Peripheral neuropathy

Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of the nerve or from the side-effects of systemic illness. Peripheral neuropathies vary in their presentation and origin, and may affect the nerve or the neuromuscular junction.

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Causes

The causes are broadly grouped as follows:

• Genetic diseases: Friedreich's ataxia, Charcot-Marie-Tooth syndrome ^[1]

• Metabolic/Endocrine: diabetes mellitus ^[2], Chronic renal failure, porphyria, amyloidosis, liver failure, hypothyroidism

• Toxic causes: alcoholism, drugs (vincristine, phenytoin, isoniazid), organic metals, heavy metals

• Inflammatory diseases: Guillain-Barré syndrome, systemic lupus erythematosis, leprosy, Sjögren's syndrome

• Vitamin deficiency states: vitamin B₁₂, vitamin A, vitamin E, thiamin

• Others: malignant disease, HIV ^[3], radiation, chemotherapy^[4]

Many of the diseases of the peripheral nervous system may present similarly to muscle problems (myopathies), and so it is important to develop approaches for assessing sensory and motor disturbances in patients so that a physician may make an accurate diagnosis.

Types

Peripheral neuropathies may either be symmetrical and generalized or focal and multifocal, which is usually a good indicator of the cause of the peripheral nerve disease.

Generalized peripheral neuropathy

Generalized peripheral neuropathies are symmetrical, and usually due to various systematic illnesses and disease processes that affect the peripheral nervous system in its entirety. They are further subdivided into several categories:

• Distal axonopathies are the result of some metabolic or toxic derangement of neurons. They may be caused by metabolic diseases such as diabetes, renal failure, deficiency syndromes such as malnutrition and alcoholism, or the effects of toxins or drugs.

• Myelinopathies are due to a primary attack on myelin causing an acute failure of impulse conduction. The most common cause is acute inflammatory demyelinating polyneuropathy (AIDP; aka Guillain-Barré syndrome), though other causes include chronic inflammatory demyelinating polyneuropathy (CIDP), genetic metabolic disorders (e.g., leukodystrophy), or toxins.

• Neuronopathies are the result of destruction of peripheral nervous system (PNS) neurons. They may be caused by motor neurone diseases, sensory neuronopathies (e.g., Herpes zoster), toxins or autonomic dysfunction. Neurotoxins may cause neuronopathies, such as the chemotherapy agent vincristine.

Signs and symptoms

Those with diseases or dysfunctions of their peripheral nerves can present with problems in any of the normal peripheral nerve functions.

In terms of sensory function, there are commonly loss of function (negative) symptoms, which include numbness, tremor, and gait imbalance.

Gain of function (positive) symptoms include tingling, pain, itching, crawling, and pins and needles. Pain can become intense enough to require use of opiate drugs (i.e., morphine, oxycodone).

Skin can become so hypersensitive that patients are prohibited from having anything touch certain parts of their body, especially the feet. People with this degree of sensitivity cannot have a bedsheet touch their feet or wear socks or shoes, and eventually become housebound.

Motor symptoms include loss of function (negative) symptoms of weakness, tiredness, heaviness, and gait abnormalities; and gain of function (positive) symptoms of cramps, tremor, and fasciculations.

There is also pain in the muscles (myalgia), cramps, etc., and there may also be autonomic dysfunction.

During physical examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, though those with a pathology (problem) of the peripheral nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies like Guillain-Barré syndrome); or may show focal sensory disturbance or weakness, such as in mononeuropathies, radiculopathies and plexopathies.

Common disorders of the peripheral nerves include focal entrapment neuropathies (e.g., carpal tunnel syndrome), generalized peripheral neuropathies (e.g., diabetic neuropathy), plexopathies (e.g., brachial neuritis) and radiculopathies (e.g., of cranial nerve VII; Facial nerve).

Treatment

Many treatment strategies for peripheral neuropathy are symptomatic. Some current research in animal models has shown that neurotrophin-3 can oppose the demyelination present in some peripheral neuropathies.^[5]

References

1. ^ Gabriel JM, Erne B, Pareyson D, Sghirlanzoni A, Taroni F, Steck AJ (1997). "Gene dosage effects in hereditary peripheral neuropathy. Expression of peripheral myelin protein 22 in Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies nerve biopsies". Neurology 49 (6): 1635–40. PMID 9409359.
2. ^ Kiziltan ME, Akalin MA, Sahin R, Uluduz D (2007). "Peripheral neuropathy in patients with diabetes mellitus presenting as Bell's palsy". doi:10.1016/j.neulet.2007.09.029. PMID 17933462.
3. ^ Gonzalez-Duarte A, Cikurel K, Simpson DM (2007). "Managing HIV peripheral neuropathy". Current HIV/AIDS reports 4 (3): 114–8. PMID 17883996.
4. ^ Wilkes G (2007). "Peripheral neuropathy related to chemotherapy". Seminars in oncology nursing 23 (3): 162–73. doi:10.1016/j.soncn.2007.05.001. PMID 17693343.
5. ^ Liu N, Varma S, Tsao D, Shooter EM, Tolwani RJ (2007). "Depleting endogenous neurotrophin-3 enhances myelin formation in the Trembler-J mouse, a model of a peripheral neuropathy". J. Neurosci. Res. 85 (13): 2863–9. doi:10.1002/jnr.21388. PMID 17628499.

• Dr. Lee Dellon: Pioneering Pain Relief Dr. Lee Dellon's research in the pain caused by Peripheral Neuropathy and other nerve disorders is highlighted in this recent article.

• Diseases of the peripheral system^{[dead link – history]} - These lecture notes were presented to a second year medical school class at the University of Western Ontario on 2 December 2004 by Dr. Angelika F. Hahn.

• Approach to Muscle and nerve problems^{[dead link]} - Powerpoint slides from a lecture presented to a second year medical school class at the University of Western Ontario on 2 December 2004 by Dr. Michael W. Nicolle.

See also

• Neuropathy
• Myopathy
• Myelinopathy
• Guillain-Barré syndrome