Peripheral Neuropathy: Causes and symptoms

Typical symptoms of neuropathy are related to the type of affected nerve. If a sensory nerve is damaged, common symptoms include numbness, tingling in the area, a prickling sensation, or pain. Pain associated with neuropathy can be quite intense and may be described as cutting, stabbing, crushing, or burning. In some cases, a nonpainful stimulus may be perceived as excruciating or pain may be felt even in the absence of a stimulus. Damage to a motor nerve is usually indicated by weakness in the affected area. If the problem with the motor nerve has continued over a length of time, muscle shrinkage (atrophy) or lack of muscle tone may be noticeable. Autonomic nerve damage is most noticeable when an individual stands upright and experiences problems such as light-headedness or changes in blood pressure. Other indicators of autonomic nerve damage are lack of sweat, tears, and saliva; constipation; urinary retention; and impotence. In some cases, heart beat irregularities and respiratory problems can develop.

Symptoms may appear over days, weeks, months, or years. Their duration and the ultimate outcome of the neuropathy are linked to the cause of the nerve damage. Potential causes include diseases, physical injuries, poisoning, and malnutrition or alcohol abuse. In some cases, neuropathy is not the primary disorder, but a symptom of an underlying disease.

Diseases that cause peripheral neuropathies may either be acquired or inherited; in some cases, it is difficult to make that distinction. The diabetes-peripheral neuropathy link has been well established. A typical pattern of diabetes-associated neuropathic symptoms includes sensory effects that first begin in the feet. The associated pain or pins-and-needles, burning, crawling, or prickling sensations form a typical "stocking" distribution in the feet and lower legs. Other diabetic neuropathies affect the autonomic nerves and have potentially fatal cardiovascular complications.

Several other metabolic diseases have a strong association with peripheral neuropathy. Uremia, or chronic kidney failure, carries a 10–90% risk of eventually developing neuropathy, and there may be an association between liver failure and peripheral neuropathy. Accumulation of lipids inside blood vessels (atherosclerosis) can choke-off blood supply to certain peripheral nerves. Without oxygen and nutrients, the nerves slowly die.

Mild polyneuropathy may develop in persons with low thyroid hormone levels. Individuals with abnormally enlarged skeletal extremities (acromegaly), caused by an overabundance of growth hormone, may also develop mild polyneuropathy.

Neuropathy can also result from severe vasculitides, a group of disorders in which blood vessels are inflamed. When the blood vessels are inflamed or damaged, blood supply to the nerve can be affected, injuring the nerve.

Both viral and bacterial infections have been implicated in peripheral neuropathy. Leprosy is caused by the bacteria M. leprae, which directly attack sensory nerves. Other bacterial illness may set the stage for an immunemediated attack on the nerves. For example, one theory about Guillain-Barré syndrome involves complications following infection with Campylobacter jejuni, a bacterium commonly associated with food poisoning. This bacterium carries a protein that closely resembles components of myelin. The immune system launches an attack against the bacteria; but, according to the theory, the immune system confuses the myelin with the bacteria in some cases and attacks the myelin sheath as well. The underlying cause of neuropathy associated with Lyme disease is unknown; the bacteria may either promote an immune-mediated attack on the nerve or inflict damage directly.

Infection with certain viruses is associated with extremely painful sensory neuropathies. A primary example of such a neuropathy is caused by shingles. After a case of chickenpox, the causative virus, varicella-zoster virus, becomes inactive in sensory nerves. Years later, the virus may be reactivated. Once reactivated, it attacks and destroys axons. Infection with HIV is also associated with peripheral neuropathy, but the type of neuropathy that develops can vary. Some HIV-linked neuropathies are noted for myelin destruction rather than axonal degradation. Also, HIV infection is frequently accompanied by other infections, both bacterial and viral, that are associated with neuropathy.

Several types of peripheral neuropathies are associated with inherited disorders. These inherited disorders may primarily involve the nervous system, or the effects on the nervous system may be secondary to an inherited metabolic disorder. Inherited neuropathies can fall into several of the principal syndromes, because symptoms may be sensory, motor, or autonomic. The inheritance patterns also vary, depending on the specific disorder. The development of inherited disorders is typically drawn out over several years and may herald a degenerative condition—that is, a condition that becomes progressively worse over time. Even among specific disorders, there may be a degree of variability in inheritance patterns and symptoms. For example, Charcot-Marie-Tooth disease is usually inherited as an autosomal dominant disorder, but it can be autosomal recessive or, in rare cases, linked to the X chromosome. Its estimated frequency is approximately one in 2,500 people. Age of onset and sensory nerve involvement can vary between cases. The main symptom is a degeneration of the motor nerves in legs and arms, and resultant muscle atrophy. Other inherited neuropathies have a distinctly metabolic component. For example, in familial amyloid polyneuropathies, protein components that make up the myelin are constructed and deposited incorrectly.

Accidental falls and mishaps during sports and recreational activities are common causes of physical injuries that can result in peripheral neuropathy. The common types of injuries in these situations occur from placing too much pressure on the nerve, exceeding the nerve's capacity to stretch, blocking adequate blood supply of oxygen and nutrients to the nerve, and tearing the nerve. Pain may not always be immediately noticeable, and obvious signs of damage may take a while to develop.

These injuries usually affect one nerve or a group of closely associated nerves. For example, a common injury encountered in contact sports such as football is the "burner," or "stinger," syndrome. Typically, a stinger is caused by overstretching the main nerves that span from the neck into the arm. Immediate symptoms are numbness, tingling, and pain that travels down the arm, lasting only a minute or two. A single incident of a stinger is not dangerous, but recurrences can eventually cause permanent motor and sensory loss.

The poisons, or toxins, that cause peripheral neuropathy include drugs, industrial chemicals, and environmental toxins. Neuropathy that is caused by drugs usually involves sensory nerves on both sides of the body, particularly in the hands and feet, and pain is a common symptom. Neuropathy is an unusual side effect of medications; therefore, most people can use these drugs safely. A few of the drugs that have been linked with peripheral neuropathy include metronidazole, an antibiotic; phenytoin, an anticonvulsant; and simvastatin, a cholesterol-lowering medication.

Certain industrial chemicals have been shown to be poisonous to nerves (neurotoxic) following work-related exposures. Chemicals such as acrylamide, allyl chloride, and carbon disulfide have all been strongly linked to development of peripheral neuropathy. Organic compounds, such as N-hexane and toluene, are also encountered in work-related settings, as well as in glue-sniffing and solvent abuse. Either route of exposure can produce severe sensorimotor neuropathy that develops rapidly.

Heavy metals are the third group of toxins that cause peripheral neuropathy. Lead, arsenic, thallium, and mercury usually are not toxic in their elemental form, but rather as components in organic or inorganic compounds. The types of metal-induced neuropathies vary widely. Arsenic poisoning may mimic Guillain-Barré syndrome; lead affects motor nerves more than sensory nerves; thallium produces painful sensorimotor neuropathy; and the effects of mercury are seen in both the CNS and PNS.

Burning, stabbing pains and numbness in the feet, and sometimes in the hands, are distinguishing features of alcoholic neuropathy. The level of alcohol consumption associated with this variety of peripheral neuropathy has been estimated as approximately 3 L of beer or 300 mL of liquor daily for three years. However, it is unclear whether alcohol alone is responsible for the neuropathic symptoms, because chronic alcoholism is strongly associated with malnutrition.

Malnutrition refers to an extreme lack of nutrients in the diet. It is unknown precisely which nutrient deficiencies cause peripheral neuropathies in alcoholics and famine and starvation patients, but it is suspected that the B vitamins have a significant role. For example, thiamine (vitamin B₁) deficiency is the cause of beriberi,a neuropathic disease characterized by heart failure and painful polyneuropathy of sensory nerves. Vitamin E deficiency seems to have a role in both CNS and PNS neuropathy.

— Julia Barrett