Use of the experience sampling method in adolescents with Duchenne muscular dystrophy: a feasibility study.

Experience sampling methods (ESM) using mobile health (mHealth) technology with a smartphone application are increasingly used in clinical practice and research. Still, recommendations are limited in young people, and adaptations may be necessary. Patients with Duchenne muscular dystrophy (DMD) are chronically treated with steroids from a young age. However, the impact of intermittent treatment schedules on fluctuations in somatic, cognitive and behavioural symptoms is poorly investigated. Existing studies are often cross-sectional and occur in controlled clinical settings, which do not provide sufficiently detailed insights into possible correlations. ESM might alleviate these problems. ESM innovates data collection with a smartphone application, which repeatedly assesses specific symptoms and contextual factors at random moments in daily life. We aimed to evaluate its feasibility in adolescents with DMD. In three (without/with/without steroids) 4-day periods of ESM, that were nested in 10/10 or 11/9 day on/off-medication periods, we evaluated its user-friendliness and compliance, and explored its ability to objectify fluctuations in somatic, cognitive and behavioural symptom severity and their relationship with contextual factors in seven DMD patients (age range 12-18 years) using intermittent corticosteroid treatment (dosage range 0.3-0.6 mg/kg/day). Patients reported that ESM was convenient and user-friendly. We were able to capture extensive intra-individual symptom fluctuations during intermittent corticosteroid treatment that were not revealed by routine clinical assessment. Implementing ESM to evaluate symptom fluctuation patterns in relation to treatment effects shows promise in adolescents with DMD. Optimization in further research is needed.

Computerized working memory training in males with Duchenne muscular dystrophy: A single case experimental design study.

Learning disabilities (LDs) and working memory problems (WM) are common brain-related comorbidities in Duchenne muscular dystrophy (DMD). Despite growing evidence on the efficacy of computerized WM training in children with LDs, research in DMD is lacking. This exploratory study assessed whether training (1) improves dystrophin-associated WM problems in DMD, (2) effects are present at post-intervention, 3 and 8 months follow-up, and (3) improves problems that arise from their LDs. A single case non-concurrent multiple baseline across patients design evaluated the target behaviour i.e. parental reports of WM problems of four DMD participants with LDs. Additionally, participants completed cognitive tests of verbal and visual WM, academics, attention, processing speed and fluid reasoning. Parents and teachers completed behavioural questionnaires. Testing and questionnaires were administered at baseline, post-intervention (T2), 3 (T3) and 8 (T4) months follow-up. Positive effects on target behaviour were found for three of four participants, but parental bias cannot be ruled out. Short and long-term, near-and far transfer effects were found for verbal and visual WM (T2:n = 2, T3&T4:n = 1), reading (T2:n = 4,T3:n = 3,T4:n = 2), arithmetic (all T:n = 1), processing speed (all T:n = 4) and fluid reasoning (T2:n = 1,T3&T4:n = 2). Behavioural questionnaires displayed minimal changes (T2:n = 1,T3&T4:n = 2). Promising WM training results are shown in DMD that merit further research.

Dystrophin is expressed in smooth muscle and afferent nerve fibers in the rat urinary bladder.

INTRODUCTION: With increasing life expectancy, comorbidities become overt in Duchenne muscular dystrophy (DMD). Although micturition problems are common, bladder function is poorly understood in DMD. We studied dystrophin expression and multiple isoform involvement in the bladder during maturation to gain insights into their roles in micturition. METHODS: Dystrophin distribution was evaluated in rat bladders by immunohistochemical colocalization with smooth muscle, interstitial, urothelial, and neuronal markers. Protein levels of Dp140, Dp71, and smooth muscle were quantitated by Western blotting of neonatal to adult rat bladders. RESULTS: Dystrophin colocalized with smooth muscle cells and afferent nerve fibers. Dp71 was expressed two- to threefold higher compared with Dp140, independently of age. Age-related muscle mass changes did not influence isoform expression levels. DISCUSSION: Dystrophin is expressed in smooth muscle cells and afferent nerve fibers in the urinary bladder, which underscores that micturition problems in DMD may have not solely a myogenic but also a neurogenic origin. Muscle Nerve 60: 202-210, 2019.

Instruments for the Assessment of Behavioral and Psychosocial Functioning in Duchenne and Becker Muscular Dystrophy; a Systematic Review of the Literature.

OBJECTIVE: This systematic review aims to provide an overview of instruments used to assess behavioral and psychosocial functioning of patients with Duchenne and Becker muscular dystrophy, as well as to review the psychometric properties and applicability of these instruments. METHODS: Five databases (Embase, Psyc.info, ERIC, Pubmed/Medline, and Cochrane) were searched from inception to June, 2018. Potential articles were rated by two independent reviewers. A predefined PROSPERO form (CRD42017074518) was used to extract data from included articles. RESULTS: Sixty-one instruments were used in 54 studies. The Child Behavior Checklist is commonly used, but it lacks disease specific psychometric information. Sixteen instruments that contained disease specific psychometric information were included for final evaluation. The results displayed three instruments that are potentially valid for screening of psychosocial problems: The Psychosocial Adjustment and Role Skills Scale 3rd edition, the Pediatric Quality of Life Inventory Generic module, and the Life Satisfaction Index for Adolescents with Duchenne muscular dystrophy. Appropriate instruments for screening of behavioral problems may be: the Strengths and Difficulties Questionnaire, the Generalized Anxiety Disorder-7 item questionnaire, and the Patient Health Questionnaire-9 item questionnaire. CONCLUSIONS: Further research on psychometric properties of screening instruments is crucial to ascertain a gold standard for clinical and research purposes. Meanwhile, for definite diagnostics purposes we recommend a multimethod, multisource, multisetting assessment in this high-risk population.

The neurocognitive profile of adults with Becker muscular dystrophy in the Netherlands.

BACKGROUND: In Becker muscular dystrophy evidence for neurocognitive and behavioral comorbidity is evolving. More insight into the extend of these problems is of great importance for early detection and remediation in clinical practice. OBJECTIVE: In this study we aimed to describe the neurocognitive and behavioral features of a Dutch adult cohort of BMD patients, and to evaluate correlations to motor function outcomes. METHODS: 28 adult BMD patients were included. Intelligence, executive functioning, verbal memory and reaction times were assessed cross-sectionally. Additionally, patients completed questionnaires on behavioral and emotional symptoms, psychosocial and executive functions. Results were compared to normative data and correlated with disease severity as measured by the 10-meter run/walk test and Performance of the Upper Limb version 1.2. RESULTS: 15 patients (53.6%) had a high educational level despite frequent grade repeating (48.3%) during primary or secondary school. Neuropsychological testing revealed that intellectual abilities, verbal memory, processing speed and executive functioning were statistically significant below average, but still within normal range. Regarding outcomes of the behavioral questionnaires, no significant differences were reported compared to the norm population. No relevant correlations with disease severity were found. CONCLUSIONS: This cohort of adult BMD patients exhibits minor cognitive impairments and no significant behavioral problems. The lower outcomes on processing speed and verbal memory, combined with the relatively high prevalence of grade repeating during primary and secondary school, implies that these minor impairments played a role in childhood. However, the on average high educational levels suggests that they grow out of their cognitive impairments with ageing.

Cognitive and behavioral functioning in two neurogenetic disorders; how different are these aspects in Duchenne muscular dystrophy and Neurofibromatosis type 1?

The presence of neurocognitive and behavioral problems are common features in various neurogenetic disorders. In Duchenne muscular dystrophy (DMD), these problems have been linked to mutations along the dystrophin gene affecting different brain dystrophin isoforms. However, comparable cognitive and behavioral problems have been found in Neurofibromatosis type 1 (NF1). This study aims to assess disorder specific differences in cognition and behavior between DMD and NF1. Retrospective data of 38 male patients with DMD were aged-matched with data of 38 male patients with NF1. Patients of both groups underwent neurocognitive assessment for regular clinical care. Intellectual abilities, sequential and simultaneous processing, verbal memory and sustained attention were evaluated. In addition, parents and teachers completed behavioral questionnaires. Males with DMD exhibited low intellectual abilities and sequential processing problems, but these outcomes not significantly differed from males with NF1. Simultaneous processing, verbal memory and sustained attention outcomes were equal for both groups. Outcomes of questionnaires displayed higher rates of aggressive behavior (13.2%) in DMD, whereas in NF1 higher rates of problems with thinking (15.8%), withdrawn (10.5%) and social behavior (10.5%) were noticed. In the neurogenetic disorders DMD and NF1, on average overlapping cognitive and behavioral problems are noticed, suggesting that these are not only caused by gene mutations resulting in a lack of one specific protein.

The Neurocognitive and Behavioral Profiles of 3 Brothers With Becker Muscular Dystrophy.

Becker muscular dystrophy patients generally carry in-frame mutations in the dystrophin gene, allowing the production of partially functional dystrophin protein. The presence of cognitive and behavioral comorbidities and the relation with the location of mutations has been scarcely investigated in Becker. This case report describes the neurocognitive and behavioral profiles of 3 brothers with Becker carrying an in-frame deletion of exons 45-48. The 3 cases underwent 2 consecutive neuropsychological assessments of which one assessment took place when they completed their primary education (age range of the cases: 11.2 -12.1 years). Intellectual abilities were normal to high and all cases had difficulties with processing speed and math. The brothers differed in intellectual abilities, executive functions, working memory, attention and reading abilities. Variability in cognitive development was noted as well. This report suggests that cognitive and behavioral functions in Becker vary regardless of gene mutation and exposer to similar environmental factors.

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.

Methylphenidate use in males with Duchenne muscular dystrophy and a comorbid attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common comorbidity in Duchenne muscular dystrophy (DMD). Until now, treatment with methylphenidate (MPH) has never been systematically assessed and described in this population. Our aim was to evaluate the effectiveness and safety of short acting MPH for learning problems in males with DMD and ADHD. Neuropsychological (cognition and behavior) and medical data of a sample of ten males (mean age = 8.1 years, range 6.3-9.8) with DMD and an ADHD diagnosis was retrospectively analyzed at baseline (T0; without MPH), short-term follow-up (T1; with MPH; mean interval T0-T1 = 8.3 months, range 4.3-15.6), and long-term follow-up (T2; mean interval T1-T2 = 23.1 months, range 2.6-77.7). An initial MPH dose of 5 mg/day was given on school mornings, with an increase of 2.5-5 mg/week depending on individual tolerance and treatment response, until a sufficiently effective dose was reached (range 0.2-0.6 mg/kg/day). At T1, results demonstrated an improvement in attention (i.e. concentration, impulsivity, and distractibility) in four patients. Suboptimal effects were reported in four patients, and no effects in two patients. At T2, seven patients showed considerable improvement in attention. No major side effects were reported. Overall, our data show that short acting MPH can be clinically effective for learning problems in males with DMD and ADHD, with regular cardiac follow-up, and close monitoring of side effects and neuropsychological effects. Furthermore, this underscores the importance of the use of validated cognitive and behavioral measurement tools with adequate sensitivity to objectively evaluate the effect of MPH.