Epileptiform Activity Research Articles

Lacosamide decreases neonatal seizures without increasing apoptosis.

Many seizing neonates fail to respond to first-line anticonvulsant medications. Phenobarbital, an allosteric modulator of γ-aminobutyric acid type A (GABAA ) receptors, has low efficacy in treating neonatal seizures and causes neuronal apoptosis. Nonetheless, it is one of the most used anticonvulsants in this age group. In neonatal mice, phenobarbital's poor effectiveness is due in part to high intraneuronal chloride concentration, which causes GABA to exert depolarizing actions. Therefore, another approach to treat neonatal seizures could be to use anticonvulsants that do not rely on GABAergic modulation. We evaluated whether lacosamide decreases seizures in neonatal mice and whether it increases apoptosis in vitro and in vivo. In vitro, we measured the effect of different lacosamide concentrations on seizure-like activity induced by the pro-convulsant drug 4-aminopyridine in neocortical brain slices (layer IV/V) from neonatal (postnatal day 8-11) and adult (1-1.6 months old) C57BL/6J mice. In vivo, we recorded the effect of different lacosamide concentrations on neonatal behavioral seizures induced by kainic acid. We studied neocortical apoptosis in vitro and in vivo, measuring terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling signal and cleaved-caspase 3. Lacosamide reduced epileptiform activity in neocortical brain slices of neonates and adults in a concentration-dependent manner. In vivo, lacosamide reduced the duration and number of behavioral seizures. Lacosamide did not increase total or neuronal apoptosis in the neocortex in vitro or in vivo. Lacosamide reduces neocortical seizure-like activity in neonatal mice in vitro and in vivo without an acute increase in apoptosis. Our results support the use of lacosamide to treat neonatal seizures, with the advantage of not increasing apoptosis acutely.

Recruitment of interictal- and ictal-like discharges in posterior piriform cortex by delta-rate (1–4 Hz) focal bursts in anterior piriform cortex in vivo

The development and propagation of seizure-related activity was studied in piriform cortex (PC) and areas in the medial temporal lobe to which it projects. In the urethane anesthetized adult rat at normal body temperature, tiny injections of convulsants in anterior PC (APC) generate an epileptogenic zone (focus) that can recruit electrographic seizures in untreated posterior PC (PPC) when bursts in the focus are paced at delta frequency (1–4 Hz) by stimulating the lateral olfactory tract. Epileptiform activity initiated by this ‘paced-recruitment’ procedure propagates throughout PPC and into other areas involved in mesial temporal lobe epilepsy (mTLE) at an exceedingly low velocity (< 1 mm/sec) as reported for focal seizures in human cortex. Proconvulsants increased the probability of recruiting electrographic seizures relative to disinhibiting agents that typically recruited interictal discharges. Through methods including realtime recording of current source-density (CSD) with vertical 22-site silicon-based electrodes, and membrane potential with transmembrane microelectrode pairs, insights were gained into mechanisms for epileptogenesis from PC. These findings also may apply to seizure initiation from epileptogenic zones in other areas that project to PPC in addition to APC. Findings from surgical studies indicating that PC plays a critical role in mTLE suggest that the results may be relevant to finding new approaches for blocking seizures from this common, virulent form of epilepsy. Immediate implications for treatment include the optimal placement and patterning of deep brain stimulation to increase its effectiveness for blocking seizures from mTLE while reducing the risk to vasculature from direct stimulation of PC.

Features of neurological status in children with autism spectrum disorders

Purpose of the study: to study the neurological status, anamnesis data and electroencephalography in patients with autism spectrum disorders.Material and methods. The study involved 54 children with autism spectrum disorders aged from 3 to 7 years. Anamnestic data were studied, neurological and electroencephalographic studies were performed.Results. The following were identified as the main antenatal and intranatal risk factors for the formation of neurological disorders: gestosis, the threat of termination of pregnancy, weakness of labor and an increase in the duration of the anhydrous period in mothers. A significant number of children were born prematurely and had signs of intrauterine hypoxia at birth. When examining the neurological status, the majority of patients revealed motor and coordination disorders, disorders of tactile sensitivity. Electroencephalography made it possible to register in most patients a delay in the formation of the rhythm of the bioelectrical activity of the brain. Periodic regional decelerations were detected in 9 cases, and epileptiform activity — in 5 cases.Conclusion. Disorders in the neurological status in children with autism spectrum disorders were noted in the form of mild motor symptoms, disorders of motor coordination and tactile sensitivity.

НОВЫЙ ПОДХОД К АВТОМАТИЗИРОВАННОМУ ОБНАРУЖЕНИЮ ДИАГНОСТИЧЕСКИХ ПОКАЗАТЕЛЕЙ ОТСРОЧЕННОЙ ИШЕМИИ ГОЛОВНОГО МОЗГА ПОСЛЕ СУБАРАХНОИДАЛЬНОГО КРОВОИЗЛИЯНИЯ В ДАННЫХ ДЛИТЕЛЬНОГО ЭЭГ МОНИТОРИНГА

Based on the analysis delayed ischemia after subarachnoid hemorrhage indicators, a new approach to the analysis of data from long-term electroencephalographic patients monitoring is proposed and described. It is based on the analysis of the wavelet transforms ridges, in which the power spectrum density, frequency and phase, are equal to the square amplitude, the frequency and the phase of the signal respectively. The main formulas justifying this approach are given. Illustrations of the use Morlet wavelet spectrograms in the electroencephalogram’s analysis of the patient in prefrontal leads are presented the first day after subarachnoid hemorrhage before the development of delayed cerebral ischemia and the seventh day, when the patient had an acute period of delayed ischemia. One of the indicators of delayed ischemia, which has a prognostic value of its development, is the number of events of epileptiform activity per unit of time (usually per hour). A new method for detecting epileptiform activity based on the detection of interchannel synchronization of wavelet spectrogram ridges has been proposed and described.

Genomic analysis, immunomodulation and deep phenotyping of patients with nodding syndrome.

The aetiology of nodding syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with nodding syndrome, investigate potential contributors to disease aetiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for nodding syndrome and with a conducive family structure for genomic analyses. Of the eight family members who participated in the study at the National Institutes of Health (NIH) Clinical Center, three had nodding syndrome. The three affected patients were extensively evaluated with metagenomic sequencing for infectious pathogens, exome sequencing, spinal fluid immune analyses, neurometabolic and toxicology testing, continuous electroencephalography and neuroimaging. Five unaffected family members underwent a subset of testing for comparison. A distinctive interictal pattern of sleep-activated bursts of generalized and multifocal epileptiform discharges and slowing was observed in two patients. Brain imaging showed two patients had mild generalized cerebral atrophy, and both patients and unaffected family members had excessive metal deposition in the basal ganglia. Trace metal biochemical evaluation was normal. CSF was non-inflammatory and one patient had CSF-restricted oligoclonal bands. Onchocerca volvulus-specific antibodies were present in all patients and skin snips were negative for active onchocerciasis. Metagenomic sequencing of serum and CSF revealed hepatitis B virus in the serum of one patient. Vitamin B6 metabolites were borderline low in all family members and CSF pyridoxine metabolites were normal. Mitochondrial DNA testing was normal. Exome sequencing did not identify potentially causal candidate gene variants. Nodding syndrome is characterized by a distinctive pattern of sleep-activated epileptiform activity. The associated growth stunting may be due to hypothalamic dysfunction. Extensive testing years after disease onset did not clarify a causal aetiology. A trial of immunomodulation (plasmapheresis in two patients and intravenous immunoglobulin in one patient) was given without short-term effect, but longer-term follow-up was not possible to fully assess any benefit of this intervention.

SUPERIOR SAGITTAL SINUS THROMBOSIS PRESENTING AS DETERIORATING RESIDUAL WEAKNESS

SUPERIOR SAGITTAL SINUS THROMBOSIS PRESENTING AS DETERIORATING RESIDUAL WEAKNESS

Subcortical band heterotopia: analysis of 5 cases

Subcortical band heterotopia (SBH) is a diffuse deterioration of cortical development, which is characterized by the location of heterotopic neurons in deep and subcortical regions of the brain parallel to the cortex, which creates the illusion of duplication of the cortex, from what this variant was named the «double cortex» syndrome. Data of five patients including three girls and 2 boys were analyzed. The average age was 12.6 years (from 5 to 15). In all cases, heterotopia was bilaterally symmetrical: in 2 cases - diffuse, in 1 it was fronto-parietal, in 1 - temporal-occipital, and in 1 it was fronto-parietal-occipital. Concomitant cerebral malformations were presented in all patients: ventriculomegaly in 5 cases (100%), frontal pachygyria in 1 case (20.0%), diffuse pachygyria in 1 case (20.0%), and dysgyria in 1 case (20.0%). All 5 (100%) patients had epilepsy. The age of onset of epileptic seizures was 6.1 [5.6; 7.5] years. In 3 (60.0%) people epilepsy was focal, in 2 (40.0%) - generalized. There were the following types of epileptic seizures: infantile spasms - 1 (20.0%), focal - 3 (60.0%), tonic-clonic - 4 (80.0%), myoclonic - 2 (40.0%), attacks of cessation of motor activity - 1 (20.0%), atonic - 1 (20.0%). Status epilepticus and febrile-provoked seizures were no observed in any case. Interictal epileptiform activity was presented in all cases: regional in 3 (60.0%), diffuse in 1 (20.0%), and multiregional + diffuse in 1 (20.0%). Drug resistant course was in 3 (60.0%) people. Intellectual impairments were detected in 3 (60.0%) patients: mild - in 1 (20.0%), moderate - in 1 (20.0%), severe - in 1 (20.0%). In 2 (40.0%) observations, intelligence was intact, and in both cases these were patients without drug-resistant epilepsy and without concomitant pachygyria. Speech disorder was detected in 3 (60.0%) people, mild movement disorders - in 1 (20.0%), microcephaly - in 1 (20.0%). Thus, the leading clinical manifestation of SBH is epilepsy with a predominantly drug resistant course. More data are needed on the possibility of using alternative drug treatments.

Learning to generalize seizure forecasts.

Epilepsy is characterized by spontaneous seizures that recur at unexpected times. Nonetheless, using years-long electroencephalographic (EEG) recordings, we previously found that patient-reported seizures consistently occur when interictal epileptiform activity (IEA) cyclically builds up over days. This multidien (multiday) interictal-ictal relationship, which is shared across patients, may bear phasic information for forecasting seizures, even if individual patterns of seizure timing are unknown. To test this rigorously in a large retrospective dataset, we pretrained algorithms on data recorded from a group of patients, and forecasted seizures in other, previously unseen patients. We used retrospective long-term data from participants (N=159) in the RNS System clinical trials, including intracranial EEG recordings (icEEG), and from two participants in the UNEEG Medical clinical trial of a subscalp EEG system (sqEEG). Based on IEA detections, we extracted instantaneous multidien phases and trained generalized linear models (GLMs) and recurrent neural networks (RNNs) to forecast the probability of seizure occurrence at a 24-h horizon. With GLMs and RNNs, seizures could be forecasted above chance in 79% and 81% of previously unseen subjects with a median discrimination of area under the curve (AUC)=.70 and .69 and median Brier skill score (BSS) = .07 and .08. In direct comparison, individualized models had similar median performance (AUC=.67, BSS=.08), but for fewer subjects (60%). Moreover, calibration of pretrained models could be maintained to accommodate different seizure rates across subjects. Our findings suggest that seizure forecasting based on multidien cycles of IEA can generalize across patients, and may drastically reduce the amount of data needed to issue forecasts for individuals who recently started collecting chronic EEG data. In addition, we show that this generalization is independent of the method used to record seizures (patient-reported vs. electrographic) or IEA (icEEG vs. sqEEG).

A Case of Landau-Kleffner Syndrome with Autism Spectrum Disorder Symptoms Improved After Corticosteroid Treatment

Çok nadir rastlanan bir çocukluk-çağı hastalığı olan Landau-Kleffner Sendromu (LKS), elektroensefalogramdaki (EEG) epileptiform etkinlik ile ilişkili edinsel afazidir. Landau-Kleffner Sendromu’nun klinik görünümü bazı çocuklarda Otizm Spektrum Bozukluğu’na (OSB) benzeyebilir. Bu yazıda Çocuk ve Ergen Ruh Sağlığı ve Hastalıkları (ÇRS) polikliniğine OSB belirtileri ile başvuran, ancak nörolojik tetkikler sonucunda LKS tanısı konulan, LKS medikal tedavisi sonrası nöropsikiyatrik semptomlarında belirgin düzelme gösteren bir vaka sunulmuştur. Dört yaş yedi aylık erkek çocuk, konuşmada gerileme, sosyal iletişimde azalma ve tekrarlayıcı davranış kalıpları şeklindeki yakınmaları ile ÇRS polikliniğine getirilmiştir. İlk olarak OSB tanısı konulmuş ve Çocuk Nöroloji’ye yönlendirilmiş olan vakanın yapılan nörolojik değerlendirmeleri sonrasında, hastaya LKS tanısı konulmuş ve antiepileptik tedavi başlanmıştır. Üç ay kadar kullanılan konvansiyonel antiepileptik tedaviden fayda görmeyen hastaya kortikosteroid tedavi başlanmış ve 1 ay içerisinde konuşma regresyonunda ve LKS’ye bağlı olan OSB belirtilerinde klinik olarak azalma görülmüştür, 3 ay içinde ise bu belirtilerde belirgin düzelme olduğu gözlenmiştir. Bu makalede, LKS’de konvansiyonel antiepileptik tedavi ile bilişsel ve dil fonksiyonlarında ve EEG patolojisinde düzelme olmayan vakalarda kortikosteroid tedavisiyle hem nöropsikiyatrik semptomlarında hem de EEG bulgularında hızlı düzelme sağlanabileceği bildirilmiştir. Alanyazında, LKS’de bilinen tedavilerin konuşma regresyonunu düzeltmede etkili olduğuna yönelik daha fazla bilgi olmakla birlikte, LKS’ye bağlı ortaya çıkan OSB belirtilerini azaltmasına yönelik çok az vaka bildirimi vardır.

Forebrain epileptiform activity is not required for seizure-induced apnea in a mouse model of Scn8a epilepsy.

Sudden unexpected death in epilepsy (SUDEP) accounts for the deaths of 8–17% of patients with epilepsy. Although the mechanisms of SUDEP are essentially unknown, one proposed mechanism is respiratory arrest initiated by a convulsive seizure. In mice, we have previously observed that extended apnea occurs during the tonic phase of seizures. Although often survived, tonic seizures became fatal when breathing did not immediately recover postictally. We also found that respiratory muscles were tonically contracted during the apnea, suggesting that muscle contraction could be the cause of apnea. In the present study, we tested the hypothesis that pyramidal neurons of the motor cortex drive motor units during the tonic phase, which produces apnea. Mice harboring the patient-derived N1768D point mutation of an Scn8a allele were crossed with transgenic mice such that inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADD) receptors were selectively expressed in excitatory forebrain neurons. We then triggered audiogenic and hippocampal (HC) stimulated seizures under control conditions and when excitatory forebrain neurons were inhibited with the synthetic ligand Clozapine-N-Oxide (CNO). We found that inhibition with CNO was sufficient to increase seizure threshold of HC stimulated, but not audiogenic, seizures. In addition, regardless of seizure type, CNO nearly eliminated epileptiform activity that occurred proximal to the tonic phase; however, the seizure behaviors, notably the tonic phase and concomitant apnea, were unchanged. We interpret these results to indicate that while cortical neurons are likely critical for epileptogenesis and seizure initiation, the behavioral manifestations of tonic seizures are generated by neural circuitry in the mid- and/or hindbrain.

The Glycolysis Inhibitor 2-Deoxy-D-Glucose Exerts Different Neuronal Effects at Circuit and Cellular Levels, Partially Reverses Behavioral Alterations and does not Prevent NADPH Diaphorase Activity Reduction in the Intrahippocampal Kainic Acid Model of Temporal Lobe Epilepsy.

Temporal lobe epilepsy is the most drug-resistant type with the highest incidence among the other focal epilepsies. Metabolic manipulations are of great interest among others, glycolysis inhibitors like 2-deoxy d-glucose (2-DG) being the most promising intervention. Here, we sought to investigate the effects of 2-DG treatment on cellular and circuit level electrophysiological properties using patch-clamp and local field potentials recordings and behavioral alterations such as depression and anxiety behaviors, and changes in nitric oxide signaling in the intrahippocampal kainic acid model. We found that epileptic animals were less anxious, more depressed, with more locomotion activity. Interestingly, by masking the effect of increased locomotor activity on the parameters of the zero-maze test, no altered anxiety behavior was noted in epileptic animals. However, 2-DG could partially reverse the behavioral changes induced by kainic acid. The findings also showed that 2-DG treatment partially suppresses cellular level alterations while failing to reverse circuit-level changes resulting from kainic acid injection. Analysis of NADPH-diaphorase positive neurons in the CA1 area of the hippocampus revealed that the number of positive neurons was significantly reduced in dorsal CA1 of the epileptic animals and 2-DG treatment did not affect the diminishing effect of kainic acid on NADPH-d+ neurons in the CA1 area. In the control group receiving 2-DG, however, an augmented NADPH-d+ cell number was noted. These data suggest that 2-DG cannot suppress epileptiform activity at the circuit-level in this model of epilepsy and therefore, may fail to control the seizures in temporal lobe epilepsy cases.

Transition dynamics and optogenetic control of epileptiform activity in a modified mean filed model of human cortex

Physiological experiments have shown that inhibitory interneurons can induce and maintain epileptiform activities, and different interneuron subtypes may be responsible for different types of seizures. Here we aim to link these electrophysiological experimental phenomena with theoretical dynamic mechanisms based on an improved Liley mean field model. Fascinatingly, the number of synapses between inhibitory neural populations can induce a rich state transition. Typically, the system will experience normal rhythm discharges, multispike discharges, spike wave discharges (SWD), generalized periodic discharges (GPD), the beta band oscillation, and eventually return to the normal state. Interestingly, the transition process can also be reversed. Meanwhile, disinhibition circuits can cause more epileptiform activities after taking into account the delay of synaptic information transmission. Furthermore, we are committed to designing different control strategies for epileptiform activities. As we expected, both deep brain stimulation and optogenetic technology can destroy or even eliminate pathological waves. It is need to emphasis that the cell type specificity of optogenetic regulation allows it to precisely target inhibitory neural populations, which is agree with experiment. Particularly, three different optogenetic regulatory strategies targeting inhibitory neural populations are modeled and proposed, of which the intermittent is designed to save energy. These modeling results reproduce the experimental phenomena and more significantly, help understand the mechanism of epilepsy to guide the clinical practice.

TU-233. Is epileptiformic activity related to developmental language disorder? Findings from the HelSLI Study

TU-233. Is epileptiformic activity related to developmental language disorder? Findings from the HelSLI Study

WE-173. Combining excitability and connectivity measures from interictal invasive-EEG estimates the epileptogenic zone, even in the absence of frank epileptiform activity

WE-173. Combining excitability and connectivity measures from interictal invasive-EEG estimates the epileptogenic zone, even in the absence of frank epileptiform activity

Pediatric electroencephalography

Background Routine electroencephalography (EEG) is a widely used test in children for the evaluation of many neurological conditions. It is specifically important in the diagnosis of epilepsy and the differentiation of epilepsy from nonepileptic events. Aim This study aimed to evaluate the current situation of EEG recording at Alexandria University Children’s Hospital. Patients and methods All patients who had a routine EEG recording during a period of 6 months were included in the study. Review of the records was done including personal data, place and indication of referral, and initial diagnosis. EEG data included condition during recording, activation procedures, EEG interpretation regarding background activity, presence or absence of epileptiform activity, type and origin of epileptiform discharges, and the final yield of EEG. Results The study included 570 children, comprising 336 males and 234 females, with a mean age of 5.5±4.1 years. The main indication for referral was epilepsy in 69.8%. Most of the cases (83.3%) had an awake recording. Photic stimulation and hyperventilation were done in 93.3 and 31.9%, respectively, and abnormal response to hyperventilation was observed in 9.9% of them. Ictal recording was done in 22 (3.8%) cases. Abnormal epileptiform discharges were detected in 173 (30.4%) of the studied children; of them, 162 cases were initially referred for established epilepsy and 11 cases for other reasons. The abnormality was generalized in 53.8% and focal in 46.2% of the cases. The commonest types of epileptiform discharges were spikes (65.9%) followed by spike-and-wave complexes (56.1%). Hypsarrhythmia, 3-Hz spike-and-wave complexes, and nonconvulsive status epilepticus were detected in 12.7, 10.4, and 2.9%, respectively. Phase reversal, sharp waves, and polyspikes were detected in 15.6, 5.2, and 2.3%, respectively. Conclusion Routine EEG is a valuable test for evaluation of seizures and epilepsy. Specific abnormal epileptiform discharges are diagnostic for certain epileptic syndromes. EEG finding may be normal in children with epilepsy and should be interpreted in the context of the clinical settings.

Modulation of in vitro epileptiform activity by optogenetic stimulation of parvalbumin-positive interneurons.

GABAA signaling is surprisingly involved in the initiation of epileptiform activity since increased interneuron firing, presumably leading to excessive GABA release, often precedes ictal discharges. Field potential theta (4-12 Hz) oscillations, which are thought to mirror the synchronization of interneuron networks, also lead to ictogenesis. However, the exact role of parvalbumin-positive (PV) interneurons in generating theta oscillations linked to epileptiform discharges remains unexplored. We analyzed here the field responses recorded in the CA3, entorhinal cortex (EC), and dentate gyrus (DG) during 8-Hz optogenetic stimulation of PV-positive interneurons in brain slices obtained from PV-ChR2 mice during 4-aminopyridine (4AP) application. This optogenetic protocol triggered similar field oscillations in both control conditions and during 4AP application. However, in the presence of 4AP, optogenetic stimuli also induced: 1) interictal discharges that were associated in all regions with 8-Hz field oscillations and 2) low-voltage fast onset ictal discharges. Interictal and ictal events occurred more frequently during optogenetic activation than during periods of no stimulation. 4AP also increased synchronicity during PV-interneuron activation in all three regions. In opsin-negative mice, optogenetic stimulation did not change the rate of both types of epileptiform activity. Our findings suggest that PV-interneuron recruitment at theta (8 Hz) frequency contributes to epileptiform synchronization in limbic structures in the in vitro 4AP model.NEW & NOTEWORTHY Previous studies have identified contradictory roles of PV-interneurons in ictogenesis and the link between theta oscillations and epileptiform activity remains unexplored. Here, we investigated in vitro the effect of PV-interneuron optogenetic stimulation under 4AP in temporal lobe regions obtained from PV-ChR2 transgenic mice. Under theta (8 Hz) optogenetic stimulation and 4AP application, interictal spikes and low-voltage fast onset ictal discharges were triggered, suggesting that the activation of PV-interneurons favors synchronization and ictogenesis.

An Epitope-Specific LGI1-Autoantibody Enhances Neuronal Excitability by Modulating Kv1.1 Channel.

Leucine-rich Glioma-Inactivated protein 1 (LGI1) is expressed in the central nervous system and its genetic loss of function is associated with epileptic disorders. Additionally, patients with LGI1-directed autoantibodies have frequent focal seizures as a key feature of their disease. LGI1 is composed of a Leucine-Rich Repeat (LRR) and an Epitempin (EPTP) domain. These domains are reported to interact with different members of the transsynaptic complex formed by LGI1 at excitatory synapses, including presynaptic Kv1 potassium channels. Patient-derived recombinant monoclonal antibodies (mAbs) are ideal reagents to study whether domain-specific LGI1-autoantibodies induce epileptiform activities in neurons and their downstream mechanisms. We measured the intrinsic excitability of CA3 pyramidal neurons in organotypic cultures from rat hippocampus treated with either an LRR- or an EPTP-reactive patient-derived mAb, or with IgG from control patients. We found an increase in intrinsic excitability correlated with a reduction of the sensitivity to a selective Kv1.1-channel blocker in neurons treated with the LRR mAb, but not in neurons treated with the EPTP mAb. Our findings suggest LRR mAbs are able to modulate neuronal excitability that could account for epileptiform activity observed in patients.

Epileptiform activity predicts epileptogenesis in cerebral hemorrhage.

This retrospective case–controlled study was performed to evaluate whether Epileptiform Activity, suspected clinical seizures, and/or 2HELPS2B/S after nontraumatic Intraparenchymal Hemorrhage or Subarachnoid Hemorrhage can predict Epilepsy. Hundred and thirty‐two patients were included—29 (Epilepsy), 103 (Control Group). After matching, the average effect for all three risk factors was significant as follows: (1) Epileptiform Activity (p = 0.012, odds ratio 3.14), (2) suspected seizures (p = 0.021, odds ratio 3.78), and (3) 2HELPS2B/S score (p < 0.001, odds ratio 4.94). This study shows that Epileptiform Activity, suspected seizures, and particularly, the 2HELPS2B/S score in the acute phase are risk factors for the development of epilepsy after nontraumatic intraparenchymal and subarachnoid hemorrhage.

The value of EEG attenuation in the prediction of outcome in COVID-19 patients

IntroductionDuring the COVID-19 pandemic, electroencephalography (EEG) proved to be a useful tool to demonstrate brain involvement. Many studies reported non-reactive generalized slowing as the most frequent pattern and epileptiform activity in a minority of patients.ObjectiveTo investigate the prevalence of diffuse unreactive background attenuation or suppression and its correlation with outcome in a cohort of COVID-19 patients.MethodsThe EEGs recorded during the first year of the COVID-19 pandemic were retrospectively evaluated to identify the main pattern and focus on the occurrence of a low-voltage background, either attenuated (10–20 μV) or suppressed (< 10 μV). We sought a correlation between in-hospital mortality and low-voltage EEG. In a subsample of patients, biomarkers of inflammation, hypoxemia and organ failure were collected. Brain imaging was also evaluated.ResultsAmong 98 EEG performed in 50 consecutive patients, diffuse unreactive slowing was the most prevalent pattern (54%), followed by unreactive attenuation or suppression pattern (26%), being the latter significantly correlated with an unfavourable outcome (p = 0.0004). Survivors showed significantly lower interleukine-6 values compared to non-survivors. Patients with attenuated EEG and non-survivors also showed lower PaO2/FiO2 values. Neuroradiological findings were very heterogeneous with a prevalence of lesions suggestive of a microangiopathic substrate.ConclusionsEEG attenuation or suppression may be more frequent than previously reported and significantly associated with a poor outcome. SARS-CoV-2 infection may result in encephalopathy and reduced EEG voltage through mechanisms that are still unknown but deserve attention given its negative impact on prognosis.

The Effects of Acute and Chronic Metformin Treatment on Penicillin Induced Epileptiform Activity in Rats

The Effects of Acute and Chronic Metformin Treatment on Penicillin Induced Epileptiform Activity in Rats