Disorders In Depth
Pure Autonomic Failure (PAF)
Introduction
Pure autonomic failure (PAF), or Bradbury-Eggleston syndrome, is a peripheral degenerative disorder of the autonomic nervous system presenting in middle to late life, and affecting men more often than women. The disorder appears to be confined to the sympathetic and parasympathetic nervous systems.
Clinical Features
- The initial feature in men is often erectile dysfunction.
- The symptom that usually brings patients to the physician is orthostatic hypotension, or a fall in blood pressure with standing. The orthostatic hypotension may be described as unsteadiness, dizziness, or faintness upon standing. It is worse in the morning, after meals or exercise, or in hot weather.
- Complaints of pain in the neck or back of the head, relieved by lying down are sometimes present.
- The orthostatic hypotension is frequently accompanied by supine hypertension, or increased blood pressure while lying, even when the patient is on no medications to raise blood pressure. Yet, even when the supine hypertension is quite severe, cardiac function is well-preserved and contractility may sometimes even be raised.
- There is usually hypohidrosis or at least an asymmetrical distribution of sweating.
- Nocturia is common and may cause the patient to get up as many as three or more times per night to pass substantial amounts of urine. Urinary hesitancy, urgency, dribbling, and occasional incontinence might also occur.
- Some patients develop signs of neurogenic urinary retention and these individuals may have repeated urinary tract infections in consequence.
- Evidence of normal sympathetic and parasympathetic activity, such as nausea and pallor, may not occur when expected.
Pathology
There is a loss of cells in the intermediolateral column of the spinal cord and a loss of catecholamine uptake and catecholamine fluorescence in sympathetic postganglionic neurons. Autonomic failure should be distinguished from two other disorders classified as primary autonomic failure: Multiple System Atrophy (MSA) and idiopathic Parkinson’s Disease (PD). PAF generally induces fewer disabling symptoms than do these other syndromes. In PAF, there should be no indication from the history or physical examination of cerebellar, striatal, pyramidal or extrapyramidal dysfunction. Autonomic failure patients have greatly reduced levels of catecholamines and an impaired response to stimuli that normally raise plasma norepinephrine and DHPG. Plasma and urinary norepinephrine levels are sometimes only 10% of normal. There is marked hypersensitivity to all pressor and depressor stimuli, especially sympathomimetic amines.
Treatment
- An important aspect of treatment is patient education. Patients should understand the relatively benign nature of PAF but need to learn to live within the limitations imparted by their symptoms. Some patients find that leg-crossing helps to maintain upright posture.
- Other nonpharmacological treatment options include squatting, abdominal compression, bending forward and compression stockings.
- Pharmacological options include droxidopa, fludrocortisone, midodrine, yohimbine, octreotide, erythropoietin, and other vasopressor agents.
- Finally, an important treatment option is water. Sixteen ounces of water can raise blood pressure as much as 40 mm Hg for about 90 minutes, with a peak at 30 minutes after ingestion. Conversely, a carbohydrate-rich meal will lower blood pressure about the same amount over the same time course.
Outlook
Patients with PAF have a generally good outlook; many live normal life spans and sometimes well into their 80s.
