Tropical spastic paraparesis

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Tropical spastic paraparesis
Other namesHTLV-I-associated myelopathy (HAM) or HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [1]
HTLV-1 EM 8241 lores.jpg
HTLV-1 which causes TSP
Specialty Neurology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Bowel dysfunction [2]
Causes HTLV-1 retrovirus causes 80% of cases [3]
Diagnostic method Lumbar puncture, MRI [2]
TreatmentInterferon alpha, corticosteroids [3]

Tropical spastic paraparesis (TSP), is a medical condition that causes weakness, muscle spasms, and sensory disturbance 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. [4] Blood transfusion products are screened for human T-lymphotropic virus 1 (HTLV-1) antibodies, as a preventive measure. [5]

Contents

Signs and symptoms

Some of the signs of Tropical spastic paraparesis are: [2]

Polymyositis Polymyositis HE.jpg
Polymyositis
  • Leg instability
  • Urinary dysfunction.
  • Bowel dysfunction
  • Back pain
  • Erectile problems
  • Psoriasis

Individuals with 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). [6]

HTLV-1 can be transmitted via breastfeeding (mother to child), sexual contact, via blood contact (transfusion or needle sharing). [7]

Pathogenesis

In Tropical spastic paraparesis, HTLV-1 shows elevated cellular acquired immune response as well as high production of proinflammatory cytokines. IFN overexpression has been demonstrated as well. Also the number of NK cells (CD56+ and CD16+) is diminished. [8]

Diagnosis

Among the methods of diagnosing tropical spastic paraparesis are MRI (magnetic resonance imaging) and lumbar puncture (which may show lymphocytosis). [2]

Often, the diagnosis process is based on symptoms and one's risk of exposure to the virus. A spinal tap or lumbar puncture may be used to obtain blood and CSF samples which can then be tested for parts of the virus or antibodies produced to combat the virus. MRI may be performed on the brain and spinal cord to check for abnormalities such as spinal cord degeneration and other potential causes of symptoms. [9]

Treatment

Immunoglobulin Immunoglobulin.png
Immunoglobulin

Treatment of TSP involves corticosteroids to help with inflammation. Though any success with corticosteroids is short-lived, with symptoms worsened as the dosage is reduced. A synthetic derivative, 17-alpha-ethinyltestosterone, can be used to treat Tropical spastic paraparesis, improvement in motor and bladder function was reported but not sustainable. [10]

Mogamulizumab, an anti-CCR4 IgG1 monoclonal antibody, is also being researched as a possible treatment for Tropical spastic paraparesis. The antibody reduces HTLV-1 proviral load and production of proinflammatory cytokines. Valproic acid has also succeeded in reducing the proviral load of HTLV-1 (though clinical benefits were minimal or none). A further combination of valproic acid and zidovudine has demonstrated a decrease in proviral loads (in animals). [11]

Prognosis

The prognosis for Tropical spastic paraparesis indicates some improvement in a percentage of cases due to immunosuppressive treatment. A higher percentage will eventually lose the ability to walk within a ten-year interval. [12]

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).[ medical citation needed ]

Tropical myeloneuropathies are classified as two separate syndromes: tropical ataxic neuropathy (TAN) and tropical spastic paraparesis (TSP). They are placed together because they are found in tropical countries, although tropical spastic paraparesis has occurred in temperate countries (e.g., Japan). [13]

Related Research Articles

Inclusion body myositis (IBM) is the most common inflammatory muscle disease in older adults. The disease is characterized by slowly progressive weakness and wasting of both proximal muscles and distal muscles, most apparent in the finger flexors and knee extensors. IBM is often confused with an entirely different class of diseases, called hereditary inclusion body myopathies (hIBM). The "M" in hIBM is an abbreviation for "myopathy" while the "M" in IBM is for "myositis". In IBM, two processes appear to occur in the muscles in parallel, one autoimmune and the other degenerative. Inflammation is evident from the invasion of muscle fibers by immune cells. Degeneration is characterized by the appearance of holes, deposits of abnormal proteins, and filamentous inclusions in the muscle fibers. sIBM is a rare disease, with a prevalence ranging from 1 to 71 individuals per million.

<span class="mw-page-title-main">Transverse myelitis</span> Medical condition of the spinal cord

Transverse myelitis (TM) is a rare neurological condition wherein the spinal cord is inflamed. The adjective transverse implies that the spinal inflammation (myelitis) extends horizontally throughout the cross section of the spinal cord; the terms partial transverse myelitis and partial myelitis are sometimes used to specify inflammation that affects only part of the width of the spinal cord. TM is characterized by weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional urethral and anal sphincter activities, and dysfunction of the autonomic nervous system that can lead to episodes of high blood pressure. Signs and symptoms vary according to the affected level of the spinal cord. The underlying cause of TM is unknown. The spinal cord inflammation seen in TM has been associated with various infections, immune system disorders, or damage to nerve fibers, by loss of myelin. As opposed to leukomyelitis which affects only the white matter, it affects the entire cross-section of the spinal cord. Decreased electrical conductivity in the nervous system can result.

Myelitis is inflammation of the spinal cord which can disrupt the normal responses from the brain to the rest of the body, and from the rest of the body to the brain. Inflammation in the spinal cord, can cause the myelin and axon to be damaged resulting in symptoms such as paralysis and sensory loss. Myelitis is classified to several categories depending on the area or the cause of the lesion; however, any inflammatory attack on the spinal cord is often referred to as transverse myelitis.

<span class="mw-page-title-main">Human T-lymphotropic virus 1</span> Species of virus

Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseases including very aggressive adult T-cell lymphoma (ATL), HTLV-I-associated myelopathy, uveitis, Strongyloides stercoralis hyper-infection and some other diseases. It is thought that about 1–5% of infected persons develop cancer as a result of the infection with HTLV-I over their lifetimes.

Encephalomyelitis is inflammation of the brain and spinal cord. Various types of encephalomyelitis include:

<span class="mw-page-title-main">Adult T-cell leukemia/lymphoma</span> Human disease

Adult T-cell leukemia/lymphoma is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role of the virus in the cause of the neoplasm. A small amount of HTLV-1 individuals progress to develop ATL with a long latency period between infection and ATL development. ATL is categorized into 4 subtypes: acute, smoldering, lymphoma-type, chronic. Acute and Lymphoma-type are known to particularity be aggressive with poorer prognosis.

Internexin, alpha-internexin, is a Class IV intermediate filament approximately 66 KDa. The protein was originally purified from rat optic nerve and spinal cord. The protein copurifies with other neurofilament subunits, as it was originally discovered, however in some mature neurons it can be the only neurofilament expressed. The protein is present in developing neuroblasts and in the central nervous system of adults. The protein is a major component of the intermediate filament network in small interneurons and cerebellar granule cells, where it is present in the parallel fibers.

This is a list of AIDS-related topics, many of which were originally taken from the public domain U.S. Department of Health Glossary of HIV/AIDS-Related Terms, 4th Edition.

<span class="mw-page-title-main">Arachnoiditis</span> Inflammation of the arachnoid mater

Arachnoiditis is an inflammatory condition of the arachnoid mater or 'arachnoid', one of the membranes known as meninges that surround and protect the nerves of the central nervous system, including the brain and spinal cord. The arachnoid can become inflamed because of adverse reactions to chemicals, infection from bacteria or viruses, as the result of direct injury to the spine, chronic compression of spinal nerves, complications from spinal surgery or other invasive spinal procedures, or the accidental intrathecal injection of steroids intended for the epidural space. Inflammation can sometimes lead to the formation of scar tissue and adhesion that can make the spinal nerves "stick" together, a condition where such tissue develops in and between the leptomeninges. The condition is extremely painful, especially when progressing to adhesive arachnoiditis. Another form of the condition is arachnoiditis ossificans, in which the arachnoid becomes ossified, or turns to bone, and is thought to be a late-stage complication of the adhesive form of arachnoiditis.

<span class="mw-page-title-main">Neurosyphilis</span> Infection of the central nervous system in a patient with syphilis

Neurosyphilis refers to infection of the central nervous system in a patient with syphilis. In the era of modern antibiotics, the majority of neurosyphilis cases have been reported in HIV-infected patients. Meningitis is the most common neurological presentation in early syphilis. Tertiary syphilis symptoms are exclusively neurosyphilis, though neurosyphilis may occur at any stage of infection.

<span class="mw-page-title-main">Neuromuscular disease</span> Medical condition

A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junction, or skeletal muscle, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and weakness. Issues with sensation can also occur.

Bovine leukemia virus (BLV) is a retrovirus which causes enzootic bovine leukosis in cattle. It is closely related to the human T‑lymphotropic virus type 1 (HTLV-I). BLV may integrate into the genomic DNA of B‑lymphocytes as a DNA intermediate, or exist as unintegrated circular or linear forms. Besides structural and enzymatic genes required for virion production, BLV expresses the Tax protein and microRNAs involved in cell proliferation and oncogenesis. In cattle, most infected animals are asymptomatic; leukemia is rare, but lymphoproliferation is more frequent (30%).

<span class="mw-page-title-main">HLA-DR1</span>

HLA-DR1 (DR1) is a HLA-DR serotype that recognizes the DRB1*01 gene products. It has been observed to be common among centenarians.

<span class="mw-page-title-main">Central nervous system disease</span> Disease of the brain or spinal cord

Central nervous system diseases, also known as central nervous system disorders, are a group of neurological disorders that affect the structure or function of the brain or spinal cord, which collectively form the central nervous system (CNS). These disorders may be caused by such things as infection, injury, blood clots, age related degeneration, cancer, autoimmune disfunction, and birth defects. The symptoms vary widely, as do the treatments.

<span class="mw-page-title-main">Primate T-lymphotropic virus</span> Informal grouping of virus species

The primate T-lymphotropic viruses (PTLVs) are a group of retroviruses that infects primates, using their lymphocytes to reproduce. The ones that infect humans are known as human T-lymphotropic virus (HTLV), and the ones that infect Old World monkeys are called simian T-lymphotropic viruses (STLVs). PTLVs are named for their ability to cause adult T-cell leukemia/lymphoma, but in the case of HTLV-1 it can also cause a demyelinating disease called tropical spastic paraparesis. On the other hand, newer PTLVs are simply placed into the group by similarity and their connection to human disease remains unclear.

<span class="mw-page-title-main">Human T-lymphotropic virus 2</span> Species of virus

A virus closely related to HTLV-I, human T-lymphotropic virus 2 (HTLV-II) shares approximately 70% genomic homology with HTLV-I. It was discovered by Robert Gallo and colleagues.

Mogamulizumab, sold under the brand name Poteligeo, is a humanized, afucosylated monoclonal antibody targeting CC chemokine receptor 4 (CCR4). The U.S. Food and Drug Administration (FDA) approved it in August 2018 for treatment of relapsed or refractory mycosis fungoides and Sézary disease. It was approved in Japan in 2012, for the treatment of relapsed or refractory CCR4+ adult T-cell leukemia/lymphoma (ATCLL) and in 2014, for relapsed or refractory CCR4+ cutaneous T cell lymphoma (CTCL). The latter approval was based on study with 28 subjects.

Tropical ataxic neuropathy is a disease or category of diseases that commonly causes disability and increases mortality. The causes of TAN are not understood; there is no generally accepted treatment, and the reported outcomes are inconsistent. The disease affects poor tropical populations; there are no good statistics on how many people are affected worldwide, but in some populations, more than a quarter of people are affected. Malnutrition may play a role.

Tropical neuropathy is a class of illnesses with similar signs and symptoms, including konzo, tropical spastic paraparesis (TSP), and tropical ataxic neuropathy (TAN). TAN is poorly understood, and some researchers subdivide it further into separate illnesses.

References

  1. Oh, Unsong; Jacobson, Steven (23 December 2016). "Treatment of HTLV-I-Associated Myelopathy / Tropical Spastic Paraparesis: Towards Rational Targeted Therapy". Neurol Clin. 26 (3): 781–x. doi:10.1016/j.ncl.2008.03.008. PMC   2610848 . PMID   18657726.
  2. 1 2 3 4 "Tropical Spastic Paraparesis. About TSP medical condition | Patient". Patient. Retrieved 24 July 2016.
  3. 1 2 "Tropical Spastic Paraparesis Information Page | National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 3 January 2018.
  4. "Tropical Spastic Paraparesis Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". www.ninds.nih.gov. Archived from the original on 2016-12-15. Retrieved 2015-08-13.
  5. Centers for Disease Control (CDC) (1988). "Licensure of screening tests for antibody to human T-lymphotropic virus type I". MMWR. 37 (48): 736–40, 745–7. PMID   3143058.
  6. Clarke, Charles; Howard, Robin; Rossor, Martin; Shorvon, Simon D. (2011-09-09). Neurology: A Queen Square Textbook. John Wiley & Sons. ISBN   9781444356359.
  7. "HTLV-1 associated myelopathy/tropical spastic paraparesis | Disease | Overview | Office of Rare Diseases Research (ORDR-NCATS)". rarediseases.info.nih.gov. Retrieved 2015-08-13.
  8. Yamano, Yoshihisa; Sato, Tomoo (2012). "Clinical Pathophysiology of Human T-Lymphotropic Virus-Type 1-Associated Myelopathy/Tropical Spastic Paraparesis". Frontiers in Microbiology. 3: 389. doi: 10.3389/fmicb.2012.00389 . PMC   3494083 . PMID   23162542.
  9. "HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)". Merck Manual Consumer Version. Retrieved 28 February 2023.
  10. Ali, A (2006). "Tropical spastic paraparesis and polymyositis: a still unfolding story". West Indian Medical Journal. 55 (6): 459–63. doi: 10.1590/S0043-31442006000600023 . PMID   17691249.
  11. Human T-Cell Lymphotropic Viruses~treatment at eMedicine
  12. Prayson, Richard A. (2011-11-15). Neuropathology. Elsevier Health Sciences. ISBN   978-1437709490.
  13. Tropical Myeloneuropathies at eMedicine

Further reading