AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Autonomic failure has many causes and manifestations.

It may result from a primary disturbance of autonomic regulation or more commonly as a secondary effect of another systemic disorder (eg, diabetes, amyloidosis). This article focuses on primary syndromes of generalized autonomic failure and includes a discussion of pure autonomic failure (PAF) and idiopathic orthostatic hypotension, autoimmune autonomic neuropathy (AAN), and multiple system atrophy (MSA). The selective sympathetic disturbance of postural orthostatic tachycardia syndrome (POTS) is also discussed briefly.

On clinical examination, the syndromes sometimes may be difficult to differentiate, particularly in the early stages of disease. This has led to some confusion over the nomenclature of these disorders. The terminology continues to evolve and become more precise as a result of our improving understanding of the different pathophysiologic mechanisms leading to autonomic dysfunction.

The term PAF was coined by Roger Bannister. It encompasses disorders of autonomic function that do not affect the CNS. The term is more descriptive of a clinical presentation than of a single pathologic process. Idiopathic orthostatic hypotension, sometimes also referred to as Bradbury-Eggleston syndrome, falls into this general category. Although patients with PAF may share many common clinical features, especially orthostatic hypotension, it is now evident that the underlying disease processes are heterogeneous. Many patients with PAF may actually have an immunologically mediated autonomic neuropathy, whereas others may develop MSA or other diseases that fall outside the PAF definition.

AAN has been increasingly recognized as an important cause of autonomic failure. It typically presents as a subacute or chronic condition. Antibodies to ganglionic acetylcholine receptors (AChR) are present in about two thirds of all subacute cases and in one third of chronic cases. Acute pandysautonomia may also occur and is likely part of the spectrum of other immunologically mediated disease such as AAN and acute inflammatory demyelinating polyneuropathy (AIDP, or Guillain-Barré syndrome) Mild somatic sensory and motor disturbances are sometimes seen in autonomic neuropathies.

MSA is a progressive, adult-onset disorder characterized by a combination of autonomic dysfunction, parkinsonism, and ataxia. Numerous accounts of the disorder were recorded throughout the 20th century under different labels such as olivopontocerebellar atrophy, striatonigral degeneration, or Shy-Drager syndrome. MSA with prominent autonomic abnormalities is still sometimes referred to as Shy-Drager syndrome. The disparate clinical presentations were not widely recognized as being histopathologically related until 1989. Today the dominant clinical features provide the basis for further classification of MSA into parkinsonian and cerebellar variants.

POTS is a common, relatively benign disturbance of the sympathetic nervous system that primarily affects young women. POTS either develops slowly in adolescence, or abruptly after a febrile illness or other immunological challenge. This latter presentation may be due to an autoimmune mechanism. POTS is characterized by excessive adrenergic symptoms when the patient stands up. Syncope may occur but is unusual. A greater than 30-bpm increase in heart rate on standing without substantial blood pressure reduction are diagnostic. The causes of POTS are likely heterogeneous.

Pathophysiology

Dysfunction of central or peripheral nervous system pathways may cause autonomic dysfunction. A precise balance of sympathetic and parasympathetic inputs modulates the function of most major organ systems. Primary disorders of autonomic function almost never exclusively affect either sympathetic or parasympathetic function. POTS is an exception, involving only sympathetic function.

The hypothalamus, midbrain, brainstem, and intermediolateral cell columns in the spinal cord are the major regions in the CNS that are important in regulating autonomic activity. Sympathetic outputs arise in brain and brainstem centers, descend into the spinal cord, and synapse with neurons in the intermediolateral cell mass in the thoracic and upper lumbar segments. Axons originating in the spinal cord synapse with cells in paravertebral ganglia, which, in turn, provide sympathetic output to remote target organs. Parasympathetic outflow originates from the cranial and sacral segments. These axons synapse in ganglia located near their target organs.

Both sympathetic and parasympathetic preganglionic synapses use acetylcholine (ACh) as the major neurotransmitter; postganglionic parasympathetic synapses and sympathetic sweat synapses also use acetylcholine. Other postganglionic sympathetic synapses use noradrenaline.

Symptoms frequently result from a disturbance of the relative contributions of sympathetic and parasympathetic activity. Depending on the organ system, the major input may be sympathetic or parasympathetic. For example, in the cardiovascular system, absence of sympathetic input may be especially problematic, contributing to orthostatic hypotension.

Frequency

United States

All of these syndromes are relatively uncommon with the exception of POTS. The prevalence of MSA is 1.9-4.9 cases per 100,000 population, as reported in several series. No accurate data on the frequency of AAN, PAF, or POTS are available.

Mortality/Morbidity

Autonomic dysfunction may cause clinically significant functional impairment. POTS is usually a benign, sometimes self-limiting condition, though rare patients have severe limitation in their activities.

Severe autonomic dysfunction may directly cause death. More often, chronic disability increases the patient's susceptibility to other potentially fatal complications, such as infection.

Race

No reliable data regarding race are available.

Sex

AAN and MSA have no clear sex predilection. In the literature about PAF, men were affected more often than women. POTS affects women 5 times more often than men.

Age

The diseases discussed here are primarily disorders of adulthood, with the exception of POTS, which primarily affects adolescents and young adults.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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. 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 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 AAN.
  • In previous literature, the terms PAF and idiopathic orthostatic hypotension were sometimes used interchangeably. Orthostatic hypotension is the most common complaint in this group of patients.
  • However, many affected individuals have other symptoms of autonomic involvement in addition to blood pressure abnormalities. Detailed history-taking may reveal problems with blurry vision, abnormal sweating or heat intolerance, constipation, urinary retention, or sexual dysfunction
• 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.
  • Autonomic dysfunction is a common finding in MSA but not 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 lightheadedness, blurry vision or tunnel vision, dimming of vision, palpitations, fatigue, tremulousness, leg weakness, confusion, and anxiety.
  • Other associated symptoms include neurocognitive or sleep disorders, exercise intolerance, hyperpnea, dyspnea, nausea, abdominal pain, and sweating.

Physical

• 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.
• AAN: 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.
• MSA: 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
  • Patients with the MSA cerebellar variant have evidence of cerebellar dysfunction that manifests as ataxia, dysmetria, dysdiadokinesia, and incoordination. Eye-movement abnormalities are frequently present.
• POTS: A greater than 30-bpm increase in heart rate on standing, without a clinically significant decrease in blood pressure are diagnostic.

Causes

• Pure autonomic failure
• • Patients who are initially identified as having PAF may have underlying pathology consistent with MSA, or they may be found to have AAN after extensive testing.
  • Involvement of the intermediolateral cell column with the loss of small sympathetic neurons has been observed in some patients.
• Autoimmune autonomic neuropathy
• • The cause of AAN is presumed to be autoimmune.
  • Autoantibodies against ganglionic AChRs are seen in one- to two-thirds of patients with this condition.
  • A preceding infection or other antecedent illness is noted in some cases.
  • In rare cases, patients have a coexisting thymus tumor.
• Multiple system atrophy
• • In MSA with autonomic involvement, changes in the intermediolateral cell column also may be seen; in addition, widespread abnormalities are apparent in the brain.
  • Histopathologically, alpha-synuclein immunostaining demonstrates glial cytoplasmic inclusions.
  • Associated clinical findings are related to the constellation of affected areas.
  • Neuronal loss may be noted in the basal ganglia, pons, cerebellum, substantia nigra, locus ceruleus, nucleus of Edinger-Westphal, hypothalamus, thalamus, and vestibular complex.
• Postural orthostatic tachycardia syndrome
• • A norepinephrine transporter deficiency has been identified in 1 family.
  • Beta-receptor supersensitivity, reduced vagal function, brainstem dysfunction are other proposed mechanisms.
  • Some patients have restricted autonomic neuropathy.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Transthyretin-related amyloidosis
Diseases of tetrapyrrole metabolism - Refsum disease, hepatic porphyrias

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The patient's clinical history directs the evaluation of orthostatic hypotension and autonomic failure.
• • An acute onset of autonomic symptoms without other neurologic problems or with features such as, subtle weakness, or numbness, should prompt an evaluation for AIDP. Elevated cerebrospinal fluid (CSF) protein levels without notable cellularity may be seen (albuminocytologic dissociation) but may take a few days to develop.
  • A subacute onset without other neurological or systemic findings may indicate AAN. Ganglionic AChR antibody titers can be measured. These antibodies are different from the antibodies against nicotinic muscle AChRs.
  • A chronic onset should trigger a search for other neurologic abnormalities. In particular, evaluation for Parkinson disease and MSA is essential. A few patients with classic idiopathic Parkinson disease have autonomic failure early in the course of the illness. No specific laboratory test is useful for confirming this diagnosis.
• Drug or toxin exposure may cause generalized or organ-specific acute autonomic dysfunction. The predominant abnormality (ie, increased or decreased sympathetic or parasympathetic activity) should be identified. The patient's medications should be reviewed carefully.
• • Increased sympathetic activity may be caused by amphetamines, cocaine, tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and beta-adrenergic agonists.
  • Decreased sympathetic activity may be seen with centrally active agents, such as clonidine, methyldopa, reserpine, or barbiturates. Peripherally acting agents (eg, alpha- or beta-adrenergic antagonists) may cause a similar picture.
  • Increased parasympathetic activity can be seen in the setting of cholinergic agonists, such as bethanechol or pilocarpine. Anticholinesterase inhibitors, such pyridostigmine or organophosphate pesticides may create a similar clinical picture.
  • Decreased parasympathetic activity may be seen in the setting of antidepressants, phenothiazines, anticholinergic agents, and botulinum toxicity.
• A positive family history with onset the first decades of life may suggest a hereditary sensory and autonomic neuropathy (HSAN).
• Tests for other systemic disorders causing secondary pandysautonomia may be ordered according to clues from the history.
• • Glycosylated hemoglobin may be indicated to test for diabetes.
  • Anti-Hu antibody titers may be needed if the patient has associated sensory neuropathy or cognitive changes.
  • Anti-calcium channel antibody titers for Lambert-Eaton myasthenic syndrome (LEMS), a presynaptic disorder of neuromuscular transmission, are sometimes associated with acute or subacute autonomic symptoms. About one half of patients have an associated neoplasm. As many as 80% of these may be small cell lung cancer. Patients may give a history of smoking or recent weight loss.
  • Screen stool for botulinum toxin. Botulism is another presynaptic disorder of neuromuscular transmission that may be associated with autonomic symptoms. However, a negative result does not exclude the possibility of botulism. Consultation with the Centers for Disease Control and Prevention may be a prerequisite of ordering the test because of heightened bioterrorism surveillance.
  • Serum and urine protein electrophoresis may be ordered to evaluate myeloma with amyloidosis, or genetic testing to evaluate for familial amyloidosis.
  • Rapid plasma reagent (RPR) or Venereal Disease Research Laboratory test (VDRL) may be needed to test for syphilis.
  • HIV testing may be indicated.
  • Autoimmune screening helps to evaluate for collagen-vascular disease. This testing may include antinuclear antibody levels, erythrocyte sedimentation rate, and other autoimmune tests (eg, rheumatoid factor, SS-A and SS-B antibodies), as the clinical syndrome dictates.
  • Assessment of the urinary porphyrins and erythrocyte porphobilinogen deaminase levels are indicated if the clinical history suggests the possibility of porphyria.

Imaging Studies

• Brain MRI may be useful, particularly in cases of centrally mediated dysautonomia.
• In MSA, brainstem or cerebellar atrophy may be seen, with T2 hyperintensity of the pons (the hot-crossed bun sign); these findings differentiate MSA from the other conditions of primary autonomic dysfunction
• No imaging abnormalities are expected in PAF, AAN, or POTS.

Other Tests

• In addition to supine and standing blood pressure and pulse measurements, additional cardiovascular evaluation (eg, ECG, cardiac telemetry) may be indicated to identify tachycardia, bradycardia, or other dysrhythmias.
• • Assessment of heart rate variability with deep breathing or Valsalva maneuver can further define the extent of cardiac involvement.
  • If the patient is unable to stand, 45° head-up tilt testing can be performed.
• Nerve conduction studies (NCS) and electromyography (EMG) are important to document any coexisting neuropathy or disorder of neuromuscular transmission.
• Additional autonomic testing, such as sympathetic skin response, is available in some electrodiagnostic laboratories. Skin vasomotor responses and sweat testing are 2 highly specialized autonomic tests that can be performed in a few autonomic laboratories. Skin vasomotor responses may help distinguish PAF from MSA. Sweat testing, either with acetylcholine iontophoresis or thermoregulatory testing, may be helpful even if the patient does not complain specifically of sweating abnormalities.
• GI motility can be evaluated in a number of ways, including an upper or lower GI series, cine videofluoroscopy, endoscopy, and gastric-emptying studies.
• Bladder ultrasound and postvoiding residual volumes should be assessed in patients with urinary symptoms. Urodynamic studies and intravenous urography also may help to define the cause of urinary retention or incontinence.
• Male impotence can be evaluated by using penile plethysmography and response to intracavernosal papaverine.
• Measurement of levels of plasma noradrenalin with the patient supine may help distinguish central from peripheral autonomic failure. MSA patients, who have centrally mediated autonomic failure, have normal supine levels of noradrenalin.

Procedures

• Because of the frequency of autonomic dysfunction in AIDP, acute onset of autonomic abnormalities must prompt consideration of AIDP in the differential diagnosis.
• • A lumbar puncture is indicated for CSF studies.
  • Patients with AIDP typically develop elevated protein levels but no elevation of the cell counts (ie, albuminocytologic dissociation).
  • Highly cellular CSF suggests alternate diagnoses, such as infection or inflammation.
• Sural nerve biopsy may be indicated if the clinical presentation suggests amyloidosis or if an unexplained axonal neuropathy is present on NCS or EMG testing.
• • If the clinical suspicion for amyloidosis is high, biopsy of the abdominal fat pad or a rectal biopsy should be performed to look for amyloid deposits. Patients with amyloid neuropathy, may have patchy deposition of the abnormal proteins in nerve, but sural nerve biopsy may still be helpful, especially if the findings on fat pad and rectal biopsy are normal.
  • Nerve biopsy is unnecessary if NCS reveals clear evidence of focal demyelination, or if the course of disease and clinical findings are otherwise consistent with AAN.

Histologic Findings

Biopsy of the CNS is never part of the routine evaluation for these disorders (see Procedures above). However, brain autopsy specimens in MSA show distinct glial cytoplasmic inclusions composed of 20- to 30-nm multilayered tubular filaments that are argyrophilic. The inclusions are found in the basal ganglia, the supplementary and primary motor cortex, the reticular formation, and the pontocerebellar system.

Alpha-synuclein is present in the glial inclusions and appears to play an important role in MSA. The autonomic failure in MSA likely results from cell loss in the dorsal motor nucleus of vagus nerve, locus coeruleus, and the catecholaminergic neurons of the ventrolateral medulla. Cell loss in the pontomedullary reticular formation, parasympathetic preganglionic nuclei of the spinal cord, and sympathetic intermediolateral column of the spinal cord are also important.

Other limited data on PAF demonstrate additional nerve cell loss and Lewy bodies, which stain for ubiquitin in the paravertebral sympathetic ganglia. It is unclear if these patients had a form fruste of MSA.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The treatment of AAN is based on anecdotal evidence. No data from large, controlled trials are available owing to the rarity of the disorder. The treatment of chronic PAF syndromes is symptomatic only. POTS can be treated by using low doses of beta-blockers as patients are normally sensitive to their adverse effects.

• Nonpharmacologic measures are useful for all patients with autonomic dysfunction.
• • Discontinue antihypertensive medications and other medications known to lower blood pressure, if feasible.
  • Increase fluid and salt intake.
  • Equipment aids may be helpful. These include tight support stockings, abdominal binders, or antigravity suits for symptomatic hypotension and bladder catheterization for urinary retention.
  • Dietary fiber and enemas may help improve bowel motility and decrease straining during defecation.
  • Patients with decreased sweating should limit their physical activity, particularly in hot weather. Sponging with water during activity may help prevent overheating.
  • Large meals may exacerbate hypotension and should be avoided.
  • Perform positional changes, such as standing up, slowly and gradually.
  • Elevate the head of the bed and avoid prolonged recumbency.
• Intravenous immunoglobulin (IVIg) and prednisone have been used successfully to shorten the duration of symptoms and improve overall prognosis in acute pandysautonomia.
• • Cases in which clinical improvement began within a few days of IVIg administration (2 g/kg body weight over 2-5 d), along with normalization of autonomic test parameters, have been reported.
  • Presumably, IVIg has an immunomodulatory action, but the exact mechanism of its effect in this disorder is unclear.
  • In 1 series, 2 patients with acute pandysautonomia were treated with prednisone 60 mg/d for several months and reported subjective improvement. No quantitative follow-up data were obtained.
  • Other pharmacologic treatment options are directed toward symptomatic relief only (See Medication section below).

Activity

Symptoms limit activity. Precautions for falling should be taken in patients who have orthostatic hypotension. In those with decreased sweating, vigorous exercise should be limited, and patients should be advised to have spray bottles of water or wet sponges available during hot weather or during physical activity.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Several medications are available to help manage symptoms of autonomic dysfunction. The most commonly used are listed below.

Drug Category: Mineralocorticoids

These agents play a role in hemodynamics and can be used to control orthostatic hypotension.

Drug Category: Alpha-adrenergic agonists

These agents improve the hemodynamic status by increasing myocardial contractility and heart rate, resulting in increased cardiac output. They also increase peripheral resistance by causing vasoconstriction. Increased cardiac output and increased peripheral resistance lead to increased blood pressure.

Drug Category: Beta-adrenergic blocking agents

These agents limit heart rate and reduce blood pressure.

Drug Category: Vasopressors

These agents augment both coronary and cerebral blood flow that occurs during the low flow state associated idiopathic hypotension.

Drug Category: Erythropoietins

Anemia may occur due to low blood levels of endogenous erythropoietin, which can result from a lack of sympathetic innervation. Erythropoietins may also increase blood pressure through other mechanisms.

Drug Category: Gastroprokinetic agents

These agents promote motility of the GI tract.

Drug Category: Anticholinesterase inhibitors

These agents inhibit acetylcholinesterase (AChE), raising the concentration of ACh at cholinergic synapses and increasing the chance of activating the AChR.

Drug Category: Bulk agents

Chronic treatment of constipation

Drug Category: Antispasmodic agents

These agents may be helpful for urinary symptoms.

Drug Category: Cholinergic agents

These agents stimulate cholinergic receptors in the smooth muscle of the urinary bladder for stimulation of bladder emptying.

Drug Category: Phosphodiesterase inhibitors

These oral agents act peripherally to induce smooth muscle relaxation of the corpora cavernosa.

Drug Category: Corticosteroids

These agents regulate key factors in the immune system.

Drug Category: Immune globulins

These agents are used to improve clinical and immunologic aspects of the disease. May decrease autoantibody production, and increase solubilization and removal of immune complexes.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Physical therapy is useful for gait training. Patients also should be instructed in safety precautions.
• Patients should be monitored closely for drug efficacy and adverse effects. Doses should be adjusted accordingly.

Prognosis

• The prognosis for AAN is poor without treatment, and many patients have residual autonomic symptoms. With IVIg therapy, a few patients who are treated early in the disease course can have excellent recovery of function. However, additional patients must be treated to confirm the initial favorable findings.
• Patients with PAF have symptoms that remain confined to the autonomic nervous system. These patients generally improve little over time, and their symptoms may worsen. Some may later develop MSA or Parkinson disease.
• The prognosis for patients with MSA is poor overall. Neurologic function declines gradually over time. The autonomic symptoms often become debilitating.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose and treat AIDP
• Failure to detect an associated malignancy at the time of presentation
• Failure to prevent fatal cardiac events

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Bannister R, Mathias CJ, Polinsky R. Autonomic failure--A comparison between UK and US experience. In: 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. In: Autonomic Failure: A Textbook of Disorders of the Autonomic Nervous System. New York, NY: Oxford University Press;1992:564-85.
• Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. Feb 1 1999;163(1):94-8. [Medline].
• Heafield MT, Gammage MD, Nightingale S, Williams AC. Idiopathic dysautonomia treated with intravenous gammaglobulin. Lancet. Jan 6 1996;347(8993):28-9. [Medline].
• Kaufmann H. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy. Clin Auton Res. Apr 1996;6(2):125-6. [Medline].
• Klein CM, Vernino S, Lennon VA, et al. The spectrum of autoimmune autonomic neuropathies. Ann Neurol. 2003;53:752-8. [Medline].
• Mathias CJ. Disorders of the Autonomic Nervous System. In: Neurology in Clinical Practice. Boston, Mass: Butterworth-Heinemann;1996:1953-81.
• Matthews MR. Autonomic ganglia in multiple system atrophy and pure autonomic failure. In: Autonomic Failure: A Textbook of Disorders of the Autonomic Nervous System. New York, NY: Oxford University Press;1992:593-621.
• Quan D, Rich MM, Bird SJ. Acute idiopathic dysautonomia: electrophysiology and response to intravenous immunoglobulin. Neurology. Feb 8 2000;54(3):770-1. [Medline].
• Quinn NP, Wenning G, Marsden CD. The Shy-Drager syndrome. What did Shy and Drager really describe?. Arch Neurol. Jul 1995;52(7):656-7. [Medline].
• Sandroni P, Vernino S, Klein CM, et al. Idiopathic autonomic neuropathy: comparison of cases seropositive and seronegative for ganglionic acetylcholine receptor antibody. Arch Neurol. Jan 2004;61(1):44-8. [Medline].
• Schroeder C, Vernino S, Birkenfeld AL, et al. Plasma exchange for primary autoimmune autonomic failure. N Engl J Med. Oct 13 2005;353(15):1585-90. [Medline].
• Smit AA, Vermeulen M, Koelman JH, Wieling W. Unusual recovery from acute panautonomic neuropathy after immunoglobulin therapy. Mayo Clin Proc. Apr 1997;72(4):333-5. [Medline].
• Suarez GA, Fealey RD, Camilleri M, Low PA. Idiopathic autonomic neuropathy: clinical, neurophysiologic, and follow-up studies on 27 patients. Neurology. Sep 1994;44(9):1675-82. [Medline].
• van Ingelghem E, van Zandijcke M, Lammens M. Pure autonomic failure: a new case with clinical, biochemical, and necropsy data. J Neurol Neurosurg Psychiatry. Jun 1994;57(6):745-7. [Medline].

Article Last Updated: Dec 8, 2006