The phenotype of "pure" autonomic failure.

Purpose: Identifying features of patients who remain pure autonomic failure has implications on disease definition and offers insights into synucleinopathy progression. We sought to determine symptom timeline and autonomic features in patients who retain the pure autonomic failure phenotype with prolonged follow-up.

Methods: We reviewed all patients diagnosed with pure autonomic failure from 2001 to 2011 evaluated at Mayo Clinic, Rochester, with autonomic reflex screen and over 1 year of in-person follow-up. Clinical evaluations and patient telephone calls were used to assess timeline of symptoms.

Results: Of 202 patients, 133 remained pure autonomic failure with median follow-up time of 9.05 years (interquartile range (IQR) 4.2-13.1). Additional autonomic symptoms included constipation (N = 60; 45%), bladder symptoms (N = 78; 59%), which were severe in 50 patients (37.6%) with incontinence or requiring catheterization, sexual dysfunction (N = 53; 40%) and thermoregulatory dysfunction (N = 51; 38%). Assessment of dream enactment behavior was completed in 86 patients and endorsed in 45 patients (52%). Median time to dream enactment behavior onset from orthostatic hypotension was 7.00 years (1.55-13.50). Other autonomic symptoms tended to occur near orthostatic hypotension. Autonomic testing showed moderate to severe autonomic failure with median composite autonomic score of 6 (IQR 4-8; N = 133) and median percentage anhidrosis of 51% (IQR 3-93%; N = 105).

Conclusions: Patients with pure autonomic failure typically have symptom onset near development of orthostatic hypotension while dream enactment behavior may occur later. Our findings underscore that not all patients with pure autonomic failure will develop motor or cognitive symptoms, even with prolonged follow-up.