Functional and Structural Network Disorganizations in Typical Epilepsy With Centro-Temporal Spikes and Impact on Cognitive Neurodevelopment

Abstract

Epilepsy with Centrotemporal Spikes (ECTS) is the most common form of self-limited focal epilepsy. The pathophysiological mechanisms by which ECTS induces neuropsychological impairment in 15–30% of affected children remain unclear. The objective of this study is to review the current state of knowledge concerning the brain structural and functional changes that may be involved in cognitive dysfunctions in ECTS. Structural brain imaging suggests the presence of subtle neurodevelopmental changes over the epileptogenic zone and over distant regions in ECTS. This structural remodeling likely occurs prior to the diagnosis and evolves over time, especially in patients with cognitive impairment, suggesting that the epileptogenic processes might interfere with the dynamics of the brain development and/or the normal maturation processes. Functional brain imaging demonstrates profound disorganization accentuated by interictal epileptic spikes (IES) in the epileptogenic zone and in remote networks in ECTS. Over the epileptogenic zone, the literature demonstrates changes in term of neuronal activity and synchronization, which are effective several hundred milliseconds before the IES. In the same time window, functional changes are also observed in bilateral distant networks, notably in the frontal and temporal lobes. Effective connectivity demonstrates that the epileptogenic zone constitutes the key area at the origin of IES propagation toward distant cortical regions, including frontal areas. Altogether, structural and functional network disorganizations, in terms of: (i) power spectral values, (ii) functional and effective connectivity, are likely to participate in the cognitive impairment commonly reported in children with ECTS. These results suggest a central and causal role of network disorganizations related to IES in the neuropsychological impairment described in ECTS children.

Time Interval between First and Last Epileptic Seizures and Electroencephalogram Normalization in Benign Childhood Epilepsy with Centrotemporal Spikes: Influencing Factors

“…28 Otherwise, epileptogenic process may also be associated with delaying the normal cortical maturation process. 29 The consideration above agrees with our findings regarding the influence of the age of onset of crises over the interval between the first and last seizure, since the younger the child at the first seizure, the longer this interval will be, so that for each month of increase in the age of the child at the first seizure occurrence, the interval is reduced by 0.43 months. Likewise, age also had a strong impact on EEG normalization.…”

Impact of Antiepileptic Drugs on Cognition and Neuromagnetic Activity in Childhood Epilepsy With Centrotemporal Spikes: A Magnetoencephalography Study

“…To date, numerous studies have demonstrated that the restingstate brain activity of children with CECTS has been altered (McGinnity et al, 2017;Bourel-Ponchel et al, 2019;Zhang et al, 2020). On this basis, several studies based on functional magnetic resonance (fMRI) have further investigated brain alterations in CECTS during AEDs treatment, the results of which have shown that AEDs have an effect on functional connectivity (FC) (Jiang et al, 2019(Jiang et al, , 2020), and regional activity (Zhang et al, 2017(Zhang et al, , 2018.…”

Neural correlates of verbal working memory in children with epilepsy with centro-temporal spikes

“…ECTS is often associated with neuropsychological deficits believed to reflect the interference between the epileptic focus and other brain regions during development. The cognitive dysfunctions observed in children with ECTS, including altered WM, have been linked to an abnormal developmental trajectory of brain structures, particularly those affected by epilepsy ( Besseling et al, 2013a , Bourel-Ponchel et al, 2019 , Ciumas et al, 2014 , Garcia-Ramos et al, 2015 , Garcia-Ramos et al, 2016 , Hutchinson et al, 2010 , Lin et al, 2012 , Tosun et al, 2011 , Widjaja et al, 2013 ). Task-based functional neuroimaging studies have shown that ECTS is associated with: 1) reduced activity during verbal generation task within language-related regions, in particular over the anterior language network ( Lillywhite et al, 2009 ), 2) a wider network recruitment during sentence reading comprehension ( Malfait et al, 2015 ), 3) reduced language laterality index, with more bilateral and right-hemispheric activations ( Datta et al, 2013 ) , 4) remodelling of language networks ( Vannest et al, 2013 ) and 5) altered responses to fearful stimuli ( Ciumas et al, 2017 ).…”