Background

Sturge-Weber syndrome is a rare neurovascular disorder associated with capillary malformation, seizures, cognitive impairments, and stroke-like episodes (SLEs), arising from a somatic activating mutation in GNAQ. Studies suggest this mutation may cause hyperactivation of the mammalian target of rapamycin pathway. Sirolimus is an mammalian target of rapamycin inhibitor studied in other vascular anomalies and a potentially promising therapy in Sturge-Weber syndrome.

Methods

Ten patients with Sturge-Weber syndrome brain involvement and cognitive impairments were enrolled. Oral sirolimus was taken for six months (maximum dose: 2 mg/day, target trough level: 4-6 ng/mL). Neuropsychological testing, electroencephalography, and port-wine score were performed at baseline and after six months on sirolimus. Neuroquality of life, adverse events, and Sturge-Weber Syndrome Neurological Score (neuroscore) were recorded at each visit.

Results

Sirolimus was generally well tolerated; one subject withdrew early. Adverse events considered related to sirolimus were mostly (15/16) grade 1. A significant increase in processing speed was seen in the overall group (P = 0.031); five of nine patients with available data demonstrated statistically rare improvement in processing speed. Improvements were seen in the neuroquality of life subscales measuring anger (P = 0.011), cognitive function (P = 0.015), and depression (P = 0.046). Three subjects experiencing SLEs before and during the study reported shortened recovery times while on sirolimus.

Conclusions

Sirolimus was well tolerated in individuals with Sturge-Weber syndrome and may be beneficial for cognitive impairments, especially in patients with impaired processing speed or a history of SLE. A future, randomized, placebo-controlled trial of sirolimus in patients with Sturge-Weber syndrome is needed to further understand these potentially beneficial effects.

中文翻译：

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Sturge-Weber 综合征的西罗莫司治疗

背景

Sturge-Weber 综合征是一种罕见的与毛细血管畸形、癫痫发作、认知障碍和中风样发作 (SLE) 相关的神经血管疾病，由 GNAQ 中的体细胞激活突变引起。研究表明，这种突变可能导致哺乳动物雷帕霉素靶点通路的过度激活。西罗莫司是在其他血管异常中研究的雷帕霉素抑制剂的哺乳动物靶标，也是 Sturge-Weber 综合征的潜在有希望的治疗方法。

方法

招募了 10 名 Sturge-Weber 综合征大脑受累和认知障碍患者。口服西罗莫司 6 个月（最大剂量：2 mg/天，目标谷浓度：4-6 ng/mL）。在基线和西罗莫司治疗六个月后进行神经心理学测试、脑电图和葡萄酒评分。在每次就诊时记录神经生活质量、不良事件和 Sturge-Weber 综合征神经学评分（neuroscore）。

结果

西罗莫司通常耐受性良好；一名受试者提前退出。与西罗莫司相关的不良事件大多为（15/16）1级。整个组的处理速度显着提高（P  = 0.031）；有可用数据的 9 名患者中有 5 名在处理速度方面表现出统计学上罕见的改善。在测量愤怒（ P  = 0.011）、认知功能（P  = 0.015）和抑郁（P  = 0.046）的生活神经质量分量表中看到了改善。三名在研究之前和期间经历过 SLE 的受试者报告说，服用西罗莫司时恢复时间缩短。

结论

西罗莫司在 Sturge-Weber 综合征患者中具有良好的耐受性，并且可能对认知障碍有益，特别是在处理速度受损或有 SLE 病史的患者中。未来需要对 Sturge-Weber 综合征患者进行西罗莫司的随机、安慰剂对照试验，以进一步了解这些潜在的有益作用。