Abstract
IntroductionPatients with dystrophinopathies show low levels of neuronal nitric oxide synthase (nNOS), due to reduced or absent dystrophin expression, as nNOS is attached to the dystrophin‐associated protein complex. Deficient nNOS function leads to functional ischemia during muscle activity. Dystrophin‐like proteins with nNOS attached have also been identified in the brain. This suggests that a mechanism of cerebral functional ischemia with attenuation of normal activation‐related vascular response may cause changes in brain function.MethodsThe aim of this study was to investigate whether the brain response of patients with Becker muscular dystrophy (BMD) is dysfunctional compared to that of healthy controls. To investigate a potential change in brain activation response in patients with BMD, median nerve somatosensory evoked stimulation, with stimulation durations of 2, 4, and 10 s, was performed while recording electroencephalography and blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging.ResultsResults in 14 male patients with BMD (36.2 ± 9.9 years) were compared with those of 10 healthy controls (34.4 ± 10.9 years). Compared to controls, the patients with BMD showed sustained cortical electrical activity and a significant smaller BOLD activation in contralateral primary somatosensory cortex and bilaterally in secondary somatosensory cortex. In addition, significant activation differences were found after long duration (10 s) stimuli in thalamus.ConclusionAn altered neurovascular response in patients with BMD may increase our understanding of neurovascular coupling and the pathogenesis related to dystrophinopathy and nNOS.
Highlights
Patients with dystrophinopathies show low levels of neuronal nitric oxide synthase, due to reduced or absent dystrophin expression, as nNOS is attached to the dystrophin-associated protein complex
Investigating the neurovascular response in patients with Becker muscular dystrophy (BMD), we found a decreased blood oxygen level-dependent (BOLD) response contralateral to the stimulation in the primary somatosensory cortex (SI), as well as bilaterally in the secondary somatosensory cortex (SII), and thalamus, compared with healthy controls
A sustained EEG activity was detected during electrical somatosensory stimulation in patients with BMD in contrast to controls where the electrical activity dropped and levelled off, which may represent neural adaptation
Summary
Patients with dystrophinopathies show low levels of neuronal nitric oxide synthase (nNOS), due to reduced or absent dystrophin expression, as nNOS is attached to the dystrophin-associated protein complex. Dystrophin-like proteins with nNOS attached have been identified in the brain. This suggests that a mechanism of cerebral functional ischemia with attenuation of normal activation-related vascular response may cause changes in brain function. Methods: The aim of this study was to investigate whether the brain response of patients with Becker muscular dystrophy (BMD) is dysfunctional compared to that of healthy controls. To investigate a potential change in brain activation response in patients with BMD, median nerve somatosensory evoked stimulation, with stimulation durations of 2, 4, and 10 s, was performed while recording electroencephalography and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Duchenne (DMD) and Becker (BMD) muscular dystrophies, collectively called dystrophinopathies, are X-linked and caused by mutations in the dystrophin gene. The pathophysiology of brain involvement in dystrophinopathies is not yet understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
