Objective: To clarify the interactions among clinical features and imaging markers, and to identify factors contributing to disease severity in MSA.

Background: Multiple system atrophy (MSA) presents with cerebellar ataxia, Parkinsonism, and autonomic dysfunction, but relationships among these degenerative systems remain unclear. Recent clinical trials often use the Unified Multiple System Atrophy Rating Scale (UMSARS) total score as a primary outcome. However, established biological markers reflecting clinical progression are lacking. We previously developed perfusion patterns estimating cerebellar ataxia and Parkinsonian severity in MSA, termed MSA-AP (ataxia-related pattern) and MSA-PP (parkinsonism-related pattern).

Method: A total of 122 patients with MSA were randomly divided into a training cohort (n=70) and a validation cohort (n=52). Principal component analysis of brain perfusion SPECT (¹²³I-IMP) images in the training cohort identified MSA-AP and MSA-PP associated with International Cooperative Ataxia Rating Scale (ICARS) and Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Individual pattern expressions were calculated in the validation cohort. Clinical variables associated with the UMSARS total score were selected by partial least squares regression. Structural equation modeling (SEM) was applied to evaluate relationships among imaging pattern expression (MSA-AP and MSA-PP), clinical variables, and disease severity.

Results: Age, disease duration, ICARS, UPDRS-III, overactive bladder symptom score (OABSS), postvoid residual urine (PVR), and Addenbrooke’s Cognitive Examination-III (ACE-III) were associated with UMSARS total score and were included in the SEM analysis together with MSA-AP and MSA-PP. The best-fitting model (CFI=0.96) showed that longer disease duration increased ICARS scores, whereas older age increased OABSS and MSA-PP. Increased OABSS was associated with reduced MSA-PP and higher UPDRS-III scores. Lower ACE-III scores contributed to higher UMSARS scores through increased ICARS. ICARS, UPDRS-III, and PVR showed direct associations with UMSARS total score.

Conclusion: Imaging patterns reflecting cerebellar and Parkinsonian motor systems (MSA-AP and MSA-PP) were integrated with autonomic and cognitive factors in determining disease severity. SEM revealed interactions among these domains, suggesting a framework for the multidomain progression of MSA.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-significance-of-imaging-markers-for-cerebellar-ataxia-and-parkinsonism-in-multiple-system-atrophy/