Clinical and Electroencephalographic Evidence for Sites of Origin of Seizures with Diffuse Electrodecremental Pattern

Epilepsia, 35(5): 974-987, 1994 Raven Press, Ltd., New York 0 International League Against Epilepsy

Clinical and Electroencephalographic Evidence for Sites of Origin of Seizures with Diffuse Electrodecremental Pattern

“Santiago Arroyo, *?$Ronald P. Lesser, *?Robert S. Fisher, *§Eileen P. Vining, *Gregory L. Krauss, “Karen Bandeen-Roche, *John Hart, *Barry Gordon,

fSumio Uematsu, and *Robert Webber

*Department of Neurology, The Johns Hopkins Epilepsy Center, ?Department of Neurosurgery, #The Zanvyl Krieger MindlBrain Institute, and $Department of Pediatrics, The Johns Hopkins University School of Medicine; and

IlDepartment of Biostatistics, The Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, U.S .A .

Summary: A diffuse electrodecremental ictal pattern (DEP) has been associated with tonic seizures and, less often, with other forms of epilepsy and has been considered to reflect a generalized seizure disorder of diffuse cortical or subcortical (brainstem) origin. In some seizures associated with DEP, however, focal ictal manifestations have been observed. We reviewed the records of all patients admitted to our seizure monitoring unit for 3 years and detected 39 patients with seizures associated with DEP. In 23 of 39 patients, clinical ictal behaviors resembled seizures of unilateral supero/mesiofrontal lobe origin and interictal EEG showed a prominent unilateral frontal component. Nine of 39 had complex absences

(CA)/complex partial seizures (CPS); 4 of them were of unilateral frontal lobe origin. Seven of 39 patients had tonic or atonic seizures. Seven patients were studied further with subdural electrodes. Ictal onsets showed a high- frequency frontal lobe discharge. We conclude that in a subgroup of patients a generalized electrodecremental pattern on scalp EEG results from a regional cortical high-frequency ictal discharge originating in a single frontal lobe. Key Words: Epilepsy-Electroencephalogra- phy-Electrodecremental-Frontal lobe seizures-Tonic seizures-Supplementary motor area-Hlgh-frequency activity-Lennox-Gastaut syndrome.

The electrodecremental EEG pattern is defined as low-voltage fast activity that subsequently in- creases in voltage and decreases in frequency, with evolution to recurrent rhythmic spikes (Jasper and Kershman, 1949). Two types of electrodecremental patterns have been described: focal and diffuse (generalized). A focal electrodecremental pattern occurs at onset of some seizures, e.g., during complex partial seizures (CPS) of temporal lobe origin (Blume et al., 1984; Morris et al., 1987a). A diffuse electrodecremental pattern (DEP) (Bickford and Klass, 1960; Fariello et al., 1979) has been considered to represent a generalized cortical seizure pat-

Received August 1993; revision accepted October 1993. Address correspondence and reprint requests to Dr. S. Arroyo

at Department of Neurology, Meyer Building 2-147, The Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21287-7247, U.S.A.

Dr. Fisher’s present address is The Barrow Neurologic Insti- tute, SJHMC, 350 West Thomas Road, Phoenix, AZ 85013-4496, U.S.A.

Presented in part at the American Epilepsy Society Meeting, December 9, 1991, Philadelphia, PA, U.S.A. [Epilepsia 1991; 32(suppl 3):241.

tern, possibly of brainstem origin (Gastaut et al., 1963; Egli et al., 1985). It also has been termed diffuse flattening or attenuation of EEG activity (Blume, 1988), or generalized desynchronization (Gastaut et al., 1963). It is similar to the “grand mal” pattern defined by Gibbs et al. (1943) and the paraoxysmal beta activity described by Brenner and Atkinson (1982), although these patterns were not necessarily of low voltage.

DEP has been described as a seizure pattern in infantile spasms (IS) (Druckman and Chao, 1955; Kellaway et al., 1979), in atonic seizures (Courjon and Favel, 1961; Hooshmand et al., 1980), and in tonic seizures (Gastaut et al. 1966, 1975; Fariello et al., 1979; Tassinari and Ambrosetto, 1988). It is especially prevalent in seizures (tonic or atonic) of the Lennox-Gastaut syndrome (LGS) (Gastaut et al., 1966; Blume, 1988; Niedermeyer, 1988; Donat and Wright, 1991; Yaqub, 1993). However, at least some patients with this generalized seizure pattern have clinical ictal behaviors, interictal EEG activity, and neuroradiologic data that indicate a localized cortical epileptogenic area (Fisher and Nieder-

974

ORIGIN OF DEP 975

meyer, 1987; Burnstine et al., 1991). Examples include asymmetric IS (consisting of posturing of the extremities in a fencer position) (Kellaway et al., 1979; Gaily and Shewmon, 1992; Carranza et al., 1993) or partial seizures of orbitofrontal, mesiofrontal (Ludwig et al., 1976; Fusco et al., 1990), or supplementary motor area (SMA) origin (Morris et al. , 1988).

Because many patients with DEP have severe medially intractable seizures, knowing whether such patients might respond to surgical therapy and what features suggest than an individual patient might respond to surgical intervention is of impor- tance. We investigated the clinical and EEG patterns associated with a diffuse electrodecremental response. Although we noted diffuse disease in our patients, we also noted further evidence suggesting that in a subset of patients with DEP the seizures (although generalized by scalp recordings) reflected a more localized underlying cortical epileptogenic region.

METHODS DEP wasdefined as an electrophysiologic seizure

pattern characterized either by diffuse low-voltage fast activity with <25 p,V and frequency >15 Hz (Fig. l), or by diffuse flattening of the scalp EEG activity without visible fast activity (Fig. 2) (Gas- taut et al., 1963; Fariello et al., 1979). To differen- tiate DEP from a nonspecific arousal reaction, we required DEP to occur at the same time as the first seizure clinical manifestations. Seizures themselves may produce arousal reactions that may be associated with low-voltage EEG, but arousal without a seizure differs clinically from arousal with a seizure.

We reviewed records of patients admitted to the Johns Hopkins epilepsy monitoring unit between

1988 and 1991 for whom seizures with ictal diffuse low-voltage fast activity or “flattening” of the EEG were reported. Thirty-nine such patients were detected. All available EEG records and seizure vid- eotapes for these patients were analyzed, yielding 722 seizures. The patients had been monitored with continuous video-EEG for G 1 week with 32-64 EEG channels with both bipolar and referential derivations. In each patient, a group of electrode pairs was placed symmetrically (i.e., over the two hemi- spheres), but other electrodes were added asym- metrically (according to 10% system method) (Mor- ris and Luders, 1985) over specific cortical regions believed to be of particular interest in the individual patient because of clinical history, results of imaging studies, or video or EEG characteristics of seizures already recorded. Synchronous time and date markers were generated for EEG and video.

Interictal spike activity and bursts of spike and wave were detected and analyzed with a locally designed automated spike detection program. Ran- dom samples of unedited data also were evaluated. Sites of maximal voltage and spread of epileptiform activity were assessed in referential recordings by locally designed computer software. Patients were considered to have multifocal spikes if three or more separate cortical spike foci (temporal, parietal, frontal, or occipital) were shown on EEG recordings. These separate regions were defined by phase reversals in bipolar derivations and by corre- sponding sites with maximal amplitude spikes in referential derivations. For patients with multifocal spikes, we defined each site of maximum spike involvement in two ways: in cases of focal spikes as the region in which spikes were of maximum voltage (at least 80% of maximum voltage) and in which >80% of the spikes occurred and, in cases of poly- spikes and spike and wave bursts. as the area in

FZ-CZ

cz-PZ

CHl-PZ

83-PZ

Fl l-PZ

011-PZ

Cll-PZ

09-PZ

13-PZ

CHP-PZ

84-PZ

Fl2-PZ

012-PZ

c12-PZ

14-PZ

FIG. 1. Scalp recorded ictal onset of patient 3. After a burst of sharp and slow wave, a diffuse low-voltage 15- to 20- Hz activity was followed by sernirhythrnic 2- to 4-Hz activity first over left posteroparietooc- cipital regions and then generalized (vertical scale = 300 WV).

Epilepsia, Vol. 35, No. 5, 1994

976 S . ARROYO ET AL.

AF3-PZ

F3-PZ -- CHl-PZ --- FP-PZ ------ F 1 9- PZ ------- 13-PZ - - -

A- FIG. 2. Scalp-recorded ictal onset of Tg-PZ x__y__^

patient 32. After a brief burst of Dolvsoikes. anterior maximum. diffuse T5-PZ __xc_

i a t i e i i n g of the EEG activity was followed by 9- to 12-Hz rhythmic activity and then generalized rhythmic spikes

AF4-PZ

F4-pz

(vertical scale = 300 UV). CH2-PZ ~

FlO-PZ

FTlO-PZ

T4-PZ .

TlO-PZ - 16-PZ ’-*

EKG-EKG +--*- d

which the burst had maximal voltage in 80% of bursts.

Some patients showed symptoms consisting of staring with or without automatisms, followed by dystonic arm posturing and head deviation, which clinically could be termed either complex absence (CA) or CPS. Because of the possibility of using either term and because each term reflects a con- clusion regarding focality of seizure onset (which is what we studied), we used the abbreviation CA/ CPS in this article. The following clinical signs during CA/CPS were considered lateralizing features: (a) dystonic posturing of one limb (Kotagal et al., 1989; Newton et al., 1992); (b) forced head deviation (Wyllie et al., 1986); (c) hemiclonic activity; and (d) side of onset and/or “maximal involvement” during the seizure. The latter was defined as the side in which the first motor activity was observed and the side in which clonic activity was of a frequency at least double that on the contralateral side, respectively. Dystonic seizures were defined as those with facial grimacing, uni- or bilateral tonic arm posturing in abduction and flexion or extension, and head turning ipsilateral or contralateral to the elevated arm, followed by hemiclonic or generalized tonic-clonic (GTC) activity. We considered the focus to be located contralateral to the arm that was first elevated and presented a more prominent dystonic posture in flexion (Penfield and Jasper, 1954; Fusco et al., 1990; Wieser et al., 1992). These seizures were frequently followed by herniclonic or GTC activity, especially when antiepileptic drug (AED) treatment was discontinued. Tonic seizures were defined as episodes manifested by sudden bi-

laterally symmetric arm extension with or without trunk flexion and with no initial versive movement of the head. Notably, in patients with seizures ini- tially consisting mainly of grimacing, when AEDs were discontinued, we observed asymmetric posturing involving the proximal axial musculature of both upper extremities or even the appearance of a full dystonic seizure.

Subdural electrode recording and analysis Seven of the 39 patients exhibiting DEP on scalp

recordings were studied with subdural electrodes placed unilaterally or bilaterally over specific regions because previous recordings and other clinical and imaging information indicated that seizures might originate in those regions (Lesser et al., 1981; Liiders et al., 1987). Before having subdural electrodes implanted, 1 patient had bilateral frontotemporal epidural electrodes and another had bilateral depth electrodes implanted in fronto- and mesiotemporal regions to determine further whether seizures were of unilateral onset. All patients with implanted grids were monitored for 10-14 days except for patient 15, in whom the grid was removed at day 3 because of persistent fever and symptoms of increased intracranial pressure.

The EEG was digitized at 200 samplesls (Nyquist frequency cutoff of 100 Hz), except in 2 patients (patient 1 was digitized at 400 samples/s, and patient 8 was digitized at 300 samples/s). Digitization, recording, and display of the amplifier output was performed with customized software (Fisher et al., 1992; Lesser et al., 1992).

We selected and analyzed the high-frequency

Epilepsia, Vol. 35, No. 5 , 1994

ORIGIN OF DEP 977

components of the first three seizures recorded in the 48 h after the patient was admitted to the monitoring unit (-72 h after operation). Review of all seizures in these patients indicated that the three seizures were representative of their successors both clinically and by EEG. In every channel of each of these seizures, we obtained a 2.6-s sample at electrographic onset of the seizure and another sample 10 s before it. A computer performed a fast fourier transformation (FFT) and power spectral density (PSD) transformation for data from each channel of EEG. Channels that displayed obvious artifact on visual inspection or in the FFT display were disregarded. We analyzed the high-frequency PSD in the range from 30 to 100 Hz. Because the original PSD data differed widely among patients and regions, we applied a log transformation to the high-frequency (30-100 Hz) PSD before statistical analysis.

Statistical analysis We first determined whether high-frequency PSD

was increased overall at seizure onset. We performed paired t tests comparing PSD before and at seizure onset, pooling all channels in all seizures and with both raw data and transformed data. We next used the generalized estimating equation approach (Liang and Zeger, 1986) to compare mean differences between anatomic locations. In our ap- plication this approach is analogous to analysis of variance (ANOVA), but takes intraperson and intratrial (a trial was each seizure) correlation into account. We defined the following locations: superior lateral (SL), including electrodes located over the upper half of laterofrontal neocortex and postcentral cortex; inferior lateral (IL), including electrodes located over the lower half of laterofrontal cortex and postcentral cortex; mesofrontal (M), located over the SMA and anteromesiofrontal cortex; temporal (T), including lateral and basotemporal cortex; posterior (P), including the area beginning 8 cm from the temporal tip and extending to the occipital pole; contralateral electrodes (C), including electrodes located contralateral to the seizure focus over the SL frontal, postcentral, M, and lateral T regions. For each individual patient, we first analyzed whether high-frequency PSD differed by electrode location and then performed analyses pooling patients for locations measured in two or more subjects (SL, IL, M, T, and C, but not P). We ran three different models: (a) only SL, IL, M, and T data; (b) SL, IL, M, T, and C data; (c) both A and B, but with patient 13 removed because this patient had one trial with PSD distribution quite different from that the other two trials, which accounts for her high

intratrial correlation relative to other patients. For each model, the outcome was equal to the mean, over the three trials (i.e., seizures) of the log differences in PSD, per site. Because all analyses were qualitatively the same, we report model b.

RESULTS During surface monitoring, the 39 patients had

582 seizures (mean 14.92 per patient, range 2-43): Of these, 324 seizures (56% of seizures analyzed) showed DEP. The rest were obscured by artifact or showed other generalized seizure patterns. During subdural electrode recording, 140 seizures were recorded (mean 20.0 per patient, range 6-40). Of the 464 seizures (324 plus 140) analyzed, 265 (57%) occurred during sleep.

Patient characteristics Mean age at first admission to our monitoring unit

was 19.0 years (SD 9.3, range 2-44 years; 13 fe- males and 26 males). Mean age at seizure onset was 47 months (SD 44.6 months, range 1 month to 13 years). Thirty patients had a history of mental retardation. IQ testing was performed in 24 of 39 patients, of whom only 5 had Full-scale IQ (FSIQ) X O . Mean FSIQ was 64.4 (SD 18.22, range 30- 102). Of the remaining 15 patients, 1 1 had mental retardation and 4 had normal intelligence by history and on neurologic examination. LGS had been di- agnosed in 17 patients, 15 had delayed milestones, and 16 had hemiparesis. No patient had a family history of seizures. Pos-

sible etiologic or risk factors associated with the seizures were complicated pregnancy or delivery in 14 patients, meningitis or encephalitis in 7, tumors in 2, head trauma in 2, tuberous sclerosis in 2, and heterotopic gray matter in 1. No known etiologic factors were observed in 11 patients.

All patients had computed tomography (CT) and/ or magnetic resonance imaging (MRI) scans (12 patients, CT only; 14, MRI only; 13 both CT and MRI). Twenty-two patients (56%) had abnormal scans: 15 of them had lateralized or localized lesions (porencephalic cysts, hemiatrophy, tumors, vascular malformation, migration disorder); 7 had nonlateralized abnormalities (diffuse cortical atrophy, cerebellar atrophy, Dandy-Walker malformation, bilateral subependymal modules).

Seizure types In 23 patients (59%), behavior during seizures

with DEP consisted of bilateral grimacing (tonic facial contraction) and sudden elevation and flexion of one arm, followed by opposite arm tonic extension or flexion and head deviation (fencer posture), frequently becoming secondily generalized, espe-

Epilepsia, Vol. 35, NO. 5, 1994


cially when AEDS were discontinued. The head was deviated toward the elevated arm in 13 patients, toward the nonelevated arm in 8, and se- quentially toward each in 1. The legs were frequently involved in the seizures, showing tonic flexion ipsilateral to the first or most elevated arm. However, we were unable to study leg positioning in many cases because the video camera was di- rected toward the head, arms, and trunk. These dystonic (Fariello et al., 1979) episodes had clinical characteristics consistent with seizures previously shown to be of unilateral onset, originating in superolaterofrontal cortex and/or SMA of either the left or right hemisphere (Penfield and Welch, 1949, 1951; Morris et al., 1987b).

Nine of 39 patients (23%) had CA/CPS consisting of staring, with or without automatisms, followed by motor phenomena and generalization. Three of 9 also had tonic seizures; 7 of 39 patients also had tonic or atonic seizures.

Interictal surface EEG activity In 32 patients, background EEG activity was dif-

fusely slow (5- showed hemispheric voltage asym- metry). In 29 (74%), interictal spikes were multifocal, although most patients (21) with multifocal spikes had a single brain area or hemisphere of maximal spike involvement (described in the Methods section). Spike maxima were lateralized in 26 of 39 patients (67%): in 14 over one frontal or frontocentral region, in 2 over one temporal region, and in 10 over one frontotemporal region or diffusely over one hemisphere. Of the 16 patients with both dystonic seizures and interictal spike maxima, interictal activity was maximal over the frontal or frontocentral regions of one hemisphere in 10, over one frontotemporal region in 1, over the posterotemporal regions on one side in 1, and over one hemisphere in 3. One patient had bitemporal spikes. Of the 8 patients with both CAlCPS and interictal spike maxima, bilateral activity was maximum over the frontal or frontocentral regions in 4, suggesting frontal lobe (but possibly bifrontal) origin and was lateralized over one hemisphere or frontotemporal region in 3; 1 patient focal spikes over one temporal region.

In 32 of 39 patients, seizures had onset with ictal lateralizing clinical signs as already defined; and 23 of 32 also had a clear site of maximal spike amplitude. In 17 of 23 (73.9%), concordance was evident between the side presumably generating the lateralizing ictal clinical behaviors and the side of maximal interictal activity (Table 1). Four of the other 6 showed evidence of false lateralization (Sammari- tan0 et al., 1987). Thus, a convergence of ictal clin-

TABLE 1. Convergence of clinical ictal behaviors and interictal EEG activity in patients with DEP

Total no. of patients

Seizures with lateralizing signs 32 (P) 7 (NP)

Lateralized interictal spike / \ I \ I \

maxima 23 (P) 9 (NP) 4 (P) 3 W"

Ictal signs and interical spike maxima lateralized to the same side 17 (P) 6 (NP)

DEP, diffuse electrodecremental pattern; P, present; NP, not present.

ical manifestations and interictal EEG activity in a subset of patients with a generalized electrodecremental seizure pattern raised the possibility that the seizures in this subset (but not all patients) might be of focal origin.

Seven patients had seizures without clinical lateralizing manifestations (tonic and atonic). How- ever, 4 of 7 had lateralized interictal EEG activity, and 3 of 7 had hemiparesis or a hemispheric lesion on the scans, suggesting that their seizures might originate in a single hemisphere or a single region in one hemisphere.

Ictal surface EEG data By definition, all seizures were characterized by

DEP. The period of voltiige flattening was variable in duration but was < 10 s. In 29 of 39 patients, DEP was preceded by a burst of slow waves, sharp waves, spikes, or spike-and-wave complexes last- ing <1. The bursts were lateralized to one hemisphere in 12 of 29 (40%); 9 of 12 had lateralized clinical manifestations; in 5 of 9 spike/slow-wave maxima during bursts agreed with the lateralizing clinical manifestations. Thus, these bursts were of indeterminate lateralizing value.

The ictal EEG activity that followed DEP was stereotyped in 36/39 patients. In 3 of 39, more than one EEG seizure pattern was observed. DEP was followed by nonlateralizing (generalized or bitemporal) ictal EEG activity in 24 of 39 and was maximal over one hemisphere in 15 patients. Twelve of 15 had dystonic or CA/CPS seizures: In 7, the side of maximal EEG seizure activity agreed with lateralization of clinical manifestations of the seizures (described in criteria for lateralizing features of CA/ CPS in the Methods section), so that ictal EEG patterns after DEP were consistent with clinical ictal behaviors in only a subset of patients (Table 2).


ORIGIN OF DEP 979

TABLE 2. Lateralization of EEG ictal data and ictal clinical manifestations

Total no. of patients 39

24 (NP) Lateralization Post-DEP EEG of / \

activity 15 (PI

I \ I \

Seizures with clinical signs lateralized to the same side as post-DEP activity 12 (P) 3 (NP)

Agreement in lateralization between ictal manifestations and

activity 7 (PI 5 W" Abbreviations as in Table 1 .

Post-DEP EEG

Patients with hemiparesis and/or unilateral CT/MRI lesion

Eighteen patients had a hemiparesis and/or a unilateral CT/MRI lesion. Of these, 15 had dystonic (11) or CALCPS secondarily generalized (4) and 3 had tonic seizures. Eleven of 15 patients with dystonic and CAiCPS seizures also had an interictal spike maximum. In 8 of 11 patients (73%) there was agreement among hemiparesis, CT/MRI lesion, clinical lateralizing features of the seizures, and interictal spike maximum (Table 3).

TABLE 3. Convergence of clinical ictal behaviors, interictal EEG activity, and neuroradiologic

lesionlhemiparesis in patients with DEP

Total no. of patients

Hemiparesis or lateralized MRI/CT lesion

Seizures with clinical signs lateralized to the same side as B

Interictal spike maximal lateralized to the same side as B to C

Agreement in lateralization among side of the lesion, hemiparesis, clinical ictal manifestations, and interictal spike maxima

39

/ \

CT, computed tomography; MRI, magnetic resonance imag-

a All 3 had tonic seizures, 2 of them with no interictal spike ing; other abbreviations as in Table 1.

maxima.

Clinical manifestations and EEG data of patients with subdural electrodes

In view of the regional features described and despite the diffuse ictal pattern recorded on scalp, we attempted further study with intracranial electrodes in 7 of 39 patients, using chronic intracranial recording with depth, epidural, and/or subdural electrodes. The seizures recorded intracranially were clinically similar to those that had occurred during the patient's previous admissions for scalp recording. Patient 13 was studied with bilateral epidural electrodes over the frontal lobes. Ictal EEG showed bilateral fast activity over both the right and left frontal electrodes more prominent (in voltage) over the right hemisphere. Patient 15 underwent bilateral implantation of depth electrodes in both fronto- and mesiotemporal regions. Seizures recorded showed left superolaterofrontal seizure onset. To delineate this region more effectively, we later implanted a left frontotemporal grid and bilateral mesiofrontal subdural strips. The other 5 patients had subdural electrodes implanted over the latero- and mesiofrontal and over the latero- and inferotemporal cortexes of one or both hemi- spheres. Electrode placements and locations of EEG seizure onsets as recorded by subdural electrodes are shown in Table 4.

At the start of all seizures in all patients, the rec- ord displayed a low-voltage high-frequency discharge over all implanted electrodes for 1-2 s, followed by rhythmical 10-25-Hz spikes over a variable number of electrodes over the frontal (in all but patients 8) and temporal (patient 8) regions (Fig. 3). The spikes tended to involve the same electrodes in all seizures in each patient, but varied in location from patient to patient.

Localized high-frequency rhythmical activity occurred over regions of seizure onset, as determined by the first appearance and location of rhythmical spikes (Fig. 4). In addition, FFT of the data showed an overall significant increase in PSD in the high- frequency band (30-100 Hz) at seizure onset as compared with baseline recording in every seizure analyzed (Fig. 5). The mean of the high-frequency PSD was 0.045 p,V2/Hz (SE 0.002) before seizure onset and 0.299 kV2/Hz (SE 0.018) at seizure onset (p < 0.0001). The logarithm of the high-frequency PSD before seizure onset was - 1.631 (SE 0.018); at seizure onset, it was - 0.987 (SE 0.024), p < 0.0001. The increase in high-frequency PSD was significant at each location for every patient except patient 10 in the temporal electrode group. (Fig. 6).

We analyzed the differences in high-frequency PSD by location for all patients, using the generalized estimating equation approach (Liang and


980 S. ARROYO ET AL.

TABLE 4. Clinical and EEG characteristics of the patients with implanted suhdural electrodes

Maximal Patiedage Seizure Grid interictaliictal

(yr) type localization“ surface activity Grid EEG seizure pattern

1/19 dystonic

2/14 dystonic

8/10 CPS

10112 dystonic

13/18 R dystonic

15/18 L dystonic

17/40 L dystonic

R: F (56), anterior F (20). mesial F (8); T (48), P -0 (32 )

L: F (481, T (24); R: F (10) (epidural)

L: F (16), T (48). P-0 ( 3 2 ) ; R: basal T (8)

L: F (56), T (8)

R: F (48), P (24)

L: F (64). mesial

L: F (24). mesial F (S), T (8) R: F (24), mesial F 09, T (8)

F and P -0

Bilateral F

L posterior T-0, multifocal

L F and multifocal

R F and multifocal

L mesial F and posterior and superior F

R mesial F and multifocal

Forty seizures beginning with low-voltage fast activity (20-1 10 H z ) ~ over areas of the R lateral and mesiofrontal lobe, followed by rhythmical 12 to 1 5 - H ~ spikes over these areas; electrical stimulation of two electrodes in right mesiofrontal area elicited a typical seizure

Ten seizures with low-voltage fast activity (2&100 Hz) over L frontal region, followed by rhythmical spikes over L and R frontal regions

Five seizures beginning with bursts of spikes over posterior T -0 region followed by diffuse low-voltage 20 to 120-Hz activity and then rhythmic 10 to 12-Hz spikes first over L posterotemporooccipital region, spreading later to frontal regionsb

Seven seizures with low-voltage fast activity and rhythmical spikes scattered over the frontal convexity, followed by rhythmical 13 to 15-Hz spikes over postero- and superolateral frontal regions

Twenty-eight seizures with low-voltage fast (20-100 Hz) activity followed by rhythmical 20 to 30-Hz spikes maximal over frontal cortex

Ten seizures with focal low-voltage fast activity (20-100 Hz) followed by rhythmical 14 to 15 Hz activity over L postero-mesiofrontal region and scattered areas of L frontal convexity

Sixteen seizures with a generalized slow wave followed by low-voltage fast (20-100 Hz) activity over the R frontal convexity and mesiofrontal regions in eight seizures and in four over L latero- and mesiofrontal regions followed by 10 to 12-Hz rhythmical spikes with variable onset over R and L mesiofrontal regions and R frontal convexity.

F, lateral frontal cortex and postcentral cortex; T , lateral temporal cortex; P, parietal cortex; 0, Occipital cortex (numbers in parentheses indicate number of electrodes placed in each region). Electrode placement was determined based on previous scalp recording with more widespread electrode placement (described in text).

* EEG of patient 1 was digitized at 400 Hz and the EEG of patient 8 was digitized at 300 Hz.

Zeger, 1986) (Table 5). Traditional ANOVA analysis controlling for “trial,” including the interaction between location and trial, yielded similar results. The 6 patients with dystonic seizures (all but patient

8) had an increase in high-frequency PSD in one frontal region as compared with other locations. In 4 of 6, this difference was significant. In 5 patients, both SL and IL electrodes were placed. All 5

1-2

3-4

5 -6

7-8

9-10

11-12

13-14

15-16

17-18 19-20

21-22

23-24

25-26 27-28

29-30

31-32

33-34 35-36

37-38

39-40

41-42 43-44

FIG. 3. lctal EEG pattern of patient 15 recorded with a grid of subdural electrodes over left frontal region and bilateral strips over mesofrontal regions with background of widespread slow waves. Low-voltage high-frequency (25-40 Hz) activity was observed over 7-8, 13-14, 15-16, 19-20, 23-24, and 33-34 (lateral frontal neocortex) that built into rhythmic 12- to 15-Hz spikes and spread to adjacent electrodes (horizontal scale = 1 s; vertical scale = 300 pV).


ORIGIN OF DEP 981

! I I I

I

FIG. 4. EEG recording at an expanded time scale (221.1 mm/s) at the start of a seizure in patient 1. Only three channels located over the laterosuperior laterofrontal lobe are shown. Recording at this time scale demonstrated that subjacent to the low-voltage fast activity there was rhythmic high-frequency activity at seizure onset. The vertical discontinuous lines occurred every 200 ms.

showed a trend toward higher PSD values in SL electrodes. In 2 of 5 , these differences were significant. In 2 of 3 with ipsilateral mesiofrontal electrodes implanted, high-frequency PSD values from mesial electrodes did not differ significantly from those from SL frontal electrodes. Thus, in these patients, high-frequency at seizure onset was most prominent in the SL and mesiofrontal episodes.

Patient 8 had CA/CPS. Seizure onset in this patient was manifested on EEG by widespread voltage decrement followed by rhythmical spikes pre- dominantly over the left temporal and posterotem-

poral region. High-frequency PSD was significantly greater at the temporal and IL than at posterotemporal electrodes.

We next analyzed pooled data from all patients by anatomic location, controlling for intraperson correlation. There was significantly greater high- frequency PSD over the SL and contralateral frontal (C) regions as compared with IL, M, and temporal regions for every patient in every location. The means of the log differences were 1.7 for SL, 1.96 for C, 1.5 for M, 1.3 for IL, and 1.1 for T. The C log difference estimates were large because the

FIG. with

5. PI subdt

0 9

0 8

h . 3 0 7

2 O 6

N

E x g 0 5

2

M

3 G-

L d

O 4

-c

2 0 3 ru 4 0 2

0 1

0 1 2 2 2 8 8 8 10 10 10 13 13 13 15 15 15 1 7 1 7 17

Patient # lot of mean high-frequency power density per seizure before seizure onset and at seizure onset in Jral electrodes X-Axis: the three seizures analyzed per patient are represented by patient number

onset

seiz :ures I 'ecor ded


982 S. ARROYO ET AL.

2.15

I

1.75

.- P (D E 1.26 Q) 0

Q) L

0.75

B e 0

0 A

~ 0.15

4.25

T T IL IL IL IL IL IL SL SL SL SL SL SL SL AF AF AF AF AF M 8 T T IL IL IL IL IL IL SL SL SL SL SL SL SL AF AF AF AF M M

Electrode pollfflon

1 -8- 10 sec. before onset - At seizure onset I

values before seizure onset were disproportionally small as compared with the values at other locations, possibly because of the 4 patients with con- tralaterally placed electrodes: In 2, the contralateral interhemispheric electrodes were placed facing the falx (i.e., both left and right hemisphere electrodes were placed on one side of the falx, one set facing the ipsilateral hemisphere directly and the other facing the contralateral hemisphere through the falx); in 1 (patient 2), the contralateral electrodes were positioned epidurally . Thus, high frequencies may have been filtered by the dural membrane or falx. In addition patients 17 had bilateral SL frontal ictal onsets.

TABLE 5. Difference estimates between log of high-frequency PSD 10 s before and at seizure onset for

each location in every patient

Location

Patient r-Value

1 0.00 2 0.14

10 -0.0 13 0.47 15 0.07 17 0.06 8 0.09

S1 IL M

2.3 1.5’ 1.9 1.5 1.2 - 1.9 1.1’ - 1.6 1.8 - 0.76 0.72 1.19 1.5 - 0.9’

2.0 - -

T

1.3’ 1.1 0.35’ - -

0.6’ 2.1

SL, superolaterofrontoparietal; IL, inferolaterofrontopari- etal; M, mesiofrontal; AF, anterofrontal; T, temporal; PA, parietal; P, posterotemporal.

a Dash indicates that no electrodes were positioned in these locations.

Significant differences from superolaterofrontal electrodes, p < 0.05.

FIG. 6. Plot of log of high-frequency power density in one of the three seizures analyzed for patient 1 shows overall increase in high-frequency power density at seizure onset as compared with 10 s before onset. X-Axis shows electrode po- sitions over cortex; T, temporal; IL, in- ferolaterofrontoparietal; SL, superolaterofrontoparietal; AF, anterior frontal; M, mesiofrontal.

Results of operation Twelve of the 39 patients underwent operation,

primarily to reduce seizures in 11 and for resection of tumor in 1. Six were among those studied with chronic subdural intracranial recording. Four (patients 15, 21, 24, and 29) had corpus callosotomy (anterior or complete) and improved significantly. In all, drop attacks caused by atonic or tonic seizures disappeared, the number of seizures was re- duced >50%, and seizures occurred mainly during sleep. In all 4, generalized tonic-clonic seizures (GTC) were greatly diminished, but unilateral motor seizures persisted over the body side contralat- era1 to the epileptogenic region, as defined (described herein) by clinical seizure manifestations and interictal EEG characteristics. Mean follow-up period was 26 months (range 6 months to 4 years).

Two (patients 2 and 4) had complete modified hemispherectomies (Smith et al., 1991), and patient 1 had subtotal hernispherectomy. In all, interictal spikes, neurologic deficits (hemiparesis), and MRI scan lesions indicated the side removed. In 2 patients, clinical seizure manifestations agreed with the other information. Two have been seizure-free for the short (6 months) follow-up period since operation, and the other has had only staring spells during 27-month follow-up.

Three patients with dystonic and tonic seizures (patients 10, 13, and 28) had frontal and frontopari- etal cortecectomies, but neither sensorimotor cortex nor SMA was removed because of the risk of provoking hemiparesis, although these areas were considered epileptogenic. The patients showed no


ORIGIN OF DEP 983

worthwhile improvement, possibly because these epileptogenic regions were not resected. Patient 8 with CA/CPS had focal resection of the posterotemporal and occipital regions. He has been followed for 13 months and is having rare seizures. Patient 31 underwent operation to decompress a mass lesion. Epileptogenic cortex was not removed and he is still having similar seizures.

DISCUSSION

Patients with an EEG DEP at seizure onset tended to be mentally retarded, with multiple very frequent seizures, and early onset of epilepsy. More than one third had electroclinical characteristics of the LGS and nearly half the patients had hemiparesis or a gross hemispheric lesion. Interictal EEGs were usually multifocal, although frequently they were maximal in amplitude and frequency of occurrence over one side or region. Two main seizure types were observed: dystonic seizures with clinical manifestations reminiscent of seizures originating in the SL frontal and/or SMA of one hemisphere in 59% (Penfield and Welch, 1949, 1951; Morris et al., 1988; Wieser et al., 1992); and CA/CPS, many with interictal EEG activity indicating a unilateral frontal lobe focus in 23%. The remaining patients had tonic or atonic seizures or combinations of various seizure types.

These patients clearly are part of a highly selected group. Many were considered potential surgical candidates before admission to our monitoring unit and indeed were referred to our center because of that possibility. Selection was based on seizure intractability (patients considered candidates for corpus callosotomy) plus lateralized seizure manifestation and neuroimaging abnormalities (patients considered candidates for cortecectomy or corpus callosotomy). The referral setting and selection process would thus increase the percentage of patients with DEP and lateralized clinical or interictal EEG manifestation. However, the issue in this report is not the frequency of such patients but their occurrence. Our goal is to highlight the data from our patients and from previous reports that support the idea that some (but not all) patients with DEP have more localized regions of seizure onset.

Fariello et al. (1979) studied seizures with DEP and described a similar patient population. The most frequent seizure type was designated as dystonic and consisted of both symmetric and asymmetric tonic posturing. Gastaut et al. (1963, 1966) described most comprehensively the clinical and EEG characteristics of tonic seizures and differen- tiated five types: tonic axial (grimacing, apnea,

cry), tonic axio-rhizomelic (tonic-axial plus partici- pation of the proximal upper extremities), global tonic, asymmetric, and unilateral tonic seizures. Most of the seizures recorded in our patients consisted of dystonic posturing, coinciding with what Gastaut et al. termed asymmetric tonic seizures, involving asymmetric posturing of the extremities and head deviation to one side. Clinical manifestations of these seizures (i.e., the characteristic asymmetric sudden bilateral arm tonic posturing) and what Fariello termed dystonic seizures are similar to the seizures of mesiofrontal origin (SMA) described by Penfield and Welch (1949, 1951).

By definition, a DEP is widespread, but we noted that ictal clinical manifestations, interictal and ictal (post-DEP) EEG activity, and neuroradiologic lesions frequently were lateralized or localized. In- terictally , many of our patients had multifocal spikes or bursts of generalized spike and wave; however, in 67% of cases, spike maxima were over one hemisphere and frequently localized over one frontocentral region. The side of spike maxima agreed with the lateralization suggested by clinical features in 74% of patients who showed both features (spike maxima and lateralized ictal behaviors). In patients with hemiparesis and/or a unilateral CT/MRI lesion, there was agreement between side of lesion, the lateralizing clinical manifestations of both dystonic and CA/CPS, and interictal spike maximum in 8 of 1 1 (73%). Thus, a convergence of interictal EEG activity and clinical manifestations pointed to a possible regional focus of the seizures in some patients. On the other hand, post- DEP ictal EEG activity was less clearly correlated with the side suggested by interictal activity and clinical behavior, possibly owing to rapid spread of epileptiform activity to the controlateral hemisphere (Lieb, et al., 1986).

Subdural electrode recordings in patients with DEP The patients studied with subdural electrodes had

(DEP) in the scalp and displayed low-voltage, high- frequency activity at seizure onset. Analysis of seizure onset at an expanded time and voltage scale showed that instead of an apparent suppression of the EEG (as evident on scalp recordings), there was rhythmical high-frequency activity that subsequently decreased in frequency and increased in voltage. Thus, seizures that in scalp recordings consisted of diffuse electrodecremental activity were shown by subdural recordings with appropriate settings to have a several-fold increase in PSD of the high-frequency component of the EEG at onset.

These observations imply that DEP is not a de- synchronized pattern, but instead results from syn-



chronized rhythmical activity in the high-frequency range. The high-frequency activity is not observed at the scalp because it is higher than can readily be observed with scalp recordings, traditional amplifier settings, and paper-based EEG playouts (Coo- per et al., 1965; Fisher et al., 1992; Lesser et al., 1992) and because of the obscuring influence of muscle potentials. We (Fisher et al., 1992) and other investigators (Allen et al. , 1992) previously reported high-frequency activity in the range of 30-100 Hz at onset of frontal and temporal lobe seizures. Activity at these frequencies may correspond to synchronous excitatory postsynaptic potentials and/or synchronous action potentials (Allen et al., 1992; Fisher et al., 1992). We know of only one instance (Mazars, 1950) in which electrocorticography showed high-frequency activity in a patient with a DEP in scalp recordings.

For obvious reasons, we did not place an equal number of implanted electrodes over all brain regions. We selected the regions for electrode implantation based on previous clinical, neuroradiologic, and interictal EEG findings that had shown the areas likely to be involved at seizure onset (most often the frontal lobes). In all patients with dystonic seizures, despite widespread EEG suppression over the implanted electrodes , high-frequency PSD was significantly greater in amplitude over the regions suspected to include the seizure focus than in other regions. In most of these patients, it was more prominent unilaterally over the SL frontal, postcentral, and M regions. Thus, an increase in the high- frequency PSD appeared to correspond to the suspected epileptogenic region in patients with dystonic seizures. In patient 8 with CPS of suspected posterotemporal lobe origin, high-frequency PSD was greater, however, over the temporal and infer- ofrontal electrodes than in the posterotemporal electrodes.

Origin of DEP On the basis of animal experiments, seizures with

DEP have been suggested to arise from the reticular formation of brainstem or other subcortical structures (Moruzzi and Magoun, 1949; Feindel and Gloor, 1954; Kriendler et al., 1958; Bergmann et al., 1963; Rossi, 1965; Rodin et al., 1969; Wagner et al., 1975; Quesney and Gloor, 1978). How far these data can be extended to humans is unclear (Fromm, 1987). These experimental data differ in several as- pects from that of the subset of patients we de- scribe. First, clinical manifestations of seizures in animals (bilaterally symmetric tonic or tonic-clonic convulsions) are different from those in our patient population (asymmetric posturing, head deviation).

Second, many of our patients had cortical structural damage or were mentally retarded and thus had separate evidence of cortical damage. Third, there was good correlation in some (but not all) of the patients between side of cortical damage and the lateralizing features of the seizures. Fourth, the asymmetries of the clinical manifestations and of the interictal EEG spike maxima suggested a lateralized epileptogenic process, not a "centrencephalic" process.

In humans, the frontal lobe, especially its mesial region, produces generalized seizures, EEG features of generalized epilepsy, and DEP (Tiikel and Jasper, 1952; Bickford and Klass, 1960; Bancaud et al., 1967, 1974; Mazars, 1969; Goldring, 1972; Fisher and Niedermeyer, 1987). Experimental unilateral epileptogenic focus in the frontal lobe in animals also can produce secondary bilateral synchrony (Ottino et al., 1971). Unilateral lesions in SMA have been shown to produce dystonic seizures (with SMA features), bilateral synchronous spike and wave discharges, and ictal DEP (Tukel and Jasper, 1952). DEP has also been described in patients with frontal lobe seizures and with drop attacks caused by frontal lobe lesions (Pazzaglia et al., 1985). Goldring et al. (1972), in a group of 5 patients with characteristics similar to those of our patients (numerous seizures, multiple seizure types, bilateral spike and wave discharges; 3 with mental retardation), implanted depth electrodes in several areas of cortex and mesial thalamus. Spontaneous seizures and seizures induced by pentylenetetrazol originated in one or both prefrontal cortexes, whereas subcortical structures were involved secondarily. Other investigators using depth electrode recording observed similar frontal lobe onset in seizures with DEP on scalp electrodes (Bickford and Klass, 1960; Bancaud, 1969; Fisher and Nieder- meyer, 1987).

Thus, in contrast to the observations in animals, findings in humans suggest a cortical (frontal) origin of seizures in many patients with DEP. However, no electrodes were placed on the brainstem by us or by other investigators; consequently, cortical- reticular interaction with epileptiform discharges beginning in the cerebral hemisphere with spreading and involvement of the brainstem reticular formation cannot be ruled out.

We postulate that DEP is a seizure pattern that may reflect secondary bilateral involvement. A key element in emergence of DEP appears to be diffuse injury or dysfunction of widespread areas of brain. Both our data and experimental data (Marcus and Watson, 1966, 1968) show that the frontal and perirolandic cortexes are most likely to be responsible for the seizures, especially the mesofrontal regions

Epilepsia, Vol. 35, No. 5 , I994

ORtGtN OF DEP 985

of one hemisphere. The rapid secondary contralat- era1 spread could be produced easily by the strong and direct connections of the frontal lobes through the corpus callosum (Bancaud et al., 1974; Wiesen- danger, 1986; Weilleux et al., 1992). Both the frontal origin of the seizures and the bilateral frontal lobe involvement may explain the good results of corpus callosotomy in controlling occurrence of generalized tonic or tonic-clonic seizures in some patients with this pattern (Harbaugh and Wilson, 1982; Waterman et al., 1987; Andermann et al., 1988; Purves et al., 1988; Nordgren et al., 1991; Oguni et al., 1991).

Focal resection of epileptogenic regions in the frontal lobe has been attempted in patients with multifocal spikes and dystonic seizures, with improvement of the epilepsy in half the cases (Gold- ring, 1972; Ludwig et al., 1976; Blume and Pillay, 1985; Burnstine et a]., 1991; Weilleux et al., 1992). We believe that DEP, like multifocal spikes, can be truly multifocal or generalized, but also can be focal and secondarily generalized. In addition, in patients with DEP in scalp and regional onset demonstrated by subdural electrodes, the perirolandic cortex can be involved, making it difficult to resect the epileptogenic tissue without creating a sensorimotor de- fect. Thus, a mixed patient population (some with generalized and some with regional onset seizures), combined with restrictions imposed on resections involving functional areas, reduces the chance of seizure relief after focal surgery.

DEP represents a high-frequency ictal discharge associated with widespread cortical dysfunction, as judged by a high incidence of associated cognitive deficits and multifocal EEG abnormalities. Never- theless, in many patients with this generalized ictal pattern, an epileptogenic region over one lateral and/or mesiofrontal lobe can be discerned by care- ful observation of ictal behaviors and correlation with nonictal segments of EEG. Both resective surgery and corpus callosotomy may succeed when they are able to alter the epileptogenicity and capacity for seizure spread in these regions. Future research is needed to determine the physiopatho- logic significance of the high-frequency component of these seizures and to develop approaches that might lead to improved seizure control.

Acknowledgment: This work was supported in part by NIH NINDS Grant No. 1 ROl NS26553, The Whittier Foundation, The Seaver Foundation, and The McDonnel- Pew Program in Cognitive Neuroscience. S.A. was supported by a grant from the Fondo de Investigaciones Sa- nitarias, Spain. We thank Dr. Ernst Niedermeyer for comments and Mane1 Wijesinha for helpful conversations and supporting analysis.

REFERENCES

Allen PJ, Fish DR, Smith DJM. Very high-frequency activity during SEEG suppression in frontal lobe epilepsy. Electro- encephalogr Clin Neurophysiol 1992;82: 155-9.

Andermann F, Olivier A, Gotman J, Sergent J. Callosotomy for the treatment of patients with intractable epilepsy and the Lennox-Gastaut syndrome. In: Niedermeyer E , Degen R, eds. The Lennox-Gastaut syndrome. New York: Alan R. Liss, 1988:361-76.

Bancaud, J. Physiopathogenesis of generalized epilepsies of or- ganic nature (stereo-electroencephalographic study). In: Gas- taut H, Jasper H, Bancaud J , Waltregny A, Eds. The physiopathogenesis of the epilepsies, Springfield, IL: Charles C Thomas, 1969: 158-85.

Bancaud J, Takairach J, Bonk A. PhysiopathogCnie des Cpilep- sies-sursaut (a propos d’une epilepsie de l’aire motrice sup- plementarie). Rev Neurol (Paris) 1967;117:429-453.

Bancaud J, Yailairach J , Morel P, et al. “Generalized” epileptic seizures elicited by electrical stimulation of the frontal lobe in man. Electroencephalogr Clin Neurophysiol 1974;37:275-82.

Bergmann F, Costin A, Gutman J. A low threshold convulsive area in the rabbits mesencephalon. Electroencephalogr Clin Neurophysiol 1963 ;I S:683-90.

Bickford RG, Klass DW. Scalp and depth electrographic studies of electrodecremental seizures. Electroencephalogr Clin Neurophysiol 1960; 12:263.

Blume WT. The EEG of the Lennox-Gastaut syndrome. In: Nie- dermeyer E, Degen R, eds. The Lennox-Gastaut syndrome. New York: Alan R. Liss, 1988:159-76.

Blume WT, Pillay N. Electrographic and clinical correlates of secondary bilateral synchrony. Epilepsia 1985;26:636-41.

Blume WT, Young GB, Lemieux JF. EEG morphology of partial epileptic seizures. Electroencephalogr Cliil Neurophysiol 1984;57:295-302.

Brenner RP, Atkinson RA. Generalized paroxysmal fast activity: electroencephalographic and clinical studies. Ann Neurol 1982;11:386-90.

Burnstine TH, Vining EPG, Uematsu S, Lesser RP. Multifocal independent epileptiform discharges in children. Ictal correlates and surgical therapy. Neurology 1991 ;41: 1223-8.

Carranza EJ, Lombroso, CT, Mikati M, Helmers S, Holmes GH. Facilitation of infantile spasms by partial seizures. Epilepsia

Cooper R, Winter AL, Crow HJ, Walter WG. Comparison of subcortical, cortical and scalp activity using chronically in- dwelling electrodes in man. Electroencephalogr Clin Neuro-

Courjon J, Favel P. L’aspect Clectrographique des crises akin& tiques. Rev Neurol (Paris) 1961;105:211-2.

Donat JF, Wright FS. Seizures in series: similarities between seizures of the West and Lennox-Gastaut syndromes. Epi- lepsia 1991;32:504-9.

Druckman R, Chao D. Massive spasms in infancy and childhood. Epilepsia 1955;4:61-72.

Egli M , Mothersill I, O’Kane M, O’Kane F. The axial spasm- the predominant type of drop seizure in patients with secondary generalized epilepsy. Epilepsia 1985;26:401-15.

Fariello RG, Doro JM, Forster FM. Generalized cortical electrodecremental event. Clinical and neurophysiological observations in patients with dystonic seizures Arch Neurol 1979;

Feindel W, Gloor P. Comparison of electrographic effects of stimulation of the amygdala and brainstem reticular formation in cats. Electroencephalogr Clin Neurophysiol 1954:6: 389402.

Fisher RS, Niedermeyer E. Depth EEG studies in the Lennox- Gastaut syndrome. Clin Electroencephalographr 1987;18:

Fisher RS, Webber WRS, Lesser RP, Arroyo S, Uematsu S . High-frequency EEG activity at the start of seizures. J Clin Neurophysiol 1992;9:44 1-8.

Fromm GH. The brain-stem and seizures: summary and synthe-

1993;34:97-109.

physiol 1965 ; 18 :2 17-28.

36~285-91.

19 1-200.



sis. In: Fromm GH, Faingold CL, Browning RA, Burnham WM, eds. Epilepsy and the reticular formation: the role of the reticular core in convulsive seizures. New York: Alan R. Liss, 1987:203-18.

Fusco L, Iani C , Faedda MT, et al. Mesial frontal lobe epilepsy: a clinical entity not sufficiently described. J Epilepsy 1990;3: 123-35.

Gaily EK, Shewmon DA. Asymmetric infantile spasms. Epilep- sia 1992;33(suppl 3):6.

Gastaut H, Gastaut JL, Goncaves DS, Fernandez Sanchez GR. Relative frequency of different types of epilepsy: a study em- ploying the classification by the International League Against Epilepsy. Epilepsia 1975;16:457-61.

Gastaut H , Roger J, Ouahchi S, Timsit M, Broughton R. An electro-clinical study of generalized epileptic seizures of tonic expression. Epilepsia 1963;4: 15-44.

Gastaut H, Roger J, Soulayrol R, Tassinari CA, Regis H , Dravet C. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as “petit ma1 variant”) or Lennox syndrome. Epilepsia 1966;7: 139-79.

Gibbs FA, Gibbs EL, Lennox G. Electroencephalographic classification of epileptic patients and control subjects. Arch Neurol Psychiatry 1943;50:115.

Goldring S. The role of prefrontal cortex in grand ma1 convul- sion. Arch Neurol 1972;26: 109-19.

Harbaugh RE, Wilson DH. Telencephalic theory of generalized epilepsy: observations in split-brain patients. Neurosurgery

Hooshmand H, Morganroth R, Corredor C. Significance of focal and lateralized beta activity in the EEG. Clin Electroenceph- alographr 1980;11:140-4.

Jasper HH, Kershman J. Classification of the EEG in epilepsy. Electroencephalogr Clin Neurophysiol 1949: l(suppl 2): 123- 31.

Kellaway P, Hrachovy RA, Frost JD Jr, Zion T. Precise char- acterization and quantification of infantile spasms. Ann Neu- 1-01 1979;6:2 1 6 8 .

Kotagal P, Luders H, Morris HH, et al. Dystonic posturing in complex partial seizures of temporal lobe onset: a new lateralizing sign. Neurology 1989;39: 196201.

Kreindler A, Zuckermann E , Steriade M, Chimion D. Electro- clinical features of convulsions induced by stimulation of brainstem. J Neurophysiol 1958;21:430-6.

Lesser RP, Webber RS, Fisher RS. Design principles for com- puterized EEG monitoring. Electroencephalogr Clin Neuro- physiol 1992;82:23947.

Lesser RP, Hahn JF, Luders H, Rothner AD, Erenberg G. The use of chronic subdural electrodes for cortical mapping of speech. Epilepsia 1981;22:240.

Liang K-Y, Zeger SL. Longitudinal data analysis using generalized linear models. Biomefrika 1986;73: 13-22.

Lieb JP, Engel J Jr, Babb TL. Interhemispheric propagation time of human hippocampal seizures I. Relationship to surgical outcome. Epilepsia 1986;27:28693.

Ludwig BI, Ajmone-Marsan C, Van Buren JM. Depth and direct cortical recording in seizure disorders of extratemporal origin. Neurology l976;26: 1085-99.

Luders H, Lesser RP, Dinner DS, et al. Commentary: chronic intracranial recording and stimulation with subdural electrodes. In: Engel J, Jr, ed. Surgical treatment of the epilepsies, New York: Raven Press, 1987:297-321.

Marcus EM, Watson CW. Bilateral synchronous spike-wave electrographic patterns in the cat. Arch Neurol 1966;14:601- 10.

Marcus EM, Watson CW. Symmetrical epileptogenic foci in monkey cerebral cortex. Mechanisms of interaction and regional variations in capacity for synchronous discharges. Arch Neurol 1968;19:99-116.

Mazars G. Cingulate gyrus epileptogenic foci as an origin for generalized seizures. In: Gastaut H , Jasper H, Bancaud J, Waltregny A, eds. The physiopathogenesis of the epilepsies. Springfield, IL: Charles C Thomas, 1969: 18697.

Mazars Y. Interpretation du pheknomene d’extintion dans la

1982; 10:725-32.

phase initiale de crisis focales corticales. Rev Neurol (Paris? 1950;82:520-22.

Morris HH, Luders H. Electrodes. In: Gotman J, Ives JR, Gloor P, eds. Long-term monitoring in epilepsy EEG suppl. no. 37. New York: Elsevier Science Publishers B.V., 1985:3-26.

Morris HH, Estes ML, Luders H , et al. Electrophysiologic pathologic correlations in patients with complex partial seizures. Arch Neurol 1987a;44:703-8.

Morris HH, Dinner DS, Luders H, Wyllie E , Kramer R. Sup- plementary motor seizures: clinical and electroencephalographic findings. Neurology 1988;38: 1075-82.

Morris HH, Luders H, Dinner DS, Wyllie E, Krarner R. Sei- zures from the supplementary motor area: clinical and electroencephalographic features. Epilepsia 19876;28:623.

Moruzzi G, Magoun HW. Brain-stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophys- iol 1949;1:455-73.

Newton MR, Berkovic SF, Austin MC, Reutens DC, McKay WJ, Bladin PF. Dystonia, clinical lateralization, and regional blood flow changes in temporal lobe seizures. Neurology

Niedermeyer E. The electroencephalogram in the differential diagnosis of the Lennox-Gastaut syndrome. In: Niedermeyer E, Degen R, eds. The Lennox-Gastaut syndrome. New York: Alan R. Liss, 1988:177-220.

Nordgren RE, Reeves AG, Viguera AC, Roberts DW. Corpus callosotomy for intractable seizures in the pediatric age group. Arch Neurol 1991;48:364-72.

Oguni H, Olivier A, Anderrnann F, Comair J. Anterior callosotomy in the treatment of medically intractable epilepsies: a study of 43 patients with a mean follow-up of 39 months. Ann Neurol 1991 ;30:357-64.

Ottino CA, Meglio M, Rossi GF, Tercero E. An experimental study of the structures mediating bilateral synchrony of epileptic discharges of cortical origin. Epilepsia 1971 ; 12:299- 311.

Pazzaglia P, D’Alessandro R, Ambrosetto G, Lugaresi E. Drop attacks: an ominous change in the evolution of partial epilepsy. Neurology 1985;35: 1725-30.

Penfield W, Jasper H. Epilepsy and the functional anatomy of the human brain. Boston: Little Brown, 1954.

Penfield W, Welch K. The supplementary motor area in the cerebral cortex of man. Trans Am Neurol Assoc 1949;74:179- 84.

Penfield W, Welch K. The supplementary motor area of the cerebral cortex. Arch Neurol Psychiatry 1951 ;66:289-317.

Purves SJ, Wada JA, Woodhurst WB, et al. Results of anterior corpus callosum section in 24 patients with medically intractable seizures. Neurology 1988;38: 1196201.

Quesney LF, Gloor P. Generalized penicillin epilepsy in the cat: correlation between electrophysiological data and distribution of 14C-Penicillin in the brain. Epilepsia 1978; 19:35-45.

Rodin E, Onuma T, Wasson S, Porzak J. Mechanisms involved in grand ma1 seizures. Electroencephalogr Clin Neurophysiol

Rodin E, Smid N, Mason K. The grand ma1 pattern of Gibbs, Gibbs and Lennox. Electroencephalogr Clin Neurophysiol 1976;40: 101-6.

Rossi GF. Brain stem influences on EEG synchronization. Ex- perimental findings and observations in man. Acta Neurochir

Sammaritano M, Lotbiniere A, Andermann F, Olivier A, Gloor P, Quesney LF. False lateralization by surface EEG of seizure onset in patients with temporal lobe epilepsy and gross focal cerebral lesions. Ann Neurol 1987;21:361-9.

Smith SJM, Andermann F , Villemure J-G, Rasmussen TB, Quesney LF. Functional hemispherectomy: EEG findings, spiking from isolated brain postoperatively, and prediction of outcome. Neurology 1991;41: 17904.

Tassinari CA, Ambrosetto G. Tonic seizures in the Lennox- Gastaut syndrome: Semiology and differential diagnosis. In:

1992 ;42:371-7.

1969 ;94: 333-5.

1965 ; 13~257-88.


ORIGIN OF DEP 987

Niedermeyer E, Degen R, eds. The Lennox-Gastaut syndrome, New York: Alan R. Liss, 1988:109-24.

Tukel K, Jasper H. The electroencephalogram in parasagittal lesions. Electroencephalogr Clin Neurophysiol 1952;4:481- 94.

Wagner HR, Feeney DM, Gullotta FP, Cote IL. Suppression of cortical epileptiform activity by generalized and localized ECoG desynchronization. Electroencephalogr Clin Neuro- physiol 1975 ;39:499-506.

Waterman K, Purves SJ, Kosaka B, Strauss E, Wada JA. An epileptic syndrome caused by mesial frontal lobe seizure foci. Neurology 1987;37:57?-82.

Weilleux F , Saint-Hilarie JM, Giard N, et al. Seizures of the human medial frontal lobe. In: Chauvel P, Delgado-Escueta AV, Halgren E , Bancaud J, eds. Frontal lobe seizures and

epilepsies. New York: Raven Press, 1992:245-55. (Advances in Neurology; vol. 57).

Wiesendanger M. Recent developments in studies of the supplementary motor area of primates. Rev Physiol Biochem Phar- macol 1986; 103: 187-216.

Wieser HG, Swartz BE, Delgado-Escueta AV, et al. Differenti- ating frontal lobe seizures from temporal lobe seizures. In: Chauvel P, Delgado-Escueta AV, Halgren E , Bancaud J , eds. Frontal lobe seizures and epilepsies. New York: Raven Press, 1992:267-85. (Advances in Neurology, vol. 57).

Wyllie E, Luders H, Morris HH, Lesser RP, Dinner DS. The lateralizing significance of versive head and eye movements during epileptic seizures. Neurology 1986;36:606-11.

Yaqub BA. Electroclinical seizures in the Lennox-Gastaut syndrome. Epilepsia 1993;34: 120-7.


Documents

Clinical and Electroencephalographic Evidence for Sites of Origin of Seizures with Diffuse Electrodecremental Pattern