Epilepsy Cap 15

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Principles of Neurosurgery,edited by Robert G. Grossman. Rosenberg 1991.Published by Raven Press, Ltd., New York.

CHAPTER 15

The EpilepsiesJerome Engel, Jr., Michel Levesque, Paul H. Crandall, D. Alan Shewmon,Rebecca Rausch, and William Sutherling

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

Basic Evaluation, 322

EEG Evaluation, 323Imaging Studies, 324Neuropsychological Testing, 326Indications for Further Evaluation, 326

Inpatient Evaluation, 328Phase I (Extracranial EEG Telemetry), 329Phase 2 (Intracranial EEG Telemetry), 334

Operative Procedures, 341Electrocorticography, 341Operative Techniques, 342

Special Considerations for the Developing Brain, 345Intractability, 345Timing of Surgery, 346Identification of the Epileptogenic Zone, 346

Outcome, 347Complications, 347Seizures, 348Psychosocial Adaptation, 350

Research Opportunities, 351References, 353

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

J. Engel, Jr: Departments of Neurology, Anatomy and CellBiology, and the Brain Research Institu te, U nivers ity of Califor-nia, Reed N eurological Research Center, Los Angeles, Califor-nia 90024-1769.

M. Levesque: Department of Surgery (Division of Neurosur-gery), University of California, Los Angeles, California 90024-6901.

P. H. Crandall: Departments of Neurology, Surgery (Divi-sion of Neurosurgery), and the Brain Research Institute, Uni-versity of California, Los Angeles, California 90024-6901.

D. A . Shewmon: D epartments of Neurology and Pediatrics,University of California, Los Angeles, California 90024-1752.

R. Rausch: Department of Psychiatry and BiobehavioralSciences, University of California, Reed Neurological Re-search Center, Los Angeles, California 90024-1769.

W. Sutherling: D epartment of Neurology, University of Cali-fornia, Reed Neurological Research Center, Los Angeles, Cali-fornia 90024-1769.

abnormalities in the human brain, and of the greatersafety and efficacy of modern diagnostic and therapeuticsurgical procedures. Despite this, however, only a small

fraction of patients who might be candidates for epilepsysurgery receive attention at epilepsy surgery centers. Al-though it has been estimated that perhaps as many asone quarter of a million people in the United Statesalone might benefit from surgical intervention, perhapsonly four or five hundred a year receive this treatment(2). This can be attributed in part to a lag in the dissemi-nation of information to primary care physicians andtheir patients concerning these new developments andthe indications for referral to epilepsy surgery centers,and in part to the limited number of epilepsy surgeryfacilities currently available. The latter results from a re-luctance on the part of medical centers to commit thepersonnel, space, and resources necessary for a dedicatedepilepsy surgery program at a time when reimbursementfor medical care involving expensive diagnostic and ther-apeutic procedures is being questioned and reduced.This chapter is intended to address the first problem di-rectly, by describing the modern role of surgical inter-vention in the treatment of epilepsy, with the hope that asubsequent increased demand for epilepsy surgery willindirectly help to resolve the second problem. The dis-cussion is primarily concerned with localized resective

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surgery for medically intractable partial epilepsy, but anincreasing number of patients with secondary general-ized epilepsies are becoming candidates for large multi-lobar resections as well as corpus callosum section, andthese procedures will also be briefly considered.

NEED FOR SURGICAL TREATMENT

The epilepsies afflict at least one million people in theUnited States. These relatively common neurologic dis-orders principally affect the lives of young people: over75 percent of all epilepsy begins before the age of 15 (3).

According to the classifications of the InternationalLeague Against Epilepsy (4), epileptic seizures can bedivided into two categories: generalized seizures (thosethat are generalized from the start and are associatedwith bilaterally synchronous EEG changes), and partialseizures (those in wh ich ictal behavior and/or EEG alter-ations indicate initial involvement of a restricted systemof neurons limited to a single hemisphere). Partial sei-zures are further divided into simple (no impairment of consciousness) and complex ( impairm ent of conscious-ness) subtypes.

In a 33-year-long study of 1,457 patients (5), a fairlyhomogeneous white population in the northern UnitedStates with recurrent seizures (either febrile or afebrile)was identified, showing a mean annual incidence of 48.7/100,000 population. Prevalence for recurrent afe-brile convulsions was approximately 6.7/1,000 popula-tion. Sixty percent of the patients studied manifestedpartial seizures, with higher incidence rates at the ex-tremes of life.

In a French population of a more heterogeneous na-

ture, nearly 40 percent of 6,562 epileptics experiencedcomplex partial seizures (6). Complex partial seizuresare believed to be the single most common seizure type.Anticonvulsant therapy is effective in only an estimated35 to 50 percent of these patients (7). However, medi-cally intractable partial seizuresand, in particular,complex partial seizurescan often be successfullytreated with surgery. Furthermore, surgical interventionmay also benefit carefully selected patients with medi-cally intractable generalized seizures that occur as symp-toms of multifocal or diffuse cerebral disease processes.

More than 60 years after Horsley first described surgi-cal therapy for partial epilepsy (1), the safety and efficacy

of surgical treatment was unequivocally demonstratedfor those patients in whom interictal EEG paroxysmswere highly unilateral and localized (8-10). Unfortu-nately, the vast majority of patients were excluded be-cause they were shown to have bilateral independent dis-charges or widespread interictal abnormalities.Regarding the application of surgical treatment in 1967,Falconer wrote: "the selection of patients has been rigor-ous, and we estimate that only about one in nine personsreferred forsurgery fulfill[our] criteria" (11). The exces-sive use of operating room time for intraoperative diag-

nostic studies, and the necessity for an integrated special-ist team, resulted in surgical treatment becomunderu tilized in the 1960s, and only a handful of cetreated significant numbers of patients.

Since the 1960s, a variety of diagnostic methods hbeen developed that fu rther enh ance reliable localizof epileptic foci (12). Our tools have been stereotsurgery (13,14), intracranial electrodes wh ich providartifact-free recordings during ictus (15-19), long-EEG monitoring (20-22), and techniques to localize ce-rebral areas demonstrating focal functional de(12,23). The principle objectives in this chapter adescribe these diagnostic techniques, the surgical otions, and the results. Introduction of these new diatic tests has resulted in identification of a progresslarger population of patients with partial seizures could significantly benef it from surgical treatment wout incurring und ue risks. In contrast to Falconer's erience, approximately 80 percent of patients evalufor surgery at UCLA eventually undergo a therapprocedure. There is, therefore, an increasing needmore facilities to provide this form of surgical ther

ETIOLOGY AND PATHOLOGY

-A distinction must be made between three terms thatare commonly used in reference to partial epilepsy:eleptic focus, epileptogenic lesion,and epileptogenicgion (24). A n epileptic focus is an electrographic conthat refers to the site of maximal EEG-recorded interspike activity. An epileptogenic lesion is a structuralcept that refers to a discrete pathological substrate of par-tial epilepsy. A n epileptogenic region is a theoretical

cept that refers to the area of cerebral tissue thanecessary and sufficient to generate recurrent partial sei-zures. It is the epileptogenic region that needs to betified by presurgical evaluation procedures and, mately, resected in the surgical treatment of epilepsy.The boundaries of the epileptogenic region, howecan only be inferred from a variety of tests that definlocation and extent of functional and structural cerebralabnormalities. The epileptic focus, epileptogenic lesand epileptogenic region are not necessarily congsince interictal spikes may be secondarily generatedfrom multiple brain areas, and habitual seizures originate at a distance from documented structura

sions. Whereas EEG studies are essential to demonstratesites of interictal spike occurrence and ictal onset, thesedata do not prove the location of the epileptogenigion. The pathological substrates of partial epilepsy maybe identified with structural imaging tests such as xcomputed tomography (XCT) and magnetic resonaimaging (MRI), bu t the underlying defects are morten demonstrated in the surgical patient population by careful histological analysis of resected brain tiThese latter studies have helped to develop an under-standing of the causes of hu man partial epilepsy (25


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Any localized injury to the cerebral cortex occurringin utero or after birth can give rise to a partial seizuredisorder. Consequently, patients may have a history of gestational or birth difficulties, head trau ma, meningitis,or other potential cerebral insults. More informationabout the pathological anatomy underlying complexpartial seizures has been gained as a result of the tech-nique of en bloc resection of the anterior temporal lobe

(see "Operative Procedures") (11,27-29), which allowscareful histologic evaluation of intact surgical speci-mens. Most lesions encountered are in the medial tem-poral structures (hippocampal pes, parahippocampalgyrus, and amygdala), and their nature is usually notsuspected from routine diagnostic evaluation. Mesialtemporal sclerosis, the most common lesion found post-mortem in patients with complex partial seizures (30), isalso the most common lesion fou nd in resected temporallobe specimens (25,26,31-33).

Controversy exists concerning whether mesial tem-poral sclerosis is a cause or an eff ect of recurrent epilepticseizures. Patients with mesial temporal sclerosis have agreater-than-expected incidence of prolonged febrileconvulsions in infancy and f ami ly history of epilepsy(31), and prolonged seizures in animals can producechanges in the hippocamp us comparable to hu man me-sial temporal sclerosis (34). Such observations have sug-gested that there is a genetic predisposition to seizureinduction of this pa rticular pattern of cell loss in the h ip-pocampus, and also to the subsequent appearance of re-current complex partial seizures in association with thelesion. The epileptogenicity of this pathological abnor-mality has been inferred from the clinical knowledgethat seizures appear to originate with in the sclerotic hip-

pocampal tissue (35), and that removal of a portion of the temporal lobe containing mesial temporal sclerosisusually results in resolution of the seizure disorder(32,33). While patients who benefit from surgery occa-sionally yield brain tissue that appears completely nor-mal, quantitative cell counts of hippocampal specimensfrom such individuals have revealed abnormal neuronalloss suggesting a mild degree of hippocampal sclerosisthat is not recognized by routine pathological analysis(36). It is currently believed that such cell loss leads toaxonal sprouting and synaptic reorganization, account-ing for the development of chronic epileptic neuronalactivity (37-39).

Besides mesial temporal sclerosis and focal scarringfrom trauma or infection, other pathologic changes com-monly noted in surgically resected specimens from pa-tients with partial epilepsy, who usually give no historyof any predisposing etiologic event, inclu de glial tum ors,meningiomas, heterotopias, angiomas, cysts, and focalcortical dysplasia (25,40,41).

A family history of epilepsy is not unusual in patientswith temporal lobe epilepsy (29,42). In contrast to thefamily history of epilepsy found in hereditary primaryseizure disorders, where the seizure manifestations are

usually similar in all affected family members, the famihistory of epilepsy in patients with complex partial szures is usually qu ite varied. Other f amily members mhave had chronic seizure disorders or isolated seizursecondary to a variety of cerebral insults . This p robabindicates a genetically determ ined lowered th reshold fseizures, perhaps necessary for the development of ucomplicated partial epilepsy in response to a single foc

lesion.M any of the diagnostic tests tha t will be discussed hewere developed under the assumption that epileptogenregions develop in, or adjacent to, areas of damagebrain and should exhibit evidence of localized functiondeficit as well as epileptic excitability. If the site of epileptic excitability, as measured by EEG-recorded interictaspike activity and ictal onset, coincides with the site focal functional deficit, measured by a variety of tests be described later, the incidence of pathologic changes ithe resected specimen is high and surgical results are excellent (23,43,44). When partial epilepsy is treated bresective surgery, careful pathologic evaluation of thspecimen is of clinical importance, as demonstration ofstructural lesion correlates with a good prognos(32,33,45). This information can be useful in preparinthe patient, family, and referring physician for the fture.

Un for tunate ly, the concept of a single isolated epileptogenic abnormality in patients with a medically intracable partial seizure disorder may be an oversimplifiction of the problem. Multifocal abnormalities are ofteencountered during the diagnostic evaluation, and patients frequ ently are only partially relieved of the ir epiletic symptoms by surgery (46). Clearly a spectrum of ep

leptic disorders ranges from simple partial seizurphenomena due to a small w ell-defined epileptogenic sion, through bilaterally independent and multifocal diorders, to the so-called secondary generalized epilepsie(47) in which the cerebral disturbances are so diffuse thseizures appear to be generalized from the start (24). Adefinitive determination of where an individual patienmay lie along this continuum can never be obtainemerely from pathologic evaluation of a resected temporal lobe or other cortical specimens removed at sur-gery. Additional lesions may still exist in the remaininbrain. Consequently, a clear picture has yet to emergconcerning the pathophysiological basis of partial se

zure disorders that may or may not respond to surgicainterven tion. Basic research p rograms at centers engagein the surgical treatment of epilepsy provide an impotant opportunity to elucidate these issues, as will be dicussed at the end of this chapter.

NATURAL HISTORY

A natural history of partial epilepsy is valuable as gauge against which to measure the eff icacy of any therpeutic interventions (48). Strictly speaking, we are no


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likely to get a true na tural h istory, since all patients nowreceive treatment. A series of articles from Oxford,which followed 100 children wi th temporal lobe epilepsyinto adulthood, is the nearest approach to a natural his-tory so far compiled (49,50-52). The subject patientswere taken from a larger unselected population of over1000 children with seizures of all kinds. The collection of the series began in 1948 and ceased in 1964. Patientswere followed until 1977. Clinical diagnosis was con-firmed by two physicians, and an EEG demonstrated afocal discharge in one or both temporal regions. Collec-tion was strictly consecutive, and it was possible to traceall of the patients in the series. N inety-f ive patients weredivided into three outcome categories (five patients diedas children before the age of 15). Thirty-three patientswere able to support themselves socially and economi-cally, were seizure-free, and were not receiving anticon-vu lsant medication. Thirty-two were also able to supportthemselves socially and economically; however, theywere receiving anticonvulsants and were not necessarilyseizure-free. Thirty patients were not able to supportthemselves 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) dailytemporal lobe attacks; (5) a left-sided EEG focus; (6) hy-perkinetic syndrome; (7) catastrophic rage; and (8) thenecessity for special schooling. In the best group, 30 of the 33 patients had three or fewer risk factors and 10 hadnone. In the worst group, 25 of the 30 patients had fouror more risk factors. Nearly all patients in the best groupwent into sustained remission before the age of 15; inretrospect, some (if not most) of these probably had the

familial condition of benign epilepsy, with centrotem-poral spikes (53), rather than temporal lobe epilepsy.It is of particular interest here that a subset of patients

in this study who continued to have seizures ultimatelyunderwent surgical treatment. An investigation fromLondon of 666 patients with temp oral lobe epilepsy (54)also contained a subset of patients who had medicallyintractable seizures and underwent surgical treatment.Whereas in both studies patients with persistent seizuresgenerally experienced functional deterioration, this didnot occur when surgical resection successfully abolishedthe habitual ictal events. Such evidence that psychoso-cial. if not physiological, disability can be progressive has

been used as an argument for early surgical intervention


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

Patients often give a history of more than one type of seizure. Most patients with partial seizures also have hadone or more secondarily generalized seizures. As a gen-eral rule, the more different types of seizures a patienthas, the more likely she or he has multifocal or diffusecerebral disease and is not a good candidate for resectivesurgery. However, careful evaluation of ictal events (asdescribed in the section on inpatient evaluation) mayreveal that what first appeared to be a variety of seizuretypes may actually be a numb er of manifestations of thesame basic seizure, consistent with a single dominantepileptogenic region.

Neurologic Examination

Even thou gh patients with partial seizures who are be-ing considered for surgical therapy usually do not dem on-strate focal deficits on neurologic examination, a carefulevaluation should always be performed. General physi-cal findings, such as cafe au lait spots with axillary freck-ling or evidence of hemiatrophy, may indicate heredi-tary or congenital disorders associated with focal brainlesions. The most comm on neurologic abnorm alitiesfou nd in patients with complex partial seizures are mem-ory disturbances, which often are revealed on specializedtesting, even w hen th ey hav e not been elicited by history.Problems in remembering verbal material and asso-ciated word-finding difficulties suggest an epileptogenicregion in the language-dominant hemisphere. More spe-cific motor or sensory neurologic deficits usually implythat the major pathologic changes are suprasylvian. For-

mal visual field testing is generally included in thescreening test battery, although visual field deficits arenot common in the absence of large mass lesions.

EEG Evaluation

Routine EEGThe most useful diagnostic tool in the evaluation of

the epileptic patient has traditionally been the EEG. Forthe potential surgical candidate, routine ou tpatient EEGstudies are important to confirm the p artial nature of theepileptic disorder by demonstrating focal interictal spikeactivity, as well as other focal intermittent or continuousabnormalities. Preliminary localizing information mayalso be obtained from the outpatient interictal EEG, butdifferences of opinion exist concerning the relative valueof interictal electrophysiological phenomena for pur-poses of localization, as compared wi th recordings of ic-tal onset (12,19,60). Although good results can be ob-tained in many cases with surgery performed entirely onthe basis of interictal scalp EEG localization, there isgeneral agreement that interictal epilep tiform dischargescan be misleading in 10 to 20 percent of patients(23,61,62). This is particularly true w ith complex partialseizures of limbic origin. Interictal EEG spikes may be

more localizing with extratemporal neocortical foci, paticularly if the interictal EEG spikes correspond with discrete structura l lesion demonstrated on XCT or M RPresently, inpatient ictal recordings are always also obtained on all patients considered for surgery at UCL(see "Inpatient Evaluation").

There are a number of potential hazards to undestand and avoid when using routine interictal EEG stuies to identify a partial seizure disorder and localize aepileptogenic lesion. A n um ber of normal EEG variantsuch as small sharp spikes, 14 and 6/sec positive spikewicket spikes, the so-called psychomotor variant an6/sec (larval or phantom) spike and wave phenomencan be mistaken for pathologic spikes if their charactertic features are not recognized (47). Abnormal spike dicharges, such as occipital spikes, periodic lateralized epleptiform discharges, and sylvian spikes, may not bassociated with epilepsy or may not indicate the locatioof a resectable epilep togenic region (47). Even epilepsrelated pathologic interictal EEG spikes may tend toshift location, particularly in children (61), and do noalways correlate reliably w ith th e site of the epileptogenregion (23,62,63). Bilateral independent temporal EEspikes are common in patients with complex partial sezures who eventually do well with unilateral temporlobectomy (23,46), and the predominant EEG focumay occasionally be contralateral to the primary epiletogenic region (23).

Special Electrodes

Basilar electrodes that are capable of recording epilep-

tiform activity originating from mesial aspects of thtemporal lobes are most commonly used in the EEevaluation of patients with complex partial seizureElectrodes placed on th e earlobes, over the zygoma, or the true temporal(T1,T2) location are at least as effectivas nasopharyngeal electrodes in identifying interictaspikes not seen with the routine 10-20 placement syste(64). Because nasopharyngeal electrodes are uncom forable, unstable, near pharyngeal muscles that cause artfacts that may be impossible to differentiate from cerbrally generated spikes, and are separated by wet mucoumembrane that makes lateralization diff icu lt, the ir usediscouraged. Sphenoidal electrodes provide a somewhhigher yield than other basilar derivations and are quistable, so that their use is recommended for long-termmonitoring (65); however, this yield is not sufficientlhigh to warrant their routine use in the outpatient EElaboratory. The use of several basilar derivations simultneously 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 spiklack their characteristic appearance w hen recorded f romesial temporal p lacements and cannot be easily diffeentiated from pathologic spike phenomena, even by tmost experienced electroencephalographer, w ithou t a


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cess to EEG patterns simultaneously derived from thescalp (47 ). Th erefore, basilar EEG studies should alwaysinclude an independent lateral temporal montage toidentify the surface electrical field of all medially re-corded spikes (as in Fig. 4). These recordings should notbe done on an 8-channel EEG machine; such machinesdo not allow sufficient independent surface monitoringto analyze medially recorded phenomena properly. Atleast 12, but preferably 16 or more, channels should beused for these studies. A good general rule is to take seri-ously only those mesial temporal spikes that have anidentifiable field over the appropriate temporal surfacenot characteristic of 14 and 6/sec positive spikes, smallsharp spikes, or other normal variants. By using thesetechniques properly, one can obtain positive recordingsfrom patients with suspected complex partial seizuressignificantly more often than by routine EEG alone(65,67).

Activation

Activation procedures such as hyperventilation, pho-tic stimulation, and sleep are routinely used in the EEGlaboratory. Hyperventilation may provoke focal slow-ing, spikes, and even partial seizures. Since photosensi-tive epilepsy is almost always a primary generalized dis-order, photic stimulation is much less likely to be usefu lin the evaluation of partial seizures, except in the differ-ential diagnosis between partial and generalized seizuredisorders. Sleep can also activate interictal EEG spikedischarges, particularly frontotemporal spikes associatedwith complex partial seizures, but it is important to ig-nore the normal and clinically insignificant sharp tran-sients associated with sleep, and to be aware that interic-tal EEG spikes activated by slow-wave sleep have lesslocalizing value than interictal spikes seen du ring wake-fulness (68). As with basilar electrode placements, sleepstudies are useful for demonstrating the presence of afocal epileptiform abnormality when the diagnosis of apartial seizure disorder is not clear from history and ex-amination and routine EEGs are equivocal; therefore,the two techniques are often used together. How ever, if the diagnosis is clear from other evidence, and the pa-tient is scheduled to undergo an inpatient presurgicalevaluation, these procedures are not necessary.

Imaging Studies

Structural Imaging

Focal structural abnormalities may be demonstratedwith XCT or MRI, although this is not as commonamong patients referred for surgical treatment of epi-lepsy as has been reported for partial and secondarilygeneralized epilepsies in general (69-75). When a well-

defined mass lesion is found, the surgical treatmenoften dictated more by the nature of this lesion than the epileptic seizures. Patients with obvious brain mors will not be considered further in this discussionsurgery for epilepsyper se. W ith the advent of high-reslution structural imaging, however, the clinical imptance of many identified abnormalities is not alwclear. D efects seen on XCT and M RI can come and (76,77), and mesial temporalunidentified bright obje(UBOs) consisting of nonspecific increases in intenson T2-weighted M RI image, unassociated with chanon the Tl-weighted image, may hav e no structural corlate (78). Nonspecific structural defects such as smcysts, areas of calcification, disgenetic disturbances, alocalized cerebral atrophy that are not in themselvesindication for surgery help confirm the location of anepileptogenic region identified by electrographic aother functional means.

If the site of a demonstrated structural abnormalitycorrelates with the site of epileptiform EEG activity ("Inpatient Evaluation"), this is helpful in localizing sectable epileptogenic tissue; however, one should bin mind that structural abnormalities may be totaunrelated to the epileptogenic area (23). Consequently,demonstration of a structural abnormality by itsshould not be considered sufficient evidence for localition of the source of epileptic seizures.

Functional Imaging

The most important confirmatory test used at UCLis positron emission tomography (PET) with 18F-fluoro-deoxyglucose (FDG) (23,43,44,79-81). Many cent

have now demonstrated that the majority of patiewith partial epilepsy who are candidates for surgicaltreatment h ave FDG-PET scans with characteristic mebolic disturbances (82-85). This consists of a zone hypometabolism (Fig. 1), usually including the siteictal onset determined by surface and depth electroEEG telemetry, and the site of a structural lesion deter-mined by microscopic evaluation of the resected spemen (43,80,81). Although temporal lobe hypometalism is encountered in 70 percent or more of patientswith medically refractory complex partial seizures mesial temporal origin, they are less commonly sewhen the epileptogenic region is neocortical (86). FD

PET may be particularly important in the presurgievaluation of infants and small children with severe ulateral or secondary generalized epilepsy (87) where nronal plasticity allows larger resections than in the aduand chronic intracranial EEG recording is difficult perform. Many of these patients show unilateral hypmetabolic zones, even when structural imaging studare unremarkable. In this situation, FDG-PET also heto conf irm that the contralateral hemisphere is functiing normally.


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FIG. 1. PET scan with FDG from a patientwith complex partial seizures of left mesialtemporal origin. This scan was performed on

a Siemens-CTI 831 tomograph with an in-plane resolution of approximately 5 mm. Fif-teen horizontal planes of section are ob-tained simultaneously, and one or more setsof pianes can then be reformatted into coro-nal, sagittal, or other planes as desired. Notethat images front this tomograph show thepatient's left side on the right and the pa-tient's right side on the left. The PET scan ofthis patient demonstrates mild left temporalhypometabolism, which can be seen on allhorizontal planes of section through thetemporal lobe shown in (A) and enlarged forone section in (B). The hypometabolism canalso be appreciated in the coronal section(C) and in sagittal section through the lefttemporal lobe (D) when compared to the sag-ittal section through the right temporal lobe(E). (From reference 24, with permission.)

Ictal FDG-PET scans reveal areas of hyper- and hypo-metabolism that correspond to the origin and/or spreadof epileptic discharge during the seizure (82,84,88). Suchictal scans may be useful for elucidating the anatomicsubstrates of specific ictal behaviors; however, becauseregions involved in propagated activity cannot be distin-guished f rom the site of seizure origin, these scans are notas useful as interictal FDG-PET studies for localizing the

primary epileptogenic region.Studies comparing FDG-PET with various EEG testshave revealed basic differences (70,89). The FDG tech-nique measures the average intensity, over time, of meta-bolic activity in all cellular elements within each cerebralstructure scanned. The results are weighted according tothe energy requirements of individual elements withoutregard to the specific function or orientation of theseelements, or to the 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 wthese structures. The results are weighted according tothe degree of synchrony of these events and their spatialorientation, without regard for the number of elementsactually involved. The FDG-PET techniq ue reveals ana-tomic localization better than EEG; the EEG is neces-sary for the temporal sequencing of events. These tests

are complementary and together provide more func-tional information about the epileptic abnormalitiesunder study than either test used alone.

Nonepileptogenic lesions can also be seen as a zone of hypometabolism. Therefore, this FDG-PET defectper seis not sufficient for identification of an epileptogbrain region and should be considered only as confirma-tion of a focus demonstrated electrophysiologically. Al-though the transformation of an interictal hypometabo-lic zone into a hypermetabolic zone during ictus may be


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pathognomonic of an epileptogenic region withou t EEGevidence of epileptogenicity, focal hypermetabolism hasbeen 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 thatnonquantitatively measure cerebral perfusion providepattern s that are similar to those of interictal FDG-PET(91-94), although the reduced spatial resolution de-creases the yield. In addition, a variety of biologicallyactive tracers does not exist, and radiation exposure tothe p atient is greater than with FDG-PET. Ictal SPECTis, however, more easily performed than ictal FDG-PET,and can reveal patterns of hyper- and hypoperfu sion thatmay be useful for identifying the epileptogenic region(93,95,96). How ever, as with ictal FDG-PET, it remainsdifficult to differentiate the site of ictal origin from areasof ictal'propagation. SPECT is currently more accessiblethan PET since it does not requ ire an on-site cyclotron;but PET technology is becoming less complicated, andmore reasonably priced clinical systems are now beingmade (97). Where PET is not available, SPECT remainsa useful alternative.

Neuropsychological Testing

Neuropsychological testing provides useful diagnosticand prognostic information and is an important part of the presurgical evaluation (98). The neuropsychologicalevaluation is frequently used in combination with otherfunctional tests for confirmation of dysfunctional brain

areas (12 ,23 ,99). P rognostic uses of the neuropsychologi-cal evaluation include information as to the probabilityof 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 psy-chosocial function (104,105).

A comprehensive neuropsychological evaluationshould assess a wide range of functions. The evaluationshould include measures of general brain integrity aswell as tests sensitive to dysfunction of the temporal lobeand extratemporal areas. Psychological domains gener-ally assessed are language, intelligence, a ttention , cogni-

tive-tracking, sensation, perception, motor skills, andmemory functioning, as well as personality and psycho-social function (98,106).

The most reliable neuropsychological index of lateral-ization of temporal lobe dysfu nction is a selective mem-ory deficit associated with one temporal lobe (107). Thememory deficit should exist independent of other neuro-psychological deficiencies. Verbal memory tests such asthe delayed recall of logical prose and delayed recall of newly learned unrelated word-pairs, both derived from

modified administration of the W echsler Me(108), have been found to be particularly dominant temporal lobe dysfunction. Nonveory tests, such as the Rey-Osterrieth draw anand the delayed recall of the visual-reproduction subtesof the WMS, are more sensitive to nondomporal lobe functions. Interpretation of the nelogical profile is dependent upon knowledgspheric dominance for language, which is detthe intracarotid sodium amobarbital procedure (IAPThis test is described in the section on inpattion.

Indications for Further Evaluation

Positive Indica tions

Localized surgical resections are done to seizures that appear to have a well-defined onset in a cortical area that can be removed wducing additional unacceptable neurological though any epileptic disorder characterized by stereotyped partial seizures can be considered indication for further evaluation, in practitients who undergo inpatient evaluation fosurgical resections have complex partial seilive indications for surgical treatments such as corpucallosum section or large multilobar resectionhemispherectomy, are less well defined. Patieondary generalized epilepsies should be con

callosotomy when drop attacks are the mofeature of their disorder.Most complex partial seizures are limbic i

that originate from one mesial temporal region, athough they also can occur as a result of eregions elsewhere that project to mesial temptures. The best surgical outcomes are obtained in patients with complex partial seizures of mesiorigin who undergo anterior temporal lobectom(9,10,32,33,45,46,100,109-113). As a groularly when the lesion is mesial temporal sclepatients have a relatively high incidence of positive fam-ily history for epilepsy, prolonged febrile con

inf ancy, and an onset of seizures in the first d(31). If an aura is present, it often has an eother autonomic component, although a widhallucinations and cognitive, affective, and sory symptoms may occur, followed by alsciousness, staring, automatic behavior, and postictaconfusion, with amnesia for the ictal eventthese patients also experience auras withoComplex partial seizures may become secondarily gener-alized, but this is a relatively infrequent o


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(Other simp le motor or special sensory seizures with pre-served consciousness generally indicate extratemporalonset, which is an indication for other types of focal cor-tical excision). Neurologic examination may reveal amoderate memory deficit and radiologic studies areusually normal. The characteristic EEG pattern consistsof unilateral or, more com monly, bilateral independentanterior temporal interictal spike foci. These features aretypical of "temporal lobe seizures"; however, such fea-tures do not invariably distinguish an epileptogenic re-gion within the temporal lobe from a primary site of seizure generation elsewhere in the limbic system, or inother cerebral areas that project to limbic structures.Consequently, patients with such seizures are good can-didates for presurgical evaluation, but conclusions re-garding the actual location of the epileptogenic regionshould not be made on this information alone.

While this profile characterizes an ideal surgical candi-date, there is an inf inite variety of manifestations of sur-gically resectable epileptogenic regions. Each patientpresents a un iqu e problem and must be dealt with inde-pendently. It may be easier, therefore, to describe thosepatients with partial epilepsy who, at this stage in theoutpatient work-up, are not candidates for further pre-surgical evaluation.

Negative Indica tions

If pharmacologic management has not been adequateto establish that the patient is medically intractable, sur-gery is generally not considered until appropriate anti-convulsants have been given a proper trial (42,55). Sur-gery should also not be considered in patients with

seizures insuf ficiently severe to seriously disrupt the qual-ity of life. Decisions regarding the severity of the seizuredisorder cannot be based on any uniform criteria, butmust take into account each patient's capabilities andneeds. For instance, a patient with a nondemanding oc-cupation, who works alone with no set schedule, maytolerate several seizures a day, while another with em-ployment involving continued interaction with the pub-lic or constant attention and quick judgment may beunable to work with just a few seizures a year. In general,patients with few er than several seizures a month are notconsidered for surgical therapy. Patients with severemental retardation are relatively poor candidates for lo-calized resection, since this usually indicates diffuse cere-bral damage and multifocal epilepsy. However, such sur-gery may be justified occasionally if a reduction inseizure frequency would significantly ease patient man-agement at home or in an institution. While lower intel-lectual scores have been correlated with poorer seizurecontrol following anterior temporal lobectomy (101),there is no universal agreement concerning the degree of mental impairment necessary before a patient should nolonger be considered a candidate for this procedure. Fur-

thermore, such patients may benefit from other surgiinterventions such as corpus callosum section or larmultilobar resections; in small children, the latter creverse a developmental delay. Chronic psychosis is ten considered a relative contraindication to surgictherapy, since this condition is rarely reversed when sei-zures are abolished and patients remain incapacitat(114). Less severe personality disturbances can imprwith abolition of habitual seizures (114), however, ashould not dissuade a decision to proceed with presurcal evaluation. When seizures are due to a known pgressive cerebral degenerative process, localized surgicintervention is usually inappropriate. Finally, patiewith medical contraindications to surgery should not considered further.

Common Misconceptions

Many good surgical candidates are never referred ffocal resective surgery as a result of misconceptions cocerning the indications for these procedures (12). Sur-gery should be considered even if medication is shownbe effective, wh en the necessary7 dose required to contrseizures also causes unacceptable side-effects. This isparticularly important concern in children, wh o do ncomplain of overmedication and whose resultant poorschool perfo rmance or bad behavior may be erroneouattributed to the epileptic disorder. Although patiewith progressive degenerative diseases are usually nconsidered candidates for localized resection, progres-sive symptoms may be due to increasing seizure frquency, more severe seizures, drug effects, or psychocial factors, rather than to an underlying irreversib

progressive neuropathological process. Memory deficand specific cognitive impairment are not a contraincation to focal resective surgery since appropriate restion does not necessarily increase these disabilities. In 'fact, memory often improves and IQ increases by average of 10 points following successful anterior teporal lobectomy (101). Seizure-related reversible pchotic symptoms, such as transient postical psychosis,are not the same as chronic psychosis, and usually rsolve postoperatively when seizures no longer occThere is no truth to the old belief that su rgery is dangous in the language-dominant hemisphere, since speeareas now can easily be identified and avoided. Patiewith partial seizures that secondarily generalize, seizuwith multiple spread patterns from a single focus, "tyII" complex partial seizures (11 5), bilateral independeor synchronous EEG spikes, and even occasional contrlateral ictal EEG onsets, usually have a single epilepgenic region that can be identified and resected with beeficial results. Such patients, therefore, should not denied surgical consideration. Since patients with mesialtemporal sclerosis often have a family history of epilep(31), this finding should not raise concern about a pr


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ation is designed to determ ine il" habitual seizures origi-nate within the brain tissue to be resected, and if thisregion also demonstrates focal functional deficits. Whenthe intended surgical procedure is a tailored resection(121,122), the presurgical evaluation must not onlyidentify the site of seizure origin, but also the presumedextent of the epileptogenic region and often the bound-aries of adjacent primary cortical areas that cannot bedamaged. This latter situation, therefore, also requiresfunctional mapping procedures.

There arc several electrophysiological approaches tothe localization of the epileptogenic region in patientswith partial seizures who may be candidates for resectivesurgical therapy ( 12 ). Some centers rely heavily on non-invasive interictal EEG recording techniques, using rou-tine scalp and basilar electrodes. These are usually sup-plemented by intraoperative electrocorticography(ECoG) (19,62,63), as described in the section on opera-tive procedures. Others feel the epileptogenic region ismore reliably localized by inpatient recording of ictalevents using long-term video EEG monitoring (16), ei-ther with scalp and sphenoidal electrodes (23), or withintracranial (epi- and/or subdural) (17 ,18) or stereotacti-cally implanted depth (13-15) electrodes. There is noconsensus on a single correct electrophysiological ap-proach to the evaluation of the presurgical candidate(12). Most now agree that ictal plus interictal data arepreferable to interictal data alone , and tha t chronic intra-cranial recording is at least sometimes appropriate. C on-siderable disagreement remains about when interictalEEG and ECoG recordings are sufficient, and whenchronic intracranial recordings are necessary (19,123).

Because of the potential for false localization f rom elec-

trophysiological measures of epileptic excitability, it isvery important to use independent measures of func-tional disturbance to confirm scalp and intracranialEEG findings, and not to base decisions on only a fewtests. Consequently, the presurgical evaluation in mostcenters now involves a variety of tests aimed at identify-ing areas of abnorma l l?rain structure and fu nction (12).The UCLA presurgical evaluation protocol utilizes ex-tracranial and, as needed, various intracranial electro-physiological approaches to localize epileptiform abnor-malities. In addition, a variety of tests which measurefocal functional deficits are employed to confirm the lo-cation of the epileptogenic region determined electro-

physiologically. This protocol, therefore, can be used toillustrate most of the diagnostic procedures currentlyavailable in epilepsy surgery centers.

Phase 1 (Extracranial EEG Telemetry)

Methods of Scalp and Sphenoidal EEG Telemetry

Patients determined by ou tpatient studies to be poten-

tial surgical candidates are initially admitted for approxi-mately one to two weeks of scalp and sphenoidal EEGtelemetry with video monitoring. In some patients withdaily seizures, phase 1 EEG telemetry can actually beachieved on an outpatient basis by recording in a teleme-try unit located in the EEG laborato ry for 8 hours a day.Sphenoidal electrodes are 50-gauge, Teflon-coated, 15-stranded stainless steel wires, which are bared at the tip.These electrodes are inserted through a 22-gauge 1.5-inch needle, as shown in Figure 3 (24). Wires have beenleft in place for over six weeks without discomfort ordeterioration in recording characteristics.

During inpatient evaluation, the EEG is recorded con-tinuously (24 hours a day) according to approved stan-dards for long-term monitoring (20), transmittedvia ra-dio or cable telemetry, and stored on videotape (124).Behavior is recorded by two video cameras and a micro-phone, and data arc continuously stored on videotape.Much of the patient's time is spent in quiet activities sovideo recordings can be made, but ambulation and exer-cise are possible w ith ou t losing the EEG signal. As a rule,

FIG. 3. Illustration to show the placement of sphenoidal elec-trodes. The needle is inserted approximately 1 inch anteriorto the tragus immediately under the zygomatic arch (black dot on lateral view). The tip of the electrode should lie close tothe foramen ovale (basilar view). Inset shows how multi-stranded Teflon-coated wire protrudes from the tip of the in-sertion needle and is bent backward on the Teflon coating toprevent breakage of wire strands. The inner lip of the needlecan also be beveled to further ensure that breakage of thesphenoidal wire does not occur. (From reference 24, with per-mission.)


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should be recorded. It is most important to be certainthat the seizures captured on the telemetry unit are theseizures ca usin g the patient's problems at home. If neces-sary, videotapes can be shown to family or friends forverification. Additional tests are then performed duringphase 1 to obtain confirmatory evidence of dysfunctionat the site of ictal onset.

Evalua tion of Focal Functional D eficits

FDG-PET and neuropsychological evaluations areimportant confirmatory tests of focal functional deficitthat are performed on an outpatient basis and have al-ready been described. Two othe r tests, thiopental activa-tion and the intracarotid sodium amytal procedure(IAP), require hospitalization and are usually done dur-ing the phase 1 telemetry admission if ictal onsets arefocal.

Barbiturate narcosis is often used in order to activateinterictal EEG spike activity, although EEG spikes thatoccur during slow-wave sleep h ave less localizing valu ethan those that occur during wakefu lness (128). This testis useful, however, because focal attenuation of barbitu-rate-induced fast activity implies a functional deficit thatmay indicate the site of the epileptogenic region(45,131,132). We prefer to use intravenous thiopentalgiven at a rate of 25 mg every 30 seconds until adequatefast activity is produced in the EEG (usually 200 to 300mg). This drug is considerably more effective than seco-barbital because it provides more control over the levelof consciousness, and the observation tim e is longer thanwith the faster acting methohexital. In patients with

complex partial seizures, focal attenuation is most oftenisolated to one sphenoidal electrode (Fig. 5); this find ingcorrelates well with the presence of a mesial temporallesion on that side, usually mesial temporal sclerosis(45,131,132).

The intracarotid sodium amobarbital procedure wasoriginally done to lateralize hemispheric dominance fo rlanguage (133), and was later used to predict whether thecontralateral temporal lobe could support memory afteranterior temporal lobectomy (107). Further research hasshown that an induced transient global memory deficit,following pharmacological ablation of one hemisphere,correlates with the presence of an epileptogenic lesion inthe contralateral temporal lobe (134). In addition,patho-logic shiftingof language dominance from the left to theright hemisphere generally indicates that the epilepto-genic lesion is in the left temporal lobe (135).

Before the patient undergoes IAP, angiographic stud-ies are recommended to provide inform ation abou t theperfusion pattern of the drug. These studies may alsoidentify arterial anomalies that would put the patient atrisk. Before injection of sodium amobarbital, baseline

measurements are made of the patient's languagememory functions to serve as a comparison for drulated behavior changes. Immediately prior to injecthe patient is asked to count aloud while bilateralstrength is continuously assessed. Over a 4-secondriod, 125 mg of sodium amobarbital in 10 cc of sasolution is injected into one internal carotid artery via atransfemoral cannula. Each hemisphere is infused rately, with at least a 30-minute delay between itions. EEG is simul taneously recorded, and the neurical status of the pa tient is continuously monitoredcritical postinjection period for behavior assessmeduring the drug-induced marked unilateral EEG slowing and hemiparesis. This period typically doelast longer than 3 minu tes. With in seconds after the dinant hemisphere injection, cessation of counting occursand marked aphasia is immediately apparent, varfrom mutism to perseverative speech.

Initial aphasia testing is carried out in the first miafter injection. The examination assesses expressivereceptive language skills and includes naming, reaand responses to simple commands. Following items to be remembered are presented. Memorythese items is tested fo llow ing retu rn of EEG and beior to baseline, and at least 10 minutes postinjectThe type of item presented should be appropriate fohemisphere being assessed. For instance, memoryverbal material, either visually or aurally presentednot expected to be intact following a dominant hesphere injection. More detailed descriptions of IAP assessment procedure have been published ewhere (136).

Skull roentgenograms, XCT, MRI, and cerebra

giograms are also obtained during phase 1 if these studieshave not been carried out previously. Nonspecific stural abnormalities revealed by these studies prouseful confirmatory information if their localization relates with the site of EEG-demonstrated epileptiactivity, although these structural findings alone donecessarily indicate an epileptogenic lesion (23,74)noted earlier, the pathological correlates of high-insity areas in T2-weighted MRI scans remain uncand these abnormalities should be interpreted with cau-tion (78).

Indica tio ns for Fur ther Procedures

If a patient has a well-localized EEG-recorded onset (130), FDG-PET scans demonstrate a hypombolic zone in the same area, and there is no confliclocalizing information from structural imaging, otests of focal functional deficit, or seizure semiologstandard anterior temporal lobectomy is recommended


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FIG. 5. Simultaneous sphenoidal, nasopharyngeal, and temporal scalp recordings during thiopentalinjection. 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 struc-tural lesions on MRI and XCT can be substituted forFDG-PET evidence of hypometabolism, but furtherstudies are necessary to determine when other tests of focal functional deficit may serve this purpose.

When patients fail to meet the criteria for surgical re-section after phase 1 evaluation, they may be considered

for phase 2 studies if seizures appear to be stereotypedand the data collected during phase 1 allow a hypothesislimiting possible epileptogenic regions to a few that canbe adequately explored with intracranial recording. If the seizures are complex partial and a limbic onset issuspected, depth electrodes are usually recommended. If phase 1 has clearly lateralized the epileptogenic region toone hemisphere and it appears to be in the lateral neo-cortex, subdural grid electrodes are preferred.

When phase 1 evaluation indicates that seizures areoccurring from multiple sites, or no localizing hypothe-sis can be derived, patients might still be considered forlarge multilobar resections, hemispherectomy, or corpus

callosum section. These aggressive procedures are mostoften justified in infants and small children in whom theseizures are life-threatening or the likely cause of severedevelopmental delay (137,138). Unilateral regions of hy-pometabolism on FDG-PET that correlate with the pre-dominance of interictal and/or ictal epileptiform EEGdischarges are the most important criteria for consider-ing large resections in these patients (87,139), w hile dropattacks as the major cause of disability are the primaryindication for callosotomy (140). Further work-up inthese patients may include spike-suppression tests (141),and more specific psychological and psychosocial evalua-tions. Patients undergoing hemispherectomy must ei-

ther have a useless contralateral hand or, in rare in-stances, be willing to accept this deficit as an inevitableconsequence of the surgical procedure. Patients who in-tend to undergo corpus callosum section must under-stand that this is a palliative procedure that is unlikely toabolish all ictal behaviors. There is some evidence thatpatients with ipsilateral hand and language dominanceare at greater risk for disabling postoperative disconnec-tion symptoms (142), but this is not considered an abso-lute contraindication to callosotomy. Most centersprefer to carry out partial callosotomy, commonly theanterior two-thirds, which is usually effective withoutcausing a disconnection syndrome. If drop attacks per-

sist, the section can be completed later with minimalsymptoms of disconnection.

Phase 2 (Intracranial EEG Telemetry)

General Considerations

Due to the serious risk (but low incidence) of injuryfrom chronic intracranial electrode recording, only pa-

tients who appear very likely to benefit from surgicaltreatment are selected for phase 2. For this group, whenphase 1 evaluation fails to localize a surgically resectabepileptogenic lesion, intracranial reco rding offers a grediagnostic advantage. With depth or subdural grid eletrodes, the ictal EEG recording is generally free of mucle and movement artifacts, making it possible to ob-

serve exquisitely focal types of ictal onset and to followthe spatiotemporal pattern of electrographic propaga-tion. Howev er, such focal onsets are observed only wha recording electrode is at, or very close to, the primaepileptogenic region. Since only a limited number of in-tracranial electrodes can be safely placed, the number of potential locations of the epileptogenic region should bereasonably narrowed by the phase 1 evaluation befothese invasive procedures are contemplated.

EEG with stereotactically placed depth electrodes(SEEG) is most frequently employed in patients withcomplex partial seizures of presumed limbic origin when(1) clear EEG lateralization of the ictal onset has n

been obtained; (2) EEG-recorded ictal onsets are welllateralized but equally prominent in extratemporal andtemporal regions; (3) EEG-recorded ictal onsets are welllocalized to one temporal lobe but confirmational evdence of focal dysfunction or a structural lesion is miing or conflicting; (4) EEG-recorded ictal onsets areclearly localized to one temporal lobe but other studiesand/or the clinical seizures (e.g., simple partial motor orspecial sensory) suggest an extratemporal disturbance; or(5) phase 1 evaluation suggests an epileptogenic region inone temporal lobe that should be treated by a larger, ormore limited, resection than the standard anterior lobec-tomy. In patients who may be candidates for selective

amygdalohippocampectomy or lateral temporal resec-tion, depth electrodes are used to confirm that ictal on-sets arise from the area of planned removal. .

Chronic recording with intracranial subdural gridelectrodes usually is utilized when (1) EEG and MRIlateralization of the epileptogenic region has been ob-tained and additional localization is necessary betweenlobes or within a large area of cortex, and (2) localizationof essential cortex is necessary to avoid deficit duringresection of nearby seizure foci. The ability of subdurgrids to localize limbic ictal onsets is unknown. The rela-tive advantages of grids versus depth electrodes is an arof active investigation.

There are some general contraindications that relato the safety of intracranial electrode EEG recordingover a number of weeks. Patients who have serious multi-ple illnesses or active infections that could lead to intra-cranial infections, or who are otherwise poor surgicalrisks (e.g., patients with diabetes mellitus who are proneto infection) obviously should not undergo chronic intra-cranial EEG. Also, certain skull defects (e.g., thinning of the bone or a prior craniotomy) make depth electrodesunstable and therefore unsafe. During phase 1 studies,


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

Methods of Electrode Implantation and Removal

Stereotactic Depth Electrode Implantation

Recent developments in neuroimaging have radicallychanged the field of Stereotactic surgery. MRI now al-lows direct visualization of brain structures in any plane.By choosing specific pulse sequences, MRI can delineatebrain-CSF boundaries, grey and white matter junctions,and even discrete pathological changes within deep cere-bral regions. We now use a method of electrode implan-tation based essentially on MRI guidance, Stereotactic

digital subtraction angiography (DSA), and StereotacticFDG-PET; these neuroimaging studies arc integrated ina computerized image-analysis system that allows pre-surgical p lanning of electrode implantation. This stereo-tactic technique is made possible by an MRI-compatiblelightweight Stereotactic frame that is used for imagingstudies and intraoperative implantation, and for postop-erative verification of electrode placement. The overallprinciple remains to survey the limbic structures medialto the temporal lobe from anterior to posterior, bilater-ally and symmetrically (15). Additional extratemporalstructures are selected for implantation according to sei-zure semiology, scalp EEGs, and/or hypometabolic ar-

eas on FDG-PET.A m odified Leksell Stereotactic fram e (the OBT, Tipal

Instruments, Montreal, Canada) (143) is used for targetlocalization and electrode implantation (Fig. 6). It is con-structed of electrically nonconducting material that iscompatible with CT, MRI, and DSA. With additionalmodifications made at UCLA (144.145), StereotacticPET can also be obtained. Targets are reached from alateral orthogonal approach in a system of Cartesian co-ordinates, where the X axis is along the anteroposterior(sagittal) plane of the f rame, the Y axis is along the infe-rior to superior (coronal) plane, and the Z axis is in theaxial plane, extending positively to the right and nega-tively to the left.

Four sets of Plexiglas plates provide fiducia l markerson each side and top of the Stereotactic frame. Threecontain a Z-shaped channel filled with an appropriatecontrast material for each image modality and are tempo-rarily attached to the Stereotactic frame. Aluminum tub-ing is used during CT scanning, copper sulfate solution(7 gm/1) is used for MRI studies, and for PET scans thechannels are filled with positron-emitting germaniumisotope. The plane of section is calculated from the loca-


>i!p;

FIG. 6. The OBT (modified Leksell) frame used for intracere-bral target localization and depth electrode implantation. Ste-reotactic brain images obtained with magnetic resonance,computerized tomography, digital angiography, and positronemission tomography are artifact-free.

tion of the center arm of the Z-shaped marker in relationto the two parallel end bars. For DSA studies, the fiducialmarkers consist of fou r 1 -mm stainless steel disks placeequidistantly at the fou r quadrants of the Plexiglas platlocated on either side of the head for a lateral view, or atthe front and back of the f rame f or an anteroposteriview. Markers closest to the x-ray source will form larger rectangle on the x-ray film because of beam diver-gence, and thus differentiate the side injected and provide data for computer analysis of depth of field.

The procedure per se is divided into three stages: (1)Stereotactic imaging, (2) computerized image analysisand (3) Stereotactic implantation.

1. Stereotactic imaging. The Stereotactic frame iplaced on the patient's head using local anesthesia sup-plemented with short-acting neuroleptics. Initially, theframe is positioned over the head using auricular pinthen five twist-drill holes are made in the outer table othe skull at the front, back, and midline. Five MR-com-patible carbon fiber pins are placed in the drilled holeand secured to the frame. Amemory ringis placed oneach pin at the outer portion of the f rame to permit exacrepositioning of the frame f or any fu ture surgical procdures. The patient is then brought to the MRI suite andplaced in a supine position, with the Stereotactic frameanchored to a custom f rame adaptor over the sliding table of the MRI. Sagittal, coronal, and axial StereotacticMR images are obtained on a 0.3 Tesla unit. We use acustom surface coil that fits closely around the frame tincrease the signal-to-noise ratio. Inversion-recovery se-quences with a slice thickness of 4.9 mm and slice intervals of 5.1 mm are obtained. Three excitations are usedin the coronal plane, and two in the axial and sagittalplanes. A Stereotactic digital angiogram in both antero-posterior and lateral projections is obtained using a stan-dard femoral catheterization approach. Four-per-second


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336 CHAPTER 15

arterial and venous phases are selected for further analy-sis. Finally, a stereotactic FDG-PET is performed. Aframe adaptor allows fixation to the tomograph slidingtable. The patient is injected with 5 mCi of FDG, and 15simultaneous 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 X5 mm. The head-frame is then removed.

2. Computerized image analysis. All stereotactic digi-tized imaging studies are analyzed after being transferredto a central workstation. Image data such as size, slicethickness and intervals, field of view, and orientation arincluded. Surgical planning and selection of recordingsites are made at the central workstation using image-analysis software. Selected images are retrieved from the

hard-disk memory and are simultaneously displayed inseparate windows (Fig. 7). D ifferent planes fro m a single

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


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T H E E P I L E P S IE S /

modality or multimodal images can be displayed andanalyzed at the same time. A cursor system intercon-nects the images and the X, Y , and Z coordinates of anypoint w ithin the stereotactic fram e can be displayed. Ini-tially , structures are selected on the sagittal M R; orthogo-nal trajectories are simulated to samp le both lateral tem-poral neocortex and mesial temporal structures(amygdala; anterior, mid, and posterior hippocampi;and anterior, mid, and posterior parahippocampal gyri).Labeled targets are au tomatical ly transposed to the coro-nal and axial MR, and the Z coordinate, denning thedepth of implantation, is then determined. Next, phasesof the arterial and venous angiogram are selected andtrajectories are corrected within an avascular window.Extratemporal targets are usually the orbito-frontal cor-tex, the supplementary motor area, the anterior and pos-terior cingulate gyri, or the occipital cortex. After com-pletion of the target localization, a printout of allcoordinates is obtained.

3. Stereotactic implantation. Under general anesthe-sia, at a subsequent surgical sitting, the stereotacticframe is replaced over the patient's head using the pre-measured skull-fixation pins and the position confirmedwith a portable skull x-ray. The frame is clamped to asupportive device attached to a Mayfield holder. A modi-fied side-carrier that slides on vertical side bars is posi-tioned at the predetermined X and Y coordinates andserves as a key landmark for measurement of electrodelength to reach the Z coordinate. The skin and skull arepenetrated from an orthogonal approach withoutbreaching the dura, which is carefully perforated with athin electrocautery, stopping at the subdural space. Aself-tapping MR-compatible titanium guide-screw is

then secured to the skull. Th e distance between th e outerport ion of the screw and the side-carrier is translated intoa specific length fo r each electrode. Temporal electrodesare multicontact rigid tubing with an outer diameter of 0.8 mm. The electrodes are constructed with MR-com-patible nickel chromium and have a hollow center per-mitting insertion of platinum alloy fine w ire (40-microndiameter) electrodes. Extratemporal electrodes are flexi-ble nichrome fine wires (100-micron diameter) withmulticontact leads. Two reference electrodes are placedin the galea. Af ter placement, electrodes are bent towardthe vertex and embedded in a thin mold of acrylic poly-mer. Additionally, stereotactic subdural strips of six oreight platinum disc electrodes imbedded in silicone(146) can be inserted over the convexity or the mesialaspects of both hemispheres, when seizures are also sus-pected of having a frontal or parietal lobe origin. Thiscan be accomplished by knowledge of the locations of major draining veins from the stereotactic angiography.Subdural strips are used assentinelelectrodes to samp lecertain areas presumed to be involved in seizure onsetthat are poorly sampled by the orthogonally placeddepth electrodes. The frame is removed postoperatively,

and the p atient is transferred to the neurosurgical intesive care unit for overnight observation. The patientsent to the telemetry unit when stable. Electrodes aremoved under local anesthesia after completion of thmon itoring period. Resective surgery is perform ed a femonths after removal of the electrodes to allow wouhealing and reduce the risk of infection.

Subdural Grid Implantation

This technique requires an initial craniotomy for thinsertion of multiple arrays of electrodes over the cortein th e subdural space (18 ,147). Wide areas of lateral cotex can be sampled as well as subtemporal, suboorbito-frontal, mesial frontal, cingulate, mesial parietor occipital areas. The grids are made of silicone andcontain up to 64 platinum discs, each with a diameter 5 mm and a center-to-center interelectrode distance of 10 mm. Afte r intraoperative def inition of the sensorimtor cortex wi th evoked responses, lateral coverage of thcentral area, including peri-sylvian cortex, operculfrontal, and superior temporal gyri, is obtained withsingle 64-contact grid. Additional grids are inserted tsample specific lobes according to the desired presurgiceval uation. Great care mu st be taken to avoid an y tear displacement of major d raining veins. The grids are tieto each other to prev ent mo vem ent or slippage. The conectors are then tunneled under the skin through separate incisions. An intracranial pressure monitor is alsoplaced to indicate significant postoperative cerebredema. The dura is closed in a water-tight fashion, anthe bone fl ap su tured in place. Corticosteroid admin istrtion and fluid restriction are used initially to allow expansion of the subdural space and accommodation othe brain to the grids. Patients are then taken to the neurosurgical intensive care unit before transfer to the telemetry ward for functional mapping and seizure monitoing (18,148).

Depth Electrode Evaluations

During the first postoperative day, while the patient still in intensive care, prolonged direct SEEG (hardwirerecordings are made to survey all depth electrode contacts, as well as any subdural strip electrodes that mahave been inserted. Chain-linkage, common referencand bipolar recordings are obtained using a 21 -channeEEG machine. Patients are then transferred to the telemetry unit for SEEG telemetry and video monitoring iorder to capture spontaneous seizures and pe rform othestudies. If indicated by the incidence of seizures durinphase 1 telemetry, anticonvulsant medications arslowly tapered. During SEEG telemetry, ictal EEG andbehavioral data are gathered and seizures are detected asdescribed for phase 1. In addition, an automatic seizure


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3 38 / C H A P T E R 1 5

detector is used to identify ictal SEEG discharges thatmight otherwise go unno ted (149 ,150). Subclinical elec-trographic ictal events are also more commonly encou n-tered with random searches during phase 2 than duringphase 1. Initial SEEG recordings are made using 30-channel montages containing symmetrical derivationsfrom each hemisphere, including the most mesial andmost superficial contacts from temporal and extratem-poral electrodes and any subdural strip electrodes. Afterseveral typical episodes are recorded and the electrogra-phic pattern is determined, montages may be changed todefine better the site of ictal onset. Even with 30 teleme-try channels, not all depth electrode contacts can be sur-veyed in the initial montage. Additional contacts mayneed to be included later, as well as scalp and sphenoidalderivations if needed to iden tify sur face correlates. Focalonsets are most clearly displayed by recording from thebipolar tip of each depth electrode.

Mesial temporal EEG-recorded ictal onsets are called

foca l(1 51 ) and considered to be localizing when they arestereotyped; when only one or two electrode contacts areinvolved initially; and when there is a clear progressionof the epileptic discharge, first to ipsilateral and then tcontralateral structures, w hich can be correlated temporally w ith the progression of behavioral ictal events (Fig8A-C). Often, however, the initial EEG changes aremore dif ficu lt to interpret, due to subtle focal onsets thamay be missed, or regional onsets (151) that initially in-volve all, or most, depth contacts in one temporal lobesimultaneously (Fig. 8D-F).

With our present knowledge, it is impossible to charac-terize definitively and classify all SEEG-recorded ictaphenomena. Although certain patterns may be correlated with good or bad prognoses (152,153) and varioupathologic findings (154), there is much yet to be learnedabout the neuronal events recorded by the ictal SEEGand the ultimate clinical significance of the abnormalities revealed by this technique. Almost every patient w

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


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see appears to be unique, andeach SEEG evaluationseems to present a new set of confounding issues.

In general local onsets appear to indicate reliably thatthe electrode contact is near the epileptogenic region,wh ile regional onsets tend to represent epilep tiform activ-ity propagated from a primary epileptogenic region dis-tant from the available recording sites. Usually, how-

ever, this distant region is still within the same temporallobe. Consequently, a regional onset is not a poor prog-nostic sign unless there is other evidence that this repre-sents propagation from an extratemporal or contralat-eral epileptogenic region. The f inding of a regional onset,however, should prompt more careful attention to thispossibility. The pattern of ictal propagation also pro-vides clues to the site of seizure generation. In particular,slow spread to contralateral limbic structures is typical of mesial temporal seizures, while rapid contralateralspread suggests a neocortical or extratempora l site of on-set (153). Frontal depth or strip electrodes are useful notonly to rule out a frontal onset, but to demonstrate thedelayed ipsilateral frontal projection typical of mesialtemporal seizures (155). The differentiation between pri-mary and propagated ictal discharges remains a prob-lem, and sampling errors from the necessarily limitedelectrode array can result in false localization.

In our experience, SEEG-recorded ictal data are stillthe most reliable indicators of the location of the epilep-togenic region, but confirmatory evidence of focal dys-function is also sought during the phase 2 evaluation.Additional functional information can be obtained bystudies that take advantage of the use of depth electrodes.Whereas focal nonepileptiform abnormalities of base-line rhythms are rarely seen dur ing scalp EEG recordingsin our patients, there is often localized slowing or attenu-ation of normal rhythmic activity recorded from intra-cranial electrodes. Attenuation of normal SEEG-re-cordcd faster rhythms is most reliably observed when theplacement of relatively equ idistant mu ltiple depth elec-trodes is bilaterally symmetrical, and chain-linkagemontages are used (Fig. 9). Con sistent attenu ation of

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normal rhy thm ic activity at most, or all, mesial temporaldepth electrodes on one side indicates a functional dis-turbance that correlates well w ith the presence of a lesion(23). Attenuation of barbiturate-induced fast activity inone temporal lobe is mu ch better revealed when intrave-nous thiopental is given during SEEG recording thanduring scalp and sphenoidal EEG, as described earlier.Unilaterally attenuated SEEG-recorded thiopental-in-duced fast activity also correlates well with the presenceof a lesion (23,132). Thiopental-induced interictal SEEGspikes, like spontaneous spikes, are not reliably localiz-ing when recorded from the temporal depth.

Electrical stimulation has been used extraoperativelyand intraoperatively to produce seizures as a means of localizing a potential epileptogenic zone; however, local-ization obtained from electrically induced events (aswith convulsant drug-induced seizures) may differ fromlocalization obtained from spontaneous events (156). De-terminations of electrically induced afterdischargethresholds have been used to indicate the location of epi-leptogenic tissue, but results are contradictory. AtUCLA , afterdischarge thresholds have been most consis-tently elevated in the ep ileptogenic hippocamp us, partic-ularly when the lesion is hippocampal sclerosis (157),while others have found a lowered afterdischarge thresh-old to indicate epileptogenic brain tissue (158). Differ-ences in stimulation parameters have been suggested asone reason for these conflicting observations (158).

Intracarotid amobarbital testing is always done as thelast study of phase 2, even if this test was carried outduring phase 1, to be certain that no significant impair-ment of memory functi on has been produced in the con-tralateral temporal lobe as a resu lt of electrode implanta-tion and/or stimulation.

Subdural Grid Evaluations

From extensive experience with temporal limbic epi-lepsy, we have learned that the highest degree of surgical

FIG. 9. Direct (hardwire) SEEG record-ing demonstrates attenuation of nor-mal rhythmic fast activity in the rightamygdala, hippocampal pes, andgyrus. Abbreviations as in Figure 8,except P, hippocampal pes. Calibra-tion 1 sec, 1,000 /j.V. Patient had me-sial temporal sclerosis on the right.(From reference 99, with permission.)


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340 CHAPTER 15

success is achieved when there is preoperative demonstra-tion I MR. CT. SPECT, PET) of a pathological substrate,proof of epileptogenesis in this same region, andcom-

pleteness of the operation with postoperative pathologyfound in the specimen. Similarly, in neocortical epi-lepsy, it has long been known that surgical outcome isbest when a specific lesion can be demonstrated preoper-atively. W hen extratemporal localization is obtained byscalp EEG techniques alone, in the absence of a lesion, itis too often incorrect. Furthermore, the absence of apathological substrate in the postoperative specimen willcorrelate with a poor outcome.

Traditional methods elaborated by Penfield and hiscolleagues utilized intraoperative electrocorticographyto identify interictal spiking discharges and direct bipo-lar electrical stimulation of the brain to demonstrate theepileptogenic cortex and functional regions acutely inthe operating room (159). Talairach and colleagues dem-onstrated the irritative cortex, lesional cortex,and epilep-tic cortexusing depth electrodes (14). However, the num -

ber of electrodes that can be used is limited. Theseregions can now be easily denned using implanted largesubdural grids. Since these electrodes cannot be movedafter implantation, a large array is necessary and sub-dural strip electrodes are inadequate for this purpose.The opportunity provided by implantation enlarges thescope of the investigation. Children and adults who forvarious reasons cannot tolerate a prolonged operativeprocedure under local anesthesia can now be comfort-ably evaluated (160,161).

In addition to localizing interictal and ictal epilepti-form discharges using telemetry monitoring techniquesidentical to those of depth electrode recordings, the ex-

tent of the functionally inactive region can be tested byelectrical stimulation, evoked potentials, and EEG back-ground activity (Fig. 10). The functionally active corticalarea may be found to be displaced by the pathology. Thespecific procedures of functional mapping using chronicsubdural electrode grids are dealt with in detail elsewhere(18,148,162). Both cortical stimulation and event-re-lated evoked potentials are utilized to localizeessentialcortical regions. The parameters for cortical stimulationare selected to avoid tissue damage. No simple rules existfor safe parameters for functional mapping by corticalstimulation. The specific parameters that are safe varywith the specific electrode size and circuit, and must be

calculated by the physician performing the stimulations(163). We define essentialcortex as that tissue that mustbe spared to avoid gross neurological deficit in sensori-motor function and language. W e assume that if carefulneurophysiologic assessment were performed, most, if not all. brain tissue would beeloquent,and some measur-able deficits would be identified after most focal exci-sions of brain tissu e. As is done with those patients wh oundergo depth electrodes, the patient is informed that totreat the seizure (a global positive deficit), he or sheusually must accept a selective deficit (a limited negative

deficit). Functional mapping is designed to localize cotex that is essentialto avoid deficits in activities of dailliving such as hand function and language. As many revant functions are tested at a site as feasible within thtime limitations and tolerance of the patient. Functionmapping usually takes about a week to perform and rquires much patient cooperation. Not all patients acapable of tolerating this procedure.

In the preceding era of epilepsy surgery, any intervetion into the primary cortices was generally avoided.With increased confidence in cortical mapping, opertions now often involve these primary cortical regionHowever, in our opinion it is not sufficient to removlesions alone; the resection must also include the epiletogenic cortex. The definition of epileptogenic cortex bmeans of interictal epileptiform discharges and recoring of the ictal activity is still under development. Isome cases, focal ictal discharges have been qu ite limitein extent and the subdural grid evaluations have allowless-than-lobar resection to be surgically successful a

with less than the expected morbidity.

Indica tions for Further Procedures

Unlike phase 1, where a specific protocol has beestablished at UCLA for selection of surgical candidates,the decision to carry out a resection after phase 2 is nbased on firm criteria. Ideally, all seizures should orignate in one area of the brain and confirmatory tesshould reveal focal dysfunction in the same area. Aftgrid recording, tailored resections are determined prmarily by the pattern of ictal onset and early spread, andesigned to avoid essential cortical tissue. With SEEG

recording, a few complex partial seizures originating con-tralateral to the presumed epileptogenic lesion (espcially if these seizures are atypical and/or occur wheanticonvulsant medications have been significantly lowered) are not considered an absolute contraindication tsurgery, since patients with such findings often do wepostoperatively (126). In our experience, when SEEGrecorded ictal onsets have been focal, there is rarely, ever, conflicting evidence of focal dysfunction elsewherHowever, in some patients, a regional SEEG-recordedictal onset has been localized to one temporal lobe bconfirmatory tests suggest the focus may lie in part, entirely, outside the standard resection. In these case

particularly if functional mapping of primary cortex also necessary, a second phase 2 with subdural grid electrodes or intraoperative corticography may be recom-mended. When the time for ictal spread to contralateral.or extratemporal structures is less than a second, or ictalonsets are inconsistent or appear only after clinical signand symptoms, focal functional deficits are used to suggest other epileptogenic regions that might justify a second phase 2 procedure with subdural grids. When ictonsets are nonlocalizing, there is no confirmatory focadysfunction, and there is no additional evidence to sug-


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FIG. 10. Focal seizure pattern from left frontal lobe. (A) Anteroposterior skull x-ray outline shows coro-nal placement of electrodes over the left lateral convexity and shows the location of focal seizure onset(heavy circles) in the lateral inferior frontal region. (B) Lateral skull x-ray outline shows that the zone ofseizure onset is near the speech cortex. Patient had simple partial seizure of forced thought and speecharrest followed by complex partial seizure with ictal vocalization. (C) Electrographic seizure recordingshows focal onset of low-amplitude fast activity and sharp wave (arrows), followed by sustained high-amplitude fast activity in the left lateral inferior frontal lobe near Broca's area. Previous depth electrodeevaluation documented seizure onset in the left lateral frontal lobe with subsequent spread to mesiallimbic structures after 1 5 to 20 seconds. Left frontal resection included most of the seizure zone,extended up to Broca's area, and gave significant seizure reduction. Calibration 100 nV, 1 sec. (Fromreference 148, with permission.)

gest specific alternatives to the areas already explored,

surgery cannot be recommended. Surgery is not per-formed when SEEG-recorded seizures appear to origi-nate with equal frequency from either side of the brain,or when subdural grid-recorded seizures originate en-tirely within primary cortex that can not be removed.

OPERATIVE PROCEDURES

Electrocorticography

In some centers intraoperative ECoG is performedroutinel under local anesthesia f62.63.120

the extent of resection is determined on the basis of in

terictal ECoG findings. Since intraoperative ECoG re-cordings are limited to th e area of craniotomy, they can-not be used to localize an epileptogenic region, butrather are used to define better the limits of epileptogenictissue already localized by other techniques. This procedure may be extremely helpful for certain neocorticallesions; however, reliable localization of a limbic epilep

Epilepsy Cap 15

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