Functional reorganization of the visual cortex in patients with Charcot–Marie–Tooth disease: A multimodal neuroimaging study

Charcot-Marie-Tooth disease (CMT), an inherited peripheral nervous system disorder, causes muscle weakness, sensory deficits, decreased or absent tendon reflexes, and skeletal deformities. Although primarily a peripheral disorder, some studies indicate central nervous system (CNS) involvement. This study systematically investigated the potential structural and functional brain alterations in patients with CMT without overt CNS symptoms using magnetic resonance imaging (MRI) techniques. In this prospective cross-sectional study, 14 patients with clinically and genetically confirmed CMT and 14 age- and sex-matched healthy controls (HCs) underwent 3 T brain MRI. Gray/white matter volume, cortical thickness, amplitude of low-frequency fluctuations (ALFF), and regional homogeneity (ReHo) were compared between groups. Compared to HCs, patients with CMT exhibited increased gray matter volume in the left cerebellar lobules IV-VI and right orbital part of the inferior frontal gyrus. The CMT group demonstrated significantly higher ALFF in the bilateral cuneus regions and decreased ALFF values in the left middle frontal gyrus. Additionally, enhanced ReHo was observed in the right middle occipital and right fusiform gyri in patients with CMT compared to that in HCs. No significant differences were observed in global brain volume or cortical thickness. Patients with CMT exhibited a CNS remodeling pattern and functional hyperactivation of the visual cortex. This phenomenon potentially underlies the neural basis of patients' increased reliance on visual feedback to compensate for proprioceptive deficits. This study provides insights into CNS involvement and neuroplastic adaptations in CMT, highlighting the importance of neuroimaging for understanding the multimodal pathophysiological mechanisms of this disorder.