Mesial temporal versus neocortical temporal lobe seizures: Demonstration of different electroencephalographic spreading patterns by combined use of subdural and intracerebral electrodes

Mesial temporal versus neocortical temporal lobe seizures: Demonstration of different electroencephalographic spreading patterns by combined use of subdural and intracerebral electrodes

I'~IUTTE I'~IE I N RWO E M A RT N H N Mesial Temporal Versus Neocortical Temporal Lobe Seizures: Demonstration of Different Electroencephalograph...

1MB Sizes 0 Downloads 3 Views

I'~IUTTE I'~IE I N

RWO E M

A

RT N

H N

Mesial Temporal Versus Neocortical Temporal Lobe Seizures: Demonstration of Different Electroencephalographic Spreading Patterns by Combined Use of Subdural and Intracerebral Electrodes G. J. F. Brekelmans, W. van Emde Boas, D. N. Velis, 1A. C. van Huffelen, R. M. Chr. Debets, and 2C. W. M. van Veelen

We investigated differences between spatiotemporal intracranial EEG characteristics of temporal lobe seizures with mesiolimbic versus neocortical onset, using both subdural and intracerebral electrodes. In 37 patients we analyzed 128 seizures, assessing time intervals from initial onset of a seizure in either mesial or neocortical temporal (NT) lobe structures to sequential ictal involvement of the contralateral mesiolimbic structures and the ipsi- and contralateral temporal and frontal neocortical areas. We noted significantly more rapid seizure spread from mesiolimbic temporal (MT) structures ipsilateral to contralateral in patients with NT versus MT seizure onset. Time values for total seizure duration and time of spread from ipsilateral limbic to contralateral limbic reliably discriminate between individual seizures of either type. Three different spreading patterns were noted in the MT group and two more were noted in the NT group. Theoretical considerations concerning routes of spread are presented. In neither the MT nor the NT group could a correlation be established between pattern of seizure spread and outcome of surgery. Key Words: Stereo-electroencephalography--Temporal lobe epilepsy--Surgery--Spatiotemporal parameters---Complex partial s e i z u r e s ~ Neocortex.

Received February 23, 1995; accepted April 19, 1995. From the Department of Clinical Neurophysiology, Instituut voor Epilepsiebestrijding "Meer en Bosch"/"De Cruquiushoeve," Heemstede; and 1Departments of Clinical Neurophysiology and 2Neurosurgery, University Hospital Utrecht, The Netherlands. Address correspondence to Dr. G. J. F. Brekelmans at Instituut voor Epilepsiebestrijding "Meer en Bosch"/"De Cruquiushoeve," Achterweg 5, 2103 S.W. Heemstede, The Netherlands.

J. Epilepsy 1995;8:309-320 © 1995 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010

Anterior t e m p o r a l l o b e c t o m y (ATL) is the m o s t f r e q u e n t l y p e r f o r m e d a n d m o s t successful t y p e of s u r g e r y for intractable partial seizures (1). For a n o p t i m a l surgical result, precise localization of a single z o n e of ictal o n s e t in a n accessible area of either t e m p o r a l lobe is m a n d a t o r y . M o r e o v e r , a distinction s h o u l d be m a d e b e t w e e n seizures w i t h either mesiolimbic- or lateral neocortical t e m p o r a l onset, b e c a u s e these m a y require different surgical p r o -

0896-6974/951510.00 SSDI 0896-6974(95)00050-X

G. I. F. BREKELMANS ET AL.

cedures and because of possible differences in postoperative morbidity and eventual clinical outcome (2-6). In 10-50% of candidates for epilepsy surgery, noninvasive presurgical evaluation will remain inconclusive regarding the exact localization and/or delineation of the area of seizure onset, and intracranial seizure monitoring will have to be performed (7). However, invasive studies with intracerebral and/or subdural electrodes, although more sensitive than noninvasive studies, are necessarily limited with respect to the number of electrodes and therefore may not sample all potentially involved regions. The identification of additional parameters, other than strict localization of electroencephalographic (EEG) seizure onset, might help overcome this limitation. Different patterns of seizure spread have been reported for limbic and lateral neocortical temporal seizures and have been used to draw further inferences regarding routes of seizure propagation (815). Further characterization of these patterns of seizure spread may provide better insight into the area of primary seizure onset as well as into the interconnections between the different brain regions and the physiological processes involved. The reliability of these different spatiotemporal EEG patterns as possible diagnostic criteria has not yet been studied, however, possibly because most of the available data derive from studies with relatively few electrodes, either intracerebral or subdural alone, resulting in limited coverage of some of the brain regions known to be involved in temporal lobe seizures. Our method, using both subdural and intracerebral electrodes implanted bilaterally in and over the temporal and frontal lobes (5), can overcome this limitation. We wished to assess whether in this way consistent differences between spatiotemporal EEG characteristics of temporal lobe seizures with mesiolimbic temporal (MT) onset versus those with neocortical temporal (NT) onset can be identified and, if so, whether these differences can be used for a reliable clinical differentiation between these entities as an alternative method in cases in which the region of seizure onset may have been insufficiently sampled by the available electrodes. Furthermore, we addressed the extent to which these possible different patterns of seizure spread provide information regarding routes of seizure propagation between different brain regions and of the neurophysiological processes involved and, finally, whether specific spreading patterns may require a specific neurosurgical ap310 J EPILEPSY, VOL. 8, NO. 4, 1995

proach and/or have any predictive value with regard to surgical outcome.

Patients and Methods Records of 73 consecutive patients with medically intractable epilepsy, investigated with intracranial seizure monitoring as part of the Dutch Collaborative Epilepsy Surgery Program from January 1982 to December 1993, were reviewed. From this series a group of 37 patients with welldocumented unilateral temporal lobe seizure onset (MT and/or NT) was selected for further analysis. The remaining 36 patients had extratemporal or nonlocalized seizure onsets (n = 26), bilateral temporal seizure onset (n = 6), no depth electrodes (n = 3), or auras only (n = 1) and were excluded from the study. All patients were investigated according to the protocol described by Van Veelen et al. (5). This included full general medical, neurological, and neuropsychological evaluation; extensive noninvasive EEG studies including long-term EEG/closedcircuit (CC) TV seizure monitoring with scalp and sphenoidal electrodes; neuroimaging studies, including computed tomography (CT), magnetic resonance imaging (MRI), and interictal positron emission tomography (PET) and/or single photon emission CT (SPECT); carotid angiography; and an intracarotid sodium amytal test (WADA test). For subchronic electrocorticography and stereoEEG (SECoG/SEEG), multiple subdural strips and/ or bundles and depth electrodes (Brain Electronics BV, De Bilt, The Netherlands) were introduced in a combined procedure bilaterally over and in the brain. Subdural strips (8-12 per patient, median 10) usually cover extensive areas of the frontoorbital, frontolateral, and lateral-temporal as well as subtemporal neocortical regions of both hemispheres. In addition, a limited number (2-4, median 3) of intracerebral multielectrode bundles was implanted stereotaxically in the anterior part of both hippocampi and in one or both amygdalas according to the coordinates described in the atlas of Delmas and Pertuiset (16). Both subdural and depth electrodes were introduced through the same symmetrical frontal trephine holes (5). Interictal and ictal intracranial EEG (bandpass filter 0.5-70 Hz, common reference montage) was acquired with custom-made 21- to 32-channel cable telemetry systems and continuously recorded on p a p e r (21-channel S i e m e n s Elema or N i h o n

EEG SPREAD OF MT VERSUS NT SEIZURES Kohden polygraph) or on optical disk (Medelec/ Vickers Medical DG32 paperless EEG). Patient behavior was continuously recorded on (S)VHS videotape. The SECoG-SEEG seizure records from the selected 37 patients were reanalyzed. Only complex partial seizures (CPS), either secondarily generalized or not, were assessed; electrographic seizures without clinical correlate were excluded. Clinical features as recorded on video were not analyzed for the present study. All records were rated according to area of seizure onset, defined as: (a) focal, with initial ictal activity on a single or two adjacent electrode points on one subdural bundle (interelectrode distance from center to center 10 mm) or intracerebral bundle (interelectrode distance from center to center 2.5 mm); (b) regional, with initial ictal activity simultaneously on three or four adjacent electrode points on a single bundle or on two or three points on two adjacent bundles; or (c) widespread, with initial ictal activity simultaneously on more than four electrodes, multiple bundles, or on both subdural and depth electrodes. Initial ictal activity was defined as any rhythmic or paroxysmal activity, including low-voltage fast activity, rhythmic alpha-beta or theta activity, repetitive or rhythmic spikes, sharp waves, polyspikes or polyspike waves, clearly distinguishable from interictal activities and evolving into a frank ictal pattern. For our present purpose, we did not consider generalized or localized desynchronization or attenuation of ongoing interictal activity to represent the moment of true seizure onset. Disappearance of the ictal patterns obviously was considered the end of the seizure. For each seizure, the total duration of the EEG seizure activity was established. Spreading patterns were identified by assessment of the time interval from initial onset of a seizure in either MT or NT lobe structures to sequential ictal involvement of other brain regions, notably the contralateral mesiolimbic structures and the ipsi- and contralateral temporal and frontal neocortical areas. Spatiotemporal parameters studied for either type of seizures are shown in Table 1 and Fig. 1. The mean values of the different parameters of each patient were analyzed. Statistical analysis was made with a nonparametric statistical test (Mann-Whitney U test). Intragroup parameters were analyzed for interindividual variations and for their relation to surgical outcome. Parameters of MT seizures were compared with those of NT

Table 1. Spatiotemporal parameters assessed for characterization of seizure spread patterns A: Mesiolimbic seizures (MT group): Time interval between onset of first unequivocal ictal activation of mesiolimbic structures and secondary activation of: Contralateral mesiolimbic structures (DI-DC) Ipsilateral temporal neocortex (DI-NI) Contralateral temporal neocortex (CI-NC) Ipsilateral frontal neocortex (DI-FI) Contralateral frontal neocortex (DI-FC) B: Neocortical temporal seizures (NT group) B1--Time interval between onset of first unequivocal ictal activation of temporal neocortical cortex and secondary activation of: Ipsilateral mesiolimbic structures (NI-DI) Ipsilateral frontal neocortex (NI-FI) Contralateral temporal neocortex (NI-NC) Contralateral frontal neocortex (NI-FC) B2--Time interval between secondary activation of ipsilateral mesiolimbic structures and subsequent involvement of contralateral mesiolimbic structures (DI-DC) D, mesiolimbic; I, ipsilateral; N, temporal neocortex; F, frontal neocortex. seizures to obtain inter- and intraindividual differences in sequential involvement to hypothesize v a r i o u s r o u t e s of s p r e a d . F u r t h e r m o r e , we grouped parameters of all MT seizures together and compared them with those of NT seizures to investigate differences between patients with different patterns of spread, using up to the first four identical seizures per patient to avoid statistical bias caused by patients with a high number of seizures.

Results Of 37 patients with well-documented unilateral temporal seizure onset, 22 (9 men, 13 women; median age 34 years, range 17-50) had consistent focal or regional right (n = 9) or left (n = 13) temporobasal limbic seizure onsets (MT group). In the other 15 patients (9 men, 6 women; median age 33 years, range 19--41, 9 right-sided onset), the seizures originated either in the temporal neocortex (n = 5) or more often in both the NT and temporobasal regions simultaneously (n = 10). For further analysis, these latter groups were considered together as the NT group. In the 22 MT patients, 79 CPS (median 4, range 2-5) were assessed for analysis. In the NT group, 49 CPS (median 4, range 2-4) were analyzed. Results of the comparison of the mean values

J EPILEPSY, VOL. 8, NO. 4, 1995 311

G. J. F. BREKELMANS ET AL.

,I,J Y ]B

G

~

D

2

E Figure 1. Different patterns of spread from the site of seizure onset to the sequentially involved areas of interest. A: Spread from temporal mesiolimbic to contralateraI temporal mesiolimbic and secondary to ipsilateral temporal neocortical. B: Spread from temporal mesiolimbic first to ipsilateral temporal neocortical and then to contralateral temporal mesiolimbic. C: Spread from temporal mesioIimbic first to ipsilateral frontal neocortical and secondary to contralateral temporal mesiolimbic. D: Spread from temporal neocortical to ipsilateral temporal mesiolimbic and secondary to contralateral temporal neocortical or ipsiIateral frontal neocortical. E: Spread from temporal neocortical to ipsilateral frontal neocortex secondary to contralateral temporal or frontal neocortex and tertiary to ipsilateral mesiolimbic. per parameter per patient are shown in Tables 2 and 3. SEEG examples are shown in Figs. 2 and 3. A striking difference was evident for the total average time duration of ictal EEG, which was significantly (p = 0.0001) longer in the MT group [119 s, 95% confidence limits (CL) 118.1-147.7, SD 56.5 s] than in the NT group (mean 83 s, 95% CL 70.995.4, SD 37.6 s). Assessment of the average time involved in seizure spread from the initial ictal zone to each of the other regions of interest (ROI), regardless of the detailed chronology between the latter, showed significant differences for all parameters expect for the time difference between involvement of the 312 J EPILEPSY, VOL. 8, NO. 4, 1995

contralateral mesiolimbic structures after initial onset in either MT or NT (Table 2). The most striking difference was the time lapse between activation of the ipsilateral NT and MT structures after seizure onset in either MT or NT; spread from the limbic region to the neocortex required an average of 34.9 s (SD 17.7 s, 95% CL 27.5-42.2) as compared with 17.3 s (SD 14.6 s, 95% CL 9.9-24.7) for spread from neocortex to the limbic region (p = 0.003). Other spreading times, i.e., ictal involvement of ipsilateral frontal and contralateral frontal and NT structures were significantly longer in the MT group as well (Table 2). Further analysis of average time delays between secondary and tertiary ictal activation between the various ROI after initial seizure spread yielded additional significant differences (Table 3). Ictal activity truly originating in the mesiolimbic structures took significantly longer (p = 0.006) to invade the contralateral mesiolimbic area as compared with ictal activity originating in the temporal neocortex and only secondarily involving the ipsilateral mesiolimbic structures before spreading into the contralateral mesiolimbic area. Likewise, seizure activity originating in the temporal neocortex took significantly longer to spread to either the ipsilateral frontal (p = 0.03) or the contralateral NT (p = 0.02) regions as compared with ictal activity, secondarily involving the ipsilateral temporal neocortex after mesiolimbic seizure onset. Mean intervals, SD, and CL are shown in Table 3. There were no significant differences between the groups for spreading time of ictal activity between tertiary involved temporal and/or frontal neocortical structures on either side. Analysis of seizures in the MT group yielded three distinct patterns of spread of ictal activity. Thirty-four seizures in 12 patients showed initial spread from ipsilateral to contralateral mesiolimbic structures followed by ipsilateral involvement of temporal and frontal neocortex (Table 4, type A seizures). Thirty-four seizures in 13 patients showed ictal activity secondarily involving the ipsilateral temporal neocortex before the contralateral mesiolimbic or ipsilateral frontal structures were activated (Table 4, type B seizures), whereas 11 seizures in 3 patients showed ictal activity invading the frontal ipsilateral neocortex first, subsequently the temporal neocortex, and only then the contralateral mesiolimbic structures (Table 4, type C seizures). Eight patients s h o w e d only type A seizure spread; in 7 other patients, all seizures spread according to type B. In only 1 patient did all seizures

EEG SPREAD OF MT VERSUS NT SEIZURES

•~

i

48 ~

0

0

0

~-~

Z8

~-~

0

~ ~o •~ ~-~ C~

"; ~

~e .~.~

~'~.~ ~5

~ ~

~

..

"~ N

~

~-~ .~ ~

.~

C

~ ~ •.

.~ .o~

~

~.~

~

~ ~ ~ "~ "N

t~

~

.~ ~.~

~u

N~ ,.~

N -~ ~,~

z

.~

E

NN

.~

~ ~

0

~

~

~ ~

~

~

e4

~

~-

~ ~g

_,~

*a

Z

J EPILEPSY, VOL. 8, NO. 4, 1995

313

~.~ ~, _~-~

~ . ~ ~ ~ ~

~ ~ ~ ~

~--~ ~ ~

~ ~

~ ~ ~

~ ~

.~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~

~ ~

~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ . ~ ~ ~ ~ •~

~

~~ '~ ~ ~~ ~~

~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~

~ ~ ~ ~

~ ~

~ ~

~ ~

~ ~ ~

~

~ ~

.

~ ~ ~ ~

~

~

~

~

~ ~

~ ~

~ ~

~

M

~ ~ ~ ~ ~ ~ ~ ~

~

~

~ ~ ' -~ ~ ~-~ ~ ~ ~ ~ ~ ~ ' ~ ~ ~ ~ ~ ~ ~

~

~ ~ .~

~ ~

~ ~ ~

~ ~

~ ~

~ ~ ~ ~

~ ~ ~ ~

~ ~.~

~ ~ ~ ~ ~.~ ~

•~

~

~ ~ ~

~ ~.~ ~

~ ~

~ ~ ~-~ ~ ~ ~ ~

~

~~

~

~ ~ ~ ~ ~.~

l~

~

~

~ ~

~ [~ ~ ~ ~ ~ •~ .~ ~ ~ ~ •~ ~ : ~ •~

~

~

~~ ~ ~ ~

~

~

~ ~

~ ~ ~

~

~ ~~

~ ~

~

I~ E

ill

G. J. F. BREKELMANS ET AL. TIME

05:58:49

I I I

O~muv

"1 s e c .

m

Figure 3. Temporal neocortical seizure onset. Almost synchronous initial ictal activity in the temporal neocortex and mesiolimbic area, with rapid involvement of the contralateral mesiolimbic structures. Seizure duration was brief. Channels 1-8 represent electrode contacts covering the left frontal (FPL/FLL) and temporal neocortex (MTL/ATL). Channels 9 and 10 are left hippocampal contacts (HCL). Channels 6-30 represent electrode contacts covering the right frontal (FPR/FLvR/FLaR) and temporal neocortex (VTR/MTR/ATR). Channels 31 and 32 are right mesial temporal contacts (UNR). Arrows depict the sequential ictal involvement of the different areas. Ipsilateral: Posterior temporal neocortex (arrow 1), mesiolimbic temporal area (arrow 2), midtemporal (arrow 3), anterior temporal (arrow 4), frontal neocortex (arrow 5). Contralateral: Mesiolimbic temporal area (arrow 6), midtemporal neocortex (arrow 7), end of the seizure (arrow 8).

show the type C pattern. The remaining 6 patients showed two different seizure spread patterns. In the NT group, two typical patterns were established. Thirty-nine seizures in 12 patients showed secondary involvement of ipsilateral mesiolimbic structures (Table 4, type D), followed by activation of either the contralateral mesiolimbicstructures (8 patients) or the ipsilateral frontal cortex in the remaining 4 patients, none of w h o m had further ictal involvement of the contralateral mesiolimbic structures. In 10 other seizures in 3 patients, ictal activity invaded the ipsilateral frontal neocortex first (type E), with subsequent activation of the contralateral temporal neocortex and finally the ipsilateral mesiolimbic structures without, in this subgroup of patients, any involvement of the contralateral frontal neocortex (Table 4). No patient in the NT group showed more than one pattern of seizure spread. 316 J EPILEPSY, VOL. 8, NO. 4, 1995

Analysis of the different temporal parameters in the individual groups for all seizures grouped together and data comparison in patients with the three different patterns of spread in the MT group yielded no statistical differences in times of spread to the structures analyzed between any subgroup, except for a statistically shorter time needed for involvement of the ipsilateral frontal neocortex in the subgroup with type C seizures as compared to those with type A (p = 0.01). Comparison of the two subgroups in the NT patients yielded a significant difference between the time needed for involvement of the ipsilateral frontal neocortex: the subgroup with type E seizures had shorter delays (p < 0.002). Results of Surgery and Follow-up

All patients in the MT group had a tailored or partial anterior temporal resection (7) (14 right and

EEG SPREAD OF MT VERSUS NT SEIZURES Table 4.

Patterns of chronologic ictal involvement: Seizure spread from ictal onset zone to other areas of interest, in chronological order

Seizures/subgroup Temporal mesiolimbic A (34 seizures, 12 patients)

First Contralateral mesiolimbic

B (34 seizures, 13 patients)

Ipsilateral temporal neocortical

C (11 seizures, 3 patients)

Ipsilateral frontal neocortical

Temporal neocortical D (39 seizures, 12 patients)

E (10 seizures, 3 patients)

Ipsilateral mesiolimbic

Ipsilateral frontal neocortical

8 left). Mean follow-up was 4 years (minimum 1,

maximum 9 years). Sixteen patients became seizure-free (Engel outcome score 1), 3 had seizure reduction >90% (Engel 2), I patient, who had only a minimal anterior resection to minimize the risk of increasing a preexistent m e m o r y impairment, showed only partial improvement (Engel 3), and 2 patients showed no improvement, 1 probably because of a necessarily restricted resection in the dominant temporal lobe. Of the 15 patients of the NT group, 13 had surgery (9 right and 4 left ATL). In the 2 remaining patients, the epileptogenic zone extended too far posterior in the dominant hemisphere to allow surgery to be performed. Median follow-up was 5 years (minimum 8 months, maximum 11 years). Eleven of the 13 patients became seizure-free (Engel 1), and 2 had significant seizure reduction (Engel 2). In neither the MT nor the NT group could a correlation between pattern of seizure spread and outcome of surgery be established.

Discussion

Our results show clear differences between seizures with MT onset and those of NT origin on the basis of seizure duration and different patterns of sequential involvement of regions outside the zone of ictal onset. With regard to temporal relation-

Second Ipsilateral temporal neocortical or ipsilateral frontal neocortical Contralateral mesiolimbic or ipsilateral frontal neocortical Contralateral temporal neocortical Contralateral mesiolimbic or ipsilateral frontal neocortical Contralateral temporal neocortical or contralateral frontal neocortical

Third

Contralateral mesiolimbic

Ipsilateral mesiolimbic

ships, the results are in general agreement with the findings of other investigators (12,13,15). As previously shown by Lieb et al. (12,13), there is significantly more rapid seizure spread from MT structures ipsilateral to contralateral in patients with NT seizure onset. Our results suggest that this parameter, together with the total time of seizure duration, can be used to a large extent to differentiate between seizures with NT onset versus those of MT origin and the significantly different values for total seizure duration (NT <95 s, MT > 118 s) and time of spread from ipsilateral limbic to contralateral limbic (NT <32 s, MT >33.5 s) indicate that it is possible to identify individual seizures of either type with 95% reliability (Tables 2 and 3). Furthermore, our results also show significantly more rapid ictal involvement of the ipsiand contralateral neocortical brain regions in the NT group. An explanation for these different time relationships might be that in MT temporal seizure onset ictal activity remains confined to the hippocampal structure proper for a considerable time, owing to the strong inhibitory action of the dentate gyrus and the relatively restricted pattern of intrinsic connectivity (17). When this blockade is overcome, seizure activity is likely to spread to adjacent limbic and extralimbic structures. Once this has occurred, seizure activity might spread much more rapidly to distant structures t h r o u g h excitatory synaptic pathways. Conversely, ictal activity originating in ] EPILEPSY, VOL. 8, NO. 4, 1995 317

G. J. F. BREKELMANS ET AL.

the temporal neocortex might spread faster, more readily, and further afield than seizures triggered in the mesial temporal structures not only because of the relatively less powerful inhibition of the surrounding neocortex but also because of the extensive nature of the neocortical excitatory interconnections. By use of different methods of evaluating seizure spread or, more appropriately, sequential ictal involvement of cerebral structures, several routes have been established in experimental animal models and postulated in humans (9-15,1721). However, the actual anatomy of some of these proposed routes of ictal spread remains controversial in view of the existing inter- and intraindividual variations in h u m a n anatomy, as does the question of whether the processes involved reflect direct neuronal propagation of seizure activity or merely sequential involvement of different potentially epileptogenic structures. Therefore, to what extent, if any, conclusions can be drawn about preferential routes of spread in the cited studies remains debatable. The combined use of bilaterally implanted subdural and intracerebral electrodes in the present study, although also limited in its possibilities, appears relatively better suited to investigation of the sequential ictal involvement for seizures emanating from either deep or superficial cerebral structures. This implantation technique, which causes little morbidity and patient discomfort (5), provides an adequate sampling of more extensive regions of neocortex of both ipsilateral and contralateral frontal and temporal lobes than was possible in the studies cited, while still providing sufficient depth electrode information from either side. Interhemispheric propagation and ictally active pathways in temporal lobe seizures have been the subject of several studies (9-15,18-22), mostly based on visual assessment of EEG patterns of seizure activity sequentially invading different brain areas but sometimes also using linear and nonlinear correlation analysis and coherence/phase analysis of seizure activity already present in these structures. Furthermore, data derive from either clinical or experimental studies and are not always directly comparable or in agreement. Several preferential axonal pathways have been hypothesized. Spread may occur from the mesiolimbic structures to the temporal neocortex along the subiculum and parahippocampal gyrus (14). Connections exist with the orbitofrontal cortex along the uncinate bundle 318

J EPILEPSY, VOL. 8, NO. 4, 1995

and with the supplementary motor cortex and cingulate gyrus (17). Connections exist with the thalamus through the fornix, mammillary nucleus, and mammillothalamic tract and with the brainstem reticular formation (15,17,20). The contributions of these connections to ictal spread in humans remain largely a matter of conjecture, however, and simple visual analysis of sequential ictal EEG patterns may be insufficient to solve this issue. Pijn et al. (23) showed that in the evolution of a seizure in kindled rats the pattern of association changes rapidly between different areas involved, stressing the need to assess short EEG epochs. By merely visually assessing the EEG, one may make an erroneous assumption that an anatomic pathway exists between different brain regions w h e n there is no strong degree of association between them. On the other hand, causality may never be i n f e r r e d f r o m s t u d i e s of a s s o c i a t i o n o n l y (23,24,30). Spread of ictal activity from the temporal and/or frontal neocortex to homologous areas on the contralateral side through the corpus callosum or the anterior and/or posterior hippocampal commissures appears likely. However, Lieb et al. (15) reported a strong interhemispheric coherence between homologous sites in only a few of their patients with either frontal temporal, NT, or MT foci. Likewise, evidence for direct spread from mesio-limbic structures through the forebrain commissures is often lacking. That, in our series, seizure invasion of the contralateral mesiolimbic structures was hardly ever preceded by seizure invasion of the contralateral temporal neocortex, as also reported by Spencer et al. (18), together with the very rapid involvement of the contralateral mesiolimbic structures after the invasion of the ipsilateral hippocampus by seizure activity originating in the homolateral temporal neocortex has occurred, is believed to provide indirect evidence for spread through the hippocampal commissures. However, Wilson et al. (21) failed to elicit a hippocampal evoked response by stimulating the contralateral hippocampuso Although the degree of association between both hippocampi in the kindled rat is high, whereas time delays for afterdischarges are almost zero (25), studies have demonstrated low coherences in humans (15,26). Possible explanations are that hippocampal commissure fibers connect only limited parts of both hippocampi, or that the most frequently and heavily damaged structures in MTS in humans, such as the dentate hilus, the CA3 area, or the entorhinal cortex, are the source of most of the commissural fibers (17). In a recent survey, Gloor et al. (27) noted electro-

EEG SPREAD OF M T VERSUS NT SEIZURES

physiological evidence of spread through the posterior hippocampal commissure and demonstrated virtual absence of a functional anterior hippocampal commissure in three h u m a n brains. They concluded that seizure propagation through this structure is very unlikely. In the present material, three distinct patterns of spread could be established in the MT group (Table 4). We confirmed the common secondary involvement of the contralateral hippocampus, almost always even before that of the homolateral temporal neocortex in most seizures. However, 1 patient showed ictal involvement of the contralab eral temporal neocortex but not of the contralateral hippocampus, which argues against the hypothesis of spread to the contralateral temporal lobe through the commissures. Because no actual ictal data are available from the thalamus, the fornix, or the reticular formation, the possible contribution of these structures to seizure propagation in humans remains unclear. When examining the possible role of the frontal lobes in seizure spread, we note that, contrary to the findings by Lieb et al. (11), w h o reported initial invasion of the ipsilateral frontal neocortex in almost all their patients, this ictal pattern was established in only 3 of 20 patients in our study. Indeed, in most patients, spread was first noted to the ipsilateral temporal neocortex. This discrepancy probably results from the sampling of different regions: Lieb et al. used intracerebral electrodes, whereas we used subdural coverage of the frontal as well as the temporal neocortex. Therefore, Lieb et al. (11) established secondary involvement of the mesial orbitofrontal area, whereas our subdural strips record mainly from lateral and basal orbitofrontal cortex. Nevertheless, a more striking finding in our study arguing against an obligatory frontal route of spread was the lack of contralateral frontal lobe involvement in subgroup B of our NT group, w h o had ictal involvement of the ipsilateral frontal neocortex first. On the strength of the statistically highly significant differences in the temporal parameters in the present study, both types of seizure onsets (NT vs. MT) can be reliably discriminated in intracranial EEG on the basis of differences in time relationships of sequential ictal involvement alone, irrespective of the location of seizure onset. Because every method of intracranial monitoring may theoretically miss the zone of ictal onset by virtue of the limitations inherent in implanting intracranial electrodes, these temporal relationships in sequential ictal involvement thus

yield important additional information w h i c h should be considered by surgeons in "tailoring" a resection. Another striking discrepancy between our study and that of Lieb et al. (12), w h o showed a better outcome in patients with mesiolimbic seizures, is the fact that we could not distinguish between any of our groups and subgroups in terms of postoperative outcome. This probably is the result of our approach of always tailoring resections, including application of intraoperative ECoG in both mesiolimbic and neocortical epilepsy surgery cases. For such an approach in patients in need of intracranial investigation, the combined use of subdural and intracerebral electrodes is a prerequisite because most of the parameters we suggest require information from both types of electrodes (28). The rather small intraindividual variation in patterns of spread observed in our study lends support to the hypothesis that in any 1 patient only a few of the many possible existing anatomic connections are being facilitated or sensitized in the evolution of the seizure disorder (29) and that this facilitation or sensitization is patient-specific. Surgically interrupting postulated pathways in 1 patient probably would not result in permanent seizure relief because of the likelihood that other pathways would become active if the zone of ictal onset itself were not removed. We showed that, whenever its use is warranted, our method of invasive seizure monitoring based on a limited number of bilaterally placed intracerebral and subdural electrodes can differentiate between neocortical and mesiolimbic seizures not only by reliably and adequately lateralizing and localizing seizure onset but also by assessment of seizure duration and pattern of sequential ictal involvement; our method provides sufficient coverage of the temporal and frontal neocortex as well as the mesial temporal structures to allow some insight into propagation patterns of ictal activity, which in turn contributes to further differentiation of seizures on EEG. Furthermore, our results agree well with those of a recent study by Binnie et al. (28), indicating that neither intracerebral electrodes nor subdural reeds should be omitted in the differentiation of MT versus NT seizure onset because seizure propagation patterns of sequential ictal involvement do not differ significantly between the two groups, at least with regard to spread to temporal and frontal neocortex. Finally, our results support the assumption that temporal lobe epilepsy is an inhomogeneous entity. One should preferably refer to either NT or J EPILEPSY, VOL. 8, NO. 4, 1995 319

G. J. F. BREKELMANS ET AL.

MT seizure onset, both of which have a distinctly different pattern of ictal spread and are ultimately related to different mechanisms and causes of epileptogenesis in humans.

Acknowledgment: All patients were investigated as part of The Dutch Collaborative Epilepsy Surgery Program.

References 1. Engel J, Van Ness P, Rasmussen TB, Ojemann LM. Outcome with respect to seizures. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1993: 359-67. 2. Wieser HG. Selective amygdalo-hippocampectomy for temporal lobe epilepsy. Epilepsia 1988;29(suppl 2):$100-13. 3. Wieser HG, Kausel W. Electroclinical semiology of the epilepsies. Limbic seizures. In: Wieser HG, Elger C, eds. Presurgical evaluation of epileptics. New York: SpringerVerlag, 1987:228-48. 4. Wieser HG, Muller RU. Neocortical temporal seizures. In: Wieser HG, Elger C, eds. Presurgical evaluation of epileptics. New York: Springer-Verlag,1987:252-66. 5. Van Veelen CWM, Debets RM Chr, Van Huffelen AC, et al. Combined use of subdural and intracerebral electrodes in preoperative evaluation of epilepsy. Neurosurgery 1990;26: 93-101. 6. Faught E, Kuzniecky RI, Hurst DC. Ictal EEG wave forms from epidural electrodes predictive of seizure control after temporal lobectomy. Electroencephalogr Clin Neurophysiol 1992;83:229-35. 7. Spencer SS, So NR, Engel J Jr, et al. Depth electrodes. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1993:359-67. 8. Spencer SS, Guimaraes P, Katz A, Kim J, Spencer DD. Morphological patterns of seizures recorded intracranially. Epilepsia 1992;33:537M~5. 9. Wieser HG. Ictally active pathways in psychomotor seizures: a stereo EEG study. In: Dam M, Gram L, Penry JK, eds. Advances in epileptology: XIIth Epilepsy International Symposium. New York: Raven Press, 1981:305-12. 10. Gotman J. Measurement of small time differences between EEG channels: method and application to epileptic seizure propagation. Electroencephalogr Clin Neurophysiol 1983; 56:501-14. 11. Lieb JP, Dasheiff RM, Engel J Jr. The role of the frontal lobes in the propagation of mesial temporal lobe seizures. Epilepsia 1991;32:822-37. 12. Lieb JP, Engel l Jr, Babb TL. Interhemispheric propagation time of human hippocampal seizures: I. Relationship to surgical outcome. Epilepsia 1986;27:286-93. 13. Lieb JP, Babb TL. Interhemispheric propagation time of human hippocampal seizures: II. Relation to pathology and cell density. Epilepsia 1986;27:294-300. 14. Brazier MAB. Electrical seizure discharges within the human brain: the problem of spread. In: Brazier MAB, ed. Epilepsy, its phenomena in man. New York: Academic Press, 1973:153-70.

320

] EPILEPSY, VOL. 8, NO. 4, 1995

15. Lieb JP, Hoque K, Skomer CE, Song X-W. Inter-hemispheric propagation of human mesial temporal lobe seizures: a coherence/phase analysis. Electroencephalogr Clin Neurophysiol 1987;67:101-19. 16. Delmas A, Pertuiset B. Cranio-cerebral topometry in man. Paris: Masson, and Oxford: Blackwell Scientific Publications, 1959. 17. Lothman EW, Bertram EH, Stringer JL. Functional anatomy of hippocampal seizures. Prog Neurobiol 1991;37:1-82. 18. Spencer SS, Williamson PD, Spencer DD, Mattson RH. Human hippocampal seizure spread studied by depth and subdural recording: the hippocampal commissure. Epilepsia 1987;28:479-89. 19. Rutecki PA, Grossman RG, Armstrong D, Irish-Loewen S. Electrophysiological connections between the hippocampus and entorhinal cortex in patients with CPS. J Neurosurg 1989;70:667-75. 20. Bertashius KM. Propagation of human complex-partial seizures: a correlation analysis. Electroencephalogr Clin Neurophysiol 1991;78:333-40. 21. Wilson CL, Isokawa-Akesson M, Babb TL, Engel J Jr, Cahan LD, Crandall PH. A comparative view of local and interhemispheric limbic pathways in humans: an evoked potential analysis. In: Engel J Jr, Ojemann GA, L~iders HO, Williamson PD, eds. Fundamental mechanisms of human brain function. New York: Raven Press, 1987:27-38. 22. Adam C, Saint-Hilaire J-M, Richer F. Temporal and spatial characteristics of intracerebral seizure propagation: predictive value in surgery for temporal lobe epilepsy. Epilepsia 1994;35:1065-72. 23. Pijn JPM, Vijn PCM, Lopes da Silva FH, Femandes de Lima VM. Evolution of interactions between brain structures during an epileptic seizure in a kindled rat. In: Manelis J, Bental E, Loeber IN, Dreifuss FE, eds. Advances in epileptology, vol 17. New York: Raven Press, 1989:67-70. 24. Pijn JPM, Lopes da Silva FH, Van Erode Boas W, Blanes W. Localization of epileptic foci using a new signal analytical approach. Neurophysiol Clin 1990;20:1-11. 25. Fernandes de Lima VM, Pijn JPM, Nunes Filipe C, Lopes da Silva FH. The role of hippocampal commissures in the interhemispheric transfer of epileptiform afterdischarges in the rat: a study using linear and non-linear regression analysis. Electroencephalogr Clin Neurophysiol 1990;76:520-39. 26. Gotman J. Interhemispheric interactions in seizures of focal onset: data from human intracranial recordings. Electroencephalogr Clin Neurophysiol 1987;67:101-19. 27. Gloor P, Salanova V, Olivier A, Quesney LF. The human dorsal hippocampal commissure. An anatomically identifiable and functional pathway. Brain 1993;116:1249-73. 28. Binnie CD, Elwes RDC, Polkey CE, Volans A. Utility of stereoelectToencephalography in preoperative assessment of temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 1994;57:58-65. 29. Engel J Jr. Clinical evidence for the progressive nature of epilepsy. In: Heinemann U et al., eds. Proceedings of the Workshop on the Neurobiology of Epilepsy (WONOEP). New York: Raven Press, 1995 (Advances in neurology). 30. Pijn JPM, Vijn PCM, Lopes da Silva FH, Van Emde Boas W, Blanes W. The use of signal analysis for the localization of an epileptic focus: a new approach. In: Manelis J, Bental E, Loeber JN, Dreifuss FE, eds. Advances in epileptology, vol 17. New York: Raven Press, 1989:272-6.