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,
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    • "Nonetheless, transient epileptic events should result in temporal changes in BOLD signal [Garrett et al., 2013], providing a sensitive approach for detecting regional brain abnormalities. Rolandic spikes during sleep are strongly correlated with spindle activity [Nobili et al., 1999], suggesting that thalamic dysfunction drives aberrant activity in the somatosensory system [Avanzini et al., 2012] or executive attention systems [Kavros et al., 2008] via Figure 2. The intertest reliability of ALFF map comparisons. (A) ALFF differences among the three group are presented on inflated surface maps by BrainNet Viewer ( "
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    ABSTRACT: Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting-state functional magnetic resonance imaging (RS-fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age-matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS-fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 07/2015; 36(10). DOI:10.1002/hbm.22884 · 5.97 Impact Factor
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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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