Evaluating Cerebellar Contributions to Physical Performance and Cognition in Multiple Sclerosis

Background: Individuals with multiple sclerosis (MS) demonstrate motor (i.e. strength and walking) and cognitive deficits. The cerebellum plays an important role in both motor and cognitive processing, and is a common site for MS-related disability. 

Objectives: The objective of this study was to examine the relationship of motor and cognitive performance to cerebellar lobule and peduncle volumes and diffusivity measures in individuals with MS. 

Methods: Twenty-nine individuals with relapsing remitting MS (mean ± SD age: 50.0 ± 11.3 years; symptom duration: 12.8 ± 9.9 years; 18 females; median [range] EDSS: 4.0 [1-6.5] and 23 age and gender-matched controls age: 51.9 ± 11.0 years; 15 females volunteered for this study.  All individuals participated in a clinical assessment and a 3T brain MRI including diffusion tensor imaging (fractional anisotropy (FA) and mean diffusivity (MD) only), MPRAGE and FLAIR sequences. We segmented the cerebellar lobules and peduncles and compared individuals with MS to controls using t-tests. We used correlation analyses to understand the relationship of the cerebellum to clinical measures.  

Results: Diffusivity (FA:  p=0.029; MD: p=0.002) of the superior cerebellar peduncle (SCP), the primary cerebellar output, was significantly worse in individuals with MS compared to controls. However, the cerebellar lobule volumes, peduncle volumes and diffusivity of the middle and inferior cerebellar peduncles in individuals with MS were not different from controls.

Increased volume of the motor lobules (I-V, VIII) was significantly associated with increased strength (r=0.37; p=0.007), faster walking speed (r=0.30; p=0.032), and better performance on the Timed 25 Foot Walk (T25FW) (r=-0.34; p=0.019), but was not related to sensory performance (r=-0.23; p=0.108). Increased volume of the cognitive lobules (VI-VII) was associated with better performance on the Symbol Digit Modality Test (r=0.36; p=0.009).

Increased diffusivity in the SCP was significantly associated with reduced falls in the past month (r=-0.37; p=0.007), increased walking speed (r=-0.28; p=0.041), and better performance on the T25FW (r=0.28; p=0.042). 

Conclusions: These data show that cerebellar volumetric and white matter connections are selectively associated with physical performance and cognition in individuals with MS. Examining structure-function relationships improves our understanding of individualized differences in this heterogeneous group and may provide an avenue for targeted rehabilitation.