Nakatsuji Hideaki, Ikeda Tetsuhiko, Hashizume Atsushi, Katsuno Masahisa, Sobue Gen, Nakajima Takashi
Department of Clinical Research, National Hospital Organization Niigata National Hospital, Kashiwazaki, Japan.
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Front Neurol. 2022 Jun 24;13:905613. doi: 10.3389/fneur.2022.905613. eCollection 2022.
Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a rare, slowly progressive, incurable, and hereditary neurodegenerative disease caused by the testosterone-dependent accumulation of pathogenic polyglutamine-expanded androgen receptor protein. After extensive review, two treatments for SBMA have recently been approved in Japan; this decision was based on the results of randomized controlled trials: First, anti-androgen therapy using leuprorelin acetate (leuprorelin), a disease-modifying drug that can inhibit the progression of dysphagia but has not yet been proved to improve gait function; second, cybernic treatment with a wearable cyborg hybrid assistive limb (HAL®) (Cyberdyne Inc. Tsukuba, Japan). The HAL is an innovative walking exercise system that has been shown to significantly improve gait function in eight neuromuscular diseases without reduction in muscle function, including SBMA. It is possible that the combination of these two approaches might yield better outcomes. However, the long-term effects of such a combined approach have yet to be clinically evaluated. Here, we describe the case of a 39-year-old male with SBMA who commenced anti-androgen therapy with leuprorelin 1 year previously; this was followed by cybernic treatment with HAL. The duration of walking exercise with HAL was 20-30 min a day in one session. Over 2 weeks, the patient underwent nine sessions (one course). The efficacy of HAL was evaluated by gait function tests before and after one course of cybernic treatment. Then, leuprorelin treatment was combined with cybernic sessions every 2 months for 2 years (13 courses in total). Walking ability, as evaluated by the 2-min walk test, improved by 20.3% in the first course and peaked 10 months after the commencement of combined therapy (a 59.0% improvement). Walking function was maintained throughout the period. Generally, SBMA is characterized by moderately increased serum levels of creatine kinase (CK), reflecting neuromuscular damage; interestingly, the patient's CK levels decreased dramatically with combined therapy, indicating remarkable functional improvement. Long-term combined therapy improved the patient's gait function with a steady reduction in CK levels. The combination of leuprorelin with cybernic treatment can, therefore, improve and maintain gait function without damaging the motor unit and may also suppress disease progression.
脊髓延髓肌肉萎缩症(SBMA),也称为肯尼迪病,是一种罕见的、缓慢进展的、无法治愈的遗传性神经退行性疾病,由致病性多聚谷氨酰胺扩展的雄激素受体蛋白在睾酮依赖下积累所致。经过广泛审查,日本最近批准了两种治疗SBMA的方法;这一决定基于随机对照试验的结果:第一,使用醋酸亮丙瑞林(亮丙瑞林)进行抗雄激素治疗,这是一种疾病修饰药物,可以抑制吞咽困难的进展,但尚未被证明能改善步态功能;第二,使用可穿戴半机械人混合辅助肢体(HAL®)(日本筑波赛博动力公司)进行控制论治疗。HAL是一种创新的步行锻炼系统,已被证明能显著改善包括SBMA在内的八种神经肌肉疾病的步态功能,且不会降低肌肉功能。这两种方法的结合可能会产生更好的效果。然而,这种联合方法的长期效果尚未进行临床评估。在此,我们描述了一名39岁患有SBMA的男性病例,他在1年前开始使用亮丙瑞林进行抗雄激素治疗;随后接受了HAL控制论治疗。使用HAL进行步行锻炼的持续时间为每天20 - 30分钟,分一次进行。在2周内,患者接受了9次治疗(一个疗程)。通过在一个疗程的控制论治疗前后进行步态功能测试来评估HAL的疗效。然后,亮丙瑞林治疗与每2个月一次的控制论治疗相结合,持续2年(共13个疗程)。通过2分钟步行测试评估的步行能力在第一个疗程中提高了20.3%,并在联合治疗开始后10个月达到峰值(提高了59.0%)。步行功能在整个期间得以维持。一般来说,SBMA的特征是血清肌酸激酶(CK)水平适度升高,反映神经肌肉损伤;有趣的是,联合治疗使患者的CK水平显著下降,表明功能有显著改善。长期联合治疗改善了患者的步态功能,同时CK水平稳步下降。因此,亮丙瑞林与控制论治疗相结合可以改善并维持步态功能,而不会损害运动单位,还可能抑制疾病进展。