Objective: To identify multiple system atrophy–cerebellar type (MSA-C) patients with marked cerebellar asymmetry and compare their features with symmetrically affected patients.

Background: While asymmetry is well-documented in MSA-parkinsonian type, MSA-C is traditionally considered symmetrical. Nevertheless, some MSA-C patients exhibit pronounced cerebellar lateralization, suggesting a distinct pathological process.

Method: Twenty-nine consecutive patients with established MSA-C, followed ≥4 years, were retrospectively analyzed. All underwent dual-phase 18F-FP-CIT PET and MRI. Early-phase PET images provided cerebellar perfusion data for asymmetry calculations. K-means clustering distinctly separated patients into asymmetric (n=8) and symmetric (n=21) groups. Clinical variables and striatal dopamine transporter (DaT) availability were compared.

Results: The asymmetric group (27.6%) was distinguished by asymmetry predominantly driven by posterior cerebellar regions below the horizontal fissure, with crus II, lobule 7b, and lobule 8 contributing most significantly to this asymmetry (all p<0.001). While disease duration (15.12±7.32 vs. 23.25±13.96 months, p=0.133) and autonomic features were similar between groups, the asymmetric group had lower UMSARS part 2 scores (21.00±8.06 vs. 30.82±7.90, p=0.021). Notably, they displayed preserved striatal DaT uptake: only 12.5% had abnormal scans versus 61.9% in the symmetric group (p<0.05). Mean DaT availability was significantly higher in both caudate (3.94±0.60 vs. 3.33±0.74, p<0.05) and putamen (4.29±0.74 vs. 3.62±0.80, p=0.047).

Conclusion: A distinct MSA-C subgroup demonstrates pronounced asymmetry in posterior cerebellar regions, better motor scores, and preserved dopaminergic function, suggesting an alternative disease trajectory that warrants further pathophysiological investigation.

PCA plot showing MSA-C patient clustering

Cerebellar asymmetry indices by patient group

Striatal DaT availability comparison

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-dopaminergic-characteristics-of-msa-c-patients-with-predominant-cerebellar-asymmetry/