A Comprehensive Approach to Disentangle the Effect of Cerebellar Damage on Physical Disability in Multiple Sclerosis

Abstract

Cerebellar damage occurs frequently in multiple sclerosis (MS) patients, with a wide exhibition of symptoms particularly as impairments of balance and gait. Recent studies implementing new postprocessing magnetic resonance imaging (MRI) techniques showed how cerebellar subregional atrophy provides an explanation of disability in MS. The aim of this work was to evaluate the relationship between quantitative measures of physical disability, cerebellar subregional atrophy, and cerebellar peduncle disruption. Forty-nine MS patients and 32 healthy subjects as controls (HS) underwent a 3-Tesla MRI including 3D T1-weighted and diffusion tensor imaging. Patients underwent static posturography to calculate the body's center of pressure (COP) displacement, Expanded Disability Status Scale (EDSS), and 25-ft walking test (25-FWT). Cerebellar lobular volumes were automatically calculated using the Spatially Unbiased Infratentorial Toolbox. Tract-based spatial statistics (TBSS) in FSL was used to process diffusion tensor imaging (DTI) Fit-generated fractional anisotropy (FA) maps to assess structural connectivity of cerebellar peduncles. Stepwise multivariate linear regression analyses were used to explore relationships between variables. Cerebellar volumes (anterior and posterior, as well as lobular volumes from I to X) were significantly lower in patients with MS than HS (p < 0.05). FA in all cerebellar peduncles was lower in MS patients than in HS (p < 0.05). EDSS and 25-FWT showed an association with atrophy of lobule VIIIb (β = −0.37, p < 0.01, and β = −0.45, p < 0.001, respectively) COP measures inversely correlated with volume of lobules I-IV (β = −0.37, p < 0.01, and β = −0.36, p < 0.01). Lower FA in the three cerebellar peduncles of MS patients positively correlated with cerebellar lobular volumes. Our findings show how sensorimotor cerebellum atrophy and disruption of both afferent and efferent cerebellar connections contribute to physical disability in MS patients.

Relation of sensorimotor and cognitive cerebellum functional connectivity with brain structural damage in patients with multiple sclerosis and no disability

“…The cerebellum is one of the major sites affected by multiple sclerosis (MS) from early disease stages [5]. Anterior and posterior cerebellar damage contributes to motor and cognitive disability across MS phenotypes [6][7][8][9]. Additionally, several structural measures of brain damage (i.e., T2-hyperintense lesion load and atrophy of cortical deep gray matter [GM]), represent well-known correlates of clinical disability and predictors of neurological impairment worsening [10][11][12].…”

Middle Cerebellar Peduncle Lesions and Their Relation to Affective and Cognitive Impairment in Multiple Sclerosis

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IntroductionCerebellum is commonly involved in multiple sclerosis (MS), and middle cerebellar peduncle (MCP) lesions have long been reported to be common in MS. 1,2 Cerebellar peduncle lesions are highly suggestive for MS, and their presence favors the diagnosis of MS rather than other mimics. 3 Being rich in myelinated axons, MCPs are vulnerable to demyelination and are affected in more than two-thirds (approximately 68%) of patients with MS. 4,5 MCPs contain the heaviest load of cerebellar afferent connections, 4 and because the cerebellum has a high afferent to efferent ration, i.e.

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“…[6][7][8][9] In MS, the impact of cerebellar damage on motor dysfunction, disability progression, and long-term prognosis has been heavily investigated. 1,5,[10][11][12][13] However, scarce data are available about its impact on cognitive and affective functions in patients with MS.As the MCPs carry most cerebellar afferents, 4 we aimed to study the impact of MCP lesions, in particular, on affective and cognitive functions in a cohort of patients with relapsing remitting MS (RRMS).…”

Neuroplasticity and Motor Rehabilitation in Multiple Sclerosis: A Systematic Review on MRI Markers of Functional and Structural Changes

“…However, a common finding of these studies was increased cerebellar connectivity with multiple brain areas. The cerebellum is a key structure involved in several cognitive and motor functions and is associated with multiple cortical areas through afferent and efferent cortico-cerebellar pathways (Stoodley and Schmahmann, 2010;Ruggieri et al, 2020). Recently, FC cerebellar changes were reported for both sensorimotor and cognitive compartments as a consequence of MS-related tissue damage, negatively associated with global and regional disability levels (Pasqua et al, 2020).…”