Sirolimus Treatment in Sturge-Weber Syndrome
| Autor: | Alison J. Sebold, Jacqueline W. Sievers, Bernard A. Cohen, Joshua B. Ewen, Anna W. Byars, Stacy J. Suskauer, Lindsay F. Smegal, T. Andrew Zabel, Tomoyuki Mizuno, Anne M. Comi, Matthew Ryan, Adrienne M. Hammill, Alyssa M. Day, Alexander A. Vinks, Cameron Thomas, Jack H. Adamek, Eric H. Kossoff |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Sturge–Weber syndrome Electroencephalography Article Young Adult Developmental Neuroscience Sturge-Weber Syndrome Internal medicine medicine Humans Cognitive Dysfunction Child Adverse effect Protein Kinase Inhibitors Stroke Depression (differential diagnoses) Sirolimus medicine.diagnostic_test business.industry Cognition medicine.disease Neurology Child Preschool Pediatrics Perinatology and Child Health Trough level Female Neurology (clinical) business medicine.drug |
| Zdroj: | Pediatr Neurol |
| ISSN: | 0887-8994 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect