How to Detect Isolated PEX10-Related Cerebellar Ataxia?

A 4-year-old boy presented with subacute onset of cerebellar ataxia. Neuroimaging revealed cerebellar atrophy. Metabolic screening tests aiming to detect potentially treatable ataxias showed an increased value (fourfold upper limit of normal) for phytanic acid and elevated very-long-chain fatty acid (VLCFA) ratios (C24:0/C22:0 and C26:0/C22:0), while absolute concentrations of VLCFA were normal. Genetic analysis identified biallelic variants in PEX10. Immunohistochemistry confirmed pathogenicity in the patients' cultured fibroblasts demonstrating peroxisomal mosaicism with a general catalase import deficiency as well as conspicuous peroxisome morphology as an expression of impaired peroxisomal function. We describe for the first time an elongated peroxisome morphology in a patient with PEX10-related cerebellar ataxia.A literature search yielded 14 similar patients from nine families with PEX10-related cerebellar ataxia, most of them presenting their first symptoms between 3 and 8 years of age. In 11/14 patients, the first and main symptom was cerebellar ataxia; in three patients, it was sensorineural hearing impairment. Finally, all 14 patients developed ataxia. Polyneuropathy (9/14) and cognitive impairment (9/14) were common associated findings. In 12/13 patients brain MRI showed cerebellar atrophy. Phytanic acid was elevated in 8/12 patients, while absolute concentrations of VLCFA levels were in normal limits in several patients. VLCFA ratios (C24:0/C22:0 and/or C26:0/C22:0), though, were elevated in 11/11 cases. We suggest including measurement of phytanic acid and VLCFA ratios in metabolic screening tests in unexplained autosomal recessive ataxias with cerebellar atrophy, especially when there is an early onset and symptoms are mild.

Martial Arts and Cognitive Control in Children with Attention-Deficit Hyperactivity Disorder and Children Born Very Preterm: A Combined Analysis of Two Randomized Controlled Trials.

INTRODUCTION: Very preterm birth and attention-deficit hyperactivity disorder (ADHD) are associated with impairments in response inhibition that often persist beyond childhood. Athletes skilled in martial arts show a neurocognitive profile that is associated with an improved inhibition processing stream, suggesting that engagement in this kind of sport has the potential to reduce impairments in this cognitive function. We investigated the behavioral and neurocognitive effects of judo training on response inhibition in children born very preterm and children with ADHD by a combined analysis of two randomized controlled trials. METHODS: In both the CHIPMANC ( n = 65) and JETPAC ( n = 63) studies, participants were randomly allocated to a waitlist or a 12-wk judo training program in a 1:1 ratio. At pretest and posttest, participants completed a Go/NoGo task, the Movement Assessment Battery for Children-2 and a physical work capacity test on a bicycle ergometer. During the cognitive task, event-related potentials (N2, P3a, P3b) were recorded via electroencephalography. RESULTS: The effects of the judo training were moderated by the study group. In contrast to children with ADHD (JETPAC), judo training reduced the commission error rate on the Go/NoGo task and increased the P3a amplitude in children born very preterm (CHIPMANC). No treatment effects were found for N2, P3b and physical fitness outcomes. CONCLUSIONS: The neurodevelopmental condition influences the cognitive benefits of judo training. Whereas judo may be ineffective in children with ADHD, children born very preterm can expect improved response inhibition due to a more effective engagement of focal attention to resolve the task-related response conflict.

Behavioral and neurocognitive effects of judo training on working memory capacity in children with ADHD: A randomized controlled trial.

BACKGROUND: Children with Attention Deficit Hyperactivity Disorder (ADHD) face deficits in working memory capacity that often persist into adulthood. In healthy peers, exercise targeting motor skill acquisition benefits visuospatial working memory, but its potential to reduce ADHD-related deficits remains unclear. We investigated the effect of a judo training program targeting motor skills on behavioral and neurocognitive indices of working memory capacity in children with ADHD. METHODS: Children with ADHD aged 8 to 12 years (N = 57) were randomly allocated to a judo training group and a wait-list control group. The training program encompassed 120 min of judo per week over three months. Before and after the intervention period, participants completed a bilateral Change Detection task with low and high memory load conditions and the Movement Assessment Battery for Children-2 (MABC-2). The contralateral delay activity (CDA) elicited by the cognitive task was recorded using electroencephalography. RESULTS: Compared to the control group, the judo training group showed a higher K-score on the Change Detection task and an increased negativity of the CDA on the high load condition following the intervention, when pretest scores (and confounders) were accounted for. In contrast, no group differences were found for MABC-2 score. CONCLUSION: In children with ADHD, judo training may complement the pharmacological treatment by increasing the effectiveness of working memory maintenance processes. On a behavioral level, this improvement is accompanied with an increased capacity to store visuospatial information.

Deletion of 7q11.21-q11.23 and infantile spasms without deletion of MAGI2.

We report on the clinical and cytogenetic findings and on the array-based characterization of an interstitial 7q11.21-q11.23 deletion initially recognized by standard karyotyping in a 15-month-old female patient. Beginning at the age of 3 months and 2 weeks the patient had severe infantile spasms. Recently, it was reported that infantile spasms are associated with deletion of the MAGI2 gene on chromosome 7q11.23. Nevertheless, not all patients reported with deletions of MAGI2 developed infantile spasms and at least one reported patient with a deletion 7q11.23 without missing the MAGI2 gene was diagnosed with infantile spasms. Molecular karyotyping of our patient confirmed a large 13 Mb deletion encompassing the 7q11.21-q11.23 region without involvement of MAGI2. Critical review of published data and the results of our patient underline the importance to map precisely the deletion boundaries of further patients to reevaluate the significance of MAGI2 hemizygosity in the pathogenesis of infantile spasms.

Factors affecting cognitive outcome in early pediatric stroke.

OBJECTIVE: We examined cognitive performance in children after stroke to study the influence of age at stroke, seizures, lesion characteristics, neurologic impairment (NI), and functional outcome on cognitive outcome. METHODS: This was a prospectively designed study conducted in 99 children who sustained an arterial ischemic stroke (AIS) between the age of 1 month and 16 years. All children underwent cognitive and neurologic follow-up examination sessions 2 years after the insult. Cognitive development was assessed with age-appropriate instruments. RESULTS: Although mean cognitive performance was in the lower normative range, we found poorer results in subtests measuring visuoconstructive skills, short-term memory, and processing speed. Risk factors for negative cognitive outcome were young age at stroke, seizures, combined lesion location (cortical and subcortical), as well as marked NI. CONCLUSIONS: We recommend that all children with a history of AIS undergo regularly scheduled neuropsychological assessment to ensure implementation of appropriate interventions and environmental adjustments as early as possible.