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Peripheral neuropathy is a general term referring to disorders of peripheral nerves. The peripheral nervous system is made up of the nerves that branch out of the spinal cord to all parts of the body.

Peripheral nerve cells have three main parts: cell body, axons, and dendrites (nerve/muscle junctions). Any part of the nerve can be affected, but damage to axons is most common. The axon transmits signals from nerve cell to nerve cell or muscle. Most axons are surrounded by a substance called myelin, which facilitates signal transmission.

Peripheral neuropathy can be associated with poor nutrition, a number of diseases, and pressure or trauma. Many people suffer from the disorder without ever identifying the cause.

Incidence and Prevalence

Peripheral neuropathy affects at least 20 million people in the United States. Nearly 60% of all people with diabetes suffer from peripheral neuropathy.

Types of Neuropathy

Peripheral neuropathy can be broadly categorized by the type of nerve that has been damaged. The peripheral nervous system is made up of three types of nerves:

  • motor nerves (responsible for voluntary movement)
  • sensory nerves (responsible for sensing temperature, pain, touch, and limb positioning); including large and small fibers
  • autonomic nerves
    (responsible for involuntary functions such as breathing, blood pressure, sexual function, digestion)

Peripheral neuropathy also can be classified by where it occurs in the body. Nerve damage that occurs in one area of the body is called mononeuropathy, in many areas, polyneuropathy. When the disorder occurs in the same places on both sides of the body, the condition is called symmetric neuropathy.

It also can be categorized by cause, such as diabeic neuropathy  and nutritional neuropathy. When a cause cannot be identified, the condition is called idiopathic neuropathy.


Risk Factors and Causes

Peripheral neuropathy can be caused by disease; nerve compression, entrapment, or laceration; exposure to toxins; or inflammation. In many cases, especially in people over the age of 60, no cause can be determined.

Conditions associated with peripheral nerve damage include the following:

  • Alcoholism
  • Amyloidosis (metabolic disorder)
  • Autoimmune disorders (e.g., Guillain-Barre syndrome)
  • Bell's palsy
  • Cancer
  • Charcot-Marie-Tooth disease
  • Carpal tunnel syndrome
  • Chronic kidney failure
  • Connective tissue disease (e.g., rheumatoid arthritis, lupus, sarcoidosis)
  • Diabetes mellitus
  • Infectious disease (e.g., Lyme disease, HIV/AIDS, hepatitis B, leprosy)
  • Liver failure
  • Medications
  • Radiculopathy
  • Vitamin deficiencies (e.g., pernicious anemia)

Radiculopathy is the term for neuropathy that affects nerve roots. The nerve roots are extensions of spinal nerves. They exit the spinal canal through a space between vertebrae, called the neural foramen. Degeneration of vertebral bone, herniation of the pulpy disc between vertebrae, narrowing of the spinal column (spinal stenosis), or trauma can compress or cut nerve roots and cause neuropathy.

Signs and Symptoms

Symptoms depend on the type of nerve(s) affected (e.g., motor, sensory, autonomic) and where the nerve is located in the body. One or more types of nerve may be damaged.

Muscle weakness, cramps, and spasms are associated with motor nerve damage. In some cases, there may be loss of balance and coordination.

Sensory nerve damage can produce tingling, numbness, and pain. Pain associated with sensory nerve damage is variously described as:

  • Sensation of wearing an invisible "glove" or "sock"
  • Burning, freezing, or electric-like
  • Extreme sensitivity to touch

If the autonomic nerves are damaged, involuntary functions may be affected. Symptoms that can result from this type of damage include abnormal blood pressure and heart rate, reduced ability to perspire, constipation, bladder dysfunction (e.g., incontinence), and sexual dysfunction.

Some neuropathies develop suddenly; others progress slowly, even over a number of years. Severity varies among individuals and may vary in the same individual throughout the day. Symptoms generally are more severe at night.

Complications

Untreated peripheral neuropathy may result in permanent loss of nerve function, tissue damage, and muscle atrophy. It is important to receive proper treatment and management of this condition to reduce the risk for irreversible damage and other serious complications.

Chronic pain can cause sleeplessness and a decline in quality of life. Pain sufferers often experience a disruption in their ability to perform daily tasks and may suffer from depression. Symptoms of depression include:

  • apathy,
  • feelings of isolation and frustration, and
  • memory loss.


                            
Diagnosis

It is important to determine the cause of the neuropathy as quickly as possible to reduce the risk for permanent nerve damage. Diagnosis involves physical and neurological examination, nerve conduction velocity studies (NCV), and electromyography (EMG).

Nerve conduction velocity studies record the speed at which impulses travel through nerves and measure electrical responses. EMG records electrical activity in muscle tissue and is used to distinguish neuropathy from muscle disease (myopathy). These tests often are used in combination and are referred to as EMG/NCV studies.

When EMG/NCV studies are inconclusive, nerve, skin, or muscle biopsy may be performed to confirm the diagnosis. Biopsy involves removing nerve, skin, and/or muscle tissue for microscopic evaluation and chemical analysis.

Electroencephalography (EEG), spinal tap (lumbar puncture), blood and urine tests, and imaging tests (e.g., CT scan, MRI scan) may be performed to determine the underlying cause of the neuropathy and to rule out other conditions.

EEG measures electrical activity in the brain and is used to evaluate brain function and detect seizure disorders.

Spinal tap, or lumbar puncture, is performed to analyze cerebrospinal fluid (CSF). This test is used to rule out infectious disease (e.g., meningitis), high or low levels of CSF, and to detect abnormal protein levels. In this procedure, a needle is inserted between two lumbar (lower spine) vertebrae and cerebrospinal fluid is collected and analyzed.


Treatment

In many cases, prompt diagnosis and treatment of the underlying cause can reduce the risk for permanent nerve damage. For example, controlling diabetes may reduce diabetic neuropathy and renal dialysis often improves neuropathy that develops as a result of chronic renal failure.

Treatment options for reducing pain include medication, injection therapy, and physical therapy. Surgery may be needed to treat some causes of neuropathy (e.g., carpal tunnel syndrome, radiculopathy).

Medication

Because analgesics (e.g., aspirin, ibuprofen) are usually ineffective against pain caused by neuropathy, treatment often involves medications that target nerve cells.

Duloxetine hydrochloride (Cymbalta®) has been approved by the Food and Drug Administration (FDA) to treat diabetic peripheral neuropathy. Common side effects include constipation, diarrhea, dry mouth, and nausea. In some cases, Cymbalta® causes dizziness and hot flashes.

Although anticonvulsants such as gabapentin (Neurontin®) and topiramate (Topamax®) and antidepressants such as amitriptyline (Elavil®) are not approved by the FDA to treat neuropathy, they are often prescribed to treat this condition. Side effects of these drugs include drowsiness, dizziness, low blood pressure, and fatigue.

Other medications include anticonvulsants (e.g., carbamazepine [Tegretol®], lamotrigine [Lamictal®]), local anesthetics (e.g., lidocaine [Xylocaine®]), and antiarrhythmics (e.g., mexiletine [Mexitil®]). Anticonvulsants may cause low white blood cell counts, nausea, vomiting, and dizziness. Side effects of lidocaine and mexiletine include nervousness, lightheadedness, drowsiness, and double vision.

Topical treatment with capsaicin cream (Zostrix®) may be prescribed for patients with focal neuropathy. Capsaicin causes stinging upon application and is often combined with a local anesthetic to reduce this side effect. Axsain® (.25% capsaicin in Lidocare® vehicle) contains a higher dose of capsaicin in a cream that reduces stinging and burning. Lidoderm® (lidocaine patch 5%) has been shown to be helpful for localized areas of tingling or burning.

Pregabalin (Lyrica®) has been approved by the Food and Drug Administration (FDA) to treat post-herpetic neuralgia (shingles pain). Common side effects include drowsiness, dizziness, nausea, weight gain, and swelling (edema).

Injection Therapy

Injection therapy involves injecting a nerve block (e.g., lidocaine) into the area surrounding affected nerves, preventing the nerve from carrying impulses to the brain and temporarily reducing symptoms. Injection therapy is often used with other treatments (e.g., medication, physical therapy).

Other Treatments

Discontinuing medication and exposure to the substance may eliminate neuropathy caused by medication and toxins. Vitamin supplements (e.g., thiamine) and metafolin (Metanx®) may be used to treat nutritional neuropathy.

Physical Therapy (e.g., exercise, massage, heat) and acupuncture (i.e., insertion of fine needles into specific points on the body) may be used to treat symptoms.








www.consultantsinneurology.com

Raymond Rybicki, MD

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