Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome that typically manifests as seizures, neurological signs, and progressive cognitive decline in the first few years of life. Although the disease is often progressive, there are, at present, no objective markers to identify patients at highest risk for a devastating outcome. The overall aim of this proposal is to collect quantitative structural and functional neuroimaging data in a prospective, longitudinal way in children with unilateral SWS, and to correlate these with clinical variables. Using positron emission tomography (PET) and magnetic resonance imaging/spectroscopy (MRI/MRS), we expect to find (based on our preliminary data) objective markers that identify children with SWS who are at major risk for progressive cognitive decline and severe seizures. Since surgical resection of affected brain regions may be an effective way of preventing clinical progression, and facilitating brain plasticity in young children, the findings will have a major impact on clinical management in SWS by establishing a ground for early surgical intervention in carefully selected patients. This expectation is based on our preliminary studies showing that brain glucose metabolic abnormalities are closely related to the clinical progression. Specifically, large cortical regions with mild hypometabolism are associated with severe seizures, while rapid unilateral structural brain damage may be paradoxically associated with good cognitive outcome, supposedly by facilitating reorganizational processes in unaffected brain regions. Increased glutamate concentration and decreased NAA detected by MRS in the affected cortex appear to be related to epileptogenicity and progressive neuronal dysfunction, respectively. In this study we propose four aims:
Aim l. To determine the changes (among 3 measurements made at one year intervals) in abnormalities of metabolism and structure in the affected hemisphere in young children (3 months - 5 years of age at time of first scans) with unilateral SWS.
Aim 2. To identify patterns of metabolic and structural brain abnormalities that are related to development of cognitive impairment.
Aim 3. To identify patterns of metabolic and structural brain abnormalities that are associated with high seizure frequency.
Aim 4. To determine whether cortical resection in SWS can reverse cognitive decline. The study will identify neuroimaging markers, which may be used as diagnostic predictors of clinical progression in SWS. This may aid in the selection of patients who could benefit from early resective surgery. The MRS studies can also provide novel data on the role of glutamatergic neurotransmitter toxicity in the pathophysiology of SWS; this may open new therapeutic approaches. Further, the findings will help to better understand the effect of early brain lesion on reorganizational processes in the developing brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS041922-03
Application #
6911477
Study Section
Special Emphasis Panel (ZRG1-BDCN-2 (02))
Program Officer
Babcock, Debra J
Project Start
2003-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$313,567
Indirect Cost
Name
Wayne State University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Luat, Aimee F; Behen, Michael E; Chugani, Harry T et al. (2018) Cognitive and motor outcomes in children with unilateral Sturge-Weber syndrome: Effect of age at seizure onset and side of brain involvement. Epilepsy Behav 80:202-207
Kumar, Ananyaa; Juhász, Csaba; Luat, Aimee et al. (2018) Evolution of Brain Glucose Metabolic Abnormalities in Children With Epilepsy and SCN1A Gene Variants. J Child Neurol 33:832-836
Kim, Jeong-A; Jeong, Jeong-Won; Behen, Michael E et al. (2018) Metabolic correlates of cognitive function in children with unilateral Sturge-Weber syndrome: Evidence for regional functional reorganization and crowding. Hum Brain Mapp 39:1596-1606
De la Torre, Alejandro J; Luat, Aimee F; Juhász, Csaba et al. (2018) A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome. Pediatr Neurol 84:11-20
Govil-Dalela, Tuhina; Kumar, Ajay; Behen, Michael E et al. (2018) Evolution of lobar abnormalities of cerebral glucose metabolism in 41 children with drug-resistant epilepsy. Epilepsia 59:1307-1315
Sundaram, Senthil K; Michelhaugh, Sharon K; Klinger, Neil V et al. (2017) GNAQ Mutation in the Venous Vascular Malformation and Underlying Brain Tissue in Sturge-Weber Syndrome. Neuropediatrics 48:385-389
Pilli, Vinod K; Behen, Michael E; Hu, Jiani et al. (2017) Clinical and metabolic correlates of cerebral calcifications in Sturge-Weber syndrome. Dev Med Child Neurol 59:952-958
Pilli, Vinod K; Chugani, Harry T; Juhász, Csaba (2017) Enlargement of deep medullary veins during the early clinical course of Sturge-Weber syndrome. Neurology 88:103-105
Juhász, Csaba (2016) Predicting and Preventing Epilepsy in Sturge-Weber Syndrome? Pediatr Neurol Briefs 30:43
Bosnyák, Edit; Behen, Michael E; Guy, William C et al. (2016) Predictors of Cognitive Functions in Children With Sturge-Weber Syndrome: A Longitudinal Study. Pediatr Neurol 61:38-45

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