Brain and heart magnetic resonance imaging/spectroscopy in duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by progressive and irreversible loss of muscular function. As muscular disease progresses, the repair mechanisms cannot compensate for cellular damage, leading inevitably to necrosis and progressive replacement by fibrous and fatty tissue. Cardiomyopathy and respiratory failure are the main causes of death in DMD. In addition to the well-described muscle and heart disease, cognitive dysfunction affects around 30% of DMD boys. Myocardial fibrosis, assessed by late gadolinium enhancement (LGE), using cardiovascular magnetic resonance imaging (CMR), is an early marker of heart involvement in both DMD patients and female carriers. In parallel, brain MRI identifies smaller total brain volume, smaller grey matter volume, lower white matter fractional anisotropy and higher white matter radial diffusivity in DMD patients. The in vivo brain evaluation of mdx mice, a surrogate animal model of DMD, showed an increased inorganic phosphate (P(i))/phosphocreatine (PCr) and pH. In this paper, we propose a holistic approach using techniques of magnetic resonance imaging, spectroscopy and diffusion tensor imaging as a tool to create a "heart and brain imaging map" in DMD patients that could potentially facilitate the patients' risk stratification and also future research studies in the field. K E Y W O R D Sbrain magnetic resonance imaging, brain magnetic resonance spectroscopy, cardiovascular magnetic resonance imaging, diffusion tensor imaging, duchenne muscular dystrophy

Pathophysiology of cognitive dysfunction and the role of combined brain/heart magnetic resonance imaging (Review)

“…However, the cognitive effects of these diseases are also important. This is due to molecular defects that significantly affect neuromotor functioning, but also participate in the functioning of neural networks involved in cognitive processes, leading to impairment of executive, behavioral and psychosocial functions (33).…”

Non-traumatic and non-drug-induced rhabdomyolysis

“…Dystrophinopathies are sex-linked disorders. The lack of dystrophin destabilizes the muscle membrane, leading to clinical features of delayed motor development, calf hypertrophy, joint contractures, and progressive muscle weakness leading to scoliosis, cardiomyopathy, respiratory insufficiency, severe physical disability and reduced life expectancy, with death occurring before the third or fourth decade of life [52,[54][55][56][57][58][59]. DMD affects 1/3,500-5,000 live-born males; it is the most common type of muscular dystrophy in childhood [57,58].…”

Dmd mdx mice have defective oligodendrogenesis, delayed myelin compaction and persistent hypomyelination

“…Patients with DMD are at a higher risk of developing attention deficit-hyperactivity disorder ( Lee et al, 2022 ; Caspers Conway et al, 2015 ; Pane et al, 2012 ), autism spectrum disorder ( Simone et al, 2021 ; Parisi et al, 2018 ; Fujino et al, 2018 ) and obsessive-compulsive disorder ( Pascual-Morena et al, 2022 ; Lee et al, 2022 ; Thangarajh et al, 2019 ). Neuroimaging studies have revealed structural brain abnormalities, including smaller total brain and gray matter volumes ( Doorenweerd et al, 2014 ; Lv et al, 2011 ; Mavrogeni et al, 2017 ), and decreased cerebral perfusion ( Doorenweerd et al, 2017 ). Diffusion tensor imaging (DTI) studies on patients with DMD also suggest microstructural white matter changes ( Fu et al, 2016 ; Preethish-Kumar et al, 2020 ; Doorenweerd et al, 2014 ), with reduced fractional anisotropy (FA) values, and increased mean and radial diffusivity in white matter tracts, including the corpus callosum, being reported ( Fu et al, 2016 ; Preethish-Kumar et al, 2020 ; Doorenweerd et al, 2014 ).…”