Reduced cerebral gray matter and altered white matter in boys with Duchenne muscular dystrophy.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness caused by DMD gene mutations leading to absence of the full-length dystrophin protein in muscle. Multiple dystrophin isoforms are expressed in brain, but little is known about their function. DMD is associated with specific learning and behavioral disabilities that are more prominent in patients with mutations in the distal part of the DMD gene, predicted to affect expression of shorter protein isoforms. We used quantitative magnetic resonance (MR) imaging to study brain microstructure in DMD. METHODS: T1-weighted and diffusion tensor images were obtained on a 3T MR scanner from 30 patients and 22 age-matched controls (age = 8-18 years). All subjects underwent neuropsychological examination. Group comparisons on tissue volume and diffusion tensor imaging parameters were made between DMD patients and controls, and between 2 DMD subgroups that were classified according to predicted Dp140 isoform expression (DMD_Dp140(+) and DMD_Dp140(-) ). RESULTS: DMD patients had smaller total brain volume, smaller gray matter volume, lower white matter fractional anisotropy, and higher white matter mean and radial diffusivity than healthy controls. DMD patients also performed worse on neuropsychological examination. Subgroup analyses showed that DMD_Dp140(-) subjects contributed most to the gray matter volume differences and performed worse on information processing. INTERPRETATION: Both gray and white matter is affected in boys with DMD at a whole brain level. Differences between the DMD_Dp140(-) subgroup and controls indicate an important role for the Dp140 dystrophin isoform in cerebral development.

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.

Psychosocial adjustment in males with Duchenne muscular dystrophy: psychometric properties and clinical utility of a parent-report questionnaire.

OBJECTIVE: The primary aim of this study was to establish the psychometric properties and clinical utility of the Personal Adjustment and Role Skills Scale (PARS-III) for assessing psychosocial adjustment in males with Duchenne muscular dystrophy (DMD). METHODS: The parents of 287 male patients with DMD aged 5-18 years completed the PARS-III and Revised Rutter Scale. RESULTS: The alpha coefficients and factor analysis indicated good reliability and validity. Overall psychosocial adjustment was not significantly different in DMD compared to males with other chronic medical conditions and was positively associated with increases in age. A clinical cutoff score for screening in the DMD population is also reported. CONCLUSIONS: The PARS-III is a reliable and valid index of youth psychosocial adjustment in DMD and can be used for both clinical screening and research purposes.