Refractory Epilepsy Patients Research Articles

Robotic surgical rehearsal on patient-specific 3D-printed skull models for stereoelectroencephalography (SEEG).

Medically refractory epilepsy patients commonly require surgical alternatives for diagnosis and treatment. Stereoelectroencephalography (SEEG) is a useful diagnostic procedure in seizure focus elucidation. Modern techniques involve the use of robotics and neuronavigation for SEEG. A steep learning curve combined with multiple complex technologies employed during the case makes this procedure a perfect candidate for surgical rehearsal. This paper tests the feasibility of the use of patient-specific 3D-printed model for surgical rehearsal of robotic SEEG. A 3D-printed model was created using the patient's cranial computed tomography and computed tomography angiography radiological imaging. A rehearsal in an operating room (OR) prior to the actual procedure date was used for surgical planning of SEEG electrodes, education of the residents and fellows as well as training of the support staff. Attention was paid to assure precise recreation of the surgical procedure. The patient-specific 3D-printed model tolerated each step of the procedure from facial registration, to drilling, bolt insertion and lead placement. Accuracy of the designed trajectory to the electrode final position was visually confirmed at the end of procedure. Important modification to the plan of eventual surgery improved the efficiency of the real operation. For surgical planning, education and training purposes in robotic SEEG, 3D-printed models may be utilized as a realistic anatomy tool. Potential applications of this technique include trajectory feasibility evaluation, patient positioning optimization, increasing OR efficiency, as well as neurosurgical education and patient counseling.

Quality of Life and Its Determinants in Adult Drug Refractory Epilepsy Patients Who Were Not Candidates for Epilepsy Surgery: A Correlational Study.

Background and PurposeThis study was performed to elucidate quality of life (QOL) and its determinants in adult drug refractory epilepsy (DRE) patients who were not candidates for epilepsy surgery.MethodsA correlational study was performed at the center of excellence, epilepsy between July 2014 to June 2016. All consecutive DRE patients who were not candidates for epilepsy surgery were enrolled. The outcomes were QOL, assessed using the quality of life inventory in epilepsy-31 items (QOLIE-31) inventory and the correlation of QOL with epilepsy-related variables like seizure severity and frequency. We also compared current QOL with QOL during the pre-surgical evaluation to strengthen our study outcome.ResultsA total of 129 adult patients were enrolled over two years. The mean age was 26.5 ± 6.7 years and male: female ratio was 3: 1. The mean age at epilepsy onset was 9.6 ± 6.6 years and mean duration of epilepsy was 14.9 ± 7.5 years. There was lower seizure frequency than during pre-surgical evaluation in 37.2% of patients, while in 62.8% the seizure frequency remained the same or was higher. Nine (6.98%) patients became seizure free. In comparison to QOL status during the pre-surgical evaluation, there was statistically significant worsening of QOL in all domains (p < 0.01). Seizure severity significantly correlated with almost all QOL domains (p ≤ 0.01), while seizure frequency significantly correlated with only the single domain of overall QOL (p = 0.03).ConclusionsThe QOL of DRE patients who were not candidates for epilepsy surgery worsened relative to the QOL during the pre-surgical evaluation period. Seizure severity significantly correlated with QOL, but seizure frequency did not.

Phase Synchronization Dynamics of Neural Network during Seizures.

Epilepsy has been considered as a network-level disorder characterized by recurrent seizures, which result from network reorganization with evolution of synchronization. In this study, the brain networks were established by calculating phase synchronization based on electrocorticogram (ECoG) signals from eleven refractory epilepsy patients. Results showed that there was a significant increase of synchronization prior to seizure termination and no significant difference of the transitions of network states among the preseizure, seizure, and postseizure periods. Those results indicated that synchronization might participate in termination of seizures, and the network states transitions might not dominate the seizure evolution.

Seizure susceptibility and infraslow modulatory activity in the intracranial electroencephalogram.

Studies of infraslow amplitude modulations (<0.15Hz) of band power time series suggest that these envelope correlations may form a basis for distant spatial coupling in the brain. In this study, we sought to determine how infraslow relationships are affected by antiepileptic drug (AED) taper, time of day, and seizure. We studied intracranial electroencephalographic (icEEG) data collected from 13 medically refractory adult epilepsy patients who underwent monitoring at Yale-New Haven Hospital. We estimated the magnitude-squared coherence (MSC) at <0.15Hz of traditional EEG frequency band power time series for all electrode contact pairs to quantify infraslow envelope correlations between them. We studied, first, hour-long background icEEG epochs before and after AED taper to understand the effect of taper. Second, we analyzed the entire record for each patient to study the effect of time of day. Finally, for each patient, we reviewed the clinical record to find all seizures that were at least 6hours removed from other seizures and analyzed infraslow envelope MSC before and after them. Infraslow envelope MSC increased slightly, but significantly, after AED taper, and increased on average during the night and decreased during the day. It was also increased significantly in all frequency bands up to 3hours preseizure and 1hour postseizure as compared to background icEEG (61 seizures studied). These changes occurred for both daytime and nighttime seizures (28 daytime, 33 nighttime). Interestingly, there was significant spatial variability to these changes, with the seizure onset area peaking at 3hours preseizure, then showing progressive desynchronization from 3hours preseizure to 1hour postseizure. Infraslow envelope analysis may be used to understand long-term changes over the course of icEEG monitoring, provide unique insight into interictal electrophysiological changes related to ictogenesis, and contribute to the development of novel seizure forecasting algorithms.

Novel and de novo mutations in pediatric refractory epilepsy

Pediatric refractory epilepsy is a broad phenotypic spectrum with great genetic heterogeneity. Next-generation sequencing (NGS) combined with Sanger sequencing could help to understand the genetic diversity and underlying disease mechanisms in pediatric epilepsy. Here, we report sequencing results from a cohort of 172 refractory epilepsy patients aged 0–14 years. The pathogenicity of identified variants was evaluated in accordance with the American College of Medical Genetics and Genomics (ACMG) criteria. We identified 43 pathogenic or likely pathogenic variants in 40 patients (23.3%). Among these variants, 74.4% mutations (32/43) were de novo and 60.5% mutations (26/43) were novel. Patients with onset age of seizures ≤12 months had higher yields of deleterious variants compared to those with onset age of seizures > 12 months (P = 0.006). Variants in ion channel genes accounted for the greatest functional gene category (55.8%), with SCN1A coming first (16/43). 81.25% (13/16) of SCN1A mutations were de novo and 68.8% (11/16) were novel in Dravet syndrome. Pathogenic or likely pathogenic variants were found in the KCNQ2, STXBP1, SCN2A genes in Ohtahara syndrome. Novel deleterious variants were also found in West syndrome, Doose syndrome and glucose transporter type 1 deficiency syndrome patients. One de novoMECP2 mutation were found in a Rett syndrome patient. TSC1/TSC2 variants were found in 60% patients with tuberous sclerosis complex patients. Other novel mutations detected in unclassified epilepsy patients involve the SCN8A, CACNA1A, GABRB3, GABRA1, IQSEC2, TSC1, VRK2, ATP1A2, PCDH19, SLC9A6 and CHD2 genes. Our study provides novel insights into the genetic origins of pediatric epilepsy and represents a starting-point for further investigations into the molecular pathophysiology of pediatric epilepsy that could eventually lead to better treatments.

Comparison of cytokines and prooxidants/antioxidants markers among adults with refractory versus well-controlled epilepsy: A cross-sectional study

PurposeThis study aims to investigate the serum adiponectin, interleukin (IL)-6 and oxidative stress in epilepsy patients who are refractory or non-refractory to treatments. MethodThe study comprised 31 refractory epilepsy, 29 well-controlled epilepsy patients and control group including 29 healthy individuals. The serum adiponectin, IL-6, total antioxidant status (TAS), total oxidant status levels (TOS) and oxidative stress index (OSİ) were determined. ResultsThe mean serum adiponectin and TAS levels were significantly lower in the refractory epilepsy patients than in the healty controls, and mean IL-6, TOS and OSİ levels were significantly higher. The serum adiponectin, IL-6, TAS, TOS and OSI levels were not significantly different between the well-controlled epilepsy patients and the healthy controls. ConclusionsThe mean serum IL-6 and oxidative stress levels in refractory epilepsy patients were higher and the serum adiponectin level was lower than the healthy control group. These findings may be associated with an increased risk of seizures, atherosclerosis and cardiovascular disease in refractory epilepsy patients.

Volumetric Trends Associated with MR-guided Stereotactic Laser Amygdalohippocampectomy in Mesial Temporal Lobe Epilepsy.

Objective: Magnetic resonance (MR)-guided stereotactic laser amygdalohippocampectomy is a minimally invasive procedure for the treatment of refractory epilepsy in patients with mesial temporal sclerosis. Limited data exist on post-ablation volumetric trends associated with the procedure.Methods: 10 patients with mesial temporal sclerosis underwent MR-guided stereotactic laser amygdalohippocampectomy. Three independent raters computed ablation volumes at the following time points: pre-ablation (PreA), immediate post-ablation (IPA), 24 hours post-ablation (24PA), first follow-up post-ablation (FPA), and greater than three months follow-up post-ablation (>3MPA), using OsiriX DICOM Viewer (Pixmeo, Bernex, Switzerland). Statistical trends in post-ablation volumes were determined for the time points.Results: MR-guided stereotactic laser amygdalohippocampectomy produces a rapid rise and distinct peak in post-ablation volume immediately following the procedure. IPA volumes are significantly higher than all other time points. Comparing individual time points within each raters dataset (intra-rater), a significant difference was seen between the IPA time point and all others. There was no statistical difference between the 24PA, FPA, and >3MPA time points. A correlation analysis demonstrated the strongest correlations at the 24PA (r=0.97), FPA (r=0.95), and 3MPA time points (r=0.99), with a weaker correlation at IPA (r=0.92).Conclusion: MR-guided stereotactic laser amygdalohippocampectomy produces a maximal increase in post-ablation volume immediately following the procedure, which decreases and stabilizes at 24 hours post-procedure and beyond three months follow-up. Based on the correlation analysis, the lower inter-rater reliability at the IPA time point suggests it may be less accurate to assess volume at this time point. We recommend post-ablation volume assessments be made at least 24 hours post-selective ablation of the amygdalohippocampal complex (SLAH).

The effectiveness of cortico-cortical evoked potential in detecting seizure onset zones

Objective The aim of the study was to evaluate the parameters for localizing the seizure onset zone in refractory epilepsy patients using cortico-cortical evoked potentials (CCEP).Methods Fifteen patients (nine females) with medically refractory partial epilepsy underwent stereo electro encephalography (SEEG) in Tsinghua University Yu-Quan Hospital from 2015 to 2016. Clinical semiology and, scalp electroencephalography (EEG) findings were analyzed during phase I preoperative evaluation. During phase II evaluation, localization of seizure onset zone (SOZ) was analyzed using SEEG by experienced epileptologists. Meanwhile, the cortico-cortical evoked potential (CCEP) paradigm was tested in all patients in phase II. The value of root-mean-square (RMS) of CCEPs amplitude from 7 ms to 300 ms after stimulation was analyzed to quantify the response.Results RMS of CCEPs amplitude in SOZ was higher than in seizure propagation zone (SPZ) (P < 0.05) and non-seizure onset zone (NSOZ) (P < 0.05). RMS of CCEPs amplitude in SOZ was higher than in NSOZ in epilepsy patients with secondary generalized tonic-clonic seizures (SGTCS) (N = 6, P < 0.05); The RMS of CCEPs amplitude in SOZ was strikingly higher than SPZ in the repetitive spiking (RS) onset pattern, and the difference was significant (N = 5, P < 0.01).Conclusions This data indicated that CCEP response is enhanced in SOZ despite different seizure types (with or without SGTCS). CCEP may be an effective method to locate SOZ.

Altered spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder: A resting-state fMRI study

ObjectiveTo investigate alterations in spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder using resting-state functional magnetic resonance imaging (RS-fMRI). MethodsEighteen MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder (PDD), 17 MRI-negative refractory temporal lobe epilepsy patients without major depressive disorder (nPDD), and 21 matched healthy controls (HC) were recruited from West China Hospital of SiChuan University from April 2016 to June 2017. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 17-item Hamilton Depression Rating Scale were employed to confirm the diagnosis of major depressive disorder and assess the severity of depression. All participants underwent RS-fMRI scans using a 3.0T MRI system. MRI data were compared and analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) to measure spontaneous brain activity. These two methods were both used to evaluate spontaneous cerebral activity. ResultsThe PDD group showed significantly altered spontaneous brain activity in the bilateral mesial prefrontal cortex, precuneus, angular gyrus, right parahippocampal gyrus, and right temporal pole. Meanwhile, compared with HC, the nPDD group demonstrated altered spontaneous brain activity in the temporal neocortex but no changes in mesial temporal structures. ConclusionThe PDD group showed regional brain activity alterations in the prefrontal-limbic system and dysfunction of the default mode network. The underlying pathophysiology of PDD may be provided for further studies.

An mHealth Application for Educating and Monitoring Patients Treated with a Ketogenic Diet Regimen.

Ketogenic Diet (KD) is a high-fat diet used to treat refractory epilepsy in patients, also including children. Because of the inherent differences with a balanced diet, patients starting KD face an abrupt switch of dietary habits. Moreover, KD is associated with several side effects that should be closely monitored. In this paper, we propose an mHealth application for training and empowering patients in managing KD. The application also acts as a bridge connecting patients with the health care staff for coaching and monitoring purposes.

Safety And Efficacy of Zonisamide in Refractory Epilepsy Patients: Clinical Experience from A Tertiary Center

Safety And Efficacy of Zonisamide in Refractory Epilepsy Patients: Clinical Experience from A Tertiary Center

Virtual localization of the seizure onset zone: Using non-invasive MEG virtual electrodes at stereo-EEG electrode locations in refractory epilepsy patients.

In some patients with medically refractory epilepsy, EEG with intracerebrally placed electrodes (stereo-electroencephalography, SEEG) is needed to locate the seizure onset zone (SOZ) for successful epilepsy surgery. SEEG has limitations and entails risk of complications because of its invasive character. Non-invasive magnetoencephalography virtual electrodes (MEG-VEs) may overcome SEEG limitations and optimize electrode placement making SOZ localization safer. Our purpose was to assess whether interictal activity measured by MEG-VEs and SEEG at identical anatomical locations were comparable, and whether MEG-VEs activity properties could determine the location of a later resected brain area (RA) as an approximation of the SOZ. We analyzed data from nine patients who underwent MEG and SEEG evaluation, and surgery for medically refractory epilepsy. MEG activity was retrospectively reconstructed using beamforming to obtain VEs at the anatomical locations corresponding to those of SEEG electrodes. Spectral, functional connectivity and functional network properties were obtained for both, MEG-VEs and SEEG time series, and their correlation and reliability were established. Based on these properties, the approximation of the SOZ was characterized by the differences between RA and non-RA (NRA). We found significant positive correlation and reliability between MEG-VEs and SEEG spectral measures (particularly in delta [0.5–4 Hz], alpha2 [10–13 Hz], and beta [13–30 Hz] bands) and broadband functional connectivity. Both modalities showed significantly slower activity and a tendency towards increased broadband functional connectivity in the RA compared to the NRA. Our findings show that spectral and functional connectivity properties of non-invasively obtained MEG-VEs match those of invasive SEEG recordings, and can characterize the SOZ. This suggests that MEG-VEs might be used for optimal SEEG planning and fewer depth electrode implantations, making the localization of the SOZ safer and more successful.

EEG-Based Detection of Epileptic Seizures Through the Use of a Directed Transfer Function Method

This paper aims to explore the automatic detection method of epileptic seizures to improve the treatment and diagnosis of medically refractory epilepsy patients. A new algorithm based on directed transfer function (DTF) method was proposed for epileptic seizure detection. First, the sliding window technique was used to segment electroencephalogram (EEG) recordings, and the cerebral functional connectivity was calculated by the DTF algorithm. Then, the total information outflow based on the DTF-derived connectivity was calculated by adding up the information flow from a single EEG channel to other channels. Finally, the information outflow was assigned as the features of support vector machine (SVM) classifier to discriminate interictal and ictal EEG segments. For 10 epilepsy patients, the proposed algorithm provided the mean correct rate of 98.45%, the mean selectivity of 64.43%, the mean sensitivity of 93.36%, the mean specificity of 98.42%, and the average detection rate of 95.89%. By applying the statistical analysis, the superiority of DTF-based method was statistically significant when compared with other algorithms in terms of five assessment criteria. Our results indicated that the DTF-derived connectivity could characterize the dynamic causal interaction patterns between brain areas during seizure states, and the proposed method was suitable for the detection of epileptic seizures.

DeepIED: An epileptic discharge detector for EEG-fMRI based on deep learning.

Presurgical evaluation that can precisely delineate the epileptogenic zone (EZ) is one important step for successful surgical resection treatment of refractory epilepsy patients. The noninvasive EEG-fMRI recording technique combined with general linear model (GLM) analysis is considered an important tool for estimating the EZ. However, the manual marking of interictal epileptic discharges (IEDs) needed in this analysis is challenging and time-consuming because the quality of the EEG recorded inside the scanner is greatly deteriorated compared to the usual EEG obtained outside the scanner. This is one of main impediments to the widespread use of EEG-fMRI in epilepsy. We propose a deep learning based semi-automatic IED detector that can find the candidate IEDs in the EEG recorded inside the scanner which resemble sample IEDs marked in the EEG recorded outside the scanner. The manual marking burden is greatly reduced as the expert need only edit candidate IEDs. The model is trained on data from 30 patients. Validation of IEDs detection accuracy on another 37 consecutive patients shows our method can improve the median sensitivity from 50.0% for the previously proposed template-based method to 84.2%, with false positive rate as 5 events/min. Reproducibility validation on 15 patients is applied to evaluate if our method can produce similar hemodynamic response maps compared with the manual marking ground truth results. We explore the concordance between the maximum hemodynamic response and the intracerebral EEG defined EZ and find that both methods produce similar percentage of concordance (76.9%, 10 out of 13 patients, electrode was absent in the maximum hemodynamic response in two patients). This tool will make EEG-fMRI analysis more practical for clinical usage.

Immunopathology in drug resistant mesial temporal lobe epilepsy with different types of hippocampal sclerosis

ABSTRACTPurpose: There is evidence that autoimmunity has a specific role in temporal lobe seizures of limbic encephalitis patients. Our aim in this study was to investigate any histopathological clues of autoimmune process in refractory temporal lobe epilepsy (TLE) patients with different pathologically proven hippocampal sclerosis (HS) types.Methods: 22 patients who had undergone epilepsy surgery due to mesial TLE-HS were included. The sera of patients are tested for neuronal antibodies to N-methyl-D-aspartate receptors (NMDAR), leucine-rich, glioma inactivated 1 (LGI1), contactin-associated protein 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), gamma-aminobutyric acid B receptor (GABABR) and glutamic acid decarboxylase (GAD). Pathological and immunohistochemical investigations including neuronal nuclei (NeuN), NMDAR, GAD, glial fibrillary acidic protein (GFAP), CD8+-CD3+ lymphocytes and immunoglobulin G (IgG) were done. Patients were grouped according to type of HS. Clinical features and immunohistochemical changes were defined in these groups.Results: Available sera of 15 patients did not have any neuronal antibodies. Thirteen of 22 patients had HS type 1, three had HS type 2 and two had HS type 3. According to immunohistochemical investigations CD3+ and CD8+ T cell infiltration was more prominent in the hippocampus of patients with classical HS (International League Against Epilepsy (ILAE) Type 1 HS) and there was a significant negative correlation between epilepsy duration and numbers of CD3+-CD8+ lymphocytes in temporal lobe parenchyma.Conclusion: The role of T cell-mediated immunopathology and immunopathological difference in a variety of drug resistant TLE-H2S patients was suggested. These findings can be helpful in understanding the epileptogenicity of HS.

Long-term follow-up of anterior thalamic deep brain stimulation in epilepsy: A 11-year, single center experience

PurposeAnterior thalamic deep brain stimulation (ATN DBS) is an emerging, effective treatment for patients with drug-resistant epilepsy, but long-term results on its efficacy and safety are lacking. To evaluate the long-term efficacy and safety of ATN DBS treatment, as well as predictors of its success, in patients with drug-refractory epilepsy (DRE). MethodWe retrospectively studied clinical outcomes in 29 consecutive refractory epilepsy patients treated by a single DBS team (two neurosurgeons, four neurologists) over an 11-year period, for whom follow-up was performed for up to 137 months (mean, 74.9 months). ResultsThe average participant was 30.7 (±10.4) years old and had epilepsy for 19.3 (±9.0) years. The mean preoperative frequency of disabling partial or generalized tonic-clonic seizures was 27.5 (±8.6, SE) seizures a month. The median percent seizure reduction was 71.3% at 1year, 73.9% at 2 years, and ranged from 61.8% to 80.0% over post-implant years 3 through 11 in the long-term study (overall 70% median reduction). In the 11-year study period, 13.8% (4/29) of subjects were seizure-free for at least 12 months during this time. There was only one symptomatic intracranial hemorrhage that happened during follow-up (3.4%). Infection requiring removal and later re-implantation of hardware occurred in only 1 of 30 patients (3.3%), who was subsequently excluded from our follow-up assessment. Hardware malfunction including lead disconnection occurred in 2 of 29 cases (6.9%). Revision of lead position to redeem poor clinical response was performed in 3 of 58 implanted leads (5.2%). ConclusionsATN DBS can be an effective therapy in a variety of patients with DRE. Importantly, we provide evidence that significant therapeutic efficacy can be sustained for up to 11 years. Neurological complications were rather rare, but long-term hardware-related complications should be followed arrectis auribus.

Cost-Effectiveness Analysis Of Stereotaxic Eeg (SEEG) As A Preoperative Diagnostic Procedure In Epilepsy Surgery

The aim of our study was to determine the health gain and the corresponding costs resulted from the introduction of stereotaxic EEG (SEEG) as a preoperative diagnostic procedure in epilepsy surgery for MRI negative refractory epilepsy patients. Furthermore, we analyzed the cost-effectiveness of the intervention compared to medical management as the standard of care in Hungary. The incremental health gains and costs of SEEG were determined with a Markov model over a 45 years’ time horizon. Transition probabilities and utilities have been derived from international literature. The intervention has not yet been financed by the National Healthcare Fund in Hungary, therefore the actual cost were determined from provider’s perspective, based on the relevant units costs and resource use at the Department of Neurology and Department of Neurosurgery regarding the intervention. Based on the result of our model the total cost of the SEEG intervention is 10,540 thousand HUF which represents a 4,490 thousand HUF additional cost and 3.086 QALY gain in 45 years compare to the standard medical management. The calculated preliminary incremental cost-effectiveness ratio is 1,455 thousand HUF/QALY. Based on our preliminary results in the treatment of patients with MR negative refractory epilepsy the preoperative SEEG diagnostic procedure in Hungary was cost-effective compared to the medical management. Based on our result we suggest the SEEG to be introduced into the Hungarian reimbursement system as a new procedure.

P241 Insula connectivity during wakefulness and sleep studied through single pulse electrical stimulation during seeg recordings

Objective We aim to study the connections of the posterior insula (pI) and anterior insula (aI) through cortico-cortical evoked potentials (CCEP) by single pulse electrical stimulation (SPES). Method We performed SPES stimulation protocol in a group of 8 refractory epilepsy patients presurgically explored with intracerebral depth electrodes, out of which 6 were operated on and are currently seizure-free. We selected the early responses (ER) obtained from contacts of 24 electrodes that were included in the anterior and posterior insula, when this structure was outside the seizure onset zone (SOZ). Responses were analyzed in terms of amplitude variations during wakefulness and sleep. Effective connectivity betweeen cortical was calculated based on the measured CCEPs. Results The ER amplitudes by SPES stimulation in the insula during wakefulness compared to sleep showed statistically significant ( p 0.05 ) differences in 6 patients. There are constant connections between aI and pI. We identified connectivity of the pI with language-related brain stuctures during wakefulness, and with the temporal mesial structures during sleep, possibly influenced by the SOZ. Right pI stimulation seems to elicit ampler reponses in the rolandic operculum and parietal structures during wakefulness, and in the primary motor and premotor cortex during sleep. Anterior insula has preferential connectivity with anterior cingulate gyrus during wakefulness and with the fusiform gyrus during sleep. Discussions Connectivity of the aI versus pI, as well as right versus left insula during wakefulness and sleep is different, partially supporting previous observations. Conclusion Sleep has been shown to alter the physiological connectivity of the insula. Further investigations are in progress to confirm these results. Significance These findings describe insular connectivity and variability during sleep, with possible implications in epilepsy surgery, sleep disorders understanding and language studies.

Potentially Pathological Alpha-Pattern as a Variant of Vigilance EEG in Drug-Resistant Epilepsy

As a result of pathomorphosis affecting the mechanisms of electrical activity generation interictal EEG may show reduced epileptiform changes whereas clinically apparent epileptic seizures may be present. In these cases patterns of dominant alpha activity are sometimes recorded on the scalp. In this study variations of alpha activity in patients with refractory epilepsy are classified. A group of 50 refractory epilepsy patients aged between 20 and 55 years who were submitted to Polenov Russian Scientific Research Institute of Neurosurgery in 2014-2017 was included in this study. They underwent scalp EEG as a part of their presurgical assessment. In 12 cases patterns of potentially pathological alpha activity were observed. Three variations of alpha-patterns were described: 1) alpha-rhythm with decreased regional diversity and a marked synchronization in temporal areas; 2) alpha-rhythm with reduced epileptiform complexes integrated into the spindles, 3) decelerated non-rhythmic alpha activity distorted by the higher frequency components. Distinguished varieties of potentially pathological alpha-activity according to their order here represent gradual functional decline of normal thalamo-cortical interaction. Considering clinical manifestation of drug-resistant epilepsy with frequent seizures in these patients, reported varieties of alpha activity can not be interpreted as Landolt’s syndrome (forced normalization of EEG). Invasive electrocorticographic monitoring demonstrated that bursts of sharpened polyphasic waves coinciding with alpha-rhythm on scalp EEG are consistent with epileptic discharges on the brain cortex surface. This allows to think of these components as correlates of epileptic activity. Therefore, on a number of occasions in patients with epilepsy a dissonance between clinical signs and electroencephalographic patterns recorded during restful wakefulness may be observed, when epileptiform components are absent or reduced to nonspecific complexes.

Time-of-day influences on respiratory sequelae following maximal electroshock-induced seizures in mice.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. Although specific mechanisms underlying SUDEP are not well understood, evidence suggests most SUDEP occurs due to seizure-induced respiratory arrest. SUDEP also tends to happen at night. Although this may be due to circumstances in which humans find themselves at night, such as being alone without supervision or sleeping prone, or to independent influences of sleep state, there are a number of reasons why the night (i.e., circadian influences) could be an independent risk factor for SUDEP. We explored this possibility. Adult male WT mice were instrumented for EEG, EMG, and EKG recording and subjected to maximal electroshock (MES) seizures during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep during the nighttime/dark phase. These data were compared with data collected following seizures induced during the daytime/light phase. Seizures induced during the nighttime were similar in severity and duration to those induced during the daytime; however, seizures induced during the nighttime were associated with a lesser degree of respiratory dysregulation and postictal EEG suppression. Seizures induced during REM sleep during the nighttime were universally fatal, as is seen when seizures are induced during REM during the daytime. Taken together, these data implicate a role for time of day in influencing the physiological consequences of seizures that may contribute to seizure-induced death.NEW & NOTEWORTHY Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP frequently occurs during the night, which has been attributed to an effect of sleep. We have shown that sleep state does indeed influence survival following a seizure. That SUDEP occurs during the night could also implicate a circadian influence. In this study we found that time of day independently affects the physiological consequences of seizures.