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Delineation of seizure onset regions using intracranial electroencephalography (icEEG) is vital in the surgical workup of drug-resistant epilepsy cases. However, it is unknown whether the complete resection of these regions is necessary for seizure freedom, or whether postsurgical seizure recurrence can be attributed to the incomplete removal of seizure onset regions. To address this gap, we retrospectively analyzed icEEG recordings from 63 subjects, identifying seizure onset regions visually and algorithmically. We assessed onset region resection and correlated this with postsurgical seizure control. The majority of subjects had more than half of their onset regions resected (82.46% and 80.65% of subjects using visual and algorithmic methods, respectively). There was no association between the proportion of the seizure onset zone (SOZ) that was subsequently resected and better surgical outcomes (area under the receiver operating characteristic curve [AUC] < .7). Investigating the spatial extent of onset regions, we found no substantial evidence of an association with postsurgical seizure control (all AUC < .7). Although seizure onset regions are typically resected completely or in large part, incomplete resection is not associated with worse postsurgical outcomes. We conclude that postsurgical seizure recurrence cannot be attributed to an incomplete resection of the icEEG SOZ alone. Other network mechanisms beyond icEEG seizure onset likely contribute., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Patients with epilepsy, who later succumb to sudden unexpected death, show altered brain tissue volumes in selected regions. It is unclear whether the alterations in brain tissue volume represent changes in neurons or glial properties, since volumetric procedures have limited sensitivity to assess the source of volume changes (e.g., neuronal loss or glial cell swelling). We assessed a measure, entropy, which can determine tissue homogeneity by evaluating tissue randomness, and thus, shows tissue integrity; the measure is easily calculated from T1-weighted images. T1-weighted images were collected with a 3.0-Tesla MRI from 53 patients with tonic-clonic (TC) seizures and 53 healthy controls; images were bias-corrected, entropy maps calculated, normalized to a common space, smoothed, and compared between groups (TC patients and controls using ANCOVA; covariates, age and sex; SPM12, family-wise error correction for multiple comparisons, p<0.01). Decreased entropy, indicative of increased tissue homogeneity, appeared in major autonomic (ventromedial prefrontal cortex, hippocampus, dorsal and ventral medulla, deep cerebellar nuclei), motor (sensory and motor cortex), or both motor and autonomic regulatory sites (basal-ganglia, ventral-basal cerebellum), and external surfaces of the pons. The anterior and posterior thalamus and midbrain also showed entropy declines. Only a few isolated regions showed increased entropy. Among the spared autonomic regions was the anterior cingulate and anterior insula; the posterior insula and cingulate were, however, affected. The entropy alterations overlapped areas of tissue changes found earlier with volumetric measures, but were more extensive, and indicate widespread injury to tissue within critical autonomic and breathing regulatory areas, as well as prominent damage to more-rostral sites that exert influences on both breathing and cardiovascular regulation. The entropy measures provide easily-collected supplementary information using only T1-weighted images, showing aspects of tissue integrity other than volume change that are important for assessing function., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy., Methods: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit)., Results: Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE)., Interpretation: In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939., (© 2021 American Neurological Association.)

Objective: To analyze the association between peri-ictal brainstem posturing semiologies with postictal generalized electroencephalographic suppression (PGES) and breathing dysfunction in generalized convulsive seizures (GCS)., Methods: In this prospective, multicenter analysis of GCS, ictal brainstem semiology was classified as (1) decerebration (bilateral symmetric tonic arm extension), (2) decortication (bilateral symmetric tonic arm flexion only), (3) hemi-decerebration (unilateral tonic arm extension with contralateral flexion) and (4) absence of ictal tonic phase. Postictal posturing was also assessed. Respiration was monitored with thoracoabdominal belts, video, and pulse oximetry., Results: Two hundred ninety-five seizures (180 patients) were analyzed. Ictal decerebration was observed in 122 of 295 (41.4%), decortication in 47 of 295 (15.9%), and hemi-decerebration in 28 of 295 (9.5%) seizures. Tonic phase was absent in 98 of 295 (33.2%) seizures. Postictal posturing occurred in 18 of 295 (6.1%) seizures. PGES risk increased with ictal decerebration (odds ratio [OR] 14.79, 95% confidence interval [CI] 6.18-35.39, p < 0.001), decortication (OR 11.26, 95% CI 2.96-42.93, p < 0.001), or hemi-decerebration (OR 48.56, 95% CI 6.07-388.78, p < 0.001). Ictal decerebration was associated with longer PGES ( p = 0.011). Postictal posturing was associated with postconvulsive central apnea (PCCA) ( p = 0.004), longer hypoxemia ( p < 0.001), and Spo 2 recovery ( p = 0.035)., Conclusions: Ictal brainstem semiology is associated with increased PGES risk. Ictal decerebration is associated with longer PGES. Postictal posturing is associated with a 6-fold increased risk of PCCA, longer hypoxemia, and Spo 2 recovery. Peri-ictal brainstem posturing may be a surrogate biomarker for GCS severity identifiable without in-hospital monitoring., Classification of Evidence: This study provides Class III evidence that peri-ictal brainstem posturing is associated with the GCS with more prolonged PGES and more severe breathing dysfunction., (© 2020 American Academy of Neurology.)

Personalized medicine requires that treatments adapt to not only the patient but also changing factors within each individual. Although epilepsy is a dynamic disorder characterized by pathological fluctuations in brain state, surprisingly little is known about whether and how seizures vary in the same patient. We quantitatively compared within-patient seizure network evolutions using intracranial electroencephalographic (iEEG) recordings of over 500 seizures from 31 patients with focal epilepsy (mean 16.5 seizures per patient). In all patients, we found variability in seizure paths through the space of possible network dynamics. Seizures with similar pathways tended to occur closer together in time, and a simple model suggested that seizure pathways change on circadian and/or slower timescales in the majority of patients. These temporal relationships occurred independent of whether the patient underwent antiepileptic medication reduction. Our results suggest that various modulatory processes, operating at different timescales, shape within-patient seizure evolutions, leading to variable seizure pathways that may require tailored treatment approaches., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Background: Ictal and postictal testing carried out in long-term epilepsy monitoring units is often sub-optimal. Recently, a European consensus protocol for testing patients during and after seizures was developed by a joint taskforce of the International League Against Epilepsy - Commission on European Affairs and the European Epilepsy Monitoring Unit Association., Aim: Using this recently developed standardised assessment battery as a framework, the goal of this narrative review is to outline the proposed testing procedure in detail and explain the rationale for each individual component, focusing on the underlying neurobiology. This is intended to serve as an educational resource for staff working in epilepsy monitoring units., Methods: A literature review of PubMed was performed; using the search terms "seizure", "ictal", "postictal", "testing", "examination", and "interview". Relevant literature was reviewed and relevant references were chosen. The work is presented as a narrative review., Results: The proposed standardised assessment battery provides a comprehensive and user-friendly format for ictal-postictal testing, and examines consciousness, language, motor, sensory, and visual function., Conclusion: The standardised approach proposed has the potential to make full use of data recorded during video EEG increasing the diagnostic yield with regards to lateralisation and localisation, aiding both presurgical and diagnostic studies., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Ictal (ICA) and postconvulsive central apnea (PCCA) have been implicated in sudden unexpected death in epilepsy (SUDEP) pathomechanisms. Previous studies suggest that serotonin reuptake inhibitors (SRIs) and benzodiazepines (BZDs) may influence breathing. The aim of this study was to investigate if chronic use of these drugs alters central apnea occurrence in patients with epilepsy., Methods: Patients with epilepsy admitted to epilepsy monitoring units (EMUs) in nine centers participating in a SUDEP study were consented. Polygraphic physiological parameters were analyzed, including video-electroencephalography (VEEG), thoracoabdominal excursions, and pulse oximetry. Outpatient medication details were collected. Patients and seizures were divided into SRI, BZD, and control (no SRI or BZD) groups. Ictal central apnea and PCCA, hypoxemia, and electroclinical features were assessed for each group., Results: Four hundred and seventy-six seizures were analyzed (204 patients). The relative risk (RR) for ICA in the SRI group was half that of the control group (p = 0.02). In the BZD group, ICA duration was significantly shorter than in the control group (p = 0.02), as was postictal generalized EEG suppression (PGES) duration (p = 0.021). Both SRI and BZD groups were associated with smaller seizure-associated oxygen desaturation (p = 0.009; p ≪ 0.001). Neither presence nor duration of PCCA was significantly associated with SRI or BZD (p ≫ 0.05)., Conclusions: Seizures in patients taking SRIs have lower occurrence of ICA, and patients on chronic treatment with BZDs have shorter ICA and PGES durations. Preventing or shortening ICA duration by using SRIs and/or BZD in patients with epilepsy may play a possible role in SUDEP risk reduction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Generalized tonic-clonic seizures are accompanied by cardiovascular and respiratory sequelae that threaten survival. The frequency of these seizures is a major risk factor for sudden unexpected death in epilepsy (SUDEP), a leading cause of untimely death in epilepsy. The circumstances accompanying such fatal events suggest a cardiovascular or respiratory failure induced by unknown neural processes rather than an inherent cardiac or lung deficiency. Certain cortical regions, especially the insular, cingulate, and orbitofrontal cortices, are key structures that integrate sensory input and influence diencephalic and brainstem regions regulating blood pressure, cardiac rhythm, and respiration; output from those cortical regions compromised by epilepsy-associated injury may lead to cardiorespiratory dysregulation. The aim here was to assess changes in cortical integrity, reflected as cortical thickness, relative to healthy controls. Cortical alterations in areas that influence cardiorespiratory action could contribute to SUDEP mechanisms., Methods: High-resolution T1-weighted images were collected with a 3.0-Tesla MRI scanner from 53 patients with generalized tonic-clonic seizures (Mean age ± SD: 37.1 ± 12.6 years, 22 male) at Case Western Reserve University, University College London, and the University of California at Los Angeles. Control data included 530 healthy individuals (37.1 ± 12.6 years; 220 male) from UCLA and two open access databases (OASIS and IXI). Cortical thickness group differences were assessed at all non-cerebellar brain surface locations ( P  < 0.05 corrected)., Results: Increased cortical thickness appeared in post-central gyri, insula, and subgenual, anterior, posterior, and isthmus cingulate cortices. Post-central gyri increases were greater in females, while males showed more extensive cingulate increases. Frontal and temporal cortex, lateral orbitofrontal, frontal pole, and lateral parietal and occipital cortices showed thinning. The extents of thickness changes were sex- and hemisphere-dependent, with only males exhibiting right-sided and posterior cingulate thickening, while females showed only left lateral orbitofrontal thinning. Regional cortical thickness showed modest correlations with seizure frequency, but not epilepsy duration., Significance: Cortical thickening and thinning occur in patients with generalized tonic-clonic seizures, in cardiovascular and somatosensory areas, with extent of changes sex- and hemisphere-dependent. The data show injury in key autonomic and respiratory cortical areas, which may contribute to dysfunctional cardiorespiratory patterns during seizures, as well as to longer-term SUDEP risk.

Profound cardiovascular and/or respiratory dysfunction is part of the terminal cascade in sudden unexpected death in epilepsy (SUDEP). Central control of ventilation is mediated by brainstem rhythm generators, which are influenced by a variety of inputs, many of which use the modulatory neurotransmitter serotonin to mediate important inputs for breathing. The aim of this study was to investigate epileptic seizure-induced changes in serum serotonin levels and whether there are potential implications for SUDEP. Forty-one epileptic patients were pooled into 2 groups based on seizure type as (1) generalized tonic-clonic seizures (GTCS) of genetic generalized epilepsy and focal to bilateral tonic-clonic seizures (FBTCS; n = 19) and (2) focal seizures (n = 26) based on clinical signs using surface video-electroencephalography. Postictal serotonin levels were statistically significantly higher after GTCS and FBTCS compared to interictal levels (P = .002) but not focal seizures (P = .941). The change in serotonin (postictal-interictal) was inversely associated with a shorter duration of tonic phase of generalized seizures. The interictal serotonin level was inversely associated with a shorter period of postictal generalized electroencephalographic suppression. These data suggest that peripheral serum serotonin levels may play a role in seizure features and earlier postseizure recovery; these findings merit further study., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Objective: The aim of this study was to investigate periictal central apnea as a seizure semiological feature, its localizing value, and possible relationship with sudden unexpected death in epilepsy (SUDEP) pathomechanisms., Methods: We prospectively studied polygraphic physiological responses, including inductance plethysmography, peripheral capillary oxygen saturation (SpO 2 ), electrocardiography, and video electroencephalography (VEEG) in 473 patients in a multicenter study of SUDEP. Seizures were classified according to the International League Against Epilepsy (ILAE) 2017 seizure classification based on the most prominent clinical signs during VEEG. The putative epileptogenic zone was defined based on clinical history, seizure semiology, neuroimaging, and EEG., Results: Complete datasets were available in 126 patients in 312 seizures. Ictal central apnea (ICA) occurred exclusively in focal epilepsy (51/109 patients [47%] and 103/312 seizures [36.5%]) (P < .001). ICA was the only clinical manifestation in 16/103 (16.5%) seizures, and preceded EEG seizure onset by 8 ± 4.9 s, in 56/103 (54.3%) seizures. ICA ≥60 s was associated with severe hypoxemia (SpO 2 <75%). Focal onset impaired awareness (FOIA) motor onset with automatisms and FOA nonmotor onset semiologies were associated with ICA presence (P < .001), ICA duration (P = .002), and moderate/severe hypoxemia (P = .04). Temporal lobe epilepsy was highly associated with ICA in comparison to extratemporal epilepsy (P = .001) and frontal lobe epilepsy (P = .001). Isolated postictal central apnea was not seen; in 3/103 seizures (3%), ICA persisted into the postictal period., Significance: ICA is a frequent, self-limiting semiological feature of focal epilepsy, often starting before surface EEG onset, and may be the only clinical manifestation of focal seizures. However, prolonged ICA (≥60 s) is associated with severe hypoxemia and may be a potential SUDEP biomarker. ICA is more frequently seen in temporal than extratemporal seizures, and in typical temporal seizure semiologies. ICA rarely persists after seizure end. ICA agnosia is typical, and thus it may remain unrecognized without polygraphic measurements that include breathing parameters., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

There is currently no international consensus procedure for performing comprehensive periictal testing of patients in the epilepsy monitoring units (EMUs). Our primary goal was to develop a standardized procedure for managing and testing patients during and after seizures in EMUs. The secondary goal was to assess whether it could be implemented in clinical practice (feasibility). A taskforce was appointed by the International League Against Epilepsy (ILAE)-Commission on European Affairs and the European Epilepsy Monitoring Unit Association, to develop a standardized ictal testing battery (ITB) based on expert opinion and experience with various local testing protocols. ITB contains a comprehensive set of 10 items that evidence the clinically relevant semiologic features, and it is adaptive to the dynamics of the individual seizures. The feasibility of the ITB was prospectively evaluated on 250 seizures from 152 consecutive patients in 10 centers. ITB was successfully implemented in clinical practice in all 10 participating centers and was considered feasible in 93% of the tested seizures. ITB was not feasible for testing seizures of very short duration., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Direct electrical cortical stimulation (CS) is widely used to map eloquent cortex. It can be applied extraoperatively in patients undergoing intracranial EEG recordings using chronically implanted electrodes (subdural, depth or a combination), or it can be used intraoperatively. Seizures can be induced by CS but there is controversy regarding the utility of CS induced seizures in defining the epileptogenic zone and hence practice varies considerably between centres. Some centres use seizures induced by direct CS routinely to aid in defining the epileptogenic zone. In contrast, others do not rely on such information and explicitly avoid stimulating seizures during cortical mapping. Intra- and extraoperative techniques have been used to stimulate seizures with varying results, which may in part reflect these methodological differences. We here aim to review current views, definitions and studies on seizures induced by direct electrical CS. In addition we discuss mechanisms and methodological considerations of this procedure., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: We set out to determine clinical and EEG features of seizures presenting with falls, epileptic drop attacks and atonia in the video EEG monitoring unit., Methods: We searched the video EEG monitoring reports over a 5-year-period for the terms "drop", "fall" and "atonic"., Results: Seizures presenting as epileptic drop attacks, falls or atonia were found in 23/1112 (2%) admissions. About half of the patients suffering from these seizure types had developmental delay and learning difficulties and in half of the patients a lesion was seen on MRI which was often frontal. The presumed epileptogenic zone was frontal in many cases (43%), unclear with regards to a region or multifocal in 48% and posterior temporal/occipital in 2 patients (9%). EEG patterns recorded were paroxysmal fast activity, spike and wave discharges and EEG attenuation. Seizure related falls were seen in 8 cases (34%) with injuries recorded during Video EEG monitoring in half of those., Conclusion: Clinical and EEG features outlined here can help the clinician to recognise patients at risk for these devastating seizure types., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623)., Methods: Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS., Results: Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials., Conclusions: The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine whether resection of areas with evidence of intense, synchronized neural firing during seizures is an accurate indicator of postoperative outcome., Methods: Channels meeting phase-locked high gamma (PLHG) criteria were identified retrospectively from intracranial EEG recordings (102 seizures, 46 implantations, 45 patients). Extent of removal of both the seizure onset zone (SOZ) and PLHG was correlated with seizure outcome, classified as good (Engel class I or II, n = 32) or poor (Engel class III or IV, n = 13)., Results: Patients with good outcomes had significantly greater proportions of both SOZ and the first 4 (early) PLHG sites resected. Improved outcome classification was noted with early PLHG, as measured by the area under the receiver operating characteristic curves (PLHG 0.79, SOZ 0.68) and by odds ratios for resections including at least 75% of sites identified by each measure (PLHG 9.7 [95% CI: 2.3-41.5], SOZ 5.3 [95% CI: 1.2-23.3]). Among patients with resection of at least 75% of the SOZ, 78% (n = 30) had good outcomes, increasing to 91% when the resection also included at least 75% of early PLHG sites (n = 22)., Conclusions: This study demonstrates the localizing value of early PLHG, which is comparable to that provided by the SOZ. Incorporation of PLHG into the clinical evaluation may improve surgical efficacy and help to focus resections on the most critical areas., (© 2015 American Academy of Neurology.)

This study aimed to determine clinical features of adult patients with gelastic seizures recorded on video -electroencephalography (EEG) over a 5-year period. We screened video-EEG telemetry reports for the occurrence of the term "gelastic" seizures, and assessed the semiology, EEG features, and duration of those seizures. Gelastic seizures were identified in 19 (0.8%) of 2,446 admissions. The presumed epileptogenic zone was in the hypothalamus in one third of the cases, temporal lobe epilepsy was diagnosed in another third, and the remainder of the cases presenting with gelastic seizures were classified as frontal, parietal lobe epilepsy or remained undetermined or were multifocal. Gelastic seizures were embedded in a semiology, with part of the seizure showing features of automotor seizures. A small proportion of patients underwent epilepsy surgery. Outcome of epilepsy surgery was related to the underlying pathology; two patients with hippocampal sclerosis had good outcomes following temporal lobe resection and one of four patients with hypothalamic hamartomas undergoing gamma knife surgery had a good outcome., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

This study sought to determine the frequency and clinical significance of nonhabitual seizures in 101 consecutive patients undergoing presurgical intracranial electroencephalography intracranial (icEEG) recording. We compared clinical data, recording details, and postsurgical outcome in patients with nonhabitual seizures to those without nonhabitual seizures during icEEG. In patients with nonhabitual seizures we compared icEEG recordings of nonhabitual seizures to recordings of habitual seizures. Nonhabitual seizures were recorded in 10% of patients. Those patients had a significantly higher rate of procedure-related complications compared to patients without nonhabitual seizures. Ultimate seizure outcome did not differ between the groups. Nonhabitual seizures often occurred within the first 3 days of icEEG recording and had larger seizure-onset zones compared to the patient's habitual seizures. Nonhabitual seizures have no effect on outcome of epilepsy surgery but may serve as important markers of procedure-related complications during icEEG., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Background: Since intracranial electrode implantation has limited spatial sampling and carries significant risk, placement has to be effective and efficient. Structural and functional imaging of several different modalities contributes to localising the seizure onset zone (SoZ) and eloquent cortex. There is a need to summarise and present this information throughout the pre/intra/post-surgical course., Methods: We developed and implemented a multimodal 3D neuroimaging (M3N) pipeline to guide implantation of intracranial EEG (icEEG) electrodes. We report the implementation of the pipeline for operative planning and a description of its use in clinical decision-making., Results: The results of intraoperative application of the M3N pipeline demonstrated clinical benefits in all 15 implantation surgeries assessed. The M3N software was used to simulate placement of intracranial electrodes in 2 cases. The key benefits of using the M3N pipeline are illustrated in 3 representative case reports., Conclusion: We have demonstrated feasibility of the developed intraoperative M3N pipeline which serves as a prototype for clinical implementation. Further validity studies with larger sample groups are required to determine the utility of M3N in routine surgical practice., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

A 28-year-old patient with pharmacoresistant non-lesional right frontal epilepsy underwent extra-operative intracranial EEG recordings and electrical cortical stimulation (ECS) to map eloquent cortex. Right supplementary motor area (SMA) ECS induced a brief seizure with habitual symptoms involving neck tingling followed by asymmetric tonic posturing. An additional feature was neck atonia. During atonia and sensory aura, discharges were seen in the mesial frontal electrodes and precentral gyrus. Besides motor signs, atonia, although rare and not described in the neck muscles, and sensations have been reported with SMA stimulation. The mechanisms underlying neck atonia in seizures arising from the SMA can be explained by supplementary negative motor area (SNMA) - though this was not mapped in electrodes overlying the ictal onset zone in our patient - or primary sensorimotor cortex activation through rapid propagation. Given the broad spectrum of signs elicited by SMA stimulation and rapid spread of seizures arising from the SMA, caution should be taken to not diagnose these as non-epileptic, as had previously occurred in this patient., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Asymmetric cortical representation of cardiac function is a matter of debate and large inter-individual variability of cortical autonomic networks and different study designs may contribute to this controversy. Lateralised seizure activity in individual patients may provide valuable insights into cortical regulation of cardiac function. We report two patients with focal epilepsy who had seizures arising from both hemispheres. In Patient 1, heart rate increased over two-fold with seizures arising from the right hemisphere, whereas heart rate increased invariably less with seizures arising from the left hemisphere. In Patient 2, heart rate increased 1.3 fold or less with seizures arising from the left hemisphere, whereas a seizure with right-sided onset was followed by bradycardia and asystole. Our findings support the notion that effects on autonomic function are lateralised, although lateralisation varies from patient to patient. This may partially explain the difficulty in determining cortical representation of cardiac autonomic function.

We describe a 42-year old patient with right hand sensorimotor seizures who underwent extraoperative cortical stimulation mapping (CSM) of the left primary motor cortex (M1). Cortical stimulation of the region where primary motor cortex was expected evoked exclusively complex motor responses with proximal right arm and proximal left leg asymmetric tonic movements that are usually observed on stimulation of the supplementary motor area (SMA). Right hand function could not be isolated during either extraoperative or intraoperative cortical stimulation of the anatomical M1 representation. Ictal and interictal activity was contained within the region with the abnormal motor response, and MEG of interictal activity showed spike propagation from the left mesial to lateral frontal cortex. This propagation pathway may have facilitated M1-to-SMA connectivity and therefore explain the unusual motor response after stimulation of M1. This case highlights the potential impact of interictal activity on plasticity of the motor cortex., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The postictal state is defined as manifestation of seizure-induced reversible alterations in neuronal function, but not structure. Following a seizure, it is common to experience feelings of exhaustion, both mental and physical, that can last a day or two. There are three major hypotheses regarding what cellular and molecular mechanisms could cause the observed postictal symptoms: neurotransmitter depletion or changes in receptor concentration, active inhibition, and cerebral blood flow changes. Here, we describe the contributions of functional neuroimaging studies to the understanding of postictal symptoms., (Copyright © 2010 Elsevier Inc. All rights reserved.)

[March 2008-Cleveland Case Report]. There is a well-described association between the occurrence of developmental tumors and the presence of cortical dysplasia in the neighboring brain tissue. The main surgical approaches in the treatment of medically refractory epilepsy related to such developmental tumors include a lesionectomy versus a tailored cortical resection, often guided by an invasive evaluation. This case report describes the surgical management of a 26-year-old female with olfactory auras evolving into automotor seizures and convulsions, occurring in the context of a right temporo-parietal developmental lesion. It illustrates the pros and cons of various surgical approaches, and discusses some pathophysiological aspects of developmental tumors, dysplasia and epilepsy. [Published with video sequences].

OBJECTIVE: To determine the relationship between serum serotonin (5-HT) levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA) in epileptic seizures. METHODS: We prospectively evaluated video EEG, plethysmography, capillary oxygen saturation (SpO2), and ECG for 49 patients (49 seizures) enrolled in a multicenter study of sudden unexpected death in epilepsy (SUDEP). Postictal and interictal venous blood samples were collected after a clinical seizure for measurement of serum 5-HT levels. Seizures were classified according to the International League Against Epilepsy 2017 seizure classification. We analyzed seizures with and without ICA (n = 49) and generalized convulsive seizures (GCS) with and without PCCA (n = 27). RESULTS: Postictal serum 5-HT levels were increased over interictal levels for seizures without ICA (p = 0.01), compared to seizures with ICA (p = 0.21). In patients with GCS without PCCA, serum 5-HT levels were increased postictally compared to interictal levels (p < 0.001), but not in patients with seizures with PCCA (p = 0.22). Postictal minus interictal 5-HT levels also differed between the 2 groups with and without PCCA (p = 0.03). Increased heart rate was accompanied by increased serum 5-HT levels (postictal minus interictal) after seizures without PCCA (p = 0.03) compared to those with PCCA (p = 0.42). CONCLUSIONS: The data suggest that significant seizure-related increases in serum 5-HT levels are associated with a lower incidence of seizure-related breathing dysfunction, and may reflect physiologic changes that confer a protective effect against deleterious phenomena leading to SUDEP. These results need to be confirmed with a larger sample size study.

Introduction: Peri-ictal breathing dysfunction was proposed as a potential mechanism for SUDEP. We examined the incidence and risk factors for both ictal (ICA) and post-convulsive central apnea (PCCA) and their relationship with potential seizure severity biomarkers (i. e., post-ictal generalized EEG suppression (PGES) and recurrence. Methods: Prospective, multi-center seizure monitoring study of autonomic, and breathing biomarkers of SUDEP in adults with intractable epilepsy and monitored seizures. Video EEG, thoraco-abdominal excursions, capillary oxygen saturation, and electrocardiography were analyzed. A subgroup analysis determined the incidences of recurrent ICA and PCCA in patients with ≥2 recorded seizures. We excluded status epilepticus and obscured/unavailable video. Central apnea (absence of thoracic-abdominal breathing movements) was defined as ≥1 missed breath, and ≥5 s. ICA referred to apnea preceding or occurring along with non-convulsive seizures (NCS) or apnea before generalized convulsive seizures (GCS). Results: We analyzed 558 seizures in 218 patients (130 female); 321 seizures were NCS and 237 were GCS. ICA occurred in 180/487 (36.9%) seizures in 83/192 (43.2%) patients, all with focal epilepsy. Sleep state was related to presence of ICA [RR 1.33, CI 95% (1.08-1.64), p = 0.008] whereas extratemporal epilepsy was related to lower incidence of ICA [RR 0.58, CI 95% (0.37-0.90), p = 0.015]. ICA recurred in 45/60 (75%) patients. PCCA occurred in 41/228 (18%) of GCS in 30/134 (22.4%) patients, regardless of epilepsy type. Female sex [RR 11.30, CI 95% (4.50-28.34), p < 0.001] and ICA duration [RR 1.14 CI 95% (1.05-1.25), p = 0.001] were related to PCCA presence, whereas absence of PGES was related to absence of PCCA [0.27, CI 95% (0.16-0.47), p < 0.001]. PCCA duration was longer in males [HR 1.84, CI 95% (1.06-3.19), p = 0.003]. In 9/17 (52.9%) patients, PCCA was recurrent. Conclusion: ICA incidence is almost twice the incidence of PCCA and is only seen in focal epilepsies, as opposed to PCCA, suggesting different pathophysiologies. ICA is likely to be a recurrent semiological phenomenon of cortical seizure discharge, whereas PCCA may be a reflection of brainstem dysfunction after GCS. Prolonged ICA or PCCA may, respectively, contribute to SUDEP, as evidenced by two cases we report. Further prospective cohort studies are needed to validate these hypotheses.

ObjectiveGeneralized tonic-clonic seizures are accompanied by cardiovascular and respiratory sequelae that threaten survival. The frequency of these seizures is a major risk factor for sudden unexpected death in epilepsy (SUDEP), a leading cause of untimely death in epilepsy. The circumstances accompanying such fatal events suggest a cardiovascular or respiratory failure induced by unknown neural processes rather than an inherent cardiac or lung deficiency. Certain cortical regions, especially the insular, cingulate, and orbitofrontal cortices, are key structures that integrate sensory input and influence diencephalic and brainstem regions regulating blood pressure, cardiac rhythm, and respiration; output from those cortical regions compromised by epilepsy-associated injury may lead to cardiorespiratory dysregulation. The aim here was to assess changes in cortical integrity, reflected as cortical thickness, relative to healthy controls. Cortical alterations in areas that influence cardiorespiratory action could contribute to SUDEP mechanisms.MethodsHigh-resolution T1-weighted images were collected with a 3.0-Tesla MRI scanner from 53 patients with generalized tonic-clonic seizures (Mean age ± SD: 37.1 ± 12.6 years, 22 male) at Case Western Reserve University, University College London, and the University of California at Los Angeles. Control data included 530 healthy individuals (37.1 ± 12.6 years; 220 male) from UCLA and two open access databases (OASIS and IXI). Cortical thickness group differences were assessed at all non-cerebellar brain surface locations (P