CORTICAL TUBER COUNT - A BIOMARKER INDICATING NEUROLOGIC SEVERITY OF TUBEROUS SCLEROSIS COMPLEX

The relationship between the number of cortical tubers observed by mag netic resonance imaging (MRI) and the severity of cerebral dysfunction of tuberous sclerosis patients has been examined in a meta-analysis o f the published literature. The Literature review has identified five independent studies for examining the association. These studies consi stently reveal that the cortical tuber count detected on MRI scans Is increased among those with more severe cerebral disease. Severity of t he cerebral dysfunction is measured by the seizure status and its cont rol and by the developmental status and the level of mental retardatio n. Meta-analysis demonstrates that within a study population, the MRI- detected cortical tuber count is six times more likely to be above the median count for tuberous sclerosis patients with severe cerebral dys function (poor seizure control or moderate-severe retardation or both) than more mildly affected tuberous sclerosis patients. Similarly, acr oss studies, moderately to severely affected patients are five times m ore likely to have greater than seven MRI-detected cortical tubers tha n those more mildly affected. These associations are both statisticall y significant and strong. The cortical tuber count is a biomarker that reasonably predicts the severity of cerebral dysfunction of tuberous sclerosis. Cortical tubers of tuberous sclerosis form in the early ges tational period. The embryologic disruption determining the clinical s everity of the cortical dysfunction of tuberous sclerosis is set in th e early gestational period.