Objective: To highlight the limitations in clinically differentiating PD and MSA.

Background: The antemortem differentiation of parkinsonian syndromes remains challenging due to overlapping symptomatology, particularly between PD and MSA. Despite the 2022 diagnostic criteria update for MSA, atypical presentations continue to complicate diagnosis. This case illustrates the diagnostic complexity and evolving clinical picture in a patient initially diagnosed with PD who ultimately had pathologically-confirmed MSA.

Method: N/A

Results: A 47-year-old female presented with parkinsonism characterized by left-sided bradykinesia, rigidity, and reduced arm swing. Examination revealed hypomimia, hypometric saccades, and bilateral upper extremity rigidity. DaTscan demonstrated decreased uptake in bilateral posterior greater than anterior putamen, consistent with nigrostriatal degeneration. The patient was diagnosed with idiopathic PD and exhibited excellent initial response to carbidopa-levodopa therapy (UPDRS: 34 OFF, 11 ON).

Disease progression over four years required increasing medication doses, precipitating orthostatic hypotension, with a 10 point systolic drop and a 20 point diastolic drop. She met criteria for bilateral subthalamic nucleus DBS, which yielded initial symptomatic improvement and medication reduction. However, within 18 months post-DBS, she experienced rapid progression despite optimized treatment, along with worsening orthostatic hypotension requiring oral vasopressors. Autonomic testing confirmed severe neurogenic dysautonomia, prompting diagnostic reconsideration to MSA. Post-mortem neuropathological examination 12 years after symptom onset and 7 years after DBS confirmed this revised diagnosis.

Conclusion: This case highlights the limitations of current clinical diagnostic criteria in differentiating parkinsonian syndromes. The patient’s presentation initially fulfilled MDS-PD criteria with excellent levodopa response and supportive neuroimaging, yet MSA was the ultimate pathological diagnosis. Recent postmortem studies demonstrate that dysautonomia alone is insufficient for MSA diagnosis, as many patients with PD and dysautonomia lack MSA pathology. This clinicopathological dissonance underscores the need for reliable biomarkers to differentiate predominately glial (MSA) from predominantly neuronal (PD) alpha-synucleinopathies, which would significantly improve diagnostic accuracy and facilitate earlier disease-modifying interventions.

References: 1. Koga S, Aoki N, Uitti RJ, et al. When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology. 2015;85(5):404-412. doi:10.1212/WNL.0000000000001807
2. Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Movement Disorders. 2022;37(6):1131-1148. doi:https://doi.org/10.1002/mds.29005
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MDS Abstracts - https://www.mdsabstracts.org/abstract/rethinking-parkinsonism-limitations-in-clinical-diagnosis/