drug toxicity can adversely 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 concern (196-198 ) and to constitute a minor additional motive for favoring a potentially curative procedure over the chronic administration of multiple, high-dose antiepileptic medications. Although controversies continue over whether the kindling phenomenon in animals is relevant to humans
Identification of the Epileptogenic Zone
Some children with seizure disorders presently classified 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 diff use cerebral abnormalities (55), p erhaps as many as a third of the cases are actually due to focal or unilateral pathology (206-209) and could respond favorably to focal resection or hemispherectomy (138,210). In such cases, localization of the epileptogenic region is accomplished by the convergence, or at least noncontradiction, of complementary types of evidence from structural imag ing studies, tests of epilep tic excitability, an d tests of cortical dysfunction. Even when the ictal onsets are difficult to localize or lateralize and the epileptiform discharges have a multifocal or widespread distribution, a safely resectable lesion can be strongly suggested by dem -
T H E E P I L E P S IE S
onstration of a substantial focal functional deficit and a structural lesion. In this instance, intraoperative ECoG may be h elpful 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 mapping (161). Indicators of focal cortical dysfunction are important for two reasons: first, it is very likely that the epileptogenic region is anatomically identical to, or approximates, a zone of markedly dysfu nctional cortex; and second, the excision of such an area will not introduce a significant new neurological deficit. Because the neurological examination in young children is much less localizing tha n 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 abnormalities), sodium thiopental activation, median nerve somatosensory and visual evoked potentials, intracarotid amobarbital injection (Wada test) f or older children in whom the lateralization of memory and language can be tested, and local cerebral metabolic patterns on interictal FDG-PET scan. If hemispherectomy is contemplated, these tests are also important for determining the relative fu nctio nal integrity of the other hemisphere.
Of all these tests, the most useful in this group of patients is by far the FD G-PET scan, which can reveal welldemarcated areas of marked dysfunction, even in the context of normal CT and MRI studies (87,139,208). These focal FDG-PET abnormalities h ave 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 in traoper ative electrocorticography are now Used to guide multilobar resections in small children with catastrophic secondary generalized epilepsies, particularly infantile spasms, even when epileptiform abnormalities are not localizing (208). Surgical resection in these chil dren not on ly abolishes epilep-
tic seizures, but reverses developmental delay, which is th e most p ressing criterion for considering surgical intervention in this situation. OUTCOME
Complications A detailed analysis of surgical complications follo wing 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.
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Complications of Diagnostic Procedu res
Invasive monitoring by stereotactic depth electrode imp lan tatio n carries a mortality rate of approxim ately 1 percent and a morbidity rate of app roxim atel y 4 percent (212). No major complications have yet occurred using magnetic resonance guidance associated with stereotactic angiography (145). Transient hemiparesis has been described with cerebral angiography, bu t the risk of ma jor com plications, such as per ma ne nt neu rological de ficit or death, is reported to be only 0.1 to 0.3 percent (213). The use of stereotactic angiography has decreased the num ber of hemorrhagic complications of depth electrode implantations in most centers. Infectious compli-
cations of chron ic depth electrode recording are reported to vary between 1 and 5 percent. These consist of cerebral 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 Creutzfeldt-Jacob disease (214). Epidu ral grid recording as described by Goldring and Gregorie did not produce any m ortality in 100 patients (215). They did report one scalp infection and one case of aseptic necrosis of the bone flap in this series. Subdural grid implantation for chronic recording can produce a transient rise in intracranial pressure (ICP), presumably from cerebral edema, in the first 48 hours. We now u se ICP monitoring concomitantly w ith steroids for the first three days after electrode implantation. Acute or delayed hemorrahgic comp lications 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 (2 12), and we hav e 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 implantation appear to prevent this reaction.
Complications ofResective Procedures
Lo cal ize d Corti cal Resection Aseptic meningitis presenting with fever and neck rigidity is reported to occur in approxima tely 15 percent of patients who undergo cortical resection (2 12). Cerebrospinal fluid studies show an increase in white blood cells and p rotein and a decrease in glucose. Repeated cultures remain negative. This complication improves without treatment in 2-3 weeks. In all series of anterior temporal l obectomy th e m ortality rate is extremely low. Minor side effects are frequent, however. Most frequent is a superior quadrantanopsia opposite to the side of surgery. Fortun ately, this usua lly
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C HA PTE R
15
remains unnoticed by the patient. Complete homonymou s hem ianop sia 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. Transient oculomotor or trochlear nerve palsy is also described 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 ("manip ulation hemiplegia") or by injury to the anterior choroidal artery supplying the internal capsule or cerebral peduncle. Complications from resections of the dominant hemisphere include speech difficulty, dysnomia, and dysphasia. These are, however, transient and occur in approximately 5 percent of cases. Severe m emory def icit 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 removal. No attempt to describe these in detail will be made here, but the reader may wish to consult Van Buren's chapter (212).
He mis pherectomy 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 conr sisted of delayed superficial cerebral hemosiderosis leading to subdural me mbrane form ation causing late hemorrhagic 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 Rasmussen, was intended to decrease the amount of movement 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 intracranial pressure because of the decreased reabsorption capacity of the arachnoid villi. Acute hydrocephalus is also a major complication, attributed to granular ependymitis blocking the ventricular system. Additionally, the absorption capacity of the remaining hemisphere may be
decreased, creating a degree of nonobstructive hydrocephalus. Shunting of the surgical cavity to the peritoneal space appears to decrease the amount of hydrocephalus and subdural membrane formation by decreasing the amount of fibrinogen and blood breakdown products (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 afte r an anterior or a complete section of the corpus callosum. This may be due in part to intraoperative retraction over the supplementary motor area. In some patients with mixed cerebral dominance, callosotomy produced permanent speech and language dysfu nction (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 eff icacy 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 w ho 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 extratcmpo ral
resections were somewhat less beneficial. The best results follow ing extratemporal surgery were obtained with hem ispherectom y and large mu ltilobar resections, although 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 anterior temporal lobectomy are better if mesial temporal structures are routinely removed (26,113). On the other hand, mem ory impairme nt may be more common wh en
lobectomy includes the h ippocampal pes. Postoperative results with respect to epileptic seizures comprise the most important category of data for determining th e therapeutic u sefulness of presurgical evaluation 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 outcome 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 imiportant consideration. Also, the term seizure-free does not necessarily mean free of seizures since surgery because, from a practical point of view, a patient who has had a few seizures in the first year or two after surgery
THE EPILEPSIES
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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
Anterior temporal lobectomy
88 17
68 77.3(0-100) 16 18.2 4 4.5 (0-33)
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. Although some studies have lumped seizure-free and almost seizure-free patients together, in m ost cases there is a considerable difference between the two in terms of social rehabilitation. The outcome classification scheme suggested by the Internatio nal League Against Epilepsy is shown in Table 2. The seizure-free and rare seizure categories are relatively straightforward. However, w hen deciding whe ther or not to perform an operation on a particular patient, the probability of worthwhile improvement rather than complete cure is usually the determining factor. Therefore, in order to evaluate the literature on a specific procedure or the track record of a particular center, it is the definition of this borderline group that should be most carefully considered. U nfortu nately, criteria for differentiating patients with wo rthwh ile improvem ent who continue 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 determined 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 regarding 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 followup time for assessing results. Patients should be cautioned, how ever, th at one or two seizures in the first two years foll owin g surgery do not necessarily mean they will not ulti matel y become seizure-free, nor does the absence of seizures during the first two years guarantee that seizures will never return (Figs. 13 and 14). Because outcome status can change from year to year, in order to compare groups of patients with different follow-up periods it is preferable to use year-by-year outcome data (Fig. 15). Outcome statistics for surgical treatment of epilepsy reflect selection philosop hy 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 indicates 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 percent of patients who do not benefit from surgery in almost 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 fr om th is procedure. Absolu te data are impossible to derive, but some information is available to indicate that there is impr ove men t in this area. For instance, in 1967 only 11 percent of patients evaluated in Falconer's series were selected for surgery (1 1) , wh ile approximately 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.)
Psychosocial Adaptation
Behav ioral changes associated w ith tem poral lobe surgery for epilepsy are related to psychosocial factors, as well as to relief from seizures. It is generally agreed that personality traits are more lik ely to imp rov e after successful surgery than are psychoses. Depression during the first year following surgical treatment has been reported, but is usually transient (217,218). While long-term depression may be no more prominent postoperatively than p reoperatively, 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 interv ention on psychoses have been consistent. Surgical treatment, while helping the epilepsy, does not improve a chronic psychotic condition, which is usually the ma jor ha ndi cap fo r the patient ( 11 4) . This is not the case fo r rare ictal or postictal transient psychoses that usu ally resolve when the epilepsy is cured (219).
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 patients are those who were classified as Class 3 and Class 4. Outcome classifications are defined in Table 2. (From reference 46, with permission.)
The extent of control of seizures is a significant factor und erly ing imp rovem ent in social status following surgical treatment for epilepsy (105). We found that patients tend to be slightly more dependent upon others two mo nth s after the operation regardless of outcome, apparently du e to recovery from the recent surgery (101). But by one year after surgery, patients whose seizure frequencies are significantly reduced show the expected gains in social independence when compared to their preoperative social level. This is reflected by the percentage of patients wh o become employed or receive educational retraining. Similar social changes are not seen in patients whose seizures are not controlled by surgery. At one year after surgery, interpersonal relationships also imp rove f or the seizure-controlled patients. This improvement seems to be largely attributable to increased non-family interactions, apparently associated with newly developed social independence. The family relationships of patients are more resistant to change; in some cases, interpersonal family relationships have even
TH E EPILEPSIES
——— 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 percentage 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, divorce appears to be more common in patients who have become seizure-free. In this situation, the marital relationship apparently has required the patient to maintain a depend ent role (101 ). In selected cases, fa mily cou nseling has proved beneficial. Postoperative psychosocial adaptation improves in most patients who experience relief from, or reduction in, epileptic seizures. Risk fac tors fo r a poor psychosocial outcome include inadequate family support, operation after the age of 30, and evidence of an addictive personality (104). Patients with improved seizure control show higher scores on intelligence tests as early as one to two mon ths after surgery, and scores continue to increase for at least one year. An av erage 10 po int increase in IQ scores in the first year is of particular significance, since all patients are maintained during this time on preoperative anticonvulsant medication levels. Intellectual changes seen at this time, therefore, cannot be attributed to reduction of medication levels, but probably reflect a general improvement in adaptive abilities heretofore depressed by
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an active epileptic focus. Increases in intellectual scores were not found postoperatively in patients whose seizures were not controlled, nor in evaluated but unoperated epileptic patients tested at comparable periods (1 01). Selective memory deficits have been well documented following surgical excision of either the left or right temporal lobe. Difficulties in learning verbal material, presented either aurally or visually, have been associated with the language-dominant temporal lobe. Difficulties in learning material not easily verbalized have been associated with the nondominant, temporal lobe (220,221). The degree of memory deficit has been related to the extent of hipp ocampu s removed (107), and to the extent of intactness of the opp osite hippo camp us (103). Recent evidence indicates that these selective learning deficiencies occur wh eth er 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 temporal lobe (101,222). This phenom enon is undoubtedly related to the same process responsible for p ostope rative increases in intellectual skills. In Western societies a deficiency in verbal memory, which is associated with dominant temporal lobe resection, is usually a greater handicap tha n a deficit in nonverbal 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 m emory deficit may be m ore devastating than an uncon trolled seizure disorder. In our experience, the lifestyles of most patients considered for language-dominant temporal lobe resection have not been heavily depend ent up on strong verbal me mory 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 tempo ral lobe, particularly wh en seizures continue , and th e consequences of this potential handi-
cap should be considered. RESEARCH OPPORTUNITIES
Quite apart from the clinical success of surgical therapy for individual epileptic patients, and the value of
data collection for improving the efficacy of these procedures, it is appropriate to discuss the im portance of this work to the more general problem of understanding epilepsy. In the classical tradition of Hughlings Jackson (223), and P enfield and Jasper (159), m uch of ou r knowledge of the functional anatomy of the human brain has
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been derived from studies of epileptic patients. Centers engaged in the surgical treatment of epilepsy have un iq ue access to correlative behavioral, neurop hysiological, neuroanatomical, neuropathological, and neurochemical information from epileptic patients that provides an extraordinary opportunity to investigate basic mechanisms of epileptogenesis and normal brain function in humans (224). Because most basic research carried out on epilepsy has employed a nima l models, the relationships, if any, between the wide variety of experimental epilepsies (225) and the human epilepsies (226)
are for the m ost part unknow n. The fact that therapeutic advances have generally come from studies utilizing experimental animal models has important clinical significance. For example, the failure of antiepileptic pharmaceutical agents to control certain forms of complex partial seizures may be directly related to the possibility
that this human disorder involves mechanisms significantly diff eren t f rom those responsible for seizures in the animal models used for developing antiepileptic drugs.
A limited amou nt of data from studies in hu man s suggests that some aspects of the more popular laboratory models of epilepsy are common to human epileptogenesis. The paroxysmal depolarization shift and afterhyperpolarization recorded intracellu larly f rom a wide variety of experimental epileptic foci produce a burst of neuronal firing followed by inhibition, which correlate with the EEG spike and slow wave respectively (227). Extracellular recordings from the human epileptic hippocampus have demonstrated similar relationships between unit firing and EEG waves (228), although the percentage of bursting neurons in the human epileptogenic region appears to be considerably smaller than in experimental neocortical penicillin foci. Golgi stains of cortex from chronic alumina foci have demonstrated neurons with shrunken dendrites denuded of dendritic spines (229). Similar cells hav e been fo und in resected temporal lobe specimens taken from patients with complex partial seizures (230). Although it is not yet known whether
these anatomically abnorm al neu rons are responsible fo r the epileptic activity, a result of the epileptic activity, or totally unrelated, their existence has figu red prom inently in some theories of epileptogenesis (231 ,232). M orphological 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 spro uting of granu le cell mossy fiber axons back o nto their ow n dendrites, creating recurrent excitatory circuits (39). Similar morphological changes have
now been identified in the human epileptogenic hippocampus (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, epilep tiform discharges (233). These multifocal abnormalities may be the result of functional changes such as those that occur with secondary epileptogenesis (23 4) or kind ling (235), or of structura l damage induced by frequent seizures (34). It is not yet clear whether the multifocal abnormalities observed in patients under evaluation for surgery represent features common to all forms of secondary partial seizure disorders in hu ma ns, or whether these findings are peculiar to those pa tients who se seizures are medically intractable and sufficiently severe to be considered for surgical therapy. Evidence from primate models, however, suggests that bilateral foci may be necessary before complex partial 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 seizures, w ith th e unde rstanding tha t other distant areas of epileptogenic tissue may very likely remain. This explains 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 studies, 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, electrophysiological 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 ap pearance of hypersynchronous ictal epileptiform discharges (238,239). Since depth electrode recordings have identified 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 transition to ictus in hu man p artial epilepsy may inv olve more than one mechanism, one perhaps requiring disinhibition, while the other involves hypersynchronization as a result of enhanced excitatory and inhibitory mechanisms similar to that proposed for petit mal type absences (239). Anoth er important difference between hu man and experimental epilepsy is illustrated by the variety of patterns of regional metabolism seen with ictal FDG-PET in human partial epilepsy (88) compared to the stereotyped 2DG autoradiographic patterns seen in animals with e xperim ental seizures induced by cortical penicillin (240,241) and amygdaloid kindling (242). Whereas the
