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Background: Firearm homicides disproportionately affect young Black men, which in turn have lasting impact of communities of color as a whole. Previous cross-sectional studies have highlighted the role of discriminatory housing policies on the incidence of urban firearm violence. We sought to estimate the effects of racist housing policies on firearm incidence., Methods: Firearm incident data were obtained from the Boston Police Department and point locations spatially joined with vector files outlining the original 1930 Home Owner Loan Corporation (HOLC) Redlining maps. A regression discontinuity design was used to assess the increased rate of firearm violence crossing from historically "desirable" neighborhoods (Green) to historically "hazardous" neighborhoods (Red and Yellow) based on HOLC definitions. Linear regression models were fit on either side of the geographic boundaries with firearm incidents graphed at varying distances and the regression coefficient calculated at the boundary., Results: Crossing from desirable to Red hazardous designation there was a significant discontinuity with an increase of 4.1 firearm incidents per 1,000 people (95% CI 0.68,7.55). Similarly, when crossing from desirable areas to the Yellow hazardous designation there was a significant discontinuity and increase of 5.9 firearm incidents per 1,000 people (95% CI 1.85,9.86). There was no significant discontinuity between the two hazardous HOLC designations (coefficient -0.93, 95% CI -5.71, 3.85)., Conclusions: There is a significant increase in firearm incidents in historically redlined areas of Boston. This suggests that interventions should focus on downstream socioeconomic, demographic, and neighborhood detriments of historically discriminatory housing policies in order to address firearm homicides., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest, (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: Violence-related reinjury impacts both patients and health care systems. Mental illness (MI) is prevalent among violently injured individuals. The relationship between preexisting MI and violent reinjury among women has not been fully characterized. Our objective was to determine if risk of hospital reencounter-violent reinjury and all-cause-was associated with preexisting MI at time of index injury among female victims of violence., Methods: All females (15-100 + years) presenting to a level I trauma center with violent injury (2002-2019) surviving to discharge were included (N = 1,056). Exposure was presence of preexisting MI. The primary outcome was hospital reencounters for violent reinjury and all-cause within one year (through 2020). The secondary outcome was the development of a new MI within one year of index injury. Odds of reencounter and development of new MI for those with and without preexisting MI were compared with multivariable logistic regression, stratified for interaction when appropriate., Results: There were 404 women (38%) with preexisting MI at time of index injury. Approximately 11% of patients with preexisting MI experienced violent reinjury compared to 5% of those without within 1 year ( p < 0.001). Specifically, those with MI in the absence of concomitant substance use had more than three times the odds of violent reinjury (adjusted Odds Ratio, 3.52 (1.57, 7.93); p = 0.002). Of those with preexisting MI, 64% had at least one reencounter for any reason compared to 46% of those without ( p < 0.001 ) . Odds of all-cause reencounter for those with preexisting MI were nearly twice of those without (adjusted Odds Ratio, 1.81 [1.36, 2.42]; p < 0.0001)., Conclusion: Among female victims of violence, preexisting MI is associated with a significantly increased risk of hospital reencounter and violent reinjury within the first year after index injury. Recognition of this vulnerable population and improved efforts at addressing MI in trauma patients is critical to ongoing prevention efforts to reduce violent reinjury., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Much of the recorded medical literature focuses on individual-level factors that contribute to firearm violence. Recently, studies have highlighted higher incidence of firearm violence in historically redlined and marginalized areas, but few have gone on to study the downstream associations causing these differences. This study aims to understand the effects of historic redlining and current income mobility on firearm violence., Methods: Using a retrospective cross-sectional design, shooting incidents were spatially joined with redlining vector files and linked to income mobility data (how much a child makes in adulthood). Participants included all assault and homicide incidents involving a firearm in the city of Boston, between 2016 and 2019. The exposure of interest was redlining designation as outlined by the Home Owner's Loan Corporation (HOLC) in the 1930s and income mobility, stratified by race, defined as the income of a child in their 30s compared with where they grew up (census tract level). The outcome measured was shooting rate per census block., Results: We find that increases in Black income mobility (BIM) and White income mobility (WIM) are associated with significant decreases in rates of firearm incidents in all HOLC designations; however, there is a larger decrease with increasing BIM (relative risk, 0.47 per unit increase in BIM [95% confidence interval, 0.35-0.64]; relative risk, 0.81 per unit increase in WIM [95% confidence interval, 0.71-0.93]). Plotting predicted rates of firearm violence in each HOLC designation at different levels of BIM, there were no significant differences in shooting rates between historically harmful and beneficial classifications above $50,000 of BIM. Despite level of WIM, there were continued disparities between harmful and beneficial HOLC classification., Conclusion: These findings highlight the importance of structural racism in the form of redlining and discriminatory housing policies, and the preclusion from economic mobility therein, on the incidence of firearm violence today., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Following the declaration of the COVID-19 pandemic, there were reports of decreased trauma hospitalizations, although violent crime persisted. COVID-19 has had the greatest impact on minoritized and vulnerable communities. Decreases in traumatic events may not extend to these communities, given pandemic-related socioeconomic and psychological burdens that increase the risk of exposure to trauma and violence., Materials and Methods: This was a retrospective cohort study (n = 1634) of all trauma activations presenting to our institution January 1, 2020 to May 31, 2020, and same time periods in 2018 and 2019. Census tracts and associated Social Vulnerability Index quartiles were determined from patient addresses. Changes in trauma activations pre and post Massachusetts' state-of-emergency declaration compared to a historical control were analyzed using a difference-in-differences methodology., Results: Weekly all-cause trauma activations fell from 26.44 to 8.25 (rate ratio = 0.36 [0.26, 0.50]) postdeclaration, with significant difference-in-differences compared to a historical control (P < 0.0001). Nonviolent trauma activations significantly decreased from 21.11 to 5.17 after the declaration (rate ratio = 0.27 [0.37, 0.91]; P < 0.0001), whereas there was no significant decrease in violent injury (5.33 to 3.08 rate ratio = 0.69 [0.39, 1.22]; P = 0.20). Stratified by vulnerability, the most vulnerable quartile had an increased proportion of all-cause trauma postdeclaration and had no decrease in violent trauma activations following the declaration compared to the historical control (rate ratio = 0.84 [0.38-1.86]; P = 0.67)., Conclusions: The state-of-emergency declaration was associated with significant decreases in overall trauma, to a greater extent in nonviolent injuries. Among those living in the most socially vulnerable communities, there was no decrease in violent trauma. These findings highlight the need for violence and injury prevention programs in vulnerable communities, particularly in times of crisis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Firearm injury remains a major cause of morbidity and mortality in the United States. Because of prior lack of comprehensive data sources, there is a paucity of literature on nonfatal firearm injury. Associations have previously been shown between state-level firearm laws and firearm fatalities, but few studies have examined the effects of these laws on nonfatal firearm hospitalization rates. Our objective was to examine the relationship between state firearm laws and firearm injury-related hospitalization rates across all 50 states over a 17-year period., Methods: In this panel study design, we used fixed effects multivariate regression models to analyze the relationship between 12 laws and firearm state-level injury-related hospitalization rates from 2000 to 2016 using the RAND Corporation Inpatient Hospitalizations for Firearm Injury Database. We used difference-in-differences to determine the impact of law passage in a given state compared with those states without the law, controlling for state-level covariates. The main outcome measure was the change in annual firearm injury-related inpatient hospitalization rates after passage or repeal of a state-level firearm law., Results: Examining each law individually, passage of violent misdemeanor, permitting, firearm removal from domestic violence offenders, and 10-round limit laws were associated with significant firearm injury-related hospitalization rate reductions. Examining multiple laws in the same model, passage of violent misdemeanor laws was associated with a 19.9% (confidence interval, 11.6%-27.4%) reduction, and removal of firearms from domestic violence offenders was associated with a 17.0% (confidence interval, 9.9%-23.6%) reduction in hospitalization rates., Conclusion: State laws related to preventing violent offenders from possessing firearms are associated with firearm injury-related hospitalization rate reductions. Given significant physical, mental, and social burdens of nonfatal firearm injury, determining the efficacy of firearm-related policy is critical to violence and injury prevention efforts., Level of Evidence: Prognostic and Epidemiologic; Level IV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Firearm homicides disproportionately affect Black communities. Redlining - discriminatory lending practices of the early 20 th century - are associated with current increased rates of firearm violence. Poverty and concentrated disadvantage are also associated with firearm violence. The interaction of these factors with racist redlining housing practices remains unclear., Methods: We used generalized structural equation modeling to characterize the mediators through which redlining practices of the 1930s led to present rates of firearm violence in Boston using a negative binomial model. Principle component analysis was used to create four distinct mediating variables representing census block socioeconomic and built environment information, while reducing dimensionality. We calculated the direct effect between harmful (Red and Yellow) vs beneficial (Green) designations and firearm incident rate, indirect effect between redlining designation and firearm incident rate through each mediating variable, and the total effect. The percentage mediation of each mediator was subsequently calculated., Findings: Red and Yellow areas of Boston were associated with an 11•1 (95% CI 5•5,22•4) and 11•4 (5•7,22•8) increased incident rate of shooting when compared to Green. In the pathway between Red designation and firearm incident rate, poverty and poor educational attainment mediated 20% of the interaction, share of rented housing mediated 8%, and Black share of the population 3%. In the pathway between Yellow designation and firearm incident rate, poverty and poor educational attainment mediated 16% of the association, and Black share of the population mediated 13%., Interpretation: Redlining practices of the 1930s potentially contribute to increased rates of firearm violence through changes to neighborhood environments, namely through preclusion from homeownership, poverty, poor educational attainment, and concentration (i.e. segregation) of Black communities. These downstream mediating factors serve as points for policy interventions to address urban firearm violence., Funding: Michael Poulson and Miriam Neufeld were supported by T32 Training Grants (HP10028, GM86308)., Competing Interests: Declaration of interest The authors have nothing to disclose.

While "stay-at-home" orders for COVID-19 were in effect, many American cities witnessed a rise in community and interpersonal violence. Our own institution, the largest regional trauma facility and Boston's safety net hospital, saw a paradoxical rise in penetrating violent trauma admissions despite decreases in other hospital admissions, leading to our most violent summer in five years. It has been established that minoritized and marginalized communities have faced the harshest impacts of the pandemic. Our findings suggest that the conditions created by the COVID-19 pandemic have amplified the inequities that exist in communities of color that place them at risk for exposure to violence. The pandemic has served to potentiate the impacts of violence already plaguing the communities and patients we serve., (Copyright © 2021. Published by Elsevier Inc.)

Background: Acute cholecystitis is a common reason for emergency general surgery admission. The declaration of the COVID-19 pandemic may have resulted in treatment delays and corresponding increases in severity of disease. This study compared cholecystitis admissions and disease severity pre- and postdeclaration of pandemic., Materials and Methods: Retrospective review of adult acute cholecystitis admissions (January 1,2020-May 31, 2020). Corresponding time periods in 2018 and 2019 comprised the historical control. Difference-in-differences analysis compared biweekly cholecystitis admissions pre- and postdeclaration in 2020 to the historical control. Odds of increased severity of disease presentation were assessed using multivariable logistic regression., Results: Cholecystitis admissions decreased 48.7% from 5.2 to 2.67 cases (RR 0.51 [0.28,0.96], P = 0.04) following pandemic declaration when comparing 2020 to historical control (P = 0.02). After stratifying by severity, only Tokyo I admissions declined significantly postdeclaration (RR 0.42 [0.18,0.97]), when compared to historical control (P = 0.02). There was no change in odds of presenting with severe disease after the pandemic declaration (aOR 1.00 [95% CI 0.30, 3.38] P < 0.99) despite significantly longer lengths of symptoms reported in mild cases., Conclusions: Postpandemic declaration we experienced a significant decrease in cholecystitis admissions without corresponding increases in disease severity. The pandemic impacted healthcare-seeking behaviors, with fewer mild presentations. Given that the pandemic did not increase odds of presenting with increased severity of disease, our data suggests that not all mild cases of cholecystitis progress to worsening disease and some may resolve without medical or surgical intervention., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The coronavirus disease 2019 pandemic restricted movement of individuals and altered provision of health care, abruptly transforming health care-use behaviors. It serves as a natural experiment to explore changes in presentations for surgical diseases including acute appendicitis. The objective was to determine if the pandemic was associated with changes in incidence of acute appendicitis compared to a historical control and to determine if there were associated changes in disease severity., Methods: The study is a retrospective, multicenter cohort study of adults (N = 956) presenting with appendicitis in nonpandemic versus pandemic time periods (December 1, 2019-March 10, 2020 versus March 11, 2020-May 16, 2020). Corresponding time periods in 2018 and 2019 composed the historical control. Primary outcome was mean biweekly counts of all appendicitis presentations, then stratified by complicated (n = 209) and uncomplicated (n = 747) disease. Trends in presentations were compared using difference-in-differences methodology. Changes in odds of presenting with complicated disease were assessed via clustered multivariable logistic regression., Results: There was a 29% decrease in mean biweekly appendicitis presentations from 5.4 to 3.8 (rate ratio = 0.71 [0.51, 0.98]) after the pandemic declaration, with a significant difference in differences compared with historical control (P = .003). Stratified by severity, the decrease was significant for uncomplicated appendicitis (rate ratio = 0.65 [95% confidence interval 0.47-0.91]) when compared with historical control (P = .03) but not for complicated appendicitis (rate ratio = 0.89 [95% confidence interval 0.52-1.52]); (P = .49). The odds of presenting with complicated disease did not change (adjusted odds ratio 1.36 [95% confidence interval 0.83-2.25])., Conclusion: The pandemic was associated with decreased incidence of uncomplicated appendicitis without an accompanying increase in complicated disease. Changes in individual health care-use behaviors may underlie these differences, suggesting that some cases of uncomplicated appendicitis may resolve without progression to complicated disease., (Published by Elsevier Inc.)

Despite being a common form of abuse, there is a paucity of literature describing shackling and wrist restraint injuries among survivors of torture. Forensic evaluation of alleged wrist restraint/handcuff injuries in survivors of torture presents challenges to the evaluator, especially if the injuries are remote and do not leave lasting marks nor neurologic deficits. Thorough history-taking and physical examination are critical to effective forensic documentation. Guidance is provided in The Manual on Effective Investigation and Documentation of Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment (Istanbul Protocol), the gold standard for the medicolegal documentation of torture. This guidance relies primarily on physical findings, with less direction provided on how to interpret historical evidence or when historical evidence provided by the patient can be interpreted as highly consistent with alleged injury in the absence of current physical findings. Through a case-based review, we present diagnostic strategies for the evaluation of alleged abuse involving wrist restraints/handcuffs, focusing on skin, neurologic, and osseous injuries. We highlight key findings from both the history and physical examination that will allow the evaluator to improve the accuracy of their expert medical opinion on the degree to which medical findings correlate with the patient's allegations of wrist restraint injuries.

Background: Violent trauma has lasting psychological impacts. Our institution's Community Violence Response Team (CVRT) offers mental health services to trauma victims. We characterized implementation and determined factors associated with utilization by pediatric survivors of interpersonal violence-related penetrating trauma., Methods: Analysis included survivors (0-21 years) of violent penetrating injury at our institution (2011-2017). Injury and demographic data were collected. Nonparametric regression models determined factors associated with utilization., Results: There was initial rapid uptake of CVRT (2011-2013) after which it plateaued, serving >80% of eligible patients (2017). White race and higher injury severity were associated with receipt and duration of services. In post-hoc analysis, race was found to be associated with continued treatment but not with initial consultation., Conclusion: Successful implementation required three years, aiding >80% of patients. CVRT is a blueprint to strengthen existing violence intervention programs. Efforts should be made to ensure that barriers to providing care, including those related to race, are overcome., (Published by Elsevier Inc.)

Objectives: We aimed to estimate the frequency of epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) with atypical duration in our epilepsy monitoring unit (EMU), in order to raise awareness of atypical durations of both types of events., Materials & Methods: We retrospectively reviewed all consecutive video-electroencephalogram (vEEG) recordings in our medical center's EMU from January 2013 to December 2017 and identified patients with seizures with atypical duration. Short PNES were defined as those lasting fewer than 2 min and long ES as those lasting for more than 5 min., Results: The files of 830 adult (age >16 years) patients were reviewed, of whom 26 patients (3.1%, mean age: 33.3 ± 9.8 years, 12 females) were diagnosed as having an unusual seizure duration. Among 432 patients with ES during monitoring, fourteen patients [3.2% (95% confidence interval (CI): 1.5%-5.0%), mean age: 33.0 ± 12.2, 5 females [had long ES durations (exceeding 5 min). In 64% of patients with long ES, the events were provoked by antiepileptic drug (AED) withdrawal during vEEG, 62% had focal lesion on brain imaging, and 64% had a frontotemporal or a temporal seizure focus. Among 223 patients diagnosed with PNES, 12 patients [5.4% (95% CI: 2.2%-8.6%), mean age: 33.6 ± 6.6, 7 females] had short PNES durations (less than 2 min) and demonstrated motor (9/12, 75%), altered responsiveness (6/12, 50%), and vocalization (5/12, 42%) as the most prominent clinical features., Conclusions: The data from our case files highlight two main considerations in the diagnosis of paroxysmal events: prolonged event can be due to ES, while short events can be psychogenic., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Multiple studies have demonstrated that, compared with their full code counterparts, patients with do-not-resuscitate or do-not-intubate status have higher in-hospital and postdischarge mortality than predicted by clinical characteristics alone. We sought to determine whether patient code status affects surgical resident decision making., Methods: We created an online survey that consisted of 4 vignettes, followed by 10 questions regarding decisions on possible diagnostic and therapeutic interventions. All program directors of Accreditation Council for Graduate Medical Education-accredited general surgery residencies were randomized to receive 1 of 2 survey versions that differed only in the code status of the patients described, with requests to distribute the survey to their residents. Responses to each question were based on a Likert scale., Results: A total of 194 residents completed the survey, 51% of whom were women, and all years of surgical residency were represented. In all vignettes, patient code status influenced perioperative medical decisions, ranging from initiation of dialysis to intensive care unit transfer. In 2 vignettes, it affected decisions to proceed with indicated emergency operations., Conclusion: When presented with patient scenarios pertaining to clinical decision making, surgical residents tend to assume that patients with a do-not-resuscitate or do-not-intubate code status would prefer to receive less aggressive care overall. As a result, the delivery of appropriate surgical care may be improperly limited unless a patient's goals of care are explicitly stated. It is important for surgical residents to understand that a do-not-resuscitate or do-not-intubate code status should not be interpreted as a "do-not-treat" status., (Published by Elsevier Inc.)

Status epilepticus (SE) is a life-threatening condition characterized by ongoing seizure activity which can lead to severe brain damage and death if not treated properly. Recent work suggests that alterations in blood-brain barrier (BBB) function and subsequent cortical exposure to coagulation factors may initiate, promote, and/or sustain SE. This suggestion is based on the observation that the serine protease thrombin, which plays a fundamental role in the blood coagulation cascade, increases neural excitability through the activation of protease-activated receptor 1 (PAR1). However, it remains unclear whether systemic inhibition of thrombin asserts "anti-epileptic" effects in vivo. We here used the pilocarpine model of SE in adult 3-month-old male mice to address the question whether intraperitoneal injection of the thrombin inhibitor α-NAPAP (0.75 mg/kg) counters SE. Indeed, pharmacological inhibition of thrombin ameliorates the behavioral outcome of pilocarpine-induced SE. Similar results are obtained when the thrombin receptor PAR1 is pharmacologically blocked using intraperitoneal injection of SCH79797 (25 μg/kg) prior to SE induction. Consistent with these results, an increase in thrombin immunofluorescence is detected in the hippocampus of pilocarpine-treated animals. Moreover, increased hippocampal serine protease activity is detected 90 min after SE induction, which is not observed in animals treated with α-NAPAP prior to SE induction. Together, these results corroborate and extend recent studies suggesting that novel oral anticoagulants which target thrombin (and PAR1) may assert anti-epileptic effects in vivo. KEY MESSAGES: Systemic thrombin/PAR1-inhibition ameliorates anticoagulants behavioral seizures. Status epilepticus increases thrombin levels in the hippocampus. Increased serine protease activity in the hippocampus after status epileptic. Anti-epileptic potential of clinically used anticoagulants must be evaluated.

Objectives. To compare donations to individual politicians from physician organization political action committees (PACs) and from the National Rifle Association Political Victory Fund (NRA PVF) in 2018. Methods. We identified 7 organizations with published firearm injury prevention policy. We determined the difference in funds received from physician organization PACs and the NRA PVF for each congressmember. We examined their voting records on firearm-related legislation. Results. A total of 141 congressmembers received funds from both physician organization PACs and the NRA PVF. Of these, 99.3% voted for legislation not consistent with organization recommendations. The majority (70.2%) received more funds from the combined physician organization PACs than from the NRA PVF. Conclusions. Physician organization PACs have a financial impact on NRA-backed congressmembers. They currently contribute to politicians with voting records inconsistent with their own policy recommendations. Firearm violence prevention does not currently outweigh other legislative priorities for physician organization PAC contributions.

Objective: Experiential phenomena (EP), such as illusions and complex hallucinations, are vivid experiences created in one's mind. They can occur spontaneously as epileptic auras or can be elicited by electrical brain stimulation (EBS) in patients undergoing presurgical evaluation for drug-resistant epilepsy. Previous work suggests that EP arise from activation of different nodes within interconnected neural networks mainly in the temporal lobes. Yet, the anatomical extent of these neural networks has not been described and the question of lateralization of EP has not been fully addressed. To this end, an extended number of brain regions in which electrical stimulation elicited EP were studied to test whether there is a lateralization propensity to EP phenomena., Methods: A total of 19 drug-resistant focal epilepsy patients who underwent EBS as part of invasive presurgical evaluation and who experienced EP during the stimulation were included. Spatial dispersion of visual and auditory illusions and complex hallucinations in each hemisphere was determined by calculation of Euclidean distances between electrodes and their centroid in common space, based on (x, y, z) Cartesian coordinates of electrode locations., Results: In total, 5857 stimulation epochs were analyzed; 917 stimulations elicited responses, out of which 130 elicited EP. Complex visual hallucinations were found to be widely dispersed in the right hemisphere, while they were tightly clustered in the occipital lobe of the left hemisphere. Visual illusions were elicited mostly in the occipital lobes bilaterally. Auditory illusions and hallucinations were evoked symmetrically in the temporal lobes., Conclusions: These findings suggest that complex visual hallucinations arise from wider spread in the right compared to the left hemisphere, possibly mirroring the asymmetry in the white matter organization of the two hemispheres. These results offer some insights into lateralized differences in functional organization and connectivity that may be important for functional mapping and planning of surgical resections in patients with epilepsy.

Background: Epilepsy is one of the most common chronic neurological conditions and its treatment during pregnancy is challenging. Levetiracetam (LEV) is an antiepileptic medication frequently used during pregnancy. Only a few small studies have been published on LEV monitoring during pregnancy, demonstrating decreased serum LEV levels during the first and second trimester; however, the most significant decrease was observed during the third trimester of pregnancy. In this study we aimed to evaluate LEV pharmacokinetics during different stages of pregnancy., Methods: We followed up and monitored serum levels of pregnant women treated with LEV for epilepsy., Results: Fifty-nine women with 66 pregnancies during the study period were included. The lowest raw LEV serum concentrations were observed during the first trimester. Compared with the pre-pregnancy period, raw serum concentration was lower by 5.76 mg/L [95% confidence interval (CI) (2.78, 8.75), p  = 0.039] during the first trimester. Comparing the decrease in the first trimester with either the second or the third, no significant changes were observed ( p  = 0.945, p  = 0.866). Compared with pre-pregnancy measurements, apparent clearance was increased by 71.08 L/day [95%CI (16.34, 125.83), p  = 0.011] during the first trimester. About 30% of LEV serum levels during pregnancy were below the laboratory quoted reference range., Conclusions: Raw LEV serum levels tend to decrease during pregnancy, mainly during the first trimester contrary to previous reports. Monitoring of LEV serum levels is essential upon planning pregnancy and thereafter if pre-pregnancy LEV levels are to be maintained. However, more studies are needed to assess the correlation with clinical outcome., Competing Interests: Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones., Methods: We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls., Results: There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 μmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three., Conclusions: Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Although simultaneous recording of EEG and MRI has gained increasing popularity in recent years, the extent of its clinical use remains limited by various technical challenges. Motion interference is one of the major challenges in EEG-fMRI. Here we present an approach which reduces its impact with the aid of an MR compatible dual-array EEG (daEEG) in which the EEG itself is used both as a brain signal recorder and a motion sensor., Methods: We implemented two arrays of EEG electrodes organized into two sets of nearly orthogonally intersecting wire bundles. The EEG was recorded using referential amplifiers inside a 3T MR-scanner. Virtual bipolar measurements were taken both along bundles (creating a small wire loop and therefore minimizing artifact) and across bundles (creating a large wire loop and therefore maximizing artifact). Independent component analysis (ICA) was applied. The resulting ICA components were classified into brain signal and noise using three criteria: 1) degree of two-dimensional spatial correlation between ICA coefficients along bundles and across bundles; 2) amplitude along bundles vs. across bundles; 3) correlation with ECG. The components which passed the criteria set were transformed back to the channel space. Motion artifact suppression and the ability to detect interictal epileptic spikes following daEEG and Optimal Basis Set (OBS) procedures were compared in 10 patients with epilepsy., Results: The SNR achieved by daEEG was 11.05±3.10 and by OBS was 8.25±1.01 (p<0.00001). In 9 of 10 patients, more spikes were detected after daEEG than after OBS (p<0.05)., Significance: daEEG improves signal quality in EEG-fMRI recordings, expanding its clinical and research potential., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The vocational parameters regarding epilepsy are not well established. Our aim was to assess the risk of seizures as a function of occupational stress and disease severity in military recruits of the IDF (Israel Defense Force) and to examine the effect of new classification criteria (used between the late nineties and early two thousands) in comparison with that of previous criteria (used during the mid-eighties to mid-nineties)., Methods: The medical records of over 150,000 18-year-old men recruited to the IDF between the mid-nineties and the mid-two thousands were used to assemble a cohort, which was followed for a period of 36months. The severity of the disease was determined according to 3 categories, according to the medical history. The recruits were subdivided according to their occupational categories to Combat Units (CUs), Maintenance Units (MUs), and Administrative Units (AUs). We compared the incidence rates of the different groups with the findings from a previous follow-up., Results: The annual incidence rates during 36months of follow-up were 0.026%, 4.7%, and 8.8%, in categories 1 to 3, respectively. The relative risk of seizure incidence in CU and MU was lower than in AU (0.42 and 0.81, p<0.0001). Similar findings were found in other disease categories., Conclusions: Job assignment to CU (less convenient conditions like sleep deprivation and strenuous physical activity) did not increase the incidence of seizures. It was found that EEG examination is an important criterion in the vocational evaluation of subjects that have had one or more seizures. This study supports the establishment of vocational criteria and recommends the integration of people diagnosed with epilepsy in most occupations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

OBJECTIVE Providing a reliable assessment of language lateralization is an important task to be performed prior to neurosurgery in patients with epilepsy. Over the last decade, functional MRI (fMRI) has emerged as a useful noninvasive tool for language lateralization, supplementing or replacing traditional invasive methods. In standard practice, fMRI-based language lateralization is assessed qualitatively by visual inspection of fMRI maps at a specific chosen activation threshold. The purpose of this study was to develop and evaluate a new computational technique for providing the probability of each patient to be left, right, or bilateral dominant in language processing. METHODS In 76 patients with epilepsy, a language lateralization index was calculated using the verb-generation fMRI task over a wide range of activation thresholds (from a permissive threshold, analyzing all brain regions, to a harsh threshold, analyzing only the strongest activations). The data were classified using a probabilistic logistic regression method. RESULTS Concordant results between fMRI and Wada lateralization were observed in 89% of patients. Bilateral and right-dominant groups showed similar fMRI lateralization patterns differentiating them from the left-dominant group but still allowing classification in 82% of patients. CONCLUSIONS These findings present the utility of a semi-supervised probabilistic learning approach for presurgical language-dominance mapping, which may be extended to other cognitive domains such as memory and attention.

Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis., Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate., Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically., Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies., (© 2016 American Academy of Neurology.)

Objectives: Psychogenic non-epileptic seizures (PNES) may resemble epileptic events. Epileptic and non-epileptic seizures are not mutually exclusive phenomena and may coexist in the same patient. The aim of this study was to evaluate the long-term outcome of psychogenic events in patients with PNES alone and those with both PNES and epilepsy (PNES + EPI) as diagnosed by video-EEG (vEEG) monitoring., Materials and Methods: All adult admissions to the Tel-Aviv Medical Center's vEEG unit between 2004 and 2009 were screened for the presence of PNES. We retrospectively retrieved data from their medical files and supplemented the follow-up by a telephonic questionnaire., Results: Eligible patients (n = 51) were divided into those with PNES + EPI (n = 24) and those with PNES alone (n = 27). The follow-up period was 4.8 ± 0.3 and 4.3 ± 0.3 years, respectively. Both groups had similar female predominance and similar age at admission to the vEEG unit. Time from PNES onset to hospitalization was longer in PNES patients compared to those with PNES + EPI. The majority of subjects in each group reported a history of at least one major stressful life event. Opisthotonus was significantly more frequently observed in PNES patients, and they had more events during vEEG hospitalization. Psychogenic events ceased during the follow-up period in 22% of the PNES patients and in 58% of the PNES + EPI patients (P > 0.001)., Conclusion: Our results indicate that following vEEG-based diagnosis of PNES, the long-term outcome of PNES cessation may be more favorable for patients with concomitant epilepsy than for patients without epilepsy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Surveys among women with epilepsy (WWE) show that they receive their essential pregnancy-related information from many sources, including the internet. Our aim was to assess the types of websites provided by searching Google for the use of four antiepileptic drugs (AEDs) during pregnancy and lactation. The search was performed on 40 computers used by health-care professionals, on 40 computers used by nonhealth-care professionals, and on 5 computers used by WWE in Israel and on 8 computers used by nonhealth-care professionals in the U.S. On each computer, a Google search was conducted for term combinations that included one AED name ("carbamazepine","valproic acid", "lamotrigine", "levetiracetam", or "Keppra") and "Pregnancy", "Lactation", or "Breastfeeding". The top three and top ten websites retrieved in every search were mapped (a total of 45 and 150 websites, respectively, from each computer). Across all searches in English, on both U.S. and Israeli computers, the majority of websites listed among the first three and first ten results were those of independent health portals. The representation of the Epilepsy Foundation website was 10% or less, and only a few results were obtained from the NIH's general public-oriented MedlinePlus. In Hebrew, results included almost exclusively Israeli or Hebrew-translated websites. As in English, results from public-oriented, professionally-written websites in Hebrew accounted for less than 50% of entries. Overall, the availability of readable and high-quality information on AEDs used by pregnant and breastfeeding women is limited. Guiding patients towards accurate web resources can help them navigate among the huge amount of available online information., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: As pharmacists play an important role in managing antiepileptic drug (AED) therapy, they should be aware of different aspects of the treatment. Our aim was to evaluate pharmacists' knowledge of the pharmacological treatment of epilepsy, and their recommendations under hypothetical situations, through a written questionnaire., Methods: The questionnaire included 22 questions divided into three sections: demographic data (eight questions), knowledge of specific aspects of AED therapy (true/false; four questions), and actions taken in theoretical situations involving AED therapy (multiple choice; ten questions). The questionnaire was distributed to pharmacists practicing in Israel and working in pharmacies and/or participating in professional meetings and continued education programs., Results: One hundred and twenty one pharmacists completed the questionnaire (response rate 19%). The mean overall score was 48 ± 15% correct answers. Most pharmacists were aware of the need to continue AED treatment during pregnancy, the risk of generic switches, and the need to call the physician for loss of seizure control (92%, 89% and 81% of responders, respectively). Twelve percent identified correctly all three situations in which the clinicians should be contacted urgently, and 27% did not identify any of them. The total score was related to the academic degree (PharmD vs. other) and to the duration since training completion., Conclusion: Pharmacists were knowledgeable regarding some aspects of care of people with epilepsy. However, our study, as in previous studies among health care professionals, identified some gaps in knowledge. These findings indicate the need for better education of pharmacists regarding epilepsy and its treatment., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Early identification of cardiac asystole as a reason for syncope is of uttermost significance, as insertion of a cardiac pacemaker can save the patient's life and prevent severe injury. The aim of this work was to emphasize the subtle and unusual presentations of asystole in patients evaluated in epilepsy units., Methods: We reviewed the clinical presentation, ECG and EEG data of a series of seven patients who were evaluated in four epilepsy units and were diagnosed with asystole., Results: Three patients had unusual clinical manifestations of cardiac asystole, resembling epileptic seizures. Three patients had asystole induced by epileptic seizures and in one patient the diagnosis was not clear. All patients except one were implanted with a pacemaker and improved clinically., Conclusions: Seizure-induced asystole is a rare complication of epilepsy and asystole may clinically mimic epileptic seizures. A high level of suspicion and thorough prolonged cardiac and EEG monitoring are mandatory for reaching the right diagnosis. As the diagnosis is rare and difficult to reach, a flow chart to assist diagnosis is suggested.

Objective: Up to one-third of individuals diagnosed as having epilepsy continue to have seizures despite appropriate anti-epileptic drug treatment. These patients are often referred for presurgical evaluation, and many are rejected from focal resective surgery due to medical reasons or, alternatively, they choose not to undergo it. We compared the outcomes and characteristics of the non-operated patients who continued on medical therapy alone with those who underwent vagus nerve stimulator (VNS) implantation in addition to medical therapy., Methods: The medical records of consecutive adult patients referred for presurgical evaluation for suitability for epilepsy surgery in the Tel-Aviv Sourasky Medical Center between 2007 and 2011 and were rejected from or decided against surgery were reviewed. Updated information on seizure frequency was supplemented by telephone interviews between April and July, 2013., Results: Fifty-two patients who continued solely on medical therapy and 35 patients who additionally underwent VNS implantation were included in the study. Forty-seven of the former and 33 of the latter agreed to be interviewed. There was a significant improvement in the seizure frequency between the time of the presurgical evaluation and the time of the interview in both groups. Eight medically treated patients (17%) and 2 patients who also underwent VNS implantation (6%) reported being seizure-free during the preceding 3 months., Conclusions: A considerable minority of patients with refractory epilepsy who were rejected or chose not to undergo epilepsy surgery may improve over time and even become seizure-free following adjustment of anti-epileptic drugs with or without concomitant VNS., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Our emotions tend to be directed towards someone or something. Such emotional intentionality calls for the integration between two streams of information; abstract hedonic value and its associated concrete content. In a previous functional magnetic resonance imaging (fMRI) study we found that the combination of these two streams, as modeled by short emotional music excerpts and neutral film clips, was associated with synergistic activation in both temporal-limbic (TL) and ventral-lateral PFC (vLPFC) regions. This additive effect implies the integration of domain-specific 'affective' and 'cognitive' processes. Yet, the low temporal resolution of the fMRI limits the characterization of such cross-domain integration. To this end, we complemented the fMRI data with intracranial electroencephalogram (iEEG) recordings from twelve patients with intractable epilepsy. As expected, the additive fMRI activation in the amygdala and vLPFC was associated with distinct spatio-temporal iEEG patterns among electrodes situated within the vicinity of the fMRI activation foci. On the one hand, TL channels exhibited a transient (0-500 msec) increase in gamma power (61-69 Hz), possibly reflecting initial relevance detection or hedonic value tagging. On the other hand, vLPFC channels showed sustained (1-12 sec) suppression of low frequency power (2.3-24 Hz), possibly mediating changes in gating, enabling an on-going readiness for content-based processing of emotionally tagged signals. Moreover, an additive effect in delta-gamma phase-amplitude coupling (PAC) was found among the TL channels, possibly reflecting the integration between distinct domain specific processes. Together, this study provides a multi-faceted neurophysiological signature for computations that possibly underlie emotional intentionality in humans., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To investigate whether extending the 10-20 array with 6 electrodes in the inferior temporal chain and constructing computed montages increases the diagnostic value of ictal EEG activity originating in the temporal lobe. In addition, the accuracy of computer-assisted spectral source analysis was investigated., Methods: Forty EEG samples were reviewed by 7 EEG experts in various montages (longitudinal and transversal bipolar, common average, source derivation, source montage, current source density, and reference-free montages) using 2 electrode arrays (10-20 and the extended one). Spectral source analysis used source montage to calculate density spectral array, defining the earliest oscillatory onset. From this, phase maps were calculated for localization. The reference standard was the decision of the multidisciplinary epilepsy surgery team on the seizure onset zone. Clinical performance was compared with the double banana (longitudinal bipolar montage, 10-20 array)., Results: Adding the inferior temporal electrode chain, computed montages (reference free, common average, and source derivation), and voltage maps significantly increased the sensitivity. Phase maps had the highest sensitivity and identified ictal activity at earlier time-point than visual inspection. There was no significant difference concerning specificity., Conclusions: The findings advocate for the use of these digital EEG technology-derived analysis methods in clinical practice.

Despite the profound reduction in conscious awareness associated with sleep, sensory cortex remains highly active during the different sleep stages, exhibiting complex interactions between different cortical sites. The potential functional significance of such spatial patterns and how they change between different sleep stages is presently unknown. In this electrocorticography study of human patients, we examined this question by studying spatial patterns of activity (broadband gamma power) that emerge during sleep (sleep patterns) and comparing them to the functional organization of sensory cortex that is activated by naturalistic stimuli during the awake state. Our results show a high correlation (p < 10(-4), permutation test) between the sleep spatial patterns and the functional organization found during wakefulness. Examining how the sleep patterns changed through the night highlighted a stage-specific difference, whereby the repertoire of such patterns was significantly larger during rapid eye movement (REM) sleep compared with non-REM stages. These results reveal that intricate spatial patterns of sensory functional organization emerge in a stage-specific manner during sleep.

Background: To report an unusual case of cyclic oculomotor nerve paresis and spasms, which developed 5 years following brain radiotherapy for cerebellar medulloblastoma., Methods: Observational case report., Results: The cyclic oculomotor nerve paresis and spasms resolved in our patient when treated with carbamazepine. However, because of severe photophobia and tearing, carbamazepine had to be discontinued leading to reappearance of the eye movement disorder., Conclusion: Cyclic oculomotor nerve paresis and spasms appear to be a delayed effect of radiotherapy and respond to carbamazepine therapy. It may be a rare form of ocular neuromyotonia.

Hashimoto's encephalopathy is defined by the coexistence of encephalopathy and antithyroid antibodies. We report two cases of adult-onset temporal lobe epilepsy with subacute cognitive decline, high titers of antithyroid antibodies, multi-antiepileptic drug hypersensitivity, and good response to immunomodulatory treatment. The relevance of multidrug hypersensitivity in the setting of adult-onset epilepsy and the importance of searching for autoimmune causes for epilepsy are discussed.

Objectives: Hospital admission in otherwise healthy patients following a first unprovoked seizure is controversial. We aimed to evaluate the influence of admission in a neurology department on the identification of risk factors for seizure recurrence in patients with a first unprovoked seizure., Materials and Methods: We retrospectively reviewed the medical records of patients with a first unprovoked seizure, who were admitted to the neurology departments at two medical centers between 2007 and 2009. Risk factors for seizure recurrence included the following: abnormal neurological examination, abnormal brain CT scan, and epileptiform discharges on the EEG., Results: The study group included 97 patients (52 men) aged 18-85 years (mean 42). Eighty-seven (90%) patients were admitted following a generalized tonic-clonic seizure. Risk factors were identified in the emergency room (ER) in 36 (37%) patients, mainly including abnormalities of the neurological examination and brain CT scan. Nineteen (20%) patients had a risk factor which was not apparent during ER evaluation, consisting of epileptiform activity on the EEG. Five (5%) patients had recurrent seizures during admission, three of them without risk factors during the ER evaluation., Conclusions: Risk factors for seizure recurrence were detected during admission in nearly a quarter of the patients who presented to the emergency room with a first unprovoked seizure. Because the main advantage of admission is the EEG recording, we suggest that an early EEG should be obtained in these patients either during admission or through a special accelerated outpatient arrangement., (© 2013 John Wiley & Sons A/S.)

A fundamental debate in the study of cortical sensory systems concerns the scale of functional selectivity in cortical networks. Brain imaging studies have repeatedly demonstrated functional selectivity in entire cortical areas and networks using predetermined stimuli. However, it is not clear to what extent these networks are heterogeneous, i.e., whether the selectivity profiles in subregions within each sensory network show significant dissimilarity. Here, we studied local functional selectivity in the human cortex using naturalistic movie clips shown to 12 patients implanted with intracranial electrocorticography electrodes (590 in total), providing extensive cortical coverage. We examined the similarity of response profiles (40- to 80-Hz gamma-power modulations) across electrodes using a novel data driven approach without assuming any predefined category. Our results show that the functional selectivity of each highly responsive electrode was different from that of all other electrodes across the sensory cortex. Thus most responsive electrodes showed an activation profile that was unique in each patient and was similar to that of only 0.3% (1-2) of all other electrodes across all patients. Functional similarity between electrodes was linked to anatomical proximity. While in most electrodes the source of selectivity was complex, a small subset showed the well-documented selectivity to faces and actions. Our results indicate that the human sensory cortex is organized as a mosaic of functionally unique subregions in which each site manifests its own special response profile.

Objectives: To evaluate unilateral memory function by the means of a modified Montreal etomidate speech and memory procedure (e-SAM) in epilepsy patients who were candidates for standard anterior temporal lobectomy involving resection of mesial temporal lobe structures., Materials and Methods: After the first three patients experienced significant side effects with the e-SAM procedure, we modified the procedure to a single bolus injection. The neuropsychological data of all 21 patients who underwent unilateral memory testing by means of intracarotid injection of etomidate were analyzed., Results: There was a significant difference in memory scores when injections were on the side ipsilateral to the epileptogenic focus compared with when the injections were on the contralateral side (P < 0.01), supposedly reflecting unilateral hippocampal memory function and dysfunction. In addition, the procedural modification resulted in eradication of all major side effects in the ensuing 18 patients., Conclusions: The technical modification of the Montreal procedure from continuous to bolus injection effectively enabled the demonstration of the relative weakness of the memory function of the epileptogenic hemisphere. The revised etomidate procedure provided the clinical information on unilateral hippocampal memory function necessary for surgical decision., (© 2012 John Wiley & Sons A/S.)

One of the puzzling aspects in the visual attention literature is the discrepancy between electrophysiological and fMRI findings: whereas fMRI studies reveal strong attentional modulation in the earliest visual areas, single-unit and local field potential studies yielded mixed results. In addition, it is not clear to what extent spatial attention effects extend from early to high-order visual areas. Here we addressed these issues using electrocorticography recordings in epileptic patients. The patients performed a task that allowed simultaneous manipulation of both spatial and object-based attention. They were presented with composite stimuli, consisting of a small object (face or house) superimposed on a large one, and in separate blocks, were instructed to attend one of the objects. We found a consistent increase in broadband high-frequency (30-90 Hz) power, but not in visual evoked potentials, associated with spatial attention starting with V1/V2 and continuing throughout the visual hierarchy. The magnitude of the attentional modulation was correlated with the spatial selectivity of each electrode and its distance from the occipital pole. Interestingly, the latency of the attentional modulation showed a significant decrease along the visual hierarchy. In addition, electrodes placed over high-order visual areas (e.g., fusiform gyrus) showed both effects of spatial and object-based attention. Overall, our results help to reconcile previous observations of discrepancy between fMRI and electrophysiology. They also imply that spatial attention effects can be found both in early and high-order visual cortical areas, in parallel with their stimulus tuning properties.

In 1997, the US Food and Drug Administration approved the use of intermittent stimulation of the left vagal nerve as adjunctive therapy for seizure control. Vagal nerve stimulation (VNS) has since been considered a safe and effective treatment for medically intractable seizures. The objective of this study is to present our experience with the surgical procedure and outcomes after VNS insertion in the first 100 consecutive patients treated at the Tel-Aviv "Sourasky" Medical Center (TASMC). All patients who underwent VNS device implantation by the authors at TASMC between 2005 and 2011 were studied. The collected data included age at onset of epilepsy, seizure type, duration of epilepsy, age at VNS device implantation, seizure reduction, surgical complications, and adverse effects of VNS over time. Fifty-three males and 47 females, age 21.2 ± 11.1 years, underwent VNS implantation. Indications for surgery were medically refractory epilepsy. The most common seizure type was focal (55 patients, 55 %). Seizure duration until implantation was 14.4 ± 9 years. Mean follow-up time after device insertion was 24.5 ± 22 months. Complications were encountered in 12 patients. The most common complication was local infection (6 patients, 6 %). Six devices were removed-four due to infection and two due to loss of clinical effect. Currently, 63 patients remain in active long-term follow-up; of these, 35 patients have >50 % reduction in frequency of attacks.VNS is a well-tolerated and effective therapeutic alternative in the management of medically refractory epilepsy. The surgical procedure is safe and has a low complication rate.

The interictal epileptiform discharge (IED) yield of long-term video-EEG (LTVEEG) monitoring is increased compared to a single out-patient EEG, but was not studied specifically in frontal lobe epilepsy. Since IED recording can influence the length of monitoring when seizures are not recorded during LTVEEG, we aimed to assess the IED yield of LTVEEG recording in patients with frontal seizures. We retrospectively reviewed the medical records of 20 patients with frontal seizures during non-invasive LTVEEG in Tel Aviv Medical Center between 2003 and 2008 and compared them with the results of out-patient EEG. The study group included 11 (55%) men and 9 women aged 15-82 years (mean: 27 years). LTVEEG duration ranged between 4 and 29 days (mean: 14 days). IEDs were detected by each of the tests in eight (40%) patients. We conclude that non-invasive LTVEEG and out-patient EEG have a similar diagnostic yield for IEDs in patients with frontal seizures. Therefore, seizures remain the most relevant clinical outcome of LTVEEG.

Purpose: Ictal video-electroencephalography (EEG) is commonly used to establish ictal onset-zone location. Recently software development has enabled systematic studies of ictal magnetoencephalography (MEG). In this article, we evaluate the ability of ictal MEG signals to localize the seizure-onset zone., Methods: Twenty-six patients underwent ictal MEG and epilepsy surgery. Prediction of seizure-onset zone by ictal and interictal MEG was retrospectively compared with ictal-onset area found by intracranial EEG in 12 patients. The specificity and sensitivity of the prediction were calculated at hemisphere-lobe (HL) and at hemisphere-lobe-surface (HLS) levels., Key Findings: The sensitivity of ictal MEG source localization was 0.958 on HL and 0.706 on HLS levels, and its specificity was 0.900 on HL and 0.731 on HLS levels. The interictal MEG dipole cluster, defined as >10 dipoles on one lobar surface, had sensitivity of 0.400 and specificity of 0.769. Ictal MEG was equally sensitive and specific on dorsolateral and nondorsolateral neocortical surfaces up to a depth of 4 cm from the scalp., Significance: Sources of ictal-onset MEG signals and interictal dipole clusters are essentially equally specific in estimation of the ictal-onset zone on lobar surface resolution, but ictal MEG is more sensitive. On the lobe resolution, ictal MEG estimates ictal-onset zone with high sensitivity and specificity., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

While research of human cortical function has typically focused on task-related increases in neuronal activity, there is a growing interest in the complementary phenomenon-namely, task-induced reductions. Recent human BOLD fMRI studies have associated such reductions with a specific network termed the default mode network (DMN). However, detailed understanding of the spatiotemporal patterns of task-negative responses and particularly how they compare across different cortical networks is lacking. Here we examined this issue in a large-scale electrocorticography study in patients performing a demanding backward masking task. Our results uncovered rapid (<1 s) task-induced reductions in gamma power, often concomitant with power increase in alpha/beta bands. Importantly, these responses were found both in the DMN and sensory-motor networks. Comparing the task-negative responses across these different networks revealed similar spectral signatures and dynamics. We hypothesize that the task-negative responses may reflect a cortical switching mechanism whose role is to steer activity away from cortical networks, which are inappropriate for the task at hand.

Background: The effects of postponing the morning dose of antiepileptic drugs (AEDs) before undergoing an electroencephalogram (EEG) on the likelihood of recording interictal epileptiform activity (IEA) in patients with epilepsy are unclear., Methods: This was a prospective study on patients undergoing video-EEG monitoring. The 3-h recordings used for evaluation started at 08:00 am. Each subject received the usual AED dosage at 08:00 am on the first full day of recording but not until 11:00 am on the following day. IEA (spikes, sharp waves, and spike and wave complexes) was counted at 1-h intervals on each day and compared. Each subject served as his/her own control. The measureable serum drug levels were obtained at 10:00 am on both days., Results: Fifty patients (age 32 ± 11.7 years, 22 women) were enrolled. Forty-seven had focal epilepsy, and three had generalized epilepsy. Six were on monotherapy, and 44 were on polytherapy. The number of IEAs w/wo medication was similar throughout each hour. Twenty-five patients had IEA on the 1st day, and 28 had IEA on the 2nd day. Twenty-one had IEA on both days, while 18 had none on either day. Seven of the 25 without IEA on the 1st day had IEA on the 2nd day, and 4 of the 25 with IEA had no IEA on the 2nd day. Age, gender, epilepsy type, disease duration, seizure frequency, and AED type did not influence IEA., Conclusions: Delaying the morning dose of AEDs prior to an EEG tracing was not associated with increased IEA in patients with epilepsy., (© 2012 John Wiley & Sons A/S.)

Objectives: To identify the patients who are more likely to experience a seizure during routine electroencephalography (EEG) recording., Methods: We retrospectively reviewed the EEG recordings and medical records of 262 patients, who were admitted in the Neurology Department in Assaf Harofeh Medical Center and referred to the EEG laboratory between October 2006 and 2008 after a seizure., Results: Eighteen (6.8%) patients had seizures during routine EEG [patients with seizures (PWS)]. The likelihood of seizure occurrence during routine EEG was increased by the presence of interictal epileptiform discharges (odds ratio, 29.85; 95% confidence interval, 6.54-136.21; P=0.001) and abnormal state of consciousness (odds ratio, 9.04; 95% confidence interval, 1.02-80.33; P=0.037). Increased seizure frequency before admission, localization-related epilepsy, and EEG background slowing were significantly more common among PWS compared with patients without seizures on routine EEG (P=0.009, 0.042, and 0.036, respectively)., Conclusions: The presence of interictal epileptiform discharges and decreased state of consciousness increase significantly the likelihood of seizure occurrence during routine EEG. Localization-related epilepsy, increased seizure frequency before admission, and EEG background slowing are more common among PWS.

Actions are often internally guided, reflecting our covert will and intentions. The dorsomedial prefrontal cortex, including the pre-Supplementary Motor Area (pre-SMA), has been implicated in the internally generated aspects of action planning, such as choice and intention. Yet, the mechanism by which this area interacts with other cognitive brain regions such as the dorsolateral prefrontal cortex, a central node in decision-making, is still unclear. To shed light on this mechanism, brain activity was measured via fMRI and intracranial EEG in two studies during the performance of visually cued repeated finger tapping in which the choice of finger was guided by either a presented number (external) or self-choice (internal). A functional-MRI (fMRI) study in 15 healthy participants demonstrated that the pre-SMA, compared to the SMA proper, was more active and also more functionally correlated with the dorsolateral prefrontal cortex during internally compared to externally guided action planning (p < 0.05, random effect). In a similar manner, an intracranial-EEG study in five epilepsy patients showed greater inter-regional gamma-related connectivity between electrodes situated in medial and lateral aspects of the prefrontal cortex for internally compared to externally guided actions. Although this finding was observed for groups of electrodes situated both in the pre-SMA and SMA-proper, increased intra-cluster gamma-related connectivity was only observed for the pre-SMA (sign-test, p < 0.0001). Overall our findings provide multi-scale indications for the involvement of the dorsomedial prefrontal cortex, and especially the pre-SMA, in generating internally guided motor planning. Our intracranial-EEG results further point to enhanced functional connectivity between decision-making- and motor planning aspects of the PFC, as a possible neural mechanism for internally generated action planning.

Purpose: To compare subclinical balance dysfunction in patients with various epilepsy syndromes with apparently healthy subjects., Methods: Twenty-seven patients with localization-related epilepsy (LRE), 19 with primary generalized epilepsy (PGE), who had no subjective complaints of impaired balance and no abnormal neurologic findings on examination, and 22 apparently healthy subjects, underwent static posturography using the Posture Scale Analyzer (PSA) system., Results: Sway index was higher in patients compared to healthy subjects in all tests, significant for single leg stance (p=0.005). Patients with PGE had a higher sway index compared to patients with LRE in six of the tests, also significant for single leg stance (p=0.027). This difference was not affected by the type of AED treatment or disease duration., Conclusion: Posturography can improve balance function assessment in patients with epilepsy, demonstrate subclinical impairment in seemingly asymptomatic patients, and further characterize balance deficits in different epilepsy syndromes., (Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Scalp electroencephalography and magnetoencephalography studies have revealed a rapid evoked potential "adaptation" where one visual stimulus suppresses the event-related potential (ERP) of the second stimulus. Here, we investigated a similar effect revealed in subdural intracranial recordings in humans. Our results show that the suppression of the subdural ERP is not associated with a reduction in the gamma frequency power, considered to reflect the underlying neural activity. Furthermore, the evoked potential suppression (EPS) phenomenon was not reflected in recognition behavior of the patients. Rather, the EPS was tightly linked to the level of gamma activity preceding the event, and this effect was independent of the interstimulus time interval. Analyzing other frequency bands failed to reveal a similar link. Our results thus show a consistent antagonism between subdural ERP and gamma power although both are considered markers for neural activity. We hypothesize that the ERP suppression is due to a desynchronization of neuronal firing resulting from recurrent neural activity in the vicinity of the freshly stimulated neurons and not an attenuation of the overall neural activity.

A leftward bias is well known in humans and animals, and commonly related to the right hemisphere dominance for spatial attention. Our previous fMRI study suggested that this bias is mediated by faster conduction from the right to left parietal cortices, than the reverse (Siman-Tov et al., 2007). However, the limited temporal resolution of fMRI and evidence on the critical involvement of sub-cortical regions in orienting of spatial attention suggested further investigation of the leftward bias using multi-scale measurement. In this simultaneous EEG-fMRI study, healthy participants were presented with face pictures in either the right or left visual fields while performing a central fixation task. Temporo-occipital event related potentials, time-locked to the stimulus onset, showed an association between faster conduction from the right to the left hemisphere and higher fMRI activation in the left pulvinar nucleus following left visual field stimulation. This combined-modal finding provides original evidence of the involvement of sub-cortical central attention-related regions in the leftward bias. This assertion was further strengthened by a DCM analysis designated at cortical (i.e., inferior parietal sulcus; IPS) and sub-cortical (pulvinar nucleus) attention-related nodes that revealed: 1. Stronger inter-hemispheric connections from the right to left than vice versa, already at the pulvinar level. 2. Stronger connections within the right than the left hemisphere, from the pulvinar to the IPS. This multi-level neural superiority can guide future efforts in alleviating attention deficits by focusing on improving network connectivity., (Copyright © 2010 Elsevier Inc. All rights reserved.)