There are convergent and divergent changes in the way the cerebellum communicates with the rest of the brain and the transcriptomic signatures associated with these changes between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), a new study reported. This finding provides “insight into shared and unique neurobiological mechanisms underlying these two diseases,” according to the study authors.
The role of the cerebellum in the pathophysiology of MS and NMOSD is well established. However, the way in which these 2 diseases affect how it communicates with the rest of the brain is unclear.
Read more about the pathophysiology of NMOSD
The study is published in the Journal of Translational Medicine.
In the present study, a team of researchers from China, Pakistan, and the United Kingdom characterized convergent and divergent changes in morphological and functional connectivity within the cerebellum and between the cerebellum and the rest of the brain in patients with MS and NMOSD.
To do so, the researchers used multimodal magnetic resonance imaging (MRI) data from 208 patients with MS, 200 patients with NMOSD, and 228 healthy controls.
They reported many common changes in both conditions. However, they also found changes specific to each disease. For example, they found increases in morphological connectivity in the secondary motor module of the cerebellum in patients with MS. On the other hand, they found increases in connectivity between the primary motor module of the cerebellum and the motor- and sensory-related areas of the brain in patients with NMOSD.
Moreover, the team reported decreased functional connectivity between the motor modules of the cerebellum and the cortex associated with the brain in both conditions. However, there was a decrease in functional connectivity within the secondary motor module of the cerebellum specific to MS only and a decrease between the motor modules of the cerebellum and the limbic and default-mode regions of the brain in NMOSD only.
More than 37.5% of the variance in functional changes in the cerebellum of patients with MS could be explained by transcriptional data. The most correlated genes were enriched in processes related to signaling and ion transport. These were preferentially located in excitatory and inhibitory neurons.
Similar results were found in patients with NMOSD. However, the most correlated genes were preferentially located in astrocytes and microglia.
Finally, the researchers showed that cerebellar connectivity could help distinguish patients with MS, those with NMOSD, and healthy controls. Morphological connectivity was the predominant feature to distinguish patients with MS and NMOSD from healthy controls. On the other hand, functional connectivity was the predominant feature to distinguish patients with MS from those with NMOSD.
Yang Y, Li J, Li T, et al. Cerebellar connectome alterations and associated genetic signatures in multiple sclerosis and neuromyelitis optica spectrum disorder. J Transl Med. Published online May 27, 2023. doi:10.1186/s12967-023-04164-w