Experimental Neurosurgery and Neuroanatomy, Department of Neurosciences, University of Leuven, Leuven, Belgium; Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium.
Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium.
Neuromodulation. 2024 Apr;27(3):440-446. doi: 10.1016/j.neurom.2023.10.187. Epub 2023 Nov 24.
Guanine nucleotide-binding protein alpha-activating activity polypeptide O (GNAO1) syndrome, a rare congenital monogenetic disorder, is characterized by a neurodevelopmental syndrome and the presence of dystonia. Dystonia can be very pronounced and even lead to a life-threatening status dystonicus. In a small number of pharmaco-refractory cases, deep brain stimulation (DBS) has been attempted to reduce dystonia. In this study, we summarize the current literature on outcome, safety, and outcome predictors of DBS for GNAO1-associated dystonia.
We conducted a systematic review and meta-analysis on individual patient data. We included 18 studies describing 28 unique patients.
The mean age of onset of symptoms was 2.4 years (SD 3.8); 16 of 28 patients were male, and dystonia was nearly always generalized (20/22 patients). Symptoms were present before DBS for a median duration of 19.5 months, although highly variable, occurring between 3 and 168 months. The exact phenotype, genotype, and radiologic abnormalities varied and seemed to be of little importance in terms of DBS outcome. All studies described an improvement in dystonia. Our meta-analysis focused on pallidal DBS and found an absolute and relative improvement in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) of 32.5 points (37.9%; motor part; p = 0.001) and 5.8 points (21.5%; disability part; p = 0.043) at last follow-up compared with preoperative state; 80% of patients were considered responders (BFMDRS-M reduction by ≥25%). Although worsening over time does occur, an improvement was still observed in patients after >10 years. All reported cases of status dystonicus resolved after DBS surgery. Skin erosion and infection were observed in 18% of patients.
Pallidal DBS can be efficacious and safe in GNAO1-associated dystonia.
鸟嘌呤核苷酸结合蛋白α亚基激活活性多肽 O（GNAO1）综合征是一种罕见的先天性单基因遗传疾病，其特征为神经发育障碍和出现肌张力障碍。肌张力障碍可能非常明显，甚至导致危及生命的发作性肌张力障碍状态。在少数药物难治性病例中，已尝试使用深部脑刺激（DBS）来减轻肌张力障碍。本研究总结了 GNAO1 相关肌张力障碍的 DBS 治疗的结果、安全性和结果预测因素的现有文献。
我们对个体患者数据进行了系统评价和荟萃分析。我们纳入了 18 项研究，共描述了 28 例独特的患者。
症状的平均发病年龄为 2.4 岁（标准差 3.8）；28 例患者中有 16 例为男性，且肌张力障碍几乎总是全身性的（22 例患者中有 20 例）。症状在 DBS 治疗前存在的中位时间为 19.5 个月，尽管变化很大，但发生时间在 3 至 168 个月之间。确切的表型、基因型和放射学异常各不相同，而且似乎与 DBS 结果无关紧要。所有研究均描述了肌张力障碍的改善。我们的荟萃分析重点关注苍白球 DBS，并发现在 Burke-Fahn-Marsden 肌张力障碍评定量表（BFMDRS）中，绝对和相对改善分别为 32.5 分（37.9%；运动部分；p=0.001）和 5.8 分（21.5%；残疾部分；p=0.043），与术前状态相比；80%的患者被认为是有反应者（BFMDRS-M 减少≥25%）。尽管随着时间的推移确实会恶化，但在 >10 年后仍观察到患者有改善。所有报道的发作性肌张力障碍状态在 DBS 手术后均得到缓解。18%的患者出现皮肤侵蚀和感染。
苍白球 DBS 对 GNAO1 相关肌张力障碍是有效且安全的。
