Chapter 27 - Pure autonomic failure
Introduction
Pure autonomic failure (PAF) is a rare sporadic neurodegenerative disorder characterized by progressive failure of autonomic regulation. Described initially in 1925 by Bradbury and Eggleston, the disease is characterized by an indolent course associated with worsening orthostatic hypotension (OH) and other markers of sympathetic and parasympathetic dysregulation. PAF is often distinguished as a separate entity from autonomic failure associated with diseases of the CNS such as Parkinson's disease (PD) with autonomic features. Symptoms of cerebral hypoperfusion and supine hypertension can make autonomic failure difficult to manage. α-Synucleinopathy and formation of Lewy bodies in the peripheral autonomic nervous system often underlie the pathology of PAF, although occasional cases have lacked Lewy bodies. This chapter describes the characteristics of PAF as a disease including history, presentation, diagnosis, pathology and treatment, and focuses on neurophysiologic findings, evaluation and treatment.
Section snippets
History
The 1996 PAF consensus statement mentions three characteristic features of the disease: OH, absence of other neurologic features, and reduced supine plasma norepinephrine levels. The original Bradbury and Eggleston series published in 1925 discussed 3 patients who described symptoms of OH. On examination, the authors noted other symptoms of autonomic failure in these patients including a slow, unchanging pulse rate, anhidrosis, erectile dysfunction, and constipation. Symptoms improved somewhat
Presentation
The most common presenting feature of autonomic failure is OH. Patients are typically middle-aged males (70% male with a mean age of 63 presenting with symptoms for about 5 years as noted in Kaufmann et al., 2017). Symptoms progress slowly initially with presyncope and lightheadedness. A coat-hanger distribution headache due to hypoperfusion of the neck muscles upon standing is common, as noted by Bleasdale-Barr and Mathias (1998). Exacerbation of symptoms by heat or a large meal is common.
Pathophysiology
The protein α-synuclein occurs in neuronal or glial cytoplasm of patients with PD, DLB, MSA, and PAF. It remains unclear whether the protein itself causes disruption of cellular function. In PAF, the largest concentrations of Lewy bodies are found in the sympathetic and parasympathetic ganglia and pre- and postganglionic autonomic neurons. Lewy bodies can also be found in a number of other peripheral tissues, including adipose and the urinary bladder. Lewy bodies can also be found in the
Treatment/Management (Brief Overview)
Treatment strategies for PAF focus on symptom control with a tri-pronged approach. Typically, the patient is symptomatic mainly due to neurogenic orthostatic hypotension. Treatment involves avoiding exacerbating factors, use of conservative measures and lifestyle changes, and, finally, pharmacologic treatment.
Avoidance of exacerbating factors such as use of diuretics, vasodilators (sildenafil, nitrates), and norepinephrine release blockers (alpha blockers or tricyclic antidepressants) is
Future Directions
Prognosis in PAF remains good overall, with a greater than 20-year survival expected in most patients. However, a number of PAF patients progress to more severe forms of synucleinopathy. The pathogenic role of α-synuclein still appears somewhat unclear. Patients with PAF who do not demonstrate evidence of α-synuclein deposition may have a different disorder. Further identification and evaluation of these patients will help elucidate the pathophysiology, nature, prognosis, and management of this
References (29)
- et al.
Postural hypotension: a report of three cases
Am Heart J
(1925) - et al.
Effects of patient controlled abdominal compression on standing systolic blood pressure in adults with OH
Arch Phys Med Rehabil
(2015) Consensus statement of the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome
Auton. Neurosci
(2011)- et al.
Autonomic failure
- et al.
Neck and other muscle pains in autonomic failure: their association of orthostatic hypotension
J R Soc Med
(1998) Consensus statement on the definition of OH, PAF, and MSA. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology
Neurology
(1996)- et al.
Skin nerve misfolded a-synuclein in pure autonomic failure and Parkinson disease
Ann Neurol
(2016) - et al.
The value of cardiovascular autonomic function tests: 10 years experience in diabetes
Diabetes Care
(1985) - et al.
Pharmacological probes to measure the importance of the autonomic nervous system
Clin. Auton. Res.
(2007) - et al.
Contribution of endothelial nitric oxide to blood pressure in humans
Hypertension
(2007)