Hypothesis: Presymptomatic treatment of Sturge-Weber Syndrome With Aspirin and Antiepileptic Drugs May Delay Seizure Onset.
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SUBMITTER: Day AM
PROVIDER: S-EPMC7288478 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
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Hypothesis: Presymptomatic treatment of Sturge-Weber Syndrome With Aspirin and Antiepileptic Drugs May Delay Seizure Onset.
Day Alyssa M AM Hammill Adrienne M AM Juhász Csaba C Pinto Anna L AL Roach E Steve ES McCulloch Charles E CE Comi Anne M AM
Pediatric neurology 20181124
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Project description:BackgroundNinety percent of infants with Sturge-Weber syndrome (SWS) brain involvement have seizure onset before 2 years of age; this is associated with worse neurologic outcome. Presymptomatic treatment before seizure onset may delay seizure onset and improve outcome, as has been shown in other conditions with a high-risk of developing epilepsy such as tuberous sclerosis complex. Electroencephalogram (EEG) may be a biomarker to predict seizure onset. This retrospective clinical data analysis aims to assess impact of presymptomatic treatment in SWS.MethodsThis two-centered, IRB-approved, retrospective study analyzed records from patients with SWS brain involvement. Clinical data recorded included demographics, age of seizure onset (if present), brain involvement extent (unilateral versus bilateral), port-wine birthmark (PWB) extent, family history of seizure, presymptomatic treatment if received, neuroscore, and anti-seizure medication. EEG reports prior to seizure onset were analyzed.ResultsNinety-two patients were included (48 females), and 32 received presymptomatic treatment outside of a formal protocol (5 aspirin, 16 aspirin and levetiracetam; 9 aspirin and oxcarbazepine, 2 valproic acid). Presymptomatically-treated patients were more likely to be seizure-free at 2 years (15 of 32; 47% versus 7 of 60; 12%; p<.001). A greater percentage of presymptomatically-treated patients had bilateral brain involvement (38% treated versus 17% untreated; p=.026). Median hemiparesis neuroscore at 2 years was better in presymptomatically-treated patients. In EEG reports prior to seizure onset, the presence of slowing, epileptiform discharges, or EEG-identified seizures was associated with seizure onset by 2 (p=.001).ConclusionPresymptomatic treatment is a promising approach to children diagnosed with SWS prior to seizure onset. Further study is needed, including prospective drug trials, long-term neuropsychological outcome, and prospective EEG analysis to assess this approach and determine biomarkers for presymptomatic treatment.
| S-EPMC11090403 | biostudies-literature
Project description:Sturge-Weber syndrome is a neurocutaneous disorder with skin, eye, and brain involvement. Prior series suggest about 50% of patients have seizures/neurodeterioration. Low-dose (3-5 mg/kg/d) aspirin use in this population is controversial. This study further addresses the side effects and outcomes of low-dose aspirin usage in Sturge-Weber syndrome. Fifty-eight subjects on aspirin with brain involvement were analyzed in a retrospective chart review. Charts were evaluated for brain involvement, age at first seizure, and side effects. Subjects' clinical stability was compared using neurologic scores. The majority of subjects had neurologic scores reflecting reasonable seizure control (91%), none or mild hemiparesis (57%), no vision impairment (71%), and none or mild cognitive impairment (80%). Forty-nine reported no significant side effects, and 9 reported either allergic reaction or minimal to significant bleeding on aspirin. This cohort's clinical experience adds significant support for low-dose aspirin use to optimize neurodevelopmental outcome in Sturge-Weber syndrome with minimal side effects.
| S-EPMC4373084 | biostudies-literature
Project description:IntroductionSecondary analysis of hospital-hosted clinical data can save time and cost compared with prospective clinical trials for neuroimaging biomarker development. We present such a study for Sturge-Weber syndrome (SWS), a rare neurovascular disorder that affects 1 in 20 000-50 000 newborns. Children with SWS are at risk for developing neurocognitive deficit by school age. A critical period for early intervention is before 2 years of age, but early diagnostic and prognostic biomarkers are lacking. We aim to retrospectively mine clinical data for SWS at two national centres to develop presymptomatic biomarkers.Methods and analysisWe will retrospectively collect clinical, MRI and neurocognitive outcome data for patients with SWS who underwent brain MRI before 2 years of age at two national SWS care centres. Expert review of clinical records and MRI quality control will be used to refine the cohort. The merged multisite data will be used to develop algorithms for abnormality detection, lesion-symptom mapping to identify neural substrate and machine learning to predict individual outcomes (presence or absence of seizures) by 2 years of age. Presymptomatic treatment in 0-2 years and before seizure onset may delay or prevent the onset of seizures by 2 years of age, and thereby improve neurocognitive outcomes. The proposed work, if successful, will be one of the largest and most comprehensive multisite databases for the presymptomatic phase of this rare disease.Ethics and disseminationThis study involves human participants and was approved by Boston Children's Hospital Institutional Review Board: IRB-P00014482 and IRB-P00025916 Johns Hopkins School of Medicine Institutional Review Board: NA_00043846. Participants gave informed consent to participate in the study before taking part. The Institutional Review Boards at Kennedy Krieger Institute and Boston Children's Hospital approval have been obtained at each site to retrospectively study this data. Results will be disseminated by presentations, publication and sharing of algorithms generated.
| S-EPMC8819809 | biostudies-literature
Project description: Not available
| S-EPMC3997529 | biostudies-literature
Project description:BackgroundSturge-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.MethodsTen 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.ResultsSirolimus 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.ConclusionsSirolimus 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.
| S-EPMC8209677 | biostudies-literature
Project description:Sturge-Weber syndrome is a vascular malformation syndrome consisting of a facial port-wine birthmark associated with malformed leptomeningeal blood vessels and a choroid "angioma" of the eye. It is a rare neurocutaneous disorder that occurs sporadically, is not inherited, and is caused by a somatic mosaic mutation in GNAQ. In patients with Sturge-Weber syndrome, brain involvement typically presents in infancy with seizures, strokes, and stroke-like episodes, and a range of neurologic impairments. Standard treatment includes laser therapy for the birthmark, control of glaucoma through eyedrops or surgery, and the use of anticonvulsants. Increasingly low-dose aspirin is offered. Treatment with propranolol has been tried generally without the dramatic results seen in hemangiomas. Treatment with an anticonvulsant or low-dose aspirin or both before the onset of seizures is an option. Surgical resection may be offered to those whose seizures are medically refractory. Endocrine, medical rehabilitation and cognitive comorbidities are important to manage. In the future, new therapeutic options are likely to be offered stemming from preclinical studies and small pilot clinical trials currently ongoing. Discovery of the causative somatic mosaic mutation suggests new insights into the pathophysiology of this vascular malformation disorder, and potential novel treatment strategies for future study. The mutation results in constitutive overactivation of the Ras-Raf-MEK-ERK and the HIPPO-YAP pathways and inhibitors of these pathways may in the future prove useful in the treatment of Sturge-Weber syndrome.
| S-EPMC4943027 | biostudies-literature
Project description:Sturge-Weber syndrome is a rare nonhereditary developmental condition with neurological and skin disorder, characterized by presence of port wine stain on the face along with ocular disorders, oral manifestations and leptomeningeal angiomas. Here we present an unusual case of Sturge-Weber syndrome with osseous hypertrophy of maxilla.
| S-EPMC3681312 | biostudies-literature
Project description:We sought to estimate the risk of seizure-related events associated with refilling prescriptions for antiepileptic drugs (AEDs) and to estimate the effect of switching between brand-name and generic drugs or between two generic versions of the same drug. We conducted a case-crossover study using health-care databases from British Columbia, Canada, among AED users who had an emergency room visit or hospitalization for seizure (index seizure-related event), defined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes 345.xx (epilepsy and recurrent seizures) and 780.3x (convulsions), between 1997 and 2005. AED prescription refilling itself was associated with 2.3-fold elevated odds of seizure-related events when the refill occurred within 21 days before the index event (odds ratio (OR) 2.31; 95% confidence interval (CI) 1.56-3.44). The OR was 2.75 (95% CI 0.88-8.64) for refills that involved switching, yielding a refill-adjusted OR for switching of 1.19 (95% CI 0.35-3.99). Refilling the same AED prescription was associated with an elevated risk of seizure-related events whether or not the refill involved switching from a brand-name to a generic product.
| S-EPMC2996138 | biostudies-literature
Project description:AimWe 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.MethodsSubjects 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.ResultsCognitive 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.ConclusionsThe 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.
| S-EPMC7288751 | biostudies-literature
Project description:Sturge-Weber Syndrome (SWS) is a sporadic (non-inherited) syndrome characterized by capillary vascular malformations in the facial skin, leptomeninges, or the choroid. A hallmark feature is the mosaic nature of the phenotype. SWS is caused by a somatic mosaic mutation in the GNAQ gene (p.R183Q), leading to activation of the G protein, Gαq. Decades ago, Rudolf Happle hypothesized SWS as an example of "paradominant inheritance", that is, a "lethal gene (mutation) surviving by mosaicism". He predicted that the "presence of the mutation in the zygote will lead to death of the embryo at an early stage of development". We have created a mouse model for SWS using gene targeting to conditionally express the GNAQ p.R183Q mutation. We have employed two different Cre-drivers to examine the phenotypic effects of expression of this mutation at different levels and stages of development. As predicted by Happle, global, ubiquitous expression of this mutation in the blastocyst stage results in 100% embryonic death. The majority of these developing embryos show vascular defects consistent with the human vascular phenotype. By contrast, global but mosaic expression of the mutation enables a fraction of the embryos to survive, but those that survive to birth and beyond do not exhibit obvious vascular defects. These data validate Happle's paradominant inheritance hypothesis for SWS and suggest the requirement of a tight temporal and developmental window of mutation expression for the generation of the vascular phenotype. Furthermore, these engineered murine alleles provide the template for the development of a mouse model of SWS that acquires the somatic mutation during embryonic development, but permits the embryo to progress to live birth and beyond, so that postnatal phenotypes can also be investigated. These mice could then also be employed in pre-clinical studies of novel therapies.
| S-EPMC10894004 | biostudies-literature