[1] 14w The Role of the Intracarotid Amobarbital Procedure in Evaluation of Patients for Epilepsy Surgery

[1] 263w To examine the role of the intracarotid amobarbital procedure (IAP) in the presurgical evaluation of patients with medically refractory localization-related epilepsy.Methods: We retrospectively studied 1 11 patients who underwent cortical resective surgery at our center between 1991 and 1996. In patients with mesial temporal lobe epilepsy (mTLE), a presurgical determination of the epileptogenic zone was compared with localization based on IAP memory asymmetry scores, and with ultimate localization after resective surgery. In patients with neocortical or mesial frontal epilepsy, the IAP was evaluated for evidence of unilateral or bilateral poor memory performance.Resultx Of 68 patients with mTLE localized by noninvasive tests, 60 had concordant lateralized memory deficits on IAP. Eight patients had lateralized memory deficits on IAP that were discordant with noninvasive tests and with localization as determined by surgical outcome. All l l mTLE patients requiring invasive EEG monitoring were correctly lateralized by IAP, including one patient in whom the noninvasive evaluation otherwise provided false lateralization. Of 32 patients with neocortical or mesial frontal lobe epilepsy, 21 displayed memory deficits on IAP. Of 10 patients with bilateral deficits, five had mesial frontal lobe epilepsy. In 13 patients with lateralized memory deficits, seven underwent electrode implantation in the mesial temporal lobe, and four ultimately underwent resection of an epileptogenic mesial temporal lobe in addition to a neocortical resection.Conclusions: In patients with mTLE, lateralized memory deficits on IAP usually confirm localization provided by noninvasive tests. However, in mTLE not well lateralized by the noninvasive evaluation, and in neocortical or mesial frontal epilepsy, the IAP may provide information regarding localization that ultimately alters surgical management.

[1] 7w Group 1: patients with mTLE(n = 79)

[2] 187w Of 79 patients, 68 (86%) met the noninvasive criteria for unilateral mTLE (Fig. 1). TAP was concordant with the noninvasive evaluation in 60 (88%) of 68 patients and was discordant in eight (12%) cases. In all eight cases in which TAP data were discordant, ultimate localization agreed with the noninvasive evaluation (Table 1). Five of eight patients incorrectly lateralized by IAP had a lower memory score after dominant hemisphere injection. Preoperative neuropsychological testing, if lateralized, agreed with the noninvasive evaluation. Several patients (patients 1, 2, 4, and 7) showed such low scores with injection ipsilateral to the seizure focus that concern was raised about global memory impairment. In three of these cases, the patient underwent superselective (selective posterior cerebral artery) TAP that demonstrated adequate memory function with ipsilateral injection, and in one instance, the standard IAP was repeated and showed adequate memory using the contralateral hemisphere. Abnormal IAP bilaterally (n=10) patients with neocortical or mesial frontal lobe epilepsy (n = 32) Of 32 patients, 21 (66%) with neocortical or mesial frontal lobe onset seizures had abnormal performance on -Mesial No Mesial temporal Temporal lobe lobe epilepsy epilepsy

[3] 118w the IAP as defined earlier (Fig. 2). Ten patients had poor performance on memory testing after each injection. The mean full-scale IQ scores of these 10 patients did not differ from those of the group as a whole (90.6 vs. 88.6). Patients with mesial frontal lobe epilepsy (mFLE) were overrepresented in this group; five of seven patients with mFLE scored poorly on memory testing after each injection, compared with five of 25 non-mFZE patients (p < 0.05, x2). Of those with very poor memory scores bilaterally (score <4 bilaterally), mFLE patients were again overrepresented (four of five had mFLE (p < 0.01, x2). Standard neuropsychological testing indicated expected memory abilities for IQ level in all patients with mFLE.

[4] 123w Thirteen (40%) patients showed lateralized deficits on IAP. Of these, seven (54%) underwent additional electrode implantation of mesial temporal structures, and four (31%) ultimately showed evidence of mTLE, and underwent mesial temporal lobe resection in addition to neocortical resection (Table 2). Six of 13 patients with lateralized deficits on IAP showed worse performance on memory testing after dominant hemisphere injection. Presence of dual pathology was definitively established by identifying mesial temporal sclerosis by neuropathology (patient 2), by documenting mesial temporal onset seizures on invasive EEG monitoring (patient 3), or by class 1 outcome after a two-step surgical procedure [i.e., resection of extramesial temporal cortex with persistent seizures followed by seizure freedom after anterior temporal lobectomy including mesial temporal structures (patients 1 and 4)].

[1] 106w The IAP is frequently used in the preoperative evaluation for epilepsy surgery to provide information about language lateralization and memory function (1). In many instances, language lateralization may not be critical, such as when the proposed resection is distant from language cortex or when a standard conservative anterior temporal lobectomy may be carried out safely. Memory testing may be more important, both as an additional localizing tool in mTLE (in which a lateralized memory deficit is anticipated), and as a test for safety of mesial temporal lobe resection (as a predictor of global amnesia in bitemporal disease). The latter role was not addressed in this study.

[2] 192w This study examined the localizing value of the IAP in surgical decision making, not as an independent predictor of outcome, but in the context of the entire evaluation. In our cases of mesial temporal epilepsy, the IAP added little additional localizing information. In 12% of cases otherwise localized by the noninvasive presurgical evaluation, the IAP provided false localizing information; in no instance did a discordant IAP correctly lateralize. Five of eight patients whose epileptogenic region was falsely localized by the IAP had seizure onset in the language-dominant hemisphere. Other investigators have noted lower scores after injection of the languagedominant hemisphere, and some have advocated correcting scores based on language dominance (8). It is possible that this inherent asymmetry in memory scores played a role in some of our false localization; however, a recent study suggested that modification of IAP memory scores based on language dominance ("language handicap") may decrease the probability of obtaining clinically useful lateralizing data (22). In the smaller number of patients with mTLE requiring invasive monitoring, the IAP was concordant with ultimate localization, and in only one instance was this different from the suspected localization determined by noninvasive testing.

[3] 57w Lateralized IAP memory scores correlate with MRIdemonstrated mesial temporal sclerosis and with hippocampal neuronal loss by neuropathology (4,5,7,9,23). Sass et al. (9) found that lateralized IAP memory scores correlated specifically with cell loss in the CA3 hippocampal subfield, but O'Rourke et al. ( 5 ) noted correlation only with cell loss in the hilum and dentate gyrus.

[4] 81w Several investigators have found that asymmetry in IAP memory scores is an independent predictor of postsurgical outcome in mTLE (6,8,10). One study found a direct relation between the degree of asymmetry and surgical outcome (6). These carefully selected patients (most studies excluded any MRI pathology except mesial temporal sclerosis) likely showed high positive predictive value in other tests as well, and these studies did not address whether the IAP contributed information that was useful in the context of this other testing.

[5] 151w Our findings suggest that the localizing value of the IAP varies by the location of the epileptogenic region in patients with medically intractable localization-related epilepsy. The IAP added little additional localizing information in our cases of mTLE that could otherwise be localized by the noninvasive presurgical evaluation, and the IAP provided falsely localizing information in some instances. Many centers now perform the IAP selectively in cases of mTLE and may not perform the test unless neuropsychological testing raises concerns about memory function, or atypical language organization is suspected. Our study does not address whether the IAP might be more helpful in these selected "difficult" cases. The correct identification of the epileptogenic temporal lobe by lateralized IAP memory scores in those patients requiring invasive monitoring suggests that the TAP may play an important but limited role in localizing seizure onset in these patients. A larger study examining this specific issue is needed.

[6] 89w In neocortical and mFLE, however, the IAP provided valuable localizing information. The IAP identified patients with additional epileptogenic regions in the mesial temporal lobe structures. Of the neocortical and mFLE patients with lateralized IAP scores, 3 1 % had mTLE in addition ("dual pathology"). Poor 1AP memory performance was evenly distributed between language-dominant and nondominant hemisphere injections, arguing against false lateralization resulting from greater difficulty after injection of the language-dominant hemisphere. A surprising number of patients with mFLE performed poorly bilaterally on the IAP. This observation requires further investigation.

[7] 118w Although the mechanism for this poor performance bilaterally on the IAP is not known, it is possible that cingulate or supplementary motor area lesions may impair memory processing. There is some evidence to suggest that a unilateral focus in patients with frontal lobe epilepsy may disrupt functional memory circuits ipsilat-era1 and contralateral to the focus (24). Studies from the PET literature have implicated mesial frontal lobe structures in various memory tasks (24)(25)(26)(27). Recent functional MRI studies have identified some of the same regions (28,29). Whatever the mechanism, this may be a significant clinical observation. mFLE should be considered in any patient performing poorly on the IAP bilaterally who does not show significant memory impairment on standard neuropsychological testing.

[8] 64w In summary, the IAP adds little independent localizing information to the presurgical evaluation in this series of patients with mTLE. However, the IAP may make significant contributions in patients with neocortical and mFLE by suggesting additional epileptogenic mesial temporal structures or by demonstrating a characteristic pattern of bilateral memory dysfunction seen in patients with mFLE. Acknowledgment: Dr. Spencer is supported by the Susan E.

[1] 120w The study population consisted of all 141 patients who underwent surgery for medically intractable epilepsy between 1991 and 1996 at the Stanford Comprehensive Epilepsy Center. Patients ranged in age from 9 to 58 years at surgery, with a mean age at surgery of 32.0 years. Ten of the patients were children (younger than 18 years). Mean age at seizure onset was 11.8 years, and mean duration of epilepsy before surgery was 19.8 years. Patients were excluded from the study if they had IQ <75, nonresective surgery (e.g., corpus callosotomy), or if they did not undergo bilateral IAP. The remaining 11 1 patients (79 with mTLE and 32 with neocortical or mesial frontal epilepsy) were evaluated by using the protocols described.

[2] 57w All patients underwent preoperative evaluation that included interictal and ictal scalp video-EEG monitoring, brain MRI, neuropsychological testing, and the IAP. Some patients also underwent functional neuroimaging tests [single-photon emission computed tomography/ positron emission tomography (SPECT/PET)] or invasive electrophysiologic monitoring. Surgical outcome was reported at 1 year by using the classification system proposed by Engel et al. (14).

[3] 78w A battery of tests was administered preoperatively, including standardized interview, the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, the California Verbal Learning Test, the Rey-Osterreith Complex Figure, Wisconsin Card Sorting Test, as well as motor, personality, quality of life measures (15-19). The Wechsler Intelligence Scale for Children-Revised was administered to children (20). A summary statement from the neuropsychologist indicated whether "lateralized" memory deficits (e.g., verbal deficits out of proportion to visuospatial deficits or vice versa) were present.

[4] 218w A pretest angiogram was performed to define the intracranial vasculature and assess for interhemispheric cross-filling. EEG monitoring was performed by using a 2 1 -channel Nihon-Kohden Neurofax 4400 machine. The internal carotid artery supplying the suspected epileptogenic hemisphere was injected by hand first with 125 mg of amobarbital over a 5-s period. After documentation of unilateral hemiparesis, language testing was performed. After confirmation of unilateral EEG slowing (usually at t = 90 s), a series of three objects, three words, and three designs was presented to the patient within 3 min of injection. The patient was allowed to recover to baseline EEG, and neurologic function and recognition memory for previously presented stimuli were tested. The three object stimuli were presented randomly with six new objects (foils), the three word stimuli with six new words, and the three design stimuli with six new designs. The procedure was repeated with injection of the contralateral hemisphere by using a different set of stimuli, with a minimum interval of 30 min between injections. A score for each injection was calculated by assigning one point for each correct response (true positive), and then subtracting 0.5 points for each incorrect response (false positive), for a maximum corrected score of 9.0 and minimum score of -9.0. Random responses would be expected to cluster around 0.0.

[5] 41w Based on retrospective analysis of preoperative evaluation, patients were assigned to one of two groups. Group 1 (79 patients) comprised patients with suspected mTLE. Group 2 (32 patients) included all patients with suspected neocortical or mesial frontal lobe onset epilepsy (mFLE).

[6] 70w Group 1: patients in whom the epileptogenic region localized to mesial temporal lobe Localization of seizure onset was determined independent of the IAP by using the following noninvasive protocol modified from Sperling et al. (21). Those patients not meeting the criteria (one major electrophysiologic and one major imaging concordant OY ictal EEG localization with imaging not discordant) underwent invasive electrophysiologic evaluation with subdural andlor depth electrode monitoring to determine localization.

[7] 73w 1. Major electrophysiologic criteria: (a) Ictal onset demonstrated by phase reversal at sphenoidal or anterior temporal leads within 30 s of behavioral onset; and (b) significant interictal lateralized abnormalities (state-independent frequent theta or delta slowing, spike and slow wave, or sharp and slow wave discharges). 2. Major imaging criteria: (a) MRI structural lesion or mesial temporal sclerosis; and (b) if MRI normal, PET or ictal SPECT that is not discordant with electrophysiologic localization.

[8] 55w Cases were then reevaluated by using the memory scores from the IAP. These data were considered discordant if there was a >2-point difference between left and right injection memory scores, with the lower score after injection of the carotid artery ipsilateral to the presumed seizure focus. Ultimate localization was determined by outcome after resective surgery.

[1] 140w The Wada test, or intracarotid amobarbital procedure (IAP), is used in the assessment of patients with medically intractable epilepsy before epilepsy surgery (1). Originally designed to assess language lateralization, it was later modified to include memory testing (2,3). Although no standardized testing protocol has come into wide use, certain features are a part of most protocols. Goals include identifying lateralized language dominance and pathologically lateralized memory function. This information is used to assess the safety of resective surgery by identifying eloquent language cortex and confirming the integrity of contralateral memory function before resection of mesial temporal lobe structures. It Accepted October 8, 1999. Address correspondence and reprint requests to Dr. D. C. Spencer at OHSU Epilepsy Center, 3181 Sam Jackson Park Rd., CDW-3, Portland, OR 97201, U.S.A. E-mail: spencerd@ohsu.edu also provides additional data to confirm localization of the epileptogenic region.

[2] 87w With recent advances in anatomic and functional neuroimaging, accumulated experience with the presurgical evaluation, and the current cost-conscious medical environment, the need to perform the IAP has been questioned. Previous studies have addressed whether the IAP independently predicts mesial temporal sclerosis [by using magnetic resonance imaging (MRI) or neuropathology as the "gold standard"], localizes the epileptogenic focus in temporal lobe epilepsy (TLE), or predicts postsurgical outcome (4-10). Few studies have addressed the role of the IAP in epilepsy originating outside the mesial temporal lobes (1 1-1 3).

[3] 40w This study examines the usefulness of the IAP in presurgical decision making in a consecutive series of patients who underwent cortical resective surgery for medically intractable, localization-related epilepsy (temporal and non-temporal lobe epilepsy) between 1991 and 1996 at this institution.

[4] 34w Noninvasive evaluation suggested seizures of neocortical or mesial frontal lobe onset in this group of patients. Noninvasive determination of the epileptogenic zone (to guide intracranial electrode placement) was made by using the following criteria:

[5] 67w 1. Electrophysiologic: (a) ictal onset localized to electrodes other than SP1/SP2, T1/T2, T3/T4, or F7/F8; and (b) frequent state-independent theta or delta range slowing or epileptogenic discharges such as spike and slow wave or sharp and slow wave discharges localized to electrodes other than SP1/SP2, T1/T2, T3/T4, or F7/F8. 2. Imaging: (a) MRT structural lesion; and (b) PET or SPECT that is not discordant with electrophysiologic localization.

[6] 74w Cases were then reexamined by using the memory scores from the IAP. A memory deficit on IAP was interpreted as suggesting possible mesial temporal pathology, even in patients whose epileptogenic region was not otherwise believed to be in the mesial temporal lobe. A significant IAP memory deficit was arbitrarily defined as (a) a >2-point difference in memory scores between left and right carotid injection; and (b) Memory scores of <6 after each carotid injection.

[7] 10w Intracranial electrodes and/or outcome after resective surgery determined ultimate localization.