What causes peripheral neuropathy?
Peripheral neuropathy may be either inherited or acquired through disease processes or trauma. In manycases, however, a specific cause cannot be identified. Doctors usually refer to neuropathies with no known cause as idiopathic.
Causes of acquired peripheral neuropathy include:
Physical injury (trauma) is the most common cause of acquired nerve injury.
Injury or sudden trauma, such as from automobile accidents, falls, sports-related activities, and surgical procedures 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 severe traumas also can cause serious nerve damage. Broken or dislocated bones can exert damaging pressure on neighboring nerves.
Repetitive stress frequently leads to entrapment neuropathies, a form of compression injury. Cumulative damage can result from repetitive, awkward, and/or forceful activities that require movement 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. Ulnar neuropathy and carpal tunnel syndrome are examples of the most common types of neuropathy from trapped or compressed nerves at the elbow or wrist.
Diseases or disorders and their related processes (such as inflammation) can be associated with peripheral neuropathy.
Metabolic and endocrine disorders impair the body’s ability to transform nutrients into energy and process waste products, and this can lead to nerve damage. 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 that can affect sensory, motor, and autonomic nerves and present with varied symptoms. Some metabolic liver diseases also lead to neuropathies as a result of chemical imbalances. Endocrine disorders that lead to 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, causing pain.
Small vessel disease can decrease oxygen supply to the peripheral nerves and lead to serious nerve tissue damage. Diabetes frequently leads to impaired blood flow to nerves. 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. Vasculitis is an example of nerve damage called mononeuritis multiplex or multifocal mononeuropathy, in which isolated nerves in two or more areas are damaged.
Autoimmune diseases, in which the immune system attacks the body’s own tissues, can lead to nerve damage. Sjogren’s syndrome, lupus, and rheumatoid arthritis are among the autoimmune diseases that can be associated with peripheral neuropathy. When the tissue surrounding nerves becomes inflamed, the inflammation can spread directly into nerve fibers. Over time, these chronic autoimmune conditions can destroy joints, organs, and connective tissues, making nerve fibers more vulnerable to compression injuries and entrapment. Chronic conditions may alternate between 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 autoimmune syndrome although severe cases can be life threatening. Chronic inflammatory demyelinating polyneuropathy (CIDP) 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.
Kidney disorders may cause neuropathies. Kidney dysfunction can lead to abnormally high amounts of toxic substances in the blood that can damage nerve tissue. A majority of indviduals who require dialysis because of kidney failure develop polyneuropathy.
Cancers can infiltrate nerve fibers or exert damaging compression forces on nerve fibers. Tumors also can arise directly from nerve tissue cells. 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. Toxicity from the chemotherapeutic agents and radiation used to treat cancer also can cause peripheral neuropathy. An estimated 30 to 40 percent of people who undergo chemotherapy develop peripheral neuropathy and it is a leading reason why people with cancer stop chemotherapy early. The severity of chemotherapyinduced peripheral neuropathy (CIPN) varies from person to person. In some cases people may be able to ease their symptoms by lowering their chemotherapy dose or by stopping it temporarily. In others, CIPN may persist long after stopping chemotherapy.
Neuromas are benign tumors that are caused by an overgrowth of nerve tissue that develops after a penetrating injury that severs nerve fibers. Neuromas are often associated with intense pain and sometimes they 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. Widespread polyneuropathy is often associated with neurofibromatosis, a genetic disorder in which multiple benign tumors grow on nerve tissue.
Infections can cause peripheral neuropathy. Viruses and bacteria that can attack nerve tissues include herpes varicellazoster (shingles), Epstein-Barr virus, West Nile virus, cytomegalovirus, and herpes simplex members of the large family of human herpes viruses. These viruses can severely damage sensory nerves, causing attacks of sharp, lightning-like pain. Postherpetic neuralgia is long-lasting, particularly intense pain that often occurs after an attack of shingles. Lyme disease, diphtheria, and leprosy are bacterial diseases characterized by extensive peripheral nerve damage. Diphtheria and leprosy are rare in the United States, but the incidence of Lyme disease is on the rise.
The tick-borne infection can involve a wide range of neuropathic disorders, including a rapidly developing, painful polyneuropathy, often within a few weeks of being infected. West Nile virus is spread by mosquitoes and is associated with a severe motor neuropathy. The inflammation
triggered by infection sometimes results in various forms of inflammatory neuropathies that develop quickly or slowly.
The human immunodeficiency virus (HIV) that causes AIDS is associated with several different forms of neuropathy, depending on the nerves affected and the specific stage of active immunodeficiency disease. A rapidly progressive, painful polyneuropathy affecting the feet and hands can be the first clinically apparent symptom of HIV infection. An estimated 30 percent of people who are HIV positive develop peripheral neuropathy; 20 percent develop distal neuropathic pain.
Exposure to toxins may damage nerves and cause peripheral neuropathy.
Medication toxicity can be caused by many agents in addition to those for fighting cancer. Other agents that commonly cause peripheral neuropathy as a side effect include those used to fight infection such as antiretroviral agents for treating HIV. In addition, anticonvulsant agents and some heart and blood pressure medications can commonly cause peripheral neuropathy. In most cases, the neuropathy resolves when these medications are discontinued or dosages are adjusted.
Environmental or industrial toxins such as lead, mercury, and arsenic can cause peripheral neuropathy. In addition, certain insecticides and solvents have also been known to cause neuropathies.
Heavy alcohol consumption is a common cause of peripheral neuropathy. Damage to the nerves associated with long-term alcohol abuse may not be reversible when a person stops drinking alcohol, however, doing so may provide some symptom relief and prevent further damage. Chronic alcohol abuse also frequently leads to nutritional deficiencies (including B12, thiamine, and folate) that contribute to the development of peripheral neuropathy.