Evaluation of Brain Dysfunction in Patients with Duchene Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is the second most common inherited genetic disease. It is an X-linked disease that affects approximately one in 3300 live male birth. It is caused by the absence or disruption of the dystrophin protein that is a main component of the dystrophin-glycoprotein complex (DGC). It is found in a variety of tissues, mostly skeletal muscle and neuron cells in specific regions of the CNS ashippocampus, the cerebellum and the neocortex. [1, 2] Clinically DMD is characterized by a severe pathology of the skeletal musculature that results in progressive weakness of muscles including cardiac \& respiratory muscles leading to the premature death of the individual.

An important aspect of DMD is the neurocognitive function of patients which, despite its non-progressive nature, still greatly affects the quality of life of the patients and their caregivers.[3]

While not all patients exhibit global cognitive impairments, many do show significant deficits in areas such as arithmetic, verbal fluency, working memory, attention, and executive function. A study by Wingeier et al. (2011) found that boys with DMD scored lower than average on IQ tests, particularly in verbal IQ. Other studies have linked specific cognitive impairments to the absence of certain dystrophin isoforms suggesting a genotype-phenotype correlation between mutation and brain affection, particularly Dp140 and Dp260, which are associated with learning disabilities, ADHD, and autism spectrum disorders (ASD).[1, 3, 4]

Many DMD patients face learning difficulties like those seen in developmental dyslexia, this was attributed to the potential role of cerebellar dysfunction \& choline deficit in these cognitive dysfunctions, suggesting that metabolic abnormalities in the cerebellum may contribute to the observed impairments. Overall, the research findings emphasize the need for early intervention and highlight the complex interplay of genetic and non-genetic factors in cognitive function among DMD patients.[5-8]

Neuroimaging studies have revealed structural and functional brain abnormalities, with MR spectroscopy and PET showing metabolic abnormalities. Evidence is also emerging for brain regional volume loss, blood oxygen level-dependent signal abnormalities, and altered WM integrity as measured using Diffusion Tensor Imaging. Furthermore, recent imaging studies have highlighted less severe structural abnormalities in patients with retained Dp140 expression compared with those lacking it.[9-11]