Sage Journals: Discover world-class research

Abstract

Rett syndrome is characterized by the development of stereotypic hand movements and seizures, which are often difficult to treat. Previous studies have shown conflicting results during add-on folinic acid. Here, the authors reevaluate the response to folinic acid in terms of epilepsy control and electroencephalography features. They performed a randomized, placebo-controlled, double-blind crossover trial, with a follow-up of more than 2 years. Twelve girls with Rett syndrome participated, comparable in clinical stage and disease severity. The Rett syndrome patients were given either folinic acid or placebo, for 1 year each. Only 3 girls benefited to some extent: 2 had a reduction and/or decrease in seizures, and all 3 showed some decreased epileptiform activity on electroencephalography during the addition of folinic acid. Despite this, antiepileptic drugs were adjusted. Because the effect of added folinic acid was limited and did not prevent antiepileptic drug increase, the authors do not recommend adding on folinic acid in Rett syndrome girls with epilepsy.

Keywords

Rett syndrome seizures folinic acid double-blind placebo-controlled study electroencephalography folate epilepsy

Get full access to this article

View all access options for this article.

References

Cass H. , Reilly S. , Owen L. , et al. Findings from a multidisciplinary clinical case series of females with Rett syndrome. Dev Med Child Neurol. 2003;45:325-337.

Hagberg B. , Hanefeld F. , Percy A. , Skjeldal O. An update on clinically applicable diagnostic criteria in Rett syndrome . Eur J Paediatr Neurol. 2002;6:293-297.

Amir RE , Van den Veyver IB , Wan M. , et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methylCpG-binding protein 2. Nat Genet. 1999 ;23:185-188.

Neul JL , Fang P. , Barrish J. , et al. Specific mutations in methylCpG-binding protein 2 confer different severity in Rett syndrome. Neurology. 2008 ;70:1313-1321.

Jian L. , Nagarajan L. , Klerk de N. , et al. Seizures in Rett syndrome: an overview from a one-year calendar study. Eur J Paediatr Neurol. 2007;11:310-317.

Glaze DG , Percy AK , Skinner S. , et al. Epilepsy and the natural history of Rett syndrome. Neurology. 2010;74:909-912.

Glaze DG , Schultz RJ , Frost JD Rett syndrome: characterization of seizures versus non seizures. Electroencephalogr Clin Neurophysiol. 1998;106:79-83.

Ramaekers VT , Hansen SI , Holm J. , et al. Reduced folate transport to the CNS in female Rett syndrome patients. Neurology . 2003;61:506-515.

Neul JL , Maricich SM , Islam M. , et al. Spinal fluid 5 methyltetrahydrofolate levels are normal in Rett syndrome. Neurology. 2005; 64:2151-2152.

10.

Ormazabal A. , Artuch R. , Vilaseca MA , et al. Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid. Neuropediatrics. 2005;36: 380-385.

11.

Temudo T. , Rios M. , Prior C. , et al. Evaluation of CSF neurotransmitters and folate in 25 patients with Rett syndrome disorder and effects of treatment. Brain Dev. 2009;31:46-51.

12.

Schanen C. , Houwink EJF , Dorrani N. , et al. Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome. Am J Med Genet A. 2004;126A:129-140.

13.

Dijk van JG EEG for the neurologist. Terminology of the EEG: [Dutch]. 2008;2:45.

14.

Ramaekers VT , Blau N. , Sequeira JM , et al. Folate receptor autoimmunity and cerebral folate deficiency in low functioning autism with neurological deficits. Neuropediatrics. 2007;38: 276-281.

15.

Garzia-Cazorla A. , Quadros EV , Nascimento A. , et al. Mitochondrial diseases associated with cerebral folate deficiency. Neurology . 2008;70:1360-1362.

16.

Bahi-Buisson N. , Guellec I. , Nabbout R. , et al. Parental view of epilepsy in Rett syndrome. Brain Dev. 2008 ;30:126-130.

Clinical and Electroencephalographic Effects of Folinic Acid Treatment in Rett Syndrome Patients

Abstract

Keywords

Get full access to this article

References