Abstract
PurposeThe purpose of the present study was to investigate the relationship between subcortical nuclei volume and cognition in children with post-convulsive status epilepticus (CSE). MethodsStructural T1-weighted magnetic resonance imaging (MRI) scans (Siemens Avanto, 1.5 T) and neuropsychological assessments (full-scale intelligence quotient (FSIQ) and Global Memory Scores (GMS)) were collected from subjects at a mean 8.5 years post-CSE (prolonged febrile seizures (PFS), n = 30; symptomatic/known, n = 28; and other, n = 12) and from age- and sex-matched healthy controls (HC). Subjects with CSE were stratified into those with lower cognitive ability (LCA) (CSE+, n = 22) and those without (CSE−, n = 48). Quantitative volumetric analysis using Functional MRI of the Brain Software Library (FSL) (Analysis Group, FMRIB, Oxford) provided segmented MRI brain volumes. Univariate analysis of covariance (ANCOVA) was performed to compare subcortical nuclei volumes across subgroups. Multivariable linear regression was performed for each subcortical structure and for total subcortical volume (SCV) to identify significant predictors of LCA (FSIQ <85) while adjusting for etiology, age, socioeconomic status, sex, CSE duration, and intracranial volume (ICV); Bonferroni correction was applied for the analysis of individual subcortical nuclei. ResultsSeventy subjects (11.8 ± 3.4 standard deviation (SD) years; 34 males) and 72 controls (12.1 ± 3.0SD years; 29 males) underwent analysis. Significantly smaller volumes of the left thalamus, left caudate, right caudate, and SCV were found in subjects with CSE+ compared with HC, after adjustment for intracranial, gray matter (GM), or cortical/cerebellar volume. When compared with subjects with CSE−, subjects with CSE+ also had smaller volumes of the left thalamus, left pallidum, right pallidum, and SCV. Individual subcortical nuclei were not associated, but SCV was associated with FSIQ (p = 0.005) and GMS (p = 0.014). Intracranial volume and etiology were similarly predictive. ConclusionsNine years post-CSE, SCV is significantly lower in children who have LCA compared with those that do not. However, in this cohort, we are unable to determine whether the relationship is independent of ICV or etiology. Future, larger scale studies may help tease this out.
Highlights
The degree of lower cognitive ability (LCA) is largely dependent on etiology of Convulsive status epilepticus (CSE): subjects presenting with prolonged febrile seizures (PFS) perform significantly better than those with non-PFS upon formal psychometric cognitive testing [4]
We aimed to establish (1) if subcortical volumetric differences exist among healthy controls (HC), subjects with CSE with LCA (CSE+) and subjects with CSE without LCA (CSE−) and (2) to determine if there was an association between subcortical nuclei volumes and full-scale intelligence quotient (FSIQ)/Global Memory Scores (GMS) scores at long-term follow-up post-CSE
Since we identified that there was a group effect from the analysis, we subsequently did further regression analyses restricted to the group with CSE only to identify characteristics of the patients with CSE, including subcortical volumes that were associated with FSIQ and GMS
Summary
Having recently shown in a 9-year follow-up of a unique childhood CSE cohort that children with CSE who undertook formal testing (n = 94) were shown to have significantly lower full-scale intelligence quotient (FSIQ) and Global Memory Scores (GMS) from controls, we aimed in the current study to examine the relationship between subcortical volumes and FSIQ and GMS in children who had CSE [19]. Such data may provide insight into the role of these structures in cognition and aid our understanding of the pathophysiology of LCA in CSE. The identification of structural abnormalities in the subcortical structures may allow for recognition of those susceptible to subsequent LCA, thereby facilitating the prioritization of earlier neuropsychological interventions
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