Background: Strokes are the leading cause of epileptic seizures in adults and account for 50% of seizures in those over the age of 65 years. The use of antiepileptic drugs to prevent recurrent poststroke seizures is recommended. Methods: One hundred and twenty-eight patients with poststroke seizures were randomly allocated to treatment with either levetiracetam (LEV) or sustained-release carbamazepine (CBZ) in a multicenter randomized open-label study. After a titration study phase (2 weeks), the optimal individual dose of trial medication was determined and treatment was continued for another 52 weeks. The primary endpoint was defined as the proportion of seizure-free patients; the secondary endpoints were: evaluation of time recurrence to the first seizure, EEG tracings, cognitive functions and side effects. Results: Of 128 patients, 22 discontinued the trial prematurely; thus a total of 106 patients (52 treated with LEV and 54 treated with CBZ) were included in the analysis. The results of the study were as follows: no significant difference in number of seizure-free patients between LEV and CBZ (p = 0.08); time to the first recurrence tended to be longer among patients on LEV; there was no correlation between the therapeutic effect and the EEG findings in either treatment group; LEV caused significantly fewer (p = 0.02) side effects than CBZ; attention deficit, frontal executive functions and functional scales (Activities of Daily Living and Instrumental Activities of Daily Living indices) were significantly worse in the CBZ group. Conclusions: This trial suggests that LEV may be a valid alternative to CBZ in poststroke seizures, particularly in terms of efficacy and safety. In addition, our results show that LEV has significant advantages over CBZ on cognitive functions. This trial also indicates that LEV in monotherapy is a safe and effective therapeutic option in elderly patients who have suffered epileptic seizures following a stroke.

1.
Beghi E, D’Alessandro R, Beretta S, Consoli D, Crespi V, Delaj L, Gandolfo C, Greco G, La Neve A, Manfredi M, Mattana F, Musolino R, Provinciali L, Santangelo M, Specchio LM, Zaccara G; Epistroke Group: Incidence and predictors of acute symptomatic seizures after stroke. Neurology 2011;77:1776–1778.
2.
Mohr JP, Caplan LR, Melski JW, Goldstein RJ, Duncan GM, Kistler JP, Pessin MS, Bleich HL: The Harvard Cooperative stroke Registry: a prospective registry. Neurology 1978;28:754–762.
3.
Meyer JS, Charney JZ, Rivera VM, Mathew NT: Cerebral embolization prospective clinical analysis of 42 cases. Stroke 1971;2:541–554.
4.
So EL, Annegers JF, Hauser WA, O’Brien PC, Whisnant JP: Population-based study of seizure disorders after cerebral infarction. Neurology 1996;46:350–355.
5.
Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C: Epileptic seizures after a first-ever stroke: the Oxfordshire Community Stroke Project. Br Med J 1997;315:1582–1587.
6.
Shinton RA, Gill JS, Melnick SC, Gupta AK, Beevers DG: The frequency, characteristics and prognosis of epileptic seizures at late onset of stroke. J Neurol Neurosurg Psychiatry 1988;51:272–276.
7.
Lesser RP, Luders H, Dinner DS, Morris HH: Epileptic seizures due to thrombotic and embolic cerebrovascular disease in older patients. Epilepsia 1985;26:622–630.
8.
Labovitz DL, Hauser WA: Preventing stroke-related seizures. When should anticonvulsant be started? Neurology 2003:60:365–366.
9.
Kilpatrick CJ, Davis SM, Tress BM, Rossiter SC, Hopper JL, Vandendriesen ML: Epileptic seizures in acute stroke. Arch Neurol 1990;47:157–160.
10.
Krakow K, Sitzer M, Rosenow F, Steinmetz, Foerch C; for the Arbeitsgruppe Schlaganfall Hessen: Predictors of acute poststroke seizure. Cerebrovasc Dis 2010;30:584–589.
11.
Olsen TS: Post-stroke epilepsy. Curr Atheroscler Rep 2001;3:340–344.
12.
Alvarez-Sabin J, Montaner J, Padro L, Molina CA, Rovira R, Codina A, Quintana M: Gabapentin in late-onset poststroke seizures. Neurology 2002;59:1991–1993.
13.
Kutlu G, Gomceli YB, Unal Y, Inan LE: Leviracetam monotherapy for late poststroke seizures in the elderly. Epilepsy Behav 2008;13:542–544.
14.
Shorvon SD, Lowenthal A, Janz D, Bielen E, Loiseau P: Multicenter double-blind, randomized, placebo-controlled trial of leviracetam as add-on therapy in patients with refractory seizures. Epilepsia 2000;41:1179–1186.
15.
Perruca E: Clinical pharmacokinetics of new generation antiepileptic drugs at the extremes of age. Clin Pharmacokinet 2006;45:351–363.
16.
French J: A systemic review of the safety profiles of levetiracetam: a new antiepileptic drug. Epilepsy Res 2001;47:77–90.
17.
Goldstein LB, Jones MR, Matchar DB, Edwards LJ, Hoff J, Chilukuri V, Armstrong SB, Homer RD: Improving the reliability of stroke subgroup classification using the trial of ORG 10172 in acute stroke treatment (TOAST) criteria. Stroke 2001;32:1091–1098.
18.
Folstein MF, Folstein SE, McHugh PR: Mini-mental state. A practical method for grading the cognitive state of patients for the clinical. J Psychiatr Res 1975;12:189–198.
19.
Weschsler DA: Manual for the Wechsler Adult Intelligence Scale-revised. New York, Psychological Corporation, 1981.
20.
Campo P, Morales M: Reliability and normative data for the Bentos Visual Form Discrimination Test. Clin Neuropsychol 2003;17:220–225.
21.
Wechsler D: WAIS-III Administration and Scoring Manual, San Antonio, Harcourt Brace. 1997.
22.
Stroop JR: Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:643–652.
23.
Raven JC: Coloured Progressive Matrices Sets A, AB, B. London, Lewis, 1962.
24.
Capitani E, Leiacona M: Composite neuropsychological batteries and demographic correction: standardization based on equivalent score, with a review of published data. The Italian Group for the neuropsychological Study of Ageing. J Clin Exp Neuropsychol 1997;19:795–809.
25.
Lincoln NB, Edmans JA: A revalidation of the Rivermead ADL scale for elderly patients with stroke. Age Ageing 1990;19:9–24.
26.
Shiekl JL, Yesavage JA: Geriatric Depression Scale (GDS): Recent evidence and development of a shorter version. Clin Gerontol 1986;5:165–173.
27.
EUSI Writing Committee, Olsen TS, Langhorne P, Diener HC, Hennerici M, Ferro J, Sivenius J, Wahlgren NG, Bath P: European Stroke Initiative executive Committee and the EUSI Writing Committee. European Stroke Initiative Recommendations for Stroke Managment – update 2003. Cerebrovasc Dis 2003;16:311–337.
28.
The European Stroke Initiative Writing Committee and the Writing Committee for the EUSI Executive Committee. European Stroke Initiative Recommendations for the Management of Intracranial Haemorrhage. I. Spontaneous intracerebral haemorrhage. Cerebrovasc Dis 2006;22:294–316.
29.
Rowan AJ, Ramsay RE, Collins JF, Pryor F, Boardman KD, Uthman BM, Spitz M, Frederick T, Towne A, Carter GS, Marks W, Felicetta J, Tomyanovich ML, VA Cooperative Study 428 Group: New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine and carbamazepine. Neurology 2005;64:1868–1873.
30.
Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, Cramp C, Cockerell OC, Cooper PN, Doughty J, Eaton B, Gamble C, Goulding PJ, Howell SJ, Hughes A, Jackson M, Jacoby A, Kellett M, Lawson GR, Leach JP, Nicolaides P, Roberts R, Shackley P, Shen J, Smith DF, Smith PE, Smith CT, Vanoli A, Williamson PR; SANAD study group: The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxocarbamazepine, or topiramate for treatment of partial epilepsy: an unblinded randomized controlled trial. Lancet 2007;369:1000–1015.
31.
Gilad R, Sadeh M, Rapoport A, Dabby R, Boaz M, lampl Y: Monotherapy of lamotrigine versus carbamazepine in patients with poststroke seizure. Clin Neuropharmacol 2007;30:189–195.
32.
Alvarez-Sabin J, Montaner J, Padro I, et al: Gabapentin in late onset poststroke seizures. Neurology 2002;59:1991–1993.
33.
Stephen LJ: Drug treatment of epilepsy in elderly people: focus on valproic acid. Drugs Aging 2003;20:141–152.
34.
Gulnihal K, Yasemin BG, Yasemin U, Levent EI. Levipiracetam monotherapy for late poststroke seizures in the elderly. Epilepsy Behav 2008;13:542–544.
35.
Meador KJ: Cognitive effects of epilepsy and of antiepileptic medications; in Wyllie E (ed): The Treatment of Epilepsy: Principles and Practices. Phhiladelphia, Lippincott Williams & Wilkins, 2005, pp 1185–1195.
36.
Helmstaedter C, Witt JA: Cognitive outcome of antiepileptic treatment with levipiracetam versus carbamazepine monotherapy: a non-interventional surveillance trial. Epilepsy Behav 2010;18:74–80.
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