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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.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 to where they grew up (census tract level). The outcome measured was shooting rate per census block.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 (RR 0.47 per unit increase in BIM, 95% CI 0.35, 0.64; RR 0.81 per unit increase in WIM, 95% CI 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.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.Prognostic and Epidemiological; Level IV.

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.

Background No previous study has identified the specific brands of guns owned by gun owners. This study aimed to: (1) ascertain and describe patterns of brand- and model-specific gun ownership among US gun owners; and (2) investigate the relationship between gun owners’ brand and model preferences and their attitudes towards common firearm violence prevention policies. Methods Using a national, pre-recruited internet panel of US adults in 2019, we surveyed gun owners (N = 2086) to ascertain their opinions regarding firearm violence prevention policies and to assess the brands and models of guns that they owned. Results Brand-specific gun ownership was highly concentrated and was dominated by three pistol brands, two revolver brands, three rifle brands, and three shotgun brands. There was wide variation in policy attitudes among owners of different gun brands, but little variation across owners of different gun types (i.e., pistols, rifles, revolvers, shotguns). We were able to identify the specific gun models owned by 1218 (59.4%) of the gun owners. Based on the classification of these gun models into three types we categorized the gun ownership pattern of the sample as 33.4% recreational, 45.5% self-defense, and 21.1% tactical. There were marked differences in support for firearm-related policies among the three groups, with support generally highest among the Recreation group and lowest among the Tactical group. Conclusion We conclude that gun brands and models are strong predictors of a gun owner’s attitudes regarding firearm-related policies. This information could help public health practitioners develop segment-specific communications that will appeal to each group in order to more effectively engage gun owners in firearm violence prevention.

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.

Background Rural counties in the United States have higher firearm suicide rates and opioid overdoses than urban counties. We sought to determine whether rural counties can be grouped based on these “diseases of despair.” Methods Age-adjusted firearm suicide death rates per 100,000; drug-related death rates per 100,000; homicide rate per 100,000, opioid prescribing rate, %black, %Native American, and %veteran population, median home price, violent crime rates per 100,000, primary economic dependency (nonspecialized, farming, mining, manufacturing, government, and recreation), and economic variables (low education, low employment, retirement destination, persistent poverty, and persistent child poverty) were obtained for all rural counties and evaluated with hierarchical clustering using complete linkage. Results We identified five distinct rural county clusters. The firearm suicide rates in the clusters were 5.9, 6.8, 6.4, 8.5, and 3.8 per 100,000, respectively. The counties in cluster 1 were poor, mining dependent, with population loss, cluster 2 were nonspecialized economies, with high opioid prescription rates, cluster 3 were manufacturing and government economies with moderate unemployment, cluster 4 were recreational economies with substantial veterans and Native American populations, high median home price, drug death rates, opioid prescribing, and violent crime, and cluster 5 were farming economies, with high population loss, low median home price, low rates of drug mortality, opioid prescribing, and violent crime. Cluster 4 counties were spatially adjacent to urban counties. Conclusions More than 300 counties currently face a disproportionate burden of diseases of despair. Interventions to reduce firearm suicides should be community-based and include programs to reduce other diseases of despair.

Previous geographically limited studies have shown differential impact of COVID-19 on Hispanic individuals. Data were obtained from the Centers for Disease Control and Prevention. We performed multivariate Poisson regression assessing risk of hospitalization and death in Hispanic White (HW), Hispanic Black (HB), and Hispanic Multiracial/Other (HM) groups compared to non-Hispanic Whites (NHW). The relative risk of hospitalization was 1.35, 1.58, and 1.50 (p

BACKGROUND Firearm injury remains a major cause of morbidity and mortality in the United States. Due to 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 twelve laws and firearm state-level injury-related hospitalization rates from 2000-2016 utilizing the RAND Corporation Inpatient Hospitalizations for Firearm Injury Database. We utilized difference-in-differences to determine the impact of law passage in a given state compared to 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 ten-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% (CI 11.6, 27.4) reduction and removal of firearms from domestic violence offenders was associated with a 17.0% (CI 9.9, 23.6) reduction in hospitalization rates. CONCLUSIONS 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.Study Type: EpidemiologicLevel of Evidence: III.

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.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.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).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.

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.

Health advocacy is a critical way to influence health policy and the wellbeing of our patients. Surgeons are increasingly recognizing the impact of the social determinants of health on surgical outcomes. Socially responsible surgery requires surgeons to advocate for their patients and communities to address inequity resulting from disparities related to the social determinants of health. However, further work is needed to teach aspiring surgeons how to advocate effectively. Introduction of surgical advocacy to medical students can help future surgical trainees understand that socially responsible advocacy is the work of surgeons and learn to incorporate advocacy into their future careers. To this end, we have developed a curriculum termed the Advocacy Toolbox: a program centered on surgical mentorship, advocacy didactics, and a longitudinal project. The Advocacy Toolbox aims to equip first year medical students with the tools needed to advocate for their patients and communities in a variety of contexts. The program is currently being implemented with a group of 15 first year medical students, with plans to expand the program in future years.

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.

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.

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.

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 3 T 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

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

Paroxysmal exercise-induced dyskinesia (PED) and epilepsy without intellectual disability have recently been recognized as manifestations of deficiency of the glucose transporter GLUT1, due to mutations in the gene SLC2A1. We describe a family with six definitely affected members in two generations. Two had PED, three had epilepsy, and one had both. A missense mutation in SLC2A1 (c.950A>C; p.N317T) was detected in five living affected members, but absent in three nonaffected first-degree members and in one subject believed to be a phenocopy. The clinical picture of mild epilepsy with onset in adolescence or early adulthood plus PED should raise a suspicion of GLUT1 deficiency.

Localizing the source of an epileptic seizure using noninvasive EEG suffers from inaccuracies produced by other generators not related to the epileptic source. The authors isolated the ictal epileptic activity, and applied a source localization algorithm to identify its estimated location. Ten ictal EEG scalp recordings from five different patients were analyzed. The patients were known to have temporal lobe epilepsy with a single epileptic focus that had a concordant MRI lesion. The patients had become seizure-free following partial temporal lobectomy. A midinterval (approximately 5 seconds) period of ictal activity was used for Principal Component Analysis starting at ictal onset. The level of epileptic activity at each electrode (i.e., the eigenvector of the component that manifest epileptic characteristic), was used as an input for low-resolution tomography analysis for EEG inverse solution (Zilberstain et al., 2004). The algorithm accurately and robustly identified the epileptic focus in these patients. Principal component analysis and source localization methods can be used in the future to monitor the progression of an epileptic seizure and its expansion to other areas.

Progressive myoclonus epilepsy (PME) is a syndrome characterized by myoclonic seizures (lightning-like jerks), generalized convulsive seizures, and varying degrees of neurological decline, especially ataxia and dementia. Previously, we characterized three pedigrees of individuals with PME and ataxia, where either clinical features or linkage mapping excluded known PME loci. This report identifies a mutation in PRICKLE1 (also known as RILP for REST/NRSF interacting LIM domain protein) in all three of these pedigrees. The identified PRICKLE1 mutation blocks the PRICKLE1 and REST interaction in vitro and disrupts the normal function of PRICKLE1 in an in vivo zebrafish overexpression system. PRICKLE1 is expressed in brain regions implicated in epilepsy and ataxia in mice and humans, and, to our knowledge, is the first molecule in the noncanonical WNT signaling pathway to be directly implicated in human epilepsy.

Objective – To provide functional magnetic resonance imaging-based insight into the impact of left temporal lobe epilepsy (TLE) on language-related functional re-organization. Materials and methods – Ten right-handed patients with left TLE were compared with 10 matched healthy controls. Regional brain activation during the language task was measured in the inferior frontal gyrus (IFG) and in the superior temporal gyrus (STG), and the regional inter-hemispheric lateralization index (LI) was calculated. Results – Left language lateralization was documented in all the patients and controls. Reduced lateralization in the IFG was due to decreased activity in the left frontal region rather than to increased activity in the right frontal region. The LI values in the STG correlated with the LI values in the IFG in the controls but not in the patients. Conclusions – The left IFG was most probably involved in the epileptogenesis and concomitant language-related cortical plasticity in patients with left TLE.

Objectives – To determine the importance of video-EEG monitoring (VEM) in elderly patients with various paroxysmal events. Material and methods – We retrospectively identified 16 subjects ≥ 60 years old out of 834 (1.9%; 7 females, mean age 67.8 ± 7.7 years), who were admitted to the Video-EEG Unit between 1997 and 2005 and compared data between those with and without epileptic events. Results – Epilepsy was confirmed in six patients, psychogenic non-epileptic seizures (NES) were diagnosed in seven, one patient had NES and epilepsy whereas the recorded events were non-conclusive in two. NES patients had a higher predisposition to psychiatric disturbances (P

Background and Objectives: A number of familial temporal lobe epilepsies (TLE) have been recently recognized. Mutations in LGI1 (leucine-rich, glioma-inactivated 1 gene) have been found in a few families with the syndrome of autosomal dominant partial epilepsy with auditory features (ADPEAF). The authors aimed to determine the spectrum of TLE phenotypes with LGI1 mutations, to study the frequency of mutations in ADPEAF, and to examine the role of LGI1 paralogs in ADPEAF without LGI1 mutations.Methods: The authors performed a clinical and molecular analysis on 75 pedigrees comprising 54 with a variety of familial epilepsies associated with TLE and 21 sporadic TLE cases. All were studied for mutations in LGI1. ADPEAF families negative for LGI1 mutations were screened for mutations in LGI2, LGI3, and LGI4.Results: Four families had ADPEAF, 22 had mesial TLE, 11 had TLE with febrile seizures, two had TLE with developmental abnormalities, and 15 had various other TLE syndromes. LGI1 mutations were found in two of four ADPEAF families, but in none of the other 50 families nor in the 21 individuals with sporadic TLE. The mutations were novel missense mutations in exons 1 (c.124T→G; C42G) and 8 (c.1418C→T; S473L). No mutations in LGI2, LGI3, or LGI4 were found in the other two ADPEAF families.Conclusion: In TLE, mutations in LGI1 are specific for ADPEAF but do not occur in all families. ADPEAF is genetically heterogeneous, but mutations in LGI2, LGI3, or LGI4 did not account for families without LGI1 mutations.

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.

The occurrence of transient recurrent stereotypical neurological events mandates the exclusion of an underlying brain lesion. When imaging studies demonstrate the presence of a structural brain lesion, a cause and effect relationship between the two entities is assumed, and the decision for surgical intervention may then follow almost automatically. We describe five patients with transient neurological events suspected as being seizures that were referred for surgery because of an associated structural brain lesion. Video electroencephalographic recordings revealed that the events that brought these patients to neurosurgical attention were non-epileptic seizures. None of these patients underwent surgical intervention, and all were referred for behavioral therapy. Therefore, even in the presence of a confirmed brain lesion, the presenting paroxysmal events may be of a non-organic origin and should not necessarily be assumed to be caused by the concomitantly existing structural abnormality.

Objectives – Quantitative electroencephalogram (qEEG) can be used to measure the effects of drugs on the brain. We studied the effects of rivastigmine on the qEEG in Parkinson's disease (PD) patients with dementia. Subjects and methods – Demented PD patients (n=19) were treated with rivastigmine in an open label study. Recordings were obtained prior to and following 12 weeks of treatment. Results were analyzed using two-way ANOVA with repeated measures. Results – A significant increase in the relative alpha (P

The increasing prevalence with age of antiphospholipid antibodies (aPL), of dementia and of stroke complicates the study of a causal relationship between antiphospholipid syndrome (APS) and dementia. Prolonged aPTT due to circulating anticoagulants (CAC) may serve as a more specific laboratory marker of APS. In a hospital-based study, we examined all patients with CAC and included 23 who fulfilled standard criteria for primary APS. These patients were assessed for dementia, vascular brain disease, autoimmune disease activity and dementia risk factors. Among CAC-positive APS patients, 13 of the 23 (56%) were demented and these were significantly older (mean age+/-S.E., 68+/-3 years) than the nondemented APS group (n=10, 51+/-4 years; p

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.

There is meager information in the literature regarding the characteristics and risk factors for injuries caused during epileptic seizures in adults. Previous studies focused mainly on specific types of injuries incurred, and only few explored associated risk factors. A questionnaire regarding lifetime seizures and their traumatic consequences was administered to 298 consecutive epileptic patients and their caretakers or relatives. Ninety-one of them (30%) have reported trauma: 185 events (age 39.8+/-18 years, 54 males), of which 61 were severe. This translates to one seizure-related injury every 21 patient-years, and a serious injury once every 64 patient-years. The most common site of injury was the head (55% of the events). Blunt injuries occurred most frequently (40%), followed by cuts (28%). Severe injuries included fractures and dislocations (17%), burns (6%), brain concussion (6%), subdural hematoma (3%) and intracerebral hematoma (1%). Most injuries occurred at home. The 91 patients with traumatic events were compared with the 207 epileptic patients without previous trauma (age 37.8+/-14.7 years, 112 males). Patients with seizure-related trauma had significantly earlier onset age of epilepsy. They more commonly had generalized from onset tonic-clonic, complex partial, myoclonic or absence seizures but fewer had partial seizures with secondary generalization. The risk of trauma was mostly related to seizure type (generalized tonic clonic from onset and myoclonic seizures). This information may be helpful for better management of epileptic patients.

Information on the effects of newer antiepileptic drug (AEDs) on the electroencephalogram (EEG) is sparse and contradictory. Quantitative EEG (qEEG) provides a method of estimating the effects of drugs on the central nervous system. Twenty-three adult patients with difficult-to-control complex partial seizures, with or without secondary generalization, participated in an add-on study with one of three newer AEDs: vigabatrin (n = 10), lamotrigine (n = 6), and topiramate (n = 7). Frequency analysis and topographic mapping of awake EEGs before and during treatment with the drug were compared. Statistical analysis was performed using 2-way analysis of variance (ANOVA) with repeated measures. Vigabatrin administration was followed by a diffuse decrease in the absolute alpha (p < 0.05) and beta (p < 0.02) activities and a decrease in the absolute theta in the frontal and parieto-occipital regions (p < 0.03). Lamotrigine caused a significant diffuse increase in the faster frequencies (relative alpha p < 0.04 and relative beta p < 0.02), and decrease in the slower activities (relative theta in the posterior head regions p < 0.03 and relative delta diffusely p < 0.05). Topiramate increased the absolute beta (p < 0.05) and theta (p < 0.02) activities diffusely and decreased the relative alpha activity over the left hemisphere (p < 0.03). The different effect profiles of the newer AEDs on the electrical brain activity may reflect their different mechanisms of action.

Summary: Purpose: This study examined the influence of two psychosocial variables mediating between disease severity and quality of life (Qol) in epilepsy; social support and mastery (measured by locus of control and self-efficacy). A model placing these two variables as mediators between disease severity and QoL was tested with structural equation modeling. Methods: Eighty-nine patients with epilepsy (58% men, age 36 ± 12 years) were given the following instruments: Liverpool Seizure Severity Scale, Interpersonal Support Evaluation List, Epileptic Self-Efficacy Scale, Locus of Control scale, and the World Health Organization's Quality of Life Questionnaire, the WHOQOL. Results: Structural equation modeling showed good fit between the research model and the data (Bentler-Bonett Normalized Index of fit, 0.96; LISREL GFI, 0.95). Ninety percent of the variance of the WHOQOL was explained by a combination of disease severity, self-efficacy in epilepsy, social support, and locus of control. Mastery was found to mediate the correlation between disease severity and QoL, and social support was found to act as a mediator between disease severity and mastery. Conclusions: The study findings emphasize the possibility of improving QoL among patients with epilepsy by counseling and treatment aimed at reinforcing their self-efficacy and locus of control, as well as by improving their SoS.

Aim To determine the frequency and natural history of seizures having an onset during the first year of life. Methods A retrospective analysis of the files of all patients treated in the paediatric neurology clinic of our medical centre during 1975–1995. Results Of our 482 patients with seizure onset prior to age 16 years, the first seizure occurred at age 1–12 months in 80 (16.6%). Of those, 38 (48%) had West syndrome and the rest were classified as follows — partial seizures with or without secondary generalization: 19%, generalized tonic seizures: 8.5%, generalized tonic-clonic seizures: 7.5%, myoclonic: 7.5%, unclassified: 7.5%, and mixed-type seizures: 2%. Follow-up was possible in 91% of the patients. Mean follow-up period from seizure onset was 10 years. Of the non-West syndrome patients who were followed, 19 (50%) were still experiencing seizures at follow-up. Eleven of the 15 patients (73%) with partial seizures and four of the 13 patients (31%) with generalized tonic or tonic-clonic seizures had symptomatic seizures. Of the 14 followed patients with partial seizures, 10 (71%) still had seizures at follow-up, as did three (25%) of the 12 followed patients with generalized tonic or tonic-clonic seizures (p = 0.023). Conclusions: The partial seizures were most often symptomatic with unfavourable prognosis, while the generalized seizures were either symptomatic and severe or cryptogenic and rapidly responsive to anti-epileptic drugs with good outcome.

Cognitive performances of ‘Differentiation-Generalization’ processing were examined as to how they related to individual differences in cerebral alpha rhythm. Classification of types of temperament was made in accordance with the level of activation, which is isomorphic to the wave rhythm. It was claimed that one cycle of this wave can characterize a unit of capacity for the passage of information according to values of frequency and amplitude, and that this unit facilitates the mode of cognitive processing. Large or small units enable passage for many or few cues, which fit a differentiating or generalizing mode of processing, respectively. Twenty healthy subjects aged 21–40 years, 12 women and eight men, participated in this study. Alpha wave values were recorded and evaluated using a computerized EEG system, and performances of a global task and a global-analytic task bound to these modes of processing were examined. A linear relation, P < 0.01, was found between a high frequency of the alpha wave and an efficient performance of the global task. In classifying the subjects into four temperamental types according to high and low amplitude and frequency, differences were found in the chosen width of categorization: those who produced low frequency and high amplitude chose narrow, and those with high frequency and low amplitude chose wide, P < 0.025. It was speculated that the individual rhythm may reflect both the emotional and the cognitive aspects of behavior.

Cholinergic deficiency was postulated to play an important role in the mental decline observed in Alzheimer's (AD), Parkinson's (PD) and multiinfarct (MID) dementia. In the present study, 11 AD, 8 MID and 7 PD patients (DSM III-R diagnostic criteria for dementia) and 9 healthy age-matched controls (CTRL) were given IV 0.5 mg scopolamine (SCO) or placebo (PLA) in random order (double blind) within one week. The Hebrew Short Mental Test (SMT) and Wechsler Memory Scale (WMS) were administered before and after SCO and PLA in each patient. A comparison of SCO vs. PLA utilizing MANCOVA (the covariate being the basal mental performance [BAS] with SMT or WMS) showed that SCO affected all the groups similarly, except for the Wechsler subtest of logic memory which showed larger deterioration in CTRL compared to demented patients. ANOVA and MANCOVA analyses did not distinguish between the three demented groups. SCO administration does not differentiate between demented patients and CTRL and does not enable discrimination between patients with AD, MID and PD. Moreover, some CTRL with still normal cognitive performance, but lower BAS may be more vulnerable to SCO than others. The integrity of the cholinergic system may be responsible for the different sensitivity to SCO challenge.