Interest in muscle MRI has been largely stimulated in the last few years by the recognition of an increasing number of genetic defects in the field of inherited neuromuscular disorders. Muscle ultrasound (US) and computed tomography (CT) have been used to detect the presence of muscle involvement in patients affected by these disorders, but until recently the use of muscle MRI has been, with a few exceptions, limited to detecting inflammatory forms. The aim of this review is to illustrate how muscle MRI, in combination with clinical evaluation, can contribute to the selection of appropriate genetic tests and more generally in the differential diagnosis of genetically distinct forms of neuromuscular disorders. Possible future applications of muscle MRI are also discussed. J. Magn. Reson. Imaging 2007.

Aim: Duchenne muscular dystrophy (DMD) is associated with neuropsychiatric disorders. The aim of the study was to characterize the DMD neuropsychiatric profile fully and to explore underlying genotype/phenotype associations.Method: One hundred and thirty males with DMD (mean age 9y 10mo, range 5–17y) in four European centres were included and completed IQ assessment and a neurodevelopmental‐screening questionnaire. Of these, 87 underwent comprehensive neuropsychiatric assessment using structured diagnostic interview and parent‐reported questionnaires.Results: The overall mean score on the neurodevelopmental questionnaire was significantly abnormal compared with the general population of children (p<0.001). On average, intelligence was below the population mean, with intellectual disability observed in 34 males (26%). Autistic spectrum disorder was identified in 18 (21%), hyperactivity in 21 (24%), and inattention in 38 (44%). Clinical levels of internalizing and externalizing problems were observed in 21 (24%) and 13 (15%) respectively. Over a third of males scored more than two measures of emotional, behavioural, or neurodevelopmental problems. Males with mutations at the 3′ end of the DMD gene affecting all protein isoforms had higher rates of intellectual disability and clusters of symptoms.Interpretation: Males with DMD are at very high risk of neuropsychiatric disturbance, and this risk appears to increase with mutations at the 3′ end of the gene. Patterns of symptom clusters suggest a DMD neuropsychiatric syndrome, which may require prompt evaluation and early intervention.

Duchenne Muscular Dystrophy (DMD) is caused by mutations in the dystrophin gene leading to dystrophin deficiency, muscle fiber degeneration and progressive fibrotic replacement of muscles. Givinostat, a histone deacetylase (HDAC) inhibitor, significantly reduced fibrosis and promoted compensatory muscle regeneration in mdx mice. This study was conducted to evaluate whether the beneficial histological effects of Givinostat could be extended to DMD boys. Twenty ambulant DMD boys aged 7 to <11 years on stable corticosteroid treatment were enrolled in the study and treated for ≥12 months with Givinostat. A muscle biopsy was collected at the beginning and at the end of treatment to evaluate the amount of muscle and fibrotic tissue. Histological effects were the primary objectives of the study. Treatment with Givinostat significantly increased the fraction of muscle tissue in the biopsies and reduced the amount of fibrotic tissue. It also substantially reduced tissue necrosis and fatty replacement. Overall the drug was safe and tolerated. Improvement in functional tests was not observed in this study, but the sample size of the study was not sufficient to draw definitive conclusions. This study showed that treatment with Givinostat for more than 1 year significantly counteracted histological disease progression in ambulant DMD boys aged 7 to 10 years.