Pure autonomic failure

Bradbury and Eggleston, in 1925, provided the initial account of pure autonomic failure (PAF). The consensus statement in 1996 defined it as an idiopathic sporadic disorder with orthostatic hypotension, including widespread autonomic dysfunction and reduced supine norepinephrine levels without other neurological features. Autonomic investigations were consistent with efferent, likely postganglionic, adrenergic failure. Because patients with multiple system atrophy, a neurodegenerative disorder with poor prognosis, mimicked PAF during the initial few years after onset, clinical investigators in the 1980s and 1990s focused on developing tests that distinguished PAF (postganglionic dysfunction) from multiple system atrophy (preganglionic dysfunction). Earlier neuropathological studies observed Lewy bodies in the substantia nigra, locus coeruleus, dorsal motor nucleus of the vagus, intermediolateral column cells of the spinal cord, and sympathetic ganglia. Later studies reported A-synuclein aggregates in PAF, idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, thus challenging the existence of PAF as an independent entity. PAF patients have a relatively benign course but with severe symptoms. Failure of nonpharmacologic modalities such as rapid water drinking, abdominal compression, and physical counter maneuvers requires use of drugs to reduce the impact of orthostatic hypotension. Midodrine and droxidopa are FDA-approved drugs, and fludrocortisone has been prescribed off label since 1959. Appropriate specialty consultation is warranted in patients with severe bladder or bowel disturbances.