Effectiveness of Daily Prednisolone to Slow Progression of Human T-Lymphotropic Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis: A Multicenter Retrospective Cohort Study

Abstract

Millions of people are infected with human T-lymphotropic virus type 1 (HTLV-1) worldwide; notable endemic areas include Brazil, the Caribbean islands, Iran, and Japan. A small number of those infected develop the progressive neurodegenerative disease HTLV-1-associated myelopathy (HAM), also known as tropical spastic paraparesis (TSP), which is characterized by chronic spinal cord inflammation and accompanying myelopathic symptoms. The corticosteroid prednisolone (PSL) is a classic treatment for HAM/TSP, yet its effectiveness remains controversial owing to insufficient and conflicting studies. We conducted a multicenter retrospective study using data collected by physicians monitoring patients with HAM/TSP at 7 hospitals throughout Japan. The Osame Motor Disability Score (OMDS) was used to evaluate 57 patients treated with low-dose PSL (mean 4.8 mg/day) versus 29 untreated patients. Roughly half of the evaluations spanned < 3 years (Short-Term) and half > 3 years (Long-Term), with a mean of 3.4 years. While the OMDS of most untreated patients remained unchanged in the Short-Term (87%) and worsened in the Long-Term (79%), most treated patients improved in the Short-Term (52%) and remained unchanged or improved in the Long-Term (68%). Overall, the mean change in OMDS per year was -0.13 in the Steroids group and +0.12 in the Untreated group (p < 0.01). This study addressed the effectiveness of PSL for HAM/TSP in 3 novel ways: 1) continuous low-dose administration; 2) comparison with an untreated group; and 3) Long-Term evaluation. These findings provide robust evidence supporting PSL maintenance therapy for HAM/TSP.

Human T-cell Lymphotropic Virus Type I Associated with Amyotrophic Lateral Sclerosis Syndrome: Immunopathological Aspects and Treatment Options

“…The different workgroups have attracted controversies regarding their use and have reported improvement in response rates and relief of symptoms in patients with high viral loads [2]. The results of a recent study that evaluated patients for several years highlighted the improvement in disability scales in the group that took prednisone in both the short and long term when compared with untreated patients [8,9]. Initial schemes involve methylprednisolone 100 mg IV per day for three days, followed by oral prednisone 15 mg per day [2,8,9].…”

“…The results of a recent study that evaluated patients for several years highlighted the improvement in disability scales in the group that took prednisone in both the short and long term when compared with untreated patients [8,9]. Initial schemes involve methylprednisolone 100 mg IV per day for three days, followed by oral prednisone 15 mg per day [2,8,9]. There are alternative proposals with anti-inflammatory drugs such as cyclosporine, pentoxifylline, danazol, and interferons [8,10].…”

“…The drug mogamulizumab (antibody against chemokine receptor CCR4, which is used in the treatment of adult T cell leukemia-lymphoma associated with HTLV-I retrovirus) has been found to reduce viral load, the proliferation of T and B cells expressing CCR4, and the production of inflammatory cytokines. Recent work has focused on assessing the usefulness of this neurological syndrome [8][9][10][11].…”

Spastic Paraplegias Due to Non-Traumatic Spinal Cord Disorders

“…Whole-exome sequencing of his DNA did not identify pathogenic variants of the SPG3A and other SPG genes. We treated him with oral prednisolone [19], the symptoms did not worsen after that.…”

HTLV-1, the Other Pathogenic Yet Neglected Human Retrovirus: From Transmission to Therapeutic Treatment

“…Until now, corticosteroids effectiveness in patients with TSP/HAM has largely been controversial among clinical studies, with none of them using a placebo-controlled trial, nor evaluating the long-term efficiency of the treatment. A recent retrospective study, however, analyzed prednisolone-treated TSP/HAM patients and untreated TSP/HAM patients for several years [ 188 ]. Continuous uptake of low-doses of prednisolone by TSP/HAM patients improved their Osame Motor Disability Score both in short-term (less than 3 years) and long-term (more than 3 years) durations of treatment, in comparison to untreated TSP/HAM patients.…”