Cui Zhiqiang, Lan Yina, Chang Yan, Liu Xinyun, Wang Jian, Lou Xin, Wang Ruimin
Department of Neurosurgery, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Department of Radiology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Front Neurol. 2023 Sep 27;14:1246430. doi: 10.3389/fneur.2023.1246430. eCollection 2023.
Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is a rare neurodegenerative disease for which there is no specific treatment. Very few cases have been treated with single-target deep brain stimulation (DBS), and the results were not satisfactory. We applied multi-target DBS to an SCA3/MJD patient and performed positron emission computed tomography (PET) before and after DBS to explore the short-term clinical therapeutic effect.
A 26-year-old right-hand-dominant female with a family history of SCA3/MJD suffered from cerebellar ataxia and dystonia. Genetic testing indicated an expanded CAG trinucleotide repeat in the gene and a diagnosis of SCA3/MJD. Conservative treatment had no obvious effect; therefore, leads were implanted in the bilateral dentate nucleus (DN) and the globus pallidus internus (GPi) and connected to an external stimulation device. The treatment effect was evaluated in a double-blind, randomized protocol in five phases (over a total of 15 days): no stimulation, GPi, DN, or sham stimulation, and combined GPi and DN stimulation. F-fluoro-2-deoxy-d-glucose and dopamine transporter PET, Scale for the Assessment and Rating of Ataxia, Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM), Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), and SF-36 quality of life scores were compared before and after DBS.
The Total Scale for the Assessment and Rating of Ataxia scores improved by ~42% (from 24 to 14). The BFMDRS movement scores improved by ~30% (from 40.5 to 28.5). The BFMDRS disability scores improved by ~12.5% (from 16 to 14). Daily living activities were not noticeably improved. Compared with the findings in pre-DBS imaging, F-fluoro-2-deoxy-d-glucose uptake increased in the cerebellum, while according to dopamine transporter imaging, there were no significant differences in the bilateral caudate nucleus and putamen.
Multi-target acute stimulation (DN DBS and GPi DBS) in SCA3/MJD can mildly improve cerebellar ataxia and dystonia and increase cerebellar metabolism.
3型脊髓小脑共济失调（SCA3），也称为Machado-Joseph病（MJD），是一种罕见的神经退行性疾病，尚无特异性治疗方法。很少有病例采用单靶点脑深部电刺激（DBS）治疗，且效果不理想。我们对1例SCA3/MJD患者应用多靶点DBS，并在DBS前后进行正电子发射断层扫描（PET），以探讨其短期临床治疗效果。
1例26岁右利手女性，有SCA3/MJD家族史，患有小脑共济失调和肌张力障碍。基因检测显示该基因中CAG三核苷酸重复序列扩增，诊断为SCA3/MJD。保守治疗效果不明显；因此，将电极植入双侧齿状核（DN）和内侧苍白球（GPi），并连接至体外刺激装置。采用双盲、随机方案分五个阶段（共15天）评估治疗效果：无刺激、GPi刺激、DN刺激、假刺激以及GPi和DN联合刺激。比较DBS前后的氟代脱氧葡萄糖和多巴胺转运体PET、共济失调评估与评分量表、法恩-托洛萨-马林震颤临床评分量表（FTM）、伯克-法恩-马斯登肌张力障碍评分量表（BFMDRS）以及SF-36生活质量评分。
共济失调评估与评分量表总分改善约42%（从24分降至14分）。BFMDRS运动评分改善约30%（从40.5分降至28.5分）。BFMDRS残疾评分改善约12.5%（从16分降至14分）。日常生活活动未见明显改善。与DBS前影像学检查结果相比，小脑氟代脱氧葡萄糖摄取增加，而根据多巴胺转运体成像，双侧尾状核和壳核无显著差异。
SCA3/MJD患者的多靶点急性刺激（DN DBS和GPi DBS）可轻度改善小脑共济失调和肌张力障碍，并增加小脑代谢。
