Foundations in physiology: an introductory course using the core concepts.

As one element of an extensive revision to program curriculum, the Integrative Physiology and Health Science Department at a small, private, liberal arts institution developed a novel introductory course for the major, focusing specifically on the "core concepts" of physiology. Intended to provide the initial step in explicit scaffolding for student success and, ultimately, transfer of knowledge across the curriculum, development and assessment of the first offering of the course were completed. In the fall of 2021, IPH 131: Foundations in Physiology was launched. The specific core concepts covered were as follows: causality, scientific reasoning, physics/chemistry, structure-function, homeostasis, flow-down gradients, cell membrane, energy, cell-cell communication, and interdependence/integration. To assess student learning, the Phys-MAPS (Measuring Achievement and Progress in Science for Physiology) assessment tool was administered to students during the first week of class and again in the final week of the semester. Average scores revealed significant learning gains by the end of the semester (0.497 ± 0.058 vs. 0.538 ± 0.108 correct as a proportion of the total number of questions, P = 0.0096). While a modest gain in learning outcomes, these data provide early evidence that a course specifically addressing the core concepts of physiology can be an appropriate introduction to the physiology curriculum.NEW & NOTEWORTHY This article will detail the development and implementation of an introductory course using the "core concepts." Specifics of course design, assessment, and challenges encountered will be presented for those interested in this approach.

Lasers, Birthmarks, and Sturge-Weber Syndrome: A Pilot Survey.

BACKGROUND AND OBJECTIVES: There is limited or no data on the experience of patients with Sturge-Weber Syndrome (SWS) and/or their parents who seek out laser treatments for their port-wine birthmark (PWB). Our study aimed to develop a survey to understand patient perspectives on laser therapy and subsequent behaviors while focusing on three elements of the health belief model: perceived susceptibility, perceived benefits, and perceived barriers. STUDY DESIGN/MATERIALS AND METHODS: A 31 item survey was developed and sent to 650 members of the Sturge-Weber Foundation. The survey included questions regarding four domains: demographics, disease severity, laser experience, and perceptions and behaviors. Logistic regression models and bivariate analyses were conducted to analyze the results. RESULTS: Among the 123 respondents, earlier initiation of laser treatments was associated with greater birthmark satisfaction. Overall satisfaction increased up to 20 treatments and then leveled off. Color satisfaction increased up to 100 laser treatments; however, the flatness of the PWB was not associated with the number of laser treatments. The perceived benefits of lasers were not associated with the number of lifetime treatments or with spending. However, the perceived susceptibility was associated with greater spending on travel and medical expenses. CONCLUSION: The results of our survey provide insight into SWS patient experiences, beliefs, and behaviors regarding laser therapy. Further exploration of these variables may allow for the improvement of the care experience. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Sturge-Weber Syndrome Patient Registry: Delayed Diagnosis and Poor Seizure Control.

OBJECTIVE: To examine the symptomatology and treatment of Sturge-Weber syndrome (SWS) from a large patient registry to identify common symptoms, clinical outcomes, and areas of unmet clinical need. STUDY DESIGN: An online patient questionnaire was completed by 628 patients with clinically diagnosed SWS and/or a port-wine birthmark over a 19-year period. Statistical analysis focused on seizures as a primary outcome measure, as well as associated neurologic, ophthalmologic, and dermatologic attributes to understand some of the natural history of the disorder. RESULTS: The majority (92%) of patients had a port-wine birthmark, and 60% of the patients had neurologic symptoms, including seizures and stroke-like episodes. Glaucoma was present in 48% of the patients. Other common symptoms included behavioral (46%) and hearing (or vestibular) disorders (24%). Delayed diagnosis of SWS beyond 1 year after presentation of initial symptoms occurred in 16% of the patients, with 68% having clear preexisting comorbidities, especially headaches. Birthmarks on the forehead and scalp were associated with seizures (P < .001), whereas bilaterality of birthmarks was not. Only 49% of patients being treated for epilepsy were free of seizures. CONCLUSIONS: Seizures and glaucoma were the primary drivers for a diagnosis of SWS in patients with delayed diagnosis, and hearing (or vestibular) and behavioral problems were also prevalent. The diagnosis of SWS was delayed when the predominant symptom was headache. Seizure control was quite poor in many patients with SWS. Our findings highlight an important need for detailed, longitudinal data to improve our understanding of SWS and develop better treatment strategies for patients with this disorder.

Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement.

AIM: To review recent developments in the understanding, diagnosis, and treatment of Sturge-Weber syndrome (SWS). METHOD: Members of the Brain Vascular Malformation Consortium Sturge-Weber Syndrome National Workgroup contributed their expertise to review the literature and present promising directions for research. RESULTS: The increasing number of reports dealing with SWS over the last decade reflects progress in the diagnosis and understanding of the neurological involvement. The proliferation of centers and advocacy groups to care for patients with SWS and to stimulate research has aided the development of new insights into the clinical manifestations and the pathophysiology of neurological progression, and the development of novel hypotheses to direct future research. Many key questions remain, but the tools and networks to answer them are being developed. INTERPRETATION: This review summarizes important new knowledge and presents new research directions that are likely to provide further insights, earlier diagnosis, improved treatments, and possibly, prevention of this syndrome.

Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome.

BACKGROUND: Epilepsy in typical Sturge-Weber syndrome (SWS) is common, and many questions remain regarding the treatment outcomes. We analyzed a large multicenter database with focus on neurological drug treatment in different demographic and SWS characteristic groups. METHODS: A total of 268 patients with brain involvement and a history of seizures were selected from a research data registry generated from a multicenter cross-sectional questionnaire. We examined associations between medication use and binary variables such as sex, ethnicity, and brain, skin, and eye involvement laterality. We analyzed group differences in mean number of antiseizure medications and age at diagnosis, enrollment, and seizure onset and examined differences in median SWS neurological scores in groups of interest. RESULTS: The most frequently used medications were levetiracetam (48.1%), low-dose aspirin (44.8%), oxcarbazepine (39.9%), and phenobarbital (14.9%). Lamotrigine was more frequently used in adults than in children (P = 0.001). History of neurosurgery was associated with no current antiseizure medication use (P = 0.001), whereas bilateral brain involvement and family history of seizures were associated with using a higher number of antiseizure medications (P = 0.002, P = 0.027, respectively). Subjects with bilateral brain involvement and early seizure onset were associated with using a higher number of antiseizure medications (P = 0.002) and phenobarbital use (0.003). CONCLUSIONS: Levetiracetam, low-dose aspirin, and oxcarbazepine were the most frequently used medications. More severely affected patients were frequently on a greater number of antiseizure medications. Surgery for epilepsy was associated with the ability to discontinue antiseizure medication. Longitudinal studies are needed to further investigate medication use in patients with SWS.

Consensus Statement for the Management and Treatment of Sturge-Weber Syndrome: Neurology, Neuroimaging, and Ophthalmology Recommendations.

BACKGROUND: Sturge-Weber syndrome (SWS) is a sporadic, neurocutaneous syndrome involving the skin, brain, and eyes. Because of the variability of the clinical manifestations and the lack of prospective studies, consensus recommendations for management and treatment of SWS have not been published. OBJECTIVE: This article consolidates the current literature with expert opinion to make recommendations to guide the neuroimaging evaluation and the management of the neurological and ophthalmologic features of SWS. METHODS: Thirteen national peer-recognized experts in neurology, radiology, and ophthalmology with experience treating patients with SWS were assembled. Key topics and questions were formulated for each group and included (1) risk stratification, (2) indications for referral, and (3) optimum treatment strategies. An extensive PubMed search was performed of English language articles published in 2008 to 2018, as well as recent studies identified by the expert panel. The panel made clinical practice recommendations. CONCLUSIONS: Children with a high-risk facial port-wine birthmark (PWB) should be referred to a pediatric neurologist and a pediatric ophthalmologist for baseline evaluation and periodic follow-up. In newborns and infants with a high-risk PWB and no history of seizures or neurological symptoms, routine screening for brain involvement is not recommended, but brain imaging can be performed in select cases. Routine follow-up neuroimaging is not recommended in children with SWS and stable neurocognitive symptoms. The treatment of ophthalmologic complications, such as glaucoma, differs based on the age and clinical presentation of the patient. These recommendations will help facilitate coordinated care for patients with SWS and may improve patient outcomes.

Consensus Statement for the Management and Treatment of Port-Wine Birthmarks in Sturge-Weber Syndrome.

Importance: Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome involving the skin, brain, and eyes. Consensus recommendations for management are lacking. Objective: To consolidate the current literature with expert opinion to make recommendations that will guide treatment and referral for patients with port-wine birthmarks (PWBs). Evidence Review: In this consensus statement, 12 nationally peer-recognized experts in dermatology with experience treating patients with SWS were assembled. Key topics and questions were formulated for each group and included risk stratification, optimum treatment strategies, and recommendations regarding light-based therapies. A systematic PubMed search was performed of English-language articles published between December 1, 2008, and December 1, 2018, as well as other pertinent studies identified by the expert panel. Clinical practice guidelines were recommended. Findings: Treatment of PWBs is indicated to minimize the psychosocial impact and diminish nodularity and potentially tissue hypertrophy. Better outcomes may be attained if treatments are started at an earlier age. In the US, pulsed dye laser is the standard for all PWBs regardless of the lesion size, location, or color. When performed by experienced physicians, laser treatment can be safe for patients of all ages. The choice of using general anesthesia in young patients is a complex decision that must be considered on a case-by-case basis. Conclusions and Relevance: These recommendations are intended to help guide clinical practice and decision-making for patients with SWS and those with isolated PWBs and may improve patient outcomes.

Sturge-Weber syndrome: soft-tissue and skeletal overgrowth.

Sturge-Weber syndrome (SWS) is characterized by capillary malformation, glaucoma, leptomeningeal vascular anomalies, and variable facial overgrowth. The purpose of this study was to document the prevalence and morbidity of facial hypertrophy in 2 cohorts: group 1, surveyed patients registered in the SWS Foundation, and group 2, patients treated at our Vascular Anomalies Center. Predictive variables included age, sex, region of capillary stain, and ocular or cerebral involvement. Outcome variables were soft-tissue and bony overgrowth, as well as the type of operative correction. In group 1, the response rate to our questionnaire was 29.3% (108/368). Facial overgrowth was documented in 60.0% of patients. Soft-tissue hypertrophy was present in 55.0%; the lip (81.0%) was the most commonly affected site. Skeletal hypertrophy was reported in 22% of patients; the maxilla (83.0%) was the most frequently overgrown bone. Overall, 23.0% of patients (36.5% with overgrowth) had an operation: 34.0% of patients with soft tissue hypertrophy and 9.0% with skeletal enlargement. In group 2, 47 patients with SWS were treated at our center: 83% had facial overgrowth, either a localized cutaneous lesion (18.0%), soft-tissue enlargement (70.0%), or bony hypertrophy (45.0%). As in group 1, the lip (75.0%) and maxilla (94.0%) were the most commonly enlarged structures. Operations were necessary for localized cutaneous lesions (86.0%), soft-tissue hypertrophy (53.0%), or skeletal overgrowth (11.0%). In conclusion, facial hypertrophy is a major component of SWS; these patients should be counseled about the risk of overgrowth and about the types of possible operative correction.

Neurological Complications of Sturge-Weber Syndrome: Current Status and Unmet Needs.

OBJECTIVE: We aimed to identify the current status and major unmet needs in the management of neurological complications in Sturge-Weber syndrome. METHODS: An expert panel consisting of neurologists convened during the Sturge-Weber Foundation Clinical Care Network conference in September 2018. Literature regarding current treatment strategies for neurological complications was reviewed. RESULTS: Although strong evidence-based standards are lacking, the implementation of consensus-based standards of care and outcome measures to be shared across all Sturge-Weber Foundation Clinical Care Network Centers are needed. Each patient with Sturge-Weber syndrome should have an individualized seizure action plan. There is a need to determine the appropriate abortive and preventive treatment of migraine headaches in Sturge-Weber syndrome. Likewise, a better understanding and better diagnostic modalities and treatments are needed for stroke-like episodes. As behavioral problems are common, the appropriate screening tools for mental illnesses and the timing for screening should be established. Brain magnetic resonance imaging (MRI) preferably done after age one year is the primary imaging modality of choice to establish the diagnosis, although advances in MRI techniques can improve presymptomatic diagnosis to identify patients eligible for preventive drug trials. CONCLUSION: We identified the unmet needs in the management of neurological complications in Sturge-Weber syndrome. We define a minimum standard brain MRI protocol to be used by Sturge-Weber syndrome centers. Future multicenter clinical trials on specific treatments of Sturge-Weber syndrome-associated neurological complications are needed. An improved national clinical database is critically needed to understand its natural course, and for retrospective and prospective measures of treatment efficacy.

Physical and Family History Variables Associated With Neurological and Cognitive Development in Sturge-Weber Syndrome.

BACKGROUND: Sturge-Weber syndrome (SWS) is caused by a somatic mutation in GNAQ leading to capillary venous malformations in the brain presenting with various neurological, ophthalmic, and cognitive symptoms of variable severity. This clinical variability makes accurate prognosis difficult. We hypothesized that the greater extent of physical factors (extent of skin, eye, and brain involvement), presence of possible genetic factors (gender and family history), and age of seizure onset may be associated with greater symptom severity and need for surgery in patients with SWS. METHODS: The questionnaire was collected from 277 participants (age: two months to 66 years) with SWS brain involvement at seven US sites. RESULTS: Bilateral brain involvement was associated with both learning disorder and intellectual disability, whereas port-wine birthmark extent was associated with epilepsy and an increased likelihood of glaucoma surgery. Subjects with family history of vascular birthmarks were also more likely to report symptomatic strokes, and family history of seizures was associated with earlier seizure onset. Learning disorder, intellectual disability, strokelike episodes, symptomatic stroke, hemiparesis, visual field deficit, and brain surgery were all significantly associated with earlier onset of seizures. CONCLUSION: The extent of brain and skin involvement in SWS, as well as the age of seizure onset, affect prognosis. Other genetic factors, particularly variants involved in vascular development and epilepsy, may also contribute to neurological prognosis, and further study is needed.

A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome.

BACKGROUND: Sturge-Weber syndrome is a neurocutaneous disorder associated with port-wine birthmark, leptomeningeal capillary malformations, and glaucoma. It is associated with an unpredictable clinical course. Because of its rarity and complexity, many physicians are unaware of the disease and its complications. A major focus moving ahead will be to turn knowledge gaps and unmet needs into new research directions. METHODS: On October 1-3, 2017, the Sturge-Weber Foundation assembled clinicians from the Clinical Care Network with patients from the Patient Engagement Network of the Sturge-Weber Foundation to identify our current state of knowledge, knowledge gaps, and unmet needs. RESULTS: One clear unmet need is a need for consensus guidelines on care and surveillance. It was strongly recommended that patients be followed by multidisciplinary clinical teams with life-long follow-up for children and adults to monitor disease progression in the skin, eye, and brain. Standardized neuroimaging modalities at specified time points are needed together with a stronger clinicopathologic understanding. Uniform tissue banking and clinical data acquisition strategies are needed with cross-center, longitudinal studies that will set the stage for new clinical trials. A better understanding of the pathogenic roles of cerebral calcifications and stroke-like symptoms is a clear unmet need with potentially devastating consequences. CONCLUSIONS: Biomarkers capable of predicting disease progression will be needed to advance new therapeutic strategies. Importantly, how to deal with the emotional and psychological effects of Sturge-Weber syndrome and its impact on quality of life is a clear unmet need.

Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research.

Sturge-Weber syndrome (SWS) is a vascular neurocutaneous disorder that results from a somatic mosaic mutation in GNAQ, which is also responsible for isolated port-wine birthmarks. Infants with SWS are born with a cutaneous capillary malformation (port-wine birthmark) of the forehead or upper eyelid which can signal an increased risk of brain and/or eye involvement prior to the onset of specific symptoms. This symptom-free interval represents a time when a targeted intervention could help to minimize the neurological and ophthalmologic manifestations of the disorder. This paper summarizes a 2015 SWS workshop in Bethesda, Maryland that was sponsored by the National Institutes of Health. Meeting attendees included a diverse group of clinical and translational researchers with a goal of establishing research priorities for the next few years. The initial portion of the meeting included a thorough review of the recent genetic discovery and what is known of the pathogenesis of SWS. Breakout sessions related to neurology, dermatology, and ophthalmology aimed to establish SWS research priorities in each field. Key priorities for future development include the need for clinical consensus guidelines, further work to develop a clinical trial network, improvement of tissue banking for research purposes, and the need for multiple animal and cell culture models of SWS.

Comorbidity of epilepsy and headache in patients with Sturge-Weber syndrome.

Sturge-Weber syndrome is associated with leptomeningeal angioma, trigeminal port-wine stain, epilepsy, and glaucoma. Clinically, many patients with Sturge-Weber syndrome are observed to have both seizures and headaches, but this has never been described in the literature. A questionnaire was mailed to 190 patients with reported comorbid epilepsy and headache as identified by the Sturge-Weber Foundation. Sixty-eight surveys were returned anonymously; 55 reported both seizures and headaches. The median age at headache onset was 8 years, with a median of three headaches per month. Fifty-eight percent felt that headaches were an equal or greater problem. Ibuprofen and acetaminophen were the most frequently tried abortive medications; 22% had tried sumatriptan. Only 22% reported a neurologist suggesting the use of an anticonvulsant as a preventive agent. Subjects with a family history of headaches had an earlier age at headache onset (7.5 vs 11 years; P = .02), and those with a family history of seizures were more likely to report behavior problems (69% vs 33%; P = .02). Subjects reporting learning problems or hemiparesis had an earlier age at seizure onset. Migraine-like headaches can be as significant a problem as epilepsy for patients with Sturge-Weber syndrome. Despite this, triptans and prophylactic medications (including anticonvulsants) were used in less than half of the patients. Correlations of family history with both age at symptom onset and behavior problems suggest that genetic substrate could be one factor determining the variable neurologic manifestations seen in Sturge-Weber syndrome.

Brain Vascular Malformation Consortium: Overview, Progress and Future Directions.

Brain vascular malformations are resource-intensive to manage effectively, are associated with serious neurological morbidity, lack specific medical therapies, and have no validated biomarkers for disease severity and progression. Investigators have tended to work in "research silos" with suboptimal cross-communication. We present here a paradigm for interdisciplinary collaboration to facilitate rare disease research. The Brain Vascular Malformation Consortium (BVMC) is a multidisciplinary, inter-institutional group of investigators, one of 17 consortia in the Office of Rare Disease Research Rare Disease Clinical Research Network (RDCRN). The diseases under study are: familial Cerebral Cavernous Malformations type 1, common Hispanic mutation (CCM1-CHM); Sturge-Weber Syndrome (SWS); and brain arteriovenous malformation in hereditary hemorrhagic telangiectasia (HHT). Each project is developing biomarkers for disease progression and severity, and has established scalable, relational databases for observational and longitudinal studies that are stored centrally by the RDCRN Data Management and Coordinating Center. Patient Support Organizations (PSOs) are a key RDCRN component in the recruitment and support of participants. The BVMC PSOs include Angioma Alliance, Sturge Weber Foundation, and HHT Foundation International. Our networks of clinical centers of excellence in SWS and HHT, as well as our PSOs, have enhanced BVMC patient recruitment. The BVMC provides unique and valuable resources to the clinical neurovascular community, and recently reported findings are reviewed. Future planned studies will apply successful approaches and insights across the three projects to leverage the combined resources of the BVMC and RDCRN in advancing new biomarkers and treatment strategies for patients with vascular malformations.