Efficacy of methylphenidate treatment in childhood myotonic dystrophy type 1 and comorbid attention deficit hyperactivity disorder: A case report using eye tracking assessment.

INTRODUCTION: Despite the increased prevalence of comorbid attention deficit hyperactivity disorder (ADHD) in children with myotonic dystrophy type 1, the effects of methylphenidate treatment on associated cognitive deficits in this population is not yet investigated. CASE: We describe a case study of an eleven-year-old male patient with myotonic dystrophy type 1 and comorbid ADHD that was treated with methylphenidate in a twice daily regime (0.60 mg/kg/day). Positive effects on learning and cognition were reported by the parents and teachers. No negative side effects were reported. Sequential neuropsychological assessments before and 45 minutes after methylphenidate intake were conducted to quantify the cognitive effects of methylphenidate treatment. Significant improvements in regulation of attention were behaviorally observed and were quantified using eye tracking technology. CONCLUSION: We conclude that methylphenidate may be an effective treatment for ADHD-related cognitive deficits and learning difficulties in children with myotonic dystrophy type 1 which merits further research.

Cognitive phenotype of childhood myotonic dystrophy type 1: A multicenter pooled analysis.

INTRODUCTION/AIMS: There is clear evidence for brain involvement in childhood myotonic dystrophy type 1 (DM1) from imaging studies and the prevalence of intellectual impairment and neurodevelopmental disorders. The cognitive profile of children with DM1 however is poorly understood. The aim of this study was to assess the cognitive profile of children with DM1. METHODS: Neuropsychological examination reports of 45 children aged 2-17 y were analyzed. All cognitive subtests used in this cohort were pooled in 10 cognitive domains. For every patient a composite z-score was calculated for every assessed domain. Composite scores were classified as average (z > -1), mild cognitive impairment (-1 ≥ z > -2), or major cognitive impairment (z ≤ -2). RESULTS: The nature and extent of neuropsychological examinations differed between centers and patients. The domains with the highest frequency of major cognitive impairment were social cognition (4/9 children tested; 44%), attention (13/32; 41%), and fine motor skills (3/10; 30%). Combining mild and major cognitive impairment, working memory (20/28; 71%), attention (21/32; 66%), and visuospatial functions (16/28; 57%) were the most frequently affected domains. Long-term memory was least affected, with mild impairment only in 5/29 (17%). DISCUSSION: Children with DM1 may have specific cognitive deficits, most frequently affecting working memory, attention, and visuospatial functions, in addition to the previously described global intellectual impairments. We recommend including a standardized neuropsychological examination in the standards of care for DM1 children. Early recognition of cognitive deficits and behavioral disorders in children with DM1 can improve their management.

Wechsler Scale Intelligence Testing in Males with Dystrophinopathies: A Review and Meta-Analysis.

BACKGROUND: Intelligence scores in males with Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) remain a major issue in clinical practice. We performed a literature review and meta-analysis to further delineate the intellectual functioning of dystrophinopathies. METHOD: Published, peer-reviewed articles assessing intelligence, using Wechsler Scales, of males with DMD or BMD were searched from 1960 to 2022. Meta-analysis with random-effects models was conducted, assessing weighted, mean effect sizes of full-scale IQ (FSIQ) scores relative to normative data (Mean = 100, Standard Deviation = 15). Post hoc we analysed differences between performance and verbal intelligence scores. RESULTS: 43 studies were included, reporting data on 1472 males with dystrophinopathies; with FSIQ scores available for 1234 DMD (k = 32) and 101 BMD (k = 7). DMD males score, on average, one standard deviation below average (FSIQ = 84.76) and significantly lower than BMD (FSIQ = 92.11). Compared to a previous meta-analysis published in 2001, we find, on average, significantly higher FSIQ scores in DMD. CONCLUSION: Males with Duchenne have, on average, significantly lower FSIQ scores than BMD males and the general population. Clinicians must consider lower intelligence in dystrophinopathies to ensure good clinical practice.

Clinical Utility of Eye Tracking in Assessing Distractibility in Children with Neurological Disorders or ADHD: A Cross-Sectional Study.

This study aims to investigate distractibility quantified by recording and analyzing eye movements during task-irrelevant distraction in children with and without ADHD and in children with and without neurological disorders. Gaze behavior data and press latencies of 141 participants aged 6−17 that were collected during a computerized distraction paradigm with task-irrelevant stimuli (IDistrack) were analyzed. Children using attention-regulating medication were excluded from participation. Data were analyzed for subgroups that were formed based on the presence of neurological disorders and the presence of ADHD separately. Participants with ADHD and participants with neurological disorders spent less time fixating on the target stimuli compared to their peers without ADHD (p = 0.025) or their peers without neurological disorders (p < 0.001). Participants with and without ADHD had equal press latencies (p = 0.79). Participants with neurological disorders had a greater press latency compared to their typically developing peers (p < 0.001). Target fixation duration shows a significant association with parent-reported attention problems (r = −0.39, p < 0.001). We conclude that eye tracking during a distraction task reveals potentially valid clinical information that may contribute to the assessment of dysfunctional attentional processes. Further research on the validity and reliability of this paradigm is recommended.

Longitudinal follow-up of verbal span and processing speed in Duchenne muscular dystrophy.

Neurocognitive deficits are frequently described in Duchenne muscular dystrophy (DMD), but it is unknown how these progress over time. Our aim was to longitudinally assess verbal span capacity and information processing speed in DMD and to explore a genotype-phenotype relation. Verbal span and processing speed scores were available of 28 males with DMD on two time-points, with a mean time interval of 28.34 months (SD = 16.09). The cohort contained of six patients missing only dystrophin isoform Dp427, sixteen missing Dp427 and Dp140, and six were undeterminable. A lower verbal span capacity was found at the first and second assessment, whereas processing speed was normal at both time-points. Post-hoc analyses suggested lower scores on verbal span and processing speed for patients missing Dp427 and Dp140. In DMD, a developmental stagnation in verbal span capacity, irrespective of normal processing speed, is detected through longitudinal follow-up. This appears more pronounced in patients missing Dp427 and Dp140.