The National Institute of Neurological Disorders and Stroke has renewed a five-year, $1,662,500 million grant to Wayne State University School of Medicine faculty member Csaba Juhasz, M.D. Ph.D., to develop better diagnostic tools for a rare disorder present at birth that affects the brain, eye and skin in the form of venous blood vessel malformations.
The malformations, a skin lesion called port-wine stain, commonly appears on the face. The facial marker allows early diagnosis, often before neurological symptoms begin.
"This opens a unique, early window for intervention to prevent or diminish neurological symptoms; however, current imaging techniques often miss early brain involvement and no effective preventive treatments exist," said Dr. Juhasz, professor of pediatrics and neurology, and the principal investigator on "Longitudinal neuroimaging in Sturge-Weber syndrome."
"The overall aim of our research is to develop better diagnostic tools to detect brain involvement early and uncover new treatment paradigms to fundamentally alter neurocognitive outcome. For this, we study children affected by the disease in a prospective, longitudinal fashion using advanced multimodal imaging techniques, such as magnetic resonance imaging and positron emission tomography," Dr. Juhasz said.
More than 75 percent of children with Sturge-Weber will develop seizures. They also have a 60 percent risk of developing a learning disability and variable motor deficits such as weakness in the arms and legs.
The renewed grant phase will build upon results from the previous funding period and collect data for preventive antiepileptic treatment guided by advanced neuroimaging for children with the disorder who are at risk for severe epilepsy.
They also will study feasibility of a new treatment approach to block abnormal vessel proliferation in the affected brain vessels, utilizing imaging and surgical tissue data and the recent discovery of a somatic gene mutation in the syndrome.
"Finally, we will determine how surgical brain resection - applied in SWS children with drug-resistant seizures - alters long-term disease trajectory and improves neurocognitive outcome, thus reversing the devastating effects of the disease on brain development," he said.
Dr. Juhasz works with co-investigators from Children's Hospital of Michigan, Pediatric Neurology; in the PET Center; and in WSU MR Research Facility, as well as with representatives of the Sturge-Weber Foundation. He also is the WSU site leader of the Brain Vascular Malformation Consortium, a collaborative network involving several Sturge-Weber centers across the country. They have already built, together with Professor Harry Chugani, M.D., chief of Pediatric Neurology and director of the PET Center at Children's Hospital of Michigan, an internationally recognized clinical research and imaging program for children with SWS.
"We recruit patients from the United States and Canada. Families travel to Detroit for testing, which typically lasts two days to complete," he said.
Imaging studies are performed at the PET Center and Translational Imaging Laboratory at Children's Hospital of Michigan and at WSU's MR Research Facility.
The grant, R01NS041922, has been funded continuously by the National Institutes of Health since July 1, 2003.
Since the initial grant cycle, the researchers have determined the natural disease course, identified a critical age window (younger than 4 years) for progressive brain damage in affected children and identified potential mechanisms related to early epileptogenesis, a process in the brain that leads to clinical seizures and as potential drivers of disease progression.
They hope to identify and validate new imaging markers of epileptogenesis and abnormal angiogenesis (the process of new blood vessels forming from pre-existing vessels), providing targets for novel drug treatments during the early disease course. The imaging markers could be applied to children with epilepsy caused by other underlying etiologies.
"We will also understand the effects of early brain surgery on brain plasticity and functional reorganization, leading to better neurological and cognitive outcomes. These latter results can be translated to other focal pediatric brain disorders amenable for surgical resection," Dr. Juhasz said.
Tissue studies will be carried out at the Translational Neuro-Oncology Research Laboratory at the Barbara Ann Karmanos Cancer Institute, led by Associate Professor of Neurosurgery and Oncology Sandeep Mittal, M.D., along with co-investigator and Professor of Pathology William Kupsky, M.D.
For more information on Sturge-Weber syndrome, visit the National Institute of Neurological Disorders and Stroke or The Sturge-Weber Foundation.