Pure autonomic failure

Pure autonomic failure (PAF), also known as Bradbury-Eggleston syndrome or idiopathic orthostatic hypotension, is a rare neurodegenerative disorder of the autonomic nervous system. It is classified as a synucleinopathy, characterized by abnormal accumulation of alpha-synuclein in peripheral autonomic neurons. PAF primarily affects the autonomic (involuntary) nervous system, which controls functions such as blood pressure regulation, heart rate, bladder function, sweating, and gastrointestinal motility. Unlike other synucleinopathies such as multiple system atrophy or Parkinson disease with autonomic failure, PAF does not involve significant central nervous system degeneration, at least in its early stages. The hallmark symptom of PAF is severe orthostatic hypotension — a dramatic drop in blood pressure upon standing — which leads to dizziness, lightheadedness, blurred vision, and fainting (syncope). Other common symptoms include urinary dysfunction (urinary frequency, urgency, or retention), constipation, reduced sweating (anhidrosis or hypohidrosis), erectile dysfunction in men, and supine hypertension (elevated blood pressure when lying down). Symptoms typically develop insidiously in middle to late adulthood. Notably, some patients with PAF may eventually convert (phenoconvert) to other synucleinopathies, including Parkinson disease, dementia with Lewy bodies, or multiple system atrophy, making long-term follow-up essential. There is currently no cure or disease-modifying therapy for PAF. Treatment is symptomatic and focuses primarily on managing orthostatic hypotension and other autonomic symptoms. Non-pharmacological measures include increased fluid and salt intake, wearing compression garments, and avoiding sudden postural changes. Pharmacological options include midodrine (a vasopressor), droxidopa (a norepinephrine precursor approved for neurogenic orthostatic hypotension), and fludrocortisone (a mineralocorticoid to expand blood volume). Management of supine hypertension, which often coexists with orthostatic hypotension, requires careful balancing of treatments. Patients benefit from multidisciplinary care involving neurologists, cardiologists, and urologists.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Pure autonomic failure