Diabetic and Hereditary Polyneuropathies

Polyneuropathy is the simultaneous malfunction of many peripheral nerves throughout the body.

  • Infections, toxins, drugs, cancers, nutritional deficiencies, and other 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)
  • Chronic (developing gradually, often over months or years)


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-Barré syndrome (see Guillain-Barré Syndrome)

  • Drugs, including the anticonvulsant phenytoin, some antibiotics (such aschloramphenicol, nitrofurantoin, 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

  • Certain toxins, such as organophosphate insecticides, triorthocresyl phosphate (TOCP), and thallium

The cause of chronic polyneuropathy is often unknown. Known causes include the following:

  • Diabetes (the most common—see Diabetes Mellitus)

  • Excessive use of alcohol

  • Nutritional deficiencies (such as thiamin deficiency), an uncommon cause in the United States, except among alcoholics who are malnourished

  • Vitamin B 12 deficiency, which causes subacute combined degeneration of the spinal cord (see Subacute Combined Degeneration) and often pernicious anemia (see Inadequate absorption)

  • An underactive thyroid gland (hypothyroidism)

  • Toxic substances, including heavy metals such as lead and mercury

  • Kidney failure

  • Certain cancers, such as lung cancer

  • Rarely, vitamin B 6 (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 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.)

Some people have a hereditary form of polyneuropathy (see Hereditary Neuropathies).

Depending on the cause, polyneuropathies may affect motor nerves (which control muscle movement), sensory nerves (which transmit sensory information), cranial nerves (which connect the head, face, eyes, nose, muscles, and ears to the brain), or a combination.


Acute polyneuropathy (as occurs in Guillain-Barré syndrome) begins suddenly in both legs and progresses rapidly upward to the arms. Symptoms include weakness and a pins-and-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. Then, muscles may become stiff and permanently shortened (called contractures).

Diabetic neuropathy commonly causes painful tingling or burning sensations in the hands and feet—a 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 may have 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 neurogenic arthropathy (Charcot joints—see Neurogenic Arthropathy (Charcot 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, sexual dysfunction, and fluctuating blood pressure—most 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. Much less often, control of bowel movements or urination is lost, leading to fecal or urinary incontinence.

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 with mild symptoms may not notice the symptoms or may consider them unimportant. Other people are severely affected.

How completely people recover depends on the cause of polyneuropathy.


  • A doctor's evaluation

  • Electromyography and nerve conduction studies

  • Blood and urine tests to determine the cause

Doctors usually recognize polyneuropathy by the symptoms. A physical examination and tests such as electromyography and nerve conduction studies (see Tests for 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. This information suggests possible causes. Blood and urine tests may detect a disorder that is causing polyneuropathy, such as 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 a hereditary neuropathy that affects other family members so mildly that the disorder was never suspected.

If weakness is widespread and rapidly worsening, doctors do other tests:

  • A spinal tap (lumbar puncture—see Figure: How a Spinal Tap Is Done) is done to obtain a sample of cerebrospinal fluid, which surrounds the brain and spinal cord. If the protein level in the fluid is high and few or no white blood cells are present, the cause may be Guillain-Barré syndrome.

  • Spirometry is done to determine whether the muscles that control breathing are affected. Spirometry is used to measure how much air the lungs can hold as well as how much and how quickly air can be exhaled.


  • Treatment of the cause

  • Relief of pain

  • Sometimes physical and occupational therapy

Specific treatment depends on the cause, as for the following:

  • Diabetes: Careful control of blood sugar levels may slow progression of the disorder and occasionally relieves symptoms. Transplantation of cells that produce insulin (islet cells—see Pancreas Transplantation), located in the pancreas, is sometimes done and may result 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 plasma exchange (filtering of toxic substances, including abnormal antibodies, from the blood), immune globulin given intravenously, corticosteroids, and drugs that inhibit the immune system (immunosuppressants).

  • Drugs and toxins : Stopping the drug or avoiding exposure to the toxin can sometimes reverse the polyneuropathy. Antidotes are available for certain drugs and toxins and can reverse some toxic effects.

  • Excessive amounts of vitamin B 6 : If the vitamin is stopped, polyneuropathy may resolve.

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 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, andmexiletine (used to treat abnormal heart rhythms). Lidocaine, an anesthetic applied as a lotion, an ointment, or a skin patch, may also help.