Cutaneous alpha-synuclein deposition in postural tachycardia patients.

Objective: To report a case series of patients with neuropathic POTS and cutaneous phosphorylated alpha-synuclein (P-SYN) deposition on skin biopsy and compare these to neuropathic POTS patients without P-SYN deposition.

Methods: The medical history, physical examination findings, autonomic function testing, and skin biopsy neuropathology of patients under the age of 50 with a postural tachycardia and a diagnosis of POTS were retrospectively reviewed. Included patients completed the composite autonomic severity score (COMPASS 31), the Wood Mental Fatigue Inventory, the Epworth Sleepiness scale, the REM Behavior Disorder Questionnaire, the Patient-Reported Outcomes Measurement Information System (PROMIS-10), and the Gastroparesis Cardinal Symptom Index.

Results: Of 296 patients seen with POTS, 22 patients with suspected neuropathic POTS had skin biopsies performed during their evaluation. Seven of 22 patients had P-SYN present on skin biopsy, while 15 individuals did not. Those with P-SYN on biopsy: (1) were more likely to be male; (2) had features of REM sleep behavioral disorder; (3) reported less sleepiness and cognitive impairment; and (4) noted greater symptoms of gastroparesis. On autonomic testing, the group with P-SYN deposition was more likely to have a hypertensive response to tilt-table testing and abnormal QSART responses.

Interpretation: Phosphorylated alpha-synuclein deposition is present in some postural tachycardia patients with neuropathic features. Individuals with a postural tachycardia and cutaneous phosphorylated alpha-synuclein deposition may be distinguished from other patients with neuropathic POTS.