Abstracts

Rationale: In patients with epilepsy, the efficacy of functional MRI (fMRI) and tractography in localizing eloquent areas and relevant white matter tracts is challenged by possible reorganization of cortical functions. Several groups have pointed out that atypical representation of language occurs more frequently in individuals with epilepsy compared to controls, but most studies have been retrospective and on adults submitted to temporal lobectomies.  Four small longitudinal studies evaluated reorganization of cortical function after epilepsy surgery. In this study, we assessed patterns and predictors of cortical organization in 40 children and young adults with lesional epilepsy and explored possible postoperative modifications of language representation in 20 of them. Methods: This is a prospective study. Forty patients (22 F; mean age at surgery; 12.8 ± 5.6 years) underwent preoperative structural and functional 3T brain MRI during sensorimotor, language tasks, or both. Twenty patients also underwent postoperative fMRI during language tasks. DTI data were acquired in 24 patients. We hypothesized a causal model to test whether clinical features would influence fMRI results and the latter has an impact on cognitive outcome. First, we performed an exploratory analysis for each of the three groups of variables (clinical, fMRI and neuropsychological), and then a factorial analysis for mixed data (FAMD) in order to identify the variables better explaining data variability. For the postoperative study, we performed an analysis of associations between possible changes of Laterality Index (LI) and clinical variables. Results: The component which explained most of the variability of the preoperative data was mainly correlated with interictal EEG (R² = 0.640, p <0.001). We found a correlation between diffuse EEG abnormalities and more atypical language dominance (regr. coeff = -0.401 p = 0.014), which in turn correlated with pathological attention (p=0.0358) and low cognitive level (p = 0.0136). Normal postoperative EEG (p=0.003) and seizure freedom (p=0.015) were associated with shifting towards a more typical lateralization of language, which in turn correlated with improved or stable fluency after surgery. A longer disease duration correlated with more atypical LI values prior to and after surgery. The analysis of DTI data did not detect preoperative asymmetry in the arcuate fasciculus or correlation with language functional dominance. Conclusions: Atypical representation of language appears to be a general mechanism of functional organization in patients with drug-resistant epilepsy, irrespective from site and type of lesion, but closely related to epilepsy duration and topography of EEG abnormalities. This observation is supported by the more frequent postoperative shift to typical language representation in patients with normal EEG and seizure freedom after surgery. Functional reorganization of cortical functions appears to be associated with pathological attention and low intelligence quotient scores in patients with lesional epilepsy and is potentially reversible after effective epilepsy surgery, with possible cognitive improvement. Funding: European Union Seventh Framework Programme FP7/2007– 2013 under the project DESIRE (Grant Agreement: 602531), Italian Ministry of Health and Tuscany Region under the project ‘Reorganization of cortical function after surgery for lesional epilepsy in children’ (RF-2010-2309954)