Cerebellar atrophy and its contribution to motor and cognitive performance in multiple system atrophy

Abstract

Objective Neuroanatomical differences in the cerebellum are among the most consistent findings in multiple system atrophy (MSA) patients. This study performed a detailed cerebellar morphology in MSA patients and its two subtypes: MSA-P (parkinson's symptoms predominate) and MSA-C (cerebellar symptoms predominant), and their relations to profiles of motor and cognitive deficits. Materials and methods Structure MRI data were acquired from 63 healthy controls and 61 MSA patients; voxel-based morphometry and the Spatially Unbiased Infratentorial Toolbox cerebellar atlas were performed to identify the cerebellar gray volume changes in MSA and its subtypes. Further, the gray matter changes were correlated with the clinical motor/cognitive scores. Results Patients with MSA exhibited widespread loss of cerebellar volume bilaterally, relative to healthy controls. In those with MSA-C, gray matter loss was detected from anterior (bilateral lobule IV-V) to posterior (bilateral crus I/II, bilateral lobule IX, left lobule VIII) cerebellar lobes. Lower anterior cerebellar volume negatively correlated with disease duration and motor performance, whereas posterior lobe integrity positively correlated with cognitive assessment. In patients with MSA-P, atrophy of anterior lobe (bilateral lobules IV-V) and posterior lobe in part (left lobule VI, bilateral IX) was evident; and in left cerebellar lobule IX, gray matter loss negatively correlated with motor scores. Direct comparison of MSA-P and MSA-C group outcomes showed divergence in right cerebellar crus II only. Conclusions Our data suggest that volumetric abnormalities of cerebellum contribute substantially to motor and cognitive performance in patients with MSA. In patients with MSA-P and MSA-C, affected regions of cerebellum differed.

Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type

“…Atrophy of the cerebellum and brainstem are common features of MSA‐C and SAOA . In addition, microstructural alterations of the white matter have been reported in previous studies in MSA‐C patients .…”

“…Previous volumetric and VBM studies in MSA‐C have consistently shown cerebellar and brainstem volume loss . In SAOA, volume loss has been reported as being most prominent in the cerebellum, although some studies also detected involvement of the cerebellar peduncles and brainstem.…”

Alterations in Degree Centrality and Functional Connectivity in Parkinson’s Disease Patients With Freezing of Gait: A Resting-State Functional Magnetic Resonance Imaging Study

“…The synergistic effect of the cerebellum with the frontal network has indicated that aside from its traditional integration of motor function, the cerebellum also participates in the regulation of non-motor functions such as cognition. Yang et al (2019) reported that cerebellar abnormalities in patients with MSA are related to the cognitive impairment process. Wang et al (2018) suggested that the cerebellum plays a key role in emotion regulation in PD patients with depression.…”

Neuroimaging Advances in Parkinson's Disease and Atypical Parkinsonian Syndromes

“…• Structural MRI MRI signs: putaminal rim sign, hot cross bun sign, middle cerebellar peduncles (MCP) sign Striatonigral and olivopontocerebellar atrophy is observed in MSA vs. NC ↓ in putamen, MCP, cerebellum, and pons in MSA-P vs. PD Supratentorial atrophy (putamen) in MSA-P, whereas infratentorial atrophy in MSA-C may be more predominant (11,28,71,99,102,103,(106)(107)(108)(109)(110) (Continued) • Proton MRS ↓ NAA/Cr ratio in putamen in MSA-P, and in pontine base in both MSA-P and MSA-C vs. NC ↓ NAA/Cr ratio in putamen and pontine base may discriminate MSA-P from PD (120) • PET and SPECT b Glucose metabolism: MSA-related spatial covariance pattern may involve metabolic ↓ in putamen and cerebellum (273,279) Dopaminergic system: b ↓ striatal presynaptic DAT binding and ↓ dopamine D2 receptor binding vs. NC (225,241,242) Neuroinflammation: ↑ microglial activity in dorsolateral prefrontal cortex, putamen, pallidum, pons, and SN vs. NC (332) • Transcranial S b ↑ LN echogenicity along with normal or ↑ SN echogenicity may be seen (188,197) AD clinical outcomes (320). Some of the developmental challenges [see reference (321)], although similar to those of tau PET radiotracers, include the intracellular nature of most α-synuclein aggregates requiring ideal lipophilicity and molecular size, multiple α-synuclein strains that may interact differently with some tracers, colocalization of α-synuclein with other protein aggregates, relatively less abundance of α-synuclein over amyloid and tau aggregates requiring higher tracer selectivity, as well as the potential for off-target binding which may necessitate further validation.…”

“…Likewise, VBM analysis in MSA-P vs. PD revealed atrophy in the superior cerebellar peduncle (SCP), MCP, cerebellum, pons, midbrain, and putamen, but not in the globus pallidus ( 71 ). Cerebellar atrophy was evident in both MSA-P and MSA-C subtypes to varying degrees ( 28 , 108 ). In an analysis of cerebellar neuroanatomical differences in MSA subtypes, a relatively greater GM atrophy was observed in MSA-C cases (vs. MSA-P) in the right Crus II—a cerebellar region involved in executive motor control ( 108 ).…”