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Neurobiological mechanisms that explain the association of multiple sclerosis and neuromyelitis optica spectrum disorder with the cerebellum include alterations in the cerebello–cerebral and within-cerebellar connectivity and relevant genetic changes.

The cerebellum is integral to the pathology of neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS); however, the underlying mechanisms to explain this association and the genetic correlation are not entirely known. 

This study utilized multimodal magnetic resonance imaging (MRI) data from NMOSD patients, MS patients, and healthy controls. The study findings support the evidence regarding alterations in cerebellocerebral connectivity and the cerebellum, along with the distinct transcriptomic signatures in NMOSD and MS patients. The findings are published in the Journal of Translational Medicine.

Baseline Characteristics of the Participants

The study included 200 NMOSD patients, 228 healthy controls, and 208 MS patients. Significant group effects were observed for the sex and age of the participants. A higher female-to-male ratio was recorded in both MS and NMOSD patients.

Altered Cerebellar Morphological Connectivity

The results revealed that both MS and NMOSD patients demonstrated a decrease in both the somatomotor network and cerebellar secondary motor module (SM) in most of the cerebral components. Wide disruption of cerebello-cerebral morphological loops is associated with poor performance among NMOSD and MS patients, which are specific to the secondary modules. 

A reduction in the morphological connectivity between the cerebellar primary non-motor nodule (PMN) and default mode network (DMN) and association cortex 2 (AC2) among MS patients was also found.

Altered Cerebellar Functional Connectivity

Alterations in functional connectivity, primarily involving the cerebral association cortices and cerebellar motor nodules, were relatively fewer among the MS and NMOSD patients. Cerebellar SM functional connectivity exhibited MS-specific decreases in the study participants. Both MS and NMOSD patients demonstrated a decrease in MS and cerebellar primary motor B module connectivity with the frontoparietal network and the cerebral association cortex. This indicates the weakening of information exchange between the cerebral and cerebellar areas.

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Genetic Basis of Altered Cerebellar Functional Connectivity

Significant genetic associations were found to support altered cerebellar functional connectivity in MS and NMOSD patients. The relevant genes are implicated in the transmission of genetic information and the maintenance of cell homeostasis.

Potential Biomarkers for Disease Classification

These results suggest that cerebellar morphological and functional connectivity can help distinguish between patients and controls and between MS and NMOSD, respectively; however, the accuracy of this classification is low.

The study concluded that there are alterations in the functional and morphological connectivity between the cerebellum and the cerebrum in MS and NMOSD patients, with these alterations associated with genetic changes.  


Yang, Y., Li, J., Li, T., Li, Z., Zhuo, Z., Han, X., Duan, Y., Cao, G., Zheng, F., Tian, D., Wang, X., Zhang, X., Li, K., Zhou, F., Huang, M., Li, Y., Li, H., Li, Y., Zeng, C., . . . Wang, J. (2023). Cerebellar connectome alterations and associated genetic signatures in multiple sclerosis and neuromyelitis optica spectrum disorder. Journal of Translational Medicine, 21(1). https://doi.org/10.1186/s12967-023-04164-w