Abstracts

Rationale: Tuberous sclerosis complex (TSC) is a systemic organ disease and caused by TSC1/TSC2 mutations. Cerebral cortical tubers and surrounding cerebral tissues resembling focal cortical dysplasia relate to epileptogenesis and cognitive problems in TSC patients. The previous studies about the findings of brain magnetic resonance imaging (MRI) revealed that the number of cortical tubers, the volume of tubers or the occurrence of cyst-like tubers correlate to the severities of epilepsy and/or the cognitive developments in TSC patients. However, there have been only a few studies that evaluated the cerebral lesions including both cortical and white matter lesions. We clarified the correlations between neurological outcomes and MRI lesion patterns, including both cerebral cortex and white matter, in TSC patients. Methods: We collected 40 TSC patients with 1) brain MRI >=2 yo, 2) developmental/intellectual evaluations >=3 yo. Using FLAIR images, we visually analyzed: 1) cyst-like tubers, 2) white matter atrophy, 3) white matter defect, 4) diffuse lesion including cortex and white matter, and 5) total cortical tubers (cyst-like and non-cyst-like). We evaluated outcomes of 1) cognitive development and 2) severity of West syndrome (WS grade). We statistically analyzed the correlations between the neurological outcomes and MRI lesions, using univariate and multivariate ordinal logistic regression analyses (significant level: p<0.05). Results: The ages at MRI scanning ranged 3-39 yo (mean: 15). Mental retardation and history of WS were seen in 25 and 17 patients, respectively. The brain MRI showed 1-10 cyst-like tubers in 14 patients, 1-2 sides of white matter atrophy in 7 patients, 1-3 areas of white matter defect in 6 patients, 1-6 areas of diffuse lesion in 11 patients. Cortical tubers (non-cyst-like) were uncountable on the diffuse lesions in the 11 patients. In univariate analyses, all findings of cyst-like tubers, white matter atrophy, white matter defect and diffuse lesion significantly correlated with the development/intelligence and/or WS grade. In multivariate analyses, only the diffuse lesion significantly correlated with development/intelligence (p=0.012) and WS grade (p=0.012). Conclusions: Only the diffuse lesion showed the significant correlations with the neurological outcomes in multivariate analyses. Compared with the other MRI findings evaluated in the previous studies, the diffuse lesion pattern may be a better predictor of cognitive outcome and severity of epilepsy in TSC patients. Funding: No funding