Volumetric brain alterations in children with primary complex motor stereotypies: a baseline and longitudinal report

Primary complex motor stereotypies (pCMS) are early-onset, repetitive movements in otherwise typically developing children. Although symptoms often improve during adolescence, neuroanatomical mechanisms underlying the pathophysiology of movements and symptom reduction remails unclear. Structural MRI studies have implicated multiple structures within cortical-basal ganglia-thalamo-cortical circuits, but findings have been inconsistent and limited by small, cross-sectional childhood cohorts. It remains unclear whether reported volumetric differences represent static markers of pCMS or developmental changes related to clinical severity.

Volumetric MRI examined frontal cortical, basal ganglia, and cerebellar regional volumes in participants with pCMS and typically developing (TD) controls at childhood (8-12 years) and adolescence/young adulthood (15-23 years). Cross-sectional analyses evaluated diagnostic effects on regional volumes (childhood: pCMS n = 33, TD n = 33; adolescence: pCMS n = 12, TD n = 9) and clinical severity correlations in pCMS (childhood n = 31, adolescence n = 10). Longitudinal analyses in pCMS evaluated whether changes in regional volumes from childhood to adolescence/young adulthood correlated with changes in stereotypy severity (n = 10).

Cross-sectional analyses in childhood revealed smaller left putamen volume and an association of smaller medial prefrontal volume with greater clinical severity in pCMS (neither finding survived FDR correction). Cerebellar analyses demonstrated larger anterior vermis gray matter and smaller anterior and posterior white matter volumes (surviving FDR correction); furthermore, larger cerebellar volumes were nominally associated with greater clinical severity (not surviving FDR correction). In adolescence/young adulthood, no frontal lobe or basal ganglia differences were detected. Cerebellar analyses identified nominally smaller anterior white matter volumes and associations between larger posterior white matter volumes and greater clinical severity (neither finding survived FDR correction). Longitudinal analyses revealed within-subject increases in frontal lobe gray matter volumes (predominantly right hemisphere), was associated with increased pCMS severity (not surviving FDR correction).

Findings suggest that pCMS may be associated with regionally specific and developmentally dynamic structural differences rather than a single neuroanatomical abnormality. Childhood cerebellar sensorimotor regions demonstrated volumetric differences, while additional cross-sectional and longitudinal findings raise the possibility that frontal cortical, basal ganglia, and cerebellar regions may contribute differentially to stereotypy severity across development. Collectively, these findings are consistent with, but do not establish a circuit-level framework for understanding pCMS.