Tropical spastic paraparesis (TSP) is a slowly progressive spastic paraparesis caused by the human T-cell lymphotropic virus-1 (HTLV-1), with an insidious onset in adulthood. It has been found all around the world (except in the poles), mainly in tropical and subtropical regions.
Description
For several decades the term tropical spastic paraparesis (TSP) was used to describe a chronic and progressive clinical syndrome that affected adults living in equatorial areas of the world. Neurological and modern epidemiological studies found that in some individuals no one cause could explain the progressive weakness, sensory disturbance, and sphincter dysfunction that affected individuals with TSP. During the mid-1980s, an important association was established between the first human HTLV-1 virus and idiopathic TSP. 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 retrovirus that results in immune dysfunction. The main neurological features of HAM/TSP consist of spasticity and hyperreflexia (increased reflex action) of the lower extremities, urinary bladder disturbance, lower-extremity muscle weakness, sensory disturbances, and loss of coordination. Patients with HAM/TSP may also exhibit arthritis, lung changes, and inflammation of the skin.
Co-factors that may play a role in transmitting the disorder include being a recipient of transfusion blood products, breast-feeding from an infected mother, intravenous drug use, or being the sexual partner of an infected individual for several years.
Demographics
Sporadic cases of TSP have been reported in the United States, mostly in immigrants from countries where this disease is endemic (naturally occurring). In the United States, the lifetime risk of an HTLV-1-infected person developing TSP/HAM has been calculated to be 1.7–7%, similar to that reported for United Kingdom, Africa, and the Caribbean.
The international incidence is difficult to estimate because of the insidious nature of this disease. HAM/TSP is common in regions of endemic HTLV-1, such as the Caribbean, equatorial Africa, Seychelles, southern Japan, and South America. However, it also has been reported from non-endemic areas, such as Europe and the United States. The prevalence in southern Japan is in the range of 8.6–128 per 100,000 inhabitants. An estimated 10–20 million individuals worldwide are carriers of HTLV-1.
HAM/TSP generally affects women more than men, with a female-to-male ratio of 3:1. This disease may occur at any age, with a peak in the third or fourth decade.
Causes and symptoms
The cause of HAM/TSP is still a matter of debate. Whereas only a small proportion of HTLV-1-infected individuals develop HAM/TSP, the mechanisms responsible for the progression of an HTLV-1 carrier state to clinical disease are not clear. However, three hypotheses are considered by scientists as the most likely cause of TSP: direct toxicity, autoimmunity, and bystander damage. The direct toxicity theory of HAM/TSP pathogenesis suggests that HTLV-1-infected cells are directly damaged by certain white blood cells. The autoimmunity theory postulates that the immune system attacks cells that react to HTLV-1 infected cells. In the bystander damage hypothesis, circulating antivirus-specific cells migrating through the central nervous system produce damage to nearby cells that is directed against the infected cells.
Symptoms may begin years after infection. In response to the infection, the body's immune response may injure nerve tissue, causing symptoms including:
spasms and loss of feeling or unpleasant sensations in the lower extremities, accompanied by weakness
decreased sense of touch in mid-body areas
a vibration sensation, especially in the lower extremities, resulting from spinal cord or peripheral nerve involvement
low lumbar pain with irradiation to the legs
increased reflexes of the upper extremities
increased urinary frequency and associated increased incidence of urinary tract infection
Less frequently observed symptoms include tremors in the upper extremities, optical nerve atrophy, deafness, abnormal eye movements, cranial nerve deficits, and absent or diminished ankle jerk reflex.
Diagnosis
During the clinical examination, it is important to exclude other disorders causing progressive spasticity and weakness in the legs. Diagnosis of HAM/TSP criteria typically involve documenting the following:
absence of a history of difficulty walking or running during school age
within two years of onset: increased urinary frequency, nocturia, or retention, with or without impotence; leg cramps or low back pain; symmetric weakness of the lower extremities
within six months of onset: complaints of numbness or dysesthesias of the legs or feet
a clinical examination documenting increased reflexes; spasticity of both legs, abnormal gait (manner of walking), and absence of normal sensory level
Persons with TPS have multiple needs and the team should include a neurologist and a physical therapist. An occupational therapist can prescribe exercises designed to develop fine coordination or compensate for tremor or weakness, or suggest assistive devices. More advanced patients require continual nursing assistance.
Treatment
The US Food and Drug Administration (FDA) has not officially approved any drug for the specific treatment of HAM/TSP in the United States. Many patients benefit from oral prednisolone or equivalent glucocorticoid therapy. A response rate of up to 91% has been reported in less advanced cases. Oral treatment with methylprednisolone may produce excellent to moderate responses in around 70% of patients. Plasmapheresis, interferon, oral azathiaprine, danazol, and vitamin C have been tried and also show transient effects. None of these treatments has been systematically studied in a controlled clinical trial. Antiviral drugs like AZT would be expected to help in reducing viral replication and associated direct cell injury.
The goal of a rehabilitation program for a person affected with HAM/TSP is to restore functions essential to daily living in individuals who have lost these capacities through injury or illness. Most rehabilitation programs are comprehensive in nature and have several different aspects.
Physical therapy is designed to help restore and maintain useful movements or functions and prevent complications such as frozen joints, contractures, or bedsores. Examples of physical therapy include:
stretching and range of motion exercises
exercises to develop trunk control and upper arm muscles
training in walking and appropriate use of assistive devices, such as ambulatory aids, braces, and wheelchairs
training in how to get from one spot to another, such as from the bed to a wheelchair or from a wheelchair to the car
training in how to fall safely in order to cause the least possible damage
Occupational therapy focuses on specific activities of daily living that primarily involve the arms and hands. Examples include grooming, dressing, eating, handwriting, and driving.
Some rehabilitation centers have innovative programs designed to help people compensate for loss of memory or slowed learning ability. Rehabilitation may be carried out in a residential or an outpatient setting.
Clinical trials
In 2004 there were some open clinical trials for the study and treatment of TSP, including:
"Phase I Study of T Cell Large Granular Lymphocytic Leukemia in Humanized MiK-Beta-1 Monoclonal Antibody Directed Toward the IL-2R/IL-15R Subunit (CD122)," sponsored by National Cancer Institute (NCI).
Further updated information on these clinical trials can be found at the National Institutes of Health website for clinical trials at <www.clinicaltrials.gov>.
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.
Special concerns
An important component in the care of patients with TSP is the prevention of infections with the HTLV-1 virus. Several studies indicate that transmission of the HTLV-1 virus occurs through sexual or other intimate contact, intrauterine exposure, newborn exposure via breast milk, sharing of needles by drug abusers, and blood transfusion from infected persons. Transfusion of HTLV-1 antibody-positive blood causes infection in about 60% of recipients. Breastfeeding is contraindicated for mothers who are carriers of HTLV-1.
BOOKS
Parker, James N., and Philip M. Parker. The Official Patient's Sourcebook on Tropical Spastic Paraparesis. San Diego: Icon Group International, 2002.
PERIODICALS
Mora, Carlos A., et al. "Human T-lymphotropic Virus Type I-associated Myelopathy/Tropical Spastic Paraparesis: Therapeutic Approach." Current Treatment Options in Infectious Diseases 5 (2003): 443–455.
National Organization for Rare Disorders (NORD). P.O. Box 1968 (55 Kenosia Avenue), Danbury, CT 06813-1968. (203) 744-0100 or (800) 999-NORD (6673); Fax: (203) 798-2291. orphan@rarediseases.org. <http://www.rarediseases.org>.
National Institute of Allergy and Infectious Diseases (NIAID). 31 Center Drive, Rm. 7A50 MSC 2520, Bethesda, MD 20892-2520. (301) 496-5717. <http://www.niaid.nih.gov>.
