Introduction to Peripheral Neuropathy

Classification of Peripheral Neuropathy

There are several different ways to classify peripheral neuropathy. One of the most common classification systems takes into account the pattern and distribution of the pain and includes:

Mononeuropathy

Mononeuropathy is characterized by involvement of a single peripheral nerve. This is most likely to be the result of:

  • Nerve entrapment such as carpal tunnel syndrome which is the most common cause of mononeuropathy or ulnar nerve entrapment (near the elbow) which is the second most common cause of mononeuropathy
  • Trauma

Mononeuropathy multiplex

In mononeuropathy multiplex, two or more non-contiguous peripheral nerves in separate parts of the body are affected. The pattern of involvement is random, multifocal, and typically evolves quickly. Mononeuropathy multiplex is associated with:

  • Vasculitis - inflammation in the part of the vascular system that is innervated by the affected nerves. Vasculitis could also be systemic. Vasculitis needs to be diagnosed and treated quickly.
  • Diabetic amyotrophy - a type of neuropathy with acute pain, weakness and/or wasting of the muscles in the lower extremity
  • Sarcoidosis - inflammation that produces tiny lumps of cells in various organs in the body
  • Lyme disease
  • Lymphoma
  • Carcinoma
  • HIV
  • Amyloidosis - amyloid protein deposits in limited organs or throughout the body
  • Polyarteritis nodosa - An autoimmune disease that causes inflammation of the small and medium-sized arteries and can lead to problems with muscles, joints, and other organs

Polyneuropathy

While mononeuropathy affects a single nerve, polyneuropathy affects multiple nerves and may affect more than one extremity - often on both sides of the body (symmetric). Symptoms appear more commonly in the legs than the arms and usually are felt first in the toes and soles of the feet. It is the most common type of peripheral neuropathy and is associated with diabetes, alcoholism, vitamin B deficiency or HIV. Polyneuropathy can also involve the autonomic nervous system which can lead to symptoms described above.

Most polyneuropathies evolve slowly, involve sensory and motor nerves, and progress symmetrically. Polyneuropathies involve more than one type of nerve but there is usually one (e.g. sensory or motor, large fiber or small fiber) that is predominant.

The most common type of polyneuropathy is called distal symmetric polyneuropathy. It involves long sensory nerves and symptoms usually appear first in the toes and the soles of the feet. Early symptoms include numbness, tingling, paresthesia, and burning. As the name implies, symptoms are symmetric and involve both legs. Distal symmetric polyneuropathy is associated with:

  • Diabetes
  • Idiopathic neuropathy
  • Connective tissue disease
  • Inherited neuropathies
  • HIV
  • Cancer
  • Chemotherapy
  • Metabolic disorders

There are several types of polyneuropathy, including acute and chronic polyneuropathy.

Acute Polyneuropathy

This type of polyneuropathy evolves suddenly and tends to progress rapidly. Approximately half of the patients have a history of respiratory or gastrointestinal infection within the 2-3 weeks prior to onset. Acute polyneuropathy is associated with:

  • Guillain-Barre syndrome - a disorder in which the body's immune system attacks part of the peripheral nervous system. Symptoms usually begin with weakness or tingling sensations in the leg and can progress to the arms and upper body. This condition requires immediate diagnosis and treatment since it can deteriorate quickly and cause paralysis and respiratory insufficiency if respiratory muscles are affected. Approximately 25-30% of patients with Guillain-Barre syndrome require ventilation support.
  • Porphyria (a group of genetic disorders caused by problems with how the body makes a substance called heme, a component of hemoglobin)
  • Diphtheria
  • Vasculitis
  • Tumor
  • Certain medications

Chronic Polyneuropathy

Chronic polyneuropathy, sometimes called chronic distal neuropathy is the most common type of polyneuropathy and may develop over a period of months or years. It can involve large and/or small fibers and can affect sensory, motor, and/or autonomic pathways. There are several subtypes of chronic polyneuropathy including:

  • Chronic Demyelinating Polyneuropathy - demyelination refers to the destruction and loss of myelin from the sheath surrounding the axon and affects both near and far segments of the nerve. It is characterized by progressive weakness and impaired sensory function in the legs and arms. It is more common in males than females and in young adults. This condition is either genetic or may be acquired (inflammatory or immunological conditions).

    • Genetic etiology reflects a duplication of the PMP22 gene which is highly associated with Charcot-Marie-Tooth (CMT) disease.
    • Acquired etiology is related to immunological conditions - most commonly to chronic inflammatory demyelinating polyneuropathy (CIDP) which is thought to affect 2 out of 100,000 people, or multifocal motor neuropathy.

  • Chronic Axonal Polyneuropathy - This is the most common of the polyneuropathy conditions. It is more common than demyelinating polyneuropathy and is characterized by ascending nerve damage, meaning that the nerve fibers most distant from the brain and spinal cord are affected first. Pain or other symptoms may appear in both feet and gradually progress up the legs and then appear in the fingers, hands, and arms. It is associated with many conditions including:

    • diabetes (most common)
    • nutritional deficiencies (e.g. vitamin B12)
    • cancer
    • renal failure
    • medication toxicity
    • alcohol abuse

While acute neuropathies tend to appear suddenly, progress rapidly, be potentially life threatening, and resolve slowly, chronic neuropathies progress slowly and worsen over time but are typically not fatal. Some patients find that symptoms plateau at a given point while for other patients, symptoms relapse and remit.

In approximately 20-25% of cases, no cause can be found for chronic polyneuropathy and these patients are said to have idiopathic peripheral neuropathy. Most cases of idiopathic peripheral neuropathy involve sensory nerves. Symptoms are symmetrical and typically start distally, (usually in the feet) with pain, numbness, or burning. Idiopathic peripheral neuropathy affects primarily older patients. Progression of symptoms is slow and usually does not result in serious physical disability although quality of life can be significantly impacted due especially to pain and dysesthesia (distorted sensation where light touch is perceived as painful).

For more in-depth information regarding various types of peripheral neuropathy, please click on the following link: http://www.medifocus.com/abstracts.php?gid=NR021&ID=15220040

Underlying medical conditions that may cause specific types neuropathy include:

  • Acute motor paralysis with minimal sensory disturbance

    • Guillan-Barre syndrome
    • diphteritic polyneuropathy (muscles of swallowing and speech are also involved)

  • Mononeuropathy multiplex

    • diabetes mellitus
    • sarcoidosis
    • polyarteritis nodosa

  • Subacute sensorimotor polyneuropathy

    • nutritional deficiencies - thiamine, niacin, or vitamin B12 deficiency
    • poisoning with heavy metals and solvents
    • drug intoxication
    • metabolic syndrome
    • diabetes mellitus

  • Chronic sensorimotor polyneuropathy

    • connective tissue diseases
    • uremia - the buildup of urea in the blood because the kidneys are not working effectively)
    • beriberi (disease caused by a deficiency of thiamine (vitamin B1) that affects many systems of the body)
    • carcinoma (e.g., paraneoplastic syndrome)
    • paraproteinemia (the presence of excessive amounts of a single monoclonal gammaglobulin, also called "monoclonal gammopathy")
    • hypothyroidism
    • amyloidosis
    • diabetes mellitus
    • leprosy