The system epilepsies: A pathophysiological hypothesis

Department of Neurophysiology, IRCCS Foundation Neurological Institute Carlo Besta, Milan, Italy.
Epilepsia (Impact Factor: 4.57). 05/2012; 53(5):771-8. DOI: 10.1111/j.1528-1167.2012.03462.x
Source: PubMed


We postulate that "system epilepsies" (SystE) are due to an enduring propensity to generate seizures of functionally characterized brain systems. Data supporting this hypothesis-that some types of epilepsy depend on the dysfunction of specific neural systems-are reviewed. The SystE hypothesis may drive pathophysiologic and clinical studies that can advance our understanding of epilepsies and can open up new therapeutic perspectives.

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Available from: Stefano Meletti, Oct 08, 2015
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    • "Reflex function-related mechanisms are known to play an important role in the pathogenesis of generalized epilepsy [101] [102] [103]. Spontaneous and reflex seizures have similar patterns [111] and are supposed to represent the two extremities of a continuum on which seizures are generated by extrinsic and intrinsic triggers [112]. "
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    ABSTRACT: Human epilepsy is usually considered to result from cortical pathology, but animal studies show that the cortex may be secondarily involved in epileptogenesis, and cortical seizures may be triggered by extracortical mechanisms. In the audiogenic kindling model, recurrent subcortical (brainstem-driven) seizures induce secondary epileptic activation of the cortex. The present review focuses on behavioral and electrographic features of the subcortico-cortical epileptogenesis: (1) behavioral expressions of traditional and mild paradigms of audiogenic kindling produced by full-blown (generalized) and minimal (focal) audiogenic seizures, respectively; (2) electrographic manifestations of secondary epileptic activation of the cortex - cortical epileptic discharge and cortical spreading depression; and (3) persistent individual asymmetry of minimal audiogenic seizures and secondary cortical events produced by their repetition. The characteristics of audiogenic kindling suggest that this model represents a unique experimental approach to studying cortical epileptogenesis and network aspects of epilepsy. This article is part of a Special Issue entitled "Genetic Models - Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.
    Epilepsy & Behavior 07/2015; 26. DOI:10.1016/j.yebeh.2015.06.014 · 2.26 Impact Factor
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    • "The next step would be to extend this using heterogeneous patient derived connectivity instead of using homogeneous connectivity as in (Robinson et al., 2002). This approach should also be used for other 'system' epilepsies (Avanzini et al., 2012). "
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    ABSTRACT: Epilepsy is a neurological condition characterised by the recurrence of seizures. During seizures multiple brain areas can behave abnormally. Rather than considering each abnormal area in isolation, one can consider them as an interconnected functional 'network'. Recently, there has been a shift in emphasis to consider epilepsy as a disorder involving more widespread functional brain networks than perhaps was previously thought. The basis for these functional networks is proposed to be the static structural brain network established through the connectivity of the white matter. Additionally, it has also been argued that time varying aspects of epilepsy are of crucial importance and as such computational models of these dynamical properties have recently advanced. We describe how dynamic computer models can be combined with static human in vivo connectivity obtained through diffusion weighted magnetic resonance imaging. We predict that in future the use of these two methods in concert will lead to predictions for optimal surgery and brain stimulation sites for epilepsy and other neurological disorders.
    Journal of Neuroscience Methods 08/2014; 236. DOI:10.1016/j.jneumeth.2014.08.010 · 2.05 Impact Factor
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    • "" Authors generally agree that the cognitive consequences are more global and profound when epilepsy occurs early in infancy, whereas a later onset is associated with more selective neuropsychological dysfunctions. Within the EEs, different syndromes have been recently considered as examples of system epilepsies (Avanzini et al., 2012), depending on the dysfunction of complex cortical-subcortical interconnected systems. The pathophysiologic explanation of the negative impact of epileptic activity is strictly associated with the brain organization processes of synaptic pruning and, consequently , of corticosubcortical network building up. "
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    ABSTRACT: The International League Against Epilepsy (ILAE) Commission report on classification and terminology indicates that "diagnosing an individual as having an encephalopathic course requires demonstration of a failure to develop as expected relative to the same-aged peers or to regress in abilities." In this chapter, basing our discussion on the theoretical framework of neuroconstructivism, on the latest results deriving from functional neuroimaging and on the concept of system epilepsy, we use continuous spike-waves during slow-wave sleep (CSWS) as an example of how non-rapid eye movement (NREM) sleep spikes interfere with the organization and consolidation of neuropsychological networks in the sensitive phase of development, affecting also interconnected systems. Indeed, recent discoveries show that the normal overnight downscaling of slow wave activity (SWA) from the first to the last hours of sleep is absent in electrical status epilepticus during sleep (ESES) patients, thus impairing the neural process and possibly the local plastic changes associated with learning and other cognitive functions. Moreover, specific patterns of spike-induced activation (especially in perisylvian and/or prefrontal areas) and deactivation of default mode network (DMN) have been shown in patients with CSWS. Consequently, to date, we may conceive that the possible mechanisms underlying neuropsychological disorders in encephalopathic epilepsy (EE) may be double, since NREM sleep interictal epileptic discharges (IEDs) induce both a pathologic activation in epileptogenic areas and a pathologic deactivation of DMN beyond the epileptogenic zone. The growing body of literature on the effects of ESES in CSWS provides us with increasing knowledge on the complexity of brain development and a better understanding of plasticity, enlightening the pathogenesis of damage on developing neuropsychological functions. Finally, the need for an individually tailored interpretation of the neuropsychological testing results, expected to integrate neurophysiology and functional neuroimaging data, is suggested.
    Epilepsia 11/2013; 54 Suppl 8(s8):38-44. DOI:10.1111/epi.12422 · 4.57 Impact Factor
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