Performance of Skin Biopsy for Cutaneous Phosphorylated Alpha-synuclein in Autonomic Disorders
Michael Rigby1, Elizabeth Coon1, Zachary Trottier1, Wolfgang Singer1, Stuart McCarter2
1Neurology, 2Neurology, Mayo Center for Sleep Medicine, Mayo Clinic
Objective:
To assess performance and clinical characteristics of skin biopsy for phosphorylated alpha-synuclein in autonomic dysfunction at an academic neurology center.
Background:
The clinical diagnosis of synucleinopathies can be challenging warranting development of reliable biomarkers. Cutaneous phosphorylated alpha-synuclein was found in 98.2-100% of those meeting clinical consensus criteria for multiple system atrophy (MSA) and 100% of those with pure autonomic failure (PAF); the pattern of positivity was more widespread in MSA/PAF compared to Parkinson’s disease.
Design/Methods:
Six patients presenting with autonomic dysfunction underwent commercially available skin biopsy at three sites (posterior cervical, distal thigh, distal leg) to assess for phosphorylated alpha-synuclein via immunohistochemistry. Autonomic reflex screen (ARS) results were quantified using the Composite Autonomic Scoring Scale (CASS, range 0-10). Thermoregulatory sweat test (TST) evaluated regions and percentage of anhidrosis.
Results:
Median age was 63 years old (range 57-83) with 1 of 6 (17%) female. Skin biopsy was positive for phosphorylated alpha-synuclein in 3 of 6 (50%) cases. Two patients with positive biopsies (all 3 sites involved) met criteria for clinically established MSA-C thus supporting the diagnosis. One patient with positive biopsy did not meet clinical criteria for a synucleinopathy and was diagnosed with autonomic neuropathy. Of those with negative biopsies, one met criteria for clinically established MSA-C, one was diagnosed with sporadic adult onset ataxia, and one was diagnosed with progressive supranuclear palsy. Those with positive skin biopsies had CASS ≥5 versus those with negative skin biopsies with CASS ≤3. Those with positive biopsies had higher degree of anhidrosis on TST (median 10.2% vs 6.5%). There was no association between presence of cutaneous phosphorylated alpha-synuclein at biopsy locations and regions of anhidrosis on TST or sudomotor function on ARS.
Conclusions:
In this small case series, higher CASS and percent anhidrosis on TST was associated with presence of cutaneous phosphorylated alpha-synuclein.
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