Peripheral Neuropathy
On this page:
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.
Return to top 
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 predominately motor neuropathy, predominately sensory
neuropathy, sensory-motor neuropathy, or autonomic neuropathy to
describe a patient's condition.
Return to top
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
oversensitized, 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.
Return to top
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.
Return to top
Diagnosing peripheral neuropathy is often difficult because the
symptoms are highly variable. A thorough neurological examination is
usually required and involves taking an extensive patient history
(including the patient's symptoms, work environment, social habits,
exposure to any toxins, history of alcoholism, risk of HIV or other
infectious disease, and family history of neurological disease),
performing tests that may identify the cause of the neuropathic
disorder, and conducting tests to determine the extent and type of
nerve damage.
A general physical examination and related tests may reveal the
presence of a systemic disease causing nerve damage. Blood tests can
detect diabetes, vitamin deficiencies, liver or kidney dysfunction,
other metabolic disorders, and signs of abnormal immune system
activity. An examination of cerebrospinal fluid that surrounds the
brain and spinal cord can reveal abnormal antibodies associated with
neuropathy. More specialized tests may reveal other blood or
cardiovascular diseases, connective tissue disorders, or
malignancies. Tests of muscle strength, as well as evidence of
cramps or fasciculations, indicate motor fiber involvement.
Evaluation of a patient's ability to register vibration, light
touch, body position, temperature, and pain reveals sensory nerve
damage and may indicate whether small or large sensory nerve fibers
are affected.
Based on the results of the neurological exam, physical exam,
patient history, and any previous screening or testing, additional
testing may be ordered to help determine the nature and extent of
the neuropathy.
Computed tomography, or CT scan, is a noninvasive, painless
process used to produce rapid, clear two-dimensional images of
organs, bones, and tissues. X-rays are passed through the body at
various angles and are detected by a computerized scanner. The data
is processed and displayed as cross-sectional images, or "slices,"
of the internal structure of the body or organ. Neurological CT
scans can detect bone and vascular irregularities, certain brain
tumors and cysts, herniated disks, encephalitis, spinal stenosis
(narrowing of the spinal canal), and other disorders.
Magnetic resonance imaging (MRI) can examine muscle quality and
size, detect any fatty replacement of muscle tissue, and determine
whether a nerve fiber has sustained compression damage. The MRI
equipment creates a strong magnetic field around the body. Radio
waves are then passed through the body to trigger a resonance signal
that can be detected at different angles within the body. A computer
processes this resonance into either a three-dimensional picture or
a two-dimensional "slice" of the scanned area.
Electromyography (EMG) involves inserting a fine needle into a
muscle to compare the amount of electrical activity present when
muscles are at rest and when they contract. EMG tests can help
differentiate between muscle and nerve disorders.
Nerve conduction velocity (NCV) tests can precisely measure the
degree of damage in larger nerve fibers, revealing whether symptoms
are being caused by degeneration of the myelin sheath or the axon.
During this test, a probe electrically stimulates a nerve fiber,
which responds by generating its own electrical impulse. An
electrode placed further along the nerve's pathway measures the
speed of impulse transmission along the axon. Slow transmission
rates and impulse blockage tend to indicate damage to the myelin
sheath, while a reduction in the strength of impulses is a sign of
axonal degeneration.
Nerve biopsy involves removing and examining a sample of nerve
tissue, most often from the lower leg. Although this test can
provide valuable information about the degree of nerve damage, it is
an invasive procedure that is difficult to perform and may itself
cause neuropathic side effects. Many experts do not believe that a
biopsy is always needed for diagnosis.
Skin biopsy is a test in which doctors remove a thin skin sample
and examine nerve fiber endings. This test offers some unique
advantages over NCV tests and nerve biopsy. Unlike NCV, it can
reveal damage present in smaller fibers; in contrast to conventional
nerve biopsy, skin biopsy is less invasive, has fewer side effects,
and is easier to perform.
Return to top
No medical treatments now exist that can cure inherited
peripheral neuropathy. However, there are therapies for many other
forms. Any underlying condition is treated first, followed by
symptomatic treatment. Peripheral nerves have the ability to
regenerate, as long as the nerve cell itself has not been killed.
Symptoms often can be controlled, and eliminating the causes of
specific forms of neuropathy often can prevent new damage.
In general, adopting healthy habits-such as maintaining optimal
weight, avoiding exposure to toxins, following a
physician-supervised exercise program, eating a balanced diet,
correcting vitamin deficiencies, and limiting or avoiding alcohol
consumption-can reduce the physical and emotional effects of
peripheral neuropathy. Active and passive forms of exercise can
reduce cramps, improve muscle strength, and prevent muscle wasting
in paralyzed limbs. Various dietary strategies can improve
gastrointestinal symptoms. Timely treatment of injury can help
prevent permanent damage. Quitting smoking is particularly important
because smoking constricts the blood vessels that supply nutrients
to the peripheral nerves and can worsen neuropathic symptoms.
Self-care skills such as meticulous foot care and careful wound
treatment in people with diabetes and others who have an impaired
ability to feel pain can alleviate symptoms and improve quality of
life. Such changes often create conditions that encourage nerve
regeneration.
Systemic diseases frequently require more complex treatments.
Strict control of blood glucose levels has been shown to reduce
neuropathic symptoms and help people with diabetic neuropathy avoid
further nerve damage. Inflammatory and autoimmune conditions leading
to neuropathy can be controlled in several ways. Immunosuppressive
drugs such as prednisone, cyclosporine, or azathioprine may be
beneficial. Plasmapheresis-a procedure in which blood is removed,
cleansed of immune system cells and antibodies, and then returned to
the body-can limit inflammation or suppress immune system activity.
High doses of immunoglobulins, proteins that function as antibodies,
also can suppress abnormal immune system activity.
Neuropathic pain is often difficult to control. Mild pain may
sometimes be alleviated by analgesics sold over the counter. Several
classes of drugs have recently proved helpful to many patients
suffering from more severe forms of chronic neuropathic pain. These
include mexiletine, a drug developed to correct irregular heart
rhythms (sometimes associated with severe side effects); several
antiepileptic drugs, including gabapentin, phenytoin, and
carbamazepine; and some classes of antidepressants, including
tricyclics such as amitriptyline. Injections of local anesthetics
such as lidocaine or topical patches containing lidocaine may
relieve more intractable pain. In the most severe cases, doctors can
surgically destroy nerves; however, the results are often temporary
and the procedure can lead to complications.
Mechanical aids can help reduce pain and lessen the impact of
physical disability. Hand or foot braces can compensate for muscle
weakness or alleviate nerve compression. Orthopedic shoes can
improve gait disturbances and help prevent foot injuries in people
with a loss of pain sensation. If breathing becomes severely
impaired, mechanical ventilation can provide essential life
support.
Surgical intervention often can provide immediate relief from
mononeuropathies caused by compression or entrapment injuries.
Repair of a slipped disk can reduce pressure on nerves where they
emerge from the spinal cord; the removal of benign or malignant
tumors can also alleviate damaging pressure on nerves. Nerve
entrapment often can be corrected by the surgical release of
ligaments or tendons.
Return to top
The National Institute of Neurological Disorders and Stroke
(NINDS), a component of the Federal government's National Institutes
of Health (NIH) within the U.S. Department of Health and Human
Services, has primary responsibility for research on peripheral
neuropathy. Current research projects funded by the NINDS involve
investigations of genetic factors associated with hereditary
neuropathies, studies of biological mechanisms involved in
diabetes-associated neuropathies, efforts to gain greater
understanding of how the immune system contributes to peripheral
nerve damage, and efforts to develop new therapies for neuropathic
symptoms.
Because specific genetic defects have been identified for only a
fraction of the known hereditary neuropathies, the Institute
sponsors studies to identify other genetic defects that may cause
these conditions. Presymptomatic diagnosis may lead to therapies for
preventing nerve damage before it occurs, and gene replacement
therapies could be developed to prevent or reduce cumulative nerve
damage.
Several NINDS-funded studies are investigating some of the
possible biological mechanisms responsible for the many forms of
neuropathy, including the autonomic neuropathies that affect people
with diabetes. The Institute also is funding studies to measure the
frequency and progression rates of diabetic neuropathies, examine
the effects of these disorders on quality of life, and identify
factors that may put certain individuals at greater risk for
developing diabetes-associated neuropathies.
Scientists have found that the destructive effects of abnormal
immune system activity cause many neuropathies for which a cause
could not previously be identified. However, the exact biological
mechanisms that lead to this nerve damage are not yet well
understood. Many NINDS-sponsored studies are studying inflammatory
neuropathies, both in research animals and in humans, to clarify
these mechanisms so that therapeutic interventions can be
developed.
Neuropathic pain is a primary target of NINDS-sponsored studies
aimed at developing more effective therapies for symptoms of
peripheral neuropathy. Some scientists hope to identify substances
that will block the brain chemicals that generate pain signals,
while others are investigating the pathways by which pain signals
reach the brain.
Studies of neurotrophic factors represent one of the most
promising areas of research aimed at finding new, more effective
treatments for peripheral neuropathies. These substances, produced
naturally by the body, protect neurons from injury and encourage
their survival. Neurotrophic factors also help maintain normal
function in mature nerve cells, and some stimulate axon
regeneration. Several NINDS-sponsored studies seek to learn more
about the effects of these powerful chemicals on the peripheral
nervous system and may eventually lead to treatments that can
reverse nerve damage and cure peripheral nerve disorders.
Return to top
BRAIN
Neuropathy Association
American Chronic Pain Association
(ACPA)
Charcot-Marie-Tooth
Association (CMTA)
Muscular Dystrophy Association
National Chronic Pain
Outreach Association (NCPOA)
American Diabetes Association
National Diabetes
Information Clearinghouse (NDIC)
Return to top
