Structural Connectome Alterations in Alternating Hemiplegia of Childhood

This study investigated structural connectivity in Alternating Hemiplegia of Childhood (AHC) using advanced tractography and connectome analysis, as characterizing brain network alterations in this rare disorder may clarify its cognitive and motor impairments. This prospective monocentric study included 10 individuals with AHC (mean age 23.2 years) and 20 matched healthy controls. All participants underwent 3T MRI with 3D T1-weighted and high-angular resolution diffusion sequences. Brain structural networks were evaluated using global and nodal graph measures, modular organization, and network-based statistics. Associations with motor and cognitive performance were examined using the Wechsler scales, Vineland Adaptive Behavior Scales-II, International Cooperative Ataxia Rating Scale, and the Movement and Disability sections of the Burke-Fahn-Marsden Dystonia Rating Scale. At the global level, AHC participants exhibited reduced network integration, reflected by higher characteristic path length (P = 0.04) and lower global efficiency (P = 0.04) compared to controls. Mean degree (P = 0.03) and normalized betweenness (P = 0.04) were also decreased. Network-based statistics revealed a single subnetwork of reduced connectivity involving basal ganglia, frontal, and insular regions bilaterally (P = 0.01). At the nodal level, 21 of 84 nodes showed reduced degree, mainly within frontal, limbic, temporal, occipital lobes, and basal ganglia. Nodal graph-theoretical metrics showed widespread, region-specific correlations with motor severity and cognitive performance, particularly involving sensorimotor, fronto-striatal, temporal, limbic, cerebellar, and subcortical regions. In summary, AHC is characterized by a globally less integrated and sparser structural brain network, with prominent disruption of cortico-striatal and associative circuits and region-specific nodal alterations that correlate with motor severity and cognitive impairment.