Nation-wide epidemiological study of Japanese patients with rare viral myelopathy using novel registration system (HAM-net)

Abstract

BackgroundAt least one million people are infected with human T-lymphotropic virus type 1 (HTLV-1) in Japan, a small percentage of whom develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia/lymphoma (ATLL). Patients with HAM/TSP suffer from progressively worsening myelopathic symptoms, such as motor disability and bladder dysfunction, and may become wheelchair-bound or even bedridden.MethodsTo learn more about this rare, debilitating disease, we established the national registration system “HAM-net” in March 2012. We continuously obtain detailed data from enrolled patients using the registration forms and an annual telephone interview. In this retrospective study, we describe the demographics and clinical histories of 383 registered patients from all over Japan.ResultsPatients were diagnosed at a median of 53 years old, long after disease onset at 45. Most (55.3 %) were originally from the southernmost regions, Kyushu and Okinawa. The main initial symptoms were difficulty walking (81.9 %), urinary dysfunction (38.5 %), and lower limb sensory disturbances (13.9 %). Many patients reported frequent leg numbness and leg pain, and the vast majority required medical intervention for urinary symptoms and constipation. A median of 8 years elapsed from the onset of motor symptoms to Osame Motor Disability Score (OMDS) 5 (requiring unilateral support), 12.5 years to OMDS 6 (requiring bilateral support), and 18 years to OMDS 9 (unable to walk). Health Assessment Questionnaire - Disability Index (HAQ-DI) tasks related to mobility, as opposed to hand motions, were very difficult for HAM/TSP patients and well-correlated with OMDS. Scores on the MOS 36-Item Short-Form Health Survey (SF-36) indicated that physical functioning was severely impaired in HAM/TSP patients. Patients with a history of blood transfusion (19.1 %) were older and suffered from more severe disability as indicated by their high HAQ-DI scores. Patients with a family history of HAM/TSP (8.4 %) were younger and had relatively mild symptoms given their long disease durations; many (15.6 %) also had a relative with ATLL.ConclusionsThe HAM-net national registration system has been an effective tool for gathering personal and clinical data from HAM/TSP patients scattered throughout Japan. We expect to conduct many retrospective and prospective epidemiological studies using HAM-net in the future.

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

“…It should be noted that not only was this study national in scope, but the data suggest that our patients were a nationally representative sample: demographics and clinical features were similar between this study and our nationwide epidemiological study, in which 74.2% of respondents were female and reported an age of onset of 45 years old, age at diagnosis of 53 years, age at presentation of 63 years, and disease duration of 17 years [30]. Thus, though not without its limitations, our study suggests that PSL effectively slows, stops, or even somewhat reverses the course of HAM/TSP when taken continuously over several years, and we believe our results are applicable to the general HAM/TSP patient population.…”

“…Patients were divided into groups based on period of evaluation; we decided to divide them into BShort-Term^(<3 years) and BLong-Term^(> 3 years) groups because reports indicated that changes in OMDS typically appear over 3 years, meaning that a typical untreated patient evaluated over at least 3 years would be expected to exhibit an increase in OMDS [30].…”

Efficacy of mirabegron for overactive bladder with human T cell lymphotropic virus‐1 associated myelopathy

“…In addition, several studies have reported that the incidence of adverse events, such as dry mouth and constipation, was similar between patients treated with mirabegron and those treated with placebo . However, some studies reported that many HAM/TSP patients suffered from constipation and dry mouth even before treatment . Thus, mirabegron may be more convenient to administer in HAM/TSP patients with OAB than anticholinergic agents.…”

Proposal of Classification Criteria for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Disease Activity

“…For clinical course analysis, retrospective data from patients who had enrolled in the Japanese HAM/TSP patient registry called “HAM-net” were used ( Coler-Reilly et al, 2016 ). There were 453 patients registered with “HAM-net” from March 2012 until December 2015 ( Figure 1 ).…”

“…There exists a wide variation in the progression rates of HAM/TSP ( Coler-Reilly et al, 2016 ), which suggests the need for stratified medicine. Some studies have reported a subgroup of patients with rapid progression and another subgroup with very slow progression.…”