Tropical spastic paraparesis (TSP), also known as HTLV-associated myelopathy or chronic progressive myelopathy, is an infection of the spinal cord by Human T-lymphotropic virus resulting in paraparesis, weakness of the legs. As the name suggests, it is most common in tropical regions, including the Caribbean and Africa.
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 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) was established. 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, 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 toward 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 bloodâ€"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 20â€"30 years after infection.
Vaccine Development
Currently, there is no licensed vaccine to protect against HTLV-1 or HTLV-2 in the US. At least 500,000 of the individuals infected with HTLV-1 eventually develop an often rapidly fatal leukemia, while others will develop a debilitative myelopathy, and yet others will experience uveitis, infectious dermatitis, or another inflammatory disorder. HTLV-2 is associated with milder neurologic disorders and chronic pulmonary infections. The novel HTLV-3 and HTLV-4 have been isolated only in a few cases. Human T cell lymphotropic virus types I and II (HTLV-I/II) are endemic in certain areas of the world. They cause two life-threatening diseases, adult T cell leukaemia/lymphoma and tropical spastic paraparesis. A vaccine is needed because in developing countries there are no other feasible preventive interventions against these diseases and in Western countries intravenous drug users at high risk for HTLV-I and HTLV-II infections and the health workers in contact with such populations must be protected. A recombinant adenovirus vector that expresses the HTLV-I envelope glycoprotein env in HeLa cells in the clinical trial stage. A pneumococcalpolysaccharide vaccine has elicited significant increases in concentrations of IgG against all 5 serotypes tested at 1 and 6 months after immunization. While there is no present licensed vaccine, there are many factors which make a vaccine against HTLV-1 feasible. The virus displays relatively low antibody production variability, natural immunity does occur in humans, and experimental vaccination using envelope antigens has been shown to be successful in animal models.
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 baclofen 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.
Similar disorders
A similar disorder can occur in patients with HIV.
References
- Machigashira N, Yoshida Y, Wang S, Osame M (9 January 2001). "HTLV-1-associated myelopathy/tropical spastic paraparesis with pseudohypoparathyroidism". Neurology 56 (1): 104â€"6. doi:10.1212/wnl.56.1.104. PMID 11148245.Â
External links
- International Retrovirology Association