CHAPTER 124

Autonomic Nervous System Disorders

The autonomic nervous system regulates certain body processes, such as blood pressure and the rate of breathing. This system works automatically (autonomously), without a person’s conscious effort.

Disorders of the autonomic nervous system can affect any body part or process. Autonomic disorders may result from other disorders that damage autonomic nerves (such as diabetes), or they may occur on their own. Autonomic disorders may be reversible or progressive.

Anatomy: The autonomic nervous system is the part of the nervous system that supplies the internal organs, including the blood vessels, stomach, intestine, liver, kidneys, bladder, genitals, lungs, pupils and muscles of the eye, heart, and sweat, salivary, and digestive glands (see also page 627).

The autonomic nervous system has two main divisions: the sympathetic and the parasympathetic. After the autonomic nervous system receives information about the body and external environment, it responds by stimulating body processes, usually through the sympathetic division, or inhibiting them, usually through the parasympathetic division.

An autonomic nerve pathway involves two nerve cells. One cell is located in the brain stem or spinal cord. It is connected by nerve fibers to the other cell, which is located in a cluster of nerve cells (called an autonomic ganglion). Nerve fibers from these ganglia connect with internal organs. Most of the ganglia for the sympathetic division are located just outside the spinal cord on both sides of it. The ganglia for the parasympathetic division are located near or in the internal organs.

Function: The autonomic nervous system controls blood pressure, heart and breathing rates, body temperature, digestion, metabolism (thus affecting body weight), the balance of water and electrolytes (such as sodium and calcium), the production of body fluids (saliva, sweat, and tears), urination, defecation, sexual response, and other processes.

Many organs are controlled primarily by either the sympathetic or the parasympathetic division. Sometimes the two divisions have opposite effects on the same organ. For example, the sympathetic division increases blood pressure, and the parasympathetic division decreases it. Overall, the two divisions work together to ensure that the body responds appropriately to different situations.

Generally, the sympathetic division prepares the body for stressful or emergency situations—fight or flight. Thus, it increases heart rate and the force of heart contractions and widens (dilates) the airways to make breathing easier. It causes the body to release stored energy. Muscular strength is increased. This division also causes palms to sweat, pupils to dilate, and hair to stand on end. It slows body processes that are less important in emergencies, such as digestion and urination.

The parasympathetic division controls body process during ordinary situations. Generally, it conserves and restores. It slows the heart rate and decreases blood pressure. It stimulates the gastrointestinal tract to process food and eliminate waste. Energy from the processed food is used to restore and build tissues.

Both the sympathetic and parasympathetic divisions are involved in sexual activity, as are the parts of the nervous system that control voluntary actions and transmit sensation from the skin (somatic nervous system).

Two chemical messengers (neurotransmitters), acetylcholine and norepinephrine, are used to communicate within the autonomic nervous system. Nerve fibers that secrete acetylcholine are called cholinergic fibers. Fibers that secrete norepinephrine are called adrenergic fibers. Generally, acetylcholine has parasympathetic (inhibiting) effects and norepinephrine has sympathetic (stimulating) effects. However, acetylcholine has some sympathetic effects. For example, it sometimes stimulates sweating or makes the hair stand on end.

Symptoms

In men, difficulty initiating and maintaining an erection (erectile dysfunction) can be an early symptom of an autonomic disorder. Autonomic disorders commonly cause dizziness or light-headedness due to an excessive decrease in blood pressure when a person stands (orthostatic hypotension).

People may sweat less or not at all and thus become intolerant of heat. The eyes and mouth may be dry.

After eating, a person with an autonomic disorder may feel prematurely full or even vomit because the stomach empties very slowly (gastroparesis). Some people pass urine involuntarily (urinary incontinence), often because the bladder is overactive. Other people have difficulty emptying the bladder (urine retention) because the bladder is underactive. Constipation may occur, or control of bowel movements may be lost.

The pupils may not dilate and narrow (constrict) as light changes.

Diagnosis

Doctors can check for signs of autonomic disorders during the physical examination. They measure blood pressure and heart rate while a person is lying down or sitting and after the person stands. They examine the pupils for abnormal responses or lack of response to changes in light.

Other tests can provide additional information. Tilt table testing may be done to check blood pressure and heart rate responses to changes in position (see page 328). Blood pressure is measured after the person, who is lying flat on a pivoting table, is tilted into an upright position. Blood pressure is also measured continuously while the person performs a Valsalva maneuver (forcefully trying to exhale without letting air escape, as during a bowel movement). Electrocardiography is done to determine whether the heart rate changes as it normally does during deep breathing and the Valsalva maneuver.

Sweat testing is also done. For this test, the sweat glands are stimulated by electrodes that are filled with acetylcholine and placed on the legs and wrist. Then, the volume of sweat is measured to determine whether sweat production is normal. A slight burning sensation may be felt during the test. In another test (thermoregulatory sweat test), a dye is applied to the skin, and a person is placed in a closed, heated compartment to stimulate sweating. Sweat causes the dye to change color. As a result, doctors can identify which areas of the body sweat too much or too little.

Other tests may be done to check for disorders that can cause the autonomic disorder.

Treatment

Disorders that may be contributing to the autonomic disorder are treated. If no other disorders are present or if such disorders cannot be treated, the focus is on relieving symptoms.

Simple measures can help relieve some symptoms:

Orthostatic hypotension: People are advised to elevate the head of the bed by about 4 inches (10 centimeters) and to stand up slowly. Wearing a compression or support garment, such as an abdominal binder or compression stockings, may help. Consuming more salt and water helps maintain blood volume and thus blood pressure. Sometimes drugs (midodrine, pyridostigmine, or fludrocortisone taken by mouth) are used.

Decreased or absent sweating: If sweating is reduced or absent, avoiding warm environments is useful.

Urinary retention: If urinary retention is caused by inability of the bladder to contract normally, people can be taught to insert a catheter into the bladder themselves. They insert it several times a day and remove it after the bladder is empty. Bethanechol can be used to increase bladder tone and thus ease bladder emptying.

Constipation: A high-fiber diet and stool softeners are recommended. If constipation persists, enemas may be necessary.

Erectile dysfunction: Usually, treatment consists of drugs such as sildenafil, tadalafil, or vardenafil taken by mouth.

Autonomic Neuropathies

Autonomic neuropathies are disorders affecting the peripheral nerves that particularly damage the nerves that automatically (without conscious effort) regulate body processes (autonomic nerves).

Causes include diabetes, amyloidosis, autoimmune disorders, cancer, excessive alcohol consumption, and certain drugs.

People may feel light-headed when they stand and have urination problems, constipation, vomiting, and men may have erectile dysfunction.

Doctors do a physical examination and various tests to check for autonomic malfunction and possible causes.

The cause is corrected or treated if possible.

The nervous system has central and peripheral parts. The central nervous system includes the brain and spinal cord. The peripheral nervous system includes the nerves that connect the body’s tissues with the brain and spinal cord. Peripheral nerves include autonomic nerves, which automatically (unconsciously) regulate body processes. Peripheral nerves also include somatic nerves, the nerves that connect with muscles under voluntary (conscious) control or with sensory receptors in the skin.

Autonomic neuropathies are a type of peripheral neuropathy, a disorder in which peripheral nerves are damaged throughout the body. In autonomic neuropathies, there is much more damage to the autonomic nerves than to the somatic nerves.

Causes

Common causes include diabetes, amyloidosis (accumulation of an abnormal protein in tissues), and autoimmune disorders (when the immune system misinterprets the body’s tissues as foreign and attacks them). Viral infections may trigger an autoimmune reaction that results in destruction of autonomic nerves. Some of the antibodies produced by the immune system attack acetylcholine receptors (the part of nerve cells that enables them to respond to acetylcholine). Acetylcholine is one of the chemical messengers (neurotransmitters) used to communicate within the autonomic nervous system. A similar reaction often occurs in Guillain-Barré syndrome. Other causes include cancer, drugs, excessive alcohol consumption, and toxins.

SOME DRUGS USED TO TREAT SYMPTOMS OF AUTONOMIC DISORDERS

SYMPTOM	DRUG	DRUG’S EFFECT
Constipation	Fiber supplements (such as bran or psyllium) Stool softeners (such as docusate, lactulose, or polyethylene glycol)	Fiber supplements add bulk to the stool and thus stimulate the natural contractions of the intestine. Fiber supplements and stool softeners help move food through the intestine more quickly.
Fullness in the stomach	Metoclopramide	This drug stimulates contractions in the gastrointestinal tract and thus helps move food through it more quickly.
Erectile dysfunction	Sildenafil Tadalafil Vardenafil	These drugs increase the frequency, rigidity, and duration of erections.
Orthostatic hypotension	Fludrocortisone	This drug helps the body retain salt and thus helps maintain blood volume and blood pressure.
	Midodrine	This drug causes small arteries (arterioles) to constrict and thus helps maintain blood pressure.
	Pyridostigmine	This drug causes arterioles to constrict only when people stand and thus helps maintain blood pressure when people stand but does not increase blood pressure when they are lying or sitting down.
Urinary incontinence	Oxybutynin Tolterodine	These drugs relax the muscles of an overactive bladder.
Urine retention	Bethanechol	This drug stimulates contractions of the bladder and thus helps the bladder empty.

Symptoms

A common symptom is an excessive decrease in blood pressure when the person stands (orthostatic hypotension). As a result, the person feels lightheaded or as if about to faint. Men may have difficulty initiating and maintaining an erection (erectile dysfunction). Some people involuntarily pass urine (urinary incontinence), often because the bladder is overactive. Other people have difficulty emptying the bladder (urine retention) because the bladder is underactive. After eating, some people feel prematurely full or even vomit because the stomach empties slowly (gastroparesis). Severe constipation may occur.

When somatic nerves are damaged, people may lose sensation or feel a tingling (pins-and-needles) sensation in the hands and feet, or muscles may become weak.

Diagnosis and Treatment

A physical examination and certain tests are done to check for signs of autonomic disorders and possible causes (such as diabetes or amyloidosis). Blood tests are done to check for antibodies to acetylcholine receptors, which indicate an autoimmune reaction. About one half of people with an autonomic neuropathy due to an autoimmune reaction have these antibodies.

The cause, if identified, is treated. Neuropathies due to an autoimmune reaction are sometimes treated with drugs that lessen the reaction, such as azathioprine, cyclophosphamide, or prednisone. If symptoms are severe, immune globulin (a solution containing many different antibodies collected from a group of donors) may be given intravenously, or plasma exchange (plasmapheresis) may be done. In plasmapheresis, blood is withdrawn, filtered to remove abnormal antibodies, then returned to the person.

Horner’s Syndrome

In Horner’s syndrome, on one side of the face, the eyelid droops, the pupil is small (constricted), and sweating is decreased. The cause is disruption of the nerve fibers that connect the eye and the brain.

Horner’s syndrome may occur on its own or result from a disorder that disrupts nerve fibers connecting the eyes and brain.

The upper eyelid droops, the pupil remains small, and the affected side of the face may sweat less.

Doctors test the pupil to see whether it can widen, and may do imaging tests to look for a cause.

The cause, if identified, is treated.

Horner’s syndrome can develop in people of any age.

Causes

Some of the nerve fibers that connect the eyes and brain take a circuitous route. From the brain, they go down the spinal cord. They exit the spinal cord in the chest, then go back up the neck beside the carotid artery, through the skull, and into the eye. If these nerve fibers are disrupted anywhere along their pathway, Horner’s syndrome results. Horner’s syndrome may occur on its own or be caused by another disorder. For example, it can be caused by disorders of the head, brain, neck, or spinal cord, such as lung cancer, other tumors, swollen lymph glands in the neck (cervical adenopathy), dissection of the aorta or carotid artery, a thoracic aortic aneurysm, and injuries. Horner’s syndrome may be present at birth (congenital).

Symptoms

Horner’s syndrome affects the eye on the same side as the disrupted nerve fibers. Symptoms include a drooping upper eyelid (ptosis) and a constricted pupil (miosis). The affected side of the face may sweat less than normal or not at all, and rarely, it appears flushed. In the congenital form, the iris of the affected eye remains blue-gray as it is at birth.

Diagnosis and Treatment

The disorder is suspected based on symptoms. To confirm the diagnosis, doctors may apply eye drops that contain small amounts of cocaine to the affected eye. If the pupil does not widen (dilate) after 30 minutes, Horner’s syndrome is diagnosed. Doctors may apply other drugs to the eye later. How the pupil reacts to them indicates the general location of the damage. Magnetic resonance imaging (MRI) or computed tomography (CT) of the brain, spinal cord, chest, or neck is often needed to look for tumors and other serious disorders.

The cause, if identified, is treated. However, there is no specific treatment for Horner’s syndrome. Often, no treatment is necessary because, typically, the eyelid only droops very slightly.

Pure Autonomic Failure

Pure autonomic failure is dysfunction of many of the processes controlled by the autonomic nervous system, such as blood pressure. It is not fatal.

The cause is usually unknown but sometimes is an autoimmune disorder.

Blood pressure may decrease when people stand, and they may sweat less and may have eye problems, retain urine, become constipated, or lose control of bowel movements.

Doctors do a physical examination and tests to look for signs of autonomic malfunction.

Treatment focuses on relieving symptoms.

In pure autonomic failure (previously called idiopathic orthostatic hypotension or Bradbury-Eggleston syndrome), many processes regulated by the auto-nomic nervous system malfunction. They malfunction because nerve cells that are part of autonomic pathways are lost. The affected cells are located in clusters (called autonomic ganglia) on either side of the spinal cord or near or in internal organs. The brain and spinal cord are not affected. The peripheral nerves other than the autonomic ganglia are also unaffected. Pure autonomic failure affects more women and tends to begin in a person’s 40s or 50s. It does not lead to death.

The cause is usually unknown. Sometimes the cause is an autoimmune disorder, which occurs when the immune system misinterprets the body’s tissues (in this case, a part called the A3 acetylcholine receptor) as foreign and attacks them.

The most common symptom is an excessive decrease in blood pressure when a person stands (orthostatic hypotension). People may sweat less and become intolerant of heat. The pupils may not widen (dilate) and narrow (constrict) normally. Vision may be blurred. People may have difficulty emptying the bladder (urine retention). They may be constipated or lose control of bowel movements. Men may have difficulty initiating and maintaining an erection (erectile dysfunction).

Diagnosis and Treatment

Doctors check for signs of autonomic dysfunction during the physical examination and with tests. For example, doctors measure levels of norepinephrine, one of the chemical messengers (neurotransmitters) used by nerve cells to communicate with each other. No test can confirm the diagnosis, so doctors diagnose this disorder by excluding other disorders.

There is no specific treatment, so the focus is on relieving symptoms (see page 832).