Abstracts

Rationale: Continuous spike-and-wave in slow-wave-sleep (CSWS) is a childhood epileptic encephalopathy characterized by a combination of epilepsy, neuropsychological impairment and electrical status epilepticus in sleep (ESES, defined by spike-wave activity in ≥ 85% of slow-wave sleep). Previous studies suggested a role of thalamic abnormalities in the pathophysiology of CSWS and hypothesized  abnormal thalamo-cortical connections. We applied diffusion tensor imaging (DTI)-based whole brain connectome analysis to explore patterns of thalamo-cortical connectivity during the evolution of CSWS from the prodromal stage (seizure onset to age at neuropsychological regression) to the acute stage (after onset of neuropsychological regression and during period of active ESES). Refining such imaging metrics could improve understanding of the neuroanatomical substrates and epileptic circuitry in children with CSWS. Methods: We recruited 13 CSWS patients (age: 7.0 ± 3.4 years, 8 boys, epilepsy duration: 2.3 ± 2.1 years) including 6 patients with prodromal (age: 6.4 ± 3.1 years) and 7 patients with acute CSWS (age: 7.6 ± 4.1 years). Seizure frequency of individual patients was categorized into five levels of severity, 0: no ongoing seizure, 1: yearly, 2: monthly, 3: weekly, 4: daily. DTI data were acquired using a 3-tesla MRI at 55 encoding gradient directions with b-value=1000 sec/mm2. A total of 116 cortical regions of interest (ROI) were parcellated using automated anatomical labeling (http://www.gin.cnrs.fr/AAL-216) for DTI-whole connectome analysis. At each ROI, nodal degree was evaluated as the measure of local connectivity strength respectively (higher values indicate more axonal projections to neighboring ROIs). One-way ANOVA with a covariate of age was used for the subgroup comparisons, prodromal vs. acute CSWS to identify ROIs showing significant subgroup differences.  Results: Children with acute CSWS showed significantly increased nodal degree in left frontal ROIs; these were most prominent in inferior orbital gyrus and operculum (p-value < 0.015), resulting from increased projection to ipsilateral thalamus. Interestingly, non-parametric correlation analysis found that this increased connection shows significant positive correlation with seizure frequency (Spearman’s rho= 0.59, p-value= 0.03). Other cortico-thalamic projections showed no significant changes between the two subgroups. Conclusions: The present study suggests that children in the acute stage of CSWS have an atypical developmental pattern of axonal centrality in frontal lobe which is significantly increased compared to that in children in the prodromal stage of CSWS. The unilaterality of our findings could be due to the small number of subjects in two different subgroups rather than a longitudinal design. Even so, the increased fronto-thalamic connections were positively correlated with seizure frequency suggesting that this projection may be integral to the generation of ESES and neuropsychological consequences seen in CSWS.  If further developed, DTI connectomes could be potential markers for children with acute CSWS. Funding: None