Pure autonomic failure (PAF) is an uncommon, sporadic

neurodegenerative A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

condition marked by a steadily declining autonomic regulation. Bradbury and Eggleston originally described pure autonomic failure in 1925. Patients usually present with

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

or syncope in midlife or later. In addition, genitourinary,

thermoregulatory Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...

, and bowel dysfunction can be signs of autonomic failure. Pure autonomic failure originates from peripheral autonomic nervous system lesions. The diagnosis of pure autonomic failure relies on the absence of other neurologic abnormalities, specifically

Parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), Rigidity (neurology), rigidity, and balance disorder, postural instability. Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic f ...

, cognitive impairment,

cerebellar ataxia Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias. Cerebellar ataxia can occur as a result of many diseases and may present with symptoms ...

, or tremors, and on compatible clinical features of subtle, progressive pan autonomic failure, most notably

Signs and symptoms

The majority of symptoms that patients with PAF exhibit are associated with neurogenic

, or orthostatic hypotension brought on by severe sympathetic failure. Within three minutes of standing up straight,

is defined as a drop in systolic

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

of at least 20 mm Hg or a drop in diastolic blood pressure of 10 mm Hg. About half of PAF patients also have concurrent supine hypertension, even though all PAF patients by definition have orthostatic hypotension. For some PAF patients, genitourinary dysfunction may be the first or presenting symptom. Urgency and frequency are the most common bladder symptoms in PAF, but more severe dysfunction including

urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include urinary incont ...

and

incontinence Incontinence or Incontinent may refer to: * Urinary incontinence, the most commonly occurring type of incontinence, the involuntary excretion of urine *Fecal incontinence Fecal incontinence (FI), or in some forms, encopresis, is a lack of con ...

can also occur. Over half of PAF patients report having

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

, which is frequently an early sign of the illness. About half of all PAF patients report abnormal sweating, which can manifest as either excessive or decreased sweating, with the latter being the result of compensatory

hyperhidrosis Hyperhidrosis is a medical condition in which a person exhibits excessive perspiration, sweating, more than is required for the Thermoregulation, regulation of body temperature. Although it is primarily a physical burden, hyperhidrosis can deterio ...

Pathology

The

pathology Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...

of pure autonomic failure is not yet completely understood. However, a loss of cells in the intermediolateral column of the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

has been documented, as has a loss of

catecholamine A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Cate ...

uptake and catecholamine fluorescence in sympathetic postganglionic

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

. In general, levels of catecholamines in these patients are very low while lying down, and do not increase much upon standing.

Treatment

Pharmacological methods of treatment include

fludrocortisone Fludrocortisone, sold under the brand name Florinef among others, is a corticosteroid used to treat congenital adrenal hyperplasia, postural hypotension, and adrenal insufficiency. In adrenal insufficiency, it is generally taken together wit ...

midodrine Midodrine, sold under the brand names ProAmatine and Orvaten among others, is an antihypotensive medication used to treat orthostatic hypotension (low blood pressure when standing) and urinary incontinence. It is taken oral administration, by m ...

somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...

erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...

, and other

vasopressor An antihypotensive, also known as a vasopressor, is an agent that raises blood pressure by constricting blood vessels, thereby increasing systemic vascular resistance. This is different from inotropes which increase the force of cardiac contrac ...

agents. However, often a patient with pure autonomic failure can mitigate his or her symptoms with far less costly means. Compressing the legs and lower body, through crossing the legs, squatting, or the use of

compression stockings Compression stockings (Flight Socks, Support Bandage) are a specialized hosiery designed to help prevent the occurrence of, and guard against further progression of, venous disorders such as edema, phlebitis and thrombosis. Compression stockings ...

can help. Use of an abdominal binder is even more effective. Also, ingesting more water than usual can increase blood pressure and relieve some symptoms.

History

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. Each of these patients felt much worse during the heat of summer." Further research identified multiple causes for these syndromic findings, now grouped as primary autonomic disorders (also called primary dysautonomia), including Pure Autonomic Failure, Multiple System Atrophy, and Parkinson's. The primary differentiating characteristic of Pure autonomic failure is decreased circulation and synthesis of norepinephrine, and dysfunction localized peripherally. It is relevant to note that progression to central nervous system neurodegeneration can also occur.

Eponym

It is also known as Bradbury-Eggleston syndrome, named after Samuel Bradbury and Cary Eggleston who first described it in 1925.S. Bradbury, C. Eggleston. Postural hypotension: A report of three cases. American Heart Journal, St. Louis, 1925, 1: 73-86.

References

External links

Stanford Health Care

Merck Manual
{{Autonomic diseases Peripheral nervous system disorders