Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, 2168511, Japan.
Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Orphanet J Rare Dis. 2021 Aug 9;16(1):355. doi: 10.1186/s13023-021-01990-3.
Most patients with human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) develop neurogenic bladder dysfunction. However, longitudinal changes and treatment effects remain poorly understood. This study aimed to characterize the clinical course of urinary dysfunction in this population.
This prospective observational study included 547 patients enrolled in HAM-net, a nationwide registry for HAM/TSP in Japan. Urinary dysfunction severity was evaluated using the HAM/TSP-bladder dysfunction symptom score (HAM-BDSS) and the HAM/TSP-bladder dysfunction severity grade (HAM-BDSG). These specific measures were recently developed for assessing urinary dysfunction in HAM/TSP. We analyzed longitudinal changes over a 6-year follow-up period, associations between urinary and gait dysfunction, and treatment efficacy of urinary catheterization and mirabegron (a β3-adrenergic agonist for overactive bladder symptoms).
The mean (standard deviation [SD]) age and disease duration at enrollment were 61.9 (10.7) years and 16.6 (11.6) years, respectively, and 74.6% of patients were women. Only 8.0% were free from urinary symptoms (HAM-BDSG 0), 65.4% had urinary symptoms or were on medication (HAM-BDSG I), and 23.2% and 3.3% used intermittent and indwelling catheters (HAM-BDSG II and III), respectively. HAM-BDSG and BDSS were worse in patients with greater gait dysfunction (p < 0.001 for both). During the 6-year follow-up, 66.7% of patients with HAM-BDSG 0 developed new urinary symptoms. Of those with HAM-BDSG I at enrollment, 10.8% started using urinary catheters. Importantly, HAM-BDSS significantly improved after initiating catheterization (mean [SD] change, - 8.93 [10.78], p < 0.001). The number of patients receiving mirabegron increased in the fourth year. Multivariable linear regression analysis significantly associated mirabegron with improvement in HAM-BDSS (- 5.82, 95% confidence interval - 9.13 to - 2.51, p = 0.001).
Urinary dysfunction affected 92% of patients and progressed over the 6-year follow-up. Urinary symptoms were more severe in patients with poorer gait function. Urinary catheterization and mirabegron were effective in relieving symptoms. Effective utilization of real-world data is key to establishing evidence for rare diseases, such as HAM/TSP.
大多数人类 T 细胞白血病病毒 1 相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者会出现神经源性膀胱功能障碍。然而，其纵向变化和治疗效果仍知之甚少。本研究旨在描述该人群中尿功能障碍的临床病程。
这是一项前瞻性观察性研究，纳入了日本 HAM/TSP 全国登记处 HAM-net 中的 547 例患者。使用 HAM/TSP-膀胱功能障碍症状评分（HAM-BDSS）和 HAM/TSP-膀胱功能障碍严重程度分级（HAM-BDSG）评估尿功能障碍严重程度。这些特定的措施是最近为评估 HAM/TSP 中的尿功能障碍而开发的。我们分析了 6 年随访期间的纵向变化，尿功能与步态功能障碍之间的关系，以及导尿和米拉贝隆（用于治疗膀胱过度活动症的β3-肾上腺素能激动剂）治疗的疗效。
纳入患者的平均（标准差[SD]）年龄和发病时间分别为 61.9（10.7）岁和 16.6（11.6）年，74.6%为女性。仅有 8.0%的患者无尿症状（HAM-BDSG 0），65.4%有尿症状或正在用药（HAM-BDSG I），23.2%和 3.3%分别使用间歇性和留置导尿管（HAM-BDSG II 和 III）。HAM-BDSG 和 BDSS 在步态功能障碍更严重的患者中更差（均 p<0.001）。在 6 年随访期间，HAM-BDSG 0 的 66.7%患者出现新的尿症状。在入组时 HAM-BDSG I 的患者中，有 10.8%开始使用导尿管。重要的是，导尿后 HAM-BDSS 显著改善（平均[SD]变化，-8.93[10.78]，p<0.001）。第四年开始接受米拉贝隆治疗的患者人数增加。多变量线性回归分析显示米拉贝隆与 HAM-BDSS 改善显著相关（-5.82，95%置信区间-9.13 至-2.51，p=0.001）。
尿功能障碍影响了 92%的患者，且在 6 年随访期间逐渐加重。步态功能更差的患者尿症状更严重。导尿和米拉贝隆可有效缓解症状。有效利用真实世界数据对于 HAM/TSP 等罕见疾病的证据建立至关重要。
