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Effects of anterior corpus callosotomy on the electroencephalogram
/ Epilzpsy 0 1989
1989;2:7>81
Demos Publications
Effects of Anterior Corpus Callosotomy on the Electroencephalogram ‘William
E. Goldberg,
‘Gregory
L. Holmes, and ‘Jodie Gould
In order to determine if the EEG is predictive of outcome following anterior corpus callosotomy, preoperative and postoperative EEGsof 30 patients who underwent the procedure were retrospectively reviewed. Twenty-eight of the 30 patients (93.3%) had generalized discharges on the preoperative EEG compared to only 9 of 30 patients (30.0%) on the postoperative EEGs. Whereas the number of epileptiform foci increased, the number of epileptiform discharges decreased on the postoperative EEG. There was no relationship between outcome and presence or absence of generalized discharges, number of epileptic foci, and frequency of postoperative epileptiform activity. Neither the preoperative nor postoperative EEG is a useful predictor of outcome following anterior corpus callosotomy. Key Words: Anterior corpus callosotomy-Epileptiform activity-Electroencephalography.
In 1940, the first forebrain commissurotomies for intractable seizures were reported by Van Wagenen and Heren (1). The goal of their operation, as it is today, was to limit the epileptogenic discharge from spreading to the contralateral hemisphere. In recent years, numerous reports of corpus callosotomy for intractable seizures have been published (2-14). This increased interest in the procedure is attributable to the reported clinical benefit in some patients. Despite the increased reporting of outcome in these patients, there has yet to be a consensus regarding which patients are likely to benefit from the procedure. For example, minimal attention has been paid to the possibility that the pre- and postoperative EEGs may have some predictive value in determining outcome. This is unfortunate, since in other types of surgical procedures for epilepsy, e.g., temporal
From the ‘Department of Neurology, Medical College of Georgia, Augusta, GA, and *The Children’s Hospital, Harvard Medical School, Boston, MA, U.S.A. Address correspondence and reprint requests to Dr. G. L. Holmes at Clinical Neurophysiology Laboratory, The Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, U.S.A.
lobectomies and hemispherectomies, the EEG is widely used in both the preoperative and postoperative evaluation of patients. Changes in the EEG following corpus callosotomy may also offer clues into the pathophysiology of seizures in these patients. If the primary purpose of the anterior corpus callosotomy is to prevent or reduce secondary generalization, it is logical to assume that the procedure should decrease the number of generalized discharges as well as increase the number of focal discharges. Conversely, if the anterior corpus callosotomy offers benefits other than decreasing the generalization of epileptiform discharges, reduction of generalized EEG discharges may not be correlated with outcome. In this study, we have retrospectively reviewed and compared the pre- and postoperative EEGs of 30 patients who underwent anterior two-thirds corpus callosum division. The effect of anterior corpus callosotomy on background activity and distribution, type, and frequency of epileptiform discharges was compared in the pre- and postoperative EEG. In addition, we attempted to determine if there were any preoperative or postoperative findings that were correlated with prognosis. ] EPILEPSY, VOL. 2, NO. 2, 1989
73
W. E. GOLDBERG
ET AL.
Methods . The last 30 consecutive patients who underwent corpus callosotomy for intractable seizures and who had a minimum of 12 months’ follow-up at the Medical College of Georgia were reviewed. As previously described (ll), the following criteria were required before patients were considered candidates for an anterior corpus callosotomy: 1. The presence of intractable, generalized tonicclonic, atonic, tonic, atypical absence, myoclonic, or partial complex seizures was necessary. Seizure frequency or character had to adversely affect daily living. 2. A minimum of 2 years of unsuccessful treatment with antiepileptic drugs was required. All patients received trials of carbamazepine, phenytoin, phenobarbital, and valproic acid. Some patients were also previously treated with the ketogenic diet, investigational drugs, biotin, pyridoxine, and steroids such as prednisone and adrenocorticotropin hormone. 3. Patients were excluded as candidates for focal ablative surgery. This eliminated patients with clearly focal EEG epileptiform discharges or focal structural lesions. 4. A potential for functional improvement with reduction or elimination of seizure frequency was required. Whereas the patients with mental retardation were not excluded, children who were severely mentally retarded and nonambulatory because of severe cerebral palsy were excluded. 5. Patients were eliminated from consideration if
Figure
74
1.
Postoperative
1 EPILEPSY, VOL 2, NO. 2, 1989
they had a medical condition that prohibited a lengthy surgical procedure. Each patient was admitted to the hospital for a preoperative evaluation, including history and physical examination, computerized tomography (CT) with contrast enhancement or magnetic resonance imaging (MRI), and when possible, neuropsychological evaluation. Cerebral angiography was performed in all patients. When possible, intracarotid amytal examination of language representation and memory function was performed. Long-term simultaneous EEG and video recording was performed on all patients. Scalp electrodes were placed according to the lo-20 International System of electrode placement. Typically, the patients were monitored until they had at least three of their most disabling habitual seizures. Seizures were classified according to the International Classification of Epileptic Seizures based on review of videotaped attacks or a family description of seizures not recorded during the monitoring sessions. Anterior corpus callosotomy was performed in all cases using previously described techniques (9-11). All patients were followed by one of the staff neurologists as outpatients, and antiepileptic drugs (AEDs) were adjusted by the physician as necessary. As a general rule, no attempt was made to reduce AEDs during the first postoperative year. Forty percent of the patients had postoperative MRI scans, which in all cases confirmed the intended procedure (Figs. 1 and 2). Follow-up seizure frequency was determined by telephone or personal interviews.
MRZ scans demonstrating
a section of the anterior corpus callosum.
Outcome with respect to seizures was classified according to the criteria proposed by Engel (15): Class I, seizure free; Class II, rare seizures (
multiple spike-and-wave, and multiple spike activity; (c) location of epileptiform activity-generalized, bifrontal, lateralized, or focal; and (d) frequency of epileptiform discharges per 120-s segment awake recording. Records were interpreted without knowledge of the patient’s clinical outcome.
Results Significant changes were noted between the preand postoperative EEGs. The most dramatic changes noted concerned the location, symmetry, morphology, and synchrony of the epileptiform activity. In addition, changes in background activity were also noted. J EPILEPSY, VOL. 2, NO. 2, 1989
75
h! E. GOLDBERG
ET AL.
Table 1. . Location Patient 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
of epileptiform
Focal”
discharges
Generalized
123478 , , I I -
L&8 1,2,3 7,8 3‘4 2 4‘2 7,3,1
48 WN 2,4 385 2
“1, left frontal; 2, right frontal; right parietal-central. bValues are symmetric except ‘1, paroxysmal slow; 2, sharp <2 s; b, multiple discharges of
Pre-corpus callosotomy EEGs
+ + + + + + + + + L>R + + + L>R + + + + L>R + + + + + L>R R>L + 3, left temporal;
Bifrontal
+ + R>L L>R + L>R R>L -
+ + R>L L>R L + + -
4, right temporal;
Most of the preoperative EEGs had diffuse slowing (4-7 Hz) of background activity during the awake recordings. Whereas there was no demonstrable change in frequency between the pre- and postoperative EEGs, we found that the background was asymmetrical in 12 of the 29 (41.4%) awake postoperative EEGs (Table 1).
activity
Twenty-eight of the 30 patients (93.3%) had generalized discharges on the preoperative EEG. On the 76
Background activityh
11 4 3
4-5 4-6 4-6 5-6 6-7 4-5 6-8 8 6-8 5-7(A) 5-8 5 5 6-8 6-7 7 6 6 7 7-8 7 7 5 5-6 6-7
5, left occipital;
Type of epileptiform discharges’
12 3a 3b
12 2,4 3b 5 3bb l-3 l-3 3bb 1,3,4 1,3 3,4 I,4 3
23 I,4
23 1,4a 14
23 l-3 14 14
6(A)
22
6 5 4 6
l-3 14 2 l-3
6, right occipital;
7, left parietal-central;
8,
when followed by (A) for asymmetric. waves; 3, spike-and-wave; 4, multiple spikes; 5, ~-HZ spike-and-wave; a, single discharge 2-5 s with a pause followed by another discharge; bb, multiple discharges >5 s.
Background
Epileptiform
Number of discharges
1 EPILEPSY, VOL 2, NO. 2, 1989
postoperative EEG, only 9 of 30 patients (30.0%) continued to have generalized discharges recorded (Table 2). We divided the group with generalized epileptiform activity on their preoperative EEGs into three categories: Group A (n=8) included patients with generalized spike-and-wave or sharp-and-slow-wave discharges only. Group B (n=ll) included patients with generalized discharges with a distinct anterior voltage predominance. We further subdivided Group B into records with symmetrical spike-and-wave discharges between the two hemispheres (n=4) and records with asymmetrical spike-and-wave activity (n=7). Group C (n=9) included patients with both generalized spike-and-wave or sharp-and-slow-wave
ANTERIOR
Table 2.
CORPUS CALLOSOTOMY
AND THE EEG
Postoperative EEGs
Location of epileptiform discharges Patient 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
Focal 2,3 1~3
211 LZ4,8 l,Z3,4,6,8 L2,3,4 X44,1 2 1,3,4,7 1,2,3/I
12
1,3
2,4 2,4 1,2,3
Generalized + + + R>L R>L + R>L R>L + -
Frontal
Number of discharges
R>L L>R R>L L>R L<&>R” + + L>R R>L L>R L>R R>L L>R R>L R>L R>L +
12 4-5 4
Background activityb
-
4-5 66 3-5 6-7 4W
4
5-W)
8
5-6(A) 8 5 5 5-6
664) 6-7 7 6 6
6(A) 7 7(A) 7W
f&4) 544)
Type of epileptiform discharges 3a 3b 1 4(R > L) 3(L > R) lt3
S(irreg) 1 12 1 1 1,3 3‘4 1,4
1 3
1 2,3 3 14
1 23 12
7 7 4
7W 7W
14 2,3
6(I) 5 4
L2,3 12
f&4)
1,2,3
23
Outcome IV III IV IV IV II III IV III II IV IV IV III III III III III III IV IV IV IV III IV IV IV III IV
Legend same as Table 1. “Shifting foci. “Values are symmetric except where followed by (A) for asymmetric or (I) for irregular. discharges as well as focal or multifocal spikes or sharp waves (see Table 3). Following anterior corpus callosotomy, there was a tendency for generalized discharges to become either multifocal or bifrontal. Only one of eight patients (12.5%) with generalized discharges only (Group A) had generalized discharges on the postoperative EEG. This particular patient was unusual in that his primary seizure type prior to the anterior corpus callosotomy was absence. His preoperative EEG had rhythmic ~-HZ spike-and-wave activity with bilateral synchrony. His postoperative EEG was characterized by irregular and asynchronous generalized discharges with a frequency varying between 2.5 and 3.5 Hz. In Group B (generalized discharges with anterior voltage predominance), four patients (36.6%) con-
tinued to have generalized discharges and 10 patients (90.9%) had bifrontal discharges. Three patients developed multifocal discharges on the postoperative EEG that were not present before surgery. Group C was unique preoperatively because they had a greater variety of discharge types. These EEGs had generalized discharges, generalized discharges with an anterior voltage predominance, and multifocal discharges. After corpus callosotomy, three patients continued to have generalized discharges (33.3%). Three patients (33.3%) had an increase in the number of foci present, whereas four patients (44.4%) had a decrease in number of foci. Multifocal epileptiform discharges were present in 11 of 30 (36.7%) of the preoperative EEGs and 14 of 30 of the postoperative EEGs (46.7%). Four patients ] EPILEPSY, VOL. 2, NO. 2, 1989
77
W. E. GOLDBERG
ET AL.
Table 3.
of preoperative
Comparison
and postoperative Group
Group Preoperative classification Number of patients Postoperative classification Generalized, symmetric Generalized, asymmetric Multifocal Bifrontal, symmetric Bifrontal, R > L Bifrontal, L > R No change No discharges recorded “Patient
number
A
Symmetric
8
4
l(8)
1(27) 0 2(10,17) 1wJ) 3(7,17,27) l(7) 0 0
0
4(2,15,20,29) l(9)
2CW) 1w 163) 1U1)
EEGs”
B Asymmetric
7 2(13,23) 1(25) 3(13,23,24) 0
9 1(14) 3(16,19,26) 4(16,21,26,30) l(30)
WX’)
l(W
2(6,24) 0
2(14,21) 0 2(12,18)
1w
C
in parentheses.
(13.3%) had three or more epileptiform foci on their preoperative EEGs compared to eight patients (26.7%) on their postoperative recordings. Eight patients (26.6%) had a decrease in the number of epileptiform foci from their preoperative to postoperative EEGs, whereas 12 patients (40.0%) had an increase in number of foci. Examples of EEGs are demonstrated in the figures. Figure 2A demonstrates the preoperative finding of
generalized, low-amplitude spike-and-wave discharges. The postoperative EEG (Fig. 28) demonstrates higher amplitude, right-sided spike-and-wave activity. Figure 3A demonstrates a segment of recording demonstrating bifrontal spike-and-wave activity, whereas, on the postoperative EEG, left frontal spike-and-wave activity is the primary finding (Fig. 38). Figure 4A demonstrates an irregular discharge of asymmetrical generalized spike-and-wave
Figure 3. The preoperative recording demonstrates a segment showing bifrontal spike-and-wave erative EEG (B), left frontal spike-and-wave activity is the primary finding.
78
Group
1 EPILEPSY, VOL 2, NO. 2, 1989
activity (A), whereas on the postop
ANTERIOR
Figure
4.
po&perative
CORPUS
CALLOSO’TOMY
The vreopemtive EEG demonstrates an irrexular discharge of asymnetricnl generalized spike-and-wave EEb zubs mrked by multifocal epileptifor% activity. B demomtrates left-sided spikes.
activity on the preoperative EEG. The postoperative EEG was marked by multifocal epileptiform activity. Figure 4B demonstrates left temporal spikes.
Number of epileptiform
discharges
Eleven patients (36.7%) had a decrease in the number of epileptiform discharges, whereas four patients (13.3%) had an increase in the number of epileptiform discharges from the preoperative to postoperative EEG. The number of epileptiform discharges on the preoperative EEG was significantly more than on the postoperative EEG (paired t test = 3.494; p = 0.002, two-tailed).
Outcome The outcome of the patients is listed in Table 2. The follow-up period ranged from 12 to 48 months (mean, 25.3 months). Fourteen patients (46.7%) were either seizure-free (l), had rare seizures (2), or had a worthwhile improvement (ll), whereas 16 (53.3%) had no significant improvement. There was no statistically significant relationships among Groups A, B, and C and outcome (KruskalWallis = 3.003; p = 0.223). There was no difference in outcome in patients who continued to have gen-
AND THE EEG
activity (A).
The
eralized discharges on their postoperative EEG compared to those who did not (Kruskal-Wallis = 0.330; p = 0.572). Patients with an increase in number of epileptiform foci from the preoperative to postoperative EEG did not differ significantly in outcome from patients with a decrease in foci (Kruskal-Wallis = 0.126; p = 0.722). There were also no differences in outcome between patients who had a decreased number of epileptiform discharges from the preoperative to postoperative EEG compared to patients with an increase in epileptiform activity (KruskalWallis = 0.059; p = 0.808).
Discussion There is now a considerable amount of animal evidence demonstrating that the corpus callosum is an important conduit of epileptiform activity from one hemisphere to the other. As early as 1940, Erickson (16) proposed that the corpus callosum was responsible for the interhemispheric spread of epileptic discharges. This was followed by the work of Kopeloff et al. (17), who demonstrated that section of the corpus callosum in animals prevented the spread of epileptiform activity from one hemisphere to the other. Musgrave and Gloor (18) studied the role of the
I EPILEPSY, VOL. 2, NO. 2, 1989
i’g
W. E. GOLDBERG
ET AL.
corpus callosum in bilateral synchrony of epileptiform discharges in four groups of cats with penicillinGroup A underwent complete induced epilepsy: section of the corpus callosum and anterior commissure; Group B underwent division of the massa intermedia alone; Group C underwent partial section of the corpus callosum; and in Group D, cortex was severed from all its subcortical inputs without disturbing its connections with the opposite hemisphere through the corpus callosum. In intact animals, penicillin induced bilateral epileptiform discharges. In animals with a complete section of the corpus callosum, the bilateral synchrony of the spike-andwave discharge was abolished; in the group with partial section of the corpus callosum, the bisynchrony was impaired. The other two groups with an intact corpus callosum continued to have bilateral synchrony of the epileptiform activity. These results demonstrated the key role the corpus callosum plays in the bisynchrony of epileptiform discharges. In general, our results support the work in animals, demonstrating that generalized discharges are reduced in patients following corpus callosum division. Whereas almost all of our patients had generalized discharges before sectioning, only eight continued to have generalized discharges after the operation. In the other patients, bifrontal or multifocal discharges replaced the generalized discharges. There was also a trend for epileptiform discharges to become asymmetrical and/or asynchronous. Like the epileptiform activity, background activity frequently became asymmetrical following callosotomy. These findings are similar to those of other authors reporting changes in the EEG following corpus callosotomy (5,7,12-14, 19-21). Wilson et al. (12) reported that bilateral, synchronous, spike, or spikeand-wave discharges became asynchronous after complete division of the corpus callosum but noted that lateralization of the discharges did not correlate with outcome. Geoffroy and colleagues (13), in a study of nine patients, reported that patients with lateralized EEG foci did better in the postoperative period than patients with diffuse abnormalities. Gates et al. (19) reported that the corpus callosotomy reduced the number of generalized epileptiform discharges and correlated this EEG finding with a decrease in generalized seizures in six patients. A significant difference in total number of epileptiform discharges from the preoperative to postoperative EEG was not noted. Spencer et al. (5), in a study of 22 patients analyzed 2 or more years after corpus callosotomy, reported better outcomes among patients with secondary bilateral synchrony or unilateral epileptiform activity than those with bilateral independent EEG 130 ] EPILEPSY, VOL 2, NO. 2, 1989
paroxysms. However, none of the EEG findings was statistically significant in predicting outcome. In a review of reported EEG changes after corpus callosotomy, Spencer (7) found that total or partial section of the corpus callosum and hippocampal commissure with or without the anterior commissure and fomix lead to a “lasting and marked disruption” of bilateral synchronous spike-and-wave discharges in approximately half of the patients. The finding that some but not all of the generalized discharges abated following anterior corpus callosotomy suggests that epileptiform discharges may spread from one hemisphere to the other through structures other than the anterior corpus callosum. In a recent review, Spencer (7) elegantly reviewed the interhemispheric connections through which epileptiform discharges spread. As pointed out by Spencer (7), subcortical relays may be utilized in the contralateral spread of epileptiform discharges originating in the neocortex. Whereas the corpus callosum appears to be the primary pathway in the generalization of epileptiform discharges, subcortical spread may be of equal or more importance in some patients. The findings on the preoperative EEG and on the postoperative EEG were not predictive of outcome. Patients who continued to have generalized discharges on their postoperative EEG did not fare any differently from patients without postcallosotomy generalized discharges. In addition, neither number of epileptiform discharges nor number of epileptiform foci on the postoperative EEG was related to outcome. These findings demonstrate that eliminating generalized discharges or reducing the number of foci is not necessary for improvement in seizure frequency. We conclude that, at the present time, the EEG is of no value in predicting outcome following anterior corpus callosotomy.
References 1. Van Wagenen WI’, Herren RY. Surgical division of commissural pathways in the corpus callosum. Relation to spread of an epileptic attack. Arch Neural Psychol 1940;44:740-59. 2. Wilson DH, Reeves A, Gazzaniga M, Culver C. Cere-
bral commissurotomy for control of intractable seizures. Neurology 1977;27:708-15. 3. Wilson DH, Reeves AC, Gazzaniga AM. Division of the corpus callosum for uncontrolled epilepsy. Neurology 1978;28:649-53. 4. Murro AM, Flanigin HF, Gallagher BB, King DW, Smith JR. Corpus callosotomy for the treatment of intractable epilepsy. Epilepsy Res 1988;2:44-50. 5. Spencer SS, Spencer DD, Williamson PD, Sass K, Novelly RA, Mattson RH. Corpus callosotomy for epilepsy. I. Seizure effects. Neurology 1988;38:19-24.
ANTERIOR 6. Wyllie E. Corpus callosotomy for intractable generalized epilepsy. 1 Pediatr 1988;113:255-61. 7. Spencer SS. Corpus callosum section and other disconnection procedures for medically intractable epilepsy. Epilepsia 1988;29(suppl 2):S85-S99. 8. Spencer SS, Gates JR Reeves AR, Spencer DD, Maxwell RE, Roberts D. Corpus callosum section. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:425-44. 9. Flanigin HF, King DW, Gallagher BB. Surgical treatment of epilepsy. In: Pedley T, Meldrum BS, eds. Recent advmces in epilepsy, vol. 2. Edinburgh: Churchill-Livingstone, 1984:297-339. 10. Smith JR Flanigin HF, King DW, Gallagher BB, Loring DW, Meador KJ, Murro AM. The present status of the surgical management of epilepsy. South Med J (in press). 11. Makari GS, Holmes CL, Murro AM, Smith JR, Flanigin HF, Cohen MJ, Huh K, Gallagher BS, Ackell AB, Campbell R, King DW. Corpus callosotomy for the treatment of intractable epilepsy in children. j Epilepsy 1989;2:1-7. 12. Wilson DH, Reeves AG, Gazzaniga MS. “Central” commissurotomy for intractable generalized epilepsy: series two. Neurology 1982;32:687-97. 13. Geoffroy G, Lassonde M, Delisle F, Decarie M. Corpus callosotomy for control of intractable epilepsy in children. Neurology 1983;33:891-97. 14. Rayport M, Ferguson SM, Corrie WS. Outcomes and
15. 16.
17.
18.
19. 20.
21.
CORPUS CALLOSOTOMY
AND THE EEG
indications of corpus callosum section for intractable seizure control. Appl Neurophysiol 1983;46:47-51. Engel, J Jr. Outcome with respect to epileptic seizures. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:55>71. Erickson TC. Spread of the epileptic discharge. An experimental study of the after-discharge induced by electrical stimulation of the cerebral cortex. Arch Neural Psycho1 1940;43:429-52. Kopeloff N, Kennard MA, Pacella BL, Kopeloff LM, Chusid JG. Section of corpus callosum in experimental epilepsy in the monkey. Arch Neural Psycho1 1950;63:719-27. Musgrave J, Gloor P. The role of the corpus callosum in bilateral interhemispheric synchrony of spike and wave discharge in feline generalized penicillin epilepsy. Epilepsia 1980;21:369-78. Gates JR Leppik IE, Yap J, Gumnit RJ. Corpus callosotomy: clinical and electroencephalographic effects. Epilepsia 1984;25:308-16. Huck FR, Radvany J, Avila JO, Fires de Camargo P, Marino R Jr, Ragazzo PC, Riva D, Arlant P. Anterior callosotomy in epileptics with multiform seizures and bilateral synchronous spike and wave EEG pattern. Acta Neurochir [Suppl] (Wein) 1980;30:127-35. Roberts DW, Allen CD, Allen AH, Reeves AG. Depth electrode recording in patients undergoing corpus callosotomy for intractable epilepsy. Appl Neurophysiol 1983;46:26-32.
] EPILEPSY, VOL. 2, NO. 2, 1989
81
1989;2:7>81
Demos Publications
Effects of Anterior Corpus Callosotomy on the Electroencephalogram ‘William
E. Goldberg,
‘Gregory
L. Holmes, and ‘Jodie Gould
In order to determine if the EEG is predictive of outcome following anterior corpus callosotomy, preoperative and postoperative EEGsof 30 patients who underwent the procedure were retrospectively reviewed. Twenty-eight of the 30 patients (93.3%) had generalized discharges on the preoperative EEG compared to only 9 of 30 patients (30.0%) on the postoperative EEGs. Whereas the number of epileptiform foci increased, the number of epileptiform discharges decreased on the postoperative EEG. There was no relationship between outcome and presence or absence of generalized discharges, number of epileptic foci, and frequency of postoperative epileptiform activity. Neither the preoperative nor postoperative EEG is a useful predictor of outcome following anterior corpus callosotomy. Key Words: Anterior corpus callosotomy-Epileptiform activity-Electroencephalography.
In 1940, the first forebrain commissurotomies for intractable seizures were reported by Van Wagenen and Heren (1). The goal of their operation, as it is today, was to limit the epileptogenic discharge from spreading to the contralateral hemisphere. In recent years, numerous reports of corpus callosotomy for intractable seizures have been published (2-14). This increased interest in the procedure is attributable to the reported clinical benefit in some patients. Despite the increased reporting of outcome in these patients, there has yet to be a consensus regarding which patients are likely to benefit from the procedure. For example, minimal attention has been paid to the possibility that the pre- and postoperative EEGs may have some predictive value in determining outcome. This is unfortunate, since in other types of surgical procedures for epilepsy, e.g., temporal
From the ‘Department of Neurology, Medical College of Georgia, Augusta, GA, and *The Children’s Hospital, Harvard Medical School, Boston, MA, U.S.A. Address correspondence and reprint requests to Dr. G. L. Holmes at Clinical Neurophysiology Laboratory, The Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, U.S.A.
lobectomies and hemispherectomies, the EEG is widely used in both the preoperative and postoperative evaluation of patients. Changes in the EEG following corpus callosotomy may also offer clues into the pathophysiology of seizures in these patients. If the primary purpose of the anterior corpus callosotomy is to prevent or reduce secondary generalization, it is logical to assume that the procedure should decrease the number of generalized discharges as well as increase the number of focal discharges. Conversely, if the anterior corpus callosotomy offers benefits other than decreasing the generalization of epileptiform discharges, reduction of generalized EEG discharges may not be correlated with outcome. In this study, we have retrospectively reviewed and compared the pre- and postoperative EEGs of 30 patients who underwent anterior two-thirds corpus callosum division. The effect of anterior corpus callosotomy on background activity and distribution, type, and frequency of epileptiform discharges was compared in the pre- and postoperative EEG. In addition, we attempted to determine if there were any preoperative or postoperative findings that were correlated with prognosis. ] EPILEPSY, VOL. 2, NO. 2, 1989
73
W. E. GOLDBERG
ET AL.
Methods . The last 30 consecutive patients who underwent corpus callosotomy for intractable seizures and who had a minimum of 12 months’ follow-up at the Medical College of Georgia were reviewed. As previously described (ll), the following criteria were required before patients were considered candidates for an anterior corpus callosotomy: 1. The presence of intractable, generalized tonicclonic, atonic, tonic, atypical absence, myoclonic, or partial complex seizures was necessary. Seizure frequency or character had to adversely affect daily living. 2. A minimum of 2 years of unsuccessful treatment with antiepileptic drugs was required. All patients received trials of carbamazepine, phenytoin, phenobarbital, and valproic acid. Some patients were also previously treated with the ketogenic diet, investigational drugs, biotin, pyridoxine, and steroids such as prednisone and adrenocorticotropin hormone. 3. Patients were excluded as candidates for focal ablative surgery. This eliminated patients with clearly focal EEG epileptiform discharges or focal structural lesions. 4. A potential for functional improvement with reduction or elimination of seizure frequency was required. Whereas the patients with mental retardation were not excluded, children who were severely mentally retarded and nonambulatory because of severe cerebral palsy were excluded. 5. Patients were eliminated from consideration if
Figure
74
1.
Postoperative
1 EPILEPSY, VOL 2, NO. 2, 1989
they had a medical condition that prohibited a lengthy surgical procedure. Each patient was admitted to the hospital for a preoperative evaluation, including history and physical examination, computerized tomography (CT) with contrast enhancement or magnetic resonance imaging (MRI), and when possible, neuropsychological evaluation. Cerebral angiography was performed in all patients. When possible, intracarotid amytal examination of language representation and memory function was performed. Long-term simultaneous EEG and video recording was performed on all patients. Scalp electrodes were placed according to the lo-20 International System of electrode placement. Typically, the patients were monitored until they had at least three of their most disabling habitual seizures. Seizures were classified according to the International Classification of Epileptic Seizures based on review of videotaped attacks or a family description of seizures not recorded during the monitoring sessions. Anterior corpus callosotomy was performed in all cases using previously described techniques (9-11). All patients were followed by one of the staff neurologists as outpatients, and antiepileptic drugs (AEDs) were adjusted by the physician as necessary. As a general rule, no attempt was made to reduce AEDs during the first postoperative year. Forty percent of the patients had postoperative MRI scans, which in all cases confirmed the intended procedure (Figs. 1 and 2). Follow-up seizure frequency was determined by telephone or personal interviews.
MRZ scans demonstrating
a section of the anterior corpus callosum.
Outcome with respect to seizures was classified according to the criteria proposed by Engel (15): Class I, seizure free; Class II, rare seizures (
multiple spike-and-wave, and multiple spike activity; (c) location of epileptiform activity-generalized, bifrontal, lateralized, or focal; and (d) frequency of epileptiform discharges per 120-s segment awake recording. Records were interpreted without knowledge of the patient’s clinical outcome.
Results Significant changes were noted between the preand postoperative EEGs. The most dramatic changes noted concerned the location, symmetry, morphology, and synchrony of the epileptiform activity. In addition, changes in background activity were also noted. J EPILEPSY, VOL. 2, NO. 2, 1989
75
h! E. GOLDBERG
ET AL.
Table 1. . Location Patient 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
of epileptiform
Focal”
discharges
Generalized
123478 , , I I -
L&8 1,2,3 7,8 3‘4 2 4‘2 7,3,1
48 WN 2,4 385 2
“1, left frontal; 2, right frontal; right parietal-central. bValues are symmetric except ‘1, paroxysmal slow; 2, sharp <2 s; b, multiple discharges of
Pre-corpus callosotomy EEGs
+ + + + + + + + + L>R + + + L>R + + + + L>R + + + + + L>R R>L + 3, left temporal;
Bifrontal
+ + R>L L>R + L>R R>L -
+ + R>L L>R L + + -
4, right temporal;
Most of the preoperative EEGs had diffuse slowing (4-7 Hz) of background activity during the awake recordings. Whereas there was no demonstrable change in frequency between the pre- and postoperative EEGs, we found that the background was asymmetrical in 12 of the 29 (41.4%) awake postoperative EEGs (Table 1).
activity
Twenty-eight of the 30 patients (93.3%) had generalized discharges on the preoperative EEG. On the 76
Background activityh
11 4 3
4-5 4-6 4-6 5-6 6-7 4-5 6-8 8 6-8 5-7(A) 5-8 5 5 6-8 6-7 7 6 6 7 7-8 7 7 5 5-6 6-7
5, left occipital;
Type of epileptiform discharges’
12 3a 3b
12 2,4 3b 5 3bb l-3 l-3 3bb 1,3,4 1,3 3,4 I,4 3
23 I,4
23 1,4a 14
23 l-3 14 14
6(A)
22
6 5 4 6
l-3 14 2 l-3
6, right occipital;
7, left parietal-central;
8,
when followed by (A) for asymmetric. waves; 3, spike-and-wave; 4, multiple spikes; 5, ~-HZ spike-and-wave; a, single discharge 2-5 s with a pause followed by another discharge; bb, multiple discharges >5 s.
Background
Epileptiform
Number of discharges
1 EPILEPSY, VOL 2, NO. 2, 1989
postoperative EEG, only 9 of 30 patients (30.0%) continued to have generalized discharges recorded (Table 2). We divided the group with generalized epileptiform activity on their preoperative EEGs into three categories: Group A (n=8) included patients with generalized spike-and-wave or sharp-and-slow-wave discharges only. Group B (n=ll) included patients with generalized discharges with a distinct anterior voltage predominance. We further subdivided Group B into records with symmetrical spike-and-wave discharges between the two hemispheres (n=4) and records with asymmetrical spike-and-wave activity (n=7). Group C (n=9) included patients with both generalized spike-and-wave or sharp-and-slow-wave
ANTERIOR
Table 2.
CORPUS CALLOSOTOMY
AND THE EEG
Postoperative EEGs
Location of epileptiform discharges Patient 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
Focal 2,3 1~3
211 LZ4,8 l,Z3,4,6,8 L2,3,4 X44,1 2 1,3,4,7 1,2,3/I
12
1,3
2,4 2,4 1,2,3
Generalized + + + R>L R>L + R>L R>L + -
Frontal
Number of discharges
R>L L>R R>L L>R L<&>R” + + L>R R>L L>R L>R R>L L>R R>L R>L R>L +
12 4-5 4
Background activityb
-
4-5 66 3-5 6-7 4W
4
5-W)
8
5-6(A) 8 5 5 5-6
664) 6-7 7 6 6
6(A) 7 7(A) 7W
f&4) 544)
Type of epileptiform discharges 3a 3b 1 4(R > L) 3(L > R) lt3
S(irreg) 1 12 1 1 1,3 3‘4 1,4
1 3
1 2,3 3 14
1 23 12
7 7 4
7W 7W
14 2,3
6(I) 5 4
L2,3 12
f&4)
1,2,3
23
Outcome IV III IV IV IV II III IV III II IV IV IV III III III III III III IV IV IV IV III IV IV IV III IV
Legend same as Table 1. “Shifting foci. “Values are symmetric except where followed by (A) for asymmetric or (I) for irregular. discharges as well as focal or multifocal spikes or sharp waves (see Table 3). Following anterior corpus callosotomy, there was a tendency for generalized discharges to become either multifocal or bifrontal. Only one of eight patients (12.5%) with generalized discharges only (Group A) had generalized discharges on the postoperative EEG. This particular patient was unusual in that his primary seizure type prior to the anterior corpus callosotomy was absence. His preoperative EEG had rhythmic ~-HZ spike-and-wave activity with bilateral synchrony. His postoperative EEG was characterized by irregular and asynchronous generalized discharges with a frequency varying between 2.5 and 3.5 Hz. In Group B (generalized discharges with anterior voltage predominance), four patients (36.6%) con-
tinued to have generalized discharges and 10 patients (90.9%) had bifrontal discharges. Three patients developed multifocal discharges on the postoperative EEG that were not present before surgery. Group C was unique preoperatively because they had a greater variety of discharge types. These EEGs had generalized discharges, generalized discharges with an anterior voltage predominance, and multifocal discharges. After corpus callosotomy, three patients continued to have generalized discharges (33.3%). Three patients (33.3%) had an increase in the number of foci present, whereas four patients (44.4%) had a decrease in number of foci. Multifocal epileptiform discharges were present in 11 of 30 (36.7%) of the preoperative EEGs and 14 of 30 of the postoperative EEGs (46.7%). Four patients ] EPILEPSY, VOL. 2, NO. 2, 1989
77
W. E. GOLDBERG
ET AL.
Table 3.
of preoperative
Comparison
and postoperative Group
Group Preoperative classification Number of patients Postoperative classification Generalized, symmetric Generalized, asymmetric Multifocal Bifrontal, symmetric Bifrontal, R > L Bifrontal, L > R No change No discharges recorded “Patient
number
A
Symmetric
8
4
l(8)
1(27) 0 2(10,17) 1wJ) 3(7,17,27) l(7) 0 0
0
4(2,15,20,29) l(9)
2CW) 1w 163) 1U1)
EEGs”
B Asymmetric
7 2(13,23) 1(25) 3(13,23,24) 0
9 1(14) 3(16,19,26) 4(16,21,26,30) l(30)
WX’)
l(W
2(6,24) 0
2(14,21) 0 2(12,18)
1w
C
in parentheses.
(13.3%) had three or more epileptiform foci on their preoperative EEGs compared to eight patients (26.7%) on their postoperative recordings. Eight patients (26.6%) had a decrease in the number of epileptiform foci from their preoperative to postoperative EEGs, whereas 12 patients (40.0%) had an increase in number of foci. Examples of EEGs are demonstrated in the figures. Figure 2A demonstrates the preoperative finding of
generalized, low-amplitude spike-and-wave discharges. The postoperative EEG (Fig. 28) demonstrates higher amplitude, right-sided spike-and-wave activity. Figure 3A demonstrates a segment of recording demonstrating bifrontal spike-and-wave activity, whereas, on the postoperative EEG, left frontal spike-and-wave activity is the primary finding (Fig. 38). Figure 4A demonstrates an irregular discharge of asymmetrical generalized spike-and-wave
Figure 3. The preoperative recording demonstrates a segment showing bifrontal spike-and-wave erative EEG (B), left frontal spike-and-wave activity is the primary finding.
78
Group
1 EPILEPSY, VOL 2, NO. 2, 1989
activity (A), whereas on the postop
ANTERIOR
Figure
4.
po&perative
CORPUS
CALLOSO’TOMY
The vreopemtive EEG demonstrates an irrexular discharge of asymnetricnl generalized spike-and-wave EEb zubs mrked by multifocal epileptifor% activity. B demomtrates left-sided spikes.
activity on the preoperative EEG. The postoperative EEG was marked by multifocal epileptiform activity. Figure 4B demonstrates left temporal spikes.
Number of epileptiform
discharges
Eleven patients (36.7%) had a decrease in the number of epileptiform discharges, whereas four patients (13.3%) had an increase in the number of epileptiform discharges from the preoperative to postoperative EEG. The number of epileptiform discharges on the preoperative EEG was significantly more than on the postoperative EEG (paired t test = 3.494; p = 0.002, two-tailed).
Outcome The outcome of the patients is listed in Table 2. The follow-up period ranged from 12 to 48 months (mean, 25.3 months). Fourteen patients (46.7%) were either seizure-free (l), had rare seizures (2), or had a worthwhile improvement (ll), whereas 16 (53.3%) had no significant improvement. There was no statistically significant relationships among Groups A, B, and C and outcome (KruskalWallis = 3.003; p = 0.223). There was no difference in outcome in patients who continued to have gen-
AND THE EEG
activity (A).
The
eralized discharges on their postoperative EEG compared to those who did not (Kruskal-Wallis = 0.330; p = 0.572). Patients with an increase in number of epileptiform foci from the preoperative to postoperative EEG did not differ significantly in outcome from patients with a decrease in foci (Kruskal-Wallis = 0.126; p = 0.722). There were also no differences in outcome between patients who had a decreased number of epileptiform discharges from the preoperative to postoperative EEG compared to patients with an increase in epileptiform activity (KruskalWallis = 0.059; p = 0.808).
Discussion There is now a considerable amount of animal evidence demonstrating that the corpus callosum is an important conduit of epileptiform activity from one hemisphere to the other. As early as 1940, Erickson (16) proposed that the corpus callosum was responsible for the interhemispheric spread of epileptic discharges. This was followed by the work of Kopeloff et al. (17), who demonstrated that section of the corpus callosum in animals prevented the spread of epileptiform activity from one hemisphere to the other. Musgrave and Gloor (18) studied the role of the
I EPILEPSY, VOL. 2, NO. 2, 1989
i’g
W. E. GOLDBERG
ET AL.
corpus callosum in bilateral synchrony of epileptiform discharges in four groups of cats with penicillinGroup A underwent complete induced epilepsy: section of the corpus callosum and anterior commissure; Group B underwent division of the massa intermedia alone; Group C underwent partial section of the corpus callosum; and in Group D, cortex was severed from all its subcortical inputs without disturbing its connections with the opposite hemisphere through the corpus callosum. In intact animals, penicillin induced bilateral epileptiform discharges. In animals with a complete section of the corpus callosum, the bilateral synchrony of the spike-andwave discharge was abolished; in the group with partial section of the corpus callosum, the bisynchrony was impaired. The other two groups with an intact corpus callosum continued to have bilateral synchrony of the epileptiform activity. These results demonstrated the key role the corpus callosum plays in the bisynchrony of epileptiform discharges. In general, our results support the work in animals, demonstrating that generalized discharges are reduced in patients following corpus callosum division. Whereas almost all of our patients had generalized discharges before sectioning, only eight continued to have generalized discharges after the operation. In the other patients, bifrontal or multifocal discharges replaced the generalized discharges. There was also a trend for epileptiform discharges to become asymmetrical and/or asynchronous. Like the epileptiform activity, background activity frequently became asymmetrical following callosotomy. These findings are similar to those of other authors reporting changes in the EEG following corpus callosotomy (5,7,12-14, 19-21). Wilson et al. (12) reported that bilateral, synchronous, spike, or spikeand-wave discharges became asynchronous after complete division of the corpus callosum but noted that lateralization of the discharges did not correlate with outcome. Geoffroy and colleagues (13), in a study of nine patients, reported that patients with lateralized EEG foci did better in the postoperative period than patients with diffuse abnormalities. Gates et al. (19) reported that the corpus callosotomy reduced the number of generalized epileptiform discharges and correlated this EEG finding with a decrease in generalized seizures in six patients. A significant difference in total number of epileptiform discharges from the preoperative to postoperative EEG was not noted. Spencer et al. (5), in a study of 22 patients analyzed 2 or more years after corpus callosotomy, reported better outcomes among patients with secondary bilateral synchrony or unilateral epileptiform activity than those with bilateral independent EEG 130 ] EPILEPSY, VOL 2, NO. 2, 1989
paroxysms. However, none of the EEG findings was statistically significant in predicting outcome. In a review of reported EEG changes after corpus callosotomy, Spencer (7) found that total or partial section of the corpus callosum and hippocampal commissure with or without the anterior commissure and fomix lead to a “lasting and marked disruption” of bilateral synchronous spike-and-wave discharges in approximately half of the patients. The finding that some but not all of the generalized discharges abated following anterior corpus callosotomy suggests that epileptiform discharges may spread from one hemisphere to the other through structures other than the anterior corpus callosum. In a recent review, Spencer (7) elegantly reviewed the interhemispheric connections through which epileptiform discharges spread. As pointed out by Spencer (7), subcortical relays may be utilized in the contralateral spread of epileptiform discharges originating in the neocortex. Whereas the corpus callosum appears to be the primary pathway in the generalization of epileptiform discharges, subcortical spread may be of equal or more importance in some patients. The findings on the preoperative EEG and on the postoperative EEG were not predictive of outcome. Patients who continued to have generalized discharges on their postoperative EEG did not fare any differently from patients without postcallosotomy generalized discharges. In addition, neither number of epileptiform discharges nor number of epileptiform foci on the postoperative EEG was related to outcome. These findings demonstrate that eliminating generalized discharges or reducing the number of foci is not necessary for improvement in seizure frequency. We conclude that, at the present time, the EEG is of no value in predicting outcome following anterior corpus callosotomy.
References 1. Van Wagenen WI’, Herren RY. Surgical division of commissural pathways in the corpus callosum. Relation to spread of an epileptic attack. Arch Neural Psychol 1940;44:740-59. 2. Wilson DH, Reeves A, Gazzaniga M, Culver C. Cere-
bral commissurotomy for control of intractable seizures. Neurology 1977;27:708-15. 3. Wilson DH, Reeves AC, Gazzaniga AM. Division of the corpus callosum for uncontrolled epilepsy. Neurology 1978;28:649-53. 4. Murro AM, Flanigin HF, Gallagher BB, King DW, Smith JR. Corpus callosotomy for the treatment of intractable epilepsy. Epilepsy Res 1988;2:44-50. 5. Spencer SS, Spencer DD, Williamson PD, Sass K, Novelly RA, Mattson RH. Corpus callosotomy for epilepsy. I. Seizure effects. Neurology 1988;38:19-24.
ANTERIOR 6. Wyllie E. Corpus callosotomy for intractable generalized epilepsy. 1 Pediatr 1988;113:255-61. 7. Spencer SS. Corpus callosum section and other disconnection procedures for medically intractable epilepsy. Epilepsia 1988;29(suppl 2):S85-S99. 8. Spencer SS, Gates JR Reeves AR, Spencer DD, Maxwell RE, Roberts D. Corpus callosum section. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:425-44. 9. Flanigin HF, King DW, Gallagher BB. Surgical treatment of epilepsy. In: Pedley T, Meldrum BS, eds. Recent advmces in epilepsy, vol. 2. Edinburgh: Churchill-Livingstone, 1984:297-339. 10. Smith JR Flanigin HF, King DW, Gallagher BB, Loring DW, Meador KJ, Murro AM. The present status of the surgical management of epilepsy. South Med J (in press). 11. Makari GS, Holmes CL, Murro AM, Smith JR, Flanigin HF, Cohen MJ, Huh K, Gallagher BS, Ackell AB, Campbell R, King DW. Corpus callosotomy for the treatment of intractable epilepsy in children. j Epilepsy 1989;2:1-7. 12. Wilson DH, Reeves AG, Gazzaniga MS. “Central” commissurotomy for intractable generalized epilepsy: series two. Neurology 1982;32:687-97. 13. Geoffroy G, Lassonde M, Delisle F, Decarie M. Corpus callosotomy for control of intractable epilepsy in children. Neurology 1983;33:891-97. 14. Rayport M, Ferguson SM, Corrie WS. Outcomes and
15. 16.
17.
18.
19. 20.
21.
CORPUS CALLOSOTOMY
AND THE EEG
indications of corpus callosum section for intractable seizure control. Appl Neurophysiol 1983;46:47-51. Engel, J Jr. Outcome with respect to epileptic seizures. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:55>71. Erickson TC. Spread of the epileptic discharge. An experimental study of the after-discharge induced by electrical stimulation of the cerebral cortex. Arch Neural Psycho1 1940;43:429-52. Kopeloff N, Kennard MA, Pacella BL, Kopeloff LM, Chusid JG. Section of corpus callosum in experimental epilepsy in the monkey. Arch Neural Psycho1 1950;63:719-27. Musgrave J, Gloor P. The role of the corpus callosum in bilateral interhemispheric synchrony of spike and wave discharge in feline generalized penicillin epilepsy. Epilepsia 1980;21:369-78. Gates JR Leppik IE, Yap J, Gumnit RJ. Corpus callosotomy: clinical and electroencephalographic effects. Epilepsia 1984;25:308-16. Huck FR, Radvany J, Avila JO, Fires de Camargo P, Marino R Jr, Ragazzo PC, Riva D, Arlant P. Anterior callosotomy in epileptics with multiform seizures and bilateral synchronous spike and wave EEG pattern. Acta Neurochir [Suppl] (Wein) 1980;30:127-35. Roberts DW, Allen CD, Allen AH, Reeves AG. Depth electrode recording in patients undergoing corpus callosotomy for intractable epilepsy. Appl Neurophysiol 1983;46:26-32.
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