Ictal Epileptiform Activity Research Articles

Electromagnetic Source Imaging in Presurgical Evaluation of Children with Drug-Resistant Epilepsy.

For children with drug-resistant epilepsy (DRE), seizure freedom relies on the delineation and resection (or ablation/disconnection) of the epileptogenic zone (EZ) while preserving the eloquent brain areas. The development of a reliable and noninvasive localization method that provides clinically useful information for the localization of the EZ is, therefore, crucial to achieving successful surgical outcomes. Electric and magnetic source imaging (ESI and MSI) have been increasingly utilized in the presurgical evaluation of these patients showing promising findings in the delineation of epileptogenic as well as eloquent brain areas. Moreover, the combination of ESI and MSI into a single solution, namely electromagnetic source imaging (EMSI), performed on simultaneous high-density electroencephalography (HD-EEG) and magnetoencephalography (MEG) recordings has shown higher source localization accuracy than either modality alone. Despite these encouraging findings, such techniques are performed in only a few tertiary epilepsy centers, are rarely recorded simultaneously, and are underutilized in pediatric cohorts. This study illustrates the experimental setup for recording simultaneous MEG and HD-EEG data as well as the methodological framework for analyzing these data aiming to localize the irritative zone, the seizure onset zone, and eloquent brain areas in children with DRE. More specifically, the experimental setups are presented for (i) recording and localizing interictal and ictal epileptiform activity during sleep and (ii) recording visual-, motor-, auditory-, and somatosensory-evoked responses and mapping relevant eloquent brain areas (i.e., visual, motor, auditory, and somatosensory) during visuomotor task, as well as auditory and somatosensory stimulations. Detailed steps of the data analysis pipeline are further presented for performing EMSI as well as individual ESI and MSI using equivalent current dipole (ECD) and dynamic statistical parametric mapping (dSPM).

Bilateral Todd's paralysis in a patient with left fronto-opercular epilepsy.

Postictal paresis ("Todd's paralysis") is commonly observed as a unilateral, transient motor weakness, lasting minutes to hours, after focal or focal to bilateral tonic-clonic seizures, contralateral to the epileptogenic zone. Bilateral postictal paresis is exceedingly rare and could be misinterpreted, especially if the preceding convulsive phase was not witnessed. An 18-year-old right-handed male patient with refractory focal epilepsy with seizure onset at age 3 years, was admitted for presurgical video-EEG monitoring. His seizures were predominantly nocturnal, consisting of a laryngeal somatosensory aura, occasionally evolving to bilateral tonic or tonic-clonic seizures with occasional asymmetrical limb extension during the tonic phase (right arm extension). Postictally, consciousness recovery was fast, if ever lost. At that stage, we documented severe dysarthria and bilateral symmetrical arm paresis lasting several minutes. The ictal pattern and interictal epileptiform activity were projected on the fronto-central midline. Brain MRI was highly suggestive of a bottom-of-sulcus dysplasia with underlying transmantle sign on the left premotor, fronto-opercular region and an FDG-PET-CT showed a concordant left fronto-operculo-insular hypometabolism. A complete lesionectomy was performed, with the additional guidance of intraoperative electrocorticography, resulting in sustained seizure freedom. Anatomo-pathology confirmed a type 2b focal cortical dysplasia. We speculate that, in our patient, a left fronto-opercular ictal onset with an early spread to both primary motor cortices and relative sparing of consciousness networks allowed the emergence of a clinically detectable postictal bilateral paresis.

Safety and efficacy of bihemispheric sampling via transmidline stereoelectroencephalography.

Stereoelectroencephalography (SEEG) is designed to target distributed cortical networks responsible for electroclinical seizure syndrome and to enable localization of the site of seizure onset in patients with intractable epilepsy. When the preimplantation hypothesis invokes the bilateral mesial frontal lobes, sampling of several deep-seated cortical sites in both hemispheres is required. In this study, the authors have demonstrated the feasibility of sampling bihemispheric areas with intentional implantation of an SEEG electrode crossing the midline (SECM) for sampling the cortex on both sides of the interhemispheric fissure. An analysis of 231 consecutive SEEG procedures over 8 years was used to identify instances of bihemispheric sampling by using the transmidline SEEG technique. The authors identified 53 SEEG cases, with a total of 126 electrodes that crossed the interhemispheric fissure; all were in the frontal lobes. Eighty-three electrodes targeted the cingulate gyrus (18 rostral, 43 anterior, and 22 middle), 31 targeted the posterior orbitofrontal region, 8 sampled the medial prefrontal cortex, and 4 targeted nodular heterotopia around the frontal horns. The ictal onset zone was localized to the frontal lobe in 16 cases. SECM isolated interictal and ictal activity in the contralateral hemisphere in 6 cases and independent bihemispheric seizure activity in 2 cases. No hemorrhagic or infectious complications were noted in any of these cases. Based on this extensive experience of bihemispheric sampling, the authors concluded that this technique is safe and effective. In this series, SECM showed contralateral interictal and/or ictal epileptiform activity in 8 (15%) cases, and 9 (16%) cases (with unilateral implantation) had sufficient data to discard contralateral involvement, contributing to support of the epileptogenic network. SECM may reduce the number of electrodes used to sample bilateral mesial frontal or orbitofrontal cortices, and such an approach may lower the risk of hemorrhage and costs.

Non-invasive measurements of ictal and interictal epileptiform activity using optically pumped magnetometers

Magneto- and electroencephalography (MEG/EEG) are important techniques for the diagnosis and pre-surgical evaluation of epilepsy. Yet, in current cryogen-based MEG systems the sensors are offset from the scalp, which limits the signal-to-noise ratio (SNR) and thereby the sensitivity to activity from deep structures such as the hippocampus. This effect is amplified in children, for whom adult-sized fixed-helmet systems are typically too big. Moreover, ictal recordings with fixed-helmet systems are problematic because of limited movement tolerance and/or logistical considerations. Optically Pumped Magnetometers (OPMs) can be placed directly on the scalp, thereby improving SNR and enabling recordings during seizures. We aimed to demonstrate the performance of OPMs in a clinical population. Seven patients with challenging cases of epilepsy underwent MEG recordings using a 12-channel OPM-system and a 306-channel cryogen-based whole-head system: three adults with known deep or weak (low SNR) sources of interictal epileptiform discharges (IEDs), along with three children with focal epilepsy and one adult with frequent seizures. The consistency of the recorded IEDs across the two systems was assessed. In one patient the OPMs detected IEDs that were not found with the SQUID-system, and in two patients no IEDs were found with either system. For the other patients the OPM data were remarkably consistent with the data from the cryogenic system, noting that these were recorded in different sessions, with comparable SNRs and IED-yields overall. Importantly, the wearability of OPMs enabled the recording of seizure activity in a patient with hyperkinetic movements during the seizure. The observed ictal onset and semiology were in agreement with previous video- and stereo-EEG recordings. The relatively affordable technology, in combination with reduced running and maintenance costs, means that OPM-based MEG could be used more widely than current MEG systems, and may become an affordable alternative to scalp EEG, with the potential benefits of increased spatial accuracy, reduced sensitivity to volume conduction/field spread, and increased sensitivity to deep sources. Wearable MEG thus provides an unprecedented opportunity for epilepsy, and given its patient-friendliness, we envisage that it will not only be used for presurgical evaluation of epilepsy patients, but also for diagnosis after a first seizure.

Role of the <i>GRIN1</i> gene polymorphism in the formation of post-traumatic epilepsy

Introduction: NMDA receptors are involved in the pathogenesis of seizures, as it subunit is coded for by the GRIN1 gene. Different GRIN1 mutations are known in patients with different forms of epilepsy and encephalopathy. However, no data are available on the participation of the GRIN1 gene and its polymorphisms in the development of post-traumatic epilepsy (PTE). Aim: To determine the influence of single-nucleotide rs1126442 polymorphism of GRIN1 on the risk of PTE formation. Materials and methods: A total of 140 patients were examined, which included 69 patients with PTE and 71 patients with genetic epilepsy. All patients underwent a comprehensive examination, with evaluation of history, neurological status, electroencephalography (EEG) and neuroimaging results, and genotyping of blood samples by real-time polymerase chain reaction. The control sample for genetic examination was venous blood from 60 healthy individuals. Results: Focal seizures with transition to bilateral and tonicclonic seizures were predominant in the PTE group. Neuroimaging revealed dystrophic, cystic, and cystogliotic alterations and signs of external hydrocephaly. EEG recorded interictal and ictal epileptiform activity and slowing of theta waves. Genotyping by rs1126442 polymorphism of GRIN1 revealed predominance of heterozygous G/A and homozygous A/A genotypes in patients with PTE in the codominant (odds ratio (OD)=3.43; 95% confidence index (CI) 1.567.55; p=0.0047), dominant (OR=3.24; 95% CI 1.576.68; p=0.0011), and superdominant (OR=2.90; 95% CI 1.366.22; p=0.0048) inheritance models. The carriage of heterozygous G/A rs1126442 genotype of GRIN1 was associated with an epileptiform activity in the EEG of all patients with epilepsy (OR=2.40; 95% CI 1.115.20; p=0.024). Conclusion: The carriage of heterozygous G/A genotype and homozygous A/A rs 1126442 genotype of GRIN1 in the dominant and codominant inheritance models is associated with a high risk of development of epilepsy after craniocerebral trauma. The carriage of heterozygous G/A rs 1126442 genotype of GRIN1 is associated with an epileptiform activity in EEG.

Epilepsy in “Sunflower syndrome”: electroclinical features, therapeutic response, and long-term follow-up

BackgroundSunflower syndrome (SFS) is a rare childhood-onset generalized epilepsy characterized by photosensitivity, heliotropism, and drug-resistant stereotyped seizures maybe self-induced by hand-waving maneuvers. Data on the long-term prognosis are scantly and evidence over best treatment strategies is lacking. MethodsWe retrospectively describe the electroclinical features, and therapeutic response in a group of 21 patients with SFS, without intellectual disability. Results16 patients were female (67%), with a median age at onset of 7 years. In all patients, ictal episodes began with sun-staring, and hand-waving in front of the sunlight, accompanied by brief typical absence seizures. 17 patients (81%) showed interictal EEG abnormalities, mainly characterized by spike and polyspike-and-wave discharges. Ictal epileptiform activity occurred approximately less than one second after the start of hand-waving. At the last follow-up (median length 8.2 years), 12 patients (57%) were drug-resistant. Nine of them (75%) achieved seizure control with the use of tainted lenses, either alone or compared with anti-seizure medications (ASM). Disappearance of seizures was associated with EEG improvement/normalization when tinted glasses were used during EEG recordings. ConclusionWhile the clinical and EEG characteristics of SFS are well defined, the best therapeutic approaches are still under debate. Our data confirms a high rate of drug-resistance and frequent need of polytherapy. Of note, in drug-resistant patients, lenses (but not ASM) were able to suppress PPR in our patients while wearing lenses. Regarding the role of lenses, we do not only rely on the PPR reduction but also clinically by the reduction of seizures.Although additional data are needed, lenses seem to have a powerful potential role for the management of SFS.

Clinical importance of mimics

Psychogenic nonepileptic seizures (PNES) represent a common diagnostic problem in routine neurologic practice and consist of paroxysmal, time-limited alterations in motor, sensory, autonomic, and/or cognitive signs and symptoms that are not accompanied by ictal epileptiform activity. Estimates vary but most published data suggest that about 20% patients referred to epilepsy centers for recurrent refractory seizures have PNES. Moreover, disease duration prior to establishing the diagnosis of PNES may be very long, which illustrates that PNES are usually not missed but are misclassified and inappropriately treated for a long time as epilepsy.

Musical components important for the Mozart K448 effect in epilepsy

There is growing evidence for the efficacy of music, specifically Mozart’s Sonata for Two Pianos in D Major (K448), at reducing ictal and interictal epileptiform activity. Nonetheless, little is known about the mechanism underlying this beneficial “Mozart K448 effect” for persons with epilepsy. Here, we measured the influence that K448 had on intracranial interictal epileptiform discharges (IEDs) in sixteen subjects undergoing intracranial monitoring for refractory focal epilepsy. We found reduced IEDs during the original version of K448 after at least 30-s of exposure. Nonsignificant IED rate reductions were witnessed in all brain regions apart from the bilateral frontal cortices, where we observed increased frontal theta power during transitions from prolonged musical segments. All other presented musical stimuli were associated with nonsignificant IED alterations. These results suggest that the “Mozart K448 effect” is dependent on the duration of exposure and may preferentially modulate activity in frontal emotional networks, providing insight into the mechanism underlying this response. Our findings encourage the continued evaluation of Mozart’s K448 as a noninvasive, non-pharmacological intervention for refractory epilepsy.

ВОЗРАСТНЫЕ ОСОБЕННОСТИ ГЕНЕРАЦИИ ЭПИЛЕПТИФОРМНОЙ АКТИВНОСТИ В 4-АМИНОПИРИДИНОВОЙ МОДЕЛИ В СРЕЗАХ МОЗГА КРЫСЫ

Children are more likely to develop epileptic seizures (ictal discharges lasting tens of seconds) than adults. A higher predisposition of the juvenile brain to the generation of epileptiform activity is thought to be due to a preeminence of inhibition over excitation at the early stage of brain development. However, the molecular and physiological mechanisms underlying these age-related differences are yet to be clarified. We compared the ictal activity induced by a chemoconvulsant 4-aminopyridine (4-AP) in the horizontal slices of the entorhinal cortex and hippocampus of 3- and 8-week-old Wistar rats. In 3-week-old rats, the ictal discharge was always preceded by a clearly detectable preictal activity as manifested in one or several 3−4-s GABA-glutamate events, whereas in 8-week-old rats such events were typically absent or very rare (no more than one occasional short event). The ictal activity resistance to external exposures was also age-dependent. In 8-week-old rats, by contrast to 3-week-old animals, ictal discharge generation in the entorhinal cortex was blocked completely and replaced by the 0.2−0.3 Hz interictal activity (simultaneous 1−3-s burst discharges) by a partial blockade of the KCC2-cotransporter or Na+/K+-pump, as well as by low-frequency electric stimulation. Thus, our data indicate that ictal discharges in the immature (3-week-old) brain are more resistant to external exposures than in the brain of adult rats. Interictal and ictal epileptiform activities are antagonistic in 8-week-old animals, while the appearance of interictal activity interrupts completely the generation of ictal discharges and can therefore be considered as one of the putative antiepileptic mechanisms in the mature rat brain.

The feasibility and value of extraoperative and adjuvant intraoperative stereoelectroencephalography in rolandic and perirolandic epilepsies.

The objective of this study was to illustrate the feasibility and value of extra- and intraoperative stereoelectroencephalography (SEEG) in patients who underwent resection in rolandic and perirolandic regions. The authors retrospectively reviewed all consecutive patients with at least 1 year of postoperative follow-up who underwent extra- and intraoperative SEEG monitoring between January 2015 and January 2017. Four patients with pharmacoresistant rolandic and perirolandic focal epilepsy were identified, who underwent conventional extraoperative invasive SEEG evaluations followed by adjuvant intraoperative SEEG recordings. Conventional extraoperative SEEG evaluations demonstrated ictal and interictal epileptiform activities involving eloquent rolandic and perirolandic cortical areas in all patients. Following extraoperative monitoring, patients underwent preplanned staged resections guided by simultaneous and continuous adjuvant intraoperative SEEG monitoring. Resections, guided by electrode contacts of interest in 3D boundaries, were performed while continuous real-time electrographic data from SEEG recordings were obtained. Staged approaches of resections were performed until there was intraoperative resolution of synchronous rolandic/perirolandic cortex epileptic activities. All patients in the cohort achieved complete seizure freedom (Engel class IA) during the follow-up period ranging from 18 to 50 months. Resection resulted in minimal neurological deficit; 3 patients experienced transient, distal plantar flexion weakness (mild foot drop). The seizure and functional outcome results of this highly preselected group of patients testifies to the feasibility and demonstrates the value of the combined benefits of both intra- and extraoperative SEEG recordings when resecting the rolandic and perirolandic areas. The novel hybrid method allows a more refined and precise identification of the epileptogenic zone. Consequently, tailored resections can be performed to minimize morbidity as well as to achieve adequate seizure control.

KCC2 Chloride Transport Contributes to the Termination of Ictal Epileptiform Activity.

Recurrent seizures intensely activate GABAA receptors (GABAA-Rs), which induces transient neuronal chloride ([Cl-]i) elevations and depolarizing GABA responses that contribute to the failure of inhibition that engenders further seizures and anticonvulsant resistance. The K+-Cl- cotransporter KCC2 is responsible for Cl- extrusion and restoration of [Cl-]i equilibrium (ECl) after synaptic activity, but at the cost of increased extracellular potassium which may retard K+-Cl- extrusion, depolarize neurons, and potentiate seizures. Thus, KCC2 may either diminish or facilitate seizure activity, and both proconvulsant and anticonvulsant effects of KCC2 inhibition have been reported. It is now necessary to identify the loci of these divergent responses by assaying both the electrographic effects and the ionic effects of KCC2 manipulation. We therefore determined the net effects of KCC2 transport activity on cytoplasmic chloride elevation and Cl- extrusion rates during spontaneous recurrent ictal-like epileptiform discharges (ILDs) in organotypic hippocampal slices in vitro, as well as the correlation between ionic and electrographic effects. We found that the KCC2 antagonist VU0463271 reduced Cl- extrusion rates, increased ictal [Cl-]i elevation, increased ILD duration, and induced status epilepticus (SE). In contrast, the putative KCC2 upregulator CLP257 improved chloride homeostasis and reduced the duration and frequency of ILDs in a concentration-dependent manner. Our results demonstrate that measuring both the ionic and electrographic effects of KCC2 transport clarify the impact of KCC2 modulation in specific models of epileptiform activity. Anticonvulsant effects predominate when KCC2-mediated chloride transport rather than potassium buffering is the rate-limiting step in restoring ECl and the efficacy of GABAergic inhibition during recurrent ILDs.

Commentary to Bentes et al. "Seizures, electroencephalographic abnormalities, and outcome of ischemic stroke patients".

Stroke is the most common potentially preventable etiology among older adults with epilepsy, accounting for half or more of all new-onset cases.1 The current spectrum for management of poststroke epilepsy includes primary stroke prevention,1 symptomatic therapy with antiseizure drugs and, hopefully in the future, antiepileptogenic drugs that prevent poststroke epilepsy. One of the prerequisites of successful antiepileptogenic therapy is to identify patients with a high risk for poststroke epilepsy as early as possible. This is where the work of Carla Bentes et al. (2018), the recipient of the first Clinical prize of Epilepsia Open, comes in.2 Bentes et al.2 evaluated whether early EEG abnormalities can independently predict poststroke epilepsy. The authors performed a prospective study of consecutive patients with acute anterior circulation ischemic stroke without prior epileptic seizures who were admitted to a stroke unit over 24 months and followed for 1 year. Video–electroencephalography 9EEG) was performed in the first 72 h (first EEG), daily for the first 7 days, in case of neurological deterioration, at discharge and at 12 months after stroke. Primary outcome was the occurrence of at least one unprovoked seizure at least 7 days after stroke onset (poststroke epilepsy). Secondary outcomes were the occurrence of at least one acute symptomatic seizure, defined as any seizure in the first 7 days after onset of the stroke and (interictal and/or ictal) epileptiform activity in at least one EEG during the hospital stay for acute stroke. EEG variables were defined using international criteria/terminology. One hundred fifty-one patients were included. Thirty-eight patients (25.2%) had an acute symptomatic seizure and 23 (16%) developed poststroke epilepsy. The main result of the study was that background activity asymmetry of the first EEG and the first EEG with interictal epileptiform activity were independent predictors of poststroke epilepsy during the first year after stroke (p = 0.043 and p = 0.043, respectively). No EEG abnormality independently predicted acute symptomatic seizures. However, the presence of periodic discharges on the first EEG was an independent predictor of epileptiform activity (p = 0.009) during the hospital stay. The main significance of their findings is that an early poststroke EEG can predict epilepsy in the first year after stroke, independently from clinical and infarct size as determined by magnetic resonance imaging (MRI) neuroimaging. Indeed, for the same age, and clinical and infarct severity as assessed by MRI, the risk of poststroke unprovoked seizures was 3.2 times higher in patients with first EEG background activity asymmetry and 3.8 times higher in the presence of interictal epileptiform activity in this exam. The present study further enlarges the importance of an early EEG in stroke patients, detecting those with an increased risk for epilepsy. Strengths of this work include the large sample size with prospective clinical assessment and rigorous electroencephalographic acute evaluation and follow-up. Furthermore, this work includes standardized imaging evaluation of middle cerebral artery infarct dimension and the presence of islands of preserved cortex within the infarct. Another aspect that stands out is the use of internationally recognized terminology showing good interobserver agreement, for describing the electroencephalographic features. The consideration of clinical and imaging parameters in the statistic models is also commendable. Finally, it is noteworthy that the first EEG was not useful to predict the risk of having an acute symptomatic seizure. Limitations apply as in any study. It would have been of interest to analyze only patients with clinical seizures and separately study the few patients with so-called electrographic seizures only (which are not seizures as seizure is traditionally a clinical term). Nevertheless, the study by Bentes et al. is an important work that truly deserves the first Clinical Epilepsia Open prize. Congratulations! Read the winning article “Seizures, electroencephalographic abnormalities, and outcome of ischemic stroke patients” online at https://onlinelibrary.wiley.com/doi/10.1002/epi4.12075. Emeritus Professor of Neurology, formerly Free University of Berlin.

BS10. Asystole in the video-telemetry unit-two cases

Primary asystole occurs when the cardiac purkinje fibers intrinsically fail to generate a ventricular depolarization. This is preceded by a bradyarrhythmia due to complete heart block, sick sinus syndrome, or both. Ictal asystole occurs due to synchronization of cardiac autonomic neural discharges with ictal epileptiform activity. Both types of asystole can cause similar events with loss of consciousness and collapse, and are important to differentiate from one another. Ictal asystole has been reported in as many as 0.4% of video-EEG monitored patients (Scheule et al., 2007), and is more common in temporal lobe epilepsies, where ictal bradycardia can evolve into asystole. In patients with intractable focal epilepsy, in whom a loop recorder had been placed, the incidence of significant bradycardia or asystole has been found to be much higher (up to 21% of these individuals) then previously suspected (Rugg-Gunn et al., 2004). We report the video-electrographic, clinical, and semiological features of two cases who were seen at our institution for diagnostic evaluation. The first individual was 43 year-old lady with a 33-year history of recurrent events. The events were characterised by speech arrest, staring ahead, and subjective visual disturbance, and sometimes by sudden collapse without any focal features or tonic/clonic movements. The second patient was a 35-year old man who presented with recurrent episodes of ringing in his ears, and a feeling of derealisation, with confusion afterward. The same events would frequently evolve with collapse, and/or generalised tonic-clonic movements. Both patients had asystole noted during a period of video-telemetry, one with asystole associated with a focal EEG seizure, and one with primary asystole with no ictal EEG change. We present the clinical and EEG findings in both patients. We will discuss relevant clinical features and semiology that can alert the treating clinician to the need for cardiac monitoring and video-EEG telemetry in order to discern attacks of cardiac from those of ictal origin.

Early EEG predicts poststroke epilepsy.

SummaryObjectiveElectroencephalography (EEG) can identify biomarkers of epileptogenesis and ictogenesis. However, few studies have used EEG in the prediction of poststroke seizures. Our primary aim was to evaluate whether early EEG abnormalities can predict poststroke epilepsy.MethodsA prospective study of consecutive acute anterior circulation ischemic stroke patients, without previous epileptic seizures, who were admitted to a stroke unit over 24 months and followed for 1 year. All patients underwent standardized clinical and diagnostic assessment during the hospital stay and after discharge. Video‐EEG was performed in the first 72 h (first EEG), daily for the first 7 days, in case of neurological deterioration, at discharge, and at 12 months after stroke. The occurrence of epileptic seizures in the first year after stroke (primary outcome) was evaluated clinically and neurophysiologically during the hospital stay and at 12 months. A telephone interview was also performed at 6 months. The primary outcome was the occurrence of at least one unprovoked seizure (poststroke epilepsy). Secondary outcomes were the occurrence of at least one acute symptomatic seizure and (interictal and/or ictal) epileptiform activity on at least one EEG during the hospital stay for acute stroke. The first EEG variables were defined using international criteria/terminology. Bivariate and multivariate analyses with adjustment for age, admission National Institutes of Health Stroke Scale (NIHSS) score, and Alberta Stroke Program Early CT Score (ASPECTS) were performed.ResultsA total of 151 patients were included; 38 patients (25.2%) had an acute symptomatic seizure and 23 (16%) had an unprovoked seizure.The first EEG background activity asymmetry and first EEG with interictal epileptiform activity were independent predictors of poststroke epilepsy during the first year after stroke (P = 0.043 and P = 0.043, respectively). No EEG abnormality independently predicted acute symptomatic seizures. However, the presence of periodic discharges on the first EEG was an independent predictor of epileptiform activity (p = 0.009) during the hospital stay.SignificanceAn early poststroke EEG can predict epilepsy in the first year after stroke, independently from clinical and imaging‐based infarct severity.

Frequency of post-stroke electroencephalographic epileptiform activity - a systematic review and meta-analysis of observational studies.

Cerebrovascular diseases are the most frequent risk factor for epilepsy in the elderly, and epileptic phenomenon following stroke is known to worsen the prognosis. Although electroencephalography is the gold standard epilepsy biomarker, it is rarely used in post-stroke studies, and the frequency of post-stroke epileptiform activity is still uncertain. We analysed studies indexed to MEDLINE, Embase, Web of Science, PsycINFO and OpenGrey (up to March 2015), reporting post-stroke electroencephalographic epileptiform activity frequency in adults. Epileptiform activity was classified as ictal (electrographic seizures) and interictal (non-periodic spikes and sharp waves). Data selection, extraction and appraisal were done in duplicate. Random-effects meta-analysis was used to pool frequencies. The pooled frequency of post-stroke ictal and interictal epileptiform activity was 7% (95% CI 3%-12%) and 8% (95% CI 4%-13%), respectively. The use of continuous electroencephalogram was not associated with an increased frequency of electrographic seizures (p = 0.05), nor did the management setting (Intensive Care Unit versus non- Intensive Care Unit, p = 0.31). However, studies with continuous electroencephalogram showed a higher frequency of interictal epileptiform activity (p = 0.01). This study provides the best available estimates of the frequency of post-stroke electroencephalographic epileptiform activity. Due to detection bias, it was not possible to correlate clinical and electrographic seizures. The frequency of ictal and interictal epileptiform activity in the electroencephalogram was comparable with previous frequency analyses of clinical seizures. The frequency of ictal epileptiform activity did not change with continuous record or clinical setting, while the frequency of interictal epileptiform activity increased with continuous record.

Diagnostic Yield of Routine Electroencephalography With Concurrent Video Recording in Detecting Interictal Epileptiform Discharges in Relation to Reasons for Request: A Prospective Study of 1,080 Video-Electroencephalograms.

The aim of this study was to prospectively analyze the sensitivity and specificity of routine electroencephalography with concurrent video recording (vEEG) in relation to the reasons for requesting the test and to investigate when routine vEEG should be requested. We prospectively analyzed 1,080 consecutive vEEGs performed between April 2015 and April 2016. The requests for vEEG were classified as requests with a low suspicion of epilepsy (syncope, confusion or delirium, suspicion of psychogenic nonepileptic seizures, and paroxysmal focal neurological deficit) or requests with a high suspicion of epilepsy (first clinical seizure, suspected status epilepticus, follow-up study of a patient with epilepsy, and acute symptomatic seizures). Predominant vEEG findings (ictal and interictal epileptiform activities, diffuse, or focal slowing and triphasic waves) were analyzed, and sensitivity and specificity [ZERO WIDTH SPACE][ZERO WIDTH SPACE]values calculated. The most common indication for vEEG was a follow-up study of patients with epilepsy (38%), followed by first clinical seizure (19.3%) and suspected status epilepticus (11%). The respective specificity and sensitivity values were 93% and 58% for 235 vEEGs performed in children/adolescents (≤18 years), 95% and 40% for 533 vEEGs performed in adults (>18 ≤ 65 years), and 93% and 39% for 312 vEEGs performed in older adults (>65 years). Twenty-four patients with false-positive paroxysms had a clinical diagnosis of confusional state or paroxysmal focal neurological deficit. Neurologists and neuropediatricians with experience in managing epilepsy had higher specificity values than general neurologists or physicians (P = 0.012). In our series, vEEG abnormalities were mainly observed in patients with clinical findings highly suggestive of epilepsy. In confusional states, and paroxysmal focal neurological deficit vEEG could be indicated.

Seizure activity per se does not induce tissue damage markers in human neocortical focal epilepsy.

The contribution of recurring seizures to the progression of epileptogenesis is debated. Seizure-induced brain damage is not conclusively demonstrated either in humans or in animal models of epilepsy. We evaluated the expression of brain injury biomarkers on postsurgical brain tissue obtained from 20 patients with frequent seizures and a long history of drug-resistant focal epilepsy. The expression patterns of specific glial, neuronal, and inflammatory molecules were evaluated by immunohistochemistry in the core of type II focal cortical dysplasias (FCD-II), at the FCD boundary (perilesion), and in the adjacent normal-appearing area included in the epileptogenic region. We also analyzed surgical specimens from cryptogenic patients not presenting structural alterations at imaging. Astroglial and microglial activation, reduced neuronal density, perivascular CD3-positive T-lymphocyte clustering, and fibrinogen extravasation were demonstrated in the core of FCD-II lesions. No pathological immunoreactivity was observed outside the FCD-II or in cryptogenetic specimens, where the occurrence of interictal and ictal epileptiform activity was confirmed by either stereo-electroencephalography or intraoperative electrocorticography. Recurrent seizures do not induce the expression of brain damage markers in nonlesional epileptogenic cortex studied in postsurgical tissue from cryptogenic and FCD patients. This evidence argues against the hypothesis that epileptiform activity per se contributes to focal brain injury, at least in the neocortical epilepsies considered here. Ann Neurol 2017;82:331-341.

Magnetic facial nerve stimulation in animal models of active seizure

PurposeAs part of our efforts to develop a non-invasive facial nerve stimulator as an emergency treatment for ischemic stroke, we considered possible safety consequences if the technology was misapplied to stroke mimics, e.g., seizure. We hypothesized that magnetic facial nerve stimulation would worsen epileptiform activity in two animal models of active seizures. The rat intraperitoneal kainate model and pig intracortical penicillin model were employed. Magnetic facial nerve stimulation was delivered unilaterally at a variety of stimulation parameters, and the effect on ictal epileptiform activity measured by electroencephalography was determined according to an established categorical scale. Principal resultsIn 6 rats and 3 pigs evaluated with 83 stimulation trials, only a single stimulation trial was associated with worsening epileptiform activity according to a standard categorization scheme. Surprisingly, a reduction in the severity of the epileptiform activity was observed in 20 of 50 stimulation trials using patterned stimulation (3 pulses at 30Hz repeated at 0.5–10Hz) versus 2 of 33 stimulation trials using simple monotonic patterns (P<0.005, chi-squared test). The reduction of epileptiform activity after stimulation lasted a few minutes and was reproducible.Major Conclusions Epileptiform activity measured by electroencephalography was not reliably worsened by repetitive facial nerve stimulation with pulsed magnetic energy, even when significant brain exposure to the magnetic field occurred as in the rat model. To the contrary, a temporary reduction in epileptiform activity was often, but not invariably, observed with certain stimulation parameters.

Contralateral interictal and ictal EEG epileptiform activity accentuate memory impairment in unilateral mesial temporal sclerosis patients.

Memory impairment is a recognized complication of mesial temporal sclerosis (MTS). Epileptiform activity may negatively impact on cognition. We evaluated the impact of contralateral EEG involvement on memory in unilateral MTS (uMTS) patients. Retrospective review of 121 right-handed uMTS patients (69 left) evaluated with prolonged video-EEG and verbal and nonverbal memory tests (Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex figure), with additional very delayed trials. Patients were classified according to ictal/interictal EEG findings and MTS side as left or right concordant or discordant. Thirty-nine normal individuals who underwent the same neuropsychological battery served as controls. Demographic, disease, and treatment features did not differ among groups. On the 7-day verbal memory free recall, left discordant performed significantly worse than controls and right concordant, recognized fewer words, and had more recognition errors than all other groups, including left concordant. For nonverbal memory, right discordant performed significantly worse than controls on delayed recall, and attained lower scores than other groups on immediate and 7-day recall, but this difference did not reach statistical significance. Left discordant had higher scores of memory complaints than controls and disclosed a trend toward accentuated memory impairment compared with the other groups over time. Our results suggest that contralateral electrographic involvement in uMTS was associated with more pronounced memory impairment for verbal material in left discordant patients, and to a lesser extent, for nonverbal material in right discordant patients. Left discordant group also had increased memory complaints. (PsycINFO Database Record

Protective Effect of Quinine on Chemical Kindling and Passive Avoidance Test in Rats.

BackgroundIn humans, convulsive diseases such as temporal lobe epilepsy are usually accompanied by learning and memory impairments. In recent years, the role of gap junction channels as an important target of antiepileptic drugs has been studied and discussed. Quinine, as a gap junction blocker of connexin 36, can abolish ictal epileptiform activity in brain slices.ObjectivesThe role of quinine in memory retrieval in pentylenetetrazole (PTZ)-kindled rats was examined using a step-through passive avoidance task.MethodsForty rats were used in this experimental study in groups of 10 animals. Quinine (15, 30, and 60 mg/kg, i.p.) and PTZ (35 mg/kg, i.p.) were injected into the rats before the start of the learning test. Then, retention tests were conducted after the treatments ended.ResultsQuinine could attenuate seizure severity at doses of 15, 30 and 60 mg/kg compared with the control at the beginning of the kindling experiment by lowering the mean seizure stages (P < 0.01, P < 0.001, P < 0.001). Quinine at doses of 15 and 30 mg/kg could significantly increase memory retrieval compared with the control in the retention test 24 and 48 hours after training (P < 0.05). Quinine at a dose of 60 mg/kg increased latency to enter the dark chamber 24 and 48 hours after training (P < 0.001). The results of the retention test one and two weeks after training of quinine were not significant (P > 0.05).ConclusionsQuinine may decrease the severity of seizure and improve the memory retrieval of animals by inhibiting the gap junction channel. However, further studies are needed to evaluate the molecular mechanism underlying the effects of quinine.