h1 arrowSturge-Weber Syndrome Center: Ongoing Research Studies

Lab Team

Our current research continues to build upon our past research and focuses on validating the new screening tools developed, evaluating the new treatment strategies offered, and continuing the challenging effort to determine what causes SWS.

The long-term vision for our research is the development of multi-centered clinical trials and research efforts. To that end, we welcome collaborations with other centers and foundations. Only by bringing together the resources, expertise, patients and people from around the country and the world, can we maximize the efforts already made to better treat and prevent SWS.

Please note that this information is provided for informational purposes only to those interested in supporting our work and is not for recruitment.

If you would like to participate in a study, please visit the recruiting studies page. For more information, call Dr. Anne Comi at (443) 923-9127 or email: comi@kennedykrieger.org.

Read about our studies to:

Studies to Improve Clinical Care of Sturge-Weber Syndrome

Anticonvulsant Data

Patients with SWS are often prescribed one or several anticonvulsant medications. Our current study seeks to examine these different anticonvulsants, and the associated clinical outcomes.

Stimulant Use in Patients with Sturge-Weber Syndrome: Safety and Efficacy

We are assessing the use of stimulants in patients that have Sturge-Weber syndrome in order to analyze the safety of these medications as well as how well they work in relation to these patients.

Studies to Improve the Diagnosis and Monitoring of Sturge-Weber Syndrome

NA_00038014, BVMC 6202: Innovative approaches to gauge progression of Sturge-Weber Syndrome

Our goal is to create the first standardized national clinical database for SWS research. We will also determine whether urine angiogenesis markers have clinical utility as predictors of disease progression and severity. Finally, we will test the hypothesis that the initiating event in SWS genesis is a somatic mutation in a gene(s) essential for vascular development. Please see below for some notes on our ongoing progress.

Aim 1 - Standardized SWS registry and clinical database. A centralized database and registry is needed to comprehensively define the phenotype of SWS and foster future clinical research. This national database is de-identified and housed at the University of South Florida. The recruiting centers continue to add subjects and are beginning to analyze data collected to date.

Aim 2 - Urine angiogenesis biomarkers. Urine levels of vascular biomarkers may correlate with neurologic outcome at follow up. Biomarkers of neurologic involvement are needed to select patients for aggressive treatment and to monitor treatment responses. 36 subjects with SWS and 29 family member controls have been recruited and urine samples are being collected and correlated with clinical status over a two year period of time.

Aim 3 - Somatic mutation causing SWS. It has been hypothesized that SWS is caused by a somatic mutation in a gene encoding an angiogenesis factor. In this portion of the study we hope to establish somatic mutations as an underlying disease mechanism with an eye towards adapting such knowledge into a definitive biomarker for SWS. Data analysis continues from whole genome, whole exome, and deep sequencing analyses of DNA from SWS normal and abnormal tissue.

Dr Anne Comi and Dr Josh Ewen discuss recent qEEG results

NA_00043846, BVMC 6204: Establishing reliability for Quantitative EEG, Transcranial Doppler, behavioral outcomes, and Optical Coherence Tomography in SWS

Our goal is to develop methods to improve early diagnosis, to monitor response to treatment, and to predict functional outcome of SWS. The first step in doing so has been to determine the reliability of the measures that we intend to use repeatedly over time in these patients.

Aim 1 - Quantitative EEG. Diagnosing brain involvement in infants with a facial port-wine birthmark is complicated by the low sensitivity of neuroimaging at young age. qEEG may be a useful biomarker for SWS brain involvement, especially for young patients, as an alternative to MRIs or CTs. Recruitment from this study is complete and data analysis in ongoing.

Aim 2 - Transcranial Doppler. Asymmetry in blood flow velocity, as seen on Transcranial Doppler ultrasounds, may correlate with neurologic progression. Transcranial doppler ultrasound holds promise in assessing the risk of stroke among SWS patients. Recruitment from this study is complete and data analysis in ongoing.

Aim 3 - Medical Rehabilitation Scales. Hemiparesis and fine motor skills are often problematic for SWS patients. A variety of clinical medical rehabilitation scales, may help assess functional skills and mobility issues among SWS patients. These scales may serve as practical methods for evaluating SWS progression and response to treatment. Recruitment from this study is complete and data analysis in ongoing.

Aim 4 - Optical Coherence Tomography. Glaucoma is associated with the presence of a port-wine facial birthmark around the eye region. Optical coherence tomography is a non-invasive measure that could prove useful is assessing eye pressure in SWS.

This study is completed and the following manuscript is in press: Karun SA, Quigley HA, Comi A, Rhonda BM, Jampel. Increased Choroidal Thickness in Patients with Sturge-Weber Syndrome. JAMA Opthalmology. In Press

For more information on our NIH-funded BVMC 6202, and BVMC 6204 please see the following lin:

http://www.kennedykrieger.org/node/1754
http://rarediseasesnetwork.epi.usf.edu/
http://rarediseasesnetwork.epi.usf.edu/BVMC/professional/SWS/index.htm

Clinical EEGs and their correlations

We are seeking to uncover the way that clinical EEG reading is associated with our monitoring of SWS clinical outcomes.

Noninvasive Imaging and Functional Correlation of Intracranial Pial Angiomatosis
in Patients With Sturge-Weber Syndrome

Principal Investigator: Doris Lin, MD, PhD
Co-investigators: Dr. Anne Comi & Dr. Peter Barker

This study is an important component in our work to discover better ways to use MRI imaging to diagnose and monitor Sturge-Weber Syndrome.

Children (age 8 and greater) and adults with Sturge-Weber syndrome: Participants have an imaging study of the brain to see how the vascular structures and blood flow are changed by Sturge-Weber syndrome.

Quantitative EEG Study

Principal Investigator: Anne Comi, MD

The purpose of this study is to determine whether quantitative EEG can improve early screening of SWS brain involvement in at-risk infants with a V1 facial port-wine birthmark and to determine if it will help us safely monitor response to treatment.

We have been developing quantitative EEG (see our initial study in the completed study section) as a safe tool to screen infants with a facial port-wine birthmark for brain involvement and for monitoring neurologic progression. This involves a routine EEG that is analyzed in a special way to evaluate for abnormal asymmetry in power.

Doppler and ultrasound studies of the eye in Sturge-Weber syndrome

Principal Investigator: Anne Comi, MD

The purpose of this study is to develop the optimal use of doppler and ultrasound for the understanding of abnormal blood flow in the eye and for monitoring progression in SWS.

This study is retrospectively reviewing the results of doppler and ultrasound studies done as part of the clinical evaluation of patients with SWS and eye involvement. Analyzing these studies in large numbers of patients with SWS with improve our understanding of the blood flow dynamics in the eye and how they change over time and in response to treatment.

Neuropsychological Testing

Principal Investigator: Anne Comi, MD

The purpose of this study is to better delineate the range of cognitive deficits in SWS and understand how this is associated with the extent of brain involvement and other neurologic issues.

This testing is designed to measure how well a person performs on various tasks, including memory, language, attention, and learning. Some tests may involve writing or saying the answers to questions. Other tests may involve drawing pictures or performing tasks like putting objects in order.

Studies to Better Understand the Pathogenesis (Cause) of Sturge-Weber Syndrome

These studies are conducted as part of The Sturge-Weber Syndrome and Ischemia in the Immature Brain Research Program at Kennedy Krieger Institute.

DNA Array Analysis Searching for Somatic Mutation in Sturge-Weber Syndrome

Without knowing what causes SWS or what genes are involved we are unable to develop a true animal model to test preventative or treatment strategies. Therefore, discovering the cause of SWS remains a challenging but high priority goal of this research.

The cause of SWS is unknown, however one of the leading hypotheses is a somatic mutation occurring in the first trimester of pregnancy. If this hypothesis is true then we may be able to discover this somatic mutation using powerful DNA array technology. We have already done some pilot work in this area. Below is shown data from a DNA array comparing DNA from affected and unaffected samples from the same individual with SWS. More powerful, larger DNA arrays have recently been developed and it is our goal to continue this challenging search with the latest technology in collaboration with the Pevsner laboratory at the Kennedy Krieger Laboratory.

Boston Urine Testing

The purpose of this study is to determine if urine vascular factors in SWS can help us understand more about the pathogenesis of SWS and whether it can be used to monitor response to treatment or predict outcome.

This study is measuring blood vessel factors in the urine of individuals with Sturge-Weber syndrome in collaboration with the laboratory of Dr. Marsha Moses. Urine vascular biomarkers have been developed for other vascular malformations to monitor response to treatment or predict disease severity and we are working on similar progress with Sturge-Weber syndrome.

Please see our Completed Research page for abstracts of recently published papers by Center members.