HTLV-1 associated myelopathy

Joel Oger MD FRCPC (Dr. Oger of the University of British Columbia has no relevant financial relationships to disclose.)
Anthony T Reder MD, editor. (Dr. Reder of the University of Chicago served on advisory boards and as a consultant for Bayer, Biogen Idec, Caremark Rx, Genentech, Genzyme, Novartis, Questcor/Malinkrodt, Serono, and Teva-Marion.)
Originally released April 3, 2001; last updated June 9, 2016; expires June 9, 2019

This article includes discussion of HTLV-1 associated myelopathy, TSP, tropical spastic paraparesis, and HAM/TSP. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

The author's update of this article on HTLV-1 associated myelopathy is an essential tool for physicians and virologists alike. HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is essentially a disease of persons of Caribbean and Japanese origins, which has spread among a number of other ethnic groups. Through horizontal transmission, HTLV-1 infection has started to become recognized among Caucasians and, thus, HAM/TSP. The author expands on the criteria for diagnosis and stresses their practical value. He brings to the world's attention the fact that HTLV-1 pandemy is affecting Canadian Natives of the Northwest Pacific as well as immigrants from Eastern Iran and that the disease is starting to appear among Caucasians. The author defines the similarities and differences between primary progressive multiple sclerosis and HTLV-1 associated myelopathy. He describes the main features of the disease, highlighting the progress made in the biology, epidemiology, and clinical as well as MRI phenotyping. Unfortunately, treatment of the disease has remained disappointing. His clinical experience of the disease, bench work, and insights from many scientific publications will benefit clinicians faced with diagnosing and treating this virally induced inflammatory myelopathy.

Key points

 

• HTLV-I associated myelopathy is a retroviral disease specific to certain ethnic groups and transmitted in a manner similar to HIV. It is the model of virally induced inflammatory demyelinating myelopathies.

 

• Clinically it looks like spinal cord primary progressive multiple sclerosis, and one must think about it as a differential; otherwise, it will be missed. Spinal cord MRI with serology and PCR will make the diagnosis.

 

• The evolution is progressive and leads to disability and death over a matter of years to decades. There is only symptomatic treatment for inflammation and spasticity, but no specific etiologic treatment.

Historical note and terminology

It was in 1984 that A Gessain demonstrated that blood samples from patients with “tropical spastic paraparesis” in Martinique, French Western Indies, reacted with the HTLV-1 virus (Gessain et al 1985). The results were immediately convincing: the great majority of the samples contained antibodies to the HTLV-1 virus and thus pinpointed the etiologic agent responsible for this disorder. The HTLV-1 virus had just been isolated by R Gallo from a leukemia patient living in the Pacific Northwest of North America, probably a West Coast Native (Poeisz et al 1980).

Montgomery and colleagues had posited that cases of “Jamaican neuropathy” could be divided into ataxic and spastic (Montgomery et al 1964). The ataxic form of tropical paraparesis is not yet ascribed to a specific etiology, but some suspect that it could occasionally be due to the HTLV-2 virus. The term “tropical spastic paraparesis” was coined by Mani and colleagues (Mani et al 1969). In 1986, Osame and coworker proposed the term “HTLV-1 associated myelopathy” (Osame et al 1986). Criteria for diagnosis have been updated and modernized by introducing intrathecal antibody secretion as a diagnostic criterion (De Castro-Costa et al 2006). It appears that the most solid argument for the diagnosis in the presence of spasticity comes from quantitative polymerase chain reaction (QPCR), which reveals high proviral load in blood and in CSF lymphocytes of HAM/TSP patients compared to low viral load in carriers (Furtado Mdos et al 2012).

Cases of “tropical spastic paresis” that are clinically indistinguishable from HTLV-1 associated myelopathy, but without antibody or a positive PCR, are frequently found in endemic areas (Ramirez et al 1998; Oger J, personal experience). A high degree of suspicion exists that these cases could be due to a defective virus or a virus similar to HTLV-1, but not yet identified. In some of these cases, the HTLV-1 Tax protein has been amplified despite negative PCR for other viral sequences (Cartier and Ramirez 2005). These cases should, however, retain the designation of “tropical spastic paresis.” This author wants to stress that the diagnosis of “HTLV-1 associated myelopathy” should be reserved to cases where there is evidence of myelopathy and where the presence of the virus has been proven by finding antibodies to HTLV-1 or by PCR amplification. The denomination "tropical spastic paraparesis," or even better "chronic inflammatory myelopathy,” would be more appropriately saved for those cases where the etiologic proof is lacking, rather labeling them as “possible or probable HTLV-1,” a nosological approach that has been started in the multiple sclerosis field, but has confused many physicians and patients.

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