History

Features of autonomic disturbance in any of these conditions may include orthostasis, nausea, constipation, urinary retention or incontinence, nocturia, impotence, heat intolerance, and dry mucous membranes. Less commonly, patients experience periods of apnea or inspiratory stridor. Postural orthostatic tachycardia syndrome (POTS) results in prominent excessive adrenergic symptoms, especially tachycardia.

Symptoms of decreased sympathetic function may include the following:
- Orthostatic hypotension
- Decreased sweating
- Ejaculatory dysfunction
- Ptosis associated with Horner syndrome
Symptoms of decreased parasympathetic function may include the following:
- Constipation
- Nausea
- Urinary retention
- Erectile dysfunction
Pure autonomic failure (PAF)
- PAF is by definition not associated with CNS symptoms. Careful questioning is required to exclude symptoms of CNS dysfunction, such as gait disturbance or spasticity. Patients should also be questioned in detail about sensory loss or neuropathic pain, which may suggest autoimmune autonomic neuropathy (AAN).
- In older literature, the terms PAF and idiopathic orthostatic hypotension were sometimes used interchangeably. Orthostatic hypotension is the most common complaint in this group of patients.
- Abnormalities of urination, salivation, sweating, and defecation can occur, though these are less common in PAF than in AAN.
Autoimmune autonomic neuropathy
- Patients with apparent PAF should be questioned carefully regarding dry mouth or dry eyes.
- Such sicca symptoms may be associated with ganglionic AChR autoantibodies.
- Mild sensory disturbances may be present and overshadowed by autonomic dysfunction.
Multiple system atrophy
- MSA is a chronic, progressive disorder with mixed features of chronic autonomic dysfunction, parkinsonism, and ataxia.^[9]
- Autonomic dysfunction is a common finding in MSA and in the absence of pathological findings essential to the diagnosis.
- A subset of patients with PAF may eventually develop MSA, but no clinical or diagnostic markers identify this group at the outset.
- Depending on their clinical features, patients with MSA may be categorized as parkinsonian (MSAp) or cerebellar (MSAc) variants, depending on the most prominent symptoms and findings on physical examination.
Postural orthostatic tachycardia syndrome
- POTS is a relatively benign disorder that is often self-limiting.
- Patients may complain of dizziness, blurry vision, weakness, lightheadedness, and fatigue upon standing. Palpitations, tremulousness, and anxiety can also be seen.
- Other associated symptoms include neurocognitive or sleep disorders, exercise intolerance, hyperpnea, dyspnea, nausea, abdominal pain, and sweating.

Physical

See the list below:

Pure autonomic failure
- Cardiovascular manifestations include orthostatic hypotension with an inappropriate lack of compensatory increase in heart rate with standing. Orthostatic hypotension is defined as a decrease of at least 20 mm Hg in systolic blood pressure or at least 10 mm Hg in diastolic blood pressure within 3 minutes of standing.
- Gastroparesis is common and is associated with nausea or constipation. The abdomen may be distended, and patients may have discomfort on palpation. An acute abdomen is unusual. Diarrhea may also occur, with or without fecal incontinence.
- Urinary retention is seen frequently and may cause bladder distention. A distended bladder can be detected on examination by percussion or palpation. Bladder emptying may be incomplete with post-void residuals of 100 mL or more.
- Decreased sweating manifests as heat or exercise intolerance. Patients may have noticeably warm and/or dry skin.
- The eyes may be affected. Careful ophthalmologic examination may reveal ptosis, anisocoria, Horner syndrome, or tonic pupils
- Failure of either erection or ejaculation is a common physical manifestation in males. Female sexual dysfunction has not been well studied in these disorders.
Autoimmune autonomic neuropathy: The overall physical findings are similar to those observed in PAF. Patients may have additional findings of sensory abnormalities, pain, or loss of deep tendon reflexes.
Multiple system atrophy: Autonomic manifestations are similar to those observed in AAN and PAF. However, additional neurologic features may be present.
- Pyramidal or cerebellar abnormalities including weakness, ataxia, incoordination, and eye-movement abnormalities may precede the autonomic features by as long as 2 years.
- Patients with the MSA parkinsonian variant have variable parkinsonian findings, including rigidity, bradykinesia, tremor, and truncal instability, that do not respond to levodopa.
- Patients with the MSA cerebellar variant have evidence of cerebellar dysfunction that manifests as ataxia, dysmetria, dysdiadochokinesia, and incoordination. Eye-movement abnormalities are frequently present.
Postural orthostatic tachycardia syndrome: A greater than 30-bpm increase in heart rate on standing, without a clinically significant decrease in blood pressure, is diagnostic.

Differential Diagnoses

Brooks M. FDA Clears Droxidopa for Neurogenic Orthostatic Hypotension. Medscape Medical News. Available at http://www.medscape.com/viewarticle/820786. Accessed: February 24, 2014.
Klein CM, Vernino S, Lennon VA, et al. The spectrum of autoimmune autonomic neuropathies. Ann Neurol. 2003. 53:752-8. [QxMD MEDLINE Link].
Sandroni P, Vernino S, Klein CM, et al. Idiopathic autonomic neuropathy: comparison of cases seropositive and seronegative for ganglionic acetylcholine receptor antibody. Arch Neurol. 2004 Jan. 61(1):44-8. [QxMD MEDLINE Link].
Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. 1999 Feb 1. 163(1):94-8. [QxMD MEDLINE Link].
Freeman R. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med. 2008 Feb 7. 358(6):615-24. [QxMD MEDLINE Link].
Yu X, Stavrakis S, Hill MA, Huang S, Reim S, Li H, et al. Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension. J Am Soc Hypertens. 2012 Jan-Feb. 6(1):40-7. [QxMD MEDLINE Link]. [Full Text].
Barclay L. Low B12 Linked to Orthostatic Tachycardia in Adolescents. Medscape Medical News. Dec 23 2013. Available at http://www.medscape.com/viewarticle/818279. Accessed: Jan 7 2014.
Oner T, Guven B, Tavli V, Mese T, Yilmazer MM, Demirpence S. Postural Orthostatic Tachycardia Syndrome (POTS) and Vitamin B12 Deficiency in Adolescents. Pediatrics. 2014 Jan. 133(1):e138-42. [QxMD MEDLINE Link].
Sithinamsuwan P, Orrawanhanothai P, Thithum K, Udommongkol C, Chairangsaris P, Chinvarun Y, et al. Orthostatic hypotension: a non-motor complication assessment in 82 patients with idiopathic Parkinson's disease in Phramongkutklao Hospital. J Med Assoc Thai. 2010 Nov. 93 Suppl 6:S93-9. [QxMD MEDLINE Link].
Sommer C, Lauria G. Skin biopsy in the management of peripheral neuropathy. Lancet Neurol. 2007 Jul. 6(7):632-42. [QxMD MEDLINE Link].
Schroeder C, Vernino S, Birkenfeld AL, et al. Plasma exchange for primary autoimmune autonomic failure. N Engl J Med. 2005 Oct 13. 353(15):1585-90. [QxMD MEDLINE Link].
Heafield MT, Gammage MD, Nightingale S, Williams AC. Idiopathic dysautonomia treated with intravenous gammaglobulin. Lancet. 1996 Jan 6. 347(8993):28-9. [QxMD MEDLINE Link].
Quan D, Rich MM, Bird SJ. Acute idiopathic dysautonomia: electrophysiology and response to intravenous immunoglobulin. Neurology. 2000 Feb 8. 54(3):770-1. [QxMD MEDLINE Link].
Gibbons C, Vernino S, Freeman R. Combined immunomodulation therapy in autoimmune autonomic ganglionopathy. Arch Neurol. Feb 2008. 65(2):213-217.
Bannister R, Mathias CJ, Polinsky R. Autonomic failure--A comparison between UK and US experience. Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System. New York, NY: Oxford University Press; 1988. 282-8.
Daniel SE. The neuropharmacology and neurochemistry of multiple system atrophy. Autonomic Failure: A Textbook of Disorders of the Autonomic Nervous System. New York, NY: Oxford University Press; 1992. 564-85.
Hoeldtke RD, Bryner KD, Hoeldtke ME, Hobbs G. Treatment of autonomic neuropathy, postural tachycardia and orthostatic syncope with octreotide LAR. Clin Auton Res. 2007 Dec. 17(6):334-40. [QxMD MEDLINE Link].
Kaufmann H. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy. Clin Auton Res. 1996 Apr. 6(2):125-6. [QxMD MEDLINE Link].
Mathias CJ. Disorders of the autonomic nervous system. Neurology in Clinical Practice. Boston, Mass: Butterworth-Heinemann; 1996. 1953-81.
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Suarez GA, Fealey RD, Camilleri M, Low PA. Idiopathic autonomic neuropathy: clinical, neurophysiologic, and follow-up studies on 27 patients. Neurology. 1994 Sep. 44(9):1675-82. [QxMD MEDLINE Link].
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Author

Mohini Gurme, MD Resident Physician, Department of Neurology, University of California, Davis, School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Dianna Quan, MD Professor of Neurology, Director of Electromyography Laboratory, University of Colorado School of Medicine

Dianna Quan, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Neurological Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Association of Neuromuscular and Electrodiagnostic Medicine Received research grant from: Alnylam; Pfizer; Ionis; Cytokinetics; Momenta; Viela Bio; .

Bjorn E Oskarsson, MD Assistant Professor, Department of Neurology, University of California, Davis, School of Medicine

Bjorn E Oskarsson, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Flex Pharma Serve(d) as a speaker or a member of a speakers bureau for: Grifols Received research grant from: Neuraltus, Glaxo, Eisai, Cytokinetics, Genentech,.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Neil A Busis, MD Chief of Neurology and Director of Neurodiagnostic Laboratory, UPMC Shadyside; Clinical Professor of Neurology and Director of Community Neurology, Department of Neurology, University of Pittsburgh Physicians

Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Academy of Neurology Serve(d) as a speaker or a member of a speakers bureau for: American Academy of Neurology Received income in an amount equal to or greater than $250 from: American Academy of Neurology.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK life science, Sunovion, Takeda, UCB Serve(d) as a speaker or a member of a speakers bureau for: Aquestive, Bioserenity, Eisai, Jazz, LivaNova, Neurelis, SK life science, Stratus, Sunovion, UCB Received research grant from: Cerevel Therapeutics, Ovid Therapeutics, Neuropace, Greenwich Jazz, SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Neuroelectrics Corporation, Longboard, Janssen, Equilibre Biopharmaceuticals.

Additional Contributors

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Jeffrey Tam Sing, MD to the development and writing of this article.

Sections Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes
Overview
Presentation
DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
References

Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes Clinical Presentation

History

Physical

References

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