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Community-acquired pneumonia is a considerable cause of morbidity and mortality and contributes significantly to healthcare resource utilization worldwide. Clinical practice guidelines developed by international societies have been published to improve the diagnosis, management, and prevention of community-acquired pneumonia. This review of current guidelines is aimed at choosing an appropriate therapeutic approach including local considerations, site of care decisions, diagnostic testing, antimicrobial therapy, and prevention. [ABSTRACT FROM AUTHOR]

This and the following two papers describe event-related potentials (ERPs) evoked by visual stimuli in 98 patients in whom electrodes were placed directly upon the cortical surface to monitor medically intractable seizures. Patients viewed pictures of faces, scrambled faces, letter-strings, number-strings, and animate and inanimate objects. This paper describes ERPs generated in striate and peristriate cortex, evoked by faces, and evoked by sinusoidal gratings, objects and letter-strings. Short-latency ERPs generated in striate and peristriate cortex were sensitive to elementary stimulus features such as luminance. Three types of face-specific ERPs were found: (i) a surface-negative potential with a peak latency of 200 ms (N200) recorded from ventral occipitotemporal cortex, (ii) a lateral surface N200 recorded primarily from the middle temporal gyrus, and (iii) a late positive potential (P350) recorded from posterior ventral occipitotemporal, posterior lateral temporal and anterior ventral temporal cortex. Face-specific N200s were preceded by P150 and followed by P290 and N700 ERPs. N200 reflects initial face-specific processing, while P290, N700 and P350 reflect later face processing at or near N200 sites and in anterior ventral temporal cortex. Face-specific N200 amplitude was not significantly different in males and females, in the normal and abnormal hemisphere, or in the right and left hemisphere. However, cortical patches generating ventral face-specific N200s were larger in the right hemisphere. Other cortical patches in the same region of extrastriate cortex generated grating-sensitive N180s and object-specific or letter-string-specific N200s, suggesting that the human ventral object recognition system is segregated into functionally discrete regions. [ABSTRACT FROM AUTHOR]

Introduction: Cerebellar hemorrhage following supratentorial craniotomy is rare. Its clinical symptoms are often mild and transient.Discussion: Here, we report a case of cerebellar hemorrhage associated with iliofemoral vein thrombosis as a complication of anterior temporal lobectomy and amygdalohippocampectomy for refractory medial temporal epilepsy. [ABSTRACT FROM AUTHOR]

It is increasingly understood that the epilepsies are characterized by network pathology that can span multiple spatial and temporal scales. Recent work indicates that infraslow (<0.2 Hz) envelope correlations may form a basis for distant spatial coupling in the brain. We speculated that infraslow correlation structure may be preserved even with some time lag between signals. To this end, we studied intracranial EEG (icEEG) data collected from 22 medically refractory epilepsy patients. For each patient, we selected hour-long background, awake icEEG epochs before and after antiseizure medication (ASM) taper. For each epoch, we selected 5,000 random electrode contact pairs and estimated magnitude-squared coherence (MSC) below 0.15 Hz of band power time-series in the traditional EEG frequency bands. Using these same contact pairs, we shifted one signal of the pair by random durations in 15-s increments between 0 and 300 s. We aggregated these data across all patients to determine how infraslow MSC varies with duration of lag. We further examined the effect of ASM taper on infraslow correlation structure. We also used surrogate data to empirically characterize MSC estimator and to set optimal parameters for estimation specifically for the study of infraslow activity. Our empirical analysis of the MSC estimator showed that hour-long segments with MSC computed using 3-min windows with 50% overlap was sufficient to capture infraslow envelope correlations while minimizing estimator bias and variance. The mean MSC decreased monotonically with increasing time lag until 105 s of lag, then plateaued between 106 and 300 s. Significantly nonzero infraslow envelope MSC was preserved in all frequency bands until about 1 min of time lag, both pre- and post-ASM taper. We also saw a slight, but significant increase in infraslow MSC post-ASM taper, consistent with prior work. These results provide evidence for the feasibility of examining infraslow activity via its modulation of higher-frequency activity in the absence of DC-coupled recordings. The use of surrogate data also provides a general methodology for benchmarking measures used in network neuroscience studies. Finally, our study points to the clinical relevance of infraslow activity in assessing seizure risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Joshi, Duckrow, Goncharova, Hirsch, Spencer, Godwin and Zaveri.)

Functional coactivation between human brain regions is partly explained by white matter connections; however, how the structure-function relationship varies by function remains unclear. Here, we reference large data repositories to compute maps of structure-function correspondence across hundreds of specific functions and brain regions. We use natural language processing to accurately predict structure-function correspondence for specific functions and to identify macroscale gradients across the brain that correlate with structure-function correspondence as well as cortical thickness. Our findings suggest structure-function correspondence unfolds along a sensory-fugal organizational axis, with higher correspondence in primary sensory and motor cortex for perceptual and motor functions, and lower correspondence in association cortex for cognitive functions. Our study bridges neuroscience and natural language to describe how structure-function coupling varies by region and function in the brain, offering insight into the diversity and evolution of neural network properties., (© 2024. The Author(s).)

Background: The cingulate gyrus (CG), a brain structure above the corpus callosum, is recognised as part of the limbic system and plays numerous vital roles. However, its full functional capacity is yet to be understood. In recent years, emerging evidence from imaging modalities, supported by electrical cortical stimulation (ECS) findings, has improved our understanding. To our knowledge, there is a limited number of systematic reviews of the cingulate function studied by ECS. We aim to parcellate the CG by reviewing ECS studies., Design/methods: We searched PubMed and Embase for studies investigating CG using ECS. A total of 30 studies met the inclusion criteria. We evaluated the ECS responses across the cingulate subregions and summarised the reported findings., Results: We included 30 studies (totalling 887 patients, with a mean age of 31.8±9.8 years). The total number of electrodes implanted within the cingulate was 3028 electrode contacts; positive responses were obtained in 941 (31.1%, median percentages, 32.3%, IQR 22.2%-64.3%). The responses elicited from the CG were as follows. Simple motor (8 studies, 26.7 %), complex motor (10 studies, 33.3%), gelastic with and without mirth (7 studies, 23.3%), somatosensory (9 studies, 30%), autonomic (11 studies, 36.7 %), psychic (8 studies, 26.7%) and vestibular (3 studies, 10%). Visual and speech responses were also reported. Despite some overlap, the results indicate that the anterior cingulate cortex is responsible for most emotional, laughter and autonomic responses, while the middle cingulate cortex controls most complex motor behaviours, and the posterior cingulate cortex (PCC) regulates visual, among various other responses. Consistent null responses have been observed across different regions, emphasising PCC., Conclusions: Our results provide a segmental mapping of the functional properties of CG, helping to improve precision in the surgical planning of epilepsy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Using 6-minute free-running intracranial-electroencephalogram (icEEG) during sleep, an optimized multilayer perceptron (MLP) neural network accurately maps the sensorimotor cortex (SM) and identifies the anterior lip of the central sulcus (CS) in intractable epilepsy patients. We calculated 6 performance metrics to evaluate the MLP's efficacy: accuracy, area under the curve (AUC), recall, precision, F1-scores, and specificity. Each layer had 4 neurons with hyperbolic TanH activation function and 4 with Gaussian distribution function. Conventional 10-fold cross-validation was used. Feature extension (ε) and weighted imbalanced data (w) improved MLP performance. ANN NEUROL 2024;96:187-193., (© 2024 American Neurological Association.)

Objective: Medically refractory epilepsy (MRE) often requires resection of the seizure onset zone (SOZ) for effective treatment. However, when the SOZ is in functional cortex (FC), achieving complete and safe resection becomes difficult, due to the seizure network overlap with function. The authors aimed to assess the safety and outcomes of a combined approach involving partial resection combined with focal neuromodulation for FC refractory epilepsy., Methods: The authors performed a retrospective analysis of individuals diagnosed with MRE who underwent surgical intervention from January 2015 to December 2022. Patients whose SOZ was located in FC and were treated with resection combined with simultaneous implantation of a focal neuromodulation device (responsive neurostimulation [RNS] device) with more than 12 months of follow-up data were included. All patients underwent a standard epilepsy preoperative assessment including intracranial electroencephalography and extraoperative stimulation mapping. Resections were performed under general anesthesia, followed by the concurrent implantation of an RNS device., Results: Seven patients (4 males, median age 32.3 years, all right-handed) were included. The median interval from seizure onset to surgery was 17.4 years. The epileptogenic network included sensorimotor areas (cases 2, 3, and 6), visual cortex (case 1), language areas (cases 4 and 7), and the insula (case 5). The median follow-up was 3 years (range 1-5.8 years). No significant changes in neuropsychological tests were reported. One permanent nondisabling planned neurological deficit (left inferior quadrantanopia) was observed. Six patients had stimulation activated at a median of 4.7 months after resection. All patients achieved good seizure outcomes (5 with Engel class I and 2 with Engel class II outcomes)., Conclusions: Maximal safe resection combined with focal neuromodulation presents a promising alternative to stand-alone resections for MRE epileptogenic zones overlapping with functional brain. This combined approach prioritizes the preservation of function while improving seizure outcomes.

Objective: To prospectively investigate the utility of seizure induction using systematic 1 Hz stimulation by exploring its concordance with the spontaneous seizure onset zone (SOZ) and relation to surgical outcome; comparison with seizures induced by non-systematic 50 Hz stimulation was attempted as well., Methods: Prospective cohort study from 2018 to 2021 with ≥ 1 y post-surgery follow up at Yale New Haven Hospital. With 1 Hz, all or most of the gray matter contacts were stimulated at 1, 5, and 10 mA for 30-60s. With 50 Hz, selected gray matter contacts outside of the medial temporal regions were stimulated at 1-5 mA for 0.5-3s. Stimulation was bipolar, biphasic with 0.3 ms pulse width. The Yale Brain Atlas was used for data visualization. Variables were analyzed using Fisher's exact, χ 2 , or Mann-Whitney test., Results: Forty-one consecutive patients with refractory epilepsy undergoing intracranial EEG for localization of SOZ were included. Fifty-six percent (23/41) of patients undergoing 1 Hz stimulation had seizures induced, 83% (19/23) habitual (clinically and electrographically). Eighty two percent (23/28) of patients undergoing 50 Hz stimulation had seizures, 65% (15/23) habitual. Stimulation of medial temporal or insular regions with 1 Hz was more likely to induce seizures compared to other regions [15/32 (47%) vs. 2/41 (5%), p < 0.001]. Sixteen patients underwent resection; 11/16 were seizure free at one year and all 11 had habitual seizures induced by 1 Hz; 5/16 were not seizure free at one year and none of those 5 had seizures with 1 Hz (11/11 vs 0/5, p < 0.0001). No patients had convulsions with 1 Hz stimulation, but four did with 50 Hz (0/41 vs. 4/28, p = 0.02)., Significance: Induction of habitual seizures with 1 Hz stimulation can reliably identify the SOZ, correlates with excellent surgical outcome if that area is resected, and may be superior (and safer) than 50 Hz for this purpose. However, seizure induction with 1 Hz was infrequent outside of the medial temporal and insular regions in this study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown., Objective: To test the association between pathogenic somatic variants in the hippocampus and MTLE., Design, Setting, and Participants: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from 1988 through 2019, and clinical data were collected retrospectively. Whole-exome and gene-panel sequencing (each genomic region sequenced more than 500 times on average) were used to identify candidate pathogenic somatic variants. A subset of novel variants was functionally evaluated using cellular and molecular assays. Patients with nonlesional and lesional (mesial temporal sclerosis, focal cortical dysplasia, and low-grade epilepsy-associated tumors) drug-resistant MTLE who underwent anterior medial temporal lobectomy were eligible. All patients with available frozen tissue and appropriate consents were included. Control brain tissue was obtained from neurotypical donors at brain banks. Data were analyzed from June 2020 to August 2022., Exposures: Drug-resistant MTLE., Main Outcomes and Measures: Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex., Results: Of 105 included patients with MTLE, 53 (50.5%) were female, and the median (IQR) age was 32 (26-44) years; of 30 neurotypical controls, 11 (36.7%) were female, and the median (IQR) age was 37 (18-53) years. Eleven pathogenic somatic variants enriched in the hippocampus relative to the unaffected temporal neocortex (median [IQR] variant allele frequency, 1.92 [1.5-2.7] vs 0.3 [0-0.9]; P = .01) were detected in patients with MTLE but not in controls. Ten of these variants were in PTPN11, SOS1, KRAS, BRAF, and NF1, all predicted to constitutively activate Ras/Raf/mitogen-activated protein kinase (MAPK) signaling. Immunohistochemical studies of variant-positive hippocampal tissue demonstrated increased Erk1/2 phosphorylation, indicative of Ras/Raf/MAPK activation, predominantly in glial cells. Molecular assays showed abnormal liquid-liquid phase separation for the PTPN11 variants as a possible dominant gain-of-function mechanism., Conclusions and Relevance: Hippocampal somatic variants, particularly those activating Ras/Raf/MAPK signaling, may contribute to the pathogenesis of sporadic, drug-resistant MTLE. These findings may provide a novel genetic mechanism and highlight new therapeutic targets for this common indication for epilepsy surgery.

Background and Importance: Stereotactic laser amygdalohippocampotomy (SLAH) using laser interstitial thermal therapy is a minimally invasive surgery used to treat mesial temporal lobe epilepsy. It uses laser probes inserted through occipital and temporo-occipital trajectories to ablate the hippocampus and amygdala. However, these trajectories are limited in their ability to ablate the superior amygdala and entorhinal cortex (ERC). We present a trajectory through the middle frontal gyrus as an alternative to the temporo-occipital trajectory, which provides more complete ablation of the amygdala and anterior ERC through a single pass., Clinical Presentation: A 70-year-old woman with seizures characterized by fear were localized to the left superomedial amygdala on intracranial electroencephalography. They developed after resection of a left temporal arteriovenous malformation and were refractory to medication. Her age and prior craniotomy made open resection less desirable. A frontal and occipital SLAH achieved Engel 1a at 1-year follow-up without decline in neuropsychological performance scores., Conclusion: Typical SLAH uses trajectories that have limited ability to ablate the superior and medial amygdala and ERC in a single passage. A combined approach using an occipital and frontal trajectory allows more complete ablation of the amygdala, hippocampus, and ERC., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Purpose of Review: Technological innovations in the preoperative evaluation, surgical techniques and outcome prediction in epilepsy surgery have grown exponentially over the last decade. This review highlights and emphasizes relevant updates in techniques and diagnostic tools, discussing their context within standard practice at comprehensive epilepsy centres., Recent Findings: High-resolution structural imaging has set an unprecedented opportunity to detect previously unrecognized subtle abnormalities. Machine learning and computer science are impacting the methodologies to analyse presurgical and surgical outcome data, building more accurate prediction models to tailor treatment strategies. Robotic-assisted placement of depth electrodes has increased the safety and ability to sample epileptogenic nodes within deep structures, improving our understanding of the seizure networks in drug-resistant epilepsy. The current available minimally invasive techniques are reasonable surgical alternatives to ablate or disrupt epileptogenic regions, although their sustained efficacy is still an active area of research., Summary: Epilepsy surgery is still underutilized worldwide. Every patient who continues with seizures despite adequate trials of two well selected and tolerated antiseizure medications should be evaluated for surgical candidacy. Collaboration between academic epilepsy centres is of paramount importance to answer long-standing questions in epilepsy surgery regarding the understanding of spatio-temporal dynamics in epileptogenic networks and its impact on surgical outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: The cingulate gyrus (CG) is a frequently studied yet not wholly understood area of the human cerebrum. Previous studies have implicated CG in different adaptive cognitive-emotional functions and fascinating or debilitating symptoms. We describe an unusual loss of gravity perception/floating sensation in consecutive persons with drug-resistant epilepsy undergoing electrical cortical stimulation (ECS), network analysis, and network robustness mapping., Methods: Using Intracranial-EEG, Granger causality analysis, cortico-cortical evoked potentials, and fMRI, we explicate the functional networks arising from this phenomenon's anterior, middle, and posterior cingulate cortex., Results: Fifty-four icEEG cases from 2013 to 2019 were screened. In 40.7% of cases, CG was sampled and in 22.2% the sampling was bilateral. ECS mapping was carried out in 18.5% of the entire cohort and 45.4% of the cingulate sampled cases. Five of the ten CG cases experienced symptoms during stimulation. A total of 1942 electrodes were implanted with a median number of 182 electrode contacts per patient (range: 106-274). The electrode contacts sampled all major cortex regions. Sixty-three contacts were within CG. Of those, 26 were electrically stimulated; 53.8% of the stimulated contacts produced positive responses, whereas 46.2% produced no observable responses. Our study reports a unique perceptive phenomenon of a subjective sense of weightlessness/floating sensation triggered by anterior and posterior CG stimulation, in 30% of cases and 21.42% of electrode stimulation sites. Notable findings include functional connections between the insula, the posterior and anterior cingulate cortex, and networks between the middle cingulate and the frontal and temporal lobes and the cerebellum. We also postulate a vestibular-cerebral-cingulate network responsible for the perception of gravity while suggesting that cingulate functional connectivity follows a long-term developmental trajectory as indicated by a robust, positive correlation with age and the extent of Granger connectivity (r = 0.82, p = 0.0035)., Discussion: We propose, in conjunction with ECS techniques, that a better understanding of the underlying gravity perception networks can lead to promising neuromodulatory clinical applications., Classification of Evidence: This study provides Class II evidence for CG's involvement in the higher order processing of gravity perception and related actions., (© 2022. The Author(s).)

Precise cortical brain localization presents an important challenge in the literature. Brain atlases provide data-guided parcellation based on functional and structural brain metrics, and each atlas has its own unique benefits for localization. We offer a parcellation guided by intracranial electroencephalography, a technique which has historically provided pioneering advances in our understanding of brain structure-function relationships. We used a consensus boundary mapping approach combining anatomical designations in Duvernoy's Atlas of the Human Brain, a widely recognized textbook of human brain anatomy, with the anatomy of the MNI152 template and the magnetic resonance imaging scans of an epilepsy surgery cohort. The Yale Brain Atlas consists of 690 one-square centimeter parcels based around conserved anatomical features and each with a unique identifier to communicate anatomically unambiguous localization. We report on the methodology we used to create the Atlas along with the findings of a neuroimaging study assessing the accuracy and clinical usefulness of cortical localization using the Atlas. We also share our vision for the Atlas as a tool in the clinical and research neurosciences, where it may facilitate precise localization of data on the cortex, accurate description of anatomical locations, and modern data science approaches using standardized brain regions., (© 2022. The Author(s).)

Background: Glossokinetic artifact (GKA) is a well-known scalp EEG artifact characterized by deflections within the delta to low-theta frequency bands and dynamic polarity typically attributed to the direction of tongue movement. This study aims to investigate intracranial EEG correlations of scalp-GKA. If the tongue is a dipole, per the conventional view, then volume-conducted deflections are expected in the nearest frontal intracranial EEG contacts., Materials and Methods: Simultaneous scalp and intracranial EEG recordings were evaluated in five consecutive medically resistant epilepsy patients at Yale Epilepsy Center in 2017 and 2018, who had classic GKA deflections on scalp EEG. The EEG was sampled at 2,048 to 4,096 Hz and analyzed visually, using a reference placed in the diploic space or over the convexity, and confirmed quantitatively by a statistical framework. Ten GKA deflections were analyzed per case., Results: The medians of age at the time of recording, contacts per case, and amplitude of scalp GKA deflections were 35 years (range: 20-41 years), 171 contacts (range: 165-241 contacts), and 56 μV (range: 51-72 μV), respectively. There were no slow discharges in the frontal intracranial EEG contacts synchronized with the scalp GKA, either in the delta (1-3 Hz) or in the sub-delta (0.1-1 Hz) bands. However, the expected physiologic attenuation of alpha and beta rhythms and the emergence of high-gamma activity were observed over the peri-Rolandic regions in the invasive recordings., Conclusions: The traditional view of the tongue as a dipole generator of scalp GKA is simplistic and does not account for the findings reported herein. The tongue most probably shunts other scalp and soft-tissue currents. Knowledge of tongue potentials is of interest in the education and the design of tongue-computer interfaces., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Dramatic changes have occurred recently in the field of epilepsy, including a fundamental shift in the etiology of epileptogenic substrates found at surgery. Hippocampal sclerosis is no longer the most common etiology found at epilepsy surgery and this decrease has been associated with an increase in the incidence of focal cortical dysplasia and encephaloceles. Significant advances have been made in molecular biology and genetics underlying the basis of malformations of cortical development, and our ability to detect epileptogenic abnormalities with MR imaging has markedly improved. This article begins with a discussion of these trends and reviews imaging techniques essential for detecting of subtle epilepsy findings. Representative examples of subtle imaging findings are presented, which are often overlooked but should not be missed. These include temporal lobe encephaloceles, malformations of cortical development (and especially focal cortical dysplasia), hippocampal sclerosis, hippocampal malformation (also known as HIMAL), ulegyria, autoimmune encephalitis, and Rasmussen's encephalitis. Recent findings on the pathophysiology and genetic underpinnings of several causes of localization-related epilepsy are incorporated. For instance, it has been recently found that focal cortical dysplasia IIb, tuberous sclerosis, hemimegalencephaly, and gangliogliomas are all the result of mutations of the mTOR pathway for cell growth.

We test the performance of a novel operator-independent EEG-based method for passive identification of the central sulcus (CS) and sensorimotor (SM) cortex. We studied seven patients with intractable epilepsy undergoing intracranial EEG (icEEG) monitoring, in whom CS localization was accomplished by standard methods. Our innovative approach takes advantage of intrinsic properties of the primary motor cortex (MC), which exhibits enhanced icEEG band-power and coherence across the CS. For each contact, we computed a composite power, coherence, and entropy values for activity in the high gamma band (80-115) Hz of 6-10 min of NREM sleep. Statistically transformed EEG data values that did not reach a threshold (th) were set to 0. We computed a metric M based on the transformed values and the mean Euclidian distance of each contact from contacts with Z-scores higher than 0. The last step was implemented to accentuate local network activity. The SM cortex exhibited higher EEG-band-power than non-SM cortex (P < 0.0002). There was no significant difference between the motor/premotor and sensory cortices (P < 0.47). CS was localized in all patients with 0.4 < th < 0.6. The primary hand and leg motor areas showed the highest metric values followed by the tongue motor area. Higher threshold values were specific (94%) for the anterior bank of the CS but not sensitive (42%). Intermediate threshold values achieved an acceptable trade-off (0.4: 89% specific and 70% sensitive)., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: The aim of this study was to identify predictors of a resective surgery and subsequent seizure freedom following intracranial EEG (ICEEG) for seizure-onset localization., Methods: This is a retrospective chart review of 178 consecutive patients with medically refractory epilepsy who underwent ICEEG monitoring from 2002 to 2015. Univariable and multivariable regression analysis identified independent predictors of resection vs other options. Stepwise Akaike information criteria with the aid of clinical consideration were used to select the best multivariable model for predicting resection and outcome. Discrete time survival analysis was used to analyze the factors predicting seizure-free outcome. Cumulative probability of seizure freedom was analyzed using Kaplan-Meier curves and compared between resection and nonresection groups. Additional univariate analysis was performed on 8 select clinical scenarios commonly encountered during epilepsy surgical evaluations., Results: Multivariable analysis identified the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant as independent predictors of resection ( p < 0.0001, area under the receiver operating characteristic curve 0.80, 95% CI 0.73-0.87). Focal ICEEG onset and undergoing a resective surgery predicted absolute seizure freedom at the 5-year follow-up. Patients who underwent resective surgery were more likely to be seizure-free at 5 years compared with continued medical treatment or neuromodulation (60% vs 7%; p < 0.0001, hazard ratio 0.16, 95% CI 0.09-0.28). Even patients thought to have unfavorable predictors (nonlesional MRI or extratemporal lobe hypothesis or dominant hemisphere implant) had ≥50% chance of seizure freedom at 5 years if they underwent resection., Discussion: Unfavorable predictors, including having nonlesional extratemporal epilepsy, should not deter a thorough presurgical evaluation, including with invasive recordings in many cases. Resective surgery without functional impairment offers the best chance for sustained seizure freedom and should always be considered first., Classification of Evidence: This study provides Class II evidence that the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant are independent predictors of resection. Focal ICEEG onset and undergoing resection are independent predictors of 5-year seizure freedom., (© 2022 American Academy of Neurology.)

This is the first known case report of a profound illusionary time dilation produced by direct electrical cortical stimulation. The patient with drug-resistant epilepsy was undergoing invasive EEG evaluation for the localization of the focus prior to resection. Stimulation of the non-dominant claustrum/insula and inferior right frontal gyrus correlated with the equivalent of a pacemaker of an internal clock in the brain. The site exhibited strong outflow connectivity with a wide region of the right fronto-parietal executive network and pre-motor system. The patient described the experience as unique and fascinating, and underwent resection involving the face motor area where seizures arose from, with a substantial decrease in seizure burden >90%. Extensive brain networks are employed in evaluation/assessment of time, which may be modulated via electrical stimulation. This is the first of such an incident. Further studies may investigate the potential benefit of neuromodulation of these brain regions in the management of conditions in which time-perception may be impaired.

Objective: To evaluate the role of intracranial electroencephalography monitoring in diagnosing and directing the appropriate therapy for MRI-negative epilepsy and to present the surgical outcomes of patients following treatment., Methods: Retrospective chart review between 2015-2021 at a single institution identified 48 patients with no lesion on MRI, who received surgical intervention for their epilepsy. The outcomes assessed were the surgical treatment performed and the International League Against Epilepsy seizure outcomes at 1 year of follow-up., Results: Eleven patients underwent surgery without invasive monitoring, including vagus nerve stimulation (10%), deep brain stimulation (8%), laser interstitial thermal therapy (2%), and callosotomy (2%). The remaining 37 patients received invasive monitoring followed by resection (35%), responsive neurostimulation (21%), and deep brain stimulation (15%) or no treatment (6%). At 1 year postoperatively, 39% were Class 1-2, 36% were Class 3-4 and 24% were Class 5. More patients with Class 1-2 or 3-4 outcomes underwent invasive monitoring (100% and 83% respectively) compared with those with poor outcomes (25%, P < .001). Patients with Class 1-2 outcomes more commonly underwent resection or responsive neurostimulation: 69% and 31%, respectively (P < .001)., Significance: The optimal management of MRI-negative focal epilepsy may involve invasive monitoring followed by resection or responsive neurostimulation in most cases, as these treatments were associated with the best seizure outcomes in our cohort. Unless multifocal onset is clear from the noninvasive evaluation, invasive monitoring is preferred before pursuing deep brain stimulation or vagal nerve stimulation directly., (© 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

About one-third of epilepsy cases are refractory to medical therapy. During the past decades, the availability of surgical epilepsy interventions has substantially increased as therapeutic options for this group of patients. A wide range of surgical interventions and electrophysiologic neuromodulation techniques are available, including lesional resection, lobar resection, thermoablation, disconnection, multiple subpial transections, vagus nerve stimulation, responsive neurostimulation, and deep brain stimulation. The indications and imaging features of potential complications of the newer surgical interventions may not be widely appreciated, particularly if practitioners are not associated with comprehensive epilepsy centers. In this article, we review a wide range of invasive epilepsy treatment modalities with a particular focus on their postoperative imaging findings and complications. A state-of-the-art treatment algorithm provides context for imaging findings by helping the reader understand how a particular invasive treatment decision is made., (© 2021 by American Journal of Neuroradiology.)

Objective: Temporal lobe encephaloceles (TLENs) are a significant cause of medically refractory epilepsy, but there is little consensus regarding their workup and treatment. This study characterizes these lesions and their role in seizures and aims to standardize preoperative evaluation and surgical management., Methods: Patients with TLEN who had undergone resective epilepsy surgery from December 2015 to August 2020 at a single institution were included in the study. Medical records were reviewed for each patient to collect relevant seizure workup information including demographics, radiological findings, surgical data, and neuropsychological evaluation., Results: For patients who presented to the authors' program with suspected medically intractable temporal lobe epilepsy (219 patients), TLEN was considered to be the epileptogenic focus in 5.5%. Ten patients with TLEN had undergone resection and were included in this study. Concordance between ictal scalp electroencephalography (EEG) lateralization and TLEN was found in 9/10 patients (90%), and 4/10 patients (40%) had signs suggestive of idiopathic intracranial hypertension (IIH). Surgical outcome was reported in patients with at least 12 months of follow-up (9/10). Patients with scalp EEG findings concordant with the TLEN side had a good outcome (Engel class I: 7 patients, class II: 1 patient). One patient with discordant EEG findings had a bad outcome (Engel class III). No significant neuropsychological deficits were observed after the surgery., Conclusions: TLENs are epileptogenic lesions that should be screened for in patients with medically refractory epilepsy who have signs of IIH and no other lesions on MRI. Restricted resection is safe and effective in patients with scalp EEG findings concordant with TLEN.

The objective of this study was to monitor the extracellular brain chemistry dynamics at baseline and in relation to spontaneous seizures in human patients with refractory epilepsy. Thirty patients with drug-resistant focal epilepsy underwent intracranial electroencephalography and concurrent brain microdialysis for up to 8 continuous days. Extracellular brain glutamate, glutamine, and the branched-chain amino acids (BCAAs) valine, leucine, and isoleucine were quantified in the dialysis samples by liquid chromatography-tandem mass spectrometry. Extracellular BCAAs and glutamate were chronically elevated at baseline by approximately 1.5-3-fold in brain regions of seizure onset and propagation versus regions not involved by seizures. Moreover, isoleucine increased significantly above baseline as early as 3 h before a spontaneous seizure. BCAAs play important roles in glutamatergic neurotransmission, mitochondrial function, neurodegeneration, and mammalian target of rapamycin signaling. Because all of these processes have been implicated in epilepsy, the results suggest a novel role of BCAAs in the pathogenesis of spontaneous seizures., (© 2021 International League Against Epilepsy.)

Objective: To test the hypothesis that glutamate and GABA are linked to the formation of epilepsy networks and the triggering of spontaneous seizures, we examined seizure initiation/propagation characteristics and neurotransmitter levels during epileptogenesis in a translationally relevant rodent model of mesial temporal lobe epilepsy., Methods: The glutamine synthetase (GS) inhibitor methionine sulfoximine was infused into one of the hippocampi in laboratory rats to create a seizure focus. Long-term video-intracranial EEG recordings and brain microdialysis combined with mass spectrometry were used to examine seizure initiation, seizure propagation, and extracellular brain levels of glutamate and GABA., Results: All seizures (n = 78 seizures, n = 3 rats) appeared first in the GS-inhibited hippocampus of all animals, followed by propagation to the contralateral hippocampus. Propagation time decreased significantly from 11.65 seconds early in epileptogenesis (weeks 1-2) to 6.82 seconds late in epileptogenesis (weeks 3-4, paired t test, p = 0.025). Baseline extracellular glutamate levels were 11.6-fold higher in the hippocampus of seizure propagation (7.3 µM) vs the hippocampus of seizure onset (0.63 µM, analysis of variance/Fisher least significant difference, p = 0.01), even though the concentrations of the major glutamate transporter proteins excitatory amino acid transporter subtypes 1 and 2 and xCT were unchanged between the brain regions. Finally, extracellular GABA in the seizure focus decreased significantly from baseline several hours before a spontaneous seizure (paired t test/false discovery rate)., Conclusion: The changes in glutamate and GABA suggest novel and potentially important roles of the amino acids in epilepsy network formation and in the initiation and propagation of spontaneous seizures., (© 2021 American Academy of Neurology.)

Intraoperative electrocorticography (ECoG) is a useful technique to guide resections in epilepsy surgery and is mostly performed under general anesthesia. In this systematic literature review, we seek to investigate the effect of anesthetic agents on the quality and reliability of ECoG for localization of the epileptic focus. We conducted a systematic search using PubMed and EMBASE until January 2019, aiming to review the effects of anesthesia on ECoG yield. Fifty-eight studies were included from 1016 reviewed. There are favorable reports for dexmedetomidine and remifentanil during ECoG recording. There is inadequate, or sometimes conflicting, evidence to support using enflurane, isoflurane, sevoflurane, and propofol. There is evidence to avoid halothane, nitrous oxide, etomidate, ketamine, thiopental, methohexital, midazolam, fentanyl, and alfentanil due to undesired effects. Depth of anesthesia, intraoperative awareness, and surgical outcomes were not consistently evaluated. Available studies provide helpful information about the effect of anesthesia on ECoG to localize the epileptic focus. The proper use of anesthetic agents and careful dose titration, and effective communication between the neurophysiologist and anesthesiologist based on ECoG activity are essential in optimizing recordings. Anesthesia is a crucial variate to consider in the design of studies investigating ECoG and related biomarkers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The causative link between focal cortical malformations (FCMs) and epilepsy is well accepted, especially among patients with focal cortical dysplasia type II (FCDII) and tuberous sclerosis complex (TSC). However, the mechanisms underlying seizures remain unclear. Using a mouse model of TSC- and FCDII-associated FCM, we showed that FCM neurons were responsible for seizure activity via their unexpected abnormal expression of the hyperpolarization-activated cyclic nucleotide-gated potassium channel isoform 4 (HCN4), which is normally not present in cortical pyramidal neurons after birth. Increasing intracellular cAMP concentrations, which preferentially affects HCN4 gating relative to the other isoforms, drove repetitive firing of FCM neurons but not control pyramidal neurons. Ectopic HCN4 expression was dependent on the mechanistic target of rapamycin (mTOR), preceded the onset of seizures, and was also found in diseased neurons in tissue resected from patients with TSC and FCDII. Last, blocking HCN4 channel activity in FCM neurons prevented epilepsy in the mouse model. These findings suggest that HCN4 play a main role in seizure and identify a cAMP-dependent seizure mechanism in TSC and FCDII. Furthermore, the unique expression of HCN4 exclusively in FCM neurons suggests that gene therapy targeting HCN4 might be effective in reducing seizures in FCDII or TSC., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: To recount the evolution of Electrical Cortical Stimulation (ECS) in localizing brain functions with an emphasis on epilepsy, and a discussion of related instruments and personnel., Design/methods: Literature review through historical archives implementing chain-referral sampling., Results: There were important milestones leading to the incorporation of ECS into practice: 1. Aldini's (1802) first known stimulation of exposed brain to defend Galvani's views on excitability in the frog-leg experiment against Volta's, ironically by employing the Voltaic pile. 2. Animal experiments in the 19th-century to study the brain and to optimize the procedure: Rolando (1809) reported on motor induction, Fritsch and Hitzig (ca. 1870) introduced the concepts of bipolar and threshold stimulation, and Ferrier (1873) generated reproducible homunculi in animals. 3. Parallel to 2, advances were made based on clinical observations by Bravais, Todd, Jackson, and Broca among others. 4. First known stimulation in conscious humans by Bartholow (1874) led to catastrophic outcomes. Horsley (1886) performed first intraoperative stimulation on Jackson's epileptic patient. 5. Advances accelerated in the first-half of the 20th century with Cushing (1909) performing first awake-craniotomy eliciting sensory responses to Penfield's work culminating in standardization of clinical use and generation of detailed maps including the famous sensory-motor homunculi. Parallel advances in instrumentation were made from the Leyden jar (1745) to present customizable current-controlled stimulators., Conclusions: ECS is commonly used in neurosurgery for localization of brain functions and is the benchmark for research studies. Significant leaps have been made since ECS first used in the 19th century. It evolved to remain the gold standard for localization of human brain functions in the 21st century., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: In this positron emission tomography (PET) study with [ 11 C]UCB-J, we evaluated synaptic vesicle glycoprotein 2A (SV2A) binding, which is decreased in resected brain tissues from epilepsy patients, in subjects with temporal lobe epilepsy (TLE) and compared the regional binding pattern to [ 18 F]fluorodeoxyglucose (FDG) uptake., Methods: Twelve TLE subjects and 12 control subjects were examined. Regional [ 11 C]UCB-J binding potential (BP ND ) values were estimated using the centrum semiovale as a reference region. [ 18 F]FDG uptake in TLE subjects was quantified using mean radioactivity values. Asymmetry in outcome measures was assessed by comparison of ipsilateral and contralateral regions. Partial volume correction (PVC) with the iterative Yang algorithm was applied based on the FreeSurfer segmentation., Results: In 11 TLE subjects with medial temporal lobe sclerosis (MTS), the hippocampal volumetric asymmetry was 25 ± 11%. After PVC, [ 11 C]UCB-J BP ND asymmetry indices were 37 ± 19% in the hippocampus, with very limited asymmetry in other brain regions. Reductions in [ 11 C]UCB-J BP ND values were restricted to the sclerotic hippocampus when compared to control subjects. The corresponding asymmetry in hippocampal [ 18 F]FDG uptake was 22 ± 7% and correlated with that of [ 11 C]UCB-J BP ND across subjects (R 2  = .38). Hippocampal asymmetries in [ 11 C]UCB-J binding were 1.7-fold larger than those of [ 18 F]FDG uptake., Significance: [ 11 C]UCB-J binding is reduced in the seizure onset zone of TLE subjects with MTS. PET imaging of SV2A may be a promising biomarker approach in the presurgical selection and evaluation of TLE patients and may improve the sensitivity of molecular imaging for seizure focus detection., (© 2020 International League Against Epilepsy.)

The term 'implantation effect' is used to describe an immediate and transient improvement in seizure frequency following an intracranial study for seizure onset localization. We conducted a retrospective analysis of 190 consecutive patients undergoing intracranial electroencephalogram (EEG) monitoring, of whom 41 had no subsequent resection/ablation/stimulation; 33 had adequate data and follow-up time available for analysis. Analysis of seizure frequency following an intracranial study showed 36% (12/33) responder rate (>50% seizure reduction) at one year, decreasing and stabilizing at 20% from year 4 onwards. In addition, we describe three patients (9%) who had long term seizure freedom of more than five years following electrode implantation alone, two of whom had thalamic depth electrodes. Electrode implantation perhaps leads to a neuromodulatory effect sufficient enough to disrupt epileptogenic networks. Rarely, this may be significant enough to even result in long term seizure freedom, as seen in our three patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Magnetic resonance (MR) imaging is an essential tool in the diagnosis and management of pituitary diseases, indispensable for making correct treatment decisions. Successful management and follow-up of pituitary pathology requires an understanding of the MR appearance of normal and abnormal structures in the sellar region. This review will describe the MR appearance of the normal and abnormal pituitary gland and proposes an algorithm for the management strategy of some of the most common abnormalities in or around the sella.

Seizures often exhibit striking circadian-like (~24-h) rhythms. While chronotherapy has shown promise in treating epilepsy, it is not widely used, in part because the patterns of seizure rhythmicity vary considerably among patients and types of epilepsy. A better understanding of the mechanisms underlying rhythmicity in epilepsy could be expected to result in more effective approaches which can be tailored to each individual patient. The excitatory neurotransmitter glutamate is an essential modulator of circadian rhythms, and changes in the extracellular levels of glutamate likely affect the threshold to seizures. We used a reverse translational rodent model of mesial temporal lobe epilepsy (MTLE) combined with long-term intracerebral microdialysis to monitor the hourly concentrations of glutamate in the seizure onset area (epileptogenic hippocampus) over several days. We observed significant 24-h oscillations of extracellular glutamate in the epileptogenic hippocampus ( n = 4, JTK&#95;CYCLE test, p < 0.05), but not in the hippocampus of control animals ( n = 4). To our knowledge, circadian glutamate oscillations have not been observed in a seizure onset region, and we speculate that the oscillations contribute to the rhythmicity of seizures in MTLE., (Copyright © 2020 Sandhu, Dhaher, Gruenbaum, Raaisa, Spencer, Pavlova, Zaveri and Eid.)

Dynamic attention states are necessary to navigate the ever changing task demands of daily life. Previous investigations commonly utilize a block paradigm to study sustained and transient changes in attention networks. fMRI investigations have shown that sustained attention in visual block design attention tasks corresponds to decreased signal in the default mode and visual processing networks. While task negative networks are anticipated to decrease during active task engagement, it is unexpected that visual networks would also be suppressed during a visual task where event-related fMRI studies have found transient increases to visual stimuli. To resolve these competing results, the current investigations utilized intracranial EEG to directly interrogate visual and default mode network dynamics during a visual continuous performance task. We used the electrophysiological data to model expected fMRI signals and to maximize interpretation of current results with previous investigations. Results show broadband gamma power decreases in the default mode network, corresponding to previous EEG and fMRI findings. Meanwhile, visual processing regions including the primary visual cortex and fusiform gyrus demonstrate both sustained decreases during task engagement and stimuli-driven transient increases in gamma power. Modeled fMRI based on gamma power reproduces signal decreases reported in the fMRI literature, and emphasizes the insensitivity of fMRI to transient, regularly spaced signal changes embedded within sustained network dynamics. The signal processing functions of the dynamic visual and default mode network changes explored in this study are unknown but may be elucidated through further investigation., (Copyright © 2019. Published by Elsevier Inc.)