sirolimus and Sturge-Weber-Syndrome

Sturge-Weber syndrome (SWS) is characterized by facial capillary malformation, leptomeningeal capillary malformations, and choroidal and episcleral vascular malformations. These malformations produce neurologic and ophthalmological symptoms including seizures and glaucoma. A premature male newborn without prenatal diagnosis presented with severe bilateral SWS and was started on systemic sirolimus and aspirin. The patient has remained seizure-free for 23 months and demonstrated an excellent response to pulsed dye laser treatment.

Topics: Administration, Oral; Aspirin; Drug Therapy, Combination; Electroencephalography; Humans; Infant, Newborn; Infant, Premature; Lasers, Dye; Magnetic Resonance Imaging; Male; Port-Wine Stain; Primary Prevention; Prognosis; Risk Assessment; Seizures; Severity of Illness Index; Sirolimus; Sturge-Weber Syndrome; Treatment Outcome

Sturge-Weber syndrome (SWS) is characterized by port-wine stains (PWS) affecting the face, eyes, and central nervous system. Pulsed dye laser (PDL) is the standard treatment for PWS. Unfortunately, recurrence is frequent because of reformation and reperfusion of blood vessels.. We sought to assess the clinical efficacy of topical rapamycin combined with PDL in PWS of patients with SWS.. We conducted a phase II, randomized, double-blind, intraindividual placebo-controlled, clinical trial. We recruited 23 patients with SWS and facial PWS (12 women; median age 33 years, age range 17-65 years) from the University Clinic of Navarra, Spain. Four interventions were evaluated: placebo, PDL + placebo, rapamycin, and PDL + rapamycin. Clinical and histologic responses were evaluated using a chromatographic computerized system, spectrometry, and histologic analyses at 6, 12, and 18 weeks after the intervention.. PDL + rapamycin yielded the lowest digital photographic image score and the lowest percentage of vessels in histologic analysis, and showed a statistically significant improvement compared with the other interventions. The treatment was generally well tolerated.. PDL was only applied to the lateral parts of the PWS area.. Topical rapamycin associated with PDL seems to be an effective treatment for PWS in patients with SWS.

Topics: Administration, Topical; Adolescent; Adult; Aged; Capillaries; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Lasers, Dye; Male; Middle Aged; Port-Wine Stain; Sirolimus; Sturge-Weber Syndrome; Vascular Malformations; Young Adult

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Child; Child, Preschool; Cognitive Dysfunction; Electroencephalography; Female; Humans; Male; Protein Kinase Inhibitors; Sirolimus; Sturge-Weber Syndrome; Young Adult

In the last few years, the use of oral sirolimus has shown promising results in the treatment of some complex vascular anomalies, and recently, it has been used in patients with Sturge-Weber syndrome (SWS). We present the case of an 11-year-old girl with the diagnosis of SWS and hemifacial overgrowth treated with oral sirolimus. Throughout the eight months of follow-up, improvement of the port-wine birthmark, intraocular pressure, and neurocognitive development was noted. The mTOR inhibitors may be useful in the treatment of some patients with SWS.

Topics: Child; Face; Facial Asymmetry; Female; Humans; Hyperplasia; Port-Wine Stain; Sirolimus; Sturge-Weber Syndrome