Depth electrode investigations in patients with bitemporal epileptiform abnormalities

ORIGINAL ARTICLES

Depth Electrode Investigations in Patients with Bitemporal Epilepthorm Abnormahties

Norman So, MD, Pierre Gloor, MD, PhD, L. Felipe Quesney, MD, PhD, Marilyn Jones-Gotman, PhD, Andre Olivier, MD, PhD, and Frederick Andermann, MD

Fifty-seven patients showing bitemporal independent epileptiform abnormalities on extracranial electroencepha- lograms (EEGs) in whom the epileptogenic zone could not be localized or lateralized by extracranial EEG and other noninvasive tests were investigated with stereotactic depth electrode recordings. In a majority of 44 patients (77%), seizures originated exclusively or with a strong predominance in one temporal lobe only. Of the remaining 13 patients (23%), 8 had seizures originating independently in either temporal lobe without significant lateralized predominance, and 5 had multiple seizure patterns, which were often diffuse. The patterns of seizure onset as recorded by depth electrodes tended to vary even in the same patient. Electrical stimulation studies and the determination of afterdischarge thresholds were of limited utility for lateralization of seizure onset.

So N, Gloor P, Quesney LF, Jones-Gotman M, Olivier A, Andermann F. Depth electrode investigations in patients with bitemporal epileptiform abnormalities.

Ann Neurol 1989;25:423-431

Bilateral independent interictal epileptiform abnormalities involving both temporal regions in extracranial electroencephalography (EEG) studies are found in 20 to 35% of patients with temporal lobe epilepsy 11-41. This often makes it difficult to lateralize the epileptogenic zone responsible for a patient’s seizures based on the results of extracranial EEG and other noninvasive studies. Frequently such inconclusive findings in a patient evaluated for surgical treatment lead to a decision not to operate.

Intracranial depth electrode EEG investigation of- fers the possibility of demonstrating that seizures arise from only one temporal lobe in some of these patients and thus helps to identify appropriate candidates for surgical treatment. Earlier studies from our institution on the use of ster?otactic depth electrodes for the investigation of pat ents with bitemporal epileptiform abnormalities sho7 red encouraging results in this re- gard 15, 61. We now report on our complete series of 57 consecutive patients investigated for this problem between 1972 and 1986.

Methods The study group consisted of 57 patients investigated with bilateral stereotactically implanted depth electrodes who suf- fered from medically intractable seizures of presumed temporal lobe origin, and who showed bilateral independent epileptiform discharges over the temporal regions as the major interictal epileptiform abnormality in extracranial EEG

studies. Stereotactic depth electrode investigation was under- taken because of a lack of consistent agreement in the lateralization and occasionally the precise temporal localization of the epileptogenic zone by extracranial interictal and ictal EEG findings, clinical assessment, imaging studies, and neuropsychological evaluation. Patients with nonlateralized bitemporal epileptiform abnormalities in the extracranial EEG represent approximately 70% of all patients investigated by intracranial EEG recordings at our institution. Pa- tients with extratemporal foci or multifocal abnormalities were excluded from this report.

Stereotactic Depth Electrode Investigations The technique of stereotactic depth electrode implantation used at the Montreal Neurological Institute has been described previously 177. Electrodes were made of semiflexible tresses of stainless-steel wires, with 9 contacts located 5 mm apart. Each contact formed a wire loop of 0.52 mm diameter and 0.1 mm thickness. For the temporal lobes, 2 or usually 3 pairs of electrodes were inserted symmetrically by an ortho- gonal approach. They penetrated the temporal lobe horizontally through the second temporal convolution, and their tips reached the amygdala, the anterior hippocampus, and in some patients the midportion of the hippocampus and parahippocampal gyms (Fig 1). It was therefore possible to record the intracranial EEG from the temporal limbic structures as well as from surface and deep sulcal temporal neocortex. In 39 of the 57 patients (68%), additional extratemporal electrodes were implanted because significant par- ticipation of extratemporal structures could not be entirely excluded. Thus in 38 patients, one or more pairs of elec-

From the Montreal Neurological Institute, Department of Neurol- ogy and Neurosurgery, McGill University, Montreal, Quebec, Accepted for publication Oct 14, 1988. Canada.

Received for publication Jul 11, 1988, and in revised form Oct 7.

Address correspondence to Dr Gloor, Montreal Neurological Insti- tute, 3801 University St, Montreal, Quebec H3A 2B4, Canada.

from analysis, because it was often difficult to separate these from frequently recurring interictal discharges. Seizures pre- cipitated by electrical stimulation were not included in the final analysis and chemical activation of seizures was not used.

SDEEGs were analyzed visually by experienced electroen- cephalographers (P.G. or L.F.Q., and in a few patients by Dr Rachel Ochs). Bitemporal independent interictal spiking in SDEEGs was seen in all patients and was usually abundant. Its relative lateralization was, however, highly variable, changing with the sleep-wake cycle and after seizures. This made it unsuitable for determination of the principal epileptogenic zone($. The latter was thus defined on the basis of the site or sites of seizure onset, which was determihed for each clinical attack. SDEEG-recorded seizure onsets were classified as:

Fig I . Commonly used electrode arrangement (only left side illustrated; electrodes also symmetrically inserted on the right side). Electrodes are directed respectively at the lt$t amygdala (LA), lt$t anterior hippocampus (LB), left midhippocampuslparahippocam- pal gyrus (LC), ldt superior mesial frontal cortex (LFM), and left orbital frontal cortex (LFO). (From Gloor P et al {lo).)

trodes were symmetrically inserted horizontally into the frontal lobes, usually directed at the orbitofrontal, anterior cingulate, and supplementary motor regions. One patient had additional electrodes implanted unilaterally into the pos- terior temporal and occipital regions because extracranial EEGs had revealed epileptiform abnormalities over those areas.

The stereotactic depth EEG (SDEEG) was recorded directly or by cable telemetry on 16 or occasionally on 32 channels together with video monitoring almost continu- ously throughout the 24 hours of each day, usually for sev- eral weeks. Montage selection always included channels recording from temporal limbic and neocortical strucrures bilaterally. No simultaneous extracranial EEG was recorded in order to minimize the risk of infection. Anticonvulsant medications were usually partially or completely withdrawn in the course of SDEEG recording. This has been shown not to result in any significant false localization or lateralization of seizure onset {8, 91. Only spontaneous seizures with clinical symptoms or signs, the initial electrographic changes of which were recorded and not made uninterpretable by ar- tifact, were studied. For this purpose, auras accompanied by ictal electrographic changes were rated as seizures. Sustained rhythmic discharges of various kinds without clinical accom- paniments labeled as “electrographic seizures” were excluded

1.

2.

3.

4.

5.

Focal temporal when the seizure discharge started in one discrete anatomical area within the temporal lobe, for example, the amygdala Regional temporal when the ictal discharge started simultaneously in 2 or more adjacent anatomical areas within the temporal lobe, for example, limbic involvement of both the amygdala and the hippocampus or simultaneous limbic and neocortical involvement Extratemporal for those seizures originating in an area out- side of the temporal lobe Widespread unilateral when ictal electrographic onset involved more than one lobe in one hemisphere, for example, frontotemporal onset Bilateral simultaneous when there was simultaneous electrographic onset in the two hemispheres, either in homologous regions or diffusely

Electrical Stimulation Studies Electrical stimulation through the depth electrode contacts was performed in 46 patients as described previously [lo}. Results of electrical stimulation of each patient were re- viewed to determine the area with the lowest threshold for afterdischarges (ADS) and the ability of stimulation to repro- duce the patient’s habitual aura(s) and seizure(s). The lowest current intensity required for eliciting an electrical AD on stimulating the hippocampal regions (hippocampal AD threshold) was compared for the two sides. Similarly the lowest current intensity for eliciting electrical ADS in any of the temporal limbic structures (limbic AD threshold), namely the amygdala, anterior hippocampus, and midhip- pocampal and parahippocampal regions on one side, was compared with that on the other. Responses resembling the patient’s habitual warning(s) were rated as auras, whether or not they were accompanied by ADS. ADS accompanied by altered responsiveness, impaired memory, automatisms, or convulsive phenomena were rated separately as electrically induced clinical seizures.

Extracranial EEG Studies EEGs using the 10-20 electrode system were recorded on 16 channels directly or by cable telemetry. Flexible, silver-wire sphenoidal electrodes suitable for long-term use were inserted in all cases. Prolonged recordings were performed in

424 Annals of Neurology Vol 25 No 5 May 1989

wakefulness and in sleep. In more recent years, intensive monitoring by 16-channel cable telemetry and video recording, incorporating computerized automatic spike and seizure detection programs, has been routinely employed 11 1). A ratio of lateralization was established for bitemporal independent interictal epileptiform abnormalities. This was based on the number of recordings, obtained serially over weeks to years, showing a lateralized predominance of interictal epileptiform discharges as determined by visual analysis. Within each recording, the frequency ratio of discharges on the two sides was usually less than 4 : 1. The presence of independent extratemporal epileptiform discharges and of diffuse or generalized epileptiform discharges was also noted. A ratio of lateralization was similarly obtained for nonepileptiform abnormalities, when these were localized or lateralized as in the case of slow-wave activity. Seizures recorded by extracranial EEG were classified as showing consistent or conflicting lateralization, or as showing bilateral, diffuse, or uninterpretable onset.

Clinical, Imaging, and Neuropsychological Findings Etiological factors were determined from case histories, pathology reports of surgical specimens, and sometimes by questionnaire and telephone reports. The clinical seizure symptoms that were known before SDEEG monitoring were not used as lateralizing evidence because considerable con- troversy still surrounds the lateralizing significance of certain clinical ictal phenomena in temporal lobe seizures. Signs of cerebral dysfunction found on neurological examination were used as lateralizing evidence suggesting structural cerebral pathology. Unilateral thickening of the skull vault, middle fossa asymmetry or calcified lesions on skull x-rays, ventricular asymmetry and dilatation on pneumoencephalog- raphy, and focal lesions or focal atrophic changes on com- puted tomographic (CT) scans were examples of abnormalities that provided lateralizing information. Mild ventricular asymmetry on CT scan without other accompany- ing evidence of cerebral atrophy was not considered definitely abnormal. To date too few magnetic resonance studies have been performed in this group of patients for meaningful analysis. Neuropsychological evaluation and in- tracarotid sodium amobarbital (Amytal) testing followed established protocols 112, 131. The results of neuropsychological assessment were used to determine the localization and lateralization of preoperative cerebral dysfunction. Memory impairment after amobarbital injection was taken as evidence for contralateral mesial temporal lobe dysfunction.

The chi square test (with correction for continuity when appropriate) was used for the statistical analysis of discrete variables and the Student’s t test was employed for continu- ous variables.

Results Of the 57 patients in the study, 29 were men and 28 were women. Their ages at the time of SDEEG studies ranged from 14 to 50 years (mean, 28.9). The duration of SDEEG recording ranged from 8 to 30 days (mean, 17.5). The number of spontaneous clinical seizures (including auras) recorded by SDEEG in each patient ranged from 4 to 115 (mean, 21.2). The large number

(n = 56)

d 50 55 60 65 70 75 80 85 90 95 100

Percent Predominance

Fig 2. Percent predominance is the percentage ratio of the number of seizures with ictal onset in the most active epileptogenic zone (temporal, extratemporal, or widespread unilateral) divided by the total number of spontaneous seizures recorded by stereotactic depth electroencephalography in the patient. One patient was excluded (see text).

in some patients was accounted for by the fact that all auras accompanied by detectable ictal discharges in the SDEEG were rated as seizures.

Complications arising from stereotactic depth electrode insertions were encountered in 3 patients (5%). Two patients developed brain abscesses. This occurred early during the period of implantation in 1, and the infection responded to antibiotic therapy. In the other patient, a brain abscess that required surgical drainage developed 6 years after electrode removal in the temporal lobe, where an electrode fragment had remained behind. Both patients recovered with appropriate treatment. One patient, in a postictal confusional state, pulled out some electrode strands but experienced no clinical deficits. No intracranial hemorrhage or death occurred.

Spontaneous Seizures Recorded by SDEEG For each patient the predominance of seizures arising from the most active epileptogenic zone was expressed as a percentage of all of his or her recorded spontaneous seizures. The frequency distribution of predominance is illustrated in Figure 2. (One patient was excluded from this figure because her most frequent seizure type had a diffuse generalized onset, and she was placed in Group D [see the following paragraph}.) Based on the localization, lateralization, and predominance of the epileptogenic zones as defined by SDEEG spontaneous seizure onsets, patients were divided into 4 groups.

Group A (unilateral temporal) included 25 patients (44%) in whom all seizures originated exclusively in

So et al: Bitemporal Epileptiform Abnormalities I: SDEEG 425

Table 1 . Percentage Distribution of Depth Ictal Onset Patterns

Regional Temporal ~ Total

Group Am Hipp Neo Limbic + Neo Neo temporal Unilateral Bilateral (no.) Focal Temporal Limbic Extra- Widespread Seizures

A: Unilateral 7 50 1 39 3 0 0 0 0 354 B: Unilateral predominance 8 17 3 22 43 1 1 1 5 63 5 C: Bitemporal 5 19 1 65 7 0 0 1 2 134 D: Multiple 0 1 0 10 17 1 25 33 13 83

Am = amygdala; hipp = hippocampus; neo = neocortex.

one temporal lobe. Group B (unilateral temporal predominance) was composed of 19 patients (33%) in whom 80% or more of all seizures originated in one temporal lobe. Occasional seizures arose from the contralateral temporal lobe in 12 patients. Infrequent seizures of extratemporal onset were found in 2 patients (arising from the frontal and occipital lobes, respectively). Three patients had occasional seizures of widespread unilateral frontotemporal onset, and 8 had infrequent seizures of bilateral simultaneous onset. This group included 2 patients who had fewer than 80% of their seizures arising from one temporal lobe, but all of their remaining seizures showed bitemporal simultaneous onset with a strong asymmetrical predominance on the side from which their seizures with a unilateral temporal onset arose; no seizures arose independently from the contralateral temporal lobe. Group C (bitemporal independent without significant lateralized predominance) comprised 8 patients (14%) in whom seizures originated independently in each temporal lobe but failed to attain 80% predominance on either side. Infrequent seizures of widespread unilateral fron- roremporal onset were recorded in 1 patient and of bilateral simultaneous onset in another. Groap D (multiple seizure patterns without an exclusively temporal origin) was composed of 5 patients (9%). Although these patients all showed some seizures with a temporal onset, others had extratemporal, widespread unilateral, or bilateral simultaneous onset, and no one pattern accounted for 80% or more of the seizures recorded in the patient.

As many as 44 patients (77%) belonged to Groups A and B and had seizures that originated exclusively or with a strong predominance in one temporal lobe. The largest group (Group A), numbering 25 patients, showed a strictly unilateral temporal seizure onset. The smaller number of patients in Groups C and D tended to cluster on the left of the distribution curve, close to the 50% mark (see Fig 2).

Thirty-nine of 5 7 patients (68%) had extratemporal electrodes implanted, usually into the frontal lobes. Extratemporal electrodes were employed in 68% of Group A, 58% of Group B, and 75% of Group C patients (x2 = 0.87, p = 0.65). There is therefore no

significant bias in any of these groups to have seizures erroneously locahzed to the temporal lobe from lack of sampling elsewhere. In Group D, extratemporal electrodes were employed in all cases, in keeping with the definition of this group. Even with the common prac- tice of frontal electrode insertion, only 1 patient in Group D had a signlficant number of his recorded seizures (51%) arising from the frontal lobe.

In a majority of 48 patients (84%), the precise pattern of ictal electrographic onset showed some variability, even when seizures originated exclusively in one temporal lobe. Most commonly (41 patients, 72%), a mixture of focal and regional patterns of seizure onset in the temporal lobe was observed. Thirteen patients (23%) each had seizures of focal onset arising separately from the amygdala or the hippocampus, and other seizures of regional onset from the temporal limbic structures, sometimes simultaneously involving the temporal neocortex. Stereotyped ictal onset patterns were only seen in 9 patients (16%), who were all in Group A, and consisted of focal hippocampal onsets in 6 and regional temporal limbic onsets involving the amygdala and hippocampus simultaneously in 3. The distribution of SDEEG ictal onset patterns within each group is shown in Table 1. Focal temporal onsets were more frequent in Group A (58%) than in Group B (28%) or Group C (25%). By comparison, regional temporal onsets were more frequent in Group B (66%) and Group C (72%) than in Group A (42%) (x2 = 81.90, p < 0.001). Focal temporal onsets were seen more frequently in the hippocampus than in the amygdala or the temporal neocortex, whereas regional temporal onsets most commonly involved the temporal limbic structures (amygdala and hippocampus) simultaneously. Seizures with a temporal neocortical onset were uncommon. They occurred in 10 patients but accounted for no more than 3% of recorded seizures in any SDEEG group.

Independent extratemporal onsets and widespread unilateral onsets involving more than one lobe were mainly seen in Group D patients, with only rare instances occurring in Groups B and C. Bilateral simultaneous onsets occurred in 12 patients (21%),), 8 in Group B, 1 in Group C, and 3 in Group D. In patients


Table 2. Cowelation of Tests with Stereotactic Depth Electroencephalography (SDEEG) Group

Lateralized Concordant Lateralization" (% each group lateralized) (% each group undergoing test)

A and B SDEEG Group A B C D Total A B

Extracranial EEG interictal epileptiform (n = 57)

Extracranial EEG nonepileptiform (n = 53)

Extracranial EEG ictal (n = 5 5 ) Asymmetrical hippocampal

AD threshold (n = 39) Asymmetrical limbic AD

threshold (n = 43) Abnormal neurological

signs (n = 56) Abnormal imaging (n = 56) Psychological dysfunction

Amobarbital memory dys- (n = 57)

function (n = 32)

13 (52) 11 (58) 3 (38) 2 (40) ~~

29 (51) ~ ~~

15 (63)

7 (30) 17 (32) 6 (86) 8 (57)

7 (29) 16 (83)

6 (33) 3 (38) 2 (40) 7 (70) 4 (80) 4 (80)

18 (33) 31 (79)

3 (43) 12 (75)b

19 (86) 7 (64) 4 (80) 3 (60) 13 (68)b 2 (28)b 15 (58)b 33 (77)

4 (16) 2 (11) l ( 1 3 ) 1 ( 2 0 ) 8 (14) 4 (100) 2 (100) 6 (100)

12 (48) 15 (60)

8 (44) 3 (38) 1 ( 2 0 ) 16 (84) 5 (63) 5 (100)

24 (43) 41 (72)

9 (75) 9 (60)

7 (88) 10 (63)

16 (80) 19 (61)

8 (57) 5 (42) 0 (0) l(50) 14 (44) 5 (63) 7 (54)

"Concordance with side of exclusive or predominant SDEEG seizure onset. bElevated AD ipsilateral to side of exclusive or predominant SDEEG seizure onset AD = afterdischarge.

Table 3 . Clinical Responses Obtained During Electrical Stimulation ~~ ~~

Habitual Auras Clinical Seizures

Lateralitation Group A Group B Group C Group D Group A Group B Group C Group D

Concordant 8 2 Discordant 2 0 Bilateral 6 7 2 1 1 2 1 1

1% 3" 4 2 4 3

3% 2"

*On stimulation of one temporal lobe only, but concordance could not be determined in Group C and D patients.

with such bilateral simultaneous onsets, other seizures of focal temporal or regional temporal onset were always recorded as the more frequent seizure pattern. In the 12 Group B and 8 Group C patients who had seizures recorded independently from each temporal lobe, focal and regional temporal onsets could arise from either side. There was no tendency for seizures to originate in homologous structures in these patients or for one electrographic pattern of seizure onset to occur on one side and a different pattern on the other.

Group B patients. Asymmetrical thresholds also occurred in Group C and D patients. Correlation of hippocampal and limbic AD threshold asymmetry with SDEEG ictal onset groups is presented in Table 2.

The habitual aura(s) was reproduced in 33 patients (72%) on electrical stimulation, usually of the temporal limbic structures. A variety of other subjective sensations, which were, however, not recognized as habitual auras, were elicited in 20 patients. Habitual auras occurred exclusively on stimulation of one temporal lobe in 17 patients (37%) and on stimulation of either temporal lobe in 16 (35%). When the aura occurred on stimulation of only one temporal lobe, it was concordant with the side of SDEEG ictal onset in 8 of 10 Group A patients (80%) and discordant in 2 (20%). Habitual auras on stimulation of only one temporal lobe were also seen in Group C and D patients who did not have seizures arising predominantly from one side (Table 3). In contrast, habitual auras were also obtained on stimulation of either temporal lobe in all patient groups, including 6 of 16 patients in Group A

Electrical Stimulation Studies Electrical Stimulation was performed in 46 patients. Studies were adequate for the determination of hippocampal AD threshold in 39 patients and of limbic AD threshold in 43. Hippocampal AD thresholds were asymmetrical in 31 (79%) and symmetrical in 8 (2 1 %). When asymmetrical, the hippocampal AD threshold was found elevated ipsilateral to the side of exclusive or predominant SDEEG ictal onset in 12 of 16 (75%) Group A patients, but in only 2 of 7 (29%)


(38%), who by definition had all SDEEG recorded seizures arising from one temporal lobe only.

Electrical stimulation elicited seizures in 22 patients (48%). In 19 patients seizures were induced by stimulation of the limbic structures: the amygdala in 9, the hippocampus in 6, and either of the two structures in 4. In 2 patients seizures followed stimulation of either limbic or temporal neocortical structures separately. One patient had a seizure elicited only on temporal neocortical stimulation. Seizures were produced by stimulation of one temporal lobe in 17 patients (37%) and by stimulation of either temporal lobe in 5 ( 1 1 %) (see Table 3). In Group A, electrical stimulation induced seizures from the side of exclusive SDEEG ictal onset in 4 patients, from the contralateral side in 4, and from either side in 1. Of the 5 instances in which seizures were elicited by stimulation of the side contralateral to that of exclusive seizure onset in Group A, 2 patients recognized that these seizures were different from their habitual attacks, and in the remaining 3 instances, electrical discharge spread to the other temporal lobe. In Group B, seizures were electrically induced from the side ipsilateral to that of predominant SDEEG ictal onset in 2 patients, from the contralateral side in 3, and from either side in 2. All electrically induced seizures in Groups B, C, and D except for 1 were recognized as habitual seizures either by the patient or by the observing physician, regardless of the side of stimulation. The 1 exception occurred in a Group D patient.

Results of Noninvasive Studies and Correlation with SDEEG Groups CLINICAL FEATURES. The mean age of clinical seizure onset was lower in Group A and B patients (10.6 years) than in Groups C and D (15.4 years), but the difference did not reach statistical significance. The mean duration of the seizure disorder and the propor- tion of patients with or without a major etiological factor did not differ significantly between Groups A and B and Groups C and D. A major etiological factor was found in 25 patients (44%) whereas no definite etiological factor could be established in 32. Major etiological factors included a history of one or more early convulsions before age 3 (frequently associated with fever), severe head trauma, central nervous system infection, severe perinatal anoxia, and foreign tissue lesion. A history of early convulsion(s) before age 3 (usually febrile) in 18 patients was the single most common major etiological factor. Its incidence did not differ significantly among the groups. By contrast it is notable that the 6 patients who were eventually found to have a foreign tissue lesion either showed an exclusive (2 in Group A) or predominant (4 in Group B) seizure onset in the temporal lobe that harbored the lesion.

Abnormal laterahzed neurological signs such as hemi- paresis, hemisensory impairment, hemiatrophy, and unilateral impairment of coordinated fine movements were present in 8 patients (14%). Each of these patients also had concordant lateralized abnormalities as seen on imaging studies.

EXTRACRANLAL EEG. On average, 15 extracranial EEG studies (range, 3-40) were performed in each patient before electrode implantation. Extracranial interictal epileptiform EEG abnormalities showing a 4 : 1 (80%) or greater ratio of predominance on one side as previously defined were considered lateralized. This was found in 29 patients (51%) . Forty patients (70%) had extracranial interictal epileptiform EEG abnormalities confined to the temporal regions. Thirteen (23 %) had occasional bilaterally synchronous generalized spike and wave discharges, and 4 (7%) had independent extratemporal foci in addition to the predominant bitemporal abnormalities (temporal-plus). Using the same criteria, nonepileptiform abnormalities were lateralized in only 32% of patients.

Seizures were recorded by extracranial EEG in all except 2 patients (mean, 6.22; range, 0-27), with 3 or more seizures recorded in 35 patients. Ictal lateralization was possible in only 18 patients (33%). Seizure onsets arising independently from one or the other side resulted in conflicting lateralization in 20 patients (36%). Nonlateralized bilateral or diffuse onsets occurred in 12 patients (22%) and uninterpretable recordings in 5 (9%).

IMAGING STUDIES. Imaging studies showed lateralized findings in 24 patients (43%), bilateral abnormalities in 6 ( I l s ) , and normal results in 26 (46%). The data for one patient were lost. The abnormalities seen were usually those of a longstanding atrophic pro- cess. Foreign tissue lesions were demonstrated radio- graphically in only 2 of the 6 patients who harbored them.

PSYCHOLOGICAL EVALUATION. Psychological tests showed evidence for unilateral temporal dysfunction in 8 patients (14%) and evidence for bitemporal dysfunction with predominance on one side in 33 (58%). Thus lateralized temporal dysfunction was found in 41 patients (72%), bitemporal dysfunction without lateralization in 13 (23%), and normal tests in 3 (5%). Bilat- eral amobarbital tests valid for the assessment of memory function were completed in 32 patients, while no tests were performed on 6. Thirteen patients had invalid tests on one side and 6 had incomplete unilateral testing only. Of those who completed bilateral amobarbital tests for memory, mesial temporal lobe dysfunction was lateralized in 14 (44%) and bilateral


dysfunction was present in 6 patients (19%). Twelve patients (38%) had normal tests on both sides.

The presence or absence of lateralized abnormalities as seen on each of the noninvasive tests (see Table 2 ) was not significantly correlated with the subsequent finding of exclusive or predominant SDEEG ictal onset (Groups A and B) in one temporal lobe (x2 analysis). Within SDEEG Groups A and B, concordance with the side of exclusive or predominant seizure onset was highest for abnormal neurological signs (100%) and abnormal imaging findings (80%) when these could be lateralized. However, lateralized abnormalities were also found in patients who were later shown not to have a strong predominance for seizures to originate in one temporal lobe (Groups C and D). The rate of concordant lateralization was poor for other tests (see Table 2). Unexpectedly, the concordance of extracranial interictal epileptiform and nonepileptiform EEG abnormalities was considerably higher for Group B than for Group A patients. The topographical distribution of extracranial interictal epileptiform EEG abnormalities was not significantly correlated with the results of SDEEG recordings. Thirty-two of 40 patients (80%) with temporal-only discharges in extracranial EEGs were classified in Groups A or B, as were 12 of 17 patients (70%) who had temporal-plus discharge (x2 = 0.19, p = 0.66).

An attempt was made to see if combinations of variables based on the results of noninvasive tests could accurately identify patients in Groups A or B and, furthermore, correctly lateralize the side of exclusive or predominant SDEEG ictal onset. This goal was achieved when there was agreement on the side of lateralization by extracranial EEG interictal epileptiform abnormality, imaging abnormality, and amobarbital test memory dysfunction or abnormal neurological signs. However, it allowed us to identify only 4 of the 44 patients who were eventually placed in Groups A and B.

Discussion Our study shows that stereotactic depth electrode investigation was able to reveal that seizures originated exclusively or with a strong predominance in one temporal lobe in 77% of patients with bitemporal independent epileptiform abnormalities in extracranial EEGs. It must be emphasized that our patients represent a highly selected group in whom, even with the help of ancillary clinical and laboratory data, a reliable diagnosis of the side and sometimes site of seizure origin could not be made before depth electrodes were inserted. The conclusions of this study therefore can- not be extrapolated to patients with temporal lobe epilepsy as a whole.

In the largest single group of 25 patients (44%), all of the seizures arose exclusively from one temporal

lobe. Another 33% of the patients showed a strong predominance for their seizures to originate in one temporal lobe. Only 14% had seizures arising independently from each temporal lobe without significant lateralized predominance on one side. A few remaining patients (9%) had multiple seizure patterns which were often diffuse. An 80% cutoff was selected to separate patients with strong unilateral temporal predominance from those without. This selection was mainly based on the bimodal frequency distribution of the predominance of seizure onset (see Fig 2), but also took into account the results of earlier studies on a smaller number of patients 15, 61. The current results confirm the original impression gained in those earlier studies. The utility of SDEEG recording for the investigation of this bitemporal problem had not been previously established, although it was accepted implicitly as one of the main indications for its use 114-161.

Most patients showed some variability in their patterns of SDEEG ictal onset, even when seizures originated exclusively in one temporal lobe. Only 9 patients (16%) demonstrated a stereotyped ictal onset pattern. The observation that seizures arising from the same temporal lobe in the same patient could start independently in the amygdala, hippocampus, or temporal limbic structures regionally suggests that seizures can arise from different, and at times larger or smaller, areas within a wider epileptogenic zone. The deter- minants for this variability are unknown, however. Whether some of this variability is related to failure to sample from a hidden generator, from which the seizure discharge may secondarily spread along different pathways, is a hypothesis that could not be conclu- sively tested by any presently known method. The weight of circumstantial evidence, however, seems to argue against it. Yet the restricted “tunnel vision” of depth electrode recording must be kept in mind and precise localization of ictal onset to one of the recorded structures should not be assumed too readily 117, 181.

In keeping with an earlier report 1191, SDEEG- recorded regional temporal seizure onsets were more common than focal temporal onsets. The latter were most frequently seen in the hippocampus. This hippocampal predominance may be partly due to a meth- odological bias: Strictly amygdaloid onsets can sometimes be missed because amygdaloid discharges are liable to form “closed fields” that are more likely to escape detection [l8}. On the other hand, evidence exists that the site of seizure onset is correlated with the site of maximal pathological damage, which most commonly seems to involve the hippocampus in temporal lobe epilepsy 1201, although the amygdala has to date not been studied with equal care. Focal temporal onsets were more common in Group A patients, in whom all seizures originated in one temporal lobe, as


compared with Groups B and C patients. In the latter two groups, who all had some independent seizures arising from other sites, regional temporal onsets pre- dominated. The significance of these findings is un- clear. If the pattern of regional temporal onset is a reflection of a more widespread epileptogenic zone, then it may go hand in hand with an increased tendency for independent bitemporal seizures and other seizure patterns, as found in Group B and C patients.

No reliable AD threshold asymmetry was seen on electrical stimulation of homologous mesial temporal lobe structures. Even when care was taken to select only habitual warnings for analysis, electrical stimulation often produced auras from either temporal lobe, as has also been reported by Halgren and associates {21}. When an aura occurred on stimulation of only one side, however, it was more likely to be concordant with the side of exclusive or predominant ictal onset. Clinical seizures occurred with almost equal likelihood on stimulation of either temporal lobe, although seizures elicited from the lobe contralateral to that of spontaneous seizure onset were sometimes recogniz- ably dissimilar from the patient’s habitual attacks. It is therefore doubtful that electrical stimulation studies of AD threshold, and of electrically induced auras and seizures, could be relied on for lateralization of the epileptogenic zone in the investigation of patients with bitemporal seizures. The different results reported by other investigators 122-241 may be related to the fact that all of our patients had evidence for significant bitemporal abnormalities. Patients with well-defined, unilateral temporal abnormalities may account for the sometimes high rates of concordant lateralization reported by others on electrical stimulation studies {22, 241.

The limited sensitivity of noninvasive tests, which have a relatively low rate of concordant lateralization with the results of SDEEG recording, was not unex- pected, since our patients were selected for SDEEG study precisely because all other means had failed to demonstrate consistently the epileptogenic zone responsible for their seizures. Iateralization based on abnormal neurological signs and imaging findings showed higher rates of concordance with the side of exclusive or predominant SDEEG ictal onset as compared with other tests. Even with the benefit of retrospective analysis using multiple variables, accurate identification of patients with seizures arising exclusively or predominantly from one temporal lobe (Groups A and B) and correct lateralization of the side of seizure onset were potentially possible in only 4 of 44 patients, who might thus have been spared from invasive intracranial recording.

Our results should not be taken as an argument against the clinical utility of noninvasive testing in the presurgical evaluation of patients with intractable epi-

lepsy. Reliance on the role of noninvasive tests has to take into account the quality and the clarity of the information obtained, as well as their ability to yield concordant localizing evidence in each individual clinical problem [25, 261.

Our study has not addressed the possible contribu- tion of magnetic resonance imaging and positron emis- sion tomography to the investigation of patients with bitemporal abnormalities because too few patients in this series had received these tests. It has also not addressed the question in those patients with seizures arising independently from either temporal lobe of whether the clinical seizure patterns would be suffi- ciently different to make it possible to predict bilateral independent onsets on clinical grounds. It is our impression that in only a small number of patients were the seizures arising from one temporal lobe manifestly different in their clinical pattern from those arising from the opposite side. These are issues that clearly deserve more detailed analysis.

~~ ~

We are grateful to Dr Rachel Ochs, who interpreted the SDEEGs in some patients, and to Ms Gisele Robillard for work in the prepara- tion of the manuscript.

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Depth electrode investigations in patients with bitemporal epileptiform abnormalities