Objective: To determine the clinical utility of phosphorylated alpha-synuclein (P-SYN) within skin biopsies in diagnostic and management decisions.

Background: The initial diagnosis of Parkinson’s Disease (PD) and related parkinsonian disorders is primarily made clinically, but may be incorrect in up to 25% of patients. Diagnostic accuracy increases with time after initial diagnosis as clinical features and red flags pointing to other disorders emerge. The need for earlier and accurate diagnosis of these progressive neurodegenerative disorders is a major unmet need impacting symptomatic treatment, consideration of investigational therapies, prognostication, and avoidance of inappropriate therapy. Cutaneous nerves in skin biopsies can be stained for P-SYN, which is a diagnostic biomarker for degenerative synucleinopathies, including PD, multiple system atrophy and dementia with Lewy bodies.

Method: Retrospective chart review of consecutive patients with suspected parkinsonism seen in the Beth Israel Deaconess Medical Center Department of Neurology from 2021- 2023 who received a skin biopsy for P-SYN as part of their clinical evaluation. Changes to the clinical diagnosis and treatment were assessed after P-SYN biopsy results.

Results: Ninety-Seven consecutive patients were identified and reviewed. Overall, 66% had a change in diagnosis, 55% had a change in treatment, and 34% had a diagnosis confirmed. We identified several common clinical scenarios in which the test led to changes in diagnosis and/or management: PD with unclear levodopa response, idiopathic PD vs. drug induced PD, prominent action tremor (PD vs. essential tremor), lower extremity predominant PD, autonomic predominant PD, memory disorder predominant PD, and early subtle signs of PD. Changes in treatment followed clarification of clinical diagnosis and whether phosphorylated alpha synuclein was identified on skin biopsy.

Conclusion: Skin biopsy for phosphorylated alpha synuclein can improve clinical diagnosis and impact treatment when a diagnosis of parkinsonism is uncertain.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-utility-of-synuclein-skin-biopsy-in-the-initial-diagnosis-and-evaluation-of-parkinsonian-disorders/