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      Levetiracetam versus Carbamazepine in Patients with Late Poststroke Seizures: A Multicenter Prospective Randomized Open-Label Study (EpIC Project)

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          Abstract

          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.

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          Most cited references21

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          The Harvard Cooperative Stroke Registry: a prospective registry.

          Data from 694 patients hospitalized with stroke were entered in a prospective, computer-based registry. Three hundred and sixty-four patients (53 percent) were diagnosed as having thrombosis, 215 (31 percent)as having cerebral embolism 70 (10 percent) as having intracerebral hematoma, and 45 (6 percent) as having subarachnoid hemorrhage from aneurysm or arteriovenous malformations. The 364 patients diagnosed as having thrombosis were divided into 233 (34 percent of all 694 patients) whose thrombosis was thought to involve a large artery and 131 (19 percent) with lacunar infarction. Many of the findings in this study were comparable to those in previous registries based on postmortem data. New observations include the high incidence of lacunes and cerebral emboli, the absence of an identifiable cardiac origin in 37 percent of all emboli, a nonsudden onset in 21 percent of emboli, and the occurrence of vomiting at onset in 51 percent and the absence of headache at onset in 67 percent of hematomas.
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            Recommendations for the Management of Intracranial Haemorrhage – Part I: Spontaneous Intracerebral Haemorrhage

            This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European societies which are represented in the EUSI: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.
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              Population-based study of seizure disorders after cerebral infarction.

              We performed the first population-based study that determined the magnitude of the risk and identified the factors predictive of developing seizure disorders after cerebral infarction. Five hundred thirty-five consecutive persons without prior unprovoked seizures were followed from their first cerebral infarctions until death or migration out of Rochester, Minnesota. Thirty-three patients (6%) developed early seizures (within 1 week), 78% of which occurred within the first 24 hours after infarction. Using multivariate analysis, the only factor predictive of early seizure occurrence was anterior hemisphere location of infarct (odds ratio 4.0; 95% CI 1.2 to 13.7). Twenty-seven patients developed an initial late seizure (past 1 week), whereas 18 developed epilepsy (recurrent late seizures). Compared with the population in the community, the risk during the first year was 23 times higher for initial late seizures and 17 times higher for epilepsy. The cumulative probability of developing initial late seizures was 3.0% by 1 year, 4.7% by 2 years, 7.4% by 5 years, and 8.9% by 10 years. Independent predictive factors on multivariate analysis for initial late seizures were early seizure occurrence (hazard ratio of 7.8 [95% CI 2.8 to 21.7]) and stroke recurrence (3.1 [1.2 to 8.3]). Both early seizure occurrence (16.4 [5.5 to 49.2]) and stroke recurrence (3.5 [1.2 to 10.5]) independently predicted the development of epilepsy as well. We also found that early seizure occurrence predisposed those with initial late seizures to develop epilepsy.
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                Author and article information

                Journal
                CED
                Cerebrovasc Dis
                10.1159/issn.1015-9770
                Cerebrovascular Diseases
                S. Karger AG
                1015-9770
                1421-9786
                2012
                November 2012
                01 November 2012
                : 34
                : 4
                : 282-289
                Affiliations
                aOperative Unit of Neurology, Jazzolino Hospital, Vibo Valentia, bDepartment of Neurology, S. Giovanni di Dio Hospital, Crotone, cOperative Unit of Neurophysiopathology, Monteluce Hospital and dOperative Unit of Neurology, Città di Castello Hospital, Perugia, eOperative Unit of Neurophysiopathology, S. Martino Hospital, Genoa, fOperative Unit of Neurology, Torrino Hospital, Brindisi, gS. Filippo Neri Hospital and hOperative Unit of Neurovascular Treatment, Department of Neurology and Psychiatry, La Sapienza University, Rome, Italy
                Author notes
                *Domenico Consoli, Operative Unit of Neurology, Jazzolino Hospital, Via P. Fleming, IT–89900 Vibo Valentia (Italy), E-Mail neurologiavv@live.it
                Article
                342669 Cerebrovasc Dis 2012;34:282–289
                10.1159/000342669
                23128439
                a2aca82f-ec77-4c28-be02-7f9fe4200b06
                © 2012 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 28 March 2012
                : 13 August 2012
                Page count
                Figures: 2, Tables: 4, Pages: 8
                Categories
                Original Paper

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Epilepsy,Levetiracetam,Carbamazepine,Poststroke seizures

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