Oral Sirolimus for Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome.

This case report describes an 8-year-old girl who received oral sirolimus as an adjuvant therapy for pulse dye laser of her port-wine stain and as an off-label treatment of exudative retinal detachment secondary to diffuse choroidal hemangioma.

Topical netarsudil for treatment of glaucoma with elevated episcleral venous pressure: A pilot investigation in sturge-weber syndrome.

PURPOSE: Topical netarsudil 0.02% may reduce intraocular pressure (IOP) by decreasing episcleral venous pressure (EVP), which carries theoretical utility for glaucoma associated with elevated EVP. A role for netarsudil in patients with elevated EVP is evaluated in a pilot investigation using a cohort of individuals with Sturge-Weber syndrome (SWS). METHODS: Retrospective study of patients with SWS and glaucoma who were treated with netarsudil. Five patients (six eyes) were identified. Data collected included demographics, visual acuity, IOP, glaucoma medical and surgical treatments, and adverse effects of netarsudil. RESULTS: Mean age was 13.6 ± 8.5 years. EVP elevation was presumed based on clinical stigmata and/or historical features. Mean number of baseline glaucoma medications was 3.3 ± 1.2. There was a significant reduction in the IOP at netarsudil initiation (mean 26.2 ± 4.5 mmHg) to 1 month of netarsudil therapy (mean 20.2 ± 3.8 mmHg, p = 0.0283) and latest IOP on netarsudil (mean 17.6 ± 1.4 mmHg, p = 0.0034). Mean duration of netarsudil therapy was 18.7 ± 11.8 months. Three patients required additional glaucoma procedures; one patient required an additional glaucoma medication. Three eyes (50%) developed conjunctival hyperemia. One patient discontinued netarsudil at 29 months, to reduce drop burden. CONCLUSIONS: Netarsudil can effectively reduce IOP in patients with SWS, even when used as a fourth or fifth glaucoma medication. A possible role for netarsudil in the management of patients with elevated EVP is suggested pending further future investigations.

Cannabidiol Treatment for Neurological, Cognitive, and Psychiatric Symptoms in Sturge-Weber Syndrome.

BACKGROUND: A prior drug trial of cannabidiol for treatment-resistant epilepsy in patients with Sturge-Weber syndrome (SWS), a rare neurovascular condition, implicated improvements in neurological, quality of life (QOL), neuropsychologic, psychiatric, and motor outcomes. METHODS: Ten subjects with SWS brain involvement, controlled seizures, and cognitive impairments received study drug in this Johns Hopkins institutional review board-approved, open-label, prospective drug trial. Oral cannabidiol was taken for six months (dose ranged from 5 to 20 mg/kg/day). SWS neuroscore, port-wine birthmark score, QOL, and adverse events were recorded every four to 12 weeks. Neuropsychologic, psychiatric, and motor assessments were administered at baseline and six months' follow-up. Most evaluations were conducted virtually due to the coronavirus disease 2019 pandemic. RESULTS: Cannabidiol was generally well tolerated. Six subjects reported mild to moderate side effects related to study drug and continued on drug; one subject withdrew early due to moderate side effects. No seizures were reported. Significant improvements in SWS neuroscore, patient-reported QOL, anxiety and emotional regulation, and report of bimanual ability use were noted. Migraine QOL scores were high at baseline in these subjects, and remained high. Neuropsychologic and other QOL and motor outcomes remained stable, with some within-subject improvements noted. CONCLUSIONS: Further studies are needed to determine whether Epidiolex can improve quality of life and be beneficial for neurological, anxiety, and motor impairments in SWS independent of seizure control. Large multicentered studies are needed to extend these preliminary findings.

Hematoporphyrin monomethyl ether photodynamic therapy for the treatment of Sturge-Weber syndrome and large segmental facial port-wine stain.

Hematoporphyrin monomethyl ether (HMME) is a newly authorized photosensitizer for the treatment of port-wine stain (PWS) in China. However, no research on its efficacy for treating PWS lesions of Sturge-Weber syndrome (SWS) has been made. To assess the efficacy and safety of HMME-photodynamic therapy (PDT) in the treatment of SWS and simple large segmental facial PWS. Medical records of patients with SWS and large segmental facial PWS were reviewed. Efficacy was evaluated according to color blanching and graded as excellent (≥75%), good (50%-74%), fair (25%-49%), and poor (≤24%). Adverse events were analyzed. Nineteen patients with SWS and 33 patients with large segmental facial PWS were analyzed. 52.6% SWS and 69.7% PWS patients (p > .05) achieved at least 25% improvement. Common adverse events included short-term pain, edema, pruritus, exudation, and scab. No severe adverse event occurred. HMME-PDT was effective and safe for SWS and large segmental facial PWS.

Skin necrosis due to post-treatment care failure after photodynamic therapy of facial port-wine stain in Sturge-Weber Syndrome - A case report.

We report on a case of photodynamic therapy (PDT) of large facial port-wine stain (PWS) in 5-year-old patient with Sturge-Weber Syndrome (SWS). Improvement was achieved after the first session without severe adverse reactions, however, prolonged swelling, infection and skin necrosis occurred after the second session, mainly due to failure of post-treatment care. The case demonstrates that post-treatment care is critical for PDT of large facial PWS, particularly for SWS patients.

Sturge-Weber syndrome presenting in late adulthood.

A 75-year-old woman presents to the acute medical take with confusion and headache following a road traffic accident. She had previously been fit and well, living alone with no assistance. Following multiple investigations, she was diagnosed with Sturge-Weber Syndrome, a rare neurocutaneous disorder that usually presents with seizures in childhood. This case highlights an unusual example of this syndrome, presenting for the first time later in life.

Facial hemihypertrophy in a girl with sturge-weber syndrome: Treatment with oral sirolimus.

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.

Sirolimus Treatment in Sturge-Weber Syndrome.

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.

Sirolimus as a Potential Treatment for Sturge-Weber Syndrome.

BACKGROUND: Sturge-Weber syndrome (SWS) is a rare neurocutaneous syndrome characterized by port-wine stain, leptomeningeal angiomatosis, and glaucoma. Due to the involvement of the nervous system, patients are often accompanied with epilepsy. It reported that 75% of patients with SWS did not respond to standard antiepileptic drugs. Although hemispherectomy is effective in treating these patients, the application of it has been limited due to high risk and huge trauma. Recent studies have shown that sirolimus has a positive on complex vascular malformations and seizures, so the authors attempted to treat them by using sirolimus. METHODS: The authors retrospectively analyzed 6 patients with SWS who were refractory to antiepileptic drugs and accepted oral sirolimus in their department between 2017 and 2020. RESULTS: All 6 patients were responsive to oral sirolimus treatment. Epilepsy was controlled in all patients, no epilepsy relapsed in 6 patients during the follow-up period. The facial port-wine stain of the patients were all lightened and the hypertrophy of pathological tissue was improved. Only minor adverse reactions occurred during the treatment. CONCLUSIONS: Oral sirolimus could control the occurrence of epilepsy and improve the appearance, with minor and tolerable adverse reactions. Sirolimus is especially suitable for patients with severe epilepsy, failure, or contraindications of antiepileptic drugs; it could be an alternative method for patients who are unwilling to accept the risks of neurosurgery.

The role of adenosine A1 receptor agonist in adenosine augmentation therapy for patients with refractory epilepsy in Sturge-Weber syndrome: An in vitro electrophysiological study.

PURPOSES: This study was to further explore the adenosine dysfunction in refractory epilepsy in Sturge-Weber Syndrome (SWS), to evaluate the neuronal-level effect of the A1 receptor (A1R) agonist on both excitatory pyramidal neurons and inhibitory interneurons, to discuss the possibility of adenosine augmentation therapy (AAT) using A1R agonist for treating refractory epilepsy in SWS. MATERIALS AND METHODS: The intrinsic excitatory properties of pyramidal cells (PCs) and fast-spiking (FS) interneurons from human brain tissues with SWS cases and malformations of cortical development (MCD) cases were compared using electrophysiology. With application of either A1R agonist or antagonist, the neuronal-level effect of A1R agonist was evaluated in vitro in PCs and FS interneurons from SWS cases and MCD cases. RESULTS: No significant difference of passive excitatory properties of PCs and FS interneurons was found between SWS cases and MCD cases. In terms of the neuronal-level effect of A1R agonist, with 22.88 ±â€¯1.12% percentage of decreased frequency, FS interneurons showed relatively highest sensitivity of A1R agonist application, compared with PCs from SWS cases and FS interneurons and PCs from MCD cases. CONCLUSION: Our results supported the potential of AATs using A1R agonist to be a novel therapy for reducing life burden from patients with refractory epilepsy in SWS, with application to epileptic generation region but not propagation region.

Treatment of Port Wine Birthmarks in Sturge-Weber Syndrome Using Topical Timolol.

Three patients with facial port wine birthmarks were randomly assigned to receive treatment with topical timolol or the placebo. Three masked observers evaluated photographs of the patients, noting improvement in patients who were treated with timolol and two controls. The photographic technique was not standardized. This pilot study suggests topical timolol warrants further evaluation for port wine birthmarks. [J Pediatr Ophthalmol Strabimus. 2021;58:e1-e4.].

Quality of Life in Children With Sturge-Weber Syndrome.

AIM: We assessed the utilization of the National Institutes of Health Quality of Life in Neurological Disorders (Neuro-QoL) in pediatric patients with Sturge-Weber syndrome, a rare neurovascular disorder which frequently results in seizures, brain atrophy, calcification, and a range of neurological impairments. METHODS: Subjects were seen clinically and consented for research. All 22 patients filled out the Pediatric Neuro-QoL. The Neuro-QoL subscores were converted to T-scores to compare with the referenced control population. Twenty-one participants also filled out the Brain Vascular Malformation Consortium Database Questionnaire containing data pertaining to Sturge-Weber syndrome-related medical history, medications, comorbidities, and family history. All data were analyzed with a significance threshold of P < 0.05. RESULTS: Cognitive function quality of life was significantly lower (P < 0.001) in pediatric patients with Sturge-Weber syndrome compared with referenced control subjects. Male gender (P = 0.02) was associated with lower cognitive function Neuro-QoL. The extent of skin (R = -0.46, P = 0.04), total eyelid port-wine birthmark (R = -0.56, P = 0.007), eye (R = -0.58, P = 0.005), and total Sturge-Weber syndrome involvement (R = -0.63, P = 0.002) were negatively correlated with cognitive function Neuro-QoL. A younger age at seizure onset was associated with lower cognitive function Neuro-QoL (hazard ratio = 0.90, P = 0.004) even after controlling for extent of brain, skin, or eye involvement. Antidepressant use was associated with lower cognitive function Neuro-QoL (P = 0.005), and cognitive function Neuro-QoL was negatively correlated with depression Neuro-QoL; however, after adjusting for depression this relationship was no longer significant. CONCLUSIONS: The results suggest targeting cognitive function Neuro-QoL in treatment trials and reiterate the prognostic value of early seizure onset. In addition, sex-related differences were noted, which should be further studied.

Preventive treatment with oral sirolimus and aspirin in a newborn with severe 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.

Use of antiviral medications in drug reaction with eosinophilia and systemic symptoms (DRESS): A case of infantile DRESS.

A 3-month-old girl with Sturge-Weber syndrome presented with a morbilliform rash, eosinophilia, and fulminant liver failure to our tertiary pediatric hospital. She was diagnosed with drug reaction with eosinophilia and systemic symptoms complicated by viremia and evidence of viral hepatitis on liver biopsy. We discuss the role of viral reactivation in drug reaction with eosinophilia and systemic symptoms and the relevance of antiviral therapy in management.

Potential biological targets for bioassay development in drug discovery of Sturge-Weber syndrome.

Sturge-Weber Syndrome (SWS) is a neurocutaneous disease with clinical manifestations including ocular (glaucoma), cutaneous (port-wine birthmark), neurologic (seizures), and vascular problems. Molecular mechanisms of SWS pathogenesis are initiated by the somatic mutation in GNAQ. Therefore, no definite treatments exist for SWS and treatment options only mitigate the intensity of its clinical manifestations. Biological assay design for drug discovery against this syndrome demands comprehensive knowledge on mechanisms which are involved in its pathogenesis. By analysis of the interrelated molecular targets of SWS, some in vitro bioassay systems can be allotted for drug screening against its progression. Development of such platforms of bioassay can bring along the implementation of high-throughput screening of natural or synthetic compounds in drug discovery programs. Regarding the fact that study of molecular targets and their integration in biological assay design can facilitate the process of effective drug discovery; some potential biological targets and their respective biological assay for SWS drug discovery are propounded in this review. For this purpose, some biological targets for SWS drug discovery such as acetylcholinesterase, alkaline phosphatase, GABAergic receptors, Hypoxia-Inducible Factor (HIF)-1α and 2α are suggested.

Metabolic correlates of cognitive function in children with unilateral Sturge-Weber syndrome: Evidence for regional functional reorganization and crowding.

To evaluate metabolic changes in the ipsi- and contralateral hemisphere in children showing a cognitive profile consistent with early reorganization of cognitive function, we evaluated the regional glucose uptake, interhemispheric metabolic connectivity, and cognitive function in children with unilateral SWS. Interictal 2-deoxy-2[18 F]fluoro-D-glucose (FDG)-PET scans of 27 children with unilateral SWS and mild epilepsy and 27 age-matched control (non-SWS children with epilepsy and normal FDG-PET) were compared using statistical parametric mapping (SPM). Regional FDG-PET abnormalities calculated as SPM(t) scores in the SWS group were correlated with cognitive function (IQ) in left- and right-hemispheric subgroups. Interhemispheric metabolic connectivity between homotopic cortical regions was also calculated. Verbal IQ was substantially (≥10 points difference) higher than non-verbal IQ in 61% of the right- and 71% of the left-hemispheric SWS group. FDG SPM(t) scores in the affected hemisphere showed strong positive correlations with IQ in the left-hemispheric, but not in right-hemispheric SWS group in several frontal, parietal, and temporal cortical regions. Significant positive interhemispheric metabolic connectivity, present in controls, was diminished in the SWS group. In addition, the left-hemispheric SWS group showed inverse metabolic interhemispheric correlations in specific parietal, temporal, and occipital regions. FDG SPM(t) scores in the same regions of the right (unaffected) hemisphere showed inverse correlations with IQ. These findings suggest that left-hemispheric lesions in SWS often result in early reorganization of verbal functions while interfering with ("crowding") their non-verbal cognitive abilities. These cognitive changes are associated with specific metabolic abnormalities in the contralateral hemisphere not directly affected by SWS.

Cannabidiol Treatment for Refractory Seizures in Sturge-Weber Syndrome.

BACKGROUND: Sturge-Weber syndrome results in leptomeningeal vascular malformations, medically refractory epilepsy, stroke(s), and cognitive impairments. Cannabidiol, a cannabinoid without psychoactive properties, has been demonstrated in preclinical models to possibly have anticonvulsant, antioxidant, and neuroprotective actions. METHODS: Five subjects with Sturge-Weber syndrome brain involvement and treatment-resistant epilepsy were enrolled. Motor seizure frequency, quality of life, and adverse events were recorded from the eighth week of the pretreatment period, eight weeks after starting maintenance dose (week 14), and the most recent visit. RESULTS: Four subjects had data through week 14, one of whom initially withdrew for lack of efficacy but because of other benefits re-enrolled with a lower dose. Two subjects at week 14 and three subjects with bilateral brain involvement had at the last visit a greater than 50% seizure reduction, reported an improved quality of life, and remained on cannabidiol 63-80 weeks after starting the drug. Three subjects reported mild side effects considered related to cannabidiol. CONCLUSION: This study suggests that cannabidiol may be well tolerated as adjunctive medication for seizure management and provides initial data supporting further study of cannabidiol in individuals with Sturge-Weber syndrome.

A case of 55-year-old man with first-ever generalized seizure diagnosed with Sturge-Weber syndrome type III by characteristic MRI findings.

A 55-year-old man with no mental retardation had presented a history of frequent transient clumsiness of his right upper and lower extremities for about 20 years. He was admitted to a general hospital with weakness of right side of the body, and first-ever generalized seizure attack occurred the next day. Brain CT showed calcification in the left cerebral cortices. So he was referred to our hospital. On neurological examination, he had mild clumsiness of his right upper limb and right pyramidal tract sign. He had neither facial port-wine stain nor glaucoma. The blood test and cerebrospinal fluid analysis were unremarkable. Electroencephalogram showed slowing and reduction of activity at the left frontal and parietal areas with no epileptic activities. Brain CT showed "tram-track calcification" and lobar atrophy in the left fronto-parietal cortices. Susceptibility weighted imaging (SWI) on MRI revealed enlarged transmedullary veins in the left periventricular white matter and low intensity lesions along the cortical gyri. Post gadolinium fluid-attenuated inversion recovery imaging (FLAIR-Gd) showed leptomeningeal enhancement in the left fronto-parietal lobes more extensively than those by post gadolinium T1-weighted image. Brain perfusion single photon emission computed tomography with a technetium-99m-ethyl cysteinate dimer (99mTc-ECD SPECT) revealed hypoperfusion in the fronto-parietal lobes. These clinical and neuroimaging findings were compatible with type III Sturge-Weber syndrome (SWS). His condition was improved after treatment with oral levetiracetam (1,000 mg daily). Although adult-onset type III SWS is very rare, it is important to perform SWI and post-contrast FLAIR for assessing leptomeningeal angioma in patients with seizure with focal cortical calcification even if they have no facial nevus.