Peripheral Neuropathy

views updated May 08 2018

Peripheral Neuropathy


The term peripheral neuropathy encompasses a wide range of disorders in which the nerves outside of the brain and spinal cordperipheral nerveshave been damaged. Peripheral neuropathy may also be referred to as peripheral neuritis, or if many nerves are involved, the terms polyneuropathy or polyneuritis may be used.


Peripheral neuropathy is a widespread disorder, and there are many underlying causes. Some of these causes are common, such as diabetes, and others are extremely rare, such as acrylamide poisoning and certain inherited disorders. The most common worldwide cause of peripheral neuropathy is leprosy. Leprosy is caused by the bacterium Mycobacterium leprae, which attacks the peripheral nerves of affected people. According to statistics gathered by the World Health Organization, an estimated 1.15 million people have leprosy worldwide.

Leprosy is extremely rare in the United States, where diabetes is the most commonly known cause of peripheral neuropathy. It has been estimated that more than 17 million people in the United States and Europe have diabetes-related polyneuropathy. Many neuropathies are idiopathic, meaning that no known cause can be found. The most common of the inherited peripheral neuropathies in the United States is Charcot-Marie-Tooth disease, which affects approximately 125,000 persons.

Another of the better known peripheral neuropathies is Guillain-Barré syndrome, which arises from complications associated with viral illnesses, such as cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus (HIV), or bacterial infection, including Campylobacter jejuni and Lyme disease. The worldwide incidence rate is approximately 1.7 cases per 100,000 people annually. Other well-known causes of peripheral neuropathies include chronic alcoholism, infection of the varicella-zoster virus, botulism, and poliomyelitis. Peripheral neuropathy may develop as a primary symptom, or it may be due to another disease. For example, peripheral neuropathy is only one symptom of diseases such as amyloid neuropathy, certain cancers, or inherited neurologic disorders. Such diseases may affect the peripheral nervous system (PNS) and the central nervous system (CNS), as well as other body tissues.

To understand peripheral neuropathy and its underlying causes, it may be helpful to review the structures and arrangement of the PNS.

Nerve cells and nerves

Nerve cells are the basic building block of the nervous system. In the PNS, nerve cells can be threadliketheir width is microscopic, but their length can be measured in feet. The long, spidery extensions of nerve cells are called axons. When a nerve cell is stimulated, by touch or pain, for example, the message is carried along the axon, and neurotransmitters are released within the cell. Neurotransmitters are chemicals within the nervous system that direct nerve cell communication.

Certain nerve cell axons, such as the ones in the PNS, are covered with a substance called myelin. The myelin sheath may be compared to the plastic coating on electrical wiresit is there both to protect the cells and to prevent interference with the signals being transmitted. Protection is also given by Schwann cells, special cells within the nervous system that wrap around both myelinated and unmyelinated axons. The effect is similar to beads threaded on a necklace.

Nerve cell axons leading to the same areas of the body may be bundled together into nerves. Continuing the comparison to electrical wires, nerves may be compared to an electrical cordthe individual components are coated in their own sheaths and then encased together inside a larger protective covering.

Peripheral nervous system

The nervous system is classified into two parts: the CNS and the PNS. The CNS is made up of the brain and the spinal cord, and the PNS is composed of the nerves that lead to or branch off from the CNS.

The peripheral nerves handle a diverse array of functions in the body. This diversity is reflected in the major divisions of the PNSthe afferent and the efferent divisions. The afferent division is in charge of sending sensory information from the body to the CNS. When afferent nerve cell endings, called receptors, are stimulated, they release neurotransmitters. These neurotransmitters relay a signal to the brain, which interprets it and reacts by releasing other neurotransmitters.

Some of the neurotransmitters released by the brain are directed at the efferent division of the PNS. The efferent nerves control voluntary movements, such as moving the arms and legs, and involuntary movements, such as making the heart pump blood. The nerves controlling voluntary movements are called motor nerves, and the nerves controlling involuntary actions are referred to as autonomic nerves. The afferent and efferent divisions continually interact with each other. For example, if a person were to touch a hot stove, the receptors in the skin would transmit a message of heat and pain through the sensory nerves to the brain. The message would be processed in the brain and a reaction, such as pulling back the hand, would be transmitted via a motor nerve.


NERVE DAMAGE. When an individual has a peripheral neuropathy, nerves of the PNS have been damaged. Nerve damage can arise from a number of causes, such as disease, physical injury, poisoning, or malnutrition. These agents may affect either afferent or efferent nerves. Depending on the cause of damage, the nerve cell axon, its protective myelin sheath, or both may be injured or destroyed.

CLASSIFICATION. There are hundreds of peripheral neuropathies. Reflecting the scope of PNS activity, symptoms may involve sensory, motor, or autonomic functions. To aid in diagnosis and treatment, the symptoms are classified into principal neuropathic syndromes based on the type of affected nerves and how long symptoms have been developing. Acute development refers to symptoms that have appeared within days, and subacute refers to those that have evolved over a number of weeks. Early chronic symptoms are those that take months to a few years to develop, and late chronic symptoms have been present for several years.

The classification system is composed of six principal neuropathic syndromes, which are subdivided into more specific categories. By narrowing down the possible diagnoses in this way, specific medical tests can be used more efficiently and effectively. The six syndromes and a few associated causes are listed below:

  • Acute motor paralysis, accompanied by variable problems with sensory and autonomic functions. Neuropathies associated with this syndrome are mainly accompanied by motor nerve problems, but the sensory and autonomic nerves may also be involved. Associated disorders include Guillain-Barré syndrome, diphtheritic polyneuropathy, and porphyritic neuropathy.
  • Subacute sensorimotor paralysis. The term sensorimotor refers to neuropathies that are mainly characterized by sensory symptoms, but also have a minor component of motor nerve problems. Poisoning with heavy metals (e.g., lead, mercury, and arsenic), chemicals, or drugs are linked to this syndrome. Diabetes, Lyme disease, and malnutrition are also possible causes.
  • Chronic sensorimotor paralysis. Physical symptoms may resemble those in the above syndrome, but the time scale of symptom development is extended. This syndrome encompasses neuropathies arising from cancers, diabetes, leprosy, inherited neurologic and metabolic disorders, and hypothyroidism.
  • Neuropathy associated with mitochondrial diseases. Mitochondria are organellesstructures within cellsresponsible for handling a cell's energy requirements. If the mitochondria are damaged or destroyed, the cell's energy requirements are not met and it can die.
  • Recurrent or relapsing polyneuropathy. This syndrome covers neuropathies that affect several nerves and may come and go, such as Guillain-Barré syndrome, porphyria, and chronic inflammatory demyelinating polyneuropathy.
  • Mononeuropathy or plexopathy. Nerve damage associated with this syndrome is limited to a single nerve or a few closely associated nerves. Neuropathies related to physical injury to the nerve, such as carpal tunnel syndrome and sciatica, are included in this syndrome.

Causes and symptoms

Typical symptoms of neuropathy are related to the type of affected nerve. If a sensory nerve is damaged, common symptoms include numbness, tingling in the area, a prickling sensation, or pain. Pain associated with neuropathy can be quite intense and may be described as cutting, stabbing, crushing, or burning. In some cases, a nonpainful stimulus may be perceived as excruciating or pain may be felt even in the absence of a stimulus. Damage to a motor nerve is usually indicated by weakness in the affected area. If the problem with the motor nerve has continued over a length of time, muscle shrinkage (atrophy) or lack of muscle tone may be noticeable. Autonomic nerve damage is most noticeable when an individual stands upright and experiences problems such as light-headedness or changes in blood pressure. Other indicators of autonomic nerve damage are lack of sweat, tears, and saliva; constipation; urinary retention; and impotence. In some cases, heart beat irregularities and respiratory problems can develop.

Symptoms may appear over days, weeks, months, or years. Their duration and the ultimate outcome of the neuropathy are linked to the cause of the nerve damage. Potential causes include diseases, physical injuries, poisoning, and malnutrition or alcohol abuse. In some cases, neuropathy is not the primary disorder, but a symptom of an underlying disease.


Diseases that cause peripheral neuropathies may either be acquired or inherited; in some cases, it is difficult to make that distinction. The diabetes-peripheral neuropathy link has been well established. A typical pattern of diabetes-associated neuropathic symptoms includes sensory effects that first begin in the feet. The associated pain or pins-and-needles, burning, crawling, or prickling sensations form a typical "stocking" distribution in the feet and lower legs. Other diabetic neuropathies affect the autonomic nerves and have potentially fatal cardiovascular complications.

Several other metabolic diseases have a strong association with peripheral neuropathy. Uremia, or chronic kidney failure, carries a 10-90% risk of eventually developing neuropathy, and there may be an association between liver failure and peripheral neuropathy. Accumulation of lipids inside blood vessels (atherosclerosis ) can choke-off blood supply to certain peripheral nerves. Without oxygen and nutrients, the nerves slowly die. Mild polyneuropathy may develop in persons with low thyroid hormone levels. Individuals with abnormally enlarged skeletal extremities (acromegaly), caused by an overabundance of growth hormone, may also develop mild polyneuropathy.

Neuropathy can also result from severe vasculitides, a group of disorders in which blood vessels are inflamed. When the blood vessels are inflamed or damaged, blood supply to the nerve can be affected, injuring the nerve.

Both viral and bacterial infections have been implicated in peripheral neuropathy. Leprosy is caused by the bacteria M. leprae, which directly attack sensory nerves. Other bacterial illness may set the stage for an immune-mediated attack on the nerves. For example, one theory about Guillain-Barré syndrome involves complications following infection with Campylobacter jejuni, a bacterium commonly associated with food poisoning. This bacterium carries a protein that closely resembles components of myelin. The immune system launches an attack against the bacteria; but, according to the theory, the immune system confuses the myelin with the bacteria in some cases and attacks the myelin sheath as well. The underlying cause of neuropathy associated with Lyme disease is unknown; the bacteria may either promote an immune-mediated attack on the nerve or inflict damage directly.

Infection with certain viruses is associated with extremely painful sensory neuropathies. A primary example of such a neuropathy is caused by shingles. After a case of chickenpox, the causative virus, varicella-zoster virus, becomes inactive in sensory nerves. Years later, the virus may be reactivated. Once reactivated, it attacks and destroys axons. Infection with HIV is also associated with peripheral neuropathy, but the type of neuropathy that develops can vary. Some HIV-linked neuropathies are noted for myelin destruction rather than axonal degradation. Also, HIV infection is frequently accompanied by other infections, both bacterial and viral, that are associated with neuropathy.

Several types of peripheral neuropathies are associated with inherited disorders. These inherited disorders may primarily involve the nervous system, or the effects on the nervous system may be secondary to an inherited metabolic disorder. Inherited neuropathies can fall into several of the principal syndromes, because symptoms may be sensory, motor, or autonomic. The inheritance patterns also vary, depending on the specific disorder. The development of inherited disorders is typically drawn out over several years and may herald a degenerative conditionthat is, a condition that becomes progressively worse over time. Even among specific disorders, there may be a degree of variability in inheritance patterns and symptoms. For example, Charcot-Marie-Tooth disease is usually inherited as an autosomal dominant disorder, but it can be autosomal recessive or, in rare cases, linked to the X chromosome. Its estimated frequency is approximately one in 2,500 people. Age of onset and sensory nerve involvement can vary between cases. The main symptom is a degeneration of the motor nerves in legs and arms, and resultant muscle atrophy. Other inherited neuropathies have a distinctly metabolic component. For example, in familial amyloid polyneuropathies, protein components that make up the myelin are constructed and deposited incorrectly.

Physical injury

Accidental falls and mishaps during sports and recreational activities are common causes of physical injuries that can result in peripheral neuropathy. The common types of injuries in these situations occur from placing too much pressure on the nerve, exceeding the nerve's capacity to stretch, blocking adequate blood supply of oxygen and nutrients to the nerve, and tearing the nerve. Pain may not always be immediately noticeable, and obvious signs of damage may take a while to develop.

These injuries usually affect one nerve or a group of closely associated nerves. For example, a common injury encountered in contact sports such as football is the "burner," or "stinger," syndrome. Typically, a stinger is caused by overstretching the main nerves that span from the neck into the arm. Immediate symptoms are numbness, tingling, and pain that travels down the arm, lasting only a minute or two. A single incident of a stinger is not dangerous, but recurrences can eventually cause permanent motor and sensory loss.


The poisons, or toxins, that cause peripheral neuropathy include drugs, industrial chemicals, and environmental toxins. Neuropathy that is caused by drugs usually involves sensory nerves on both sides of the body, particularly in the hands and feet, and pain is a common symptom. Neuropathy is an unusual side effect of medications; therefore, most people can use these drugs safely. A few of the drugs that have been linked with peripheral neuropathy include metronidazole, an antibiotic; phenytoin, an anticonvulsant; and simvastatin, a cholesterol-lowering medication.

Certain industrial chemicals have been shown to be poisonous to nerves (neurotoxic) following work-related exposures. Chemicals such as acrylamide, allyl chloride, and carbon disulfide have all been strongly linked to development of peripheral neuropathy. Organic compounds, such as N-hexane and toluene, are also encountered in work-related settings, as well as in glue-sniffing and solvent abuse. Either route of exposure can produce severe sensorimotor neuropathy that develops rapidly.

Heavy metals are the third group of toxins that cause peripheral neuropathy. Lead, arsenic, thallium, and mercury usually are not toxic in their elemental form, but rather as components in organic or inorganic compounds. The types of metal-induced neuropathies vary widely. Arsenic poisoning may mimic Guillain-Barré syndrome; lead affects motor nerves more than sensory nerves; thallium produces painful sensorimotor neuropathy; and the effects of mercury are seen in both the CNS and PNS.

Malnutrition and alcohol abuse

Burning, stabbing pains and numbness in the feet, and sometimes in the hands, are distinguishing features of alcoholic neuropathy. The level of alcohol consumption associated with this variety of peripheral neuropathy has been estimated as approximately 3 L of beer or 300 mL of liquor daily for three years. However, it is unclear whether alcohol alone is responsible for the neuropathic symptoms, because chronic alcoholism is strongly associated with malnutrition.

Malnutrition refers to an extreme lack of nutrients in the diet. It is unknown precisely which nutrient deficiencies cause peripheral neuropathies in alcoholics and famine and starvation patients, but it is suspected that the B vitamins have a significant role. For example, thiamine (vitamin B1) deficiency is the cause of beriberi, a neuropathic disease characterized by heart failure and painful polyneuropathy of sensory nerves. Vitamin E deficiency seems to have a role in both CNS and PNS neuropathy.


Clinical symptoms can indicate peripheral neuropathy, but an exact diagnosis requires a combination of medical history, medical tests, and possibly a process of exclusion. Certain symptoms can suggest a diagnosis, but more information is commonly needed. For example, painful, burning feet may be a symptom of alcohol abuse, diabetes, HIV infection, or an underlying malignant tumor, among other causes. Without further details, effective treatment would be difficult.

During a physical examination, an individual is asked to describe the symptoms very carefully. Detailed information about the location, nature, and duration of symptoms can help exclude some causes or even pinpoint the actual problem. The person's medical history may also provide clues as to the cause, because certain diseases and medications are linked to specific peripheral neuropathies. A medical history should also include information about diseases that run in the family, because some peripheral neuropathies are genetically linked. Information about hobbies, recreational activities, alcohol consumption, and work place activities can uncover possible injuries or exposures to poisonous substances.

The physical examination also includes blood tests, such as those that check levels of glucose and creatinine to detect diabetes and kidney problems, respectively. A blood count is also done to determine levels of different blood cell types. Iron, vitamin B12, and other factors may be measured as well, to rule out malnutrition. More specific tests, such as an assay for heavy metals or poisonous substances, or tests to detect vasculitis, are not typically done unless there is reason to suspect a particular cause.

An individual with neuropathy may be sent to a doctor that specializes in nervous system disorders (neurologist). By considering the results of the physical examination and observations of the referring doctor, the neurologist may be able to narrow down the possible diagnoses. Additional tests, such as nerve conduction studies and electromyography, which tests muscle reactions, can confirm that nerve damage has occurred and may also be able to indicate the nature of the damage. For example, some neuropathies are characterized by destruction of the myelin. This type of damage is shown by slowed nerve conduction. If the axon itself has suffered damage, the nerve conduction may be slowed, but it will also be diminished in strength. Electromyography adds further information by measuring nerve conduction and muscle response, which determines whether the symptoms are due to a neuropathy or to a muscle disorder.

In approximately 10% of peripheral neuropathy cases, a nerve biopsy may be helpful. In this test, a small part of the nerve is surgically removed and examined under a microscope. This procedure is usually the most helpful in confirming a suspected diagnosis, rather than as a diagnostic procedure by itself.


Treat the cause

Attacking the underlying cause of the neuropathy can prevent further nerve damage and may allow for a better recovery. For example, in cases of bacterial infection such as leprosy or Lyme disease, antibiotics may be given to destroy the infectious bacteria. Viral infections are more difficult to treat, because antibiotics are not effective against them. Neuropathies associated with drugs, chemicals, and toxins are treated in part by stopping exposure to the damaging agent. Chemicals such as ethylenediaminetetraacetic acid (EDTA) are used to help the body concentrate and excrete some toxins. Diabetic neuropathies may be treated by gaining better control of blood sugar levels, but chronic kidney failure may require dialysis or even kidney transplant to prevent or reduce nerve damage. In some cases, such as compression injury or tumors, surgery may be considered to relieve pressure on a nerve.

In a crisis situation, as in the onset of Guillain-Barré syndrome, plasma exchange, intravenous immunoglobulin, and steroids may be given. Intubation, in which a tube is inserted into the trachea to maintain an open airway, and ventilation may be required to support the respiratory system. Treatment may focus more on symptom management than on combating the underlying cause, at least until a definitive diagnosis has been made.

Supportive care and long-term therapy

Some peripheral neuropathies cannot be resolved or require time for resolution. In these cases, long-term monitoring and supportive care is necessary. Medical tests may be repeated to chart the progress of the neuropathy. If autonomic nerve involvement is a concern, regular monitoring of the cardiovascular system may be carried out.

Because pain is associated with many of the neuropathies, a pain management plan may need to be mapped out, especially if the pain becomes chronic. As in any chronic disease, narcotics are best avoided. Agents that may be helpful in neuropathic pain include amitriptyline, carbamazepine, and capsaicin cream. Physical therapy and physician-directed exercises can help maintain or improve function. In cases in which motor nerves are affected, braces and other supportive equipment can aid an individual's ability to move about.


The outcome for peripheral neuropathy depends heavily on the cause. Peripheral neuropathy ranges from a reversible problem to a potentially fatal complication. In the best cases, a damaged nerve regenerates. Nerve cells cannot be replaced if they are killed, but they are capable of recovering from damage. The extent of recovery is tied to the extent of the damage and a person's age and general health status. Recovery can take weeks to years, because neurons grow very slowly. Full recovery may not be possible and it may also not be possible to determine the prognosis at the outset.

If the neuropathy is a degenerative condition, such as Charcot-Marie-Tooth disease, an individual's condition will become worse. There may be periods of time when the disease seems to reach a plateau, but cures have not yet been discovered for many of these degenerative diseases. Therefore, continued symptoms, potentially worsening to disabilities are to be expected.


Afferent Refers to peripheral nerves that transmit signals to the spinal cord and the brain. These nerves carry out sensory function.

Autonomic Refers to peripheral nerves that carry signals from the brain and that control involuntary actions in the body, such as the beating of the heart.

Autosomal dominant or autosomal recessive Refers to the inheritance pattern of a gene on a chromosome other than X or Y. Genes are inherited in pairsone gene from each parent. However, the inheritance may not be equal, and one gene may overshadow the other in determining the final form of the encoded characteristic. The gene that overshadows the other is called the dominant gene; the overshadowed gene is the recessive one.

Axon A long, threadlike projection that is part of a nerve cell.

Central nervous system (CNS) The part of the nervous system that includes the brain and the spinal cord.

Efferent Refers to peripheral nerves that carry signals away from the brain and spinal cord. These nerves carry out motor and autonomic functions.

Electromyography A medical test that assesses nerve signals and muscle reactions. It can determine if there is a disorder with the nerve or if the muscle is not capable of responding.

Inheritance pattern Refers to dominant or recessive inheritance.

Motor Refers to peripheral nerves that control voluntary movements, such as moving the arms and legs.

Myelin The protective coating on axons.

Nerve biopsy A medical test in which a small portion of a damaged nerve is surgically removed and examined under a microscope.

Nerve conduction The speed and strength of a signal being transmitted by nerve cells. Testing these factors can reveal the nature of nerve injury, such as damage to nerve cells or to the protective myelin sheath.

Neurotransmitter Chemicals within the nervous system that transmit information from or between nerve cells.

Peripheral nervous system (PNS) Nerves that are outside of the brain and spinal cord.

Sensory Refers to peripheral nerves that transmit information from the senses to the brain.

A few peripheral neuropathies are eventually fatal. Fatalities have been associated with some cases of diphtheria, botulism, and others. Some diseases associated with neuropathy may also be fatal, but the ultimate cause of death is not necessarily related to the neuropathy, such as with cancer.


Peripheral neuropathies are preventable only to the extent that the underlying causes are preventable. Steps that a person can take to prevent potential problems include vaccines against diseases that cause neuropathy, such as polio and diphtheria. Treatment for physical injuries in a timely manner can help prevent permanent or worsening damage to nerves. Precautions when using certain chemicals and drugs are well advised in order to prevent exposure to neurotoxic agents. Control of chronic diseases such as diabetes may also reduce the chances of developing peripheral neuropathy.

Although not a preventive measure, genetic screening can serve as an early warning for potential problems. Genetic screening is available for some inherited conditions, but not all. In some cases, presence of a particular gene may not mean that a person will necessarily develop the disease, because there may be environmental and other components involved.



American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383.

Myelin Project Headquarters. Suite 225, 2001 Pennsylvania Ave., N.W., Washington, D.C. 20006-1850. (202) 452-8994.

Neuropathy Association. 60 E. 42nd St., Suite 942, New York, NY 10165. (800) 247-6968.

Peripheral Neuropathy

views updated May 23 2018

Peripheral neuropathy


Peripheral neuropathy is a condition involving the nerves of the peripheral portion of the nervous system. Neurobiologists describe the peripheral nervous system as any part of that system found in the arms or legs. The nerves that traverse the arms and legs occur in fibrous groups identified from the vascular system by their whitish color. These nerve tracts, or bundles of similar type nerve cell fibers, exit the brain and spinal cord from the intervertebral spaces in the spinal column to the rest of the body. The majority of the peripheral nerves are responsible for sensations such as touch, pain , and temperature. There is a greater concentration of particular types of nerve cells located in both the hands and feet. This concentration is a result of the need for sensory integration with the numerous small muscles and intricacy of movement in these regions of the body.

When certain traumatic conditions exist in the peripheral nerves, some people experience a highly uncomfortable condition in which they describe sensations as burning, tingling, shooting pain, overall persistent pain, and a wide variety of additional discomforting sensations. When this condition this persistent, it is called peripheral neuropathy. Peripheral neuropathy is also known as somatic neuropathy or distal sensory polyneuropathy.

This disorder is primarily recorded in persons with diabetes, compromised immune systems, or those who have suffered some sort of injury to these nerves. The traumas can range from overexposure to certain chemical toxins, penetration injury, fractures, staying in one position too long, severe impact, or even prolonged compression, as in the wearing of inappropriate footwear. Athletes who use their feet in sports such as tennis, basketball, soccer, or any running exercise are at moderate-to-severe risk. Among those with diabetes and HIV the risk is highest. As a result of high computer usage, the incidence of carpal tunnel syndrome , a type of peripheral neuropathy, is rising.

Many researchers assume the condition itself is caused by the loss of myelin (a waxy type substance) along the axon of the nerve cell. The role of myelin will be discussed later in the description of the nerves themselves. As a result of this loss of myelin, patients describe a variety of symptoms such as those previously described. A variety of initial complaint descriptions like aching, throbbing, the feeling of cold such as frostbite or even heat sensation so severe some patients compare it to "walking on a bed of coals," are the first clues to the possibility of advancing neuropathy.

Because the initial symptoms are similar to many other disorders, doctors are sometimes hesitant to diagnose peripheral neuropathy until the disease has reached a more advanced stage. By that time rehabilitation and treatment may take longer and be less effective.


Many persons with peripheral neuropathy in the legs experience an inability to walk properly. The incidence of injuries from falling increase, and affected persons may eventually develop a shuffling-type gait. In the hands, many people with this disorder must wear a brace or some sort of support. They lack their previous dexterity and fingers become numb. Manual tasks become difficult or almost impossible.

This disease may affect the nerves in several ways. If a single nerve is involved, the condition is called mononeuropathy. This condition is considered rare as it is unusual to find a condition in which only a single nerve maybe involved. Trauma is likely to involve multiple neurons and toxins or diabetes will most likely produce a global reaction.

Another condition likely to exist is one in which two or more nerves in separate areas of the body are affected. This case is described as multiple mononeuropathy. While this is still a less frequent scenario it is more common that the disease will occur in the same areas of either side of the body. This situation is more common when the cause is systemic rather than a physical injury.

Most often many nerves in the same vicinity are simultaneously involved, which is known as polyneuropathy. This is the most common expression of the disorder. Damage to nerve fibers may eventually result in loss of motor function or a reduction in proprioceptive or sensation types of responses. This type of neuropathy causes the greatest distress among patients. Treatment is difficult and often the nerve damage is irreversible. A halt to the advancement of the disease is one of the most promising types of relief a patient can expect.


Statistics on the occurrence of this disorder are not always reliable. Because peripheral neuropathy can accompany a great number of other disorders, many cases go undiagnosed. Carpal tunnel syndrome, which is on the increase, is just one form of peripheral neuropathy and affects millions of people worldwide. There is evidence that some forms of this disease are inherited. Those neuropathies that are inherited are called either sensorimotor neuropathies or sensory neuropathies.

Race has not been found as a contributing factor in the onset of peripheral neuropathy. In fact, the only risk factors aside from inheritance are those that result from traumas, reaction to toxic substances, and malnutrition. While malnutrition has been erroneously paired with certain social demographics this does not necessarily mean that those who suffer from inadequate nutritional intake are more susceptible. Trauma and associated diseases, such as diabetes and HIV, are the major factors associated with this neuropathy. The occurrence of peripheral neuropathy is about 2,400 cases per 100,000 population (2.4%). However with continued aging the rates increase to about 8,000 per 100,000 people (8%).

Causes and symptoms

One of the more prevalent and reasonable descriptions of how the disease is caused lies in the declining myelination of the actual nerve cells and fibers. In order to illustrate this condition, a discussion of one of the more common and most often discussed type of nerve cell will aid in the understanding of this type of neuropathy. The motor neuron, which is responsible for the initiation of movement, is a large nerve cell with a body and a long extension called the axon. The cell terminates at the end of the axon into a branched formation from which neurotransmitters are released to stimulate other motor neurons. The axon is the region of the cell along which electrical signals are passed. These electrical impulses are generated in the cell body and travel at high speeds to the ends of the neuron. The branched ends, called the synaptic end bulbs release acetylcholine which, in turn, activates the next cell body to produce an electrical signal and on down the fiber of a new nerve cell in the tract.

A waxy lipid is generated inside a specialized cell, the Schwann cell, that wraps around the axon of the nerve cell. Many Schwann cells grow along the axon and act as a kind of insulation for the nerve cell. The Schwann cells assure that the electric charge goes where the central nervous system (CNS) intends it to go. In diseases such as multiple sclerosis , the degeneration and death of these Schwann cells cause CNS electrical signals to go in random directions, preventing the muscles from responding properly.

It is assumed that in peripheral neuropathy the same sort of condition may occur. Whether due to trauma or a reaction to toxins, the myelin appears to start disappearing in many nerve cells and the otherwise contained electrical signals spread throughout the affected region. In turn, the neighboring neurons receive an overstimulation of random impulses and movement is impaired.

Muscle weakness is one of the first symptoms of peripheral neuropathy and is maximized soon after the beginning of the disease or about three to four weeks after onset. Sensory nerve cells, especially those that transmit pain are overstimulated and can cause severe aching and shooting pains, including the feeling of extreme cold or heat. Misdirected signals can cause cramping in advanced stages.


Once a physician suspects a patient may be affected with from peripheral neuropathy, the diagnosis can be confirmed by a series of tests. An EMG (a recording of electrical activity in the muscles) allows the physician to see how much of a small electrical current passing through a suspected nerve region is lost due to damage in the nerves. The difference in electrical charge from its origin to its endpoint provides a measure of potential damage.

Nerve conduction tests are performed by having a machine determine the speed at which a nerve impulse passes through a nerve region. The slower the passage, the greater the neuropathy. This may relate to the loss of myelin around the nerve axons and fibers or actual physical damage. Nerve biopsies are performed in the more serious conditions. The biopsy will permit the physician to see the actual condition of the nerve and rule out other causes for the pain the patient experiences.

Finally, a simple blood test can be administered. Toxins that may damage nerves are screened for. Vitamin levels are observed since nutrition may be a causative factor. Vitamin B6 has been demonstrated in some studies to be toxic for some patients with peripheral neuropathy. A diabetic condition is examined for presence or absence or degree of severity.

For persons with HIV, certain drugs such as didanosine (ddI, Videx), zalcitabine (ddC, Hivid), and stavudine (d4T, Zerit) are common culprits in the occurrence of peripheral neuropathy. Not everyone taking these drugs will acquire peripheral neuropathy, but those with the disease appear to have had a damaging response to these chemicals. Additionally, in some cases, alcohol consumption may be a contributing factor.

Treatment team

The family physician and a neurologist are the traditional specialists in recognizing and treating peripheral neuropathy. Alternative therapists include nutritionists and acupuncturists, who also have found a place among those seeking treatment for peripheral neuropathy. One thing agreed upon is that peripheral neuropathy is often treatable. Better results occur with those patients who receive an early diagnosis and are younger, although physical therapists working with patients in all stages of the disease have reported improvement over time.


A variety of treatments are available to patients with peripheral neuropathy. Some report a significant degree of improvement after taking higher doses of vitamin B12. Physical therapies and exercise influence the nerves to respond to correct stimuli and decrease the loss of myelin. Treatment is aimed at two goals. The first is to try and alleviate or eliminate the cause of the underlying disease. The second is to relieve its symptoms. Painkillers are often prescribed (including morphine) for the most severe cases. Prosthetic devices can be used when muscle weakness has reduced a person's ability to walk.

Managing diabetes is extremely important in those patients who have developed peripheral neuropathy as a symptom of the disease. Good nutrition, exercise, and avoiding alcohol are highly recommended. Those with HIV may experiment with alternate therapies and, again, focus on good nutrition and exercise.

Recovery and rehabilitation

The recovery from peripheral neuropathy varies. Those who are diagnosed early stand a better chance of a full recovery than those who are diagnosed after the disease has progressed over a long period. While not all cases are reversible, many patients have made a full recovery with proper treatment. For many, a halt in the progression of the disease is highly possible and often achieved. No quick cures have been found, however, and those who do improve do so after a great deal of work and commitment to recovery.

One of the aspects of the disease not often discussed is the emotional and psychological impact this disease has on its sufferers. Many find the constant pain an unbearable condition and are left to live a life dependent on pain-killing drugs. Others are distraught at the loss of movement and weakness that accompany the disorder. For these patients, there are support groups and websites devoted to the sharing of ideas and promising new therapies. Relatives and friends can be very supportive in recognizing that this is a real and diagnosable disease with proven treatments. Peripheral neuropathy is not an imaginary condition and it is not only possible to find cessation from advancing symptoms, but a partial if not total recovery.

Clinical trials

Many clinical trials are underway to search for treatments and prevention methods for peripheral neuropathy. A clinical trial is a research study designed to test or target a specific aspect of a research topic. They are designed to ask and attempt to answer very specific questions about the causation and new therapies for medical or other research types of questions. Many new vaccines or new ways of using known treatments for a specific pathology have been discovered in clinical trials. They are often the source of new drug therapies or alternate types of treatment. Often, the criteria for entering a clinical trial is very specific, but the results can prove to be enormously helpful.

Some of the current clinical trials for peripheral neuropathy include the following: The University of Chicago is undertaking two separate clinical trials for the study of a particular drug's effectiveness in relieving the pain of diabetic peripheral neuropathy, as well as slowing the rate of progression. Washington University of St. Louis School of Medicine is sponsoring a trial to study treatments for those with peripheral neuropathy resulting from HIV infection. Information on these studies and other ongoing clinical trials can be found at the National Institutes of Health website for clinical trials at <>.


Prognosis varies for persons with peripheral neuropathy. Quick identification and diagnosis is critical to beginning therapies in the early phases of the disease. Age is also a contributing factor, as younger persons fare better than older patients when they follow a multi-disciplinary approach to the disease. However, most patients can find a degree of relief from symptoms and the advancement of the disease.

Special concerns

While there are many cases in which peripheral neuropathy is unavoidable, most podiatrists recommend good foot hygiene. Recommendations include using appropriate and supportive footwear. Support measures such as arch and wrist braces may help in prevention of some types of peripheral neuropathy. If a person finds that one of the conditions of their employment is repetitive motion of the hand, as in typing, newer more ergonomic types of keyboards may reduce pressure on the nerves associated with carpal tunnel syndrome.



Golovchinsky, Vladimir. Double-Crush Syndrome. Hingham, MA: Kluwer Academic Publishers, 2000.

Senneff, John A. Numb Toes and Aching Soles: Coping with Peripheral Neuropathy. San Antonio, TX: Medpress, 1999.

Stewart, John D. and M. M. Stewart. Focal Peripheral Neuropathies, 3rd ed. New York: Lippincott Williams & Wilkins Publishers, 2000.


National Institute of Diabetes and Digestive and Kidney Diseases. " Diabetic Neuropathies: The Nerve Damage of Diabetes." January 4, 2004 (June 1, 2004). <>. "

Nerve and Muscle Disease; Peripheral Neuropathy." The Cleveland Clinic Neurosciences Center. May 15, 2004 (June 1, 2004). <>. "

NINDS Peripheral Neuropathy Information Page." National Institute of Neurological Disorders and Stroke. May 15, 2004 (June 1, 2004). <>. "

Peripheral Neuropathy." AIDS Education Global Information System. May 15, 2004 (June 1, 2004). <>.


National Institute of Neurological Disorders and Stroke (NINDS). P.O. Box 5801, Bethesda, MD 20824. (800) 352-9424. <>.

The Neuropathy Association. 60 E. 42nd Street, Suite 942, New York, NY 10165-0999. (212) 692-0662. [email protected] <>.

Brook Ellen Hall, PhD

Peripheral Neuropathy

views updated May 29 2018

Peripheral neuropathy


Peripheral neuropathy, sometimes called peripheral neuritis, is damage to the nerves that connect peripheral (outlying) portions of the body (especially the hands, arms, legs, and feet) to the central nervous system. It may involve only one peripheral nerve (mononeuropathy) or several nerves (polyneuropathy).


Similar to electrical wiring in a house, the body has a highly complex network of nerves made up of bundles of neurons, axons, and dendrites. This network originates in the brain and extends down through the spinal cord. These nerves branch off at junctures along this pathway to connect each portion of the body to the brain and spinal cord, the central nervous system. Nerves relay necessary information to and from every area, notifying the brain of sensations and external conditions. The brain, in turn, sends messages back to those areas. With peripheral neuropathy, damage has occurred to the nerves that connect peripheral portions of the body, and the patient feels pain or numbness.

Peripheral neuropathy is not usually considered a disease. It is more often thought of as a symptom of other diseases or conditions, or results from damage caused by the introduction of toxic substances. There are an estimated two million Americans who suffer from peripheral neuropathy. It becomes more common as people age, and the majority of its victims are 65 years old or older.

Causes & symptoms

The symptoms of peripheral neuropathy depend upon which type of nerve fiber is affected. Sensory nerve fiber damage is more likely to generate various sensations, while motor nerve fiber is more apt to result in weakening and wasting of muscle tissue in the affected area. It is a condition that develops quite gradually, usually over a period of months or even years. A tingling, prickly sensation in the toes and/or feet is commonly the first sign that is noticed, or there may be numbness in this area. Typically this feeling progresses to the lower legs, fingers, hands, arms, and then the trunk of the body in severe cases. As the situation worsens, the tingling sensation feels more like burning or severe discomfort followed by sharp, almost electric shock-like jabs of pain . These sensations may begin in the toes and feet, and then progress to other affected areas. Later symptoms often include increasing muscle weakness, poor coordination, numbness, and lack of feeling. Urinary incontinence, diarrhea, constipation, impotence , and postural hypotension (dramatic drops in blood pressure when a person stands) causing dizziness or dangerous falls are other potential negative effects, especially in the elderly.

Peripheral nerves are extended and delicate, easily damaged by a variety of things. Diabetes, alcoholism , diseases of the autoimmune system such as rheumatoid arthritis and lupus, and exposure to health damaging substances can cause peripheral neuropathy. Chronic liver and kidney disease, thyroid gland imbalances, bacterial or viral infections , and cancer can also cause the damage. Many of the strong anticancer drugs used and certain vitamin deficiencies can also lead to this condition. Repetitive mechanical actions that put pressure on a particular nerve, like the wrist in carpal-tunnel syndrome, or even inherited abnormalities in the body can cause peripheral neuropathy. However, in many cases no one single reason for this condition can be found.

Guillain-Barre syndrome, also called acute polyneuritis or ascending paralysis, is the only form of peripheral neuropathy that develops differently. It is a rare and very serious form that is believed to be caused by an autoimmune reaction to infection. Its primary difference from other types of peripheral neuropathy is the terrific rapidity of its onset.

A few rare forms of peripheral neuropathy are inherited. The best known inherited peripheral neuropathy is called Charcot-Marie-Tooth syndrome, or CMT. More than 20 different genes and loci on human chromosomes are now known to be associated with CMT.


Because peripheral neuropathy can be caused by a variety of factors, outcomes vary depending upon the reason for the nerve damage. Some causes, such as vitamin or metabolic deficiencies, can be reversed if caught early; other causes may not be reversible. Because of these factors, early diagnosis is very important. A neurologist (a doctor who specializes in the nervous system) can diagnose the disorder, try to determine the cause, and assess the extent of the damage. Sensations of pain, temperature, and touch in various parts of the body are tested by observing the person's ability to respond to a stimulus. If areas of either hypersensitivity or loss of sensation are found, the boundaries of that feeling are mapped by further testing.

An electromyogram (EMG) tests the electrical activity occurring in muscles and can be used in the diagnostic process. X rays, blood tests, and muscle biopsies are common tests used in determining the cause of peripheral neuropathy. For example, blood tests that show elevated blood sugar would indicate diabetes, or elevated liver function tests or thyroid levels could indicate liver or thyroid disease.


Treating the underlying cause of the peripheral neuropathy is the key to reversing this condition. For example, diabetics who closely follow their diabetic diet and keep their blood sugar in good control stand the best chance of recovering. Nutritional deficiencies often related to alcoholism may indicate that the person needs to stop drinking and requires vitamin supplements. Changes in lifestyle or treatment of the disease condition causing the neuropathy is a highly important facet of reversing, arresting, or simply reducing the symptoms of this uncomfortable condition.

Several simple self-care actions can also relieve symptoms. They include:

  • That shoes and stockings should never be tight, but rather loose cotton socks and shoes with good support and padding should be worn. Good foot care includes daily or twice daily foot soaks in tepid to cool water for 15 minutes followed by application of a moistening cream.
  • Keeping heavy bed covers off of feet at night either by turning back the covers or using a bed cradle.
  • Improving circulation and stimulating regeneration of nerves by frequently massaging the affected areas and walking as much as possible. Hydrotherapy with whirlpool baths may also be used to improve circulation.
  • Reducing the intake of caffeine and nicotine, both of which may increase pain.
  • Lowering the stress level as much as possible, including taking steps to treat the depression and/or insomnia that often accompany peripheral neuropathy. This may include relaxation therapies or herbal remedies.

Herbal remedies used for peripheral neuropathy include gingko, St. John's wort , vervain, oats, and gotu kola . Nutritional supplements that may provide relief and are thought to help repair nerve fibers include supplemental carnitine , gamma-linolenic acid, alpha-lipoic acid, magnesium, chromium , choline, inositol, vitamins B6 and B12, niacin, thiamine, biotin , and folic acid . Additional therapies thought to provide relief include detoxification and fasting , used to cleanse the system and eliminate poisons that may cause nerve damage.

Control of symptoms is a significant part of the treatment. Pain relief is usually the highest priority. Bodywork such as massage and movement therapies like t'ai chi and qigong may provide relief. Acupuncture can also be used to promote general health and provide some symptomatic relief. Meditation or yoga may help with relaxation and pain control.

Another alternative approach to peripheral neuropathy is the Feldenkrais method, which works on improving the patient's sense of balance, and thus helps to prevent falls.

Allopathic treatment

It may take months for the symptoms to subside. Milder pain can be treated with over-the-counter pain medications, including Tylenol or aspirin, while more severe episodes of pain may require pain relievers such as nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen, or narcotics such as codeine, Demerol, or morphine. Sometimes tricyclic antidepressants such as Elavil, Tofranil, or Norpramin are used both for pain relief and the depression that may accompany chronic pain. Anticonvulsant medications such as Tegretol, Neurontin, or Dilantin are effective against electric-like, jabbing pain. Less frequently used drugs include heart and blood pressure drugs such as Mexitil and clonidine, which may alleviate burning sensations.

The acute onset and potentially serious symptoms that can develop in Guillain-Barre syndrome, including nerve and muscle damage affecting swallowing and breathing, make this the type of peripheral neuropathy most likely to require in-patient hospital treatment. The person suffering from this syndrome must be carefully monitored, may require intubation in order to breathe, and may even have blood plasma removed in order to reduce the number of antibodies in the blood.

Expected results

Full recovery from peripheral neuropathy is possible if the nerves are not damaged beyond repair. The outcome is dependent upon the extent of damage. Research is now being conducted that may lead to the manufacture of substances similar to the naturally produced chemicals in the body that stimulate repair of small nerve fibers.

The majority of people suffering from Guillain-Barre syndrome recover completely, often without even receiving medical treatment, but some will develop residual, permanent weakness in the affected area or have further episodes.


The best way to prevent peripheral neuropathy is to treat the underlying disease or eliminate the toxic substance that may cause the symptoms.



Thomas, Clayton L., ed. Taber's Cyclopedic Medical Dictionary. F. A. Davis Co., 1997.


Kauffman, T. "Balance Falls Assessment: Low Tech to High Tech, Peripheral Neuropathy, and Alternative Considerations." The Gerontologist (October 15, 2001): 264.

Palau, F., A. Cuesta, L. Pedrola, et al. "Mutations in the Ganglioside-Induced Differentiation-Associated Protein 1 (GDAP1) Gene Cause Axonal Charcot-Marie-Tooth Disease." American Journal of Human Genetics 69 (October 2001): 196.


Joan Schonbeck

Rebecca J. Frey, PhD

peripheral neuropathy

views updated May 18 2018

peripheral neuropathy n. see neuropathy.