Pure Autonomic Failure

A degenerative disease of the AUTONOMIC NERVOUS SYSTEM that is characterized by idiopathic ORTHOSTATIC HYPOTENSION and a greatly reduced level of CATECHOLAMINES. No other neurological deficits are present.

Also Known As:

Networked: 192 relevant articles (6 outcomes, 13 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Orthostatic Hypotension (Postural Hypotension)
2.	Parkinson Disease (Parkinson's Disease)
3.	Multiple System Atrophy
4.	Dizziness (Lightheadedness)
5.	dopamine beta hydroxylase deficiency

Experts

1.	Goldstein, David S: 33 articles (01/2021 - 08/2002)
2.	Holmes, Courtney: 20 articles (01/2021 - 08/2002)
3.	Biaggioni, Italo: 13 articles (11/2021 - 03/2002)
4.	Sharabi, Yehonatan: 12 articles (01/2021 - 08/2003)
5.	Kaufmann, Horacio: 11 articles (01/2020 - 08/2003)
6.	Freeman, Roy: 8 articles (10/2021 - 08/2003)
7.	Robertson, David: 8 articles (01/2019 - 10/2002)
8.	Mathias, Christopher J: 7 articles (01/2015 - 05/2002)
9.	Mathias, C J: 7 articles (10/2008 - 02/2001)
10.	Pechnik, Sandra: 6 articles (02/2009 - 08/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Pure Autonomic Failure:

1.	DroxidopaIBA 04/01/2019 - "Areas covered: The authors review the effects of droxidopa in NOH with a focus on the neurodegenerative diseases PD, MSA, and pure autonomic failure (PAF). " 07/22/2014 - "Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. " 08/01/2001 - "This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). " 08/01/2001 - "L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure." 10/01/2016 - "The long-term safety of droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension in patients with Parkinson disease, pure autonomic failure, multiple system atrophy, or nondiabetic autonomic neuropathy was evaluated in a phase 3, multinational, open-label study in patients who previously participated in a double-blind, placebo-controlled clinical trial of droxidopa. "
2.	Dopamine (Intropin)FDA LinkGeneric 04/01/2008 - "Central dopamine deficiency in pure autonomic failure." 12/01/2020 - "We reviewed 18 F-dopamine (18 F-DA) positron emission tomographic images and postmortem neurochemical data across several body organs of controls and patients with the LB synucleinopathies PD and pure autonomic failure (PAF) and the non-LB synucleinopathy multiple system atrophy (MSA). " 02/01/2011 - "Therefore, we assessed leg vasoconstriction during 60° head-up tilt in five patients with pure autonomic failure (PAF) and two patients with autonomic failure due to dopamine-β-hydroxylase (DBH) deficiency. " 02/01/2011 - "The difference between patients with pure autonomic failure and those with multiple system atrophy or dopamine β-hydroxylase deficiency persisted after adjustment for age (p = 0.001). " 02/01/2011 - "Odor identification was significantly impaired in patients with pure autonomic failure relative to patients with multiple system atrophy or dopamine β-hydroxylase deficiency. "
3.	Dopamine beta-HydroxylaseIBA 07/15/2003 - "Variations in the dopamine beta-hydroxylase gene are not associated with the autonomic disorders, pure autonomic failure, or multiple system atrophy." 01/01/2006 - "DOPS improved orthostatic hypotension in patients with familial amyloid polyneuropathy, congenital deficiency of dopamine beta hydroxylase, pure autonomic failure and multiple system atrophy. " 07/15/2003 - "Recent findings of an association between human NE deficiency and variants at the dopamine beta-hydroxylase (DBH) gene [Kim et al., 2002] prompted us to investigate these markers in patients with autonomic disorders; 38 with orthostatic intolerance (OI), 26 with pure autonomic failure (PAF), and 39 with multiple system atrophy (MSA). " 08/01/1991 - "The effect of a balanced liquid meal on supine and postural blood pressure (BP) responses was investigated in three groups of patients with chronic autonomic failure; 10 with associated neurological impairment (multiple system atrophy (MSA), Shy-Drager syndrome) and seven without (of which five had pure autonomic failure (PAF); and two had a deficiency of the enzyme dopamine beta hydroxylase, DBH-deficiency). " 04/01/1995 - "The effect of supine exercise on blood pressure (BP), measured while recumbent and after head-up postural change, was investigated in three groups with marked postural hypotension due to chronic autonomic failure: 15 with associated neurological impairment (Shy-Drager syndrome, SDS, multiple system atrophy); 15 with pure autonomic failure (PAF) and two with a deficiency of the enzyme dopamine beta hydroxylase (DBH deficiency). "
4.	Mixed Function Oxygenases (Monooxygenases)IBA 02/01/2011 - "Therefore, we assessed leg vasoconstriction during 60° head-up tilt in five patients with pure autonomic failure (PAF) and two patients with autonomic failure due to dopamine-β-hydroxylase (DBH) deficiency. " 02/01/2011 - "The difference between patients with pure autonomic failure and those with multiple system atrophy or dopamine β-hydroxylase deficiency persisted after adjustment for age (p = 0.001). " 02/01/2011 - "Odor identification was significantly impaired in patients with pure autonomic failure relative to patients with multiple system atrophy or dopamine β-hydroxylase deficiency. " 02/01/2011 - "Olfactory function was evaluated with the University of Pennsylvania Smell Identification Test (UPSIT) in 12 patients with pure autonomic failure, 10 patients with multiple system atrophy, and 4 patients with dopamine β-hydroxylase deficiency. " 10/19/2016 - "Patients were adults diagnosed with symptomatic nOH associated with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. "
5.	Midodrine (Midon)FDA LinkGeneric 11/01/2004 - "We tested the hypothesis that the oral alpha1-adrenergic agonist, midodrine, would limit the fall in arterial pressure observed during exercise in patients with pure autonomic failure (PAF). " 06/01/1993 - "Therefore, a recent multicenter study evaluated the safety and efficacy of midodrine therapy in 97 patients with neurogenic orthostatic hypotension due to various etiologies: Shy Drager syndrome (No. 18); Bradbury Eggleston syndrome (idiopathic orthostatic hypotension) (No. 20); diabetic autonomic neuropathy (No. 27); Parkinson's disease (No. 22); and miscellaneous (No. 10). " 12/01/2020 - "In general, patients with low "sympathetic reserve", i.e., those with peripheral noradrenergic degeneration (pure autonomic failure, Parkinson's disease) and low plasma norepinephrine, tend to respond better to "norepinephrine replacers" (midodrine and droxidopa). " 01/01/2015 - "Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure). "
6.	Cholinergic Agents (Cholinergics)IBA 01/01/2006 - "Cevimeline hydrochloride improved cholinergic dysfunction in a patient with pure autonomic failure." 01/01/1989 - "Normal CSF acetylcholinesterase levels in those patients with pure autonomic failure are consistent with functional integrity of central cholinergic pathways and support a pathophysiologic involvement limited to the peripheral nervous system." 03/12/2009 - "They include a chronic form (pure autonomic failure) and limited autonomic neuropathies with predominant involvement of one neurotransmitter type (i.e., cholinergic vs. adrenergic) or one system (such as the gastrointestinal system) or a distal small fiber dysfunction. "
7.	ProdrugsIBA 04/01/2017 - "The norepinephrine prodrug droxidopa improves symptoms of neurogenic orthostatic hypotension, a condition that is associated with diseases of neurogenic autonomic failure (e.g., Parkinson disease, multiple system atrophy, pure autonomic failure). " 08/18/2016 - "Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. " 01/01/2015 - "Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure). "
8.	cevimeline (Evoxac)FDA Link 01/01/2006 - "Cevimeline hydrochloride improved cholinergic dysfunction in a patient with pure autonomic failure."
9.	hydroxide ionIBA 10/01/2008 - "Patients with pure autonomic failure (PAF) have an abnormal fall in blood pressure (BP) with supine exercise and exacerbation of orthostatic hypotension (OH) after exercise. " 06/01/2001 - "The authors evaluated cardiovascular responses to MCP in 11 subjects with OH: 6 with multiple system atrophy (MSA) and 5 with pure autonomic failure (PAF), along with 6 healthy control subjects. " 08/25/2018 - "Eligible patients were aged ≥ 18 years with PD, MSA, or pure autonomic failure and ≥ 1 of the following: orthostatic hypotension (OH), nOH, low blood pressure upon standing, or OH/nOH symptoms. " 03/01/2008 - "In this brief review, the pathogenesis of OH is considered, particularly in terms of autonomic neuropathy, multiple system atrophy (MSA), pure autonomic failure, baroreflex failure, and dopamine beta hydroxylase deficiency. " 02/01/2006 - "In such patients PD+OH might be confused with multiple system atrophy (MSA), in which OH is a frequent finding, or with pure autonomic failure (PAF), if OH preceded clinical manifestations of the movement disorder. "
10.	3-Iodobenzylguanidine (Iobenguane)IBA 09/01/2004 - "In pure autonomic failure, which shares similar pathological findings with PD and is thought to be associated with diffuse loss of sympathetic terminal innervation, cardiac MIBG uptake also decreases markedly. " 10/01/2017 - "In one patient, meta-iodobenzylguanidine (MIBG) myocardial scintigraphy detected cardiac sympathetic denervation, and diagnosis of pure autonomic failure was made. " 12/15/2019 - "MIBG uptakes of PD patients were significantly decreased compared with those of other diseases except dementia with Lewy bodies and pure autonomic failure (p < .05 for all). " 12/01/2008 - "The [(123)I]MIBG study showed markedly decreased myocardial uptake in Parkinson's disease, dementia with Lewy bodies and pure autonomic failure, which is a common feature of Lewy-body diseases. " 07/01/2006 - "The purpose of this study was to investigate myocardial uptake of 123I-metaiodobenzylguanidine (MIBG) in patients with pure autonomic failure (PAF), which has pathologic features in common with idiopathic Parkinson's disease (IPD) and dementia with Lewy bodies (DLB). "

Therapies and Procedures

1.	Denervation 01/01/2018 - "Does sympathetic dysfunction occur before denervation in pure autonomic failure?" 06/01/2012 - "PD+OH also entails extra-cardiac noradrenergic denervation, but this is not as severe as in pure autonomic failure. " 01/01/2004 - "To determine the critical dependence of social and emotional behaviours on bodily responses mediated by the autonomic nervous system, we examined patients with pure autonomic failure (PAF), a peripheral denervation of autonomic neurons with onset in middle age. " 04/01/2003 - "Pure autonomic failure (PAF) is characterized by an acquired, selective, peripheral denervation of the autonomic nervous system. " 07/20/2001 - "Pure Autonomic Failure (PAF) is characterized by a global cardiovascular denervation. "
2.	Therapeutics 01/01/2017 - "Rapid eye movement sleep behavior disorder as a prodromal synucleinopathy represents a defined time point at which neuroprotective therapies could potentially be applied for the prevention of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure. " 06/01/1993 - "Therefore, a recent multicenter study evaluated the safety and efficacy of midodrine therapy in 97 patients with neurogenic orthostatic hypotension due to various etiologies: Shy Drager syndrome (No. 18); Bradbury Eggleston syndrome (idiopathic orthostatic hypotension) (No. 20); diabetic autonomic neuropathy (No. 27); Parkinson's disease (No. 22); and miscellaneous (No. 10). " 06/13/2003 - "A pure autonomic failure was diagnosed and therapy with fludrocortisone, yohimbine and erythropoetine was started. "
3.	Sympathectomy (Sympathectomies) 06/01/2005 - "All four patients with bilateral sympathectomy had low septal myocardial 6-[18F]fluorodopamine-derived radioactivity (2,673 +/- 92 nCi-kg/cc-mCi at an average of 89 minutes after injection) compared with normal volunteers (3,634 +/- 311 nCi-kg/cc-mCi at 83 minutes, N = 22, P = .007) and higher radioactivity than in patients with pure autonomic failure (1,320 +/- 300 nCi-kg/cc-mCi at 83 minutes, N = 7, P = .003). " 06/01/2005 - "Data were compared with those from the interventricular septum of patients with cardiac sympathetic denervation associated with pure autonomic failure and from normal volunteers. " 01/01/2005 - "The cardiovascular and cerebrovascular responses to head-up postural change are compromised in pure autonomic failure (PAF) patients because of sympathetic denervation. " 09/01/2001 - "We therefore studied 14 subjects with documented sympathetic denervation due to pure autonomic failure, with continuous haemodynamic recordings obtained before and after ingestion of 500 ml of distilled water at room temperature. " 09/01/1991 - "Biochemical evidence of sympathetic denervation of the heart in pure autonomic failure."
4.	Bed Rest (Bedrest) 08/01/1994 - "This hypothesis is supported by studies of two groups of persons known to have low catecholamine levels: persons subjected to prolonged bedrest and persons with syndromes characterized by low circulating catecholamines (Bradbury-Eggleston syndrome and dopamine beta-hydroxylase deficiency). "
5.	Controlled Hypotension 04/01/2006 - "Stress induced hypotension in pure autonomic failure." 10/01/1996 - "The neurohumoral, peptidergic and biochemical responses to supine leg exercise were studied in two groups with primary autonomic failure: Shy-Drager syndrome (SDS, n = 15) and pure autonomic failure (PAF, n = 15), to determine if these accounted for exercise-induced hypotension and the greater blood pressure (BP) fall in PAF. " 01/01/2013 - "In contrast, patients with multiple system atrophy (MSA) and pure autonomic failure (PAF) characterized by autonomic failure exhibit exercise-induced hypotension (EIH), prolonged hypotension following the cessation of exercise and exaggerated orthostatic hypotension after exercise. " 03/01/1992 - "Hypotension-induced vasopressin release distinguishes between pure autonomic failure and multiple system atrophy with autonomic failure."