Peripheral neuropathy is an umbrella term that denotes a disorder of, or damage to, the peripheral nervous system. The peripheral nervous system consists of all the motor and sensory nerves that connect the brain and spinal cord to the rest of the body (i.e., the nerves outside the central nervous system). The symptoms and physical findings associated with peripheral neuropathies vary greatly from case to case and may be extremely complex.
More than 100 different peripheral neuropathies are recognized, each with a distinguishing set of symptoms, development path, and prognosis. Disorders affecting only one nerve are described as a mononeuropathies while disorders affecting more than one nerve are called polyneuropathies. If two nerves affecting different parts of the body are involved, the disorder is described as a mononeuritis multiplex.
In some cases, symptoms emerge abruptly, progress rapidly, and are slow to subside. Some chronic forms emerge only gradually and progress slowly. Some chronic forms appear to be resolved but are subject to relapses. Most often, symptoms such as pain, tingling, and/or muscle weakness start in both of the feet (bilateral) and progress up the legs. This is usually followed by symptoms in the hands that progress up the arms.
The symptoms of peripheral neuropathy are produced by disease of a single nerve (mononeuropathy, mononeuritis), several nerves in asymmetric areas of the body (mononeuritis multiplex), or many nerves simultaneously (polyneuropathy, polyneuritis, multiple peripheral neuritis). These symptoms may involve sensory, motor, reflex, or blood vessel (vasomotor) function. Lesions, usually degenerative and only rarely accompanied by signs of inflammation, may occur in the nerve roots or peripheral nerves.
The symptoms of peripheral nerve damage depend on the type of nerve affected. Muscle weakness, with or without muscle cramping, uncontrolled muscle twitching (fasciculations), loss of muscle mass, and bone erosion are usually the result of damage to a motor nerve. However, on occasion, such changes may be due to damage to sensory or autonomic nerves as well.
Symptoms arising from sensory nerve damage include reduced ability to touch and/or feel vibrations, with increasing numbness in the feet and hands. Many patients feel as if their hands and feet were covered, as if they were wearing gloves or stockings. Loss of posture sense or position sense leads to difficulty in walking, using buttons, or maintaining balance. Associated pain varies but may become intense and difficult to control.
It is not unusual for patients to lose the ability to feel pain or to sense changes in temperature. Such sensory loss may be particularly dangerous to patients with heart disease or diabetes. Patients may fail to register the signs of an impending heart attack or to realize the degree of damage to a foot, thus contributing to the course of preventable gangrene.
Autonomic nerve damage generates a different set of symptoms, depending on the organ or gland involved. Cardiovascular or pulmonary involvement may lead to life-threatening circumstances. Other symptoms include reduced capability to sweat properly, loss of bladder control, and the inability to control the muscles that help maintain blood pressure. Other symptoms of autonomic nerve damage include problems related to digestion, eating and swallowing.
Peripheral neuropathy may have many different causes. It may be acquired or inherited. Acquired peripheral neuropathies are caused by systemic disease, e.g. tic douloureux that is caused by damage to the trigeminal nerve, or trauma, or autoimmune disorders or infections. Inherited peripheral neuropathies include several forms of Charcot-Marie-Tooth disease, peripheral neuropathy with optic atrophy, and hereditary neuropathy with liability to pressure palsies. Peripheral neuropathies without known cause are called idiopathic.
The causes of peripheral neuropathy may be classified in the following way:
Physical injury or trauma is the most common cause of damage to a nerve. Accidents and sports-related injuries may sever, crush, stretch, or compress one or more peripheral nerves.
Systemic diseases, including metabolic and endocrine disorders such as diabetes, are often accompanied by peripheral neuropathies. The accumulation of toxic substances as a result of kidney disorders may often lead to peripheral neuropathy. Hormonal disorders such as acromegaly may lead to bone overgrowth that may exert pressure on nerve tissue leading to neuropathy. Alcoholism and/or vitamin deficiencies may lead to neuropathies because of a lack of vitamins E, B1, B6, or B12. Because alcoholism interferes with nutrition, it too may lead to vitamin deficiencies and neuropathies. Diseases of the blood and/or vascular system can have serious effects on nerve tissue if the oxygen supply is affected. Connective tissue disorders and chronic inflammation of nerve tissue may lead to neuropathies, and if sufficient connective tissue is destroyed the nerves become more vulnerable to compression and thus to damage as well. Cancers and benign tumors may compress nerves sufficiently to cause damage and neuropathy in disorders such as neurofibromatosis. Repetitive stress frequently leads to entrapment neuropathies such as carpal tunnel syndrome. People exposed to heavy metals and other toxins are often subject to peripheral neuropathies.
Infections and immune disorders, especially virus infections, can cause serious nerve damage and peripheral neuropathies. Viruses causing such disorders as Epstein-Barr syndrome or herpes varicella-zoster (shingles) are often the cause of severe nerve damage and nerve pain. Human immunodeficiency virus (HIV) causes a number of different peripheral neuropathies, depending on the stage of disease.
Inherited forms of peripheral neuropathy are the result of genetic mutations that in many instances lead to mild neuropathies, the onset of which is usually delayed to early adulthood. The more severe inherited forms, such as Charcot-Marie-Tooth disease (CMT), usually appear in childhood. In CMT disease, there are mistakes in the coding for the protective sheath (myelin sheath) that surrounds the nerve filaments.
Because the causes of peripheral neuropathy are so various, the diagnosis may be difficult. A thorough clinical evaluation, including a complete patient history and laboratory tests will be required. Less common tests such as electromyography, to measure the electrical discharge and conductivity of the nerve, may also be necessary to confirm the diagnosis of peripheral neuropathy.
Blood tests to measure the levels of several vitamins may be required as well. Sometimes, a nerve biopsy may be undertaken.
Treatment is designed to relieve the condition causing the neuropathy. If, for example, the underlying condition is diabetes, the patient may be encouraged to control blood sugar levels as a means of protecting the nerve fibers.
Stitching a nerve together, surgically breaking up adhesions around a nerve (neurolysis), or nerve transplant may be advisable in some traumatic lesions. In peripheral nerve entrapment or compression neuropathy (e.g., carpal tunnel syndrome), splinting or surgical decompression of certain nerves (e.g., ulnar, median, etc.) may be beneficial.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
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The National Cancer Institute is sponsoring clinical trials (2005) of possible treatments for peripheral neuropathy caused by complications from chemotherapy and treatment of solid tumors. In a Phase III study, the drug lamotrigine is being evaluated for effectiveness in reducing pain, numbness, tingling and other symptoms of peripheral neuropathy brought on by chemotherapy. In a Phase II study, which is co-sponsored by MD Anderson Cancer Center, the drug amifostine is being evaluated as a possible treatment for patients who have developed peripheral neuropathy following treatment for solid tumors. For information on both studies, contact the NIH Patient Recruitment Office or go to www.clinicaltrials.gov.
Smoked marijuana is being evaluated for its effectiveness in reducing pain in patients with HIV-related peripheral neuropathy. This study is being co- conducted by the Center for Medicinal Cannabis Research Center and the University of California in San Francisco. For information, write to firstname.lastname@example.org or go to www.clinicaltrials.gov.
In a recent study of individuals with peripheral neuropathy and carpal tunnel syndrome, there was an improvement in nocturnal awakening, pain, numbness, and weakness after carpal tunnel release surgery.
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