期刊
PEDIATRIC NEUROLOGY
卷 115, 期 -, 页码 29-40出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.pediatrneurol.2020.10.013
关键词
Sturge-Weber syndrome; Sirolimus; Seizure; Stroke; Cognitive function; mTOR pathway; Drug trial; qEEG
资金
- National Institutes of Health (NIH) [U54NS065705]
- NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS) [U54NS065705]
- National Institute of Neurological Disorders and Stroke (NINDS) [U54NS065705]
- Faneca 66 Foundation
- Pfizer
Studies suggest sirolimus may be beneficial in improving cognitive impairments in patients with Sturge-Weber syndrome, especially those with impaired processing speed or a history of SLE. Further randomized controlled trials are needed to confirm these potential benefits.
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. (C) 2020 Elsevier Inc. All rights reserved.
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