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

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.

Neurodevelopmental disorders in children with neurofibromatosis type 1

“…15 However, despite a limited understanding of the potential etiology of ADHD in NF1, it is of critical importance to recognize and treat these symptoms as several studies have now demonstrated the benefit of stimulant medications for the treatment of ADHD in children with NF1. 17,18 SOCIAL DEFICITS AND OVERLAP WITH ASD Children with NF1 have long been recognized to exhibit social perception problems, although the exact nature of these deficits was not explored until recently. Previously, it had been posited that the social difficulties experienced by What this paper adds • Impairments in general cognition, executive function, and visuospatial processing are common in children with neurofibromatosis type 1 (NF1).…”

Neuropsychological Functioning in Individuals with Noonan Syndrome: a Systematic Literature Review with Educational and Treatment Recommendations

“…However, preliminary research on other RASopathies suggests several avenues for intervention. For example, stimulant medications (e.g., methylphenidate) are known to be effective in improving cognitive, behavioral, and social outcomes in individuals with NF1 who have symptoms of ADHD (Mautner et al 2002;Lion-Francois et al 2014). For children with NS, the possibility of medication must be considered in consultation with medical providers familiar with the child's complex history, lending special attention to growth considerations and cardiac risk.…”

Behavioral and cognitive outcomes for clinical trials in children with neurofibromatosis type 1

“…11 Six clinical trials aimed at treating cognitive deficits in NF1 are reported in the literature (table 1). [12][13][14][15][16][17] Clearly, there is a lack of consensus on the set of outcome measures used. This article analyzes the scores on outcome measures used in the Simvastatin for cognitive deficits and behavioral problems in patients with neurofibromatosis type 1 (NF1-SIMCODA) trial, which evaluated the effect of 12-month simvastatin treatment on cognitive functioning and behavioral problems in children with NF1.…”