Polyneuropathy

Polyneuropathy is the simultaneous malfunction of many peripheral nerves throughout the

body. Infections, toxins, drugs, cancers, nutritional deficiencies, and disorders can cause many peripheral nerves to malfunction. Sensation, strength, or both may be impaired, often in the feet or hands before the arms, legs, or trunk. Doctors base the diagnosis on results of electromyography, nerve conduction studies, and blood and urine tests. If treating the underlying disorder does not relieve symptoms, physical therapy, drugs, and other measures may help.

Polyneuropathy may be acute (beginning suddenly) or chronic (developing gradually, often over months or years). Causes

Acute polyneuropathy has many causes: Infections involving a toxin produced by bacteria, as occurs in diphtheria An autoimmune reaction (when the body attacks its own tissues), as occurs in Guillain-Barr syndrome Toxic substances, including heavy metals such as lead and mercury Drugs, including the anticonvulsant phenytoin SOME TRADE NAMES DILANTIN , some antibiotics (such as chloramphenicol SOME TRADE NAMES CHLORAMPHENICOL , nitrofurantoin SOME TRADE NAMES FURADANTINMACRODANTIN , and sulfonamides), some chemotherapy drugs (such as vinblastine and vincristine), and some sedatives (such as barbital and hexobarbital) Cancer, such as multiple myeloma, which damages nerves by directly invading or putting pressure on them or by triggering an autoimmune reaction

The cause of chronic polyneuropathy is often unknown. Causes include the following: Diabetes Excessive use of alcohol Nutritional deficiencies (such as thiamin deficiency), an uncommon cause in the United States, except among alcoholics who are malnourished Anemia due to vitamin B12 deficiency (pernicious anemia) An underactive thyroid gland (hypothyroidism) Liver failure Kidney failure

Certain cancers, such as lung cancer Vitamin B6 (pyridoxine) taken in excessive amounts

The most common form of chronic polyneuropathy usually results from poor control of blood sugar levels in people with diabetes (see Diabetes Mellitus (DM): Diabetes Mellitus) but may result from excessive use of alcohol. Diabetic neuropathy refers to the several forms of polyneuropathy that diabetes can cause. (Diabetes can also cause mononeuropathy or multiple mononeuropathy, which leads to weakness, typically of the eye or thigh muscles.) In some people, the cause is hereditary. Depending on the cause, polyneuropathies may affect motor nerves (which control muscle movement), sensory (which transmit sensory information), cranial nerves (which connect the head, face, eyes, nose, muscles, and ears to the brain), or a combination. Symptoms Acute polyneuropathy (for example, as occurs in Guillain-Barr syndrome) begins suddenly in both legs and progresses rapidly upward to the arms. Symptoms include weakness and a pinsand-needles sensation or loss of sensation. The muscles that control breathing may be affected, resulting in respiratory failure. In the most common form of chronic polyneuropathy, only sensation is affected. Usually, the feet are affected first, but sometimes the hands are. A pins-and-needles sensation, numbness, burning pain, and loss of vibration sense and position sense (knowing where the arms and legs are) are prominent symptoms. Because position sense is lost, walking and even standing become unsteady. Consequently, muscles may not be used. Eventually, they may weaken and waste away. Diabetic neuropathy commonly causes painful tingling or burning sensations in the hands and feeta condition called distal polyneuropathy. Pain is often worse at night and may be aggravated by touch or by a change in temperature. People may lose the senses of temperature and pain, so they often burn themselves and develop open sores caused by prolonged pressure or other injuries. Without pain as a warning of too much stress, joints are susceptible to injuries. This type of injury is called Charcot's joints. Polyneuropathy often affects the nerves of the autonomic nervous system, which controls involuntary functions in the body (such as blood pressure, heart rate, digestion, salivation, and urination). Typical symptoms are constipation, loss of bowel or bladder control (leading to fecal or urinary incontinence), sexual dysfunction, and fluctuating blood pressuremost notably a sudden fall in blood pressure when a person stands up (orthostatic hypotension). The skin may become pale and dry, and sweating may be reduced. People who have a hereditary form may have hammer toes, high arches, and a curved spine (scoliosis). Abnormalities in sensation and muscle weakness may be mild. Affected people may not notice these symptoms or may consider them unimportant. How completely people recover depends on the cause of polyneuropathy. Diagnosis Doctors usually recognize polyneuropathy by the symptoms. A physical examination and tests such as electromyography and nerve conduction studies (see Diagnosis of Brain, Spinal Cord,

and Nerve Disorders: Electromyography and Nerve Conduction Studies) can provide additional information about absent or reduced sensation in the feet. After polyneuropathy is diagnosed, its cause, which may be treatable, must be identified. Doctors ask whether other symptoms are present and how quickly the symptoms developed. Blood and urine tests may detect a disorder that is causing polyneuropathyfor example, diabetes, kidney failure, or an underactive thyroid gland. Infrequently, a nerve biopsy is necessary. Sometimes polyneuropathy affecting the hands and feet is the first indication that people have diabetes. Sometimes, when extensive testing detects no obvious cause, the cause is an inherited neuropathy that affects other family members so mildly that the disorder was never suspected. Treatment

Specific treatment depends on the cause, as for the following: Excessive amounts of vitamin B6: If the vitamin is stopped, polyneuropathy may resolve. Diabetes: Careful control of blood sugar levels may slow progression of the disorder and occasionally relieves symptoms. Transplantation of cells that produce insulin (islet cellssee Transplantation: Pancreas Transplantation), located in the pancreas, sometimes results in a cure. Multiple myeloma or liver or kidney failure: Treatment of these disorders may result in slow recovery. Cancer: Surgically removing the cancer may be necessary to relieve pressure on the nerve. An underactive thyroid gland: Thyroid hormone is given. Autoimmune disorders: Treatments include plasmapheresis (filtering of toxic substances, including abnormal antibodies, from the blood), immune globulin given intravenously, corticosteroids, and drugs that suppress the immune system (immunosuppressants).

If the cause cannot be corrected, treatment focuses on relieving pain and problems related to muscle weakness. Physical therapy sometimes reduces muscle stiffness and can prevent shortening of muscles (contractures). Physical and occupational therapists can recommend useful assistive devices. Some drugs that are usually not considered pain relievers can lessen pain due to nerve damage. They include the antidepressant amitriptyline, the anticonvulsant gabapentin SOME TRADE NAMES NEURONTIN , and mexiletine (used to treat abnormal heart rhythms). Lidocaine SOME TRADE NAMES XYLOCAINE , an anesthetic applied as a lotion, an ointment, or a skin patch, may also help. GUILLAIN-BARR SYNDROME Guillain-Barr syndrome (acute inflammatory demyelinating polyneuropathy) is a form of polyneuropathy that causes one episode of increasing muscle weakness. The episode lasts 8 weeks or less. An autoimmune reaction may damage the myelin sheath around nerves.

Usually, weakness begins in both legs and moves up the body. Electromyography and nerve conduction studies can help confirm the diagnosis.

Plasmapheresis or immune globulin given intravenously may speed recovery.

The presumed cause is an autoimmune reaction: The body's immune system attacks the myelin sheath, which surrounds the axon of many nerves and enables nerve impulses to travel quickly. In about 80% of people with this syndrome, symptoms begin about 5 days to 3 weeks after a mild infection (such as a Campylobacter infection, mononucleosis, or another viral infection), surgery, or an immunization. Symptoms Symptoms usually begin in both legs, then progress upward to the arms. Occasionally, symptoms begin in the arms or head and progress downward. Symptoms include weakness and a pins-and-needles sensation or loss of sensation. Weakness is more prominent than abnormal sensation. Reflexes are decreased or absent. In 90% of people who have Guillain-Barr syndrome, weakness is most severe within 3 weeks. In 5 to 10%, the muscles that control breathing become so weak that a ventilator is needed. Because the facial and swallowing muscles become weak, a few people need to be fed intravenously or through a tube placed directly through the abdominal wall into the stomach (gastrostomy tube). If the disorder is very severe, internal functions controlled by the autonomic nervous system may be impaired. For example, blood pressure may fluctuate widely, heart rhythm may become abnormal, and severe constipation may develop. In a variant called Miller-Fisher syndrome, only a few symptoms develop: Eye movements become paralyzed, walking becomes difficult, and normal reflexes disappear. Diagnosis Doctors suspect the diagnosis based on the pattern of symptoms. Tests are done to confirm the diagnosis. People are usually admitted to the hospital to have the tests because the syndrome can worsen rapidly and impair the muscles involved in breathing. Analysis of cerebrospinal fluid obtained by a spinal tap (lumbar puncturesee Diagnosis of Brain, Spinal Cord, and Nerve Disorders:Procedures ), electromyography, nerve conduction studies, and blood tests can help doctors exclude other possible causes of severe weakness, such as transverse myelitis and spinal cord injuries. A combination of high protein levels and no inflammatory cells in the cerebrospinal fluid and characteristic results from electromyography strongly suggest Guillain-Barr syndrome. Prognosis Damage stops progressing within 8 weeks. Without treatment, most people improve slowly over several months. However, with early treatment, people can improve very quicklyin days or weeks. About 30% of adults and even more children with the disorder have residual weakness 3 years after the syndrome began. On average, less than 2% of people die. After improving initially, 3 to 10% of people develop a disorder called chronic inflammatory demyelinating polyneuropathy (see Peripheral Nerve Disorders: Treatment). Treatment Guillain-Barr syndrome can worsen rapidly and is a medical emergency. People who develop this syndrome should be hospitalized immediately. Establishing the diagnosis is crucial because the sooner appropriate treatment is started, the better the chance of a good outcome.

In the hospital, people are closely monitored so that breathing can be assisted with a ventilator if necessary. Nurses take precautions to prevent pressure sores and injuries by providing soft mattresses and by turning the people with severe weakness every 2 hours. If weakness is less severe, physical therapy is started to help preserve joint and muscle function. Heat therapy may be used first to relieve pain and thus make physical therapy more comfortable. Plasmapheresis (filtering of toxic substances, including antibodies to the myelin sheath) from the bloodsee Controlling Diseases by Purifying the Blood ) or immune globulin given intravenously is the treatment of choice. These treatments are relatively safe, shorten the hospital stay, speed recover, and reduce the risk of death and permanent disability. Corticosteroids do not help and may worsen the syndrome. CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY Chronic inflammatory demyelinating polyneuropathy (chronic acquired demyelinating polyneuropathy, or chronic relapsing polyneuropathy) is a form of polyneuropathy that, like Guillain-Barr syndrome, causes increasing muscle weakness, but the weakness lasts longer than 8 weeks. Chronic inflammatory demyelinating polyneuropathy develops in 3 to 10% of people with Guillain-Barr syndrome. Weakness and abnormal sensations (numbness and pins-and-needles) last longer than 8 weeks. Weakness can worsen continually or come and go. Reflexes are decreased or absent. In most people with this disorder, blood pressure fluctuates less, abnormal heart rhythms occur less often, and other internal functions are less impaired than in people with Guillain-Barr syndrome. Also, weakness may be more irregular, affecting the two sides of the body differently, and weakness may progress more slowly. Diagnosis and Treatment Doctors suspect the diagnosis based on symptoms. Electromyography, nerve conduction studies, and a spinal tap to obtain cerebrospinal fluid are done to confirm the diagnosis. Rarely, a biopsy of the nerve is needed. Corticosteroids such as prednisone can relieve symptoms. Immunosuppressants such as azathioprine SOME TRADE NAMES IMURAN may also be used. However, if chronic inflammatory demyelinating polyneuropathy is severe or progresses rapidly, plasmapheresis or immune globulin given intravenously may be preferred to corticosteroids. People may need treatment for months or years.