Peripheral Neuropathy

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A conduction problem arising in peripheral nerves is called peripheral neuropathy. Depending on the cause, the damage may be to the axons or the myelin sheaths. The neurons involved may be afferent (sensory), efferent (motor), or both.

The size of axons affected is an important first issue. Some cases of sensory neuropathy involve only the small axons, which are the C unmyelinated fibers and the A-delta fibers. If these are damaged, symptoms are linked to pain sensors in the skin and to autonomic neurons. On the other hand, damage to large sensory fibers, which are the A-alpha and A-beta fibers, cause deficits in proprioception, vibration sensation, and reduced muscle-stretch reflexes.

Axonal Neuropathies

Consider, for example, a patient with painful sensory neuropathy due to diabetes mellitus, which is a leading cause of peripheral neuropathy. Initially, the patient might complain of burning or tingling sensations in her feet. Abnormal sensations of this type are called paresthesias. There may be hyperalgesia, in which mild stimuli cause pain, and allodynia, in which ordinarily nonpainful stimuli, such as touch, cause pain. The symptoms tend to have a "glove and stocking" distribution, because the longest axons tend to be affected first. The damage in diabetes mellitus is to axons rather than myelin. The fine, unmyelinated nerve endings in the epidermis seem to degenerate first.

Sometimes a skin biopsy is performed to establish a diagnosis of neuropathy of the small, pain nerve endings. To visualize the fine nerve endings, a special immunohistochemical technique is used based on a protein found in these nerve endings. To compare such a skin biopsy from a normal person with a patient with early, diabetic sensory neuropathy, CLICK HERE ( Also, read the descriptions of two patients with early diabetic peripheral neuropathy given in this article. The Discussion portion of the article is optional. (Incidentally, a skin biopsy from a patient who has been rubbing capsiacin cream on the skin would show similar degeneration of fine, unmyelinated nerve endings.)

Indeed, the symptoms described above may be an early initial indication of diabetes. The degeneration appears to be linked to impaired glucose tolerance, which seems to impede regeneration of the fine nerve endings. Later, however, larger axons may be involved as well. With sufficient loss of pain sensation, it can be easy for a patient to seriously damage the hands or feet.

Another possibility for axonal degeneration is loss of normal blood flow to specific nerves. For example, vasculitis, which is inflammation of blood vessels, might cause damage to specific nerves.

Alcoholism is another leading cause of neuropathy linked to axonal damage. Various pathogens, such as the leprosy bacillus, also can interfer with axonal conduction. Vitamin B12 deficiency is another possibility. But often no cause is established for sensory neuropathy, especially with the small axon type.

Demyelinating Neuropathies

The Guillain-Barre Syndrome is another example of peripheral neuropathy and is one of the leading causes of severe neuromuscular paralysis. Its pathogenesis is unknown, but the symptoms typically began to develop a few days to a few weeks after an otherwise ordinary infection. Both motor and sensory deficits are found and result from inflammation and subsequent demyelination of peripheral nerves. Accumulations of lymphocytes and monocytes are found around the nerves. Weakness and paresthesias often begin in the legs and progress to the arms. The disorder can be life-threatening due to respiratory failure or autonomic problems. But most patients begin to recover in a few weeks and can return to work in a few months. The incidence increases with age.

Charcot-Marie-Tooth disease is a set of genetic disorders of nerve conduction. Most (but not all) of the types are demyelinating. Both motor and sensory deficits occur, most commonly showing up during adolescence. This disorder is diagnosed with nerve conduction studies and a nerve biopsy, in which the myelin is observed much like you did last quarter in lab. There are also specific genetic tests. Patients tend to have a very high arch in the foot.

Carpal tunnel syndrome arises when over-use causes inflammation of the region where the median nerve and tendons pass through the carpal bones. At first, damage to the median nerve is primarily demyelinating, but eventually can become axonal.

Bell's palsy is usually due to inflammmation and swelling of the facial nerve at the point where it passes through a narrow foramen in the temporal bone. Facial muscles on the affected side are paralyzed, while those on the opposite side are normal. The eyelid typically droops, although the eye cannot be closed. The onset is typical fairly sudden and then usually clears up after a month or so.

QUESTION: Why would the symptoms in diabetes mellitus tend to have a "glove and stocking" distribution?

QUESTION: Define "paresthesia".

QUESTION: Define "allodynia".