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Epilepsy is a common disorder characterized by recurrent seizures. An overwhelming majority of people with epilepsy regard the unpredictability of seizures as a major issue. More than 30 years of international effort have been devoted to the prediction of seizures, aiming to remove the burden of unpredictability and to couple novel, time-specific treatment to seizure prediction technology. A highly influential review published in 2007 concluded that insufficient evidence indicated that seizures could be predicted. Since then, several advances have been made, including successful prospective seizure prediction using intracranial EEG in a small number of people in a trial of a real-time seizure prediction device. In this Review, we examine advances in the field, including EEG databases, seizure prediction competitions, the prospective trial mentioned and advances in our understanding of the mechanisms of seizures. We argue that these advances, together with statistical evaluations, set the stage for a resurgence in efforts towards the development of seizure prediction methodologies. We propose new avenues of investigation involving a synergy between mechanisms, models, data, devices and algorithms and refine the existing guidelines for the development of seizure prediction technology to instigate development of a solution that removes the burden of the unpredictability of seizures. [ABSTRACT FROM AUTHOR]

Pharmaco-electroencephalography (pharmaco-EEG) has never gained great popularity in epilepsy research. Nevertheless, the electroencephalogram (EEG) is the most important neurological examination technique in this patient population. Development and investigation of antiepileptic drugs (AEDs) involves EEG for diagnosis and outcome evaluation. In contrast to the common use of the EEG for documenting the effect of AEDs on the presence of interictal epileptiform activities or seizures, quantitative analysis of drug responses in the EEG are not yet standard in pharmacological studies. We provide an overview of dedicated pharmaco-EEG studies with AEDs in humans. A systematic search in PubMed yielded 43 articles, which were reviewed for their relevance. After excluding studies according to our exclusion criteria, nine studies remained. These studies plus the retrieved references from the bibliographies of the identified studies yielded 37 studies to be included in the review. The most prominent method in pharmaco-EEG research for AEDs was analysis of the frequency content in response to drug intake, often with quantitative methods such as spectral analysis. Despite documenting the effect of the drug on brain activity, some studies were conducted in order to document treatment response, detect neurotoxic effects, and measure reversibility of AED-induced changes. There were some attempts to predict treatment response or side effects. We suggest that pharmaco-EEG deserves more attention in AED research, specifically because the newest drugs and techniques have not yet been subject to investigation. [ABSTRACT FROM AUTHOR]

Nodes in large-scale epileptic networks that are crucial for seizure facilitation and termination can be regarded as potential targets for individualized focal therapies. Graph-theoretical approaches based on centrality concepts can help to identify such important nodes, however, they may be influenced by the way networks are derived from empirical data. Here we investigate evolving functional epileptic brain networks during 82 focal seizures with different anatomical onset locations that we derive from multichannel intracranial electroencephalographic recordings from 51 patients. We demonstrate how the various methodological steps (from the recording montage via node and link inference to the assessment of node centralities) affect importance estimation and discuss their impact on the interpretability of findings in the context of pathophysiological aspects of seizure dynamics. [ABSTRACT FROM AUTHOR]

Abstract: Epilepsy is a malfunction of the brain that affects over 50 million people worldwide. Epileptic seizures are usually characterized by an abnormal synchronized firing of neurons involved in the epileptic process. In human epilepsy the exact mechanisms underlying seizure generation are still uncertain as are mechanisms underlying seizure spreading and termination. There is now growing evidence that an improved understanding of the epileptic process can be achieved through the analysis of properties of epileptic brain networks and through the analysis of interactions in such networks. In this overview, we summarize recent methodological developments to assess synchronization phenomena in human epileptic brain networks and present findings obtained from analyses of brain electromagnetic signals recorded in epilepsy patients. [Copyright &y& Elsevier]

The framework of the theory of nonlinear dynamics provides powerful concepts and algorithms to study complicated dynamics such as brain electrical activity (electroencephalogram, EEG). Although different influencing factors render the use of nonlinear measures in a strict sense problematic, converging evidence from various investigations now indicates that nonlinear EEG analysis provides a means to reliably characterize different states of physiological and pathophysiological brain function. We here focus on applications of nonlinear EEG analysis in epileptology. Epilepsy affects more than 50 million individuals worldwide – approximately 1% of the world's population. The disease is characterized by a recurrent and sudden malfunction of the brain that is termed seizure. Nonlinear EEG analysis techniques allow to reliably identify the seizure generating structure (epileptic focus) in different areas of the brain even during seizure-free intervals, to disentangle complex spatio-temporal interactions between the epileptic focus and other areas of the brain, and to define a specific state predictive of an impending seizure. Nonlinear EEG analysis provides supplementary information about the epileptogenic process in humans, contributes to an improvement of the presurgical evaluation of epilepsy patients, and offers a basis for the development of new therapy concepts for seizure prevention. [ABSTRACT FROM AUTHOR]

We investigate the relative merit of different linear and nonlinear synchronization measures for a characterization of the spatio-temporal dynamics of the epileptic process. Analyzing long-lasting multichannel electroencephalographic recordings from more than 20 epilepsy patients we show that all measures are able to identify brain regions of pathological synchronization associated with epilepsy, even during the seizure-free interval, and are able to detect a long-lasting transitional preseizure state. These findings render synchronization measures attractive for future prospective studies on seizure prediction. [ABSTRACT FROM AUTHOR]

In clinical practice, epileptic seizures with focal onset and subsequent generalised motor involvement are referred to as secondarily generalised seizures. The purpose of this study was to investigate the degree of electrophysiological generalisation in seizures that are clinically secondarily generalised. Intracranial EEG recordings of secondarily generalised tonic-clonic seizures were visually and quantitatively analysed for the presence of epileptiform activity. In 24 (26%) of 93 seizures recorded from 17 (27%) of 64 patients, intracranial EEG channels were found that never recorded epileptiform activity during secondarily generalised tonic-clonic seizures. Our results demonstrate that seizures that are secondarily generalised clinically are not always generalised electrophysiologically. This may have therapeutic implications. [ABSTRACT FROM AUTHOR]

Describes the application of nonlinear electroencephalography analysis technique for seizure prediction. Pre-ictal transitional phase; Use of the wavelet transform; Epileptogenic process during the interictal state; Phase synchronization.

Summary: Purpose: To assess whether EEG synchronization changes during short-term low-frequency electrical stimulation of the seizure onset zone. Methods: In 10 patients (34±11 years) with pharmaco-resistant epilepsy the seizure onset zone (9 temporal lobe, 1 frontal lobe) was electrically stimulated at 1Hz for 5min via intracranial electrodes. Bipolar stimuli were applied and four pulse widths (0.05, 0.1, 0.5, and 1.0ms) were tested. Stimulation amplitudes were held fixed at 1mA for strip electrodes and at 2mA for depth electrodes. Changes of EEG synchronization were assessed by the eigenvalue dynamics of the cross-correlation matrix computed from a 2.5s sliding window. Results: 37 stimulations were performed. We observed EEG desynchronization in 49% (18/37), an increase of EEG synchronization in 27% (10/37) and an EEG pattern with no significant change of synchronization in 24% (9/37). EEG synchronization most frequently occurred when stimulating with a pulse width of 0.5ms. In a patient with bilateral independent seizure onsets stimulation effects on EEG synchronization were different for each side. In the patient with the shortest duration of temporal lobe epilepsy, stimulation triggered periodic epileptic spikes phase-locked to stimulation. One patient experienced an aura during stimulation, which did not evolve into a seizure, and in one patient a sub-clincial seizure occurred. Discussion: Low-frequency stimulation of the seizure onset zone is associated with different changes of EEG synchronization and its effects depend on the widths of the stimulation pulses. It may be an appropriate stimulation technique for long-term studies assessing whether synchronized or desynchronized brain dynamics prevent seizure occurrence. [Copyright &y& Elsevier]

Abstract: Objective: To test whether increasing synchronization of neuronal activity might be causally related to seizure termination. Methods: Neuronal synchronization was assessed by the relative changes of the eigenvalue spectrum of the equal-time correlation matrix computed from a short window sliding along multi-channel EEGs, recorded with either intracranial or surface electrodes. Results: Synchronization dynamics of six status epilepticus EEG recordings from six patients were assessed. In all six recordings EEG synchronization fluctuated around relatively low levels during ongoing epileptiform activity. Synchronization only persistently increased before, or in one case, at the end of status epilepticus. Ongoing seizure activity stopped without pharmacological intervention in one patient. In four of the five other cases, the persistent increase of synchronization followed administration of anticonvulsant drugs. Conclusions: Our findings support the hypothesis that increasing synchronization of neuronal activity may be considered as an emergent self-regulatory mechanism for seizure termination. Significance: The traditional concept is challenged that increasing neuronal synchronization during epileptic seizures is always pathological and should be suppressed. On the contrary, our findings imply that therapeutic interventions to increase synchronization during seizures might be beneficial. [Copyright &y& Elsevier]

Abstract: Debates on six controversial topics were held during the Fourth International Workshop on Seizure Prediction (IWSP4) convened in Kansas City, KS, USA, July 4–7, 2009. The topics were (1) Ictogenesis: Focus versus Network? (2) Spikes and Seizures: Step-relatives or Siblings? (3) Ictogenesis: A Result of Hyposynchrony? (4) Can Focal Seizures Be Caused by Excessive Inhibition? (5) Do High-Frequency Oscillations Provide Relevant Independent Information? (6) Phase Synchronization: Is It Worthwhile as Measured? This article, written by the IWSP4 organizing committee and the debaters, summarizes the arguments presented during the debates. [ABSTRACT FROM AUTHOR]