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Pure autonomic failure
Pure autonomic failure (PAF) is a neurodegenerative disease that affects the sympathetic branch of the autonomous nervous system and that manifests with orthostatic hypotension.
ORPHA:441Classification level: Disorder
- Bradbury-Eggleston syndrome
- Idiopathic orthostatic hypotension
- Pure dysautonomia
- Pure idiopatic dysautonomia
- Prevalence: 1-9 / 1 000 000
- Inheritance: Not applicable
- Age of onset: Adult, Elderly
- ICD-10: G90.3
- OMIM: -
- UMLS: C0393911 C2931939
- MeSH: C544351 D054970
- GARD: 10428
- MedDRA: -
The exact prevalence is unknown.
The disease affects adults. PAF manifests initially with orthostatic hypotension, erectile dysfunction and urinary disorders. Other symptoms, including sweat disorders and Horner syndrome (see this term), indicate a deficit of the sympathetic nervous system. There are no associated neurological signs.
PAF is sporadic and its etiology is unknown. It is a synucleinopathy with Lewy bodies and neuronal rarefaction in the intermediate-lateral tract of the medulla and in the sympathetic ganglia.
Diagnosis of PAF is indicated in cases with clinical signs compatible with chronic sympathetic deficiency, without associated neurological signs. The diagnosis is confirmed with evidence of neurogenic orthostatic hypotension (falling >= 20/10 mm Hg of arterial pressure when standing without reactive tachycardia). Ambulatory blood pressure monitoring can reveal a disappearance or reversal of the day/night rhythm. Specific tests for PAF (Ewing test, pupillary or sudoral function, analysis of heart rate and blood pressure variability, sympathetic microneurography and MIBG scintigraphy) are carried out by some laboratories. Plasma levels of noradrenaline are low at rest and do not increase on standing. The EMG and cerebral MRI/CT are normal. Examinations to identify an immunologic, deficiency, metabolic or toxic cause are negative.
Differential diagnoses include iatrogenic (including cardiovascular, urologic and psychotropic drugs) or curable (dehydration, venous insufficiency, anemia) causes of orthostatic hypotension, dopamine beta-hydroxylase deficiency (see this term), which is ruled out by the presence of plasma noradrenaline in patients affected by orthostatic hypotension that is considered idiopathic, primary or secondary peripheral polyneuropathy (including diabetes, amyloidosis, renal dysfunction, Guillain-Barré syndrome (see these terms), those due to deficiency or paraneoplasic syndrome) or neurodegenerative disease dysautonomias (multiple system atrophy, Parkinson's disease; see these terms), which are ruled out by normal neurological and paraclinical examinations in patients affected by PAF. The progression of PAF is slow, which distinguishes it from acute or sub-acute pandysautonomias.
Management and treatment
Management includes non medicinal measures (tight support stockings, abdominal binders, frequent meals, standing up slowly, increased liquid and salt intake, and avoiding prolonged orthostatism, alcohol, and warm environments). Standard medical treatment is with midodrine (an alpha-adrenergic agonist) and fludrocortisone (a hypokalemic mineralocorticoid). The efficacy of indirect sympathomimetics (heptaminol) and ergot derivatives (dihydroergotamine) have not been proven. Other drugs are subject to ongoing trials (pyridostigmine, droxidopa) or are designed for particular situations such as anemia (erythropoietin) or postprandial hypotension (octreotide). Decubitus arterial hypertension can be prevented by following simple rules (avoiding taking a vasoconstrictor before sleeping, resting in a semi-sitting position over night, taking an antihypertensive drug in extreme cases).
Progression of PAF lasts over 20 years. The appearance of neurological signs during the course of autonomic deficiency progression allows orthostatic hypotension to be a posteriori linked to multiple system atrophy or Parkinson's disease.