Cutaneous alpha-synuclein deposition in postural tachycardia patients

Area of Science:

• Neurology
• Autonomic Neuroscience
• Pathology

Background:

• Postural Orthostatic Tachycardia Syndrome (POTS) is a complex condition affecting the autonomic nervous system.
• Neuropathic POTS is a subtype characterized by nerve damage, impacting autonomic function.
• Cutaneous phosphorylated alpha-synuclein (P-SYN) deposition is a potential biomarker for neurodegenerative conditions.

Purpose of the Study:

• To investigate the presence of P-SYN deposition in skin biopsies of patients with neuropathic POTS.
• To compare the clinical and autonomic characteristics of neuropathic POTS patients with and without P-SYN deposition.

Main Methods:

• Retrospective review of 296 POTS patients, focusing on 22 with suspected neuropathic POTS who underwent skin biopsy.
• Assessment of medical history, physical examination, autonomic function tests (e.g., QSART, tilt-table testing).
• Utilized validated questionnaires including COMPASS 31, Epworth Sleepiness Scale, and Gastroparesis Cardinal Symptom Index.

Main Results:

• Seven out of 22 patients with neuropathic POTS showed cutaneous P-SYN deposition.
• Patients with P-SYN deposition were more likely to be male, exhibit REM sleep behavior disorder, and report more severe gastroparesis symptoms.
• The P-SYN positive group demonstrated a higher incidence of hypertensive response to tilt-table testing and abnormal QSART responses.

Conclusions:

• Cutaneous P-SYN deposition is identified in a subset of neuropathic POTS patients.
• The presence of P-SYN in skin biopsies may help distinguish a specific subgroup of neuropathic POTS patients.
• Further research is warranted to understand the clinical implications of P-SYN deposition in POTS.