LAUSR

Drugresistant epilepsy remains one of the most challenging and impairing problems facing epilepsy patients. In the large population of patients with drugresistant epilepsy, nonmedical treatments, especially epilepsy surgery, may offer the best hope for a significant improvement in seizures and ideally seizurefreedom. However, the diagnostic evaluation for epilepsy surgery is typically complex, with many patients either being concluded not to be appropriate surgery candidates or having suboptimal outcomes following surgery. Thus, significant advances in the presurgical evaluation and approach are needed to increase the yield of identifying the epileptogenic zone (EZ) and improving epilepsy surgery outcomes. In a recent paper awarded the 2022 Epilepsia Open Clinical Science Prize,1 Hulshof et al address this issue of the presurgical diagnostic assessment in a specific cause of epilepsy, tuberous sclerosis complex (TSC), that involves some of the most complicated cases to evaluate for epilepsy surgery. TSC is a genetic disorder, caused by mutations in either the TSC1 or TSC2 genes with resultant mechanistic target of rapamycin (mTOR) pathway activation and characterized by the formation of tumors or other dysplastic lesions in multiple organs, including the brain.2,3 Neurological involvement usually accounts for the most disabling symptoms of the disease, especially in children, with up to 90% of TSC patients having epilepsy and about twothirds of those having drugresistant epilepsy.4 Epilepsy surgery evaluation in TSC is complicated due to the typical presence of multiple, bilateral focal lesions (eg, cortical tubers) that may all be candidates for the EZ, as well as multiple seizure types and multifocal EEG epileptiform abnormalities in many cases. While invasive EEG methods, such as stereoEEG, may help localize seizure onset to one or a subset of tubers, there have been extensive efforts attempting to utilize and optimize noninvasive imaging methods to identify the EZ in TSC patients. The primary radiographic and pathological findings of TSC potentially related to epilepsy are cortical/subcortical tubers. Pathologically, cortical tubers represent focal malformations of cortical development and are basically indistinguishable from focal cortical dysplasia type IIB, consisting of loss of normal cortical lamination and a variety of abnormal dysmorphic and cytomegalic cells, including classic “giant cells.” Radiographically on MRI, cortical tubers primarily not only appear as focal areas of increased T2 signal in the cortex and underlying subcortical white matter, but also have additional features often also seen in isolated focal cortical dysplasia (FCD), such as increased cortical thickness, blurring of the graywhite matter junction, and transmantle sign. Previous studies have identified specific radiographic properties of tubers as potential markers of the EZ, such as calcifications, cystlike changes, or additional FCDlike features,5– 7 but no one feature has been shown to consistently localize the EZ. The study by Hulshof et al aimed to determine whether various radiographic features, either alone or in