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      Febrile seizure recurrence reduced by intermittent oral levetiracetam

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          Abstract

          Objective

          Febrile seizure (FS) is the most common form of childhood seizure disorders. FS is perhaps one of the most frequent causes of admittance to pediatric emergency wards worldwide. We aimed to identify a new, safe, and effective therapy for preventing FS recurrence.

          Methods

          A total of 115 children with a history of two or more episodes of FS were randomly assigned to levetiracetam (LEV) and control (LEV/control ratio = 2:1) groups. At the onset of fever, LEV group was orally administered with a dose of 15–30 mg/kg per day twice daily for 1 week. Thereafter, the dosage was gradually reduced until totally discontinued in the second week. The primary efficacy variable was seizure frequency associated with febrile events and FS recurrence rate (RR) during 48-week follow-up. The second outcome was the cost effectiveness of the two groups.

          Results

          The intention-to-treat analysis showed that 78 children in LEV group experienced 148 febrile episodes. Among these 78 children, 11 experienced 15 FS recurrences. In control group, 37 children experienced 64 febrile episodes; among these 37 children, 19 experienced 32 FS recurrences. A significant difference was observed between two groups in FS RR and FS recurrence/fever episode. The cost of LEV group for the prevention of FS recurrence is lower than control group. During 48-week follow-up period, one patient in LEV group exhibited severe drowsiness. No other side effects were observed in the same patient and in other children.

          Interpretation

          Intermittent oral LEV can effectively prevent FS recurrence and reduce wastage of medical resources.

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          Most cited references21

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          Neurodiagnostic evaluation of the child with a simple febrile seizure.

          , (2011)
          To formulate evidence-based recommendations for health care professionals about the diagnosis and evaluation of a simple febrile seizure in infants and young children 6 through 60 months of age and to revise the practice guideline published by the American Academy of Pediatrics (AAP) in 1996. This review included search and analysis of the medical literature published since the last version of the guideline. Physicians with expertise and experience in the fields of neurology and epilepsy, pediatrics, epidemiology, and research methodologies constituted a subcommittee of the AAP Steering Committee on Quality Improvement and Management. The steering committee and other groups within the AAP and organizations outside the AAP reviewed the guideline. The subcommittee member who reviewed the literature for the 1996 AAP practice guidelines searched for articles published since the last guideline through 2009, supplemented by articles submitted by other committee members. Results from the literature search were provided to the subcommittee members for review. Interventions of direct interest included lumbar puncture, electroencephalography, blood studies, and neuroimaging. Multiple issues were raised and discussed iteratively until consensus was reached about recommendations. The strength of evidence supporting each recommendation and the strength of the recommendation were assessed by the committee member most experienced in informatics and epidemiology and graded according to AAP policy. Clinicians evaluating infants or young children after a simple febrile seizure should direct their attention toward identifying the cause of the child's fever. Meningitis should be considered in the differential diagnosis for any febrile child, and lumbar puncture should be performed if there are clinical signs or symptoms of concern. For any infant between 6 and 12 months of age who presents with a seizure and fever, a lumbar puncture is an option when the child is considered deficient in Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae immunizations (ie, has not received scheduled immunizations as recommended), or when immunization status cannot be determined, because of an increased risk of bacterial meningitis. A lumbar puncture is an option for children who are pretreated with antibiotics. In general, a simple febrile seizure does not usually require further evaluation, specifically electroencephalography, blood studies, or neuroimaging.
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            Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures.

            (2008)
            Febrile seizures are the most common seizure disorder in childhood, affecting 2% to 5% of children between the ages of 6 and 60 months. Simple febrile seizures are defined as brief (<15-minute) generalized seizures that occur once during a 24-hour period in a febrile child who does not have an intracranial infection, metabolic disturbance, or history of afebrile seizures. This guideline (a revision of the 1999 American Academy of Pediatrics practice parameter [now termed clinical practice guideline] "The Long-term Treatment of the Child With Simple Febrile Seizures") addresses the risks and benefits of both continuous and intermittent anticonvulsant therapy as well as the use of antipyretics in children with simple febrile seizures. It is designed to assist pediatricians by providing an analytic framework for decisions regarding possible therapeutic interventions in this patient population. It is not intended to replace clinical judgment or to establish a protocol for all patients with this disorder. Rarely will these guidelines be the only approach to this problem.
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              Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy.

              E B Menachem, Sonia M. Brodie, P. Ryvlin … (2007)
              We report the results of a prospective study of the efficacy and tolerability of levetiracetam, a new antiepileptic drug with a unique mechanism of action, in comparison with controlled-release carbamazepine as first treatment in newly diagnosed epilepsy. Adults with > or =2 partial or generalized tonic-clonic seizures in the previous year were randomly assigned to levetiracetam (500 mg twice daily, n = 288) or controlled-release carbamazepine (200 mg twice daily, n = 291) in a multicenter, double-blind, noninferiority, parallel-group trial. If a seizure occurred within 26 weeks of stabilization, dosage was increased incrementally to a maximum of levetiracetam 1,500 mg twice daily or carbamazepine 600 mg twice daily. Patients achieving the primary endpoint (6-month seizure freedom) continued on treatment for a further 6-month maintenance period. At per-protocol analysis, 73.0% (56.6%) of patients randomized to levetiracetam and 72.8% (58.5%) receiving controlled-release carbamazepine were seizure free at the last evaluated dose (adjusted absolute difference 0.2%, 95% CI -7.8% to 8.2%) for > or =6 months (1 year). Of all patients achieving 6-month (1-year) remission, 80.1% (86.0%) in the levetiracetam group and 85.4% (89.3%) in the carbamazepine group did so at the lowest dose level. Withdrawal rates for adverse events were 14.4% with levetiracetam and 19.2% with carbamazepine. Levetiracetam and controlled-release carbamazepine produced equivalent seizure freedom rates in newly diagnosed epilepsy at optimal dosing in a setting mimicking clinical practice. This trial has confirmed in a randomized, double-blind setting previously uncontrolled observations that most people with epilepsy will respond to their first-ever antiepileptic drug at low dosage.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Ann Clin Transl Neurol
                Journal ID (iso-abbrev): Ann Clin Transl Neurol
                Journal ID (publisher-id): acn3
                Title: Annals of Clinical and Translational Neurology
                Publisher: BlackWell Publishing Ltd (Oxford, UK )
                ISSN (Print): 2328-9503
                ISSN (Electronic): 2328-9503
                Publication date (Print): March 2014
                Publication date (Electronic): 24 February 2014
                Volume: 1
                Issue: 3
                Pages: 171-179
                Affiliations
                [1 ]Department of Pediatrics, Chinese PLA General Hospital Beijing, 100583, China
                [2 ]Department of Neurology, Jiang-Xi Children's Hospital Jiangxi, 330006, China
                [3 ]Department of Neurology, Beijing Children's Hospital Beijing, 100045, China
                [4 ]Department of Neurology, Children's Hospital of Chongqing Medical University Chongqing, 400014, China
                [5 ]The Beijing new century children's Hospital Beijing, 100045, China
                [6 ]Departments of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne Melbourne, Australia
                [7 ]Department of Medicine and Therapeutics, Chinese University of Hong Kong Hong Kong, China
                Author notes
                Correspondence Li-Ping Zou, Department of Pediatrics, Chinese PLA General Hospital, Beijing 100583, China. Tel: +86-10-55499016; Fax: +86-10-66939770; E-mail: zouliping21@ 123456hotmail.com
                [a]

                Co-first author.

                Funding InformationThis study was supported by the National Natural Science Foundation of China (Nos. 30770747, 1071036, 81200463, 81201013) and the Beijing Municipal Natural Science Foundation (Nos. 7081002 and 7042024), Zhejiang Provincial Natural Science Foundation of China (NO. Y2100440).

                Article
                DOI: 10.1002/acn3.34
                PMC ID: 4184546
                SO-VID: 0faccd46-704f-41c1-b2aa-007f635b5aae
                Copyright © © 2014 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
                License:

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 29 November 2013
                Date revision received : 21 December 2013
                Date accepted : 23 December 2013
                Categories
                Subject: Research Papers

                Data availability:

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