Tropical spastic paraparesis
Encyclopedia
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
.
, 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.
(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.
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.
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
.
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
of the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
by Human T-lymphotropic virus
Human T-lymphotropic virus
Human T-cell Lymphotropic Virus Type 1 , also called the Adult T-cell lymphoma virus type 1, a virus that has been seriously implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis hyper-infection, and a virus cancer link for leukemia...
resulting in paraparesis, weakness of the legs. As the name suggests, it is most common in tropical regions, including the Caribbean
Caribbean
The Caribbean is a crescent-shaped group of islands more than 2,000 miles long separating the Gulf of Mexico and the Caribbean Sea, to the west and south, from the Atlantic Ocean, to the east and north...
and Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
.
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 pallidumTreponema pallidum
Treponema pallidum is a species of spirochaete bacterium with subspecies that cause treponemal diseases such as syphilis, bejel, pinta and yaws. The treponemes have a cytoplasmic and outer membrane...
, which cause inflammation of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
) and with chronic nutritional deficiencies (such as avitaminosis
Avitaminosis
Avitaminosis is any disease caused by chronic or long-term vitamin deficiency or caused by a defect in metabolic conversion, such as tryptophan to niacin...
) or exposure to potentially toxic foods (such as bitter cassava
Cassava
Cassava , also called yuca or manioc, a woody shrub of the Euphorbiaceae native to South America, is extensively cultivated as an annual crop in tropical and subtropical regions for its edible starchy tuberous root, a major source of carbohydrates...
). 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
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
that results in immune dysfunction.
Presentation
Patients with HAM/TSP may also exhibit uveitisUveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
(inflammation of the uveal tract of the eye), arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
(inflammation of one or more joints), pulmonary lymphocytic alveolitis
Alveolitis
Alveolitis can refer to two inflammatory conditions. It can refer to inflammation of the alveoli in the lungs, or the dental alveolus in the jaw.Alveolus in the jaw is also known as dry socket...
(inflammation of the lung tissues), polymyositis
Polymyositis
Polymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:...
(an inflammatory muscle disease), keratoconjunctivitis sicca
Keratoconjunctivitis sicca
Keratoconjunctivitis sicca , also called keratitis sicca, xerophthalmia or dry eye syndrome is an eye disease caused by eye dryness, which, in turn, is caused by either decreased tear production or increased tear film evaporation. It is found in humans and some animals...
(persistent dryness of the cornea and conjunctiva), and infectious dermatitis
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...
(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
Adult T-cell leukemia
Adult T-cell leukemia/lymphoma is a rare cancer of the immune system's own T-cells.Human T cell leukemia/lymphotropic virus type 1 is believed to be the cause of it, in addition to several other diseases.-Signs and symptoms:...
/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 transendothelialEndothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
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
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
, progressing slowly, usually causing symptoms 20–30 years after infection.
Symptoms
- Progressive muscle weakness;
- Sensory disturbance
- SphincterSphincterA sphincter is an anatomical structure, or a circular muscle, that normally maintains constriction of a natural body passage or orifice and which relaxes as required by normal physiological functioning...
dysfunction - Urinary incontinence
- UveitisUveitisUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
- ArthritisArthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
- Pulmonary lymphocyte alveolitis
- PolymyositisPolymyositisPolymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:...
- KeratoconjunctivitisKeratoconjunctivitisKeratoconjunctivitis is inflammation of the cornea and conjunctiva.When only the cornea is inflamed, it is called keratitis; when only the conjunctiva is inflamed, it is called conjunctivitis....
sicca - Infectious dermatitisDermatitis-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...
Treatment
There is no established treatment program for HAM/TSP, although some patients may be given steroids. Clinical studies using interferon alphaInterferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
and plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
have not shown significant patient improvement. Spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
may be treated with baclofen
Baclofen
Baclofen is a derivative of gamma-aminobutyric acid . It is primarily used to treat spasticity and is under investigation for the treatment of alcoholism....
or tizanidine
Tizanidine
Tizanidine is a drug that is used as a muscle relaxant. It is a centrally acting α2 adrenergic agonist. It is used to treat the spasms, cramping, and tightness of muscles caused by medical problems such as multiple sclerosis, spastic diplegia, back pain, or certain other injuries to the spine or...
. Urinary dysfunction should be treated with self-catheterization or oxybutynin
Oxybutynin
Oxybutynin is an anticholinergic medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination , by decreasing muscle spasms of the bladder. It competitively antagonizes the M1, M2, and M3 subtypes of the muscarinic acetylcholine...
.