MSA & PAF (Pure autonomic failure)

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Hi :

this tells you the different between MSA and PAF (pure autonomic failure) which Anne has.

eMedicine - Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes : Article by Dianna Quan, MD

Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes

Synonyms, Key Words, and Related Terms: acute idiopathic dysautonomia, multiple system atrophy, MSA, olivopontocerebellar atrophy, pure autonomic failure, PAF, Shy-Drager syndrome, striatonigral degeneration

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eMedicine Journal > Neurology > Movement And Neurodegenerative Diseases > Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes

Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Medication | Follow-up | Bibliography

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AUTHOR INFORMATION Section 1 of 9

Authored by Dianna Quan, MD, Director of Laboratory Electromyography, Assistant Professor, Department of Neurology, University of Colorado Health Sciences CenterDianna Quan, MD, is a member of the following medical societies: American Academy of Neurology, American Association of Electrodiagnostic Medicine, and Phi Beta KappaEdited by C Luzzio, MD, Assistant Professor, Department of Neurology, University of California at San Francisco; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Neil A Busis, MD, Chief, Clinical Associate Professor, Department of Medicine, Division of Neurology, University of Pittsburgh School of Medicine; J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; and Lorenzo, MD, eMedicine Project Editor-in-Chief, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author's Email: Dianna Quan, MD

Editor's Email: C Luzzio, MD

eMedicine Journal, February 5 2002, Volume 3, Number 2

INTRODUCTION Section 2 of 9

Background: Autonomic failure has many causes and manifestations. It may result from a primary disturbance of autonomic regulation or as a secondary effect of another systemic disorder (eg, diabetes, amyloidosis). This article focuses on the 3 primary syndromes of autonomic failure: acute or subacute idiopathic pandysautonomia; pure autonomic failure (PAF); and multiple system atrophy (MSA). Pure autonomic failure and multiple system atrophy are chronic syndromes of primary autonomic dysfunction. Included under the rubric of pure autonomic failure is idiopathic orthostatic hypotension, which has orthostatic hypotension as its only clinical feature.Pathophysiology: The hypothalamus, midbrain, brain stem, and intermediolateral cell columns in the spinal cord are the major regions within the central nervous system (CNS) that are important in regulating autonomic activity. Sympathetic nervous system outputs arise from brain or 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 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. All other postganglionic sympathetic synapses are noradrenergic. Autonomic failure may be caused by dysfunction of the central or peripheral nervous system pathways. The function of all major organ systems is modulated by a precise balance of sympathetic and parasympathetic inputs. Primary disorders of autonomic function almost never exclusively affect sympathetic or parasympathetic function. Symptoms typically 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. Thus, in some organ systems (eg, gastrointestinal), parasympathetic inputs may predominate. In other systems (eg, cardiovascular), absence of sympathetic input may be more clinically significant.Frequency:

In the US: All of these syndromes are relatively uncommon. No accurate data on the frequency of acute idiopathic pandysautonomia or PAF are available.

Internationally: In the British literature, the estimated prevalence of MSA is 16.4 per 100,000. Mortality/Morbidity: Significant functional impairment may result from autonomic dysfunction.

Patients with PAF may experience fatal events related directly to autonomic dysfunction, such as cardiac arrhythmia.

More often, chronic disability results in a greater susceptibility to other potentially fatal complications, such as infection. Race: No reliable data regarding race are available. Sex: Acute idiopathic dysautonomia and MSA have no clear sex predilection. In PAF, men are affected more commonly than women. Age:

Acute or subacute idiopathic dysautonomia is an uncommon disorder that generally occurs in adulthood. However, it has been reported in patients as young as 7 years.

PAF and MSA are disorders of middle and late adulthood. CLINICAL Section 3 of 9

History: The features of autonomic involvement may be extensive in all of these conditions. Common manifestations 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.

Symptoms of decreased sympathetic function may include the following:

Orthostatic hypotension

Decreased sweating

Impotence

Ptosis associated with Horner syndrome

Symptoms of decreased parasympathetic function may include the following:

Constipation

Nausea

Urinary retention

Impotence

Acute idiopathic dysautonomia: May be associated with additional symptoms of limb numbness, tingling, or pain.

Pure autonomic failure

PAF is associated with no other neurological symptoms.

Formerly, PAF was considered by some practitioners to be synonymous with idiopathic orthostatic hypotension. Because many affected individuals have other areas of autonomic involvement in addition to blood pressure abnormalities (eg, pupillary changes, abnormal sweating, bowel or bladder dysfunction, sexual dysfunction), the term "pure autonomic failure" is preferred over the original term "idiopathic orthostatic hypotension."

Multiple system atrophy

MSA is a chronic, progressive disorder of adulthood.

MSA consists of a group of syndromes with mixed features of chronic autonomic dysfunction, parkinsonism, or 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 exist to identify this group at the outset.

Depending on their clinical features, patients with MSA may be categorized into 3 different groups:

Shy-Drager variants - Predominant autonomic symptoms

Striatonigral degeneration - Predominant parkinsonian symptoms

Olivopontocerebellar atrophy - Predominant cerebellar symptoms Physical:

Acute and subacute idiopathic pandysautonomia

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. Diarrhea is infrequent. The abdomen may be distended, and patients may have discomfort on palpation. An acute abdomen is unusual.

Urinary retention is seen frequently and may cause bladder distention. A distended bladder can be detected on examination by percussion or palpation.

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.

Impotence due to failure of either erection or ejaculation is a common physical manifestation in males. Female sexual dysfunction is not well documented in the literature.

Occasionally, sensory abnormalities, pain, or loss of deep tendon reflexes may be observed.

In PAF, the overall physical findings are similar to those observed in acute idiopathic dysautonomia. No sensory or motor disturbances should be present.

In MSA, the autonomic manifestations are similar to those observed in acute idiopathic dysautonomia and PAF. However, additional neurological features may be present.

Patients with Shy-Drager syndrome may have pyramidal or cerebellar abnormalities on examination. Weakness, ataxia, incoordination, and eye-movement abnormalities may precede the prominent autonomic features by as long as 2 years.

Patients with striatonigral degeneration have variable parkinsonian findings, including rigidity, bradykinesia, tremor, and truncal instability.

Patients with olivopontocerebellar degeneration have evidence of cerebellar dysfunction that manifests as ataxia, dysmetria, dysdiadokinesia, and incoordination. Eye-movement abnormalities are frequently present.Causes:

The cause of acute autonomic failure is unclear.

The syndrome is considered by some to be a variant of Guillain-Barré syndrome (GBS).

Some cases may arise from an acquired presynaptic defect in autonomic ganglia.

The precise roles of infection and other immune factors remain uncertain, but the lack of other CNS manifestations suggests that the lesion localizes to the peripheral nervous system.

PAF and MSA are sporadic disorders of uncertain etiology.

Intermediolateral cell column involvement with the loss of small sympathetic neurons has been observed in PAF.

In MSA with autonomic involvement, changes in the intermediolateral cell column also may be seen; in addition, widespread abnormalities are apparent in the brain.

The 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. DIFFERENTIALS Section 4 of 9

Acute Inflammatory Demyelinating Polyradiculoneuropathy

Anisocoria

Assessment of Neuromuscular Transmission

Diabetic Neuropathy

Diseases of Tetrapyrrole Metabolism: Refsum Disease and the Hepatic Porphyrias

Guillain-Barre Syndrome in Childhood

Organophosphates

Paraneoplastic Autonomic Neuropathy

Toxic Neuropathy

Other Problems to be Considered: Spinal injury WORKUP Section 5 of 9

Lab Studies:

No diagnostic laboratory study is specific for acute idiopathic dysautonomia. The evaluation of orthostatic hypotension and autonomic failure must be directed by the clinical history.

An explosive or subacute onset of autonomic symptoms without other neurological features should prompt an evaluation for treatable causes of acute dysautonomia.

A more chronic onset should trigger a search for other neurological abnormalities.

Drug or toxin exposure may cause acute autonomic dysfunction that is generalized or organ specific. 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.

Lambert-Eaton myasthenic syndrome (LEMS), a presynaptic disorder of neuromuscular transmission, sometimes is associated with acute or subacute autonomic symptoms. In half of cases, patients have an associated neoplasm. As many as 80% of these may be small cell lung cancer.

In the case of LEMS, anti-calcium channel antibody testing is sensitive but not specific.

Patients may give a history of smoking or recent weight loss.

Botulism is another presynaptic disorder of neuromuscular transmission that may be associated with autonomic symptoms. An assay is available to screen the stool for botulinum toxin. However, a negative result does not exclude the possibility of botulism.

Urinary porphyrins and erythrocyte porphobilinogen deaminase levels are indicated if the clinical history suggests the possibility of porphyria.

Further tests may be ordered to screen for other systemic disorders that cause secondary pandysautonomia.

Glycosylated hemoglobin to test for diabetes

Serum and urine protein electrophoresis to evaluate for myeloma with amyloidosis, or gene testing to evaluate for familial amyloidosis

Rapid plasma reagent (RPR) or Venereal Disease Research Laboratory test (VDRL) to test for syphilis

HIV test

Autoimmune screen to evaluate for collagen vascular disease: This may include antinuclear antibody erythrocyte, sedimentation rate, and other autoimmune tests (eg, rheumatoid factor, SS-A and SS-B antibodies), as dictated by the clinical syndrome.

Patients with chronic progressive autonomic failure must be evaluated carefully for evidence of other neurological deficits or associated medical conditions.

In particular, evaluation for Parkinson disease is essential, as a small group of patients with classical idiopathic Parkinson disease have autonomic failure late in the course of the disease.

As is the case in acute disease, no specific laboratory tests exist to confirm the diagnosis.Imaging Studies:

Brain magnetic resonance imaging (MRI) may be useful, particularly in cases of centrally mediated dysautonomia. In particular, if cerebellar or other motor findings are present, brainstem or cerebellar atrophy may be identified.Other Tests:

In addition to supine and standing blood pressure measurements, more extensive 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, 45o 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 is available in some electrodiagnostic laboratories. Sweat testing may be helpful even if the patient does not complain specifically of sweating abnormalities.

Gastrointestinal motility can be evaluated in a number of ways, including an upper or lower GI series, videocinefluoroscopy, endoscopy, and gastric emptying studies.

Bladder ultrasound and postvoid 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 using penile plethysmography and response to intracavernosal papaverine.

Measurement of supine levels of plasma noradrenaline may help distinguish central from peripherally mediated autonomic failure.

Levels should be low in PAF and normal in Shy-Drager syndrome.

In both conditions, the normal increase in noradrenaline levels with standing is attenuated. Procedures:

Because of the frequency of autonomic dysfunction in GBS, acute onset of autonomic abnormalities must prompt consideration of GBS in the differential diagnosis.

Cerebrospinal fluid (CSF) studies, with particular attention to the cellular and protein content, may reveal abnormalities.

Patients with GBS typically have acellular CSF with elevated protein (ie, albuminocytologic dissociation).

A highly cellular CSF suggests alternative diagnoses.

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 and no amyloid is found in the nerve biopsy, abdominal fat pat or rectal biopsy should be performed to look for amyloid deposits.

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 acute/subacute dysautonomia.Histologic Findings: Biopsy of the CNS is never part of the routine evaluation for these disorders (see Procedures). In chronic syndromes of primary autonomic failure, loss of small sympathetic neurons in the intermediolateral cell mass of the spinal cord is a common feature. Other limited data on PAF demonstrate additional nerve cell loss and Lewy bodies, which stain for ubiquitin in the paravertebral sympathetic ganglia. TREATMENT Section 6 of 9

Medical Care: The treatment of acute idiopathic pandysautonomia 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.

Nonpharmacologic measures are useful for all patients with autonomic dysfunction.

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.

Intravenous immunoglobulin (IVIg) and prednisone have been used successfully to shorten the duration of symptoms and improve overall prognosis in acute pandysautonomia.

Some 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.

Two patients in one series were treated with 60 mg/d of prednisone for several months and reported subjective improvement.

No quantitative follow-up data were obtained in these 2 cases.

Other pharmacologic treatment options are directed toward symptomatic relief only.Activity: Activity is limited by symptoms. Precautions for falling should be taken for patients who have orthostatic hypotension. In those with decreased sweating, vigorous exercise should be limited, and patients should be warned to have spray bottles of water or wet sponges during hot weather or during physical activity. MEDICATION

[Guest guest]

Thanks for the article. I didn't read it all yet. I'm a bit fried

from a long day.

New I'd seen the term before, and have read a similar article.

Just... forgot... would you believe? :-)

Seems to happen all the time.

Oh well, last night I almost posted a new post retracting what I had

said about being on a trial of Symmetrel. But, brain was working so

well, that I decided to do a check and see if Amantadine is the same -

bingo. Was I ever embarassed! Oh well, didn't post it - but not

too proud to mention it here. :-)

I turn 40 Friday. 39 has been a tough year. Wonder what 40 has in

store? :-)

Catch ya later.

> Hi :

> this tells you the different between MSA and PAF (pure autonomic

failure)

> which Anne has.

> http://www.emedicine.com/neuro/topic609.htm " >eMedicine -

Idiopathic Orthostatic Hypotension and other Autonomic Failure

> Syndromes : Article by Dianna Quan, MD

> Idiopathic Orthostatic Hypotension and other Autonomic Failure

Syndromes

>

>

> Synonyms, Key Words, and Related Terms: acute idiopathic

dysautonomia,

> multiple system atrophy, MSA, olivopontocerebellar atrophy, pure

autonomic

> failure, PAF, Shy-Drager syndrome, striatonigral degeneration

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> Idiopathic Orthostatic Hypotension and other Autonomic Failure

Syndromes

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> AUTHOR INFORMATION Section 1 of 9

> Authored by Dianna Quan, MD, Director of Laboratory

Electromyography,

> Assistant Professor, Department of Neurology, University of

Colorado Health

> Sciences CenterDianna Quan, MD, is a member of the following

medical

> societies: American Academy of Neurology, http://www.aaem.net/ " >American Association of

> Electrodiagnostic Medicine, and http://www.pbk.org/ " >Phi Beta KappaEdited by C

Luzzio,

> MD, Assistant Professor, Department of Neurology, University of

California at

> San Francisco; Francisco Talavera, PharmD, PhD, Senior Pharmacy

Editor,

> eMedicine; Neil A Busis, MD, Chief, Clinical Associate Professor,

Department

> of Medicine, Division of Neurology, University of Pittsburgh School

of

> Medicine; J Baker, MD, Consulting Staff, Collier Neurologic

> Specialists, Naples Community Hospital; and Lorenzo, MD,

eMedicine

> Project Editor-in-Chief, Chief Editor, eMedicine Neurology;

Consulting Staff,

> Neurology Specialists and Consultants Author's Email: http://www.emedicine.com/cgi-bin/foxweb.exe/screen@d:/em/ga?

book=neuro&authorid=741&topicid=609 " >Dianna Quan, MD

> Editor's Email: http://www.emedicine.com/cgi-

bin/foxweb.exe/screen@d:/em/ga?

book=neuro&editorid=554&topicid=609 " > C Luzzio, MD

> eMedicine Journal, February 5 2002, Volume 3, Number 2

> INTRODUCTION Section 2 of 9

> Background: Autonomic failure has many causes and manifestations.

It may

> result from a primary disturbance of autonomic regulation or as a

secondary

> effect of another systemic disorder (eg, diabetes, amyloidosis).

This article

> focuses on the 3 primary syndromes of autonomic failure: acute or

subacute

> idiopathic pandysautonomia; pure autonomic failure (PAF); and

multiple system

> atrophy (MSA). Pure autonomic failure and multiple system atrophy

are chronic

> syndromes of primary autonomic dysfunction. Included under the

rubric of pure

> autonomic failure is idiopathic orthostatic hypotension, which has

> orthostatic hypotension as its only clinical

feature.Pathophysiology: The

> hypothalamus, midbrain, brain stem, and intermediolateral cell

columns in the

> spinal cord are the major regions within the central nervous system

(CNS)

> that are important in regulating autonomic activity. Sympathetic

nervous

> system outputs arise from brain or 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 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. All other postganglionic sympathetic synapses

are

> noradrenergic. Autonomic failure may be caused by dysfunction of

the central

> or peripheral nervous system pathways. The function of all major

organ

> systems is modulated by a precise balance of sympathetic and

parasympathetic

> inputs. Primary disorders of autonomic function almost never

exclusively

> affect sympathetic or parasympathetic function. Symptoms typically

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. Thus, in some organ systems (eg,

> gastrointestinal), parasympathetic inputs may predominate. In other

systems

> (eg, cardiovascular), absence of sympathetic input may be more

clinically

> significant.Frequency:

>

> In the US: All of these syndromes are relatively uncommon. No

accurate data

> on the frequency of acute idiopathic pandysautonomia or PAF are

available.

> Internationally: In the British literature, the estimated

prevalence of MSA

> is 16.4 per 100,000. Mortality/Morbidity: Significant functional

impairment

> may result from autonomic dysfunction.

> Patients with PAF may experience fatal events related directly to

autonomic

> dysfunction, such as cardiac arrhythmia.

> More often, chronic disability results in a greater susceptibility

to other

> potentially fatal complications, such as infection. Race: No

reliable data

> regarding race are available. Sex: Acute idiopathic dysautonomia

and MSA have

> no clear sex predilection. In PAF, men are affected more commonly

than women.

> Age:

> Acute or subacute idiopathic dysautonomia is an uncommon disorder

that

> generally occurs in adulthood. However, it has been reported in

patients as

> young as 7 years.

> PAF and MSA are disorders of middle and late adulthood.

CLINICAL

> Section 3 of 9

> History: The features of autonomic involvement may be extensive in

all of

> these conditions. Common manifestations 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.

> Symptoms of decreased sympathetic function may include the

following:

> Orthostatic hypotension

> Decreased sweating

> Impotence

> Ptosis associated with Horner syndrome

> Symptoms of decreased parasympathetic function may include the

following:

> Constipation

> Nausea

> Urinary retention

> Impotence

> Acute idiopathic dysautonomia: May be associated with additional

symptoms of

> limb numbness, tingling, or pain.

> Pure autonomic failure

> PAF is associated with no other neurological symptoms.

> Formerly, PAF was considered by some practitioners to be synonymous

with

> idiopathic orthostatic hypotension. Because many affected

individuals have

> other areas of autonomic involvement in addition to blood pressure

> abnormalities (eg, pupillary changes, abnormal sweating, bowel or

bladder

> dysfunction, sexual dysfunction), the term " pure autonomic failure "

is

> preferred over the original term " idiopathic orthostatic

hypotension. "

> Multiple system atrophy

> MSA is a chronic, progressive disorder of adulthood.

> MSA consists of a group of syndromes with mixed features of chronic

autonomic

> dysfunction, parkinsonism, or 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 exist to identify this group at the outset.

> Depending on their clinical features, patients with MSA may be

categorized

> into 3 different groups:

> Shy-Drager variants - Predominant autonomic symptoms

>

>

> Striatonigral degeneration - Predominant parkinsonian symptoms

>

>

> Olivopontocerebellar atrophy - Predominant cerebellar symptoms

Physical:

> Acute and subacute idiopathic pandysautonomia

> 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.

> Diarrhea is infrequent. The abdomen may be distended, and patients

may have

> discomfort on palpation. An acute abdomen is unusual.

> Urinary retention is seen frequently and may cause bladder

distention. A

> distended bladder can be detected on examination by percussion or

palpation.

> 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.

> Impotence due to failure of either erection or ejaculation is a

common

> physical manifestation in males. Female sexual dysfunction is not

well

> documented in the literature.

> Occasionally, sensory abnormalities, pain, or loss of deep tendon

reflexes

> may be observed.

> In PAF, the overall physical findings are similar to those observed

in acute

> idiopathic dysautonomia. No sensory or motor disturbances should be

present.

> In MSA, the autonomic manifestations are similar to those observed

in acute

> idiopathic dysautonomia and PAF. However, additional neurological

features

> may be present.

> Patients with Shy-Drager syndrome may have pyramidal or cerebellar

> abnormalities on examination. Weakness, ataxia, incoordination, and

> eye-movement abnormalities may precede the prominent autonomic

features by as

> long as 2 years.

> Patients with striatonigral degeneration have variable parkinsonian

findings,

> including rigidity, bradykinesia, tremor, and truncal instability.

> Patients with olivopontocerebellar degeneration have evidence of

cerebellar

> dysfunction that manifests as ataxia, dysmetria, dysdiadokinesia,

and

> incoordination. Eye-movement abnormalities are frequently

present.Causes:

> The cause of acute autonomic failure is unclear.

> The syndrome is considered by some to be a variant of Guillain-

Barré syndrome

> (GBS).

> Some cases may arise from an acquired presynaptic defect in

autonomic

> ganglia.

> The precise roles of infection and other immune factors remain

uncertain, but

> the lack of other CNS manifestations suggests that the lesion

localizes to

> the peripheral nervous system.

> PAF and MSA are sporadic disorders of uncertain etiology.

> Intermediolateral cell column involvement with the loss of small

sympathetic

> neurons has been observed in PAF.

> In MSA with autonomic involvement, changes in the intermediolateral

cell

> column also may be seen; in addition, widespread abnormalities are

apparent

> in the brain.

> The 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. DIFFERENTIALS Section 4 of 9

> http://www.emedicine.com/NEURO/topic7.htm " >Acute

Inflammatory Demyelinating Polyradiculoneuropathy

> http://www.emedicine.com/NEURO/topic479.htm " >Anisocoria

> http://www.emedicine.com/NEURO/topic23.htm " >Assessment of

Neuromuscular Transmission

> http://www.emedicine.com/NEURO/topic88.htm " >Diabetic

Neuropathy

> http://www.emedicine.com/NEURO/topic633.htm " >Diseases of

Tetrapyrrole Metabolism: Refsum Disease and the Hepatic

> Porphyrias

> http://www.emedicine.com/NEURO/topic598.htm " >Guillain-

Barre Syndrome in Childhood

> http://www.emedicine.com/NEURO/topic286.htm " >Organophosphates

> http://www.emedicine.com/NEURO/topic298.htm " >Paraneoplastic

Autonomic Neuropathy

> http://www.emedicine.com/NEURO/topic378.htm " >Toxic

Neuropathy

>

> Other Problems to be Considered: Spinal injury WORKUP Section 5

of 9

> Lab Studies:

>

> No diagnostic laboratory study is specific for acute idiopathic

dysautonomia.

> The evaluation of orthostatic hypotension and autonomic failure

must be

> directed by the clinical history.

> An explosive or subacute onset of autonomic symptoms without other

> neurological features should prompt an evaluation for treatable

causes of

> acute dysautonomia.

> A more chronic onset should trigger a search for other neurological

> abnormalities.

> Drug or toxin exposure may cause acute autonomic dysfunction that

is

> generalized or organ specific. 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.

> Lambert-Eaton myasthenic syndrome (LEMS), a presynaptic disorder of

> neuromuscular transmission, sometimes is associated with acute or

subacute

> autonomic symptoms. In half of cases, patients have an associated

neoplasm.

> As many as 80% of these may be small cell lung cancer.

> In the case of LEMS, anti-calcium channel antibody testing is

sensitive but

> not specific.

> Patients may give a history of smoking or recent weight loss.

> Botulism is another presynaptic disorder of neuromuscular

transmission that

> may be associated with autonomic symptoms. An assay is available to

screen

> the stool for botulinum toxin. However, a negative result does not

exclude

> the possibility of botulism.

> Urinary porphyrins and erythrocyte porphobilinogen deaminase levels

are

> indicated if the clinical history suggests the possibility of

porphyria.

> Further tests may be ordered to screen for other systemic disorders

that

> cause secondary pandysautonomia.

> Glycosylated hemoglobin to test for diabetes

>

>

> Serum and urine protein electrophoresis to evaluate for myeloma

with

> amyloidosis, or gene testing to evaluate for familial amyloidosis

>

>

> Rapid plasma reagent (RPR) or Venereal Disease Research Laboratory

test

> (VDRL) to test for syphilis

>

>

> HIV test

>

>

> Autoimmune screen to evaluate for collagen vascular disease: This

may include

> antinuclear antibody erythrocyte, sedimentation rate, and other

autoimmune

> tests (eg, rheumatoid factor, SS-A and SS-B antibodies), as

dictated by the

> clinical syndrome.

> Patients with chronic progressive autonomic failure must be

evaluated c

> arefully for evidence of other neurological deficits or associated

medical

> conditions.

> In particular, evaluation for Parkinson disease is essential, as a

small

> group of patients with classical idiopathic Parkinson disease have

autonomic

> failure late in the course of the disease.

> As is the case in acute disease, no specific laboratory tests exist

to

> confirm the diagnosis.Imaging Studies:

>

> Brain magnetic resonance imaging (MRI) may be useful, particularly

in cases

> of centrally mediated dysautonomia. In particular, if cerebellar or

other

> motor findings are present, brainstem or cerebellar atrophy may be

> identified.Other Tests:

>

> In addition to supine and standing blood pressure measurements,

more

> extensive 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, 45o 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 is available in some electrodiagnostic

> laboratories. Sweat testing may be helpful even if the patient does

not

> complain specifically of sweating abnormalities.

> Gastrointestinal motility can be evaluated in a number of ways,

including an

> upper or lower GI series, videocinefluoroscopy, endoscopy, and

gastric

> emptying studies.

> Bladder ultrasound and postvoid 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 using penile plethysmography and

response to

> intracavernosal papaverine.

> Measurement of supine levels of plasma noradrenaline may help

distinguish

> central from peripherally mediated autonomic failure.

> Levels should be low in PAF and normal in Shy-Drager syndrome.

> In both conditions, the normal increase in noradrenaline levels

with standing

> is attenuated. Procedures:

>

> Because of the frequency of autonomic dysfunction in GBS, acute

onset of

> autonomic abnormalities must prompt consideration of GBS in the

differential

> diagnosis.

> Cerebrospinal fluid (CSF) studies, with particular attention to the

cellular

> and protein content, may reveal abnormalities.

> Patients with GBS typically have acellular CSF with elevated

protein (ie,

> albuminocytologic dissociation).

> A highly cellular CSF suggests alternative diagnoses.

> 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 and no amyloid is

found in

> the nerve biopsy, abdominal fat pat or rectal biopsy should be

performed to

> look for amyloid deposits.

> 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 acute/subacute dysautonomia.Histologic

Findings:

> Biopsy of the CNS is never part of the routine evaluation for these

disorders

> (see http://www.emedicine.com/neuro/#target1 " >Procedures). In

chronic syndromes of primary autonomic failure, loss of

> small sympathetic neurons in the intermediolateral cell mass of the

spinal

> cord is a common feature. Other limited data on PAF demonstrate

additional

> nerve cell loss and Lewy bodies, which stain for ubiquitin in the

> paravertebral sympathetic ganglia. TREATMENT Section 6 of 9

> Medical Care: The treatment of acute idiopathic pandysautonomia 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.

> Nonpharmacologic measures are useful for all patients with

autonomic

> dysfunction.

> 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.

> Intravenous immunoglobulin (IVIg) and prednisone have been used

successfully

> to shorten the duration of symptoms and improve overall prognosis

in acute

> pandysautonomia.

> Some 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.

> Two patients in one series were treated with 60 mg/d of prednisone

for

> several months and reported subjective improvement.

> No quantitative follow-up data were obtained in these 2 cases.

>

>

> Other pharmacologic treatment options are directed toward

symptomatic relief

> only.Activity: Activity is limited by symptoms. Precautions for

falling

> should be taken for patients who have orthostatic hypotension. In

those with

> decreased sweating, vigorous exercise should be limited, and

patients should

> be warned to have spray bottles of water or wet sponges during hot

weather or

> during physical activity. MEDICATION