Amelioration of Levetiracetam-Induced Behavioral Side Effects by Pyridoxine. A Randomized Double Blind Controlled Study.

BACKGROUND: Levetiracetam is a relatively new-generation antiseizure drug approved for the treatment of focal and generalized seizures. Despite its favorable side effect profile and minimal drug-drug interactions, neuropsychiatric side effects are reported in up to 13% of children. A few case series have suggested that supplementation of pyridoxine may mitigate these side effects, but controlled trials are lacking. To address this issue, a randomized interventional study was carried out in a pediatric tertiary hospital to qualify and quantify the potential beneficial effect of pyridoxine in attenuating the neuropsychiatric side effects of levetiracetam in children. METHODS: A total of 105 children with epilepsy who were taking levetiracetam (as a monotherapy or an adjunct) who showed behavioral symptoms coinciding with the start of levetiracetam, were included. Patients randomly and blindly received either a therapeutic (pyridoxine group, 46 of 105, 44%) or a homeopathic dose of pyridoxine (placebo, 59 of 105, 56%). A 30-item behavioral checklist was used to qualify and quantify the behavioral side effects at baseline and at different time points following initiation of treatment. RESULTS: Both placebo and pyridoxine groups experienced a statistical reduction in behavioral scores when compared with baseline. Our study indicated that although there was a placebo effect, the improvement in neuropsychiatric symptoms was more prominent in children who received therapeutic doses of pyridoxine. CONCLUSIONS: These data provide clinicians with pertinent evidence-based information that suggests that a trial of pyridoxine in patients who experience behavioral side effects due to the use of levetiracetam may avoid unnecessary change of antiseizure medications.

Widening the phenotypic spectrum - Non epileptic presentation of folate transporter deficiency.

INTRODUCTION: Folate is essential for production of DNA, neurotransmitters and myelin and regulation of genetic activity. A specific transporter protein is required to transport folate from blood to CSF. Various inherited brain-specific folate transport defects have been recognized due to mutation in Folate Receptor alpha (FOLR1). FOLR1 mutation is one of the vitamin responsive encephalopathies and is inherited as an autosomal recessive condition. It has a wide spectrum of phenotype, commonly presenting as epileptic encephalopathy. Less frequently the condition may manifest with subtle hypotonia, movement disorder as tremors, ataxia or intellectual disability and autistic spectrum disorder. We present a case of folate transporter deficiency with non-epileptic manifestations, presenting with tremors, speech delay and stable white matter changes in MRI brain. OBJECTIVE: We present a case of Folate transporter defect with Non-epileptic presentation. CONCLUSION: Folate transporter deficiency has a wide range of presenting symptoms. Presentation with slowly progressive atypical symptoms, stable white matter changes in brain MRI that does not fit a specific diagnosis, should raise a high suspicion of FOLR1 mutation, even in absence of seizures. Since folate transporter deficiency is a treatable neurodegenerative disorder, early diagnosis and supplementation with folinic acid is vital.