Download PDF
Neuropediatrics 2012; 43(01): 017-021
DOI: 10.1055/s-0032-1307454
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Bromide in Patients with SCN1A-Mutations Manifesting as Dravet Syndrome

Jan Lotte
1   Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany
,
Edda Haberlandt
2   Clinical Department of Pediatrics IV, Division of Neonatology, Neuropediatrics and Inherited Metabolic Diseases, Medical University Innsbruck, Innsbruck, Austria
,
Bernd Neubauer
3   Zentrum für Kinderheilkunde und Jugendmedizin, Abteilunge für Neuropädiatrie und Sozialmedizin, Universitätsklinikum Gießen, Gießen, Germany
,
Martin Staudt
1   Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany
4   Department of Pediatric Neurology and Developmental Medicine, University Children's Hospital, Tübingen, Germany
,
Gerhard Josef Kluger
1   Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany
5   Paracelsus Medical University, Salzburg, Austria
› Author Affiliations
Further Information

Publication History

10 August 2011

29 December 2011

Publication Date:
19 March 2012 (online)

Also available at
    Permissions and Reprints

Abstract

We report a retrospective analysis of bromide therapy in 32 patients suffering from Dravet syndrome with SCN1A-mutations who received bromide. After 3 months of bromide treatment, 26 patients (81%) showed a relevant improvement with a reduction of seizure frequency by >50% (>75%) in 18 (12) patients (56 and 37%, respectively). After 12 months, we observed a reduction of >50% (>75%) in 15 (9) patients (47 and 28%, respectively). Long-term response was noted in 18 patients (56%). Adverse reactions were mainly mild or moderate leading to treatment termination in 5/32 patients; no aggravation was reported. We conclude that bromide holds promise in patients with SCN1A-mutations suffering from Dravet syndrome.

Keywords

SCN1A-mutation - Dravet syndrome - bromide - long-term efficacy
 

  • References

  • 1 Harkin LA, McMahon JM, Iona X , et al; Infantile Epileptic Encephalopathy Referral Consortium. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain 2007; 130 (Pt 3) 843-852
    CrossrefPubMedSearch in Google Scholar
  • 2 Ohmori I, Ouchida M, Ohtsuka Y, Oka E, Shimizu K. Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy. Biochem Biophys Res Commun 2002; 295 (1) 17-23
    CrossrefPubMedSearch in Google Scholar
  • 3 Depienne C, Trouillard O, Saint-Martin C , et al. Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J Med Genet 2009; 46 (3) 183-191
    PubMedSearch in Google Scholar
  • 4 Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O. Severe myoclonic epilepsy in infancy: Dravet syndrome. Adv Neurol 2005; 95: 71-102
    PubMedSearch in Google Scholar
  • 5 Millichap JJ, Koh S, Laux LC, Nordli Jr DR. Child Neurology: Dravet syndrome: when to suspect the diagnosis. Neurology 2009; 73 (13) e59 –e62
    CrossrefPubMedSearch in Google Scholar
  • 6 Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 2001; 68 (6) 1327-1332
    CrossrefPubMedSearch in Google Scholar
  • 7 Depienne C, Trouillard O, Gourfinkel-An I , et al. Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome. J Med Genet 2010; 47 (6) 404-410
    CrossrefPubMedSearch in Google Scholar
  • 8 Escayg A, Goldin AL. Sodium channel SCN1A and epilepsy: mutations and mechanisms. Epilepsia 2010; 51 (9) 1650-1658
    CrossrefPubMedSearch in Google Scholar
  • 9 Mulley JC, Nelson P, Guerrero S , et al. A new molecular mechanism for severe myoclonic epilepsy of infancy: exonic deletions in SCN1A. Neurology 2006; 67 (6) 1094-1095
    CrossrefPubMedSearch in Google Scholar
  • 10 Nabbout R, Gennaro E, Dalla Bernardina B , et al. Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy. Neurology 2003; 60 (12) 1961-1967
    CrossrefPubMedSearch in Google Scholar
  • 11 Chiron C, Marchand MC, Tran A , et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group. Lancet 2000; 356 (9242) 1638-1642
    CrossrefPubMedSearch in Google Scholar
  • 12 Chiron C. Stiripentol. Neurotherapeutics 2007; 4: 123-125
    CrossrefPubMedSearch in Google Scholar
  • 13 Ceulemans B, Boel M, Claes L , et al. Severe myoclonic epilepsy in infancy: toward an optimal treatment. J Child Neurol 2004; 19 (7) 516-521
    CrossrefPubMedSearch in Google Scholar
  • 14 Doose H, Lunau H, Castiglione E, Waltz S. Severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures. Neuropediatrics 1998; 29 (5) 229-238
    Thieme ConnectPubMedSearch in Google Scholar
  • 15 Guerrini R, Dravet C, Genton P, Belmonte A, Kaminska A, Dulac O. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia 1998; 39 (5) 508-512
    CrossrefPubMedSearch in Google Scholar
  • 16 Ryan M, Baumann RJ. Use and monitoring of bromides in epilepsy treatment. Pediatr Neurol 1999; 21 (2) 523-528
    CrossrefPubMedSearch in Google Scholar
  • 17 Ernst JP, Doose H, Baier WK. Bromides were effective in intractable epilepsy with generalized tonic-clonic seizures and onset in early childhood. Brain Dev 1988; 10 (6) 385-388
    CrossrefPubMedSearch in Google Scholar
  • 18 Oguni H, Hayashi K, Oguni M , et al. Treatment of severe myoclonic epilepsy in infants with bromide and its borderline variant. Epilepsia 1994; 35 (6) 1140-1145
    CrossrefPubMedSearch in Google Scholar
  • 19 Steinhoff BJ, Kruse R. Bromide treatment of pharmaco-resistant epilepsies with generalized tonic-clonic seizures: a clinical study. Brain Dev 1992; 14 (3) 144-149
    CrossrefPubMedSearch in Google Scholar
  • 20 Stephani U, Diener W, Ramm S. Epilepsietherapie mit Kaliumbromid – eine Standortbestimmung. Nervenheilkunde 1999; 18: 311-316
    PubMedSearch in Google Scholar
  • 21 Tanabe T, Awaya Y, Matsuishi T , et al. Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome)—a nationwide questionnaire survey in Japan. Brain Dev 2008; 30 (10) 629-635
    CrossrefPubMedSearch in Google Scholar
  • 22 Hayashi K, Ueshima S, Ouchida M , et al. Therapy for hyperthermia-induced seizures in Scn1a mutant rats. Epilepsia 2011; 52 (5) 1010-1017
    CrossrefPubMedSearch in Google Scholar
  • 23 Almeida AC, Scorza FA, Rodrigues AM , et al. Combined effect of bumetanide, bromide, and GABAergic agonists: an alternative treatment for intractable seizures. Epilepsy Behav 2011; 20 (1) 147-149
    CrossrefPubMedSearch in Google Scholar
  • 24 Meierkord H, Grünig F, Gutschmidt U , et al. Sodium bromide: effects on different patterns of epileptiform activity, extracellular pH changes and GABAergic inhibition. Naunyn Schmiedebergs Arch Pharmacol 2000; 361 (1) 25-32
    CrossrefPubMedSearch in Google Scholar