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: 144 relevant articles (4 outcomes, 11 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.	Shy-Drager Syndrome
5.	Diabetic Neuropathies (Diabetic Neuropathy)

Experts

1.	Goldstein, David S: 21 articles (11/2015 - 08/2002)
2.	Holmes, Courtney: 15 articles (11/2015 - 08/2002)
3.	Sharabi, Yehonatan: 9 articles (11/2015 - 08/2003)
4.	Biaggioni, Italo: 7 articles (02/2015 - 03/2002)
5.	Mathias, Christopher J: 7 articles (01/2015 - 05/2002)
6.	Mathias, C J: 7 articles (10/2008 - 02/2001)
7.	Robertson, David: 6 articles (01/2013 - 10/2002)
8.	Pechnik, Sandra: 6 articles (02/2009 - 08/2003)
9.	Kaufmann, Horacio: 5 articles (05/2015 - 08/2003)
10.	Jordan, Jens: 5 articles (02/2015 - 03/2002)

Drugs and Biologics

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

1.	Idiopathic orthostatic hypotensionIBA 05/01/2014 - "Therefore, Roger Bannister proposed "pure autonomic failure" as the term for idiopathic orthostatic hypotension without other neurological symptoms. " 01/01/1995 - "The case of idiopathic orthostatic hypotension (Bradbury-Eggleston syndrome) which gradually arose in 70-years-old women was described. " 01/01/1995 - "[Idiopathic orthostatic hypotension (the Bradbury-Eggleston syndrome)]." 08/01/1997 - "Pure autonomic failure (PAF; also known as idiopathic orthostatic hypotension or Bradbury-Eggleston syndrome) is an uncommon sporadic disorder, characterized by autonomic failure without other neurological deficits and histopathologically by cell loss in intermediolateral columns and sympathetic ganglia. " 07/01/1997 - "However, most patients with idiopathic orthostatic hypotension or pure autonomic failure complain of anhidrosis and impotence, which were not noted in our patient. "
2.	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." 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). " 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. " 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). "
3.	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). " 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). "
4.	cevimeline (Evoxac)FDA Link 01/01/2006 - "Cevimeline hydrochloride improved cholinergic dysfunction in a patient with pure autonomic failure."
5.	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. " 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. " 12/01/1997 - "Orthostatic hypotension (OH) is the most disabling and serious manifestation of adrenergic failure, occurring in the autonomic neuropathies, pure autonomic failure (PAF) and multiple system atrophy (MSA). " 11/01/2005 - "Patients with Parkinson's disease (PD) and orthostatic hypotension (OH) (PD+OH) or with pure autonomic failure (PAF) have markedly decreased myocardial 6-(18)F-fluorodopamine-derived radioactivity, consistent with cardiac sympathetic denervation, a phenomenon that neurochemical, neuropharmacologic, and, most recently, postmortem neuropathologic studies have confirmed. "
6.	DroxidopaIBA 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." 01/01/2015 - "Patients with symptomatic neurogenic orthostatic hypotension and Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa titration (100-600 mg, 3× daily). " 01/01/1991 - "Treatment with L-threo-3,4-dihydroxyphenylserine (L-threo-dops), a synthetic precursor of norepinephrine, significantly increased upright blood pressure in patients with multiple system atrophy but had no effect on the upright blood pressure of patients with pure autonomic failure. "
7.	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. " 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). " 04/01/2012 - "Reduced cardiac MIBG uptake on MIBG myocardial scintigraphy has been reported in patients with Parkinson disease (PD), dementia with Lewy bodies (DLB), pure autonomic failure (PAF), and familial PD linked to SNCA duplication. " 05/01/2015 - "MIBG scintigraphy showed low uptake of MIBG in the Lewy body-related disorders, including Parkinson's disease, dementia with Lewy bodies, pure autonomic failure and rapid eye movement sleep behavior disorder. "
8.	Dopamine beta hydroxylase deficiencyIBA 04/01/1995 - "1. The cardiovascular and catecholamine responses to supine leg exercise were measured in fifteen normal subjects (controls) and in three groups with sympathetic dysfunction: fifteen with central failure (Shy-Drager syndrome; SDS), fifteen with peripheral failure (pure autonomic failure; PAF) and two with isolated dopamine beta-hydroxylase deficiency (DBH deficiency). " 01/01/1998 - "Four different forms of primary autonomic failure (multiple system atrophy, pure autonomic failure, Parkinson's disease and dopamine beta-hydroxylase deficiency) have been described. " 07/01/1994 - "We compared the three techniques under conditions of effective cardiac sympathetic denervation, pure autonomic failure (n = 4), dopamine beta-hydroxylase deficiency (n = 1), and after cardiac transplantation (n = 9) as well as in the context of sympathetic nervous activation in cardiac failure (n = 15) and with aging (n = 10). " 11/01/2015 - "Norepinephrine deficiency in NOH can arise peripherally, due to cardiovascular sympathetic denervation (as in pure autonomic failure, Parkinson's disease, and a variety of neuropathies), or centrally, due to a failure of viscerosensory signals to generate adequate sympathetic traffic to intact sympathetic nerve endings (as in multiple system atrophy). " 09/01/2006 - "This literature review confirms a high prevalence of sympathetic deficits and parasympathetic deficits in acute or subacute dysautonomia, diabetes, amyloidosis, pure autonomic failure, paraneoplastic syndromes, Sjögren syndrome, familial dysautonomia, and dopamine beta-hydroxylase deficiency. "
9.	SynucleinsIBA 02/19/2013 - "This study aimed to test whether peripheral α-synuclein staining might be useful for pure autonomic failure (PAF) diagnosis, helping to differentiate degenerative from acquired peripheral autonomic neuropathy. " 12/01/2014 - "Antemortem detection of colonic α-synuclein pathology in a patient with pure autonomic failure." 02/19/2013 - "Skin sympathetic fiber α-synuclein deposits: a potential biomarker for pure autonomic failure." 01/01/2011 - "α-Synuclein in the skin nerve of pure autonomic failure." 11/03/2015 - "Parkinson disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF) involve cytoplasmic deposition of α-synuclein and are considered to be synucleinopathies. "
10.	AntibodiesIBA 11/01/2015 - "This is because some of the patients with chronic progression mimicking neurodegenerative diseases such as pure autonomic failure were positive for these antibodies. " 06/01/2003 - "These observations expand the clinical spectrum of AAN to include chronic cases, some being indistinguishable from pure autonomic failure, and support the concept that ganglionic AChR antibodies are important diagnostically and pathophysiologically in acquired dysautonomia." 12/01/2006 - "In this study we evaluated by indirect immunohistochemistry the prevalence of cerebrospinal fluid (CSF) antibodies reacting with structures of rat pons/medulla in patients with multiple system atrophy (MSA) (n = 29), Parkinson disease with neurogenic orthostatic hypotension (n = 13), or pure autonomic failure (n = 11) and in control subjects without autonomic failure (n = 33). " 04/01/2013 - "Based on the detection of these antibodies in various dysautonomic conditions, AAG is considered a broad-spectrum disease entity that includes acute pandysautonomia as well as secondary autonomic neuropathy, restricted forms of dysautonomia (postural tachycardia syndrome and chronic intestinal pseudoobstruction), and chronic dysautonomia, mimicking pure autonomic failure. " 05/01/2014 - "Recently, autoimmune autonomic ganglionopathy associated with anti-ganglionic acetylcholine receptor antibodies has attracted attention as a differential diagnosis of pure autonomic failure, which is characterized by Lewy body pathology."

Therapies and Procedures

1.	Denervation 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. " 12/01/2005 - "Thus, abnormal spontaneous activity or marked motor unit potential changes in sphincter muscles are helpful in distinguishing MSA from PD in the first five years after the onset of symptoms and signs, and from pure autonomic failure, as well as from cerebellar ataxias, if other causes for sphincter denervation have been ruled out. "
2.	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. " 08/01/2009 - "Pure autonomic failure (PAF) and Parkinson disease (PD) both are Lewy body diseases, and both entail substantia nigra dopaminergic, locus ceruleus noradrenergic, and cardiac sympathetic denervation. "
3.	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). "
4.	Autonomic Denervation 02/01/2001 - "We tested these anatomical predictions using positron emission tomography and a human neurological model (pure autonomic failure), in which peripheral autonomic denervation prevents the emergence of autonomic responses. " 02/01/2015 - "Despite similarities in their clinical presentation, patients with multiple system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and Parkinson disease have efferent post-ganglionic autonomic denervation. "
5.	Catheters 04/01/2004 - "In 4 patients with severe pure autonomic failure (PAF), in 3 multiple system atrophy patients (MSA), and in 16 healthy young controls, we inserted a microdialysis catheter in abdominal adipose tissue. "