What is peripheral neuropathy?
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
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.
How are the peripheral neuropathies classified?
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
What are the symptoms of peripheral 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 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
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What causes peripheral neuropathy?
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
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
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
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
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
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
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
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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How is peripheral neuropathy diagnosed?
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
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
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
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.
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What treatments are available?
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.
© 2010 Vivacare. Last updated July 30, 2010.
Reference: The National Institute of Neurological Disorders and Stroke