[6] The diagnosis of pure autonomic failure relies on the absence of other neurologic abnormalities, specifically Parkinsonism, cognitive impairment, cerebellar ataxia, or tremors, and on compatible clinical features of subtle, progressive pan autonomic failure, most notably orthostatic hypotension.

Urgency and frequency are the most common bladder symptoms in PAF, but more severe dysfunction including urinary retention and incontinence can also occur.

[citation needed] In 1925, Bradbury and Eggleston first characterized three patients seemingly with a common syndrome, with what they described as "the occurrence of syncopal attacks after or during exertion or even after standing erect for some minutes.

Other features in the three patients are a slow, unchanging pulse rate, incapacity to perspire, a lowered basal metabolism and signs of slight and indefinite changes in the nervous system.

The primary differentiating characteristic of Pure autonomic failure is decreased circulation and synthesis of norepinephrine, and dysfunction localized peripherally.