Autonomic Disorders Information for Patients and Families

  • Autoimmune Autonomic Ganglionopathy
  • Baroreflex Failure
  • Dopamine Beta-Hydroxylase Deficiency (DBH)
  • Familial Dysautonomia (FD)
  • Hypovolemic Postural Tachycardia Syndrome (POTS)
  • Multiple System Atrophy (MSA)
  • Neurally Mediated Syncope (NMS)
  • Pure Autonomic Failure (PAF)

What is autoimmune autonomic ganglionopathy ?

Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by the presence of autonomic failure in association with specific antibodies directed against a specific receptor of the autonomic ganglia.

Symptoms include:

  • Severe orthostatic hypotension (low blood pressure upon standing) that persists for weeks to years
  • Fainting
  • Constipation
  • Urinary retention
  • Fixed and dilated pupils
  • Dry mouth and eyes

Who gets autoimmune autonomic ganglionopathy ?

AAG can affect people of all ages and both sexes.

What causes autoimmune autonomic ganglionopathy?

The cause of AAG is unknown.

Are there treatments for autoimmune autonomic ganglionopathy?

  • For mild cases, symptom management is the treatment.
  • Many patients remain unable to function normally and disorder modifying therapy may help.
  • There is no established treatment.
  • A therapeutic trial in autoimmune autonomic ganglionopathy is being conducted by the Autonomic Disorders Consortium.

What is baroreflex failure?

Baroreflex failure is a rare disorder characterized by change of blood pressure with episodes of severe hypertension (high blood pressure). There can be increased heart rate during stress and hypotension (low blood pressure) with normal or reduced heart rate during rest.

Symptoms may include:

  • Headache
  • Excessive sweating
  • Extremely high or volatile blood pressure and heart rate with spikes in blood pressure in response to stress, with periods of normal or even low blood pressure during rest
  • Heart rate that does not respond to medications intended to improve it

Note that baroreflex failure may resemble another rare disorder called pheochromocytoma, a catecholamine-secreting tumor.

What causes baroreflex failure?

Possible causes may include:

  • Surgery and radiation for cancer of the throat.
  • Injury to glossopharyngeal and vagus nerves (nerves involved in sensing blood pressure).
  • Cell loss on both sides in the nuclei of the solitary tract (NTS, a column of cells located in the medulla) in the setting of a degenerative neurologic disease of the brain.
  • For many patients, the cause of baroreflex failure is not known.

How is baroreflex failure diagnosed?

Baroreflex failure resembles other more common disorders, so its diagnosis is challenging.

In addition to asking detailed questions about the patient’s health and family history, the physician will conduct a physical examination, which will include checking blood pressure and heart rate in specific circumstances, such as during daily activity and with medication challenges.

Are there treatments for baroreflex failure?

Treatment for baroreflex failure involves medications to control blood pressure and heart rate and to reduce stress.

What is dopamine beta-hydroxylase deficiency (DBH)?

There is virtual absence of norepinephrine, epinephrine, and their metabolites. However, there is greatly increased dopamine in plasma, cerebrospinal fluid, and urine.

DBH Symptoms

  • As children, DBH deficient patients have had a markedly reduced ability to exercise, perhaps because of hypotension engendered by the physical exertion.
  • Symptoms have generally worsened in late adolescence and by early adulthood, patients complain of profound orthostatic hypotension, especially early in the day and during hot weather or after alcohol ingestion.
  • In addition to drooping of the eyelids, there is a tendency for nasal stuffiness to occur, especially in the supine posture.
  • Presyncopal symptoms in these patients have included dizziness, blurred vision, dyspnea, nuchal discomfort, and occasionally chest pain.

Physical Examination

  • The physical examination usually includes a normal or low normal supine blood pressure and a normal heart rate but a standing blood pressure that is less than 80 mmHg systolic.
  • Heart rate rises on standing but appears to have an attenuated elevation given the very low blood pressure with upright posture.
  • Pupils are somewhat small but respond to light and accommodation. Parasympatholytics dilate the eye appropriately.

Testing for DBH

  • Many specialized tests differentiate these patients from those with familial dysautonomia. Cholinergic sensitivity as assessed by conjunctival methacholine is normal, and intradermal histamine evokes a typical flare reaction in DBH deficiency, whereas this does not occur in familial dysautonomia. Atrial fibrillation, occasionally occurs in adults.
  • These patients have no response even to high doses of tyramine, which normally increases blood pressure by releasing neuronal norepinephrine. Dopamine, rather than norepinephrine, levels increase when the patient stands, during sustained handgrip, and after tyramine administration, while they decrease after clonidine administration.
  • Muscle sympathetic nerve traffic, as measured by direct intraneuronal recordings, is present in excess under basal conditions but is otherwise normally modulated by baroreflex mechanisms in these patients. Therefore, primary autonomic neuronal pathways are intact and respond to appropriate stimuli, but dopamine instead of norepinephrine is present in noradrenergic nerve terminals.
  • Sympathetic cholinergic function is intact, as assessed by normal sweating.
  • Parasympathetic function is also preserved, as assessed by intact sinus arrhythmia, normal heart rate increase during Valsalva, and tachycardia after atropine.
  • A diagnosis of DBH deficiency is based on the characteristic plasma catecholamine pattern of absent norepinephrine and epinephrine and elevated dopamine.

Are there treatments for dopamine beta-hydroxylase deficiency (DBH)?

  • Fludrocortisone at relatively high doses has successfully raised blood pressure with some benefit. Indomethacin has also been of modest benefit in raising blood pressure, but one patient had aggressive ideation while receiving this drug.
  • The monoamine oxidase inhibitor tranylcypromine also produced paranoid thinking in one patient.
  • There has been a reasonable response to phenylpropanolamine (25 and 50 mg), perhaps because of the hypersensitive alpha-adrenoreceptors in these patients.
  • Once the specific enzymatic defect had been elucidated, investigators knew that a better treatment for DBH deficiency could be devised.
  • Metyrosine significantly reduces urinary and plasma dopamine levels in DBH deficiency.
  • A more favorable long-term result has been achieved with L-dihydroxyphenylserine (droxidopa or L-DOPS). The administration of DOPS to these patients results in dramatic increases in blood pressure and in the restoration of plasma and urinary levels of norepinephrine toward normal. Long-term experience with this drug indicates continued effectiveness at 250 mg or 500 mg three times a day.

What is familial dysautonomia (FD)?

Familial Dysautonomia (FD) is a genetic disease primarily causing dysfunction of the autonomic and sensory nervous systems.

Symptoms displayed by a baby with FD include:

  • Hypotonia (Poor muscle tone)
  • Weak or absent suck
  • Respiratory congestion due to misdirected swallowing
  • Blotching of skin
  • Difficulty in maintaining body temperature

Symptoms in an older child with FD include:

  • Delay in developmental milestones such as walking and speech
  • Poor balance and unsteady gait
  • Scoliosis (spinal curvature)
  • Orthostatic hypotension (extreme drop in blood pressure with change in posture)
  • Breath holding in early years to the point of fainting
  • Episodic vomiting
  • Excessive drooling and sweating
  • A smooth tongue and decrease in sense of taste
  • Difficulty in maintaining body temperature
  • Poor weight gain and growth
  • Frequent lung infections
  • Decreased reaction to pain or no reaction at all
  • Cold, puffy hands and feet
  • Extremes in blood pressure
  • Corneal abrasions and dry eyes
  • Gastric dysmotility (abnormal movement through the stomach)
  • Dysautonomic "crisis" (severe reactions to physical and emotional stress)

Who gets familial dysautonomia (FD)?

FD occurs primarily in persons of Ashkenazi (central or eastern European) Jewish descent.

What causes familial dysautonomia (FD)?

Familial Dysautonomia is caused by mutations in the IKBKAP gene. The IKBKAP gene provides instructions for making a protein called IKK complex-associated protein (IKAP). This protein is found in a variety of cells throughout the body, including brain cells.

Nearly all individuals with familial dysautonomia have two copies of the same IKBKAP mutation in each cell.

More information on the IKBKAP gene can be found at Genetics Home Reference.

How are the familial dysautonomia (FD) diagnosed?

To diagnose FD, physicians use health and family history in addition to physical examination. A definitive diagnosis can be made with a blood test. Over 99% of affected individuals will have two copies of the most common gene mutation.

Are there treatments for the familial dysautonomia (FD)?

Treatment of FD is individualized, since FD symptoms may vary greatly among patients. Treatment often involves managing the most problematic symptoms, such as:

  • Blood pressure
  • Respiration problems
  • Alacrima (dry eyes)
  • Feeding difficulties
  • Speech difficulties
  • Nausea and vomiting
  • Injury
  • Orthopedic problems

What is hypovolemic postural tachycardia syndrome (POTS)?

When a patient’s heart rate speeds up 30 beats per minute or more without much change in blood pressure on standing, the patient may have orthostatic intolerance (OI). Because upright heart rate is usually greatly increased, the more common term used now is hypovolemic postural tachycardia syndrome (POTS). The increase in heart rate may be a sign that the cardiovascular system is working hard to maintain blood pressure and blood flow to the brain.

Symptoms & Signs (for at least 6 months):

  • Lightheadedness, palpitations and tremulousness during standing
  • Other upright posture symptoms may include:
    • Visual changes
    • Discomfort in the head and neck
    • Throbbing of the head
    • Poor concentration
    • Tiredness
    • Weakness
    • Occasionally fainting
    • Nausea
    • Chest discomfort
    • Shortness of breath

The Role of Hypovolemia in POTS

Hypovolemia is an abnormal decrease in blood volume, or more specifically an abnormal decrease in the volume of blood plasma. This sometimes occurs in POTS patients. It may occur due to blood pooling in the abdomen and legs.

Long-Term Outlook for Patients with POTS

The majority of patients with POTS have a relatively mild disorder which improves over weeks or months. Most patients will eventually be free of symptoms. However, in some patients, the symptoms are more severe, the duration of the illness may be longer, and the expected recovery may not occur.

Who gets POTS?

POTS is most frequently seen in young women, often less than 35 years of age. Orthostatic intolerance affects an estimated 500,000 Americans and causes a wide range of disabilities.

What causes POTS?

The cause of POTS is unknown. Sometimes, a recent viral infection happens soon before symptoms occur. Many patients remain undiagnosed because the severity changes and the disorder can be called many different names. Another problem in the diagnosis of OI is its overlap with other conditions such as Chronic Fatigue Syndrome (CFS), Neurally Mediated Syncope (NMS), or physical deconditioning.

Patients may also experience hypovolemia, or a decrease in blood plasma volume due to blood pooling in the abdomen and legs.

How is POTS diagnosed?

Treatments for POTS aim to relieve low blood pressure or regulate circulatory problems. These include:

  • Orthostatic “exercise”
  • Medication therapy, including beta blockers, alpha-2 agonists (such as Clonidine), alpha-1 agonists (such as Midodrine), or Alpha-Methyldopa (Aldomet)
  • Drinking water may help to temporarily raise blood pressure
  • Salt and /or fludrocortisones

No single treatment has been found to be effective for every patient. Some treatments are more successful than others and are often used together for best results.

What is multiple system atrophy (MSA)?

Multiple system atrophy (MSA) is a rare neurodegenerative disease marked by a combination of symptoms affecting movement, blood pressure, and other body functions; hence the label "multiple system" atrophy. According to the American Autonomic Society, MSA is a sporadic, progressive, adult-onset disorder characterized by autonomic dysfunction, parkinsonism and ataxia (a failure of muscular coordination) in any combination.

Symptoms of MSA include:

  • Orthostatic hypotension,or a significant fall in blood pressure when standing, causing dizziness, lightheadedness, fainting, or blurred vision
  • Urinary difficulties or constipation
  • Motor control symptoms, including tremor, rigidity, and loss of muscle coordination, loss of balance
  • Male impotence (inability to achieve or maintain an erection)
  • Speech or swallowing difficulties

Who gets MSA?

MSA affects both men and women primarily in their 50s.

What causes multiple system atrophy (MSA)?

MSA is associated with deterioration and shrinkage (atrophy) of portions of the brain (cerebellum, basal ganglia and brainstem) that regulate internal body functions, digestion and motor control.

There is no known cause for brain changes in MSA.

How is multiple system atrophy (MSA) diagnosed?

Diagnosis of MSA can be challenging because there is no test that can make or confirm the diagnosis in a living patient. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinson's disease, making the diagnosis more difficult.

If your doctor suspects MSA, he or she will obtain a medical history and perform a physical examination. You may receive a referral to a neurologist or other specialist for specific evaluations that can help in making the diagnosis.

Tests that may be helpful in making a diagnosis include:

  • Tilt table test - In this procedure, your blood pressure is monitored while you are on a special table that will tilt you to an almost upright position. This allows the physician to record blood pressure irregularities, and information about whether they occur with a change in physical position.
  • Blood tests
  • A sweat test to evaluate perspiration
  • Tests to assess your bladder and bowel function
  • Electrocardiogram to track the electrical signals of your heart
  • Brain-imaging tests, particularly a magnetic resonance imaging (MRI) scan, to determine if another condition might be triggering symptoms
  • Pharmacological challenge tests (administering certain medications and observing the patient’s body’s reaction to them, in controlled clinical settings)

For patients with sleep irregularities, particularly if they involve interrupted breathing or snoring, physicians may recommend an evaluation in a sleep laboratory to determine if there is an underlying and treatable sleep disorder, such as sleep apnea.

What is the treatment for multiple system atrophy (MSA)?

There is no known cure for MSA, so management of the disease focuses on treating the more disabling symptoms listed above.

Frequently Asked Questions about MSA

How common is MSA?

Between 25,000 and 100,000 Americans are believed to have MSA. The incidence (new cases per 100,000 person years) for ages 50-99 years is 3-5.

What is the progression of MSA?

Disease progression in MSA is quicker than in Parkinsonism. About 80% of patients are disabled within 5 years of onset of the motor symptoms, and only 20% survive past 12 years. The mean survival after diagnosis is roughly 6 years. The rate of progression differs in every case and speed of decline may vary widely in individual patients.

What is the prognosis of MSA / Shy-Drager Syndrome?

The probable outcome is poor. There is a progressive loss of physical functions until general debilitation develops. Early death is likely. Most people who are diagnosed with Shy-Drager syndrome die within seven to 10 years after symptoms begin.

Pneumonia is the most common cause of death, although irregularities in heartbeat or brearhing may be responsible for death in some patients. Breathing problems such as aspiration, stridor (high-pitched breathing sounds due to airway obstruction), or cardiopulmonary arrest can occur.

What is Neurally Mediated Syncope (NMS)?

Syncope (described as “fainting” or “passing out”) is a common problem, accounting for approximately 3% of emergency room visits. Neurally mediated syncope (NMS) is also called neurocardiogenic, vasovagal, vasodepressor or reflex mediated syncope.

Repeated episodes of NMS may be caused by a wide variety of medical problems, and require diagnosis and treatment. It is important to distinguish syncope from “dizziness”, which generally refers to an alteration in balance, vision, or perception of the environment, without the loss of consciousness.

What causes NMS?

NMS occurs when the part of the nervous system that regulates heart rate and blood pressure malfunctions, often in response to a trigger. The heart rate slows, and the blood vessels in the legs widen. This allows blood to pool in the legs, which lowers blood pressure. The drop in blood pressure and slowed heart rate quickly cause diminished blood flow to the brain, causing fainting.

How is NMS diagnosed?

The diagnosis of NMS often focuses on ruling out other potential causes of fainting - particularly heart-related problems. Tests may include:

  • Electrocardiogram
  • Echocardiogram
  • Exercise stress test
  • Blood tests
  • Tilt table tests to measure your blood pressure with changes in posture

What is the treatment for NMS?

In many cases, education about ways to avoid “triggers” may be enough to control NMS.

Treatment may require medications, therapies to increase blood pressure or decrease pooling of blood in the legs or the use of an electrical pace maker to regulate heartbeat. Other therapies include using compression stockings, sleeping with the head of the bed slightly elevated, and mild aerobic conditioning (especially in the water).

What is Pure Autonomic Failure (PAF)?

Pure autonomic failure (PAF) is a peripheral degenerative disorder of the autonomic nervous system.

Symptoms include:

  • In men, a common feature is impotence (inability to have or maintain an erection).
  • Orthostatic hypotension (fall in blood pressure with standing). Orthostatic hypotension may be described as unsteadiness, dizziness, or faintness upon standing. It is worse in the morning, after meals or exercise, or in hot weather. The orthostatic hypotension may also be accompanied by supine hypertension (increased blood pressure while lying down).
  • Pain in the neck or back of the head, which is relieved by lying down.
  • Loss of ability to sweat as much as the body did in the past.
  • Changes in urination including nocturia (the need to urinate during the night), urinary hesitancy (difficulty starting or maintaining a urinary stream), urgency, dribbling, and occasional incontinence.

Who gets PAF?

PAF is most frequently seen in men, in middle to late life.

What causes PAF?

The cause of PAF is not completely known.

How is PAF diagnosed?

In addition to asking detailed questions about the patient’s health, the physician will conduct a physical examination, which will include checking blood pressure and heart rate while the patient is sitting, standing and after one minute of being upright.

What is the treatment for PAF?

PAF is considered a generally mild condition. Treatments for PAF focus on managing symptoms:

  • Medication options focus on raising blood pressure (vasopressor agents).
  • Non-drug treatment options include squatting, abdominal compression, bending forward and using compression stockings.
  • To maintain upright posture, some patients find that crossing their legs helps.
  • Drinking water may help to temporarily raise blood pressure.

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