The effect of methylphenidate on neurofibromatosis type 1: a randomised, double-blind, placebo-controlled, crossover trial.

Et Réseau Nf1 Rhône Alpes Auvergne-France ,Laurence Lion-François,Diana Rodriguez,Vania Herbillon,Vincent Des Portes,Patrick Combemale,Behrouz Kassaï,Stéphane Pinson,Isabelle Kemlin,Emeline Peyric,Tiphanie Ginhoux,Virginie Coutinho,Valentine Bréant,Daniel Gérard,Catherine Mercier,François Gueyffier

doi:10.1186/s13023-014-0142-4

Abstract

BackgroundNeurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an estimated prevalence of about 1/3000, independent of ethnicity, race, or gender. Attention Deficit Hyperactivity like Disorder (ADHD)-like characteristics are often reported in patients with NF1. We hypothesised that learning disabilities in NF1 children were related to ADHD symptoms. Treatment with methylphenidate (MPD) has improved learning disabilities in ADHD by acting on neurotransmitters. Our objective was to evaluate its efficacy on ADHD-like symptoms in neurofibromatosis type 1 children (7–12 years).MethodsThis was a randomised, double blind, placebo controlled, and crossover trial comparing 0.5 to 0.8 mg/kg/d of MPD as it is indicated for ADHD to placebo in NF1 children with ADHD-like symptoms. Children aged 7 to 12 years were eligible when their IQ was between 80 and 120. The total follow-up was 9 weeks including 4 weeks for each period and 1 week wash out. Fifty subjects (25 for each period) were required for testing the primary study hypothesis. The main outcome was an improvement in scores on the simplified Conners’ Parent Rating Scale.ResultsThirty-nine patients were included between April 2004 and December 2010. Twenty participants received MPD and 19 placebo during the first period. They all completed the trial. MPD decreased the simplified Conners by 3.9 points (±1.1, p = 0. 0003).ConclusionsThis is the first randomised controlled trial showing the short-term benefit of MPD on simplified Conners scores in NF1 children.Trial registrationClinicalTrials.gov NCT00169611.

Highlights

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an estimated prevalence of about 1/3000, independent of ethnicity, race, or gender
Caused by mutation in the NF1 gene, this condition is characterised by multiple café-au lait spots, benign neurofibromas and Lisch nodules [2]
During the recruitment period, out of 664 children screened with NF1 in our registry, 625 were disqualified

Summary

Introduction

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an estimated prevalence of about 1/3000, independent of ethnicity, race, or gender. We hypothesised that learning disabilities in NF1 children were related to ADHD symptoms. Our objective was to evaluate its efficacy on ADHD-like symptoms in neurofibromatosis type 1 children (7–12 years). Neurofibromatosis type 1 (NF1), known as von Recklinghausen’s disease, is an autosomal dominant disorder with an estimated prevalence of about 1/3000 [1]. The evolution of NF1 is unpredictable and highly variable It may be undetectable by the untrained eye, lead to mild disfigurement or even life threatening conditions [3]. The main complication of NF1 in childhood is cognitive impairment, which affects quality of life and leads to learning disabilities undermining academic achievement in 30-70% of cases [4,5,6]. The incidence of mental retardation is 4-8%, which is slightly higher than in the general population [4,10,11]

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