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.
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