Predictability of uncontrollable multifocal seizures – towards new treatment options

Abstract

Drug-resistant, multifocal, non-resectable epilepsies are among the most difficult epileptic disorders to manage. An approach to control previously uncontrollable seizures in epilepsy patients would consist of identifying seizure precursors in critical brain areas combined with delivering a counteracting influence to prevent seizure generation. Predictability of seizures with acceptable levels of sensitivity and specificity, even in an ambulatory setting, has been repeatedly shown, however, in patients with a single seizure focus only. We did a study to assess feasibility of state-of-the-art, electroencephalogram-based seizure-prediction techniques in patients with uncontrollable multifocal seizures. We obtained significant predictive information about upcoming seizures in more than two thirds of patients. Unexpectedly, the emergence of seizure precursors was confined to non-affected brain areas. Our findings clearly indicate that epileptic networks, spanning lobes and hemispheres, underlie generation of seizures. Our proof-of-concept study is an important milestone towards new therapeutic strategies based on seizure-prediction techniques for clinical practice.

No evidence for critical slowing down prior to human epileptic seizures

“…Also, we found no clear-cut evidence for critical slowing down to be confined to the brain region from which epileptic seizures appear to originate. The lack of a spatial sensitivity and specificity of indicators for critical slowing down not only supports the current notion of a network mechanism to underlie the transition to the pre-seizure state 41,43,45,[59][60][61] but also indicates that the mechanism behind the critical transition assumed here (bifurcation-induced tipping) may be too simplistic for the human epileptic brain. There are other mechanisms behind tipping phenomena, such as noise-induced and rate-dependent tipping 62 .…”

Epilepsy and cognition – A bidirectional relationship?

“…single or groups of spikes or spike waves, or longer phases of epileptic activity in terms of nonconvulsive seizures) [62][63][64][65]. The occurrence of seizures not only depends on the activity of the epileptic focus but also on the activity of distant non-pathological brain areas [66]. Consequently, if non-focal brain areas are under intentional use cognitive activation can hinder seizure evolution, because it becomes difficult for epilepsy to overtake/recruit the brain areas which are already functionally occupied.…”

Centrality-based identification of important edges in complex networks

“…More recently, special emphasis has been placed on the mesoscopic structural organization (e.g., on communities 16 , on motifs 17,18 , or on core-periphery structure 19 ) as well as on microscopic aspects, such as the role of individual network constituents (i.e., vertices or edges) in structure and dynamics of interaction networks 20 . It is clear that identifying key network constituents and characterizing their importance for structure and dynamics of interaction networks is highly relevant to improve understanding and controlling of the collective dynamics [21][22][23][24][25] .…”

“…We here address this issue and propose modifications of various, widely used centrality concepts for vertices to arXiv:1908.10667v1 [physics.soc-ph] 25 Aug 2019 those for edges, in order to find which edges in a network are important between other pairs of vertices. We concentrate on eigenvector and closeness centrality, in addition to betweenness centrality 31 .…”