Idiopathic Peripheral Neuropathy

Definition

Idiopathic neuropathy is a disorder that affects the peripheral nerves and has no identifiable primary cause. According to this definition, a third of all neuropathies can be classified as idiopathic neuropathies.

Description

The nervous system is divided into two parts: the central nervous system (CNS) and the peripheral nervous system (PNS). The brain and spinal cord compose the CNS, and the nerves that lead to or branch off the CNS compose the PNS.

Peripheral neuropathies encompass a wide range of disorders in which peripheral nerves are damaged. It may also be referred to as peripheral neuritis (inflammation of peripheral nerves), or if many nerves are involved, the terms polyneuropathy or polyneuritis may be used.

Some of the causes of peripheral neuropathies are common, such as diabetes, and others are extremely rare, such as acrylamide poisoning and certain inherited disorders. Sometimes peripheral neuropathies seem to happen for no particular reason. In such cases, they are called idiopathic, meaning of unknown cause. Idiopathic neuropathies can be classified as idiopathic mononeuropathies and polyneuropathies. An idiopathic mononeuropathy, or radiculopathy, refers to the involvement of a single nerve or nerve root, respectively. A polyneuropathy usually refers to the diffuse involvement of peripheral nerves.

Clinical manifestations depend on the type and distribution of the affected nerve population, the degree to which they are damaged, and the course of the disease. For example, if a motor nerve is damaged, the neuropathy manifests as weakness and muscle atrophy, whereas if the damage involves sensory nerves, it may cause loss of sensation, pain, and sensory ataxia.

Demographics

Idiopathic peripheral neuropathies occur typically in middle-aged and elderly individuals and affect two million people in the United States. However, epidemiological studies are scarce. Available studies suggest that 2.4–8% of all adults may have some form of neuropathy. The most common cause is diabetes, which accounts for approximately one-third of all neuropathies; the remaining two thirds are idiopathic and of all other known causes.

Causes and symptoms

There are no known causes for idiopathic neuropathies, and therefore they are considered primary diseases. If a cause is detected, then the neuropathy is secondary to that, and not idiopathic.

Nonetheless, there are many different peripheral neuropathies, among them the idiopathic type, which demonstrates the functional diversity of PNS activities. Symptoms may involve sensory, motor, or autonomic functions. Symptoms are classified based on the affected nerve type and the duration of disease development. 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 are the ones that have been present for several years.

Most times, the first symptoms include numbness, tingling and pain, unsteadiness when standing or walking, muscle weakness (including weak ankles), or cramps and faintness. Depending on the affected group of nerves, secondary symptoms may vary from loss of vibratory sensation at the toes to loss of temperature perception to muscle atrophy.

Diagnosis

Several tests are necessary in order to eliminate all the possible primary causes of the disease, after which idiopathic neuropathy may be defined as a diagnosis; hence it is a diagnosis of exclusion. The patient's history plays a major role in the diagnosis and has to include all symptoms, date of onset, duration, extension of affected area, and amount of discomfort and pain. Specific details about tingling, numbness, weakness, or other symptoms are also very important.

During the neurological evaluation, a physical examination will test for loss of vibratory sensation, ankle jerks, and other reflexes. Sensations in the feet and hands will be evaluated. The purpose of these tests is to assess the neurological function, including muscle strength, autonomic nerve function, and the ability to feel different sensations.

An electromyography may be performed to measure the electrical activity of muscles and nerves. Through this measurement, the physician is able to detect the presence of nerve damage, the possible cause of the damage, and if damaged nerves are responding to treatment. If necessary, other tests can be used, such as a nerve biopsy, a lumbar puncture (spinal fluid analysis), and magnetic resonance imaging (MRI), which creates images of the body and its organs that may be used in the confirmation or exclusion of disorders with similar symptoms.

Blood tests are commonly employed to check for vitamin deficiencies, toxic elements, and evidences of abnormal immune responses. The quantitative sensory test (QST) is a method used to assess damage to small nerve endings (temperature changes) and large nerve endings (vibration changes). Autonomic tests measure how autonomic nerves respond to stimulation. Data collected will indicate if the autonomic nervous system is functioning adequately, or if nerve damage is present. The quantitative sudomotor axon reflex test (QSART) is used to assess small nerve fibers linked to sweat glands. QSART is used to diagnose painful, small fiber neuropathies when nerve conduction test results are normal.

Treatment

Treatment for idiopathic neuropathies is mostly symptomatic, including pain therapy for paresthesias, physical and occupational therapy to help improve mobility and function, supportive measures to maintain blood pressure, and bowel and bladder function if the autonomic system is involved.

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).

Because analgesics (aspirin, ibuprofen) are usually ineffective against pain caused by neuropathy, treatment often involves medications that target nerve cells. Antidepressants such as gabapentin and amitriptyline are usually the first medications prescribed. Side effects of these drugs include drowsiness, dizziness, low blood pressure, and fatigue. Other medications include anticonvulsants (carbamazepine and lamotrigine), local anesthetics (lidocaine), and antiarrhythmics (mexiletine). 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 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.

Injection therapy involves injecting a nerve block (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 such as medication and physical therapy.

Discontinuing medication or exposure to toxic substances may eliminate neuropathy caused by drugs or toxins. Vitamin supplements may be used to treat nutritional neuropathy. Physical therapy, including exercise, massage, and heat, and acupuncture (insertion of fine needles into specific points on the body) may be used to treat symptoms.

Treatment for the causes of neuropathy include antibiotics or antiviral agents for infectious neuropathies, immunomodulating agents for immune-mediated neuropathies, improved glycemic control for diabetic neuropathies, and surgery for compressive neuropathies.

Over-the-counter pain relievers can help treat mild-to-moderate pain associated with peripheral neuropathy. There are two main types of over-the-counter pain relievers: acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is used to treat mild-to-moderate pain and reduce fever, but it is not very effective at reducing inflammation. Acetaminophen provides relief from pain by increasing the pain threshold. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain, swelling, stiffness, and inflammation. Two drugs in this category, ibuprofen and naproxen, also reduce fever. When these drugs are taken regularly, they build up in the blood to levels that fight pain caused by inflammation and swelling, and also provide general pain relief.

Support groups often help patients cope with feelings of isolation and frustration and improve their quality of life.

Clinical trials

As of 2004, there were no clinical trials for idiopathic neuropathies; however, there are several that aim at other types of neuropathies, such as the diabetic neuropathy.

Prognosis

Prognosis and complications depend on the type and severity of the neuropathy. Idiopathic neuropathies range from a reversible problem to a potentially fatal complication. In the best-case scenario, 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, to the patient's age, and to the general health status. Recovery can take weeks to years due to the slow neuronal regrowth rate. Full recovery may not be achieved in some cases.

Special concerns

Complementary and alternative therapies can help manage pain caused by neuropathies. These are noninvasive, drug-free treatments that support natural body healing. They may be used alone or combined with other medications and treatments. Some alternative therapies are biofeedback, acupuncture, and relaxation techniques.

PERIODICALS

Donofrio, P. D. "Immunotherapy of Idiopathic Inflammatory Neuropathies." Muscle Nerve 28 (2003): 273–292.

Lacomis, D. "Small-Fiber Neuropathy." Muscle Nerve 26 (2002): 173–188.

Low, P. A., S. Vernino, and G. Suarez. "Autonomic Dysfunction in Peripheral Nerve Disease." Muscle Nerve 27 (2003): 646–661.

Kelkar, P., W. R. Mcdermott, and G. J. Parry. "Sensory-Predominant, Painful, Idiopathic Neuropathy: Inflammatory Changes in Sural Nerves." Muscle Nerve 26 (2002): 413–416.

OTHER

Neurology Channel. Neuropathy. January 4, 2004 (April 4, 2004). <http://www.neurologychannel.com/neuropathy>.

The Jack Miller Center for Peripheral Neuropathy, University of Chicago. Idiopathic Neuropathy. January 4, 2004 (April 4, 2004). <http://millercenter.uchicago.edu/learnaboutpn/typesofpn/idiopathic/index.shtml>.

ORGANIZATIONS

The Jack Miller Center for Peripheral Neuropathy, University of Chicago. 5841 South Maryland Avenue, MC2030, Chicago, IL 60637. (773) 702-5546. maa@myositis.org. <http://millercenter.uchicago.edu/index.shtml>.

The Neuropathy Association. 60 East 42nd Street, New York, NY 10165-0999. (212) 692-0662 or (800) 247-6968; Fax: (212) 696-0668. info@neuropathy.org. <http://www.neuropathy.org>.

Bruno Marcos Verbeno

Iuri Drumond Louro