Supratentorial brain infarcts in adult-onset seizures; the Maastricht Epilepsy Case Register

Seizure 1993; 2:221-227

Supratentorial brain infarcts in adult-onset seizures; the Maastricht Epilepsy Case Register E.P.M. HEUTS-VAN RAAK, A. BOELLAARD, M.C.T.F.M. DE KROM & J. LODDER

Department of Neurology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. Correspondenceto: E.P.M. Heuts-van Raak.

We studied the frequency of supratentorial brain infarction as the cause of late-onset epilepsy in 680 patients with a first seizure after the age of 20, registered on an epilepsy register: 65 (10%) had seizures following a symptomatic supratentorial brain infarct. Brain infarction as the presumed cause of epilepsy was related to age at first seizure. A first seizure occurred within one year after brain infarction in 62%, and later than two years in 19%. Eight of 14 patients (57%) with an early seizure (-<2 weeks), and 28 of 41 patients (68%) with a first seizure later than two weeks post-stroke had seizure recurrences despite anti-epileptic treatment. Of 38 patients who underwent computed tomography head scan (CT), 32 (84%) had a cortical infarct, whereas six (16%) had one or more lacunar infarcts. This may indicate that lacunar infarction may be associated with poststroke epilepsy. Using a detailed topographic brain atlas to localize the cortical infarcts, no 'specific epileptogenic' gyri could be identified. What factors predict future epilepsy in stroke patients need to be studied in prospective series of well-defined stroke subgroups. Key words: epilepsy; ischaemic stroke; adult-onset seizures; supratentorial brain infarcts; post-stroke epilepsy.

INTRODUCTION

Stroke leaves m a n y people disabled; a number of them will be additionally handicapped by the occurrence of seizures. The percentage of stroke patients t h a t acquire post-stroke epilepsy varies between studies from 0 to 54% 1-23, as does the percentage of epilepsy patients t h a t have sustained a prior stroke: 11 to 45% 7'24-34. Besides differences in study methods and patient inclusion criteria, these variations may in part relate to differences between studies in the number of patients with different stroke subtypes, especially in those studies carried out before the advent of computed tomography head scanning (CT), as the risk of developing post-stroke epilepsy may vary with the type of stroke 1'9'17'23. However, even when using CT to differentiate between various stroke subtypes, scanning later t h a n approximately two weeks following stroke may not differentiate reliably between infarction and hemorrhage 35. The present study was undertaken to answer the following questions: (1) to what extent does the most frequent stroke subtype (supratentor1059-1311/93/030221 +07 $08-00/0

ial brain infarction) contribute to the occurrence of epilepsy in adults, related to age; (2) what is the time-course of seizure development in such patients; (3) do such patients sustain cortical infarcts more often than lacunar infarcts; (4) can 'specific epileptogenic' cortical gyri be identified?

PATIENTS AND METHODS

Patients had been registered in the Maastricht Epilepsy Case Register (MECR). The MECR started in 1983, aiming to register all patients with epilepsy living in a geographically welldefined area in the southern part of the Netherlands (Zuid-Limburg). Patients are registered by neurologists, paediatricians, and psychiatrists, working in private practice, hospitals or other health care institutes. On registration a standardized intake form is filled out including among other details the patients' sex, date of birth, date of first seizure, number of seizures, seizure type (according to the international classification of epileptic @ 1993 Bailliere Tindall

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E.P.M. Heuts-ven Reek et aL

Table 1 : Age at first seizure in patients registered in the MECR (percentages between brackets)

Age (years) 20-29 30-39 40-49 50-59 60-69 70-79 t>80

All patients

Total

680 (100)

209 138 86 96 82 64 5

(31) (20) (13) (14) (12) (9) (1)

Patient with post-infarct epilepsy 0 (0) 4 (6) 6 (9) 13 (20) 21 (32) 16 (25) 5 (8) 65 (100)

seizures 36, date of starting anti-epileptic medication, number of seizures before medication, type of medication, electroencephalogram (EEG) abnormalities, as well as some items related to socio-economic status and occupation. The included presumed causes of epilepsy are: birth-trauma; meningo-encephalitis; metabolic encephalopathy; stroke and/or cerebral atherosclerosis; head-trauma; cerebral tumour; aneurysm; any other specific cause; unknown cause. Patients are only registered after informed consent; all information is handled in a strictly confidential manner, monitored by the MECR monitoring committee. A follow-up form is filled out on each follow-up contact. The form registers among others: number and type of seizures since latest follow-up, and any change in medication. All forms are sent to the central office in Maastricht where they are checked for completeness, and stored in the databank. We estimate t h a t at the time of the present study the number of patients registered with the MECR was not complete. Therefore, and in the absence of a population census, we decided that the MECR was not yet fit for a proper epidemiological study on post-stroke epilepsy, although patients most likely to be missing were those under the age of 20, because of minimal patient attribution to the MECR by paediatricians. For practical reasons, one of which was t h a t at the time of the study most of the patients in some parts of the study area would not have had CT, we limited the study to two of the major hospitals' adherent populations. For the aim of the study we restricted the query to those MECR patients who had experienced their first seizure after the age of 20; 680 patients fulfilled this requirement, of whom 101 had 'stroke or cerebral atherosclerosis' listed as presumed cause of epilepsy. We considered 'post-infarct epilepsy' as one or more epileptic seizures at any time following a clinically experienced supratentorial brain

Percentage of post-infarct epilepsy 0 3 7 14 26 25 100 10

Patients with other causes 209 (34) 134 (22) 80 (13) 83 (13) 61 (10) 48 (8) 0 (0) 615 (100)

infarct, without any other cause t h a n the susrained stroke, in a patient not already suffering from seizures before this stroke. CT had to either show evidence of a sustained territorial, lacunar, striatocapsular or watershed infarction, or had to be without any other specific lesion. After we studied the medical records, 65 patients met our inclusion criteria. Of these patients we noted sex, stroke-date and age at the time of stroke, time between stroke and last follow-up of death, age at first seizure, time between stroke and first seizure, number of seizures, if and when patients received antiepileptic treatment, and time between stroke and CT. In cortical lesions on CT the involved gyri were identified according to Bories' method 37. Five patients had a recurrent stroke before the first seizure; in three of them we considered the recurrent stroke most likely to be related to the occurrence of the seizures, because of the r a t h e r tong time-interval between first stroke and first seizure. In the two remaining patients the first stroke was used as the index event.

RESULTS

Of the 65 patients with post-infarct epilepsy registered in the MECR, 46 were men and 19 were women. Median follow-up (time between stroke and last contact or death) was 5.5 years (range 117 days-17.2 years). The distribution (in decades) of age at the time of the first seizure of all 680 patients, and those suffering from post-infarct epilepsy is shown in Table 1. Median age in the post-infarct epilepsy group was 65 (range 33-90) years. In seven patients the exact stroke date was unknown; in five of these CT was performed showing a lesion compatible with sustained infarction in four. In the remaining 58 patients the median period between stroke and the first post-stroke seizure was 7.5 months (range 0 days-8 years).

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Epilepsy and ischaemic stroke 'Early' a n d 'late' s e i z u r e s

N i n e p a t i e n t s had t h e i r first seizure at s t r o k e onset. T a b l e 2 shows seizure d e l a y in m o r e detail. If we consider 'early' (-<2 weeks) a n d 'late' ( > 2 weeks) seizures, t h e n h a l f of the late seizures developed w i t h i n t h e first y e a r posts t r o k e w h e r e a s 25% developed l a t e r t h a n 2 y e a r s post-stroke. All of the 14 p a t i e n t s w i t h e a r l y seizures received anti-epileptic t r e a t m e n t , t h a t was s t a r t e d after a m e d i a n of two ( r a n g e 1 - 6 ) seizures, and c o n t i n u e d at the t i m e of t h e s t u d y in all patients. E i g h t of these 14 p a t i e n t s (57%) e x p e r i e n c e d one or more recurr e n t seizures despite anti-epileptic t r e a t m e n t . T h r e e of t h e 44 p a t i e n t s w i t h late seizures received no anti-epileptic t r e a t m e n t at all following t h e i r first seizure, and were w i t h o u t r e c u r r e n c e s d u r i n g a m e d i a n follow-up of 18 months. The r e m a i n i n g 41 p a t i e n t s with late seizures received anti-epileptic t r e a t m e n t , which was s t a r t e d a f t e r a m e d i a n of two (range 1 - 6 ) seizures, and c o n t i n u e d at the t i m e of t h e s t u d y in 37 patients. T w e n t y - e i g h t of these 41 p a t i e n t s (68%) e x p e r i e n c e d one or more recurr e n t seizures despite anti-epileptic t r e a t m e n t .

S i n g l e a n d multiple s e i z u r e s

E i g h t p a t i e n t s (12%) experienced a single, late seizure, a f t e r a m e d i a n of 2.1 y e a r s (range 34 d a y s - 7 years) following stroke. T h e i r m e d i a n age at t h e t i m e of s t r o k e was 70 (range 5 2 - 8 4 ) years. Fifty-seven p a t i e n t s (88%) h a d two or m o r e epileptic seizures following stroke, in 14 of w h o m (25%) the first seizure occurred early. M e d i a n d e l a y b e t w e e n stroke a n d first seizure in t h e s e p a t i e n t s w i t h m u l t i p l e seizures was 6.9 m o n t h s (range 0 d a y s - 8 years), m e d i a n age a t t h e t i m e of stroke was 63 (range 3 3 - 9 0 ) years.

CT-findings

Fifty-two p a t i e n t s (80%) had one or more CT scans. Of 41 p a t i e n t s (79%) t h e scans were a v a i l a b l e for the study. M e d i a n delay b e t w e e n stroke and CT was 15 days (range 0 d a y s - 1 1 years). T h i r t y - e i g h t scans showed at least one lesion compatible w i t h s u s t a i n e d infarction. T a b l e 3 shows the n u m b e r of p a t i e n t s w i t h different infarct types on t h e i r CT. Table 4 shows t h e n u m b e r s of involved gyri in t h e middle cerebral a r t e r y (MCA) t e r r i t o r y

Table 2: Time between symptomatic supratentorial brain infarct and first seizure in 58 of 65 patients with post-infarct epilepsy, registered in the MECR (in seven time of stroke not certified)

Seizure delay

Number of patients

Percentage

~<2 weeks >2 weeks-~1 year-~<2 years >2 years

14 22 11 11

24 38 19 19

Table 3: Infarct types on CT in 38 patients with epileptic seizures after symptomatic supratentorial brain infarction

Infarct type

Number of patients (%)

Cortical infarct(s) only* Lacunar infarct(s) onlyt Cortical and lacunar infarct Cortical and striatocapsular infarct Cortical and watershed infarct

28 (73.7) 6 (15.8) 2 (5.3) 1 (2.6) 1 (2.6)

* Six had two infarcts, t Three had two infarcts, one had seven infarcts.

Table 4: Frequency of involved gyri in 23 post-infarct epilepsy patients with MCA infarct, six with PCA infarct and three with infarcts in both territories

MCA (26 patients) Gyrus Orbital Superior temporal Middle temporal Inferior temporal Middle frontal Inferior frontal Precentral Post-central Supramarginal Angular Occipital lobe Superior parietal lobule

n 2 15 16 3 4 7 16 12 20 12 2 3

PCA (9 patients) Gyrus Parahippocampal Fusiform Uncus Occipital lobe Cingulate Lingual Cuneus Precuneus

n 2 3 0 4 1 5 2 0

infarcts involving the cortex (n = 26) according to Bories' t e m p l a t e s 37. E i t h e r one of the t h r e e most f r e q u e n t l y involved gyri was involved in all of these 26 patients. T h e n u m b e r s of involved gyri in t h e posterior cerebral a r t e r y (PCA) t e r r i t o r y (n = 9) are also shown in Table 4.

DISCUSSION

At the t i m e of the study a p p r o x i m a t e l y 60% of all a d u l t p a t i e n t s w i t h epilepsy in our s t u d y a r e a h a d been r e g i s t e r e d w i t h the MECR, w i t h o u t disproportionate distribution differences b e t w e e n different age categories. T h e s e

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estimates are based on data from the study by Hauser and Kurland 3s who found an overall epilepsy prevalence rate of 1:185, from a recent Dutch prevalence rate estimate of 1:196 by Van de Lisdonk et al. 39, and from demographic figures acquired from the Dutch Central Statistical Office. Therefore, although at the time of the study we found the MECR not yet suited to estimate certain epidemiological data like specific incidence or prevalence rates among registered patients so far, the frequency estimate of epilepsy following a brain infarct relative to all causes unlikely suffers major bias. We were primarily interested in the question how much ischaemic stroke, that makes up approximately 80% of all strokes, contributes to the occurrence of epilepsy in adults related to age. Our overall percentage of 10 (95% CI: 8 12) is low compared to similar studies 7,24-34. The fact that we only included patients with a clear history of stroke most likely due to a supratentorial brain infarct, with compatible CT, probably accounts for this difference. Moreover, we excluded patients with cerebral haemorrhage, those with vertebrobasilar stroke, and those with the rather vague description of 'cerebral atherosclerosis', a presumed diagnosis often applied when elderly patients suffer seizures without apparent cause. Nevertheless, some of our patients without CT and some with CT performed later than 2 weeks following stroke, still might have suffered small cerebral haemorrhage, because sustained infarction cannot always fully reliably be differentiated from a scar left from haemorrhage 4°. However, if so, we expect this number to be low, probably not biasing our final results. Table 1 shows t h a t with increasing age at first seizure, brain infarction as the presumed cause of epilepsy increases as well, undoubtedly reflecting increasing frequency of stroke with increasing age. Thus, almost one quarter of epilepsy patients with first seizure after the age of 50 sustained a prior brain infarct. Sixty-two per cent of our patients experienced their first seizure within one year (24% even within 2 weeks), and 81% within 2 years following brain infarction. This differs from other studies that found 38-100% (median 73) within one year, and 75-100% (median 100) within two years following brain infarction 1'9'11'14'17'41-45 The longer period before first seizure in our series is possibly related to the prolonged follow-up with a median duration of 5.5 years, and to the above men-

E.P.M. Heuts-van Raak et al.

tioned differences in study methods. Time between stroke and first seizure in hospital series is likely to be shorter compared with a register as ours, because hospital series likely include patients with seizure at stroke onset more often, as well as patients who develop seizures and eventually die following stroke. Compared with earlier series our study might have registered more patients with late onset post-stroke epilepsy because of increasing stroke survival over the past decades. There is no consensus in the literature about what the term 'post-stroke epilepsy' signifies. Most authors do not provide a clear definition, whereas some 22 suggest the term should be restricted to indicate recurrent seizures following a stroke, but not in the early phase, which is often arbitrarily set at the first 2 weeks poststroke. However, the occurrence of late seizures is undoubtedly influenced by antiepileptic treatment in patients with early seizures. Such treatment is most likely to be initiated in cases with multiple early seizures, as was the case in our study. Therefore, we adopted a pragmatic approach in describing different aspects of post-brain infarct seizures rather than adhere to an arbitrary definition of post-stroke epilepsy. Early seizures m a y indicate an increased risk of seizure recurrences (post-stroke epilepsy) 46. Fifty-seven per cent of our patients with early seizures had seizure recurrences, and could be considered to have developed epilepsy, the more so because seizures occurred despite anti-epileptic treatment. The size of the stroke population our patients stem from is unknown. However, considering that the NINDS Stroke Data Bank 47 found subsequent seizures in only 6.5% of their stroke patients, our 44 patients that developed late seizures likely represent a very low percentage of all stroke patients without early seizures. This supports the assumption that stroke patients with early seizures are more likely to develop 'post-stroke epilepsy' than those without. Prospective stroke register data, however, could more reliably confirm such association. Our patients with multiple seizures were younger than those with a single seizure, whereas the delay between stroke and first seizure was shorter in those with recurrent seizures. Although the numbers are small, our data may indicate that younger age at stroke is related to more early, recurrent seizures. Lacunar infarcts are considered an unlikely cause of post-stroke epilepsy, but not by all

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Epilepsy and ischaemic stroke

authors 4s. Among our patients with an infarct on CT, 28 had cortical infarct(s) only, four had either lacunar or large subcortical infarcts as well, whereas six had lacunar infarcts only. Should lacunar infarcts cause seizures as often as cortical infarcts do, we would have expected to find lacunar infarcts in our series in a similar proportion as they cause supratentorially located brain infarcts, which is approximately 4 0 % 49 . Instead we found (6/38) 16%. Therefore we consider lacunar infarcts an unlikely, although not a proven impossible cause of poststroke seizures. Lacunar infarction might merely reflect more severe generalized cerebral small vessel disease that could lead to epilepsy in some cases by more generalized rather than focal disturbances, such as: decreased activity of the enzyme ATP-ase, damage to calcium channels, the GABA-ergic inhibitory system, or to receptors involved in excitatory brain activity, disturbing the delicate balance between excitatory and inhibitory neural mechanisms in favour of excitation 5°54. Still, some parts of the brain may particularly be susceptible to the development of epileptic activity, like the hippocampi and the sensorimotor cortex s3. Using a detailed topographic brain atlas we found that some gyri, especially those located in the MCA territory, were more often involved than others. The finding that in 77% of our MCA territory infarct patients the supramarginal gyrus was involved might indicate that the anterior parietal region is especially associated with the development of seizures, as was shown in patients with traumatic brain damage 53'55'56. However, overall we failed to identify 'specific epileptogenic' gyri. That some gyri located in the MCA territory were more often involved than others might merely reflect the high frequency of infarction in this brain vascular territory, a possibility that can only be studied from comparing stroke patients developing seizures with those who do not. On the other hand, complete destruction of an area with a low seizure threshold might 'protect' against epileptic activity. The fact that large cortical infarcts with persisting paresis cause epilepsy more often than small ones 17 could be due to more frequent involvement of the supramarginal gyrus, but also to the more extended cortical damage in such infarcts. Prospective series of well-defined stroke patient subgroups could give more insight into the importance of different factors involved in the development of post-stroke epilepsy, and

could also lead to identify high risk patients, in whom prophylactic anti-epileptic drug treatment could be considered, not only to p r e v e n t seizures, but to lower the chance of development of epileptic brain activity following stroke more definitely. In conclusion: (1) in approximately one quarter of epilepsy patients with first epileptic seizure after the age of 50, epilepsy could be related to sustained symptomatic brain infarction; (2) eighty per cent of the patients with seizures following a brain infarct experienced their first seizure within 2 years following brain infarction; (3) first seizures that occur early following supratentorial brain infarction in relatively young stroke patients seem to have a high recurrence rate despite antiepileptic treatment; (4) stroke patients with early seizures are more likely to develop late seizures (post-stroke epilepsy) than those without; (5) seizures following a brain infarct are associated mainly but not exclusively with infarcts involving the cortex; (6) although some cortical gyri were frequently involved~ no cortical area emerged convincingly as 'specific epileptogenic'.

ACKNOWLEDGEMENTS The authors gratefully acknowledge the following persons: C.L. Franke, J.F. Mirandolle, P.J.J. Koehler, Department of Neurology, and C.W.M. Versteege, H.A. Engelshove, Department of Radiology, De Weverziekenhuis, Heerlen; J. Bergers, M. Kruijen, Data Management Department MEMIC, University of Limburg; G.M.J. Lassouw, Department of Neurology, and F.R.J. Verhey, Department of Psychiatry, University Hospital Maastricht.

REFERENCES 1. Richardson Jr, E.P. and Dodge, P.R. Epilepsy in cerebral vascular disease. A study of the incidence and nature of seizures in 104 consecutive autopsy-proven cases of cerebral infarction and hemorrhage. Epilepsia 1954; 3: 49-74. 2. Silverstein, A. and Hollin, S. Internal carotid vs middle cerebral artery occlusions. Archives of Neurology 1965; 12: 468-471. 3. Louis, S. and McDowell, F. Epileptic seizures in nonembolic cerebral infarction. Archives of Neurology 1967; 17: 414-418. 4. Marquardson, J. The natural history of acute cerebrovascular disease. A retrospective study of 769 patients.

E.P.M. Heuts-van Raak et aL

226

Acta Neurologica Scandinavica 1969; 4-5 (suppl. 38): 9-192. 5. Fentz, V. Epileptic seizures in patients with cerebrovascular accidents. Nordisk Medicin 1971; 86: 10231025. 6. Meyer, J.S., Charney, J.Z., Rivera, V.M. and Mathew, N.T. Cerebral embolization: Prospective clinical analysis of 42 cases. Stroke 1971; 2: 541-554. 7. Hildick-Smith, M. Epilepsy in the elderly. Age and Ageing 1974; 3: 203-208. 8. De Reuck, J., Krahel, N., Sieben, G., Orban, L., de Coster, W. and vander Eecken, H. Epilepsy in patients with cerebral infarcts. Journal of Neurology 1980; 224: 101-109. 9. Holmes, G.L. The electroencephalogram as a predictor of seizures following cerebral infarction. Clinical Electroencephalography 1980; 11: 83-86. 10. Ramirez-Lassepas, M., Hauser, W.A., Bundlie, S.R. and Cleeremans, B.B. Epileptiform activity, acute seizures and epilepsy with acute cerebral vascular disease. In: Advances in Epileptology: the Xth Epilepsy International Symposium (Eds J.A. Wade and J.K. Penry). New York, Raven Press, 1980: p. 188. 11. Cocito, L., Favale, E. and Reni, L. Epileptic seizures in cerebral arterial occlusive disease. Stroke 1982; 13: 189-195. 12. Sacquegna, T., De Carolis, P., Pazzaglia, P., et al. The clinical course and prognosis of carotid artery occlus~on. Journal of Neurology, Neurosurgery and Psychiatry 1982; 45: 1037-1039. 13. Black, S.E., Norris, J.W. and Hachinski, V.C. Poststroke seizures. Stroke 1983; 14: 134. 14. De Carolis, P., D'Alessandro, R., Ferrara, R., Andreoli, A., Sacquegna, T. and Lugaresi, E. Late seizures in patients with internal carotid and middle cerebral artery occlusive disease following ischaemic events. Journal of Neurology, Neurosurgery and Psychiatry 1984; 47: 1345-1347. 15. Hauser, W.A., Ramirez-Lassepas, M. and Rosenstein, R. Risk for seizures and epilepsy following cerebrovascular insults. Epilepsia 1984; 25: 666. 16. Sacquegna, T., De Carolis, P., Andreoli, A., et al. Long term prognosis after occlusion of middle cerebral artery. British Medical Journal 1984; 288: 1490-1491. 17. Olsen, T.S., Hogenhaven, H. and Thage, O. Epilepsy after stroke. Neurology 1987; 37: 1209-1211. 18. Berger, A.R., Lipton, R.B., Lesser, M.L., Lantos, G. and Portenoy, R.K. Early seizures following intracerebral hemorrhage: implications for therapy. Neurology 1988; 38: 1363-1365. 19. Kotila, M. and Waltimo, O. Epilepsy after stroke: results of treatment. In: Modern Trends in Neurology and Neurological Emergencies. Prague, 1988: April 18-22. 20. Shinton, R.A., Gill, J.S., Melnick, S.C, Gupta, A.K. and Beevers, D.G. The frequency, characteristics and prognosis of epileptic seizures at the onset of stroke. Journal of Neurology, Neurosurgery and Psychiatry 1988; 51:273 276. 21. Faught, E., Peters, D., Bartolucci, A., Moore, L. and Miller, P.C. Seizures after primary intracerebral hemorrhage. Neurology 1989; 39: 1089-1093. 22. Sung, C.Y. and Chu, N.S. Epileptic seizures in intracerebral haemorrhage. Journal of Neurology, Ncurosurgery and Psychiatry 1989; 52: 1273-1276. 23. Kilpatrick, C.J., Davis, S.M., Tress, B.M., Rossiter, S.C., Hopper, J.L. and Vandendriesen, M.L. Epileptic

24.

25. 26.

27.

28.

29. 30.

31.

32. 33.

34.

35.

36.

37. 38.

39.

40.

41.

42. 43.

44.

seizures in acute stroke. Archives of Neurology 1990; 47: 157-160. Ang/R.T. and Utterback, R.A. Seizures with onset after forty years of age; role of cerebrovascular disease. Southern Medical Journal 1966; 59: 1404-1408. Fine, W. Epileptic syndromes in the elderly. Gerontaligia Clinica 1966; 8: 121-133. Schold, C., Yarnell, P.R. and Earnest, M.P. Origin of seizures in elderly patients. JAMA 1977; 238: 11771178. Roberts, M.A., Godfrey, J.W. and Caird, F.I. Epileptic seizures in the elderly: I. Aetiology and type of seizure. Age andAgeing 1982; 11: 24-28. Shorvon, S.D., Gilliatt, R.W., Cox, T.C.S. and Yu, Y.L. Evidence of vascular disease from CT scanning in late onset epilepsy. Journal of Neurology, Neurosurgery and Psychiatry 1984; 47: 225-230. L~ihdorf, K., Jensen, L.K. and Plesner, A.M. Etiology of seizures in the elderly. Epilepsia 1986; 27: 458-463. Daras, M., Tuchman, A.J. and Strobos, R.J. Computed tomography in adult-onset epileptic seizures in a city hospital population. Epilepsia 1987; 28: 519-522. Roberts, R.C., Shorvon, S.D., Cox, T.C.S. and Gilliatt, R.W. Clinically unsuspected cerebral infarction revealed by computed tomography scanning in late onset epilepsy. Epilepsia 1988; 29: 190-194. Sundaram, M.B.M. Etiology and patterns of seizures in the elderly. Neuroepidemiology 1989; 8: 234-238. Henny, C., Despland, P.A. and Regli, F. Premiere crise @ileptique apr~s l'&ge de 60 ans: ~tiologie, pr~sentation clinique et EEG. Schweizerische medizinische Wochenschrift 1990; 120: 787-792. Sung, C.Y. and Chu, N.S. Epileptic seizures in elderly people: aetiology and seizure type. Age and Ageing 1990; 19: 25-30. Dennis, M.S., Bamford, J.M., Molyneux, A.J. and Warlow, C.P. Rapid resolution of signs of primary intracerebral haemorrhage in computer tomograms of the brain. British Medical Journal 1987; 295: 379-381. Commission on classification and terminology of the International League Against Epilepsy. Proposal for revised clinical and EEG classification of epileptic seizures. Epilepsia 1981; 22: 489-501. Bories, J., Derhy, S. and Chiras, J. CT in hemisperic ischaemic attacks. Neuroradiology 1985; 27: 468-483. Hauser, W.A. and Kurland, L.T. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia 1975; 16: 1-66. Van de Lisdonk, E.H., Van den Bosch, W.J.H.M., Huygen, F.J.A. and Lagro-Janssen, A.L.M. (eds). Ziekten in de huisartspraktijk. Utrecht, Wetenschappelijke Uitgeverij Bunge, 1990. Franke, C.L., Van Swieten, J.C. and Van Gijn, J. Residual lesions on CT after intracerebral hemorrhage. Stroke 1991; 22: 1530-1533. Dodge, P.R., Richardson Jr, E.P. and Victor, M. Recurrent convulsive seizures as a sequel to cerebral infarction: a clinical and pathological study. Brain 1954; 77: 610-638. Fine, W. Post-hemiplegic epilepsy in the elderly. British Medical Journal 1967; 1: 199-201. Pirttimaki, R., Narva, E.V. and Ruikka, I. Epilepsy as a sequel to cerebrovascular accident. Scandinavian Journal of Social Medicine 1977; 14: 134-140. Gupta, S.R., Naheedy, M.H., Elias, D. and Rubino, F.A. Postinfarction seizures. A clinical study. Stroke 1988; 19: 1477-1481.

227

Epilepsy and ischaemic stroke 45. Sung, C.Y. and Chu, N.S. Epileptic seizures in thrombotic stroke. Journal of Neurology 1990; 237: 166-170. 46. Kilpatrick, C.J., Davis, S.M., Hopper, J.L. and Rossiter, S.C. Early seizures after acute stroke. Risk of late seizures. Archives of Neurology 1992; 49: 509-511. 47. Burdette, D.E., Foulkes, M.A., Wolf, P.A., et al. The incidence of post-stroke seizures in the NINDS stroke data bank. In: Abstracts from the International Stroke Society Second World Congress of Stroke. Washington, 8-12 September, 1992. 48. Avrahami, E., Drory, V.E., Rabey, M.J. and Cohn, D.F. Generalized epileptic seizures as the presenting symptom of lacunar infarction in the brain. Journal of Neurology 1988; 235: 472-474. 49. Boiten, J. and Lodder, J. Lacunar infarcts. Pathogenesis and validity of the clinical syndromes. Stroke 1991; 22: 1374-1378. 50. Aird, R.B., Masland, R.L. and Woodbury, D.M. Neurobiologic substrates of epilepsy. In: The Epilepsies. A

51.

52. 53.

54.

55. 56.

Critical Review (Eds R.B. Aird, R.L. Masland and D.M. Woodbury). New York, Raven Press, 1984: pp. 1-42. Heinemann, U. and Jones, R.S.G. Neurophysiology. In: Comprehensive Epileptology (Eds M. Dam and L. Gram). New York, Raven Press, 1990: pp. 17-42. Meldrum, B.S. Anatomy, physiology and pathology of epilepsy. Lancet 1990; 336: 231-234. Mouritzen Dam, A. and Dam, M. Neuropathology. In: Comprehensive Epileptology (Eds M. Dam and L. Gram). New York, Raven Press, 1990: pp. 43-55. Schousboe, A. Neurochemical alterations associated with epilepsy or seizure activity. In: Comprehensive Epileptology (Eds M. Dam and L. Gram). New York, Raven Press, 1990: pp. 1-16. Caveness, W.F. Epilepsy, a product of trauma in our time. Epilepsia 1976; 17: 207-215. Majkowski, J. Posttraumatic epilepsy. In: Comprehensive Epileptology (Eds M. Dam and L. Gram). New York, Raven Press, 1990: pp. 281-288.