Wavelet-based Gaussian-mixture hidden Markov model for the detection of multistage seizure dynamics: A proof-of-concept study

Background  

Epilepsy is a common neurological disorder characterized by recurrent electrophysiological activities, known as seizures. Without the appropriate detection strategies, these seizure episodes can dramatically affect the quality of life for those afflicted. The rationale of this study is to develop an unsupervised algorithm for the detection of seizure states so that it may be implemented along with potential intervention strategies.     

Effect of Immunotherapy on Seizure Outcome in Patients with Autoimmune Encephalitis: A Prospective Observational Registry Study

Objective

To evaluate the seizure characteristics and outcome after immunotherapy in adult patients with autoimmune encephalitis (AE) and new-onset seizure.

Methods

Adult (age ≥18 years) patients with AE and new-onset seizure who underwent immunotherapy and were followed-up for at least 6 months were included. Seizure frequency was evaluated at 2–4 weeks and 6 months after the onset of the initial immunotherapy and was categorized as “seizure remission”, “> 50% seizure reduction”, or “no change” based on the degree of its decrease.

Results

Forty-one AE patients who presented with new-onset seizure were analysed. At 2–4 weeks after the initial immunotherapy, 51.2% of the patients were seizure free, and 24.4% had significant seizure reduction. At 6 months, seizure remission was observed in 73.2% of the patients, although four patients died during hospitalization. Rituximab was used as a second-line immunotherapy in 12 patients who continued to have seizures despite the initial immunotherapy, and additional seizure remission was achieved in 66.6% of them. In particular, those who exhibited partial response to the initial immunotherapy had a better seizure outcome after rituximab, with low adverse events.

Conclusion

AE frequently presented as seizure, but only 18.9% of the living patients suffered from seizure at 6 months after immunotherapy. Aggressive immunotherapy can improve seizure outcome in patients with AE.     

Limb-shaking transient ischemic attacks: case report and review of literature

Background  

Limb shaking Transient Ischemic Attack is a rare manifestation of carotid-occlusive disease. The symptoms usually point towards a seizure like activity and misdiagnosed as focal seizures. On careful history the rhythmic seizure like activity reveals no Jacksonian march mainly precipitated by maneuvers which lead to carotid compression. We here present a case of an elderly gentleman who was initially worked up as suffering from epileptic discharge and then later on found to have carotid occlusion.     

Prediction of seizure control in non-ketotic hyperglycemic induced seizures

Background  

To study the factors predictive for seizure control in non-ketotic hyperglycemic induced seizures (NKHS).     

Brain metastases as primary manifestation of a melanocytic malignant peripheral nerve sheath tumor in a 60-year-old man

Background  

Malignant peripheral nerve sheath tumors are rare tumor entities that originate from peripheral nerve sheaths and have an unfavorable prognosis. Metastatic spread to the cerebral parenchyma is absolutely rare. This case report describes the clinical course in a 60-year-old man whose tumor came to medical attention because of a seizure.     

Pu-Erh tea and GABA attenuates oxidative stress in kainic acid-induced status epilepticus

Background  

Pu-Erh tea is one of the most-consumed beverages due to its taste and the anti-anxiety-producing effect of the gamma-aminobutyric acid (GABA) if contains. However the protective effects of Pu-Erh tea and its constituent, GABA to kainic acid (KA)-induced seizure have not been fully investigated.     

The mTOR Inhibitor Rapamycin Has Limited Acute Anticonvulsant Effects in Mice

Objective

The mammalian target of rapamycin (mTOR) pathway integrates signals from different nutrient sources, including amino acids and glucose. Compounds that inhibit mTOR kinase activity such as rapamycin and everolimus can suppress seizures in some chronic animal models and in patients with tuberous sclerosis. However, it is not known whether mTOR inhibitors exert acute anticonvulsant effects in addition to their longer term antiepileptogenic effects. To gain insights into how rapamycin suppresses seizures, we investigated the anticonvulsant activity of rapamycin using acute seizure tests in mice.

Methods

Following intraperitoneal injection of rapamycin, normal four-week-old male NIH Swiss mice were evaluated for susceptibility to a battery of acute seizure tests similar to those currently used to screen potential therapeutics by the US NIH Anticonvulsant Screening Program. To assess the short term effects of rapamycin, mice were seizure tested in ≤6 hours of a single dose of rapamycin, and for longer term effects of rapamycin, mice were tested after 3 or more daily doses of rapamycin.

Results

The only seizure test where short-term rapamycin treatment protected mice was against tonic hindlimb extension in the MES threshold test, though this protection waned with longer rapamycin treatment. Longer term rapamycin treatment protected against kainic acid-induced seizure activity, but only at late times after seizure onset. Rapamycin was not protective in the 6 Hz or PTZ seizure tests after short or longer rapamycin treatment times. In contrast to other metabolism-based therapies that protect in acute seizure tests, rapamycin has limited acute anticonvulsant effects in normal mice.

Significance

The efficacy of rapamycin as an acute anticonvulsant agent may be limited. Furthermore, the combined pattern of acute seizure test results places rapamycin in a third category distinct from both fasting and the ketogenic diet, and which is more similar to drugs acting on sodium channels.     

Acute unstable depressive syndrome (AUDS) is associated more frequently with epilepsy than major depression

Background  

Depressive disorders are frequent in epilepsy and associated with reduced seizure control. Almost 50% of interictal depressive disorders have to be classified as atypical depressions according to DSM-4 criteria. Research has mainly focused on depressive symptoms in defined populations with epilepsy (e.g., patients admitted to tertiary epilepsy centers). We have chosen the opposite approach. We hypothesized that it is possible to define by clinical means a subgroup of psychiatric patients with higher than expected prevalence of epilepsy and seizures. We hypothesized further that these patients present with an Acute Unstable Depressive Syndrome (AUDS) that does not meet DSM-IV criteria of a Major Depressive Episode (MDE). In a previous publication we have documented that AUDS patients indeed have more often a history of epileptic seizures and abnormal EEG recordings than MDE patients (Vaaler et al. 2009). This study aimed to further classify the differences of depressive symptoms at admittance and follow-up of patients with AUDS and MDE.     

Clinical course and seizure outcome of idiopathic childhood epilepsy: determinants of early and long-term prognosis

Background

Idiopathic epilepsies and epileptic syndromes predominate childhood and adolescence epilepsy. The aim of the present study was to investigate the clinical course and outcome of idiopathic childhood epilepsy and identify variables determining both early and long-term prognosis.

Methods

We followed 303 children with newly diagnosed idiopathic epilepsy aged 1–14 years old, both prospectively and retrospectively. Outcome was defined at one, 2 and 4 years of follow-up, as well as at the end of the study period for all patients. Based on the data collected, patients were classified in four patterns of clinical course: “excellent”, “improving”, “relapsing” and “poor”. Variables defined at intake and after the initial year of treatment were analyzed for their prognostic relevance towards the clinical course and outcome of the patients.

Results

The mean age at seizure onset was 6,7 years and the mean duration of follow-up was 8,3 years (range 2,0-22,0,SD 4,24). During the initial year of treatment, 70,3% of patients were seizure-free. The course of epilepsy was “excellent” in 53,1% of the subjects, “improving” in 22,8%, “relapsing” in 22,1% whereas only 6 children with idiopathic epilepsy (2%) had a “poor” clinical course exhibiting drug-resistance. After multivariate analysis, variables predictive of a poor initial response to therapy were early seizure onset, multiple seizure types and history of status epilepticus. At the end of follow-up, early response to treatment was of significant positive predictive value, while the presence of multiple seizure types and the history of migraine had a negative impact on prognosis.

Conclusions

In the vast majority of children, the long-term prognosis of idiopathic epilepsy is favorable. More than half of the patients attain seizure freedom immediately and their clinical course is considered “excellent”. About one fifth exhibit either an improving or a fluctuating course. Early seizure onset, multiple seizure types and status epilepticus are predictive of an initial poor response to treatment in children with idiopathic epilepsy. Initial non-response to treatment, multiple seizure types and history of migraine are determinants of a less favorable final outcome after long-term follow-up.

     

The Role of Resting State Networks in Focal Neocortical Seizures

Objective

The role of resting state functional networks in epilepsy is incompletely understood. While some pathologic diagnoses have been shown to have maintained but altered resting state connectivity, others have implicated resting state connectivity in disease progression. However little is known about how these resting state networks influence the behavior of a focal neocortical seizure.

Methods

Using data taken from invasively monitored patients with intractable focal neocortical epilepsy, we evaluated network connectivity (as determined by oscillatory covariance of the slow cortical potential (<0.5 Hz)) as it relates to neocortical seizure foci both in the interictal and ictal states.

Results

Similar to what has been shown in the past for sleep and anesthesia, electophysiologic resting state networks that are defined by this slow cortical potential covariance maintain their topographic correlation structure throughout an ictal event. Moreover, in the context of focal epilepsy in which the seizure has a specific site of onset, seizure propagation is not chaotic or random. Rather, the seizure (reflected by an elevation of high frequency power) preferentially propagates along the network that contains the seizure onset zone.

Significance

Taken together, these findings further undergird the fundamental role of resting state networks, provide novel insights into the network-influenced behavior of seizures, and potentially identify additional targets for surgical disconnection including informing the location for the completion of multiple subpial transections (MSPTs).     

Detection of Seizure Event and Its Onset/Offset Using Orthonormal Triadic Wavelet Based Features

Background

Epileptic seizures are unpredictable in nature and its quick detection is important for immediate treatment of patients. In last few decades researchers have proposed different algorithms for onset and offset detection of seizure using Electroencephalogram (EEG) signals.

Predictive Value of S100-B and Copeptin for Outcomes following Seizure: The BISTRO International Cohort Study

Objective

To evaluate the performance of S100-B protein and copeptin, in addition to clinical variables, in predicting outcomes of patients attending the emergency department (ED) following a seizure.

Methods

We prospectively included adult patients presented with an acute seizure, in four EDs in France and the United Kingdom. Participants were followed up for 28 days. The primary endpoint was a composite of seizure recurrence, all-cause mortality, hospitalization or rehospitalisation, or return visit in the ED within seven days.

Results

Among the 389 participants included in the analysis, 156 (40%) experienced the primary endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B (0.11 μg/l [95% CI 0.07–0.20] vs 0.09 μg/l [0.07–0.14]) and copeptin (23 pmol/l [9–104] vs 17 pmol/l [8–43]) were higher in participants meeting the primary endpoint. However, both biomarkers were poorly predictive of the primary outcome with a respective area under the receiving operator characteristic curve of 0.57 [0.51–0.64] and 0.59 [0.54–0.64]. Multivariable logistic regression analysis identified higher age (odds ratio [OR] 1.3 per decade [1.1–1.5]), provoked seizure (OR 4.93 [2.5–9.8]), complex partial seizure (OR 4.09 [1.8–9.1]) and first seizure (OR 1.83 [1.1–3.0]) as independent predictors of the primary outcome. A second regression analysis including the biomarkers showed no additional predictive benefit (S100-B OR 3.89 [0.80–18.9] copeptin OR 1 [1.00–1.00]).

Conclusion

The plasma biomarkers S100-B and copeptin did not improve prediction of poor outcome following seizure. Higher age, a first seizure, a provoked seizure and a partial complex seizure are independently associated with adverse outcomes.     

Albendazole and Corticosteroids for the Treatment of Solitary Cysticercus Granuloma: A Network Meta-analysis

Background

Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG.

Methods and Principal Findings

PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (P_best) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10–0.93, P_best 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24–7.95, P_best 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies.

Conclusions

Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available.     

Early Postnatal EEG Features of Perinatal Arterial Ischaemic Stroke with Seizures

Background

Stroke is the second most common cause of seizures in term neonates and is associated with abnormal long-term neurodevelopmental outcome in some cases.

Objective

To aid diagnosis earlier in the postnatal period, our aim was to describe the characteristic EEG patterns in term neonates with perinatal arterial ischaemic stroke (PAIS) seizures.

Design

Retrospective observational study.

Patients

Neonates >37 weeks born between 2003 and 2011 in two hospitals.

Method

Continuous multichannel video-EEG was used to analyze the background patterns and characteristics of seizures. Each EEG was assessed for continuity, symmetry, characteristic features and sleep cycling; morphology of electrographic seizures was also examined. Each seizure was categorized as electrographic-only or electroclinical; the percentage of seizure events for each seizure type was also summarized.

Results

Nine neonates with PAIS seizures and EEG monitoring were identified. While EEG continuity was present in all cases, the background pattern showed suppression over the infarcted side; this was quite marked (>50% amplitude reduction) when the lesion was large. Characteristic unilateral bursts of theta activity with sharp or spike waves intermixed were seen in all cases. Sleep cycling was generally present but was more disturbed over the infarcted side. Seizures demonstrated a characteristic pattern; focal sharp waves/spike-polyspikes were seen at frequency of 1–2 Hz and phase reversal over the central region was common. Electrographic-only seizure events were more frequent compared to electroclinical seizure events (78 vs 22%).

Conclusions

Focal electrographic and electroclinical seizures with ipsilateral suppression of the background activity and focal sharp waves are strong indicators of PAIS. Approximately 80% of seizure events were the result of clinically unsuspected seizures in neonates with PAIS. Prolonged and continuous multichannel video-EEG monitoring is advocated for adequate seizure surveillance.     

Phenytoin versus Leviteracetam for Seizure Prophylaxis after brain injury – a meta analysis

Background

Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury.

Methods

An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline population characteristics, type of intervention, study design and outcome was extracted. Our primary outcome was seizures.

Results

The literature search identified 2489 unduplicated papers. Of these 2456 papers were excluded by reading the abstracts and titles. Another 25 papers were excluded after reading their complete text. We selected 8 papers which comprised of 2 RCTs and 6 observational studies. The pooled estimate’s Odds Ratio 1.12 (95% CI?=?0.34, 3.64) demonstrated no superiority of either drug at preventing the occurrence of early seizures. In a subset analysis of studies in which follow up for seizures lasted either 3 or 7?days, the effect estimate remained insignificant with an odds ratio of 0.96 (95% CI?=?0.34, 2.76). Similarly, 2 trials reporting seizure incidence at 6?months also had insignificant pooled results while comparing drug efficacy. The pooled odds ratio was 0.96 (95% CI?=?0.24, 3.79).

Conclusions

Levetiracetam and Phenytoin demonstrate equal efficacy in seizure prevention after brain injury. However, very few randomized controlled trials (RCTs) on the subject were found. Further evidence through a high quality RCT is highly recommended.

     

Prenatal exposure of ethanol induces increased glutamatergic neuronal differentiation of neural progenitor cells

Background  

Prenatal ethanol exposure during pregnancy induces a spectrum of mental and physical disorders called fetal alcohol spectrum disorder (FASD). The central nervous system is the main organ influenced by FASD, and neurological symptoms include mental retardation, learning abnormalities, hyperactivity and seizure susceptibility in childhood along with the microcephaly. In this study, we examined whether ethanol exposure adversely affects the proliferation of NPC and de-regulates the normal ratio between glutamatergic and GABAergic neuronal differentiation using primary neural progenitor culture (NPC) and in vivo FASD models.     

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.     

Eigenspace Time Frequency Based Features for Accurate Seizure Detection from EEG Data

Background

Epilepsy is a neurological disorder that affects over 2% of the world population. Epilepsy patients suffer from recurring seizures that can be very harmful. The unpredictability of seizures is a major concern for medical practitioners because uncontrollable seizures can lead to sudden death and morbidity. A system that could warn patients and doctors alike about the impending seizure event would dramatically enhance the quality of life for patients.

A Physiology-Based Seizure Detection System for Multichannel EEG

Background

Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures. Electroencephalogram (EEG) signals play a critical role in the diagnosis of epilepsy. Multichannel EEGs contain more information than do single-channel EEGs. Automatic detection algorithms for spikes or seizures have traditionally been implemented on single-channel EEG, and algorithms for multichannel EEG are unavailable.

Methodology

This study proposes a physiology-based detection system for epileptic seizures that uses multichannel EEG signals. The proposed technique was tested on two EEG data sets acquired from 18 patients. Both unipolar and bipolar EEG signals were analyzed. We employed sample entropy (SampEn), statistical values, and concepts used in clinical neurophysiology (e.g., phase reversals and potential fields of a bipolar EEG) to extract the features. We further tested the performance of a genetic algorithm cascaded with a support vector machine and post-classification spike matching.

Principal Findings

We obtained 86.69% spike detection and 99.77% seizure detection for Data Set I. The detection system was further validated using the model trained by Data Set I on Data Set II. The system again showed high performance, with 91.18% detection of spikes and 99.22% seizure detection.

Conclusion

We report a de novo EEG classification system for seizure and spike detection on multichannel EEG that includes physiology-based knowledge to enhance the performance of this type of system.