Sirolimus Treatment in Sturge-Weber Syndrome

Abstract Background Sturge-Weber syndrome is a rare neurovascular disorder associated with capillary malformation, seizures, cognitive impairments, and stroke-like episodes (SLE), arising from a somatic activating mutation in GNAQ. Studies suggest this mutation may cause hyperactivation of the mTOR pathway. Sirolimus is an mTOR inhibitor studied in other vascular anomalies, and a potentially promising therapy in Sturge-Weber syndrome. Methods 10 patients with Sturge-Weber syndrome brain involvement and cognitive impairments were enrolled. Oral sirolimus was taken for 6 months (maximum dose 2 mg/day, target trough level 4-6 ng/mL). Neuropsychological testing, electroencephalogram (EEG), and port-wine score were done at baseline and after 6 months on sirolimus. Neuroquality of life (Neuro-QoL), 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); N=5/9 with available data demonstrated statistically rare improvement in processing speed. Improvements were seen in the Neuro-QoL sub-scales measuring anger (p=0.011), cognitive function (p=0.015), and depression (p=0.046). Three subjects experiencing SLE before and during the study reported shortened recovery times while on sirolimus. Conclusions Sirolimus was well tolerated in 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-control trial of sirolimus in Sturge-Weber syndrome patients is needed to further understand these potentially beneficial effects.