Patient-Specific Epileptic Seizure Prediction in Long-Term Scalp EEG Signal Using Multivariate Statistical Process Control

An accurate epileptic seizure prediction algorithm can alleviate the problem and reduce risks in the life of a patient suffering from epilepsy. The main motive of this work is to propose a model which can predict seizures well in advance of its occurrence. Multivariate statistical process control (MSPC) has been used for seizure predictions in long-term scalp EEG signal. It has been observed that excessive neuronal activity in the preictal period of seizure changes the electrical characteristic from chaotic to rhythmic behavior. These changes have been utilized for prediction. Eight temporal based features are used for predicting the seizures by using multivariate statistical process control, which is widely known as an anomaly monitoring method. 90 seizures from the CHB-MIT EEG data of ten patients are analyzed.ResultThe results of the proposed method demonstrated that 80 seizures out of 90 in preictal period were correctly predicted prior to the seizure onset, thereby giving a sensitivity of 88.89%. The false positive rate is observed to 0.39 per hour.ConclusionThis study proposed a temporal based patient-specific epileptic seizure prediction method using MSPC in long-term scalp EEG signals. It also provides the possibility of realizing an EEG-based epileptic seizure prediction system which requires less computational power.SignificanceThe proposed method does not require preictal data for modeling. The extracted features are computationally easy. The tested result shows good accuracy on the CHB-MIT data base.     

Epileptic seizures may begin hours in advance of clinical onset: a report of five patients

Mechanisms underlying seizure generation are traditionally thought to act over seconds to minutes before clinical seizure onset. We analyzed continuous 3- to 14-day intracranial EEG recordings from five patients with mesial temporal lobe epilepsy obtained during evaluation for epilepsy surgery. We found localized quantitative EEG changes identifying prolonged bursts of complex epileptiform discharges that became more prevalent 7 hr before seizures and highly localized subclinical seizure-like activity that became more frequent 2 hr prior to seizure onset. Accumulated energy increased in the 50 min before seizure onset, compared to baseline. These observations, from a small number of patients, suggest that epileptic seizures may begin as a cascade of electrophysiological events that evolve over hours and that quantitative measures of preseizure electrical activity could possibly be used to predict seizures far in advance of clinical onset.     

Neurosurgical management of epilepsy: a personal perspective in 1983

The therapeutic goal in the neurosurgical treatment of medically intractable epilepsy is complete seizure control, for both biologic and psychosocial reasons. Cortical resections are more likely to accomplish this than other surgical alternatives for epilepsy. Although abnormalities on new imaging techniques (CT, positron emission scanning) aid in identifying the epileptic focus, interictal epileptiform EEG changes remain the main indicator of focal origin of the seizures. Where this is equivocal, direct brain recording of spontaneous seizures with subdural electrodes is of value in identifying the side and lobe of seizure onset. The cortical resection is then tailored by the extent of the interictal electrocorticographic abnormalities and functional identification of essential areas such as those for language, using an electrical stimulation mapping technique, under local anesthesia. With this approach, half of the patients with temporal lobe foci are seizure-free since the time of operation, over two-thirds become so with time, and over three-quarters have at least very major reductions in seizure frequency.     

Scalp EEG for the diagnosis of epilepsy and photosensitivity in the baboon

Spontaneous seizures have been observed in several baboon species housed at the Southwest National Primate Research Center (SNPRC), including Papio hamadryas anubis and cynocephalus/anubis, hamadryas/anubis, and papio/anubis hybrids. The goal of this study was to establish a noninvasive, reliable electroencephalographic technique to characterize epilepsy phenotypes and assess photosensitivity in these subspecies. Thirty baboons with witnessed seizures, and 15 asymptomatic baboons underwent scalp electroencephalograms (EEGs) with photic stimulation (PS). The sensitivity and specificity of surface EEG for identifying interictal epileptic discharges (IEDs) in baboons with witnessed seizures were examined. The morphology of IEDs, electroclinical features of seizures and responses to PS, reproducibility of EEG findings, and intrarater reliability were also evaluated. Twenty-three seizure baboons (77%) demonstrated IEDs, predominantly with frequencies of 4-6 Hz in 18 baboons and 2-3 Hz in six baboons. Two seizure animals had a mixture of 2-3-Hz and 4-6-Hz IEDs. All animals with 2-3-Hz IEDs were 3 years old or younger. Myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were recorded in 13 baboons (43%). PS activated IEDs in 15 baboons (50%) and seizures in nine baboons. The presence of IEDs or seizures was not associated with a particular gender or species (Fisher exact test, alpha=0.05). Seizures were more common in animals >3 years old, while PS-induced IEDs and seizures were more prevalent in P.h. anubis/cynocephalus crosses compared to P.h. anubis. In the asymptomatic controls, IEDs were recorded in five baboons (33%), and photoparoxysmal responses were observed in two (13%). Surface EEG is a sensitive and reliable instrument for characterizing the epilepsy encountered in Papio species. Electroclinically, the seizure animals had generalized epilepsy with photosensitivity. The variation in IED morphology may be age-related or it may reflect different epileptic phenotypes. Ketamine provoked IEDs and seizures in most seizure animals and only in a few asymptomatic baboons; therefore, it may enhance the sensitivity of surface EEG for detecting a predisposition to epilepsy.     

Stability of synchronization clusters and seizurability in temporal lobe epilepsy

Purpose

Identification of critical areas in presurgical evaluations of patients with temporal lobe epilepsy is the most important step prior to resection. According to the “epileptic focus model”, localization of seizure onset zones is the main task to be accomplished. Nevertheless, a significant minority of epileptic patients continue to experience seizures after surgery (even when the focus is correctly located), an observation that is difficult to explain under this approach. However, if attention is shifted from a specific cortical location toward the network properties themselves, then the epileptic network model does allow us to explain unsuccessful surgical outcomes.

Methods

The intraoperative electrocorticography records of 20 patients with temporal lobe epilepsy were analyzed in search of interictal synchronization clusters. Synchronization was analyzed, and the stability of highly synchronized areas was quantified. Surrogate data were constructed and used to statistically validate the results. Our results show the existence of highly localized and stable synchronization areas in both the lateral and the mesial areas of the temporal lobe ipsilateral to the clinical seizures. Synchronization areas seem to play a central role in the capacity of the epileptic network to generate clinical seizures. Resection of stable synchronization areas is associated with elimination of seizures; nonresection of synchronization clusters is associated with the persistence of seizures after surgery.

Discussion

We suggest that synchronization clusters and their stability play a central role in the epileptic network, favoring seizure onset and propagation. We further speculate that the stability distribution of these synchronization areas would differentiate normal from pathologic cases.     

癫痫病人脑电信号的奇异谱

癫痫是一种常见的神经系统疾患,其唯一客观证据为脑电图的癫痫样发放。在癫痫发作间期,仅有偶发的很难辨别的癫痫样放电,为了正确诊断癫痫病,往往需要医生长时间监测病人的脑电信号,在对脑电信号进行相空间重构,进而对其进行奇异系统分析,发现癫痫病人无论在癫痫发作前、发作中、发作后,其脑电信号的奇异谱曲线不存在噪声平台,明显区别于正常人。是否可以认为脑电信号的奇异谱正代表着大脑的一种基本状态,癫痫患者在未发作时,大脑的基本状态已经处于异常。无论如休,奇异系统分析方法使得可以利用很短的一段脑电数据诊断癫痫。无疑为癫痫病人的临床诊断提供了一条简单、有效的途径。     

Complexity of Multi-Channel Electroencephalogram Signal Analysis in Childhood Absence Epilepsy

Absence epilepsy is an important epileptic syndrome in children. Multiscale entropy (MSE), an entropy-based method to measure dynamic complexity at multiple temporal scales, is helpful to disclose the information of brain connectivity. This study investigated the complexity of electroencephalogram (EEG) signals using MSE in children with absence epilepsy. In this research, EEG signals from 19 channels of the entire brain in 21 children aged 5-12 years with absence epilepsy were analyzed. The EEG signals of pre-ictal (before seizure) and ictal states (during seizure) were analyzed by sample entropy (SamEn) and MSE methods. Variations of complexity index (CI), which was calculated from MSE, from the pre-ictal to the ictal states were also analyzed. The entropy values in the pre-ictal state were significantly higher than those in the ictal state. The MSE revealed more differences in analysis compared to the SamEn. The occurrence of absence seizures decreased the CI in all channels. Changes in CI were also significantly greater in the frontal and central parts of the brain, indicating fronto-central cortical involvement of “cortico-thalamo-cortical network” in the occurrence of generalized spike and wave discharges during absence seizures. Moreover, higher sampling frequency was more sensitive in detecting functional changes in the ictal state. There was significantly higher correlation in ictal states in the same patient in different seizures but there were great differences in CI among different patients, indicating that CI changes were consistent in different absence seizures in the same patient but not from patient to patient. This implies that the brain stays in a homogeneous activation state during the absence seizures. In conclusion, MSE analysis is better than SamEn analysis to analyze complexity of EEG, and CI can be used to investigate the functional brain changes during absence seizures.     

Epilepsy and Nonlinear Dynamics

This overview summarizes findings obtained from analyzing electroencephalographic (EEG) recordings from epilepsy patients with methods from the theory of nonlinear dynamical systems. The last two decades have shown that nonlinear time series analysis techniques allow an improved characterization of epileptic brain states and help to gain deeper insights into the spatial and temporal dynamics of the epileptic process. Nonlinear EEG analyses can help to improve the evaluation of patients prior to neurosurgery, and with an unequivocal identification of precursors of seizures, they can be of great value in the development of seizure warning and prevention techniques.     

Multiway analysis of epilepsy tensors

MOTIVATION: The success or failure of an epilepsy surgery depends greatly on the localization of epileptic focus (origin of a seizure). We address the problem of identification of a seizure origin through an analysis of ictal electroencephalogram (EEG), which is proven to be an effective standard in epileptic focus localization. SUMMARY: With a goal of developing an automated and robust way of visual analysis of large amounts of EEG data, we propose a novel approach based on multiway models to study epilepsy seizure structure. Our contributions are 3-fold. First, we construct an Epilepsy Tensor with three modes, i.e. time samples, scales and electrodes, through wavelet analysis of multi-channel ictal EEG. Second, we demonstrate that multiway analysis techniques, in particular parallel factor analysis (PARAFAC), provide promising results in modeling the complex structure of an epilepsy seizure, localizing a seizure origin and extracting artifacts. Third, we introduce an approach for removing artifacts using multilinear subspace analysis and discuss its merits and drawbacks. RESULTS: Ictal EEG analysis of 10 seizures from 7 patients are included in this study. Our results for 8 seizures match with clinical observations in terms of seizure origin and extracted artifacts. On the other hand, for 2 of the seizures, seizure localization is not achieved using an initial trial of PARAFAC modeling. In these cases, first, we apply an artifact removal method and subsequently apply the PARAFAC model on the epilepsy tensor from which potential artifacts have been removed. This method successfully identifies the seizure origin in both cases.     

Dynamic Imaging of Coherent Sources Reveals Different Network Connectivity Underlying the Generation and Perpetuation of Epileptic Seizures

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis.     

Functional Connectivity Estimated from Intracranial EEG Predicts Surgical Outcome in Intractable Temporal Lobe Epilepsy

This project aimed to determine if a correlation-based measure of functional connectivity can identify epileptogenic zones from intracranial EEG signals, as well as to investigate the prognostic significance of such a measure on seizure outcome following temporal lobe lobectomy. To this end, we retrospectively analyzed 23 adult patients with intractable temporal lobe epilepsy (TLE) who underwent an invasive stereo-EEG (SEEG) evaluation between January 2009 year and January 2012. A follow-up of at least one year was required. The primary outcome measure was complete seizure-freedom at last follow-up. Functional connectivity between two areas in the temporal lobe that were sampled by two SEEG electrode contacts was defined as Pearson’s correlation coefficient of interictal activity between those areas. SEEG signals were filtered between 5 and 50 Hz prior to computing this correlation. The mean and standard deviation of the off diagonal elements in the connectivity matrix were also calculated. Analysis of the mean and standard deviation of the functional connections for each patient reveals that 90% of the patients who had weak and homogenous connections were seizure free one year after temporal lobectomy, whereas 85% of the patients who had stronger and more heterogeneous connections within the temporal lobe had recurrence of seizures. This suggests that temporal lobectomy is ineffective in preventing seizure recurrence for patients in whom the temporal lobe is characterized by weakly connected, homogenous networks. This pilot study shows promising potential of a simple measure of functional brain connectivity to identify epileptogenicity and predict the outcome of epilepsy surgery.     

基于脑电信号的癫痫发作预测特征及识别

解码癫痫发作前脑电信号的神经元集群异常痫样放电活动,对癫痫发作进行有效预测并实施病前干预,可显著减少疾病病损,是癫痫防治的研究热点之一。基于脑电信号的癫痫发作预测研究关键在于发作间期和前期的异常状态识别,研究上述两状态间的神经动力学特征差异对明确癫痫发病机制、选取高分辨特征,进而有效识别该渐进性疾病所处的发作阶段具有重要价值。目前,研究者已对当前主流特征提取及模式识别方法进行了充分的调研梳理,但忽视了神经动态特征变化对于癫痫发作预测的重要意义。基于此,本文归纳总结了5类典型的发作预测特征分析方法及其优缺点,重点剖析了发作间期至前期神经生理特征的动态变化及其动力学特性,类比分析了当前该领域主流的机器学习和深度学习特征识别方法,以期为进一步建立精准、高效的癫痫发作预测技术提供新思路。     

Analysis of Epileptic Discharges from Implanted Subdural Electrodes in Patients with Sturge-Weber Syndrome

ObjectiveAlmost two-thirds of patients with Sturge-Weber syndrome (SWS) have epilepsy, and half of them require surgery for it. However, it is well known that scalp electroencephalography (EEG) does not demonstrate unequivocal epileptic discharges in patients with SWS. Therefore, we analyzed interictal and ictal discharges from intracranial subdural EEG recordings in patients treated surgically for SWS to elucidate epileptogenicity in this disorder.MethodsFive intractable epileptic patients with SWS who were implanted with subdural electrodes for presurgical evaluation were enrolled in this study. We examined the following seizure parameters: seizure onset zone (SOZ), propagation speed of seizure discharges, and seizure duration by visual inspection. Additionally, power spectrogram analysis on some frequency bands at SOZ was performed from 60 s before the visually detected seizure onset using the EEG Complex Demodulation Method (CDM).ResultsWe obtained 21 seizures from five patients for evaluation, and all seizures initiated from the cortex under the leptomeningeal angioma. Most of the patients presented with motionless staring and respiratory distress as seizure symptoms. The average seizure propagation speed and duration were 3.1 ± 3.6 cm/min and 19.4 ± 33.6 min, respectively. Significant power spectrogram changes at the SOZ were detected at 10–30 Hz from 15 s before seizure onset, and at 30–80 Hz from 5 s before seizure onset.SignificanceIn patients with SWS, seizures initiate from the cortex under the leptomeningeal angioma, and seizure propagation is slow and persists for a longer period. CDM indicated beta to low gamma-ranged seizure discharges starting from shortly before the visually detected seizure onset. Our ECoG findings indicate that ischemia is a principal mechanism underlying ictogenesis and epileptogenesis in SWS.     

Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats

Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients.     

Mitochondrial dysfunction in epilepsy

Mitochondrial dysfunction has been identified as one potential cause of epileptic seizures. Impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon's horn sclerosis and of adult and immature animal models of epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca(2+) homeostasis and generation of reactive oxygen species, their dysfunction strongly affects neuronal excitability and synaptic transmission. Therefore, mitochondrial dysfunction is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant epilepsy. For this reason mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy.     

Solitary epileptic seizure--the risk of recurrence

Patients experiencing solitary unprovoked epileptic seizure have different risks of recurrence. The possible risk factors include in particular: structural cerebral lesion and its cause, history of febrile seizures, family history of epilepsy, the type of seizure, epileptiform EEG discharges and the problem of initiation or (or not initiation) of antiepileptic treatment after the first paroxysm. The factors shown above were evaluated in a group of 30 patients with solitary unprovoked epileptic seizure. Regarding recurrence of epileptic seizure, the only significant factor appeared to be initiation of treatment after the first unprovoked paroxysm (p<0.001). We observed a 30% and 33.33% risk of recurrence following the initial epileptic seizure in patients after the first unprovoked seizure in less than 1 and 3 years, respectively.     

Up-regulation of apelin in brain tissue of patients with epilepsy and an epileptic rat model

Prolonged epileptic seizures or SE can cause neuronal cell death. However, the exact role of neuroprotectant against brain injury during epileptic seizure needs to be further elucidated. The aim of this study was to investigate the expression of the apelin, a novel neuroprotective peptide, in brain tissues of the patients with temporal lobe epilepsy (TLE) and experimental rats using immunohistochemistry, immunofluorescence and Western blotting analysis and to discuss the possible role of apelin in TLE. Thirty temporal neocortical tissue samples from the patients with drug-refractory TLE underwent surgical therapy and nine histologically normal temporal lobes tissues as controls were used in our study. Fifty-six Sprague-Dawley rats were randomly divided into seven groups, including one control group and six groups with epilepsy induced by lithium-pilocarpine. Hippocampus and adjacent cortex were taken from the controls and epileptic rats at 1, 3, 7, 14, 30, and 60 days after onset of seizures. Apelin was mainly expressed in the neurons of TLE patients and controls, and was significantly increased in TLE patients compared with the controls. Apelin was also expressed in the neurons of experimental and control rats, it was gradually increased in the experimental rat post-seizure and reached a stable high level in chronic epileptic phase. Our results demonstrated that the increased expression of apelin in the brain may be involved in human TLE.     

Dissociation, forced normalization and dynamic multi-stability of the brain

Dissociated states represent pathological conditions where psychological trauma may emerge in a variety of forms such as psychic dissociative symptoms (hallucinations, derealization etc.) or on the other hand as somatoform symptoms (paroxysms, loss of motor control, involuntary movements etc.). Recent findings suggest that neurophysiological level of dissociative phenomena may be linked to the same neurophysiological principles that emerge in multi-stable perception of ambiguous stimuli likely caused by competing interpretations with mutual exclusivity. At this time there is evidence that temporal lobe seizure activity can produce dissociative syndrome and from these findings may be inferred that temporal lobe epileptic activity existing independently of neurological focal may share common neurobiological mechanism with dissociative symptoms. This conceptualization of dissociative phenomena is also in accordance with findings that originate from the study of the relationship between epilepsy and mental illness. The relationship was for the first time described in Meduna's concept of antagonism between epilepsy and psychosis and from the study of forced normalization introduced by Landolt in 1950s. The findings reported similar pathological conditions as in dissociative states when psychopathological symptoms and paroxysms may represent two different forms of the pathological process. Following the concept of forced normalization Tellenbach in 1965 introduced the term alternative psychosis implicating that stopping seizures does not mean vanishing or inactivity of the pathological state and that the epilepsy is still active subcortically and supplies energy for psychopathological symptoms. In the present review chaos in brain neural networks as a possible explanation of the relationship between dissociation and epileptic activity has been suggested that represents testable hypothesis for future research.     

Scale Invariance Properties of Intracerebral EEG Improve Seizure Prediction in Mesial Temporal Lobe Epilepsy

Although treatment for epilepsy is available and effective for nearly 70 percent of patients, many remain in need of new therapeutic approaches. Predicting the impending seizures in these patients could significantly enhance their quality of life if the prediction performance is clinically practical. In this study, we investigate the improvement of the performance of a seizure prediction algorithm in 17 patients with mesial temporal lobe epilepsy by means of a novel measure. Scale-free dynamics of the intracerebral EEG are quantified through robust estimates of the scaling exponents—the first cumulants—derived from a wavelet leader and bootstrap based multifractal analysis. The cumulants are investigated for the discriminability between preictal and interictal epochs. The performance of our recently published patient-specific seizure prediction algorithm is then out-of-sample tested on long-lasting data using combinations of cumulants and state similarity measures previously introduced. By using the first cumulant in combination with state similarity measures, up to 13 of 17 patients had seizures predicted above chance with clinically practical levels of sensitivity (80.5%) and specificity (25.1% of total time under warning) for prediction horizons above 25 min. These results indicate that the scale-free dynamics of the preictal state are different from those of the interictal state. Quantifiers of these dynamics may carry a predictive power that can be used to improve seizure prediction performance.     

癫痫与海马结构的改变

癫痫作为一种严重危害人类健康的常见病、多发病，其致病机理至今尚未阐明。30—60％的患者药物治疗无效，称“难治性癫痫”。随着现代医学的发展，外科手术的开展对于癫痫患者治疗也没有满意的效果。这就对于我们探求癫痫患者病灶的起源有了更深层次的要求。大量动物实验表明，海马作为中枢神经系统的重要结构不仅同学习、记忆、情绪等密切相关，还同癫痫的发生发展有着重要的联系。本文就大脑可塑性与癫痫的关系进行综述。