Abstract

The cerebellum plays an important role in motor and cognitive functions. However, whether and how the normal-appearing cerebellum is impaired in patients with neuromyelitis optica spectrum disorders remain unknown. We aimed to identify the occult structural damage of the cerebellum in neuromyelitis optica spectrum disorder and its possible causes at the level of substructures. Normal-appearing gray matter volume of the cerebellar lobules and nuclei and normal-appearing white matter volume of the cerebellar peduncles were compared between patients with neuromyelitis optica spectrum disorder and healthy controls. The cerebellar damage of patients with neuromyelitis optica spectrum disorder in the hemispheric lobule VI, vermis lobule VI, and all cerebellar nuclei and peduncles was related only to spinal lesions; and cerebellar damage in the hemispheric lobules VIII and X was related only to the aquaporin-4 antibody. The mixed cerebellar damage in the hemispheric lobules V and IX and vermis lobule Crus I was related mainly to spinal lesions; and mixed cerebellar damage in the hemispheric lobule VIIb was related mainly to the aquaporin-4 antibody. Other cerebellar substructures showed no significant cerebellar damage. We have shown that the damage in cerebellar normal-appearing white matter and normal-appearing gray matter is associated with aquaporin-4-mediated primary damage or axonal degeneration secondary to spinal lesions or both. The etiologic classifications of substructure-specific occult cerebellar damage may facilitate developing neuroimaging markers for assessing the severity and the results of therapy of neuromyelitis optica spectrum disorder occult cerebellar damage.

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