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The Primary Care Companion For CNS... Aug 2023
PubMed: 37567185
DOI: 10.4088/PCC.22cr03459 -
Experimental and Therapeutic Medicine Jul 2024Sturge-Weber syndrome (SWS) type III, a rare neurocutaneous disorder, presents diagnostic challenges due to its variable clinical manifestations. The present study...
Sturge-Weber syndrome (SWS) type III, a rare neurocutaneous disorder, presents diagnostic challenges due to its variable clinical manifestations. The present study focuses on enhancing the understanding of this syndrome by conducting a detailed analysis of two pediatric cases and providing a comprehensive review of the existing literature. The cases, managed at the Children's Hospital Affiliated to Shandong University (Jinan, China), highlight the diverse clinical presentations and successful management strategies for SWS type III. In the first case, a 4-year-old male patient exhibited paroxysmal hemiplegia, epileptic seizures and cerebral angiographic findings indicative of left pia mater and venous malformation. The second case involved a 2.5-year-old male patient presenting with recurrent seizures and angiographic findings on the right side. Both cases underscore the importance of considering epileptic seizures, acquired and transient hemiplegia and cognitive impairments in the diagnosis of SWS type III. The present study provides insights into the effective use of both pharmacological and surgical interventions, drawing from the positive outcomes observed in these cases. The findings emphasize the need for heightened awareness and a meticulous approach in diagnosing and treating SWS type III, contributing to the better management and prognosis of this condition.
PubMed: 38868613
DOI: 10.3892/etm.2024.12588 -
The Journal of Investigative Dermatology Apr 2024Mosaic variants in genes GNAQ or GNA11 lead to a spectrum of vascular and pigmentary diseases including Sturge-Weber syndrome, in which progressive postnatal...
Mosaic variants in genes GNAQ or GNA11 lead to a spectrum of vascular and pigmentary diseases including Sturge-Weber syndrome, in which progressive postnatal neurological deterioration led us to seek biologically targeted therapeutics. Using two cellular models, we find that disease-causing GNAQ/11 variants hyperactivate constitutive and G-protein coupled receptor ligand-induced intracellular calcium signaling in endothelial cells. We go on to show that the aberrant ligand-activated intracellular calcium signal is fueled by extracellular calcium influx through calcium-release-activated channels. Treatment with targeted small interfering RNAs designed to silence the variant allele preferentially corrects both the constitutive and ligand-activated calcium signaling, whereas treatment with a calcium-release-activated channel inhibitor rescues the ligand-activated signal. This work identifies hyperactivated calcium signaling as the primary biological abnormality in GNAQ/11 mosaicism and paves the way for clinical trials with genetic or small molecule therapies.
Topics: GTP-Binding Protein alpha Subunits, Gq-G11; GTP-Binding Protein alpha Subunits; Mutation; Calcium; Endothelial Cells; Mosaicism; Calcium Signaling; Ligands
PubMed: 37802293
DOI: 10.1016/j.jid.2023.08.028 -
Journal of Neurosciences in Rural... 2024The profile of seizures in neurocutaneous syndromes is variable. We aimed to define the characteristics of epilepsy in children with neurocutaneous syndromes.
OBJECTIVES
The profile of seizures in neurocutaneous syndromes is variable. We aimed to define the characteristics of epilepsy in children with neurocutaneous syndromes.
MATERIALS AND METHODS
Cross-sectional study over 18 months at a tertiary care pediatric hospital, including children with neurocutaneous syndromes aged between 1 and 15 years, using the 2017-International League Against Epilepsy classification.
RESULTS
In 119 children with neurocutaneous syndromes, 94 (79%) had epilepsy. In eight children with neurofibromatosis one with epilepsy, 5 (62.5%) had generalized motor tonic-clonic seizures, 1 (12.5%) had generalized motor epileptic spasms, 1 (12.5%) had generalized motor automatism, and 1 (12.5%) had a focal seizure. In 69 children with tuberous sclerosis complex with epilepsy, 30 (43.5%) had generalized motor epileptic spasms, 23 (33.3%) had focal seizures, and nine (13.0%) had generalized motor tonic-clonic seizures. In 14 children with Sturge-Weber syndrome with epilepsy, 13 (92.8%) had focal seizures, and 1 (7.2%) had generalized motor tonic seizures. Statistically significant associations were found between epilepsy and intellectual disability ( = 0.02) and behavioral problems ( = 0.00).
CONCLUSION
Profiling seizures in children with neurocutaneous syndromes are paramount in devising target-specific treatments as the epileptogenesis in each syndrome differs in the molecular pathways leading to the hyperexcitability state. Further multicentric studies are required to unravel better insights into the epilepsy profile of neurocutaneous syndromes.
PubMed: 38746526
DOI: 10.25259/JNRP_510_2023 -
JPMA. the Journal of the Pakistan... Feb 2024Sturge- Weber syndrome (SWS), is a rare neuro-cutaneous angiomatosis which affects male and females alike. The clinical manifestations include angiomas, haemangiomas of... (Review)
Review
Sturge- Weber syndrome (SWS), is a rare neuro-cutaneous angiomatosis which affects male and females alike. The clinical manifestations include angiomas, haemangiomas of the lips, tongue and palatine region. The oral manifestations are usually unilateral and are susceptible to bleed. Patients can also present with macroglossia and maxillary bone hypertrophy which can lead to malocclusion of the oral cavity. Food accumulation due to occlusion can cause growth of bacteria which can intensify infections and can cause gingival hyperplasia. A case of a middle-aged 39 year old female was reported in the Ziauddin Hospital, Karachi on 2nd of February,2022 with the presenting complaints of intermittent fever and drowsiness for 10 days. On examination she had massive tongue enlargement, drooling, malocclusion, difficulty in eating and breathing. She was a known case of Sturgeweber syndrome. Based on the clinical and radiological findings, she was managed along the lines of prelaryngeal soft tissue and submandibular infection.
Topics: Female; Humans; Male; Middle Aged; Adult; Sturge-Weber Syndrome; Macroglossia; Hemangioma; Hypertrophy; Malocclusion
PubMed: 38419245
DOI: 10.47391/JPMA.9033 -
Journal of Glaucoma Jan 2024Among children with unilateral glaucoma associated with Sturge-Weber syndrome (SWS), 7 of 47 demonstrated involvement in the fellow eye, and that group had had earlier...
PRCIS
Among children with unilateral glaucoma associated with Sturge-Weber syndrome (SWS), 7 of 47 demonstrated involvement in the fellow eye, and that group had had earlier first-eye surgery relative to the noninvolvement group.
PURPOSE
The aim of this study was to determine the incidence of and risk factors for fellow-eye involvement in children with unilateral SWS-associated glaucoma.
MATERIALS AND METHODS
Children diagnosed with a unilateral facial port-wine stain and ipsilateral glaucoma before the age of 5 and followed up for at least 5 years were enrolled. The incidence rates of fellow-eye glaucoma involvement were estimated per 100 person-years, and factors associated with a higher incidence of fellow-eye involvement were investigated.
RESULTS
A total of 47 children [24 (51.1%) girls] with unilateral SWS-associated glaucoma were included. All of them had facial port-wine stain involving ophthalmic division of the trigeminal nerve, and 18 (38.3%) had neurological comorbidities. The mean age at glaucoma diagnosis was 0.8±1.2 years [range, 0.08 (1 mo)-4.0 y]. Over a median follow-up of 8.4 years, glaucoma was diagnosed in the fellow eye of 7 of the children (14.9%; incidence rate of 1.8 per 100 person-years), 6 of whom were girls ( P =0.097) and 5 of whom were diagnosed before the age of 4 years ( P =0.508). The fellow-eye-involvement group showed significantly higher mean follow-up intraocular pressure in the fellow eye, older age at first-eye surgery (both P <0.005), and higher frequency of choroidal hemangioma both at first onset and in fellow eyes ( P =0.026 and 0.019, respectively).
CONCLUSIONS
In this cohort of SWS children diagnosed with unilateral glaucoma, the risk of fellow-eye involvement was higher in girls, within the first 4 years, and in cases with choroidal hemangioma. The fellow-eye-involved children underwent surgery on the first eye earlier than those without fellow-eye involvement.
Topics: Child; Female; Humans; Infant, Newborn; Child, Preschool; Male; Sturge-Weber Syndrome; Incidence; Port-Wine Stain; Intraocular Pressure; Glaucoma; Hemangioma; Risk Factors
PubMed: 37671496
DOI: 10.1097/IJG.0000000000002295 -
International Medical Case Reports... 2024Sturge-Weber syndrome (SWS) is a complex rare genetic neuro-cutaneous disorder characterized by the presence of a port-wine stain, ophthalmic and intracranial...
BACKGROUND
Sturge-Weber syndrome (SWS) is a complex rare genetic neuro-cutaneous disorder characterized by the presence of a port-wine stain, ophthalmic and intracranial angiomatosis leading to seizures, ocular, and oral abnormalities.
CASE PRESENTATION
We report a 39-year-old, non-diabetic, non-hypertensive female refugee who presented initially with heart failure due to anemia for which she received blood transfusions. Later on admission, she developed multiple focal to bilateral seizures, severe irritability, aphasia, and right-sided hemiplegia, leading to admission to the ICU. A repeat medical history and examination revealed a faint left-sided ophthalmic port-wine stain that was initially unnoticed and a remote history of unprovoked seizures 20 years ago. Imaging revealed parietal calcifications and confirmed the diagnosis of SWS. Thus, a multidisciplinary approach was taken to fully understand the patient's diagnosis and determine a treatment strategy, involving consultations with the neurology, ophthalmology, otolaryngology, and physiotherapy departments. Successful seizure control was achieved by administering IV phenytoin for 3 days and the up-titrating of oral carbamazepine to 1g daily through a nasogastric tube. Unfortunately, due to the unavailability of personnel or resources, other important assessments for patients with SWS, such as advanced neuroimaging, psychiatric, plastic and neuro-surgery evaluations, as well as dentistry reviews, could not be conducted.
CONCLUSION
This case highlights the rare occurrence of adult-onset seizures in an undiagnosed SWS and their re-emergence after almost two decades without anti-seizure medications. It also highlights the importance of a comprehensive history and clinical examination, as this patient's diagnosis of SWS could have been missed if she had not experienced seizures on admission. Our study also demonstrates the challenges associated with managing such a complex condition in settings with limited resources.
PubMed: 38933806
DOI: 10.2147/IMCRJ.S472356 -
Epilepsia Oct 2023Administrative codes to identify people with rare epilepsies in electronic health records are limited. The current study evaluated the use of keyword search as an...
OBJECTIVE
Administrative codes to identify people with rare epilepsies in electronic health records are limited. The current study evaluated the use of keyword search as an alternative method for rare epilepsy cohort creation using electronic health records data.
METHODS
Data included clinical notes from encounters with International Classification of Diseases, Ninth Revision (ICD-9) codes for seizures, epilepsy, and/or convulsions during 2010-2014, across six health care systems in New York City. We identified cases with rare epilepsies by searching clinical notes for keywords associated with 33 rare epilepsies. We validated cases via manual chart review. We compared the performance of keyword search to manual chart review using positive predictive value (PPV), sensitivity, and F-score. We selected an initial combination of keywords using the highest F-scores.
RESULTS
Data included clinical notes from 77 924 cases with ICD-9 codes for seizures, epilepsy, and/or convulsions. The all-keyword search method identified 6095 candidates, and manual chart review confirmed that 2068 (34%) had a rare epilepsy. The initial combination method identified 1862 cases with a rare epilepsy, and this method performed as follows: PPV median = .64 (interquartile range [IQR] = .50-.81, range = .20-1.00), sensitivity median = .93 (IQR = .76-1.00, range = .10-1.00), and F-score median = .71 (IQR = .63-.85, range = .18-1.00). Using this method, we identified four cohorts of rare epilepsies with over 100 individuals, including infantile spasms, Lennox-Gastaut syndrome, Rett syndrome, and tuberous sclerosis complex. We identified over 50 individuals with two rare epilepsies that do not have specific ICD-10 codes for cohort creation (epilepsy with myoclonic atonic seizures, Sturge-Weber syndrome).
SIGNIFICANCE
Keyword search is an effective method for cohort creation. These findings can improve identification and surveillance of individuals with rare epilepsies and promote their referral to specialty clinics, clinical research, and support groups.
Topics: Humans; Electronic Health Records; Epilepsy; Lennox Gastaut Syndrome; Epilepsies, Myoclonic; Seizures
PubMed: 37498137
DOI: 10.1111/epi.17725 -
Developmental Medicine and Child... Jun 2024
PubMed: 38867441
DOI: 10.1111/dmcn.15982 -
Acta Neuropathologica Communications Mar 2024Sturge-Weber syndrome (SWS), a neurocutaneous disorder, is characterized by capillary malformations (CM) in the skin, brain, and eyes. Patients may suffer from seizures,...
Sturge-Weber syndrome (SWS), a neurocutaneous disorder, is characterized by capillary malformations (CM) in the skin, brain, and eyes. Patients may suffer from seizures, strokes, and glaucoma, and only symptomatic treatment is available. CM are comprised of enlarged vessels with endothelial cells (ECs) and disorganized mural cells. Our recent finding indicated that the R183Q mutation in ECs leads to heightened signaling through phospholipase Cβ3 and protein kinase C, leading to increased angiopoietin-2 (ANGPT2). Furthermore, knockdown of ANGPT2, a crucial mediator of pro-angiogenic signaling, inflammation, and vascular remodeling, in EC-R183Q rescued the enlarged vessel phenotype in vivo. This prompted us to look closer at the microenvironment in CM-affected vascular beds. We analyzed multiple brain histological sections from patients with GNAQ-R183Q CM and found enlarged vessels devoid of mural cells along with increased macrophage-like cells co-expressing MRC1 (CD206, a mannose receptor), CD163 (a scavenger receptor and marker of the monocyte/macrophage lineage), CD68 (a pan macrophage marker), and LYVE1 (a lymphatic marker expressed by some macrophages). These macrophages were not found in non-SWS control brain sections. To investigate the mechanism of increased macrophages in the perivascular environment, we examined THP1 (monocytic/macrophage cell line) cell adhesion to EC-R183Q versus EC-WT under static and laminar flow conditions. First, we observed increased THP1 cell adhesion to EC-R183Q compared to EC-WT under static conditions. Next, using live cell imaging, we found THP1 cell adhesion to EC-R183Q was dramatically increased under laminar flow conditions and could be inhibited by anti-ICAM1. ICAM1, an endothelial cell adhesion molecule required for leukocyte adhesion, was strongly expressed in the endothelium in SWS brain histological sections, suggesting a mechanism for recruitment of macrophages. In conclusion, our findings demonstrate that macrophages are an important component of the perivascular environment in CM suggesting they may contribute to the CM formation and SWS disease progression.
Topics: Humans; Sturge-Weber Syndrome; Endothelial Cells; Capillaries; Macrophages; Tumor Microenvironment; Vesicular Transport Proteins; GTP-Binding Protein alpha Subunits, Gq-G11; Vascular Malformations
PubMed: 38532508
DOI: 10.1186/s40478-024-01757-4