Human T-lymphotropic virus 1 neurologic disease

Abstract

Human T-lymphotrophic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a disabling myelopathy, but clinical trials of specific drugs to treat it are lacking. There are many reasons for the absence of specific therapeutic studies, including difficulty in enrolling patients, inadequate measurement tools to evaluate neurologic improvement, and even lack of interest. Oral or intravenous corticosteroids are now the mainstay of HAM/TSP treatment, especially in the initial phase of the disease, when inflammation is more prominent than demyelination. Motor disability, pain, and urinary dysfunction may be ameliorated, but improvement is not sustained in many patients. Valproic acid has emerged as a potential treatment for HAM/TSP; recent evidence shows that this drug can activate viral gene expression and expose virus-infected cells to the immune system, leading to a reduction of the proviral load. Alternative drugs such as methotrexate, pentoxifylline, azathioprine, danazol, and interferon-alpha may be used if steroids fail or cannot be tolerated, but they have not been assessed in randomized clinical trials.

Update on Neurological Manifestations of HTLV-1 Infection

“…Oral or intravenous corticosteroids are still the basis of HAM/TSP treatment, particularly in the initial phase of the disease, when inflammation is more prominent than demyelination and gliosis. Motor disability, pain, and urinary dysfunction may be improved with steroids, but this improvement is usually not sustained in most of the patients [36].…”

“…Despite these theoretical advantages, the drug resulted ineffective to improve motor and other disabilities [40]. Other drugs such as interferon-alpha, cyclosporin A, methotrexate, pentoxifylline, azathioprine, and danazol may be tried if steroids fail or cannot be tolerated, but their use should be balanced in terms of their individual risk-benefit profile [36]. More recently, small open trials of prosultiamine, a vitamin B 1 derivative and known to induce apoptosis in HTLV-1-infected cells [41], and of pentosan polysulfate sodium, an heparinoid with hemorheological properties [42], have provided evidences of some clinical improvement in HAM/TSP.…”

Immunopathogenesis and neurological manifestations associated to HTLV-1 infection

“…Other common complaints are pain and muscle atrophy 67,68 . The development of neurological disability in HAM/TSP occurs mainly during the first year of the disease, and subsequently it becomes relatively stable 69 . However, there are no spontaneous remissions 70 .…”

Upper Motor Neuron Disorders in Africa

“…Some HTLV-1 subjects develop leukaemia or lymphoma. [29][30][31][32] TSP affects mainly adults between 30 and 40 years of age and is considerably more common in women than in men. In 1986, a syndrome similar to TSP was reported in Japan, and was named HTLV-1-associated myelopathy (HAM).…”

“…36 Oral or intravenous corticosteroids are the main treatment of TSP/HAM, especially in the initial phase, but other drugs -for example valproic acid, methotrexate and interferon-alpha -are also suggested if steroids fail or cannot be used. 32 In contrast to the upper MNDs (konzo, neurolathyrism and TSP/HAM), TAN is predominantly a sensory neuropathy frequently seen in malnourished populations. Symptoms of TAN include bilateral optic atrophy, bilateral neurosensory deafness, sensory gait ataxia and symmetrical sensory polyneuropathy.…”