Myelopathy, Htlv-1-Associated

A tropical spastic paraparesis associated with antibody titers to human T-lymphotropic virus type 1 in the serum was described in Martinique (Gessain et al., 1985) and in Jamaica and Colombia (Rodgers-Johnson et al., 1985); a similar disorder, termed HTLV-1-associated myelopathy, has been found in parts of southwestern Japan, where adult T-cell leukemia/lymphoma (ATLL) is endemic. Osame et al. (1986) first suggested the entity of HTLV-1-associated myelopathy. Miyai et al. (1987) described 2 families with multiple cases of HTLV-1-associated myelopathy. Even though ATLL and HAM were observed in the same area of Japan, there were no observations of the disorders in the same family. It is not known whether the virus that causes ATLL is the same as that associated with HAM, although they seem to be morphologically and immunologically similar. It is possible that they are identical and that HTLV1-associated myelopathy is determined by the ATLL-causing virus plus a specific genetic background.

Mori et al. (1988) described 3 families with slowly progressive spastic paraparesis occurring in a parent and 1 or 2 children. Neurologic examination showed pyramidal signs, with no or mild sensory disturbance. Anti-HTLV-1 antibodies in both serum and CSF were positive, and adult T-cell leukemia-like cells were demonstrated in both peripheral blood and CSF. The patients had previously been diagnosed as having hereditary spastic paraplegia. Proven modes of infection are blood transfusion, sexual contact, and mother-to-child transmission. In 2 of the families, mother-to-child transmission was suspected. In the third family, in which a father and daughter were affected, the mother was also seropositive, suggesting that this may have been a case of mother-to-child transmission also. Transmission by breast milk has been postulated. Since the frequency of HAM among seropositive carriers in Japan is only about 0.03%, genetic factors may play a role in the development of the disorder.

Denic et al. (1988) reported the first instance of familial ATLL in the United States. The patients were a 63-year-old black man, who was born in South Carolina and was living in Brooklyn, New York, and his 40-year-old daughter, who was born in Brooklyn. Both wives of the father had antibodies against HTLV-1; the second wife had acquired the infection from her husband within 3 years of marriage. Salazar-Grueso et al. (1990) presented the pedigree of a Paraguayan family in which 4 individuals in 3 successive generations had spastic paraparesis associated with HTLV-1 infection. They suggested that infection by breast milk may have occurred because the affected persons were breastfed by an infected mother and had never received a transfusion and because this route is believed to be a primary one for HTLV-1 transmission in Japan (Ando et al., 1989). Host factors may explain why some relatives contract the infection whereas others do not. The integration site for the HTLV-1 genome may determine whether there is a nonclonal expansion of peripheral lymphocytes with development of spastic paraparesis or a clonal expansion of lymphocytes leading to T-cell leukemia. In an extensive study of families in Japan, Kajiyama et al. (1986) found that none of 82 children born to seronegative mothers and seropositive fathers were seropositive. The instance of transmission from husband to wife was 61% over 10 years and from wife to husband, 0.4%. These data strongly suggested that HTLV-1 is transmitted from husband to wife by sexual transmission, and from mother to child. It was unclear whether maternal transmission occurred across the placenta or via breastfeeding. Hollsberg and Hafler (1993) discussed the pathogenesis of diseases induced by HTLV-1 infection and made reference to the possible operation of genetic factors.

Chironna et al. (1995) reported that the wife and daughter of a patient with adult T-cell leukemia due to HTLV-1 were HTLV-1 seropositive but clinically normal. The proband came from a small village in Apulia (southeastern Italy), had never received a blood transfusion, and described no risk factors for retroviral infections, such as intravenous drug use.