HTLV-1 associated myelopathy

Definition

Damage to the nerves (myelopathy) of the spinal cord caused by infection with the human T lymphotrophic virus type-1 is termed HTLV-1 associated myelopathy.

Description

HTLV-1 associated myelopathy is evident mainly as a chronic weakening of muscles, especially those in the legs. Weakening can be so severe as to produce partial paralysis. The myelin covering of spinal cord nerve cells can become damaged, as can the elongated part of the cell termed the axon.

HTLV-1 associated myelopathy is also known as tropical spastic paraparesis and additionally as HTLV-1 associated myelopathy/tropical spastic paraparesis.

Demographics

Myelopathy occurs in approximately 0.25% of those infected with HTLV-1, typically in adults aged 40–60. The viral infection is associated with diseases including adult T-cell leukaemia, Acquired Immunodeficiency Syndrome (AIDS ), various neurological disorders, inflammation of the uveal tract of the eye, and degenerative or arthritic pain .

HTLV-1 is common in Japan, the Caribbean, and some areas of Africa. Correspondingly, the associated myelopathy is more prominent in these regions, compared to other areas of the globe.

Causes and symptoms

HTLV-1 associated myelopathy is the result of infection with the HTLV-1 virus. The common routes of transmission are through breast milk, transfused blood (especially prior to 1989 when donated blood was not tested for HTLV-1), sexual intercourse, and drug injection.

Until the viral link was established in the mid-1980s, HTLV-1 associated myelopathy was thought to result in the inflammation of the central nervous system caused by infection by the bacteria Treponema pallidum (the cause of syphilis) or Treponema pertenue (the cause of yaws), or by a nutritional deficiency.

In addition to the damage to nerve myelin and axon, the white and grey matter of the spinal cord sometimes becomes infiltrated with certain white blood cells, along with nerve cell astrocytes. White lesions can develop along the length of the spinal cord. Occasionally, the entire cord can become swollen.

Along with the progressively increasing muscle weakness, patients also can display impaired sense of touch and pain receptivity, and malfunction of muscles called sphincters, which can contract to restrict the flow of some body fluids and relax to resume flow. Leakage of urine is a problem in over 90% of those with this form of myelopathy. Patients can also develop eye inflammation, arthritis, dryness of the cornea and conjunctiva, and skin inflammation.

Diagnosis

Diagnosis can be made using several clinical observations. A medical history will show that the current symptoms were not present during childhood. Within two years of the first appearance of symptoms, a person will likely have experienced an increase in the frequency of urination, and weakness, numbness, pains, or cramps in both legs. In a physical examination, an increased knee-jerk reaction is seen. Difficulty using both legs is evident. Finally, eye abnormalities such as changes in the appearance of the pupil are present.

The visualization of spinal cord nerve damage can also aid in diagnosis. Lesions and swelling associated with the spinal cord can be visualized by magnetic resonance imaging (MRI) .

Demonstration of the presence of HTLV-1 is an important part of the diagnosis. Antibodies to several viral proteins can be detected shortly after an infection begins. But, within a few months, an infection can become undetectable using antibody detection techniques. Thus, the absence of HTLV-1 antibodies does not necessarily rule out an infection. HTLV-1 genetic material can be detected from lymphocyte cells using a sensitive technique called polymerase chain reaction.

A more reliable diagnostic finding can be an increased level of a compound called neopterin in the cerebrospinal fluid (CSF) that is obtained by a lumbar puncture. Neopterin is released by immune cells called macrophages when they are stimulated as part of an immune response to the infecting virus. As well, lymphocyte cells in the CSF can adopt a characteristic flower-like appearance.

Treatment team

Family physicians, neurologists and other specialized clinicians, physical therapists, and caregivers are all part of the treatment team.

Treatment

Currently, there is no specific treatment regimen for HTLV-1 associated myelopathy. Steroid medications help lessen symptoms and discomfort in many people. Drug therapy with lioresal or tizanidine can help relieve muscle spasms. The leakage of urine due to malfunction of the urinary sphincter muscle can be treated using oxybutynin, or managed by use of a catheter.

The use of plasmapheresis, in which plasma is withdrawn, antibodies removed, and the antibody-free liquid put back into the person, has not shown promise for HTLV-1 myelopathy. Interestingly, this technique is useful in treating myelin damage caused in other disorders such as Guillain-Barré syndrome .

Recovery and rehabilitation

Physical and occupational therapy is useful in maintaining muscle function.

Clinical trials

A clinical trial sponsored by the National Institute of Neurological Disorders and Stroke has been underway since 1997 in which blood samples are collected from patients in order to evaluate the functioning of the immune system and the levels of the virus during the course of the disease.

Prognosis

While the disorder may become progressively worse, HTLV-1 associated myelopathy is seldom fatal. People with the disorder normally live for several more decades after being diagnosed. A better outcome typically results when steps are taken to lessen the chance of urinary tract infection (which can commonly occur when a catheter is used), and skin inflammation.

Resources

PERIODICALS

Zaninovic, V. "On the etiology of tropical spastic paraparesis and human T-cell lymphotropic virus-I-associated myelopathy." Int J Infect Dis. 3, no. 3 (Spring 1999): 168–76.

OTHER

National Institute of Neurological Disorders and Stroke. NINDS Tropical Spastic Paraparesis Information Page. (December 24, 2003). <http://www.ninds.nih.gov/health_and_medical/disorders/tropical_spastic_paraparesis.htm>.

ORGANIZATIONS

National Institute for Allergy and Infectious Diseases. National Institutes of Health, 31 Center Drive, Room 7A50, MSC 2520, Bethesda, MD 20892-2520. (301) 435-3848. <http://www.niaid.nih.gov>.

National Institute for Neurological Disorders and Stroke. P.O. Box 5801, Bethesda, MD 20824. (301) 496-5761 or (800) 352-9424. <http://www.ninds.nih.gov>.

National Organization for Rare Disorders. P.O. Box 1968, Danbury, CT 06813-1968. (203) 744-0100 or (800) 999-6673; Fax: (203) 798-2291. orphan@rarediseases.org. <http://www.rarediseases.org>.

Brian Douglas Hoyle, PhD