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Peripheral neuropathy describes damage to the peripheral nervous system, the vast communications network that transmits information from the brain and spinal cord (the central nervous system) to every other part of the body. Peripheral nerves also send sensory information back to the brain and spinal cord, such as a message that the feet are cold or a finger is burned. Damage to the peripheral nervous system interferes with these vital connections. Like static on a telephone line, peripheral neuropathy distorts and sometimes interrupts messages between the brain and the rest of the body.
Because every peripheral nerve has a highly specialized function in a specific part of the body, a wide array of symptoms can occur when nerves are damaged. Some people may experience temporary numbness, tingling, and pricking sensations (paresthesia), sensitivity to touch, or muscle weakness. Others may suffer more extreme symptoms, including burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction. People may become unable to digest food easily, maintain safe levels of blood pressure, sweat normally, or experience normal sexual function. In the most extreme cases, breathing may become difficult or organ failure may occur.
Some forms of neuropathy involve damage to only one nerve and are called mononeuropathies. More often though, multiple nerves affecting all limbs are affected-called polyneuropathy. Occasionally, two or more isolated nerves in separate areas of the body are affected-called mononeuritis multiplex.
In acute neuropathies, such as Guillain-Barré syndrome, symptoms appear suddenly, progress rapidly, and resolve slowly as damaged nerves heal. In chronic forms, symptoms begin subtly and progress slowly. Some people may have periods of relief followed by relapse. Others may reach a plateau stage where symptoms stay the same for many months or years. Some chronic neuropathies worsen over time, but very few forms prove fatal unless complicated by other diseases. Occasionally the neuropathy is a symptom of another disorder.
In the most common forms of polyneuropathy, the nerve fibers (individual cells that make up the nerve) most distant from the brain and the spinal cord malfunction first. Pain and other symptoms often appear symmetrically, for example, in both feet followed by a gradual progression up both legs. Next, the fingers, hands, and arms may become affected, and symptoms can progress into the central part of the body. Many people with diabetic neuropathy experience this pattern of ascending nerve damage.
Symptoms are related to the type of affected nerve and may be seen over a period of days, weeks, or years. Muscle weakness is the most common symptom of motor nerve damage. Other symptoms may include painful cramps and fasciculations (uncontrolled muscle twitching visible under the skin), muscle loss, bone degeneration, and changes in the skin, hair, and nails. These more general degenerative changes also can result from sensory or autonomic nerve fiber loss.
Sensory nerve damage causes a more complex range of symptoms because sensory nerves have a wider, more highly specialized range of functions. Larger sensory fibers enclosed in myelin (a fatty protein that coats and insulates many nerves) register vibration, light touch, and position sense. Damage to large sensory fibers lessens the ability to feel vibrations and touch, resulting in a general sense of numbness, especially in the hands and feet. People may feel as if they are wearing gloves and stockings even when they are not. Many patients cannot recognize by touch alone the shapes of small objects or distinguish between different shapes. This damage to sensory fibers may contribute to the loss of reflexes (as can motor nerve damage). Loss of position sense often makes people unable to coordinate complex movements like walking or fastening buttons, or to maintain their balance when their eyes are shut. Neuropathic pain is difficult to control and can seriously affect emotional well-being and overall quality of life. Neuropathic pain is often worse at night, seriously disrupting sleep and adding to the emotional burden of sensory nerve damage.
Smaller sensory fibers without myelin sheaths transmit pain and temperature sensations. Damage to these fibers can interfere with the ability to feel pain or changes in temperature. People may fail to sense that they have been injured from a cut or that a wound is becoming infected. Others may not detect pains that warn of impending heart attack or other acute conditions. (Loss of pain sensation is a particularly serious problem for people with diabetes, contributing to the high rate of lower limb amputations among this population.) Pain receptors in the skin can also become over sensitized, so that people may feel severe pain (allodynia) from stimuli that are normally painless (for example, some may experience pain from bed sheets draped lightly over the body)
.Symptoms of autonomic nerve damage are diverse and depend upon which organs or glands are affected. Autonomic nerve dysfunction can become life threatening and may require emergency medical care in cases when breathing becomes impaired or when the heart begins beating irregularly. Common symptoms of autonomic nerve damage include an inability to sweat normally, which may lead to heat intolerance; a loss of bladder control, which may cause infection or incontinence; and an inability to control muscles that expand or contract blood vessels to maintain safe blood pressure levels. A loss of control over blood pressure can cause dizziness, lightheadedness, or even fainting when a person moves suddenly from a seated to a standing position (a condition known as postural or orthostatic hypotension)
.Gastrointestinal symptoms frequently accompany autonomic neuropathy. Nerves controlling intestinal muscle contractions often malfunction, leading to diarrhea, constipation, or incontinence. Many people also have problems eating or swallowing if certain autonomic nerves are affected.
More than 100 types of peripheral neuropathy have been identified, each with its own characteristic set of symptoms, pattern of development, and prognosis. Impaired function and symptoms depend on the type of nerves-motor, sensory, or autonomic-that are damaged.
Motor nerves control movements of all muscles under conscious control, such as those used for walking, grasping things, or talking. Sensory nerves transmit information about sensory experiences, such as the feeling of a light touch or the pain resulting from a cut.
Autonomic nerves regulate biological activities that people do not control consciously, such as breathing, digesting food, and heart and gland functions. Although some neuropathies may affect all three types of nerves, others primarily affect one or two types.
Therefore, doctors may use terms such as predominantly motor neuropathy, predominantly sensory neuropathy, sensory-motor neuropathy, or autonomic neuropathy to describe a patient’s condition.
Peripheral neuropathy may be either inherited or acquired. Causes of acquired peripheral neuropathy include physical injury (trauma) to a nerve, tumors, toxins, autoimmune responses, nutritional deficiencies, alcoholism, and vascular and metabolic disorders. Acquired peripheral neuropathies are grouped into three broad categories: those caused by systemic disease, those caused by trauma from external agents, and those caused by infections or autoimmune disorders affecting nerve tissue. One example of an acquired peripheral neuropathy is trigeminal neuralgia (also known as tic douloureux), in which damage to the trigeminal nerve (the large nerve of the head and face) causes episodic attacks of excruciating, lightning-like pain on one side of the face. In some cases, the cause is an earlier viral infection, pressure on the nerve from a tumor or swollen blood vessel, or, infrequently, multiple sclerosis. In many cases, however, a specific cause cannot be identified. Doctors usually refer to neuropathies with no known cause as idiopathic neuropathies.
Physical injury (trauma) is the most common cause of injury to a nerve. Injury or sudden trauma, such as from automobile accidents, falls, and sports-related activities, can cause nerves to be partially or completely severed, crushed, compressed, or stretched, sometimes so forcefully that they are partially or completely detached from the spinal cord. Less dramatic traumas also can cause serious nerve damage. Broken or dislocated bones can exert damaging pressure on neighboring nerves, and slipped disks between vertebrae can compress nerve fibers where they emerge from the spinal cord.
Systemic diseases — disorders that affect the entire body —often cause peripheral neuropathy. These disorders may include: Metabolic and endocrine disorders. Nerve tissues are highly vulnerable to damage from diseases that impair the body’s ability to transform nutrients into energy, process waste products, or manufacture the substances that make up living tissue. Diabetes mellitus, characterized by chronically high blood glucose levels, is a leading cause of peripheral neuropathy in the United States. About 60 percent to 70 percent of people with diabetes have mild to severe forms of nervous system damage.
Kidney disorders can lead to abnormally high amounts of toxic substances in the blood that can severely damage nerve tissue. A majority of patients who require dialysis because of kidney failure develop polyneuropathy. Some liver diseases also lead to neuropathies as a result of chemical imbalances.
Hormonal imbalances can disturb normal metabolic processes and cause neuropathies. For example, an underproduction of thyroid hormones slows metabolism, leading to fluid retention and swollen tissues that can exert pressure on peripheral nerves. Overproduction of growth hormone can lead to acromegaly, a condition characterized by the abnormal enlargement of many parts of the skeleton, including the joints. Nerves running through these affected joints often become entrapped.
Vitamin deficiencies and alcoholism can cause widespread damage to nerve tissue. Vitamins E, B1, B6, B12, and niacin are essential to healthy nerve function. Thiamine deficiency, in particular, is common among people with alcoholism because they often also have poor dietary habits. Thiamine deficiency can cause a painful neuropathy of the extremities. Some researchers believe that excessive alcohol consumption may, in itself, contribute directly to nerve damage, a condition referred to as alcoholic neuropathy.
Vascular damage and blood diseases can decrease oxygen supply to the peripheral nerves and quickly lead to serious damage to or death of nerve tissues, much as a sudden lack of oxygen to the brain can cause a stroke. Diabetes frequently leads to blood vessel constriction. Various forms of vasculitis (blood vessel inflammation) frequently cause vessel walls to harden, thicken, and develop scar tissue, decreasing their diameter and impeding blood flow. This category of nerve damage, in which isolated nerves in different areas are damaged, is called mononeuropathy multiplex or multifocal mononeuropathy.
Connective tissue disorders and chronic inflammation can cause direct and indirect nerve damage. When the multiple layers of protective tissue surrounding nerves become inflamed, the inflammation can spread directly into nerve fibers. Chronic inflammation also leads to the progressive destruction of connective tissue, making nerve fibers more vulnerable to compression injuries and infections. Joints can become inflamed and swollen and entrap nerves, causing pain.
Cancers and benign tumors can infiltrate or exert damaging pressure on nerve fibers. Tumors also can arise directly from nerve tissue cells. Widespread polyneuropathy is often associated with the neurofibromatoses, genetic diseases in which multiple benign tumors grow on nerve tissue. Neuromas, benign masses of overgrown nerve tissue that can develop after any penetrating injury that severs nerve fibers, generate very intense pain signals and sometimes engulf neighboring nerves, leading to further damage and even greater pain. Neuroma formation can be one element of a more widespread neuropathic pain condition called complex regional pain syndrome or reflex sympathetic dystrophy syndrome, which can be caused by traumatic injuries or surgical trauma. Paraneoplastic syndromes, a group of rare degenerative disorders that are triggered by a person’s immune system response to a cancerous tumor, also can indirectly cause widespread nerve damage.
Repetitive stress frequently leads to entrapment neuropathies, a special category of compression injury. Cumulative damage can result from repetitive, forceful, awkward activities that require flexing of any group of joints for prolonged periods. The resulting irritation may cause ligaments, tendons, and muscles to become inflamed and swollen, constricting the narrow passageways through which some nerves pass. These injuries become more frequent during pregnancy, probably because weight gain and fluid retention also constrict nerve passageways.
Toxins can also cause peripheral nerve damage. People who are exposed to heavy metals (arsenic, lead, mercury, thallium), industrial drugs, or environmental toxins frequently develop neuropathy. Certain anticancer drugs, anticonvulsants, antiviral agents, and antibiotics have side effects that can include peripheral nerve damage, thus limiting their long-term use.
Infections and autoimmune disorders can cause peripheral neuropathy. Viruses and bacteria that can attack nerve tissues include herpes varicella-zoster (shingles), Epstein-Barr virus, cytomegalovirus, and herpes simplex-members of the large family of human herpes viruses. These viruses severely damage sensory nerves, causing attacks of sharp, lightning-like pain. Postherpetic neuralgia often occurs after an attack of shingles and can be particularly painful.
The human immunodeficiency virus (HIV), which causes AIDS, also causes extensive damage to the central and peripheral nervous systems. The virus can cause several different forms of neuropathy, each strongly associated with a specific stage of active immunodeficiency disease. A rapidly progressive, painful polyneuropathy affecting the feet and hands is often the first clinically apparent sign of HIV infection.
Lyme disease, diphtheria, and leprosy are bacterial diseases characterized by extensive peripheral nerve damage. Diphtheria and leprosy are now rare in the United States, but Lyme disease is on the rise. It can cause a wide range of neuropathic disorders, including a rapidly developing, painful polyneuropathy, often within a few weeks after initial infection by a tick bite.
Viral and bacterial infections can also cause indirect nerve damage by provoking conditions referred to as autoimmune disorders, in which specialized cells and antibodies of the immune system attack the body’s own tissues. These attacks typically cause destruction of the nerve’s myelin sheath or axon (the long fiber that extends out from the main nerve cell body).
Some neuropathies are caused by inflammation resulting from immune system activities rather than from direct damage by infectious organisms. Inflammatory neuropathies can develop quickly or slowly, and chronic forms can exhibit a pattern of alternating remission and relapse. Acute inflammatory demyelinating neuropathy, better known as Guillain-Barré syndrome, can damage motor, sensory, and autonomic nerve fibers. Most people recover from this syndrome although severe cases can be life threatening. Chronic inflammatory demyelinating polyneuropathy (CIDP), generally less dangerous, usually damages sensory and motor nerves, leaving autonomic nerves intact. Multifocal motor neuropathy is a form of inflammatory neuropathy that affects motor nerves exclusively; it may be chronic or acute.
Inherited forms of peripheral neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. Some genetic errors lead to mild neuropathies with symptoms that begin in early adulthood and result in little, if any, significant impairment. More severe hereditary neuropathies often appear in infancy or childhood.
The most common inherited neuropathies are a group of disorders collectively referred to as Charcot-Marie-Tooth disease. These neuropathies result from flaws in genes responsible for manufacturing neurons or the myelin sheath. Hallmarks of typical Charcot-Marie-Tooth disease include extreme weakening and wasting of muscles in the lower legs and feet, gait abnormalities, loss of tendon reflexes, and numbness in the lower limbs.
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