Tropical spastic paraparesis

Tropical spastic paraparesis (TSP) is an infection of the spinal cord by Human T-lymphotropic virus resulting in paraparesis or weakness of the legs. As the name suggests, it is most common in tropical regions, including the Caribbean and Africa.

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History

For several decades the term tropical spastic paraparesis was used to describe a chronic and progressive clinical syndrome that affected adults living in equatorial areas of the world. This condition was initially thought to be associated with infectious agents (such as Treponema pertenue and Treponema pallidum which cause inflammation of the central nervous system) and with chronic nutritional deficiencies (such as avitaminosis) or exposure to potentially toxic foods (such as bitter cassava). Neurological and modern neuroepidemiological studies found that in some individuals no single cause could explain the progressive weakness, sensory disturbance, and sphincter dysfunction that affected individuals with TSP. In spite of public health programs created to eradicate the above-mentioned infectious and nutritional conditions in the tropics, large numbers of people continued to be affected.

During the mid-1980s, an important association was established between the first human retrovirus-human T-cell lymphotrophic virus type 1 (also known as HTLV-1)-and idiopathic TSP (idiopathic means of unknown origin). Since then, this condition has been named HTLV-1 associated myelopathy/ tropical spastic paraparesis or HAM/TSP and scientists now understand that it is a condition caused by a virus that results in immune dysfunction.

Presentation

Patients with HAM/TSP may also exhibit uveitis (inflammation of the uveal tract of the eye), arthritis (inflammation of one or more joints), pulmonary lymphocytic alveolitis (inflammation of the lung tissues), polymyositis (an inflammatory muscle disease), keratoconjunctivitis sicca (persistent dryness of the cornea and conjunctiva), and infectious dermatitis (inflammation of the skin). Co-factors that may play a role in transmitting the disorder include being a recipient of transfusion blood products (especially before 1989), breastmilk feeding from a seropositive mother, intravenous drug use, or being the sexual partner of a seropositive individual for several years. Not every HTLV-1 seropositive carrier will become a HAM/TSP patient. Fewer than 5% will exhibit neurological dysfunction or, eventually, hematological malignancy such as adult T-cell leukemia/lymphoma, suggesting that other host or viral factors are responsible for disease onset.

Pathogenesis

When infected by HTLV-1 the host mounts an antigen specific immune response towards the HTLV-1 antigen. Cytotoxic T-lymphocytes of the host’s immune response release cytokines in an effort to fight the infection. These cytokines facilitate the transendothelial migration of lymphocytes across the blood-brain barrier. Once cytokines are within the central nervous system demyelination is brought as a result of bystander cell injury. The disease is chronic, progressing slowly, usually causing symptoms 20-30 years after infection.

Symptoms

• Progressive muscle weakness;
• Sensory disturbance
• Sphincter dysfunction
• Urinary incontinence
• Uveitis
• arthritis
• Pulmonary lymphocyte alveolitis
• Polymyositis
• Keratoconjunctivitis sicca
• Infectious dermatitis

Prevention

Blood transfusion products are screened for HTLV-1 antibodies.

Treatment

There is no established treatment program for HAM/TSP although some patients may be given steroids. Clinical studies using interferon alpha and plasmapheresis have not shown significant patient improvement. Spasticity may be treated with lioresal or tizanidine. Urinary dysfunction should be treated with self-catheterization or oxybutynin.

Prognosis

HAM/TSP is usually a progressive neurological disorder but it is rarely fatal. Most patients live for several decades after the diagnosis. Their prognosis improves if they take steps to prevent urinary tract infection and skin sore formation, and if they enroll in physical and occupational therapy programs.

References

• Machigashira N, Yoshida Y, Wang S, Osame M (2001). "HTLV-1-associated myelopathy/tropical spastic paraparesis with pseudohypoparathyroidism". Neurology 56 (1): 104-6. PMID 11148245.