Normal intellectual skills in patients with Rhombencephalosynapsis.

OBJECTIVES: Rhombencephalosynapsis (RES) is a very rare cerebellar malformation. Neurodevelopmental outcome of apparently isolated RES remains poorly documented and standardized cognitive assessment, reported in only nine published cases so far, is lacking. Prenatal counselling is challenging considering the uncertain prognosis of isolated RES. The aim of this study was to focus on cognitive and motor outcome of isolated RES with a clinical description of six new cases and a detailed review of the literature. METHODS: A single-centre retrospective study of all RES patients over a 15-year period. Ataxia and fine motor skills were scored using a five-grade scale, according to the degree of disturbance of daily living. Intelligence Quotient (IQ) was established according to age-related Weschler Intelligence Scales. A systematic literature review included published cases with relevant outcome data. RESULTS: Six new cases of apparently isolated RES were reported, including three diagnosed in prenatal settings. The onset age for walking was delayed in four patients. Three patients had head shaking and three had a strabismus. One patient had a mild motor disability, one had subtle ataxia that did not impair daily life and four patients had a normal neurological examination at the last visit. Intellectual abilities were normal in all patients (full IQ score from 90 to 142), although three had ADHD. All received standard schooling. Based on these six new cases, as well as cases from 12 publications in the literature, a total of 28 patients with non-syndromic RES were analysed. Concerning motor outcome, 72% had no complaint or minimal impairment, 16% moderate and 12% severe impairment. Concerning cognitive outcome, 68% had normal cognitive skills, 18% borderline intellectual functioning and 14% moderate to severe disability.

Attention and Executive Disorders in Neurofibromatosis 1: Comparison Between NF1 With ADHD Symptomatology (NF1 + ADHD) and ADHD Per Se.

Objective: To compare children with Neurofibromatosis type 1 and associated ADHD symptomatology (NF1 + ADHD) with children having received a diagnosis of ADHD without NF1. The idea was that performance differences in tasks of attention between these two groups would be attributable not to the ADHD symptomatology, but to NF1 alone. Method: One group of children with NF1 + ADHD (N = 32), one group of children with ADHD (N = 31), and one group of healthy controls (N = 40) participated in a set of computerized tasks assessing intensive, selective, and executive aspects of attention. Results: Differences were found between the two groups of patients in respect of several aspects of attention. Children with NF1 + ADHD did not always perform worse than children with ADHD. Several double dissociations can be established between the two groups of patients. Conclusion: ADHD symptomatology in NF1 does not contribute to all attention deficits, and ADHD cannot account for all attention impairments in NF1.

Outcome of isolated agenesis of the corpus callosum: A population-based prospective study.

OBJECTIVES: Neurodevelopmental outcome of apparently isolated agenesis of the corpus callosum (ACC) remains a major concern with uncertain prognosis. Despite "normal" IQ reported in a majority of patients, the rates of learning disabilities and severe outcome (ranging from 0% to 20%) are not clearly established. METHODS: A large population-based series was investigated based on a longitudinal follow-up until school age, using Wechsler Intelligence scales at 3, 5, and 7 years. RESULTS: Fifty women were referred to a tertiary referral unit for an "apparently" isolated ACC confirmed by ultrasound, foetal MRI, and karyotyping or array CGH. Twelve pregnancies were terminated, one foetus died in utero, one pregnancy outcome was unknown, and 36 babies were born. Two were lost to follow-up. Thirty-four children could be classified into three groups. Group 1 comprised two children (6%) with severe intellectual disability (one Mowat-Wilson syndrome and one ASD). Group 2 comprised 10 children (29%) who had learning disabilities and borderline intellectual functioning (VIQ and/or PIQ scores >70 and <85); three patients had hypopituitarism with additional MRI anomalies revealed after birth. Group 3 comprised 22 children (65%) who had both VIQ and PIQ >85 (-1 SD) with a normal school level. Longitudinal follow-up revealed weaker PIQ in younger children which improved with age. CONCLUSION: Our data indicate that intellectual ability is normal (IQ > 85) in approximately two thirds and borderline in just over a quarter of patients. However, a low risk of severe cognitive impairment exists, and this information should be shared with couples during prenatal counselling.

Multimodal Outcome at 7 Years of Age after Neonatal Arterial Ischemic Stroke.

OBJECTIVES: To evaluate the epileptic, academic, and developmental status at age 7 years in a large population of term-born children who sustained neonatal arterial ischemic stroke (NAIS), and to assess the co-occurrence of these outcomes. STUDY DESIGN: A cohort study including 100 term newborns with NAIS was designed. Two infants died during the neonatal period, 13 families were lost to follow-up, and 5 families declined to participate in this evaluation. Thus, 80 families completed the 7-year clinical assessment. Epileptic status, schooling, motor abilities, global intellectual functioning, spoken language, and parental opinions were recorded. Principal component analysis was applied. RESULTS: Rates of impaired language, cerebral palsy, low academic skills, active epilepsy, and global intellectual deficiency were 49%, 32%, 28%, 11%, and 8%, respectively. All were highly correlated. Eventually, 59% of children were affected by at least 1 of the aforementioned conditions. In 30% of cases, the viewpoints of health practitioners and parents did not match. CONCLUSION: The prevalence of severe disabilities at 7 years after NAIS is low, but most children exhibit some impairment in developmental profile. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02511249), Programme Hospitalier de Recherche Clinique Régional (0308052), Programme Hospitalier de Recherche Clinique Interrégional (1008026), and EudraCT (2010-A00329-30).

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

BACKGROUND: Neurofibromatosis 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). METHODS: This 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. RESULTS: Thirty-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). CONCLUSIONS: This is the first randomised controlled trial showing the short-term benefit of MPD on simplified Conners scores in NF1 children. TRIAL REGISTRATION: ClinicalTrials.gov NCT00169611.