Cerebellar Contributions to Cognitive Affective Function and Postural Tremor in Neurological Wilson's Disease

Wilson's disease (WD) causes neurological impairments, but research has traditionally focused on the basal ganglia, neglecting the potential role of the cerebellum. This study aims to investigate the relationships between emotion, cognition, and postural tremor in WD and to elucidate the role of the cerebellum in these interactions. We enrolled 57 patients with neurological WD, including 29 with postural tremor and 28 without tremor, and 16 healthy controls. All participants were assessed using the Cerebellar Cognitive Affective Syndrome scale (CCAS-S), the Implicit Positive and Negative Affect Test (IPANAT), and cranial MRI. Upper extremity postural tremor amplitude was quantitatively measured in the tremor patients. Voxel-based morphometry analysis was performed on cerebellar structural images derived from the MRI data. WD patients with postural tremor sustained multifaceted cognitive impairments. All WD patients with postural tremor exhibited basal ganglia lesions. Atrophy in the right cerebellar lobules I-IV was identified as a key differentiator between WD patients with and without postural tremor. Postural tremor amplitude in WD patients correlated with atrophy of the fastigial nuclei and brainstem lesions. Scores from the CCAS-S and IPANAT assessment were linked to the gray matter volume in several posterior cerebellar regions, primarily lobules VI, Crus II, VIIb, VIIIa, and IX. The cerebellum plays a critical role in regulating postural tremors, cognition, and emotions in WD, indicating that the pathological mechanism of WD is not confined to the basal ganglia but involves a broader network model.