Incidence & Causes

By Jeffrey W. Ralph, MD

Causes of peripheral neuropathy include:

  • Medical problems such as diabetes
  • Genetic
  • Nutritional deficiencies
  • Toxins
  • Compression/trauma
  • Infiltration by tumor

A few of these causes are discussed below. In about 30 percent of patients, a specific cause of neuropathy cannot be found—even after an exhaustive search. These neuropathies are called idiopathic. Probably, complex metabolic and genetic factors contribute to idiopathic neuropathies.

Medical Problems

Many different medical problems lead to peripheral neuropathies. It is therefore important that physicians take a careful medical history when assessing patients for neuropathy. Medical problems that may be associated with neuropathy include: 1) metabolic diseases such as diabetes mellitus; 2) autoimmune diseases such as lupus erthymatosis; 3) organ failure; 4) endocrine (hormonal) diseases such as hypothyroidism; 5) infections such as Lyme disease, HIV, and leprosy. (Until quite recently leprosy was the leading cause of polyneuropathy in the world.)

Diabetic peripheral neuropathy is the most common polyneuropathy in the United States and the world. It is estimated that there are 15-20 million cases of diabetic polyneuropathy in the United States. Given the size of this problem, it is odd that more people do not know about it. Diabetic polyneuropathy contributes to the incidence of lower limb amputations in diabetic patients because diabetics are less likely to perceive a wound in their feet or legs.

An autoimmune disease is one in which the body’s immune system attacks body tissues. Neuropathies may occur in patients with multi-system autoimmune diseases such as lupus erythematosis in which the skin, joints, and kidneys may also be affected. Sometimes an autoimmune disease may be directed selectively against nerves. A dramatic example of this is Guillain-Barré syndrome. People who have direct experience with this type of polyneuropathy will never forget it. It is characterized by a very rapid decline in strength. Sometimes patients, though alert, become completely paralyzed and need a breathing machine. With intensive care, most patients make a good recovery. This disease has inspired more than one medical student into chosing a career in intensive care medicine or neurology!

Nutritional Deficiencies

Deficiencies of certain vitamins and minerals (including the B vitamins, vitamin E, and copper) can cause a peripheral neuropathy.

Alcoholic patients may become deficient in thiamine (a B vitamin) if they do not eat well. This deficiency is thought to contribute to alcoholic polyneuropathy.

In Western societies, B12 deficiency is the most common vitamin deficiency leading to neuropathy. When it is severe, patients may have very poor balance. Anemia is also a feature of B12 deficiency.

Genetic Neuropathies

Mutations in a number of genes (sections of DNA) may lead to a peripheral neuropathy. Sometimes, as many as 50 percent of family members have it. Sometimes only a single family member has it. Genetic neuropathies tend to present early in life and progress very slowly over time. There are certain clinical clues such as the appearance of the feet that would make a physician suspect a genetic neuropathy.

Currently there are no cures and only a few specific treatments for the genetic neuropathies. Genetic disease is a rapidly evolving part of medicine, and there is hope that better therapies are on the horizon.


A wide array of industrial chemicals including solvents and heavy metals, including arsenic and lead, can cause neuropathy. Industrial workers who develop symptoms of a neuropathy should bring a list of their chemical exposures to their physicians.

In people who do not have significant occupational exposures to chemicals, the most likely culprit for causing a toxic neuropathy is a pharmaceutical drug. Certain chemotherapeutic drugs are notorious for causing peripheral neuropathies.

If the toxin can be identified and removed, the peripheral neuropathy typically stabilizes and then improves.

Idiopathic Peripheral Neuropathy

It is frustrating for both the patient and physician when a specific cause for a neuropathy cannot be found. Most idiopathic neuropathies progress over time, albeit very gradually. Usually sensory symptoms predominate over motor deficits (weakness). Over time, balance may be affected. Even after many years, however, many patients with idiopathic neuropathies usually do not have significant limb weakness.