SEMINARS IN NEUROLOGY-VO1,UME
10. NO. 4 DECEMBER 1990
Arriving at the Surgical Options for Intractable Seizures
Although many surgical procedures have been applied to uncontrolled epilepsy over the decades, at the present time only two broad classes of operations have been proven to be effective and remain in common use. These are the resective procedures and corpus callosum section. T h e resective procedures involve exactly what the name implies, removal of a small portion of the brain with the intention of stopping seizures. As such, these operations are applied only to partial epilepsies (with or without secondary generalization). They are the preferred and most common operations for epilepsy that is uncontrolled by medication because they offer the possibility of cure. Corpus callosum section is a second choice, palliative procedure, which aims only to limit the clinical expression of the generalized seizure. It is an appropriate consideration in secondarily generalized or generalized seizure disorders. T h e manner in which one arrives at these surgical options involves a complicated series of steps that begins with the same basic set of selection criteria. These are roughly similar among epilepsy surgery centers.'-"
INITIAL SELECTION CRITERIA First of all, seizures must occur with sufficient frequency and intensity to interfere significantly with a person's lifestyle. No particular frequency is required, but, rather, it is the combination of the frequency of seizures and the characteristics of the individual seizure that qualifies someone to be considered for surgery. Secondly, seizures must have been uncontrolled despite trials of all of the appropriate anticonvulsant drugs, with documented therapeutic
serum levels and with trials of monotherapy and polytherapy. Again, no specific length of' time for such trials can be given, because an adequate trial depends on the seizure frequency. Little has been written about specifically which or how many drugs should be tried to fulfill this condition, nor about the likelihood of response to secondary anticonvulsant medications once the first-line drugs have failed to achieve satisfactory seizure control. Most centers require trials of major anticonvulsant medications, including phenytoin, phenobarbital, and carbamazepine; some include primidone in this list; and valproate is achieving a place here as well, although information is still accumulating with respect to its efficacy in partial seizures."The best available information suggests that additional seizure control after failure of monotherapy is achieved with two major drugs in only 11% of pat i e n t ~ . ~It, ' is reasonable from these data to assume that only the extremely unusual patient is likely to exhibit lasting response to second-line drugs when major ones have failed in both monotherapy and polytherapy. Nevertheless, especially in patients with frequent seizures, trials of some such drugs are not unreasonable. 'Thirdly, there should be no other significant or progressive neurologic, medical, or psychiatric diseases that would interfere with the extensive evaluation, increase the risk of surgery, or inhibit successful rehabilitation after epilepsy surgery. T h e issue of baseline psychiatric status and its implications for success of epilepsy surgery is unresolved. Most of the (minimal) literature suggests that psychiatric status is an independent variable; that adjustment and neurotic disorders in some circumstances may improve if surgery successfully controls seizures; and that psychosis is generally
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut Reprint requests: Ilr. Spencer, Yale University School of Medicine, Department of Neurology, 333 Cedar Street, New Haven, CT 06510 Copyright O 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
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S w a n S. Spencer, M.D., and Amiram Katz, M.D.
SURGICAL OPTIONS FOR INTRACTABLE SEIZURES-SPENCER, KATZ
RESECTIVE PROCEDURES Because the resection procedures are the preferred operations for uncontrolled epilepsy, they will be discussed first and most extensively. It has been repeatedly shown that the success of a resective procedure in controlling epilepsy that has been unresponsive to medical therapy depends on the accurate localization of the cerebral area responsible for initiating the habitual seizures and the total removal of the area so identified. Therefore, because persons who are candidates for resective procedures must have all of their seizures beginning in a single, definable, and removable cerebral area, the localization of the focus is the single most important piece of information that must be obtained.
T h e manner in which the focus is localized differs at various centers, but all use a phased evaluation, of which the routine at Yale is representativeg-" (Table 1). PHASE 1
Phase I involves an approximately 2-week hospitalization during which the history is taken and physical, neurologic, and neuropsychologic examinations and closed circuit audiovisual and EEG monitoring are performed. Monitoring is usually continuous and sometimes requires medication withdrawal to record the habitual seizures utilizing the scalp electroencephalogram (EEG). During this phase, imaging procedures are also performed, including computerized tomography (CT), magnetic resonance imaging (MRI), single-photon emission computerized tomography (SPECT) scan, and positron emission tomography (PET) (where available). Phase 1 thus provides considerable information. Review of the videotapes of recorded seizures establishes that they are partial seizures of stereotyped onset. Centers experienced in video review of seizures have recognized certain features of complex partial seizures which implicate specific cerebral areas of origin.I2-l5Table 2 gives some of these characteristics; they are not specific, but taken together often constitute evidence pointing to a certain lobe of onset which then requires fur-
Table 2.
Phase I. Initial evaluation 1. Thorough history, medical and neurologic examination 2. Psychiatric examination 3. Neuropsychologic testing 4. MRI 5. Formal visual fields 6. Baseline EEG 7. Continuous audiolvideo monitoring to record minimum of three seizures 8. PET, SPECT if available Phase II. Preparation for implanted electrodes 1. Two-vessel cerebral angiogram 2. Left and right cerebral amobarbital testing Phase Ill. Depth and cortical electrode implantation 1. Depth and/or cortical electrodes-number and placement dependent on prior evaluation 2. Continuous audiolvideo and depth EEG monitoring to record at least three seizures Phase IV. Surgery 1. Mapping of speech and motor areas when indicated 2. Cortical resection *Reprinted with permission from Spencer et aL9
Some Characteristics of Seizures from Various Cerebral Areas
Tem~orallobe Psychical manifestations (d6jA vu, jamais vu) Complex perceptual disturbances (micropsia, macropsia, complex visual hallucinations) Motionless stare Oro-alimentary automatisms (lip-smacking, chewing) Complex motor automatisms, often of upper extremities (fumbling, picking, repetitive activity) Duration usually > 1 minute Prolonged postictal state Frequency usually 3-lO1month -
Table 1. Surgical Evaluation for Epilepsy*
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not affected. Psychotic states are therefore a contraindication if and only if they produce behavior that places the patient at undue risk during study, or if their extent is such that rational consent and improvement in lifestyle with seizure control are judged impossible." Finally, most patients considered for epilepsy surgery are under the age of 50 years. Although in the past a lower age limit of 10 was sometimes publicized, it has become increasingly evident that children can benefit substantially from surgical procedures and therefore no lower age limit is now ~ the individual meets the other advocated as l o -n as selection criteria.
0
Frontal lobe Abrupt onset and termination Vocalization Semipurposeful motor automatisms, often of lower extremities (kicking, thrashing) Sexual automatisms Tendency to frequent secondary generalization and complex partial status epilepticus Duration usually 50/month Occipital lobe Visual loss Sensation of eye movement (not observed) Forced blinking or eye fluttering Contralateral eye deviation Subsequent temporal or frontal spread with appropriate symptomatology
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ther study or confirmation. 'I'he presence of multiple seizure types must also be established. On some occasions, variability of clinical seizure types may emerge from a single focus because of variable degree or direction of spread from the focus of onset, and they should be distinguished from the presence of multiple foci which decreases the advisability of resective surgical intervention. Phase 1 also documents electrical abnormalities, both interictal and ictal, as recorded by the scalp EEG. T h e presence of focal spikes recorded by interictal scalp EEG regardless of apparent localization is a helpful item suggesting the presence of focal epilepsy, or of seizure onset from a focal cerebral region. Precise localization, however, can often be misleading when based on interictal surface EEG spikes.lG-l"f interictal spikes are multifocal, the patient may still have a single focus responsible for the onset of his habitual and uncontrolled seizures and thus remain a surgical candidate. If the interictal EEG is normal, focal seizure onset is still possible, although pseudoseizures should be excluded. The presence of 3 Hz spike and wave discharge on the interictal or (ictal) EEG without focal spikes is suggestive of primary generalized epilepsy; if this diagnosis is confirmed based on videotaped analysis of seizures, such patients are excluded from consideration for resective surgery. Some patients with bilaterally synchronous spike and wave discharge, however, may have focal seizure onset with so-called secondary bilateral synchrony. Thus, patients with bilateral spike and wave should never be categorically excluded, but rather studied further for evidence of focal seizure onset. Usually, it is most profitable to review clinical seizure types as recorded on videotape for these distinctions. If the surface EEG recording captures the onset and buildup of a clinical seizure, focal or generalized high-frequency discharge, spiking, or no change at all except for artifact may be seen. None of these patterns at our present stage of knowledge constitutes a contraindication to further surgical workup, nor does any of them imply a certain region of onset."' Furthermore, surface EEG recording of the ictal event itself, mostly because of the prevalence of artifactual changes, has been established to be unreliable and inaccurate in its localization of the area of seizure onset.2' This is underscored by the onset of clinical seizure activity prior to seizure discharge seen on surface EEG in most instances. Sphenoidal electrode recordings are believed by many electroencephalographers to provide increased yield of focal ictal scalp recording, and abnormalities recorded with them are taken to imply mesial temporal lobe localization."' This latter contention, however, has not been adequately
VOLUME 10, NUMBER 4 IIECMBER I990
verified, and it remains possible that sphenoidal electrodes may also reflect seizure discharge in other cerebral locations; it is well established that they may not detect mesial temporal discharges. Functional abnormalities from the neurologic and neuropsychologic examinations and structural abnormalities based on the imaging studies complete the data in phase 1. C T and, more often, MRI may reveal discrete or generalized cerebral abnormalities that can have significant bearing on the remainder of the evaluation and the exact course of further therapy. For example, the presence of a cerebral neoplasm with surrounding edema would establish the need for surgery by itself, regardless of the characteristics of the seizures or the EEG (although the exact approach might be modified in an attempt to treat the uncontrolled seizures as well as the lesion). Lesions such as small calcifications, vascular anomalies, or fbcal abnormal signals, although not necessarily an indication for craniotomy without the presence of epilepsy, have a greater significance in the setting of uncontrolled seizures. Numerous studies have established that such lesions are more than likely to represent a cerebral glioma, even if epilepsy has been present for more than a de~ade,~%rid in many patients these gliomas may be unexpectedly high grade.""uch lesions are now detected in 25%) of patients evaluated for epilepsy surgery. With current technology, MRI can document mesial temporal atrophy and sclerosis in another 25% of patients referred for surgical consideration. Localizing abnormalities of electrical, functional, clinical, and structural varieties are then reviewed. These may or may not be in agreement and may or may not be localizing at all. Nevertheless, provided that seizures begin in a stereotyped, partial manner and provided that it is still considered possible that all seizures begin in a single cerebral location, the patient may proceed to Phase 2. PHASE 2
Phase 2 is really another test of cerebral structure and function, but it is performed as a separate phase because it is slightly more invasive. 'Therefore we require that the patient at least be considered still to be a possible candidate for surgery. In some centers, Phase 2 is performed earlier or later in the sequence of study, but is always a necessary part of the total evaluation. A cerebral angiogram is performed, which is important for planning the further evaluation and surgery and for demonstrating vascular abnormalities. Following angiography, the intracarotid cerebral amobarbital (Amytal) test is performed. Sodium amobarbital 100 to 150 mg is injected sequentially into the carotid ar-
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SEMINARS IN NEUROLOGY
SURGICAL OPTIONS FOR INTRACTABLE SEIZURES-SPENCER, KATZ
combination localize at all or with sufficient accuracy, then it is necessary to pursue more accurate electrical localization with intracranial electrode implantation. This occurs in approximately 50% of the patients at our center. PHASE 3
Phase 3 involves the implantation of intracerebral or subdural electrodes, or both, to record seizures intracranially for better localization. This implantation is again followed by continuous audiovisual and EEG monitoring to record many habitual, spontaneous seizures. Selection of types of electrodes to be used depends on many factors. Table 3 contrasts the differences, according to presently available information, between depth and subdural electrodes. They are both multicontact electrodes. Depth electrodes may be rigid or flexible, whereas subdural electrodes may be strips, catheters, or large grids. Both kinds are inserted in the operating room in preselected sites and used for chronic recording of 1 week or more. Depth electrodes have a slightly higher risk of major complications, which are weighted toward intracerebral hemorrhage, although recent MRIIangiographic techniques are said to reduce this risk.26-" Subdural electrodes are more likely to produce infection and cerebral edema.'"'y According to the literature, in patients who have insufficient localization by previous studies, either depth electrodes or subdural electrodes are capable of localizing the focus in 60 to 70%'"3'"he success rate from surgery after a focus has been identified by these methods is slightly higher for depth electrodes, but data on patients selected by subdural study are still being accumulated. Depth electrodes are likely to be better for accurate localization in the temporal lobe because they record directly from the hippocampus, the most common site of origin of temporal lobe seizures and the most common site of pathologic change in temporal lobe epilepsy.'"~" They have been shown to be more sensitive than other techniques in detecting both simple and complex partial seizures aris," placed acing from the h i p p o c a m p ~ s . ~ ~When cording to certain protocols, they can define the anterior-posterior extent of the focus in the medial temporal lobe and, by doing so, may modify the operation." Subdural electrodes are also capable of accurately lateralizing temporal lobe epilepsy, but they are not able to define as precisely the anterior-posterior dimensions of a medial temporal lobe focus, because they do not record from the hippocampus directly; this is true despite more medial placements recently implemented.3"oth types of electrodes have been notably inaccurate in
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teries, producing temporary drug-induced anesthesia in the distribution of the ipsilateral carotid arteries, subserving the language and memory areas. During the 10-minute effect of the sodium amobarbital, the language and memory functions of the contralateral, unanesthetized hemisphere Obviously, documentation of side of are a~sessed.'~ cerebral dominance is critical in planning safe resective procedures. Furthermore, demonstration of lack of memory in one hemisphere is taken to indicate a functional abnormality in that temporal lobe, and also taken to imply that the other temporal lobe should not be removed without major the physrisk to the patient's memory.2"lthough iologic basis and the accuracy of such studies have not been proven, and, in some circumstances the accuracy is clearly questionable because of variations in vascular anatomy, this test is a widely used standard for these purposes. To my knowledge, no patient has been reported to develop an amnestic syndrome after temporal lobe resection when the intracarotid amobarbital procedure clearly demonstrated intact contralateral memory. After Phases 1 and 2, the information is reviewed to plan further patient evaluation and management. As already noted, if a well-defined lesion is demonstrated on C T or MRI, it is often a lowgrade tumor. Provided the EEG information from Phase 1 is consistent, resection of such a lesion with margins is very likely to provide cure of seizures. Further evaluation is not necessary in these circumstances unless the lesion is in close proximity to important functional areas, in which case functional mapping will be required. When the imaging studies do not demonstrate a focal structural lesion, some other confirmation of the scalp EEG localization is required to proceed with a resective procedure. If all of the abnormal localizing studies in Phase 1, including functional, electrical and structural studies, point to one temporal lobe as responsible for seizures, then it may be resected after Phases 1 and 2, provided that memory is adequate in the contralateral hemisphere. This scenario is usually fulfilled by the patient with hippocampal atrophy on MRI, neuropsychologic test profile consistent with dysfunction in the same ten~porallobe (usually represented by specific verbal or visual memory impairments), interictal and ictal surface EEG characterized by ipsilateral temporal spikes and seizure discharge, and a clinical seizure profile consistent with the temporal lobe syndrome (see 'Table 2) often with a history of febrile seizures. Extratemporal localization, however, is only very rarely possible after Phases 1 and 2, without a lesion or well-defined mass. Finally, if the several studies performed in Phases 1 and 2 localize differently, or do not in
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SEMINARS IN NEUROLOGY
Depth Versus Subdural Electrodes Depth
Subdural
Construction
Multicontact or bipolar, rigid or flexible
Strips, catheters, or grids, all multicontact
Insertion
Lateral or medial insertion in preselected sites; burr holes
Craniectomy, craniotomy in preselected sites
+
Length of recording
1 week
Risks
2-4%, hemorrhage, infection
1 week
+
Yield of localization
60-80%
1-4%, infection, edema, hemorrhage 60-70%
Reported surgical success
60-90%
60-65%
Accuracy in temporal lobe epilepsy
Excellent for lateralization, and for anteriorposterior definition in hippocampus
Excellent for lateralization but not for anterior-posterior definition in hippocampus
Sensitivity in temporal lobe epilepsy
Excellent for mesial and lateral hippocampal and neocortical detection (depends on placement)
Misses over 20% of medial hippocampal seizure discharges, including most auras and subclinical seizures
Accuracy and sensitivity in extratemporal foci
Poor data
Poor data
Mapping
Not well suited
Ideally suited
Figure 1. Simultaneous depth and subdural EEG recording of seizure onset, seen in depth electrode (LPT) traversing the left hippocampus initially with later involvement of temporal neocortex seen in subdural electrode (NEM). RMT, LTM = midtemporal depth electrode; NEM = left temporal subdural electrode. Numbers designate contact points on electrodes from superficial (1) to deep.
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Table 3.
VOLUME 10, NUMBER 4 DECEMBER 1990
SURGICAL OPTIONS FOR INTRACTABLE SEIZURES-SPENCER,KATZ
dial temporal lobectomy is performed, consisting of a limited anterior resection followed by en bloc removal of the hippocampus.g
RESULTS Sixty to 90% of appropriately selected patients will have cure of their seizures after resective proc e d u r e ~ . "Functional ~~ rehabilitation is not, however, as good as seizure control. Patients generally improve their work status or return to work, but those who have been disabled and have never worked rarely seek employment, regardless of the effects of surgery on seizures.3gPartly, this is attributable to lack of appreciable response of significant psychiatric disease to seizure control, but certainly many more factors are involved. The neurologic sequelae of resective surgery depend on the area resected.2gWith temporal lobe resections, we expect a contralateral superior quadrantanopia, but minimal memory disturbances provided that the sodium amobarbital test has demonstrated adequate memory in the contralateral hemisphere. With frontal lobe resections, personality disturbances may occur; unfortunately, there is no preoperative test to aid prediction. It is generally thought that more limited resections are less likely to cause personality deficits, underlining the importance of careful localization.
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localizing extratemporal foci unless a lesion has been demonstrated on C T or MRI to aid placement of the electrodes." Finally, depth electrodes are not well suited to mapping (see later), whereas subdural electrode grids are ideally suited for mapping of functional areas believed to closely approximate the seizure f o c ~ s . ~ " ~ ~ . ~ ~ , ~ ~ In Figure 1, an EEG demonstrates simultaneous depth and subdural recording in a patient who has both a left temporal depth electrode and subdural electrode. The precise site of seizure onset is seen in the left temporal depth electrode medially; later, the seizure involves the left temporal neocortex as recorded by the subdural electrode. T h e recordings are of high quality and free of artifact; in this instance, they confirm the usual medial temporal onset of seizures in a patient whose seizures were not well localized by scalp EEG. If the seizure focus or lesion is close to areas that are very important functionally, mapping will be necessary. This can be done acutely in the operating room under local anesthesia or chronically with implanted subdural electrode grids so that the seizure onset can be superimposed on the functional mapping. With computerized methods, the contact points of the grid can be represented on the surface of the brain so that areas of functional importance can be depicted with respect to the seizure focus. This approach is particularly suited to evaluation of patients with uncontrolled epilepsy associated with extratemporal lesions.
HEMZSPHERECTOMY PHASE 4
If a seizure focus can be accurately identified and occurs in a resectable portion of the brain, surgery can proceed in Phase 4. Complete removal of the area identified as the seizure focus correlates with success in cure of seizure^.""^' There is a 2% risk of major complications from epilepsy surgery of the resective type, and neurologic deficits may, of course, limit the possibility of fully resecting the area. In our experience, 60 to 70% of patients with uncontrolled epilepsy have seizures arising in the temporal lobe. T h e frontal lobe is the next most frequent site of origin. Seizures of partial type can originate, however, in any cerebral lobe, and portions of any lobe in the dominant or nondominant hemisphere can be safely resected with appropriate precautions. Various surgical procedures may be used, depending to some extent on the philosophy at the particular center. Thus, in temporal lobe epilepsy, more or less or exclusively medial or lateral resection may be done.g At Yale, because electrophysiologic, pathologic, and structural analyses support predominantly medial involvement, an anterome-
Hemispherectomy is the most extreme of the resective procedures, involving removal of the majority of one hemisphere. It is indicated for patients who have multiple seizure foci within one hemisphere, who have unilateral partial seizures as their major seizure type, and who have significantly impaired contralateral motor function, particularly in the hand. In such individuals, excellent response is obtained, with cure of seizures and minimal increase in motor deficits. Although the majority of the hemisphere still is removed in such operations, operative technique has been revised because of the previous long-term complication of hemosiderosis with a high mortality rate.29 Now, small portions of cerebral tissue are' left in the affected hemisphere, but functionally disconnected. So far, this modification (and others) have not been associated with hemosiderosis, but no systematic analyses have been done. CORPUS CALLOSUM SECTION
After the extensive evaluation involved in Phases 1, 2, and sometimes 3, some patients who continue to have medically uncontrolled seizures
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SEMINARS IN NEUROLOGY
patient^.^'.*^
428
Possible neurologic side effects of severing the major connections between the cerebral hemispheres are a concern. This problem has been studied.44Language impairments, usually of an expressive nature, can occur after corpus callosum section. These are rare, and they are predictable by preoperative evaluation. They have been associated with split dominance of language and handedness and are particularly prominent in righthanded patients with right hemisphere dominance for language. Although this is not an priori exclusion, the risks of expressive language impairment, including mutism must be considered in this poplat ti on.^^ Weakness or apraxia of the nondominant leg occurs on occasion. It is usually an exacerbation of a preexisting weakness and it usually improves postoperatively, although sometimes not to its baseline level. A decline in memory, although previously in dispute, has been documented to occur after corpus callosum section in rare patients4'jand appears to be related to poor postoperative control of generalized seizures. Aggressive behavior is sometimes worsened but does not appear de novo. The intelligence quotient (IQ) is usually unchanged. Some investigators believe that the mechanism of production of neurologic deficits after corpus callosum section relates to "unmasking" of previously sustained focal injury whose recovery was dependent on interhemispheric synergy me~~ may diated by the corpus ~ a l l o s u m .Retraction also play a part.
In reviewing of the literature with regard to control of generalized seizures and minimal neurologic side effects after corpus callosum section, it appears that the best candidates are individuals with an I Q over 50 who have falls, whose seizures began before the age of 5 years, and in whom handedness and language are controlled by the same hemisphere. These persons are most likely to have neither generalized seizures nor deficits.
APPROACHES TO EPILEPSY SURGERY Figure 2 is a summary of the approach to epilepsy surgery. Patients with uncontrolled epilepsy that interferes significantly with their lives are studied in Phases 1 and 2, and sometimes Phase 3. Evaluation at all centers is roughly comparable. If a focus is localized to a resectable area, a resective procedure offers a high likelihood of seizure cure. If the focus is localized to an unresectable area and mostly partial seizures are present, no operation is possible, but if the partial seizures often generalize, corpus callosum section can be considered as a palliative procedure to limit the generalized seizures. In those cases without localization, if bilateral seizure onset has been demonstrated with only partial seizures, again no operation is possible. If seizures secondarily generalize sufficiently frequently to interfere with life or safety, corpus callosum section can be considered a palliative alternative. With unilateral but multifocal seizure onset, only partial motor seizures, and significant motor impairment, hemispherectomy is indicated. However, if motor impairment is not present, no operation is recommended. Finally, with unilateral multifocal seizures that frequently generalize and without motor impairment, corpus callosum section again can be used for palliation.
SUMMARY Surgery is 80 to 90% effective in properly selected patients with uncontrolled epilepsy. T h e localization of the epileptic focus determines the applicable operation. Resective procedures are preferred because they offer the possibility of cure. However, in certain circumstances corpus callosum section can be used for palliation because it offers relief of generalized seizures and falls in a substantial proportion of individuals with uncontrolled secondarily generalized seizures who are not candidates for resection. Substantial progress in patient evaluation and protocols for surgical treatment has been made in the past decade.
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that interfere significantly with their lives are excluded from resective procedures. Their seizures are either unlocalized, localized to multiple areas bilaterally, or localized but not resectable. For the subpopulation of these patients, and others, who have uncontrolled, secondarily gen~pralzzed seizures with falls, and perhaps for patients with significantly uncontrolled primary epilepsy with falls, corpus callosum section may be considered as an alternative therapeutic option. Corpus callosum section is a two-stage, palliative procedure that aims only to prevent the generalization of seizures by disconnecting the cereThe fibers of the corpus bral callosum and hippocampal commissure are interrupted. T h e section is done in two stages to decrease the length and severity of the transient postoperative disconnection syndrome. Corpus callosum section can be expected to eliminate or markedly decrease falls and generalized seizures in 85% of patients undergoing the procedure. It is not indicated for partial seizures, which are usually unchanged, although they can improve in about 40% of patients, or can increase in either intensity o r frequency in about 25% of
VOLUME 10, NUMBER 4 DECEMBER 1990
SURGICAL O P T I O N S FOR INTRACTABLE SEIZURES-SPENCER, KATZ
-)(:
Uncontrolled epilepsy
Phase l II (111) . .
Resectable area in one lobe
\Unresectable
a'a Only
Focus ~unlocalized
"3Unilateral
/
Bilateral Partial
Partial
partial
I
Resection (any lobe or part)
seiqres
generalized seizures I
/
1 (
Functioning
4
No operation
'Partial
and generalized
motor seizures
/\
J
I
Minimal use, contralateral hand
L
Good use of contralateral
I
Corpus Callosum section
Hemispherectomy
No operation Downloaded by: University of British Columbia. Copyrighted material.
Focus localized
Figure 2. Summary of approach to epilepsy surgery. (From Spencer et aL9 Reprinted with permission.)
REFERENCES 1. Walter RD. Principles of clinical investigation of surgical candidates. Adv Neurol 1975;8:49-58 2. Browne TR, Feldman RG, eds. Epilepsy diagnosis and management. Boston: Little, Brown, 1983 3. Green JR. Temporal lobectomy, with special reference to selection of epileptic patients. J Neurosurg 1967;26: 584-93 4. McNaughton FL, Rasmussen T. Criteria for selection of patients for neurosurgical treatment. Adv Neurol 1975; 8:37-48 5. Bourgeois BFD. Valproate: clinical use. In: Levy RH, Dreifuss FE, Mattson RH, et al, eds. Antiepileptic drugs. New York: Raven Press, 1989:633-42 6. Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonicclonic seizures. N Engl J Med 1985;313: 145-51 7. Smith DB, Mattson RH, Cramer JA, et al. Results of a nationwide Veterans Administration cooperative study comparing efficacy and toxicity of carbamazepine, phenobarbital, phenytoin, and primidone. Epilepsia 1987;28 (suppl 3):S50-8 8. Spencer SS, Spencer DD. Outcome: data, dogma, directions. In: Spencer DD, Spencer SS, eds. Epilepsy surgery. Cambridge: Blackwell, in press 9. Spencer SS, Schwarz S, Spencer DD. Surgery for epilepsy. Merritt-Putnam Q 1988;5: 1-20 10. Spencer DD, Spencer SS. Surgery for epilepsy. Neurol Clin 1985;3:313-30 11. Spencer SS. Surgical options for uncontrolled epilepsy. Neurol Clin 1986;4:669-95 12. Geier S, Bancaud J, Talairach J , et al. The seizures of frontal lobe epilepsy. Neurology (Minneap) 1977;27: 95 1-8 13. Wieser HG. Electroclinical features of the psychomotor seizure. Stuttgart: Gustav Fischer, 1983 14. Williamson PD, Spencer DD, Spencer SS, et al. Complex partial seizures of frontal lobe origin. Ann Neurol 1985; 18:497-504 15. Williamson PD, Spencer SS. Clinical and EEG features of complex partial seizures of extratemporal origin. Epilepsia 1986;27 (Suppl 2):S46-63 16. Delgado-Escueta AV, Walsh GO. ?'he selection process for surgery of intractable complex partial seizures:
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Surface EEG and depth electrography. In: Ward AA, Penry JK, Purpura D, eds. Epilepsy. New York: Raven Press, 1983:295-326 Engel J, Rausch R, Lieb JP, et al. Correlation of criteria used for localizing epileptic foci in patients considered for surgical therapy of epilepsy. Ann Neurol 1981;9: 2 15-24 Spencer SS. Depth electroencephalography in selection of refractory epilepsy for surgery. Ann Neurol 1981; 9:207-14 Spencer SS, Spencer DD, Williamson PD, Mattson RH. The localizing value of depth electroencephalography in 32 refractory epileptic patients. Ann Neurol 1982; 12:248-53 Spencer SS. Intracranial recording. In: Spencer DD, Spencer SS, eds. Epilepsy surgery. Cambridge: Blackwell, in press Spencer SS, Williamson PD, Bridgers SL, et al. Reliability and accuracy of localization by scalp ictal EEG. Neurology (Cleve) 1985;35: 1567-75 Spencer DD, Spencer SS, Williamson PD, Mattson RH. Intracerebral masses in patients with refractory partial epilepsy. Neurology (Cleve) 1984;34:432-6 Rich KM, Goldring S, Gado M. Computed tomography in chronic seizure disorder caused by glioma. Arch Neurol 1985;42:26-7 Blume WT, Grabow JD, Darley FL, Aronson AE. Intracarotid amobarbital test of language and memory before temporal lobectomy for seizure control. Neurology (Minneap) 1973;23:812-9 Penfield W, Milner B. Memory deficit produced by bilateral lesions in the hippocampal zone. Arch Neurol Psychiatry 1958;79:475-97 Rosenbaum TJ, Laxer KD. Subdural electrode recordings for seizure focus localization. J Epilepsy 1989;2: 129-35 Olivier A, Marchand E, Peters T, Tyler J. Depth electrode implantation at the Montreal Neurological lnstitute and Hospital. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:595-602 Van Buren JM. Complications of surgical procedures in the diagnosis and treatment of the epilepsies. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:465-75 Spencer SS. Controversies in epileptology. Depth vs. subdural electrode studies for unlocalized epilepsy. J Epilepsy 1989;2: 123-7
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30. Brown WJ. Structural substrates of seizure foci in the human temporal lobe. In: Brazier MAB, ed. Epilepsy: its phenomena in man. New York: Academic Press, 1973: 339-74 31. Babb TL, Brown WJ. Pathological findings in epilepsy. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:5 11-40 32. Spencer SS, Williamson PD, Spencer DD, Mattson RH. Combined depth and subdural electrode investigation in uncontrolled epilepsy. Neurology (Cleve) 1990;40: 74-9 - . 33. Sperling MR, O'Connor MJ. Comparison of depth and subdural electrodes in recording temporal lobe seizures. Neurology (Cleve) 1989;39: 1497-504 34. Spencer DD, Spencer SS, Mattson RH, et al. Access to the posterior medial temporal lobe structures in surgical treatment of temporal lobe epilepsy. Neurosurgery 1984; 15:667-71 35. Luders H, Hahn J, Lesser RP, et al. 8asal temporal subdural electrodes in the evaluation of patients with intractable epilepsy. Epilepsia 1989;30: 131-42 36. Rossi GF. Considerations on the principles of surgical treatment of partial epilepsy. Brain Res 1975;95:395402 37. Soloway SS, Williamson PD, Spencer DD, Mattson RH. Surgery for epilepsy: role of depth electroencephalography. Conn Med 1980;44:70-5 38. Engel J Jr. Outcome with respect to epileptic seizures. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:5.53-72 39. Augustine EA, Novelly RA, Mattson RH, et al. Occupa-
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tional adjustment following neurosurgical treatment of epilepsy for seizure control. Ann Neurol 1984;15:68-72 Spencer SS. Corpus callosum section and other disconnection procedures for medically intractable epilepsy. Epilepsia 1988;29(Suppl 2):S85-99 Spencer SS, Gates J, Reeves A, et al. Corpus callosum section for uncontrolled epilepsy. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:425-44 Spencer SS, Spencer DD, Williamson PD, et al. Corpus callosotomy for epilepsy 1: seizure effects. Neurology (Cleve) 1988;38: 19-24 Spencer SS, Spencer DD, Glaser GH, et al. More intense focal seizure types after callosal section: the role of inhibition. Ann Neurol 1984; 16:686-93 Sass KJ, Spencer DD, Spencer SS, et al. Corpus callosotomy for epilepsy 11: neurological and neuropsychological outcome. Neurology (Cleve) 1988;38:24-8 Sass KJ, Novelly RA, Spencer DD, Spencer SS. Post-callosotomy language impairments in patients with crossed cerebral dominance. J. Neurosurg 1990;72: 85-90 Sass KJ, Spencer SS, Novelly RA, Spencer DD. Mnestic and attention impairments following corpus callosum section for epilepsy. J Epilepsy 1988; 1:6 1-6 Novelly RA, Lifrak MD. Forebrain commissurotomy reinstates effects of preexisting hemisphere lesions: an examination of the hypothesis. In: Reeves AG, ed. Epilepsy arid the corpus callosum. New York: Plenum Press, 1985:467-500
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SEMINARS IN NEUROLOGY
10. NO. 4 DECEMBER 1990
Arriving at the Surgical Options for Intractable Seizures
Although many surgical procedures have been applied to uncontrolled epilepsy over the decades, at the present time only two broad classes of operations have been proven to be effective and remain in common use. These are the resective procedures and corpus callosum section. T h e resective procedures involve exactly what the name implies, removal of a small portion of the brain with the intention of stopping seizures. As such, these operations are applied only to partial epilepsies (with or without secondary generalization). They are the preferred and most common operations for epilepsy that is uncontrolled by medication because they offer the possibility of cure. Corpus callosum section is a second choice, palliative procedure, which aims only to limit the clinical expression of the generalized seizure. It is an appropriate consideration in secondarily generalized or generalized seizure disorders. T h e manner in which one arrives at these surgical options involves a complicated series of steps that begins with the same basic set of selection criteria. These are roughly similar among epilepsy surgery centers.'-"
INITIAL SELECTION CRITERIA First of all, seizures must occur with sufficient frequency and intensity to interfere significantly with a person's lifestyle. No particular frequency is required, but, rather, it is the combination of the frequency of seizures and the characteristics of the individual seizure that qualifies someone to be considered for surgery. Secondly, seizures must have been uncontrolled despite trials of all of the appropriate anticonvulsant drugs, with documented therapeutic
serum levels and with trials of monotherapy and polytherapy. Again, no specific length of' time for such trials can be given, because an adequate trial depends on the seizure frequency. Little has been written about specifically which or how many drugs should be tried to fulfill this condition, nor about the likelihood of response to secondary anticonvulsant medications once the first-line drugs have failed to achieve satisfactory seizure control. Most centers require trials of major anticonvulsant medications, including phenytoin, phenobarbital, and carbamazepine; some include primidone in this list; and valproate is achieving a place here as well, although information is still accumulating with respect to its efficacy in partial seizures."The best available information suggests that additional seizure control after failure of monotherapy is achieved with two major drugs in only 11% of pat i e n t ~ . ~It, ' is reasonable from these data to assume that only the extremely unusual patient is likely to exhibit lasting response to second-line drugs when major ones have failed in both monotherapy and polytherapy. Nevertheless, especially in patients with frequent seizures, trials of some such drugs are not unreasonable. 'Thirdly, there should be no other significant or progressive neurologic, medical, or psychiatric diseases that would interfere with the extensive evaluation, increase the risk of surgery, or inhibit successful rehabilitation after epilepsy surgery. T h e issue of baseline psychiatric status and its implications for success of epilepsy surgery is unresolved. Most of the (minimal) literature suggests that psychiatric status is an independent variable; that adjustment and neurotic disorders in some circumstances may improve if surgery successfully controls seizures; and that psychosis is generally
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut Reprint requests: Ilr. Spencer, Yale University School of Medicine, Department of Neurology, 333 Cedar Street, New Haven, CT 06510 Copyright O 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
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S w a n S. Spencer, M.D., and Amiram Katz, M.D.
SURGICAL OPTIONS FOR INTRACTABLE SEIZURES-SPENCER, KATZ
RESECTIVE PROCEDURES Because the resection procedures are the preferred operations for uncontrolled epilepsy, they will be discussed first and most extensively. It has been repeatedly shown that the success of a resective procedure in controlling epilepsy that has been unresponsive to medical therapy depends on the accurate localization of the cerebral area responsible for initiating the habitual seizures and the total removal of the area so identified. Therefore, because persons who are candidates for resective procedures must have all of their seizures beginning in a single, definable, and removable cerebral area, the localization of the focus is the single most important piece of information that must be obtained.
T h e manner in which the focus is localized differs at various centers, but all use a phased evaluation, of which the routine at Yale is representativeg-" (Table 1). PHASE 1
Phase I involves an approximately 2-week hospitalization during which the history is taken and physical, neurologic, and neuropsychologic examinations and closed circuit audiovisual and EEG monitoring are performed. Monitoring is usually continuous and sometimes requires medication withdrawal to record the habitual seizures utilizing the scalp electroencephalogram (EEG). During this phase, imaging procedures are also performed, including computerized tomography (CT), magnetic resonance imaging (MRI), single-photon emission computerized tomography (SPECT) scan, and positron emission tomography (PET) (where available). Phase 1 thus provides considerable information. Review of the videotapes of recorded seizures establishes that they are partial seizures of stereotyped onset. Centers experienced in video review of seizures have recognized certain features of complex partial seizures which implicate specific cerebral areas of origin.I2-l5Table 2 gives some of these characteristics; they are not specific, but taken together often constitute evidence pointing to a certain lobe of onset which then requires fur-
Table 2.
Phase I. Initial evaluation 1. Thorough history, medical and neurologic examination 2. Psychiatric examination 3. Neuropsychologic testing 4. MRI 5. Formal visual fields 6. Baseline EEG 7. Continuous audiolvideo monitoring to record minimum of three seizures 8. PET, SPECT if available Phase II. Preparation for implanted electrodes 1. Two-vessel cerebral angiogram 2. Left and right cerebral amobarbital testing Phase Ill. Depth and cortical electrode implantation 1. Depth and/or cortical electrodes-number and placement dependent on prior evaluation 2. Continuous audiolvideo and depth EEG monitoring to record at least three seizures Phase IV. Surgery 1. Mapping of speech and motor areas when indicated 2. Cortical resection *Reprinted with permission from Spencer et aL9
Some Characteristics of Seizures from Various Cerebral Areas
Tem~orallobe Psychical manifestations (d6jA vu, jamais vu) Complex perceptual disturbances (micropsia, macropsia, complex visual hallucinations) Motionless stare Oro-alimentary automatisms (lip-smacking, chewing) Complex motor automatisms, often of upper extremities (fumbling, picking, repetitive activity) Duration usually > 1 minute Prolonged postictal state Frequency usually 3-lO1month -
Table 1. Surgical Evaluation for Epilepsy*
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not affected. Psychotic states are therefore a contraindication if and only if they produce behavior that places the patient at undue risk during study, or if their extent is such that rational consent and improvement in lifestyle with seizure control are judged impossible." Finally, most patients considered for epilepsy surgery are under the age of 50 years. Although in the past a lower age limit of 10 was sometimes publicized, it has become increasingly evident that children can benefit substantially from surgical procedures and therefore no lower age limit is now ~ the individual meets the other advocated as l o -n as selection criteria.
0
Frontal lobe Abrupt onset and termination Vocalization Semipurposeful motor automatisms, often of lower extremities (kicking, thrashing) Sexual automatisms Tendency to frequent secondary generalization and complex partial status epilepticus Duration usually 50/month Occipital lobe Visual loss Sensation of eye movement (not observed) Forced blinking or eye fluttering Contralateral eye deviation Subsequent temporal or frontal spread with appropriate symptomatology
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424
ther study or confirmation. 'I'he presence of multiple seizure types must also be established. On some occasions, variability of clinical seizure types may emerge from a single focus because of variable degree or direction of spread from the focus of onset, and they should be distinguished from the presence of multiple foci which decreases the advisability of resective surgical intervention. Phase 1 also documents electrical abnormalities, both interictal and ictal, as recorded by the scalp EEG. T h e presence of focal spikes recorded by interictal scalp EEG regardless of apparent localization is a helpful item suggesting the presence of focal epilepsy, or of seizure onset from a focal cerebral region. Precise localization, however, can often be misleading when based on interictal surface EEG spikes.lG-l"f interictal spikes are multifocal, the patient may still have a single focus responsible for the onset of his habitual and uncontrolled seizures and thus remain a surgical candidate. If the interictal EEG is normal, focal seizure onset is still possible, although pseudoseizures should be excluded. The presence of 3 Hz spike and wave discharge on the interictal or (ictal) EEG without focal spikes is suggestive of primary generalized epilepsy; if this diagnosis is confirmed based on videotaped analysis of seizures, such patients are excluded from consideration for resective surgery. Some patients with bilaterally synchronous spike and wave discharge, however, may have focal seizure onset with so-called secondary bilateral synchrony. Thus, patients with bilateral spike and wave should never be categorically excluded, but rather studied further for evidence of focal seizure onset. Usually, it is most profitable to review clinical seizure types as recorded on videotape for these distinctions. If the surface EEG recording captures the onset and buildup of a clinical seizure, focal or generalized high-frequency discharge, spiking, or no change at all except for artifact may be seen. None of these patterns at our present stage of knowledge constitutes a contraindication to further surgical workup, nor does any of them imply a certain region of onset."' Furthermore, surface EEG recording of the ictal event itself, mostly because of the prevalence of artifactual changes, has been established to be unreliable and inaccurate in its localization of the area of seizure onset.2' This is underscored by the onset of clinical seizure activity prior to seizure discharge seen on surface EEG in most instances. Sphenoidal electrode recordings are believed by many electroencephalographers to provide increased yield of focal ictal scalp recording, and abnormalities recorded with them are taken to imply mesial temporal lobe localization."' This latter contention, however, has not been adequately
VOLUME 10, NUMBER 4 IIECMBER I990
verified, and it remains possible that sphenoidal electrodes may also reflect seizure discharge in other cerebral locations; it is well established that they may not detect mesial temporal discharges. Functional abnormalities from the neurologic and neuropsychologic examinations and structural abnormalities based on the imaging studies complete the data in phase 1. C T and, more often, MRI may reveal discrete or generalized cerebral abnormalities that can have significant bearing on the remainder of the evaluation and the exact course of further therapy. For example, the presence of a cerebral neoplasm with surrounding edema would establish the need for surgery by itself, regardless of the characteristics of the seizures or the EEG (although the exact approach might be modified in an attempt to treat the uncontrolled seizures as well as the lesion). Lesions such as small calcifications, vascular anomalies, or fbcal abnormal signals, although not necessarily an indication for craniotomy without the presence of epilepsy, have a greater significance in the setting of uncontrolled seizures. Numerous studies have established that such lesions are more than likely to represent a cerebral glioma, even if epilepsy has been present for more than a de~ade,~%rid in many patients these gliomas may be unexpectedly high grade.""uch lesions are now detected in 25%) of patients evaluated for epilepsy surgery. With current technology, MRI can document mesial temporal atrophy and sclerosis in another 25% of patients referred for surgical consideration. Localizing abnormalities of electrical, functional, clinical, and structural varieties are then reviewed. These may or may not be in agreement and may or may not be localizing at all. Nevertheless, provided that seizures begin in a stereotyped, partial manner and provided that it is still considered possible that all seizures begin in a single cerebral location, the patient may proceed to Phase 2. PHASE 2
Phase 2 is really another test of cerebral structure and function, but it is performed as a separate phase because it is slightly more invasive. 'Therefore we require that the patient at least be considered still to be a possible candidate for surgery. In some centers, Phase 2 is performed earlier or later in the sequence of study, but is always a necessary part of the total evaluation. A cerebral angiogram is performed, which is important for planning the further evaluation and surgery and for demonstrating vascular abnormalities. Following angiography, the intracarotid cerebral amobarbital (Amytal) test is performed. Sodium amobarbital 100 to 150 mg is injected sequentially into the carotid ar-
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SEMINARS IN NEUROLOGY
SURGICAL OPTIONS FOR INTRACTABLE SEIZURES-SPENCER, KATZ
combination localize at all or with sufficient accuracy, then it is necessary to pursue more accurate electrical localization with intracranial electrode implantation. This occurs in approximately 50% of the patients at our center. PHASE 3
Phase 3 involves the implantation of intracerebral or subdural electrodes, or both, to record seizures intracranially for better localization. This implantation is again followed by continuous audiovisual and EEG monitoring to record many habitual, spontaneous seizures. Selection of types of electrodes to be used depends on many factors. Table 3 contrasts the differences, according to presently available information, between depth and subdural electrodes. They are both multicontact electrodes. Depth electrodes may be rigid or flexible, whereas subdural electrodes may be strips, catheters, or large grids. Both kinds are inserted in the operating room in preselected sites and used for chronic recording of 1 week or more. Depth electrodes have a slightly higher risk of major complications, which are weighted toward intracerebral hemorrhage, although recent MRIIangiographic techniques are said to reduce this risk.26-" Subdural electrodes are more likely to produce infection and cerebral edema.'"'y According to the literature, in patients who have insufficient localization by previous studies, either depth electrodes or subdural electrodes are capable of localizing the focus in 60 to 70%'"3'"he success rate from surgery after a focus has been identified by these methods is slightly higher for depth electrodes, but data on patients selected by subdural study are still being accumulated. Depth electrodes are likely to be better for accurate localization in the temporal lobe because they record directly from the hippocampus, the most common site of origin of temporal lobe seizures and the most common site of pathologic change in temporal lobe epilepsy.'"~" They have been shown to be more sensitive than other techniques in detecting both simple and complex partial seizures aris," placed acing from the h i p p o c a m p ~ s . ~ ~When cording to certain protocols, they can define the anterior-posterior extent of the focus in the medial temporal lobe and, by doing so, may modify the operation." Subdural electrodes are also capable of accurately lateralizing temporal lobe epilepsy, but they are not able to define as precisely the anterior-posterior dimensions of a medial temporal lobe focus, because they do not record from the hippocampus directly; this is true despite more medial placements recently implemented.3"oth types of electrodes have been notably inaccurate in
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teries, producing temporary drug-induced anesthesia in the distribution of the ipsilateral carotid arteries, subserving the language and memory areas. During the 10-minute effect of the sodium amobarbital, the language and memory functions of the contralateral, unanesthetized hemisphere Obviously, documentation of side of are a~sessed.'~ cerebral dominance is critical in planning safe resective procedures. Furthermore, demonstration of lack of memory in one hemisphere is taken to indicate a functional abnormality in that temporal lobe, and also taken to imply that the other temporal lobe should not be removed without major the physrisk to the patient's memory.2"lthough iologic basis and the accuracy of such studies have not been proven, and, in some circumstances the accuracy is clearly questionable because of variations in vascular anatomy, this test is a widely used standard for these purposes. To my knowledge, no patient has been reported to develop an amnestic syndrome after temporal lobe resection when the intracarotid amobarbital procedure clearly demonstrated intact contralateral memory. After Phases 1 and 2, the information is reviewed to plan further patient evaluation and management. As already noted, if a well-defined lesion is demonstrated on C T or MRI, it is often a lowgrade tumor. Provided the EEG information from Phase 1 is consistent, resection of such a lesion with margins is very likely to provide cure of seizures. Further evaluation is not necessary in these circumstances unless the lesion is in close proximity to important functional areas, in which case functional mapping will be required. When the imaging studies do not demonstrate a focal structural lesion, some other confirmation of the scalp EEG localization is required to proceed with a resective procedure. If all of the abnormal localizing studies in Phase 1, including functional, electrical and structural studies, point to one temporal lobe as responsible for seizures, then it may be resected after Phases 1 and 2, provided that memory is adequate in the contralateral hemisphere. This scenario is usually fulfilled by the patient with hippocampal atrophy on MRI, neuropsychologic test profile consistent with dysfunction in the same ten~porallobe (usually represented by specific verbal or visual memory impairments), interictal and ictal surface EEG characterized by ipsilateral temporal spikes and seizure discharge, and a clinical seizure profile consistent with the temporal lobe syndrome (see 'Table 2) often with a history of febrile seizures. Extratemporal localization, however, is only very rarely possible after Phases 1 and 2, without a lesion or well-defined mass. Finally, if the several studies performed in Phases 1 and 2 localize differently, or do not in
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Depth Versus Subdural Electrodes Depth
Subdural
Construction
Multicontact or bipolar, rigid or flexible
Strips, catheters, or grids, all multicontact
Insertion
Lateral or medial insertion in preselected sites; burr holes
Craniectomy, craniotomy in preselected sites
+
Length of recording
1 week
Risks
2-4%, hemorrhage, infection
1 week
+
Yield of localization
60-80%
1-4%, infection, edema, hemorrhage 60-70%
Reported surgical success
60-90%
60-65%
Accuracy in temporal lobe epilepsy
Excellent for lateralization, and for anteriorposterior definition in hippocampus
Excellent for lateralization but not for anterior-posterior definition in hippocampus
Sensitivity in temporal lobe epilepsy
Excellent for mesial and lateral hippocampal and neocortical detection (depends on placement)
Misses over 20% of medial hippocampal seizure discharges, including most auras and subclinical seizures
Accuracy and sensitivity in extratemporal foci
Poor data
Poor data
Mapping
Not well suited
Ideally suited
Figure 1. Simultaneous depth and subdural EEG recording of seizure onset, seen in depth electrode (LPT) traversing the left hippocampus initially with later involvement of temporal neocortex seen in subdural electrode (NEM). RMT, LTM = midtemporal depth electrode; NEM = left temporal subdural electrode. Numbers designate contact points on electrodes from superficial (1) to deep.
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Table 3.
VOLUME 10, NUMBER 4 DECEMBER 1990
SURGICAL OPTIONS FOR INTRACTABLE SEIZURES-SPENCER,KATZ
dial temporal lobectomy is performed, consisting of a limited anterior resection followed by en bloc removal of the hippocampus.g
RESULTS Sixty to 90% of appropriately selected patients will have cure of their seizures after resective proc e d u r e ~ . "Functional ~~ rehabilitation is not, however, as good as seizure control. Patients generally improve their work status or return to work, but those who have been disabled and have never worked rarely seek employment, regardless of the effects of surgery on seizures.3gPartly, this is attributable to lack of appreciable response of significant psychiatric disease to seizure control, but certainly many more factors are involved. The neurologic sequelae of resective surgery depend on the area resected.2gWith temporal lobe resections, we expect a contralateral superior quadrantanopia, but minimal memory disturbances provided that the sodium amobarbital test has demonstrated adequate memory in the contralateral hemisphere. With frontal lobe resections, personality disturbances may occur; unfortunately, there is no preoperative test to aid prediction. It is generally thought that more limited resections are less likely to cause personality deficits, underlining the importance of careful localization.
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localizing extratemporal foci unless a lesion has been demonstrated on C T or MRI to aid placement of the electrodes." Finally, depth electrodes are not well suited to mapping (see later), whereas subdural electrode grids are ideally suited for mapping of functional areas believed to closely approximate the seizure f o c ~ s . ~ " ~ ~ . ~ ~ , ~ ~ In Figure 1, an EEG demonstrates simultaneous depth and subdural recording in a patient who has both a left temporal depth electrode and subdural electrode. The precise site of seizure onset is seen in the left temporal depth electrode medially; later, the seizure involves the left temporal neocortex as recorded by the subdural electrode. T h e recordings are of high quality and free of artifact; in this instance, they confirm the usual medial temporal onset of seizures in a patient whose seizures were not well localized by scalp EEG. If the seizure focus or lesion is close to areas that are very important functionally, mapping will be necessary. This can be done acutely in the operating room under local anesthesia or chronically with implanted subdural electrode grids so that the seizure onset can be superimposed on the functional mapping. With computerized methods, the contact points of the grid can be represented on the surface of the brain so that areas of functional importance can be depicted with respect to the seizure focus. This approach is particularly suited to evaluation of patients with uncontrolled epilepsy associated with extratemporal lesions.
HEMZSPHERECTOMY PHASE 4
If a seizure focus can be accurately identified and occurs in a resectable portion of the brain, surgery can proceed in Phase 4. Complete removal of the area identified as the seizure focus correlates with success in cure of seizure^.""^' There is a 2% risk of major complications from epilepsy surgery of the resective type, and neurologic deficits may, of course, limit the possibility of fully resecting the area. In our experience, 60 to 70% of patients with uncontrolled epilepsy have seizures arising in the temporal lobe. T h e frontal lobe is the next most frequent site of origin. Seizures of partial type can originate, however, in any cerebral lobe, and portions of any lobe in the dominant or nondominant hemisphere can be safely resected with appropriate precautions. Various surgical procedures may be used, depending to some extent on the philosophy at the particular center. Thus, in temporal lobe epilepsy, more or less or exclusively medial or lateral resection may be done.g At Yale, because electrophysiologic, pathologic, and structural analyses support predominantly medial involvement, an anterome-
Hemispherectomy is the most extreme of the resective procedures, involving removal of the majority of one hemisphere. It is indicated for patients who have multiple seizure foci within one hemisphere, who have unilateral partial seizures as their major seizure type, and who have significantly impaired contralateral motor function, particularly in the hand. In such individuals, excellent response is obtained, with cure of seizures and minimal increase in motor deficits. Although the majority of the hemisphere still is removed in such operations, operative technique has been revised because of the previous long-term complication of hemosiderosis with a high mortality rate.29 Now, small portions of cerebral tissue are' left in the affected hemisphere, but functionally disconnected. So far, this modification (and others) have not been associated with hemosiderosis, but no systematic analyses have been done. CORPUS CALLOSUM SECTION
After the extensive evaluation involved in Phases 1, 2, and sometimes 3, some patients who continue to have medically uncontrolled seizures
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SEMINARS IN NEUROLOGY
patient^.^'.*^
428
Possible neurologic side effects of severing the major connections between the cerebral hemispheres are a concern. This problem has been studied.44Language impairments, usually of an expressive nature, can occur after corpus callosum section. These are rare, and they are predictable by preoperative evaluation. They have been associated with split dominance of language and handedness and are particularly prominent in righthanded patients with right hemisphere dominance for language. Although this is not an priori exclusion, the risks of expressive language impairment, including mutism must be considered in this poplat ti on.^^ Weakness or apraxia of the nondominant leg occurs on occasion. It is usually an exacerbation of a preexisting weakness and it usually improves postoperatively, although sometimes not to its baseline level. A decline in memory, although previously in dispute, has been documented to occur after corpus callosum section in rare patients4'jand appears to be related to poor postoperative control of generalized seizures. Aggressive behavior is sometimes worsened but does not appear de novo. The intelligence quotient (IQ) is usually unchanged. Some investigators believe that the mechanism of production of neurologic deficits after corpus callosum section relates to "unmasking" of previously sustained focal injury whose recovery was dependent on interhemispheric synergy me~~ may diated by the corpus ~ a l l o s u m .Retraction also play a part.
In reviewing of the literature with regard to control of generalized seizures and minimal neurologic side effects after corpus callosum section, it appears that the best candidates are individuals with an I Q over 50 who have falls, whose seizures began before the age of 5 years, and in whom handedness and language are controlled by the same hemisphere. These persons are most likely to have neither generalized seizures nor deficits.
APPROACHES TO EPILEPSY SURGERY Figure 2 is a summary of the approach to epilepsy surgery. Patients with uncontrolled epilepsy that interferes significantly with their lives are studied in Phases 1 and 2, and sometimes Phase 3. Evaluation at all centers is roughly comparable. If a focus is localized to a resectable area, a resective procedure offers a high likelihood of seizure cure. If the focus is localized to an unresectable area and mostly partial seizures are present, no operation is possible, but if the partial seizures often generalize, corpus callosum section can be considered as a palliative procedure to limit the generalized seizures. In those cases without localization, if bilateral seizure onset has been demonstrated with only partial seizures, again no operation is possible. If seizures secondarily generalize sufficiently frequently to interfere with life or safety, corpus callosum section can be considered a palliative alternative. With unilateral but multifocal seizure onset, only partial motor seizures, and significant motor impairment, hemispherectomy is indicated. However, if motor impairment is not present, no operation is recommended. Finally, with unilateral multifocal seizures that frequently generalize and without motor impairment, corpus callosum section again can be used for palliation.
SUMMARY Surgery is 80 to 90% effective in properly selected patients with uncontrolled epilepsy. T h e localization of the epileptic focus determines the applicable operation. Resective procedures are preferred because they offer the possibility of cure. However, in certain circumstances corpus callosum section can be used for palliation because it offers relief of generalized seizures and falls in a substantial proportion of individuals with uncontrolled secondarily generalized seizures who are not candidates for resection. Substantial progress in patient evaluation and protocols for surgical treatment has been made in the past decade.
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that interfere significantly with their lives are excluded from resective procedures. Their seizures are either unlocalized, localized to multiple areas bilaterally, or localized but not resectable. For the subpopulation of these patients, and others, who have uncontrolled, secondarily gen~pralzzed seizures with falls, and perhaps for patients with significantly uncontrolled primary epilepsy with falls, corpus callosum section may be considered as an alternative therapeutic option. Corpus callosum section is a two-stage, palliative procedure that aims only to prevent the generalization of seizures by disconnecting the cereThe fibers of the corpus bral callosum and hippocampal commissure are interrupted. T h e section is done in two stages to decrease the length and severity of the transient postoperative disconnection syndrome. Corpus callosum section can be expected to eliminate or markedly decrease falls and generalized seizures in 85% of patients undergoing the procedure. It is not indicated for partial seizures, which are usually unchanged, although they can improve in about 40% of patients, or can increase in either intensity o r frequency in about 25% of
VOLUME 10, NUMBER 4 DECEMBER 1990
SURGICAL O P T I O N S FOR INTRACTABLE SEIZURES-SPENCER, KATZ
-)(:
Uncontrolled epilepsy
Phase l II (111) . .
Resectable area in one lobe
\Unresectable
a'a Only
Focus ~unlocalized
"3Unilateral
/
Bilateral Partial
Partial
partial
I
Resection (any lobe or part)
seiqres
generalized seizures I
/
1 (
Functioning
4
No operation
'Partial
and generalized
motor seizures
/\
J
I
Minimal use, contralateral hand
L
Good use of contralateral
I
Corpus Callosum section
Hemispherectomy
No operation Downloaded by: University of British Columbia. Copyrighted material.
Focus localized
Figure 2. Summary of approach to epilepsy surgery. (From Spencer et aL9 Reprinted with permission.)
REFERENCES 1. Walter RD. Principles of clinical investigation of surgical candidates. Adv Neurol 1975;8:49-58 2. Browne TR, Feldman RG, eds. Epilepsy diagnosis and management. Boston: Little, Brown, 1983 3. Green JR. Temporal lobectomy, with special reference to selection of epileptic patients. J Neurosurg 1967;26: 584-93 4. McNaughton FL, Rasmussen T. Criteria for selection of patients for neurosurgical treatment. Adv Neurol 1975; 8:37-48 5. Bourgeois BFD. Valproate: clinical use. In: Levy RH, Dreifuss FE, Mattson RH, et al, eds. Antiepileptic drugs. New York: Raven Press, 1989:633-42 6. Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonicclonic seizures. N Engl J Med 1985;313: 145-51 7. Smith DB, Mattson RH, Cramer JA, et al. Results of a nationwide Veterans Administration cooperative study comparing efficacy and toxicity of carbamazepine, phenobarbital, phenytoin, and primidone. Epilepsia 1987;28 (suppl 3):S50-8 8. Spencer SS, Spencer DD. Outcome: data, dogma, directions. In: Spencer DD, Spencer SS, eds. Epilepsy surgery. Cambridge: Blackwell, in press 9. Spencer SS, Schwarz S, Spencer DD. Surgery for epilepsy. Merritt-Putnam Q 1988;5: 1-20 10. Spencer DD, Spencer SS. Surgery for epilepsy. Neurol Clin 1985;3:313-30 11. Spencer SS. Surgical options for uncontrolled epilepsy. Neurol Clin 1986;4:669-95 12. Geier S, Bancaud J, Talairach J , et al. The seizures of frontal lobe epilepsy. Neurology (Minneap) 1977;27: 95 1-8 13. Wieser HG. Electroclinical features of the psychomotor seizure. Stuttgart: Gustav Fischer, 1983 14. Williamson PD, Spencer DD, Spencer SS, et al. Complex partial seizures of frontal lobe origin. Ann Neurol 1985; 18:497-504 15. Williamson PD, Spencer SS. Clinical and EEG features of complex partial seizures of extratemporal origin. Epilepsia 1986;27 (Suppl 2):S46-63 16. Delgado-Escueta AV, Walsh GO. ?'he selection process for surgery of intractable complex partial seizures:
17.
18. 19.
20. 2 1. 22. 23. 24.
25. 26. 27.
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