Definition

Peripheral neuropathy is damage to the peripheral nerves. Peripheral nerves are the nerves that connect your spinal cord to the rest of your body.

	Peripheral Nerves of the Foot
	© 2008 Nucleus Medical Art, Inc.

Causes

Many diseases and conditions can cause peripheral neuropathy. The damage may occur due to:

• Lack of oxygen
• Malnutrition
• Compression
• Cancer
• Trauma
• Inflammation
• Toxins
• Medications
• Unknown causes

Diseases that can damage peripheral nerves include:

• Diabetes ( type 1 or type 2 )
• Alcoholism
• AIDS
• Lyme disease
• Rheumatoid arthritis
• Uremia from chronic kidney failure
• Autoimmune disorders
• Hypothyroidism

Compression commonly occurs when nerves are pinched or trapped somewhere along their course. Examples include:

• Carpal tunnel syndrome (nerve in the wrist)
• Sciatica (nerve roots forming the sciatic nerve in the back of the legs as they exit the spine)

Toxins that can damage the peripheral nerves include:

• Lead
• Mercury
• Thallium
• Organic solvents (hexacarbons)
• Pesticides (organophosphates)
• Carbon disulfide
• Arsenic
• Acrylamide
• Diphtheria toxin
• Alcohol

Many medications can lead to peripheral neuropathy. A partial list includes:

• Chemotherapeutic agents to treat cancer ( vincristine , paclitaxel , cisplatin , suramin)
• Anti-HIV medications ( didanosine , zalcitabine )
• Anti-tuberculosis medications ( isoniazid , ethambutol )
• Other antimicrobial drugs ( dapsone , metronidazole , chloroquine, chloramphenicol )
• Psychiatric medications ( lithium )
• Other medications ( amiodarone , aurothioglucose, phenytoin , thalidomide , colchicine , cimetidine , disulfiram , hydralazine , high levels of vitamin B6)

Other causes of peripheral nerve damage include:

• Vitamin deficiencies (thiamin and B12 deficiency, often related to alcoholism, and vitamin E deficiency)
• Injury
• A tumor pressing on a nerve
• Exposure to cold or radiation
• Leprosy
• Acute or chronic demyelinating polyneuropathy
• Porphyria
• Paraneoplatic syndromes
• Genetic disorders ( Charcot-Marie-Tooth disease, Dejerine-Sottas disease, and Refsum’s disease)
• Prolonged treatment in the intensive care unit (usually associated with having a tube inserted for a long time and taking medications that paralyze muscles)

Risk Factors

A risk factor is something that increases your chance of getting a disease or condition. Risk factors for peripheral neuropathy include:

• Diabetes (about 60% of people with diabetes have peripheral neuropathy)
• Alcohol abuse
• Autoimmune diseases, such as rheumatoid arthritis or celiac sprue
• Family member with peripheral neuropathy
• Exposure to toxins or medications known to cause neuropathy
• Vitamin deficiency (thiamin and vitamin B12)
• HIV infection
• Pressure on a nerve (may occur with repetitive stress injuries)
• Hospitalization treatment in the intensive care unit

Symptoms

Damage to the peripheral nerves often results in sensory (feeling) and motor (strength) symptoms in the arms, legs, hands, and feet. However, it can affect any part of the body. Symptoms vary, depending on which nerves are involved.

Symptoms may range from mild to severe and may seem worse at night. Sensations and pain may occur in the upper or lower limbs and move toward the trunk (eg, from the feet to the calves).

Symptoms include:

• Numbness or reduced sensation
• Tingling
• Pain, often a burning or sharp, cutting sensation
• Sensitivity to touch
• Muscle twitches
• Muscle weakness
• Muscle cramping
• Difficulty with walking
• Loss of coordination or balance
• Paralysis

If untreated, peripheral neuropathy can lead to:

• Loss of reflexes and muscle control
• Muscle atrophy (loss of muscle bulk)
• Foot deformities
• Foot ulcers
• Injuries to the feet that go unnoticed and become infected
• Autonomic dysfunction (sweating, bowel and bladder dysfunction, cardiovascular effects)
• Difficulty breathing

Diagnosis

The doctor will ask about your symptoms and medical history, and perform a physical exam. The physical exam will include tests of:

• Muscle strength
• Reflexes
• Balance
• Coordination
• Ability to feel vibration, temperature, and light touch

Additional tests may also include:

• Blood tests (including glucose, vitamin B12 level, and thyroid function tests)
• Electromyography (EMG)—measurement and recording of electrical activity generated in muscle in response to a nervous stimulation
• Nerve conduction studies
• Nerve or muscle biopsy (rarely)
• Evaluation of family members
• Genetic testing
• Serum/urine electrophoresis (protein evaluation)
• Spinal tap for demyelinating disorders

Treatment

Treatment may include:

Treatment for the Underlying Illness or Exposure

Treating the underlying illness can decrease or eliminate symptoms. For instance, if it is caused by diabetes, controlling blood sugar levels may help. In some cases, neuropathy caused by medications or toxins is completely reversed when these substances are stopped or avoided. Correction of vitamin B12 deficiency often improves symptoms.

Physical Therapy

Certain exercises may help stretch shortened or contracted muscles and increase joint flexibility. In long-standing cases, splinting the joint may be required to protect and rest it, while maintaining proper alignment.

Patients may also benefit from orthotics (supports and braces) to help with deformities, balance issues, and muscle weakness. Maintaining physical activity is also key.

Medications

Prescription and over-the-counter (OTC) pain medications are often used to ease discomfort.

Drugs to treat depression and prevent convulsions sometimes relieve neuropathy symptoms. These medications are often given at lower dosages than those prescribed for depression and seizures .

Commonly used antidepressants include:

• Amitriptyline (Elavil)
• Nortriptyline (Pamelor)
• Desipramine (Norpramin)
• Imipramine (Tofranil)

Commonly used anticonvulsants may include:

• Gabapentin (Neurontin)
• Carbamazepine (Tegretol)
  • According to the Food and Drug Administration (FDA), patients of Asian ancestry who have a certain gene, called HLA-B*1502, and take carbamazepine are at risk for dangerous or even fatal skin reactions. If you are of Asian descent, the FDA recommends that you get tested for this gene before taking carbamazepine. If you have been taking this medication for a few months with no skin reactions, then you are at low risk of developing these reactions. Talk to your doctor before stopping this medication. *
• Pregabalin (Lyrica)—recently approved for peripheral neuropathy

Some peripheral neuropathies that are severe and potentially life-threatening (such as Guillain-Barre syndrome ) require treatment with steroids (such as prednisone ) and intravenous immunoglobulins.

Other Therapies

These therapies are aimed at reducing symptoms and may include:

• Relaxation training
• Biofeedback
• Walking
• Exercise
• Yoga
• Warm baths
• Massage
• Acupuncture
• Transcutaneous electronic nerve stimulation

Surgery

Surgery can relieve the pressure on nerves. For example, surgeons commonly release fibrous bands in the wrist to treat carpal tunnel syndrome .

Prevention

• Manage chronic medical conditions with the help of your doctor. If you have diabetes, you should visit a podiatrist for yearly exams.
• Eat a healthful diet, one that is low in saturated fat and rich in whole grains, fruits, and vegetables.
• Be sure to get recommended amounts of thiamin and vitamin B12.
• Limit your alcohol intake to a moderate level. Moderate is two or fewer drinks per day for men and one or fewer for women and older adults
• Avoid:
  • Toxic chemicals
  • Repetitive movements
  • Prolonged pressure on joints, especially elbows and knees

RESOURCES:

American Chronic Pain Association
http://www.theacpa.org

The Neuropathy Association
http://www.neuropathy.org

CANADIAN RESOURCES:

Canadian Diabetes Association
http://www.diabetes.ca

Team Diabetes CanadaCanadian Diabetes Association
http://www.diabetes.ca/section_donations/TeamDiabetesIndex.asp

References:

Dyck PJ, Thomas PK, Dyck PJ, Thomas PK, eds. Peripheral Neuropathy . 4th ed. Saunders; 2004.

Merritt's Neurology . 11th ed. Lippincott Williams & Wilkins; 2005.

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health website. Available at: http://www.niddk.nih.gov/ .

National Institute of Neurological Disorders and Stroke, National Institutes of Health website. Available at: http://www.ninds.nih.gov/ .

Peripheral neuropathy. EBSCO DynaMed website. Available at: http://www.ebscohost.com/dynamed/what.php. Accessed May 12, 2008.

Samuels MA, Feske SK. Office Practice of Neurology . Philadelphia, PA: Churchill Livingstone; 2003.

Williams O. Introduction to and clinical evaluation of peripheral neuropathies. In: Gilman S, ed. MedLink Neurology. San Diego, CA: MedLink Corporation. Medlink website. Available at: http://www.medlink.com. Accessed May 12, 2008.

*12/20/2007 DynaMed's Systematic Literature Surveillance DynaMed's Systematic Literature Surveillance : 2007 safety alerts for drugs, biologics, medical devices, and dietary supplements: Carbamazepine (marketed as Carbatrol, Equetro, Tegretol and generics). Medwatch. US Food and Drug Administration website. Available at: http://www.fda.gov/medwatch/safety/2007/safety07.htm #carbamazepine .

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