Indirect treatment comparison of cenobamate to other ASMs for the treatment of uncontrolled focal seizures.

OBJECTIVE: The efficacy and safety of cenobamate relative to other antiseizure medications (ASMs) has not been evaluated. An indirect treatment comparison (network meta-analysis) was performed to determine if adjunctive cenobamate increases the odds ratio (OR) for ≥50% responder rate or for withdrawals due to treatment-emergent adverse events (TEAEs) leading to ASM discontinuation versus adjunctive therapy with other ASMs. METHODS: A systematic literature review was conducted to identify randomized, double-blind, placebo-controlled trials (maintenance phase ≥ 12 weeks) assessing adjunctive ASMs in adults with uncontrolled focal seizures. Cenobamate was compared to a group of seven other ASMs, and to subgroups of branded (brivaracetam, eslicarbazepine acetate, lacosamide, and perampanel) and older (lamotrigine, levetiracetam, and topiramate) ASMs at FDA-recommended daily maintenance doses (FDA-RDMD), at all doses, and at maximum and minimum daily doses. Statistical significance was set at p < 0.05. RESULTS: Twenty-one studies were eligible for analysis. The placebo-adjusted ≥ 50% responder rate for FDA-RDMD of cenobamate was superior (OR 4.200; 95% CI 2.279, 7.742) to FDA-RDMD of all seven assessed (OR 2.202 95% CI 1.915, 2.532; p = 0.044) and branded ASMs (OR 2.148; 95% CI 1.849, 2.494; p = 0.037). There was no significant difference for ≥50% responder rate between FDA-RDMD of cenobamate and FDA-RDMD of older ASMs (OR 2.617; 95% CI 1.767, 3.878; p = 0.202). No significant differences were identified for ≥50% responder rate when comparing all doses and maximum/minimum doses of cenobamate to all seven, branded, and older ASMs. Cenobamate demonstrated comparable TEAE withdrawal rates to all seven ASMs, branded ASMs, and older ASMs across each of the four dose ranges (all p > 0.05). SIGNIFICANCE: Patients receiving FDA-RDMD of cenobamate were more likely to have ≥50% seizure reduction compared with FDA-RDMD of the seven assessed ASMs and branded ASMs, without an increase in treatment discontinuation due to TEAEs.

Seizures and Cognitive Outcome After Traumatic Brain Injury: A Post Hoc Analysis.

INTRODUCTION: Seizures and abnormal periodic or rhythmic patterns are observed on continuous electroencephalography monitoring (cEEG) in up to half of patients hospitalized with moderate to severe traumatic brain injury (TBI). We aimed to determine the impact of seizures and abnormal periodic or rhythmic patterns on cognitive outcome 3 months following moderate to severe TBI. METHODS: This was a post hoc analysis of the multicenter randomized controlled phase 2 INTREPID2566 clinical trial conducted from 2010 to 2016 across 20 United States Level I trauma centers. Patients with nonpenetrating TBI and postresuscitation Glasgow Coma Scale scores 4-12 were included. Bedside cEEG was initiated per protocol on admission to intensive care, and the burden of ictal-interictal continuum (IIC) patterns, including seizures, was quantified. A summary global cognition score at 3 months following injury was used as the primary outcome. RESULTS: 142 patients (age mean + / - standard deviation 32 + / - 13 years; 131 [92%] men) survived with a mean global cognition score of 81 + / - 15; nearly one third were considered to have poor functional outcome. 89 of 142 (63%) patients underwent cEEG, of whom 13 of 89 (15%) had severe IIC patterns. The quantitative burden of IIC patterns correlated inversely with the global cognition score (r = - 0.57; p = 0.04). In multiple variable analysis, the log-transformed burden of severe IIC patterns was independently associated with the global cognition score after controlling for demographics, premorbid estimated intelligence, injury severity, sedatives, and antiepileptic drugs (odds ratio 0.73, 95% confidence interval 0.60-0.88; p = 0.002). CONCLUSIONS: The burden of seizures and abnormal periodic or rhythmic patterns was independently associated with worse cognition at 3 months following TBI. Their impact on longer-term cognitive endpoints and the potential benefits of seizure detection and treatment in this population warrant prospective study.

Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome.

BACKGROUND: Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy. METHODS: In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox-Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period. RESULTS: A total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percent reduction from baseline in drop-seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P=0.005 for the 20-mg cannabidiol group vs. placebo group, and P=0.002 for the 10-mg cannabidiol group vs. placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher-dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations. CONCLUSIONS: Among children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations. (Funded by GW Pharmaceuticals; GWPCARE3 ClinicalTrials.gov number, NCT02224560 .).

Time to onset of cannabidiol (CBD) treatment effect in Lennox-Gastaut syndrome: Analysis from two randomized controlled trials.

OBJECTIVE: To estimate time to onset of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]), we conducted post hoc analyses of data from two randomized, placebo-controlled, Phase 3 trials, GWPCARE3 (NCT02224560) and GWPCARE4 (NCT02224690), of patients with Lennox-Gastaut syndrome. METHODS: Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex, 100 mg/ml oral solution) at 10 mg/kg/day (CBD10; GWPCARE3) or 20 mg/kg/day (CBD20; both trials) or placebo for 14 weeks. Treatment started at 2.5 mg/kg/day for all groups and reached 10 mg/kg/day on Day 7 and 20 mg/kg/day (CBD20 and matching placebo only) on Day 11. Percentage change from baseline in drop seizure frequency was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated. RESULTS: Overall, 235 patients received CBD (CBD10 [GWPCARE3 only], n = 67; CBD20 [pooled GWPCARE3&4], n = 168) and 161 received placebo. Mean (range) age was 15.3 years (2.6-48.0). Patients had previously discontinued a median (range) of six (0-28) antiepileptic drugs (AEDs) and were currently taking a median of three (0-5) AEDs. Differences in drop seizure reduction between placebo and CBD emerged during the titration period and became nominally significant by Day 6 (p = .008) for pooled CBD treatment groups. Separation between placebo and CBD in ≥50% responder rate emerged by Day 6. Onset of the first reported AE occurred during the titration period in 45% of patients (CBD10, 46%; CBD20, 52%; placebo, 38%). In patients with AEs, resolution occurred within 4 weeks of onset in 53% of placebo and 39% of CBD patients and by end of study in 63% of placebo and 61% of CBD patients. SIGNIFICANCE: Treatment effect (efficacy and AEs) of CBD may occur within 1 week of starting treatment. Although AEs lasted longer for CBD than placebo, most resolved within the 14-week period.

Characteristics of men with conversion disorder.

OBJECTIVE: Women comprise the majority of subjects with conversion disorders in nearly all studies. The authors previously identified 96 subjects with psychogenic non-epileptic seizures (PNES) and found that female sex, alexithymia and childhood trauma were strongly correlated with the development of PNES. In order to characterize men with PNES, the authors collected questionnaire data on a series of male subjects recruited from an epilepsy monitoring unit (EMU). METHODS: Only male patients admitted to the EMU were asked to complete the Toronto Alexithymia Scale-20 (TAS-20) and the Childhood Trauma Questionnaire (CTQ). Results were correlated with diagnosis at discharge, either epileptic seizures (ES) or PNES. RESULTS: Ninety-two subjects submitted complete questionnaire data. Sixty-nine subjects (74%) were diagnosed with ES, 13 subjects (14%) were diagnosed with PNES and 10 subjects (11%) had an undetermined diagnosis. There were no significant differences on the TAS-20 or the CTQ by diagnosis. CONCLUSION: In this sample of men admitted to an EMU there was no difference in the extent of alexithymia or childhood trauma between men with ES and PNES. There was a small number of men with a PNES diagnosis, which may have limited our ability to identify differences in the groups. The clear correlation of childhood trauma and alexithymia with development of conversion disorder in women could not be demonstrated in men.

Developing epilepsy training capacity for primary care providers using the project ECHO telementoring model.

BACKGROUND: Primary care providers (PCPs) provide a large proportion of care for people with epilepsy (PWE) and need regular training for updates. However, PCPs treat patients in so many therapeutic areas that epilepsy often becomes a less important concern. We used an established telementoring program, Project ECHO (Extension for Community Healthcare Outcomes), and combined epilepsy education with general neurology topics to generate more interest among PCPs. METHODS: We offered 20 one-hour webinar sessions over a two-year period, each consisting of a panel of neurology experts, with a combination of case presentations, a 20-minute didactic presentation, and live, interactive question and answer. Attendees logged in from their own computers or phones, and all presentations were archived online for future viewing. Interviews with PCPs indicated a combination of epilepsy and general neurology topics would be better received, so epilepsy topics alternated monthly with general neurology topics (e.g., headache, stroke, and dementia). Session evaluation included participants' comfort in treating patients with neurological disorders and confidence in knowledge of the topic area. RESULTS: After the second session, mean attendance was 27.5 participants (range 15-38), with a total of 164 unique individual participants. Attendees were a mix of mostly regional, some out of state, and a few international learners, including practicing PCPs, trainees, and nurse practitioners. Archived presentations on our website were viewed 212 times; seizure topics were the most viewed. Mean evaluation scores for relevance, value, and increased knowledge were all in the "agree to strongly agree" range. Over 97% of respondents reported greater interest in improving care of patients with epilepsy or neurological disorders, and over 98% reported greater comfort and self-efficacy when treating patients with these conditions. Only eight cases were submitted for review prior to the sessions. CONCLUSIONS: We successfully piloted a telementoring program using Project ECHO methodology, which was effective in educating PCPs about epilepsy treatment. Combining epilepsy and other neurology topics was an effective strategy in garnering interest among PCPs, but additional methods are needed to encourage participants to present their own cases.

Coffee and cigarette smoking interactions with lamotrigine.

The objective of this analysis was to determine possible interactions between lamotrigine (LTG) and coffee or cigarette use. As part of the statistical analysis of factors influencing LTG pharmacokinetics (PK) in the Equigen chronic dose study, we collected prospective data from enrolled patients on their use of coffee and cigarettes. Subjects were part of a crossover replication study of generic LTG products with rigorous blood sampling and were instructed to not change their typical consumption of these products for the duration of the study. A total of 35 subjects were enrolled, with 33 subjects having sufficient data for analysis. Higher consumption of coffee was associated with a significantly lower area under the curve (AUC) and maximum concentration (Cmax) of lamotrigine (LTG). Higher cigarette use did not result in a significant change in AUC or Cmax. Coffee, but not cigarette use, either induces LTG metabolism or inhibits LTG absorption.

Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus.

Cannabidiol (CBD), a major purified nonpsychoactive component of cannabis with anticonvulsant properties, was approved by the U.S. Food and Drug Administration (FDA) in June 2018 as an adjuvant treatment for refractory epilepsy (Epidiolex; GW Pharmaceuticals). CBD is metabolized by cytochrome P450 (CYP)3A4 and CYP2C19 with a growing body of evidence suggesting it is also a potent inhibitor of these pathways. We report for the first time a significant drug-drug interaction between the purified CBD product and tacrolimus. A participant in a CBD clinical trial for epilepsy who was also receiving tacrolimus showed an approximately 3-fold increase in dose-normalized tacrolimus concentrations while receiving 2000-2900 mg/day of CBD. Our report delineates an important concern for the transplant community with the increasing legalization of cannabis and advent of an FDA-approved CBD product. Larger studies are needed to better understand the impact of this drug-drug interaction in solid organ transplant recipients.

Behavioral interventions in epilepsy.

PURPOSE OF REVIEW: Behavioral intervention describes multiple modalities of treatments which are of increasing interest in epilepsy. This review addresses recent behavioral clinical trials in epilepsy including cognitive behavioral therapy (CBT), mindfulness, progressive muscle relaxation (PMR), and self-management. Results and conclusions from updated Cochrane reviews and the recent International League Against Epilepsy Psychology task force are presented. RECENT FINDINGS: Two recent large randomized controlled trials (mindfulness and progressive muscle relaxation) reported improved seizure frequency with behavioral treatments. In both studies, participants in both the active and the attentional control arms showed significant seizure reduction, whereas quality of life and stress reduction were better noted in the active arms. Additional behavioral modalities have reported improved seizure control including yoga, bio/neurofeedback, and music therapy.Significant improvements in multiple quality of life, cognitive domains, and medication adherence have been reported from randomized and open label trials of cognitive behavioral therapy, and self-management programs. Multiple promising self-management programs have been recently reported, often utilizing the power of web-based apps, and digitally delivered group therapy. In 2018, the International League Against Epilepsy Psychology task force recommended that 'psychological interventions should be incorporated into comprehensive epilepsy care.' SUMMARY: Behavioral treatments are successful and likely underutilized in the treatment of epilepsy. Given the challenge of conducting randomized clinical trials of behavioral therapy, much remains to be studied. However, for motivated and interested patients, appropriately chosen behavioral therapies appear to be important adjuncts to standard therapy. The timing is currently optimal to take best advantage of smartphone apps and web-based delivery systems, both for research and therapeutic purposes.

Continuous Electroencephalography After Moderate to Severe Traumatic Brain Injury.

OBJECTIVES: After traumatic brain injury, continuous electroencephalography is widely used to detect electrographic seizures. With the development of standardized continuous electroencephalography terminology, we aimed to describe the prevalence and burden of ictal-interictal patterns, including electrographic seizures after moderate-to-severe traumatic brain injury and to correlate continuous electroencephalography features with functional outcome. DESIGN: Post hoc analysis of the prospective, randomized controlled phase 2 multicenter INTREPID study (ClinicalTrials.gov: NCT00805818). Continuous electroencephalography was initiated upon admission to the ICU. The primary outcome was the 3-month Glasgow Outcome Scale-Extended. Consensus electroencephalography reviews were performed by raters certified in standardized continuous electroencephalography terminology blinded to clinical data. Rhythmic, periodic, or ictal patterns were referred to as "ictal-interictal continuum"; severe ictal-interictal continuum was defined as greater than or equal to 1.5 Hz lateralized rhythmic delta activity or generalized periodic discharges and any lateralized periodic discharges or electrographic seizures. SETTING: Twenty U.S. level I trauma centers. PATIENTS: Patients with nonpenetrating traumatic brain injury and postresuscitation Glasgow Coma Scale score of 4-12 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 152 patients with continuous electroencephalography (age 34 ± 14 yr; 88% male), 22 (14%) had severe ictal-interictal continuum including electrographic seizures in four (2.6%). Severe ictal-interictal continuum burden correlated with initial prognostic scores, including the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (r = 0.51; p = 0.01) and Injury Severity Score (r = 0.49; p = 0.01), but not with functional outcome. After controlling clinical covariates, unfavorable outcome was independently associated with absence of posterior dominant rhythm (common odds ratio, 3.38; 95% CI, 1.30-9.09), absence of N2 sleep transients (3.69; 1.69-8.20), predominant delta activity (2.82; 1.32-6.10), and discontinuous background (5.33; 2.28-12.96) within the first 72 hours of monitoring. CONCLUSIONS: Severe ictal-interictal continuum patterns, including electrographic seizures, were associated with clinical markers of injury severity but not functional outcome in this prospective cohort of patients with moderate-to-severe traumatic brain injury. Importantly, continuous electroencephalography background features were independently associated with functional outcome and improved the area under the curve of existing, validated predictive models.

Seizures and movement disorders: phenomenology, diagnostic challenges and therapeutic approaches.

Seizures and movement disorders (MDs) are distinct neurological conditions presenting with abnormal movements. Despite sharing an overlap in phenomenology, these movements have different origins. In order to explore the overlaps and the narrow boundaries between these two conditions, we performed a review of the literature to explore the risk of seizures in MDs. We discussed the mimics and chameleons including MDs that look like seizure (eg, paroxysmal dyskinesia, status dystonicus) and seizures that look like MDs (eg, epilepsia partialis continua, nocturnal frontal lobe epilepsy). Additionally, we examined the therapeutic challenges as well as the anatomical and chemical pathways relevant in the interplay between epilepsy and MDs. Finally, we proposed an algorithm to guide clinicians towards the final diagnosis of conditions characterised by the co-occurrence of MDs and seizures.

The role of cigarette smoking in epilepsy severity and epilepsy-related quality of life.

Empirical evidence suggests that cigarette smoking is common among individuals with epilepsy. However, little is known about relationship between smoking and clinical features of epilepsy. Thus, the aim of the current study was to examine the differences between smokers (n = 43; 58.1% female, Mage = 43.4 years, SD = 11.6) and nonsmokers (n = 49; 63.3% female, Mage = 48.5 years, SD = 15.9) with epilepsy in terms of epilepsy severity (i.e., presence of seizures in the past year, refractory epilepsy status) and epilepsy-related quality of life. As hypothesized, smokers with epilepsy, compared with nonsmokers with epilepsy, were at an increased risk to have experienced seizures in the past year after controlling for the effect of Medicaid status as a proxy for socioeconomic status (odds ratio [OR] = 3.61). Positive smoking status was also associated with lower levels of epilepsy-related quality of life; however, this finding did not remain significant when Medicaid status was taken into consideration. Contrary to the hypotheses, smokers with epilepsy were not at an increased risk of having refractory epilepsy compared with nonsmokers with epilepsy. These findings suggest that cigarette smoking is associated with at least one aspect of epilepsy severity. Thus, in addition to the broader health benefits, smokers with epilepsy should be advised of the increased seizure risk associated with current cigarette smoking. Future work should examine the longitudinal impact of smoking on epilepsy severity, including whether successful smoking cessation ameliorates the seizure risk found in this cross-sectional study.

Fetal antiepileptic drug exposure and learning and memory functioning at 6 years of age: The NEAD prospective observational study.

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain.

Physician Burnout and Barriers to Care on Professional Applications.

We surveyed New York physicians to study their perceptions of reporting requirements related to their own mental health care on professional applications, including whether they were experiencing symptoms of burnout. Over half of the responding physicians reported experiencing symptoms of burnout and these physicians were at increased odds of perceiving a barrier to seeking mental health care if they had to report such care on professional applications and renewals for medical licensure, malpractice, and hospital privileges and credentialing compared to physicians not experiencing symptoms of burnout. As state medical boards, hospitals, and insurers seek information to help assess risks posed by physicians, it is essential to strike an appropriate balance between their duty to protect the public and the physician's right to confidentiality. This balance can be assessed based on the questions that are asked on various professional applications and how information gleaned through physician responses is used. Overly intrusive questions, though well intentioned to protect the public, may run counter to current interpretations of federal law and may inhibit care-seeking among physicians, which is critical to both patient safety and physician health.

Panic and epilepsy in adults: A systematic review.

The purpose of the current paper was to review the empirical literature on the cooccurrence of panic and epilepsy, in order to determine whether there is an increased risk of panic attacks and panic disorder among adults with epilepsy and an increased risk of epilepsy among adults with panic disorder. Given the overlap between panic and ictal fear, a preliminary aim of the current review was to critically evaluate the methodology used to differentiate between diagnoses of panic disorder and epilepsy in existing research. A literature search was conducted in relevant electronic databases, and articles that directly focused on panic and epilepsy among adults were selected for the current review (n = 17). Overall, results suggest that rates of epilepsy are elevated among individuals with panic disorder and that panic attacks are elevated among individuals with epilepsy, but rates of panic disorder among people with epilepsy are inconsistent. However, most studies did not use sufficiently rigorous methods to differentiate between panic disorder and epilepsy. Therefore, a critical next step in this area of research is to develop a standard procedure for differentiating ictal fear from panic attacks and panic disorder.

Childhood trauma in patients with self-reported stress-precipitated seizures.

OBJECTIVE: Stress is the most commonly reported precipitant of epileptic seizures, but the mechanism by which stress precipitates seizures and the risk factors for stress as a seizure precipitant are poorly understood. Previously, we observed higher levels of anxiety symptoms in patients with epilepsy who reported stress as a seizure precipitant. Given that childhood trauma increases the risk of general psychiatric symptom burden, including anxiety symptoms, we sought to examine the relationship between childhood adversity and stress as a seizure precipitant. METHODS: Sequential outpatients (N=236) evaluated at the Epilepsy Center of the University of Cincinnati Neuroscience Institute who had previously enrolled in an earlier study of stress and seizures were enrolled. Subjects either endorsed stress as a seizure precipitant [Stress (+)] or not [Stress (-)]. The Childhood Trauma Questionnaire Short Form (CTQ-SF), a 28-question scale that evaluates 5 domains of childhood adversity (physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse) was sent via mail and returned on paper or electronically from participants. Total CTQ-SF score and CTQ-SF domain scores were compared between Stress (+) and Stress (-) groups using Wilcoxon rank sum test. Spearman's rank correlation between CTQ-SF scores with depression and anxiety was also determined, and these analyses were followed by a multivariate analysis to identify the association of childhood trauma with other factors including anxiety and depression. RESULTS: A total of 119 out of 236 CTQ-SFs that were sent out were completed. Response rates were 91/195 for Stress (+) and 28/41 for Stress (-). The Stress (+) group reported higher scores in emotional abuse compared with the Stress (-) group (p=0.029); CTQ-SF total scores were higher in the Stress (+) group compared with the Stress (-) group (p=0.08), and sexual abuse scores were higher in Stress (+) group (p=0.07), but there were no statistically significant differences for other types of trauma. Depression and anxiety scores were higher in the Stress (+) group, but anxiety was the only independent factor associated with the Stress (+) group in the multivariate analysis (p=0.0021). CONCLUSION: Patients with epilepsy who report stress as a seizure precipitant are more likely to endorse a history of childhood traumatic experiences, particularly emotional abuse, compared with those who do not perceive stress as a precipitant. Further study is needed to identify how childhood trauma interacts with anxiety in modulating stress response in patients with epilepsy.

Translational models of workplace violence in health care.

Decision makers have little time to study literature on the prevention and management of workplace violence (WPV). In a health care workplace setting, identifying the person, stimulus, and environmental interactions that can lead to violence is a complicated process. Those in positions of leadership make decisions that affect many individuals, agencies, and communities. Often, they come from different professional backgrounds yet need ways of rapidly understanding concepts of violence that transcend their profession, training, or experience. Translational models (TMs) in WPV visually summarize and interprofessionally facilitate this understanding of concepts, enhancing the chances of more effective collaborative solutions to WPV. The purpose of this article is to demonstrate how TM can be used in interprofessional settings to find effective solutions to reduce WPV.

Differences in paracingulate connectivity associated with epileptiform discharges and uncontrolled seizures in genetic generalized epilepsy.

OBJECTIVE: Patients with genetic generalized epilepsy (GGE) frequently continue to have seizures despite appropriate clinical management. GGE is associated with changes in the resting-state networks modulated by clinical factors such as duration of disease and response to treatment. However, the effect of generalized spike and wave discharges (GSWDs) and/or seizures on resting-state functional connectivity (RSFC) is not well understood. METHODS: We investigated the effects of GSWD frequency (in GGE patients), GGE (patients vs. healthy controls), and seizures (uncontrolled vs. controlled) on RSFC using seed-based voxel correlation in simultaneous electroencephalography (EEG) and resting-state functional magnetic resonance imaging (fMRI) (EEG/fMRI) data from 72 GGE patients (23 with uncontrolled seizures) and 38 healthy controls. We used seeds in paracingulate cortex, thalamus, cerebellum, and posterior cingulate cortex to examine changes in cortical-subcortical resting-state networks and the default mode network (DMN). We excluded from analyses time points surrounding GSWDs to avoid possible contamination of the resting state. RESULTS: (1) Higher frequency of GSWDs was associated with an increase in seed-based voxel correlation with cortical and subcortical brain regions associated with executive function, attention, and the DMN; (2) RSFC in patients with GGE, when compared to healthy controls, was increased between paracingulate cortex and anterior, but not posterior, thalamus; and (3) GGE patients with uncontrolled seizures exhibited decreased cerebellar RSFC. SIGNIFICANCE: Our findings in this large sample of patients with GGE (1) demonstrate an effect of interictal GSWDs on resting-state networks, (2) provide evidence that different thalamic nuclei may be affected differently by GGE, and (3) suggest that cerebellum is a modulator of ictogenic circuits.

Characteristics of people with self-reported stress-precipitated seizures.

OBJECTIVE: Stress is the most common patient-reported seizure precipitant. We aimed to determine mood and epilepsy characteristics of people who report stress-precipitated seizures. METHODS: Sequential patients at a tertiary epilepsy center were surveyed about stress as a seizure precipitant. We asked whether acute (lasting minutes-hours) or chronic (lasting days-months) stress was a seizure precipitant, whether stress reduction had been tried, and what effect stress reduction had on seizure frequency. We collected information on antiepileptic drugs, history of depression and anxiety disorder, prior or current treatment for depression or anxiety, and scores on the Neurological Disorders Depression Inventory (NDDI-E) and Generalized Anxiety Disorders-7 (GAD-7) instruments, which are administered at every visit in our Epilepsy Center. We also asked whether respondents thought that they could predict their seizures to determine if stress as a seizure precipitant was correlated with seizure self-prediction. RESULTS: Two hundred sixty-six subjects were included: 219 endorsed stress as a seizure precipitant [STRESS (+)] and 47 did not [STRESS (-)]. Among STRESS (+) subjects, 85% endorsed chronic stress as a seizure precipitant, and 68% endorsed acute stress as a seizure precipitant. In STRESS (+) subjects, 57% had used some type of relaxation or stress reduction method (most commonly yoga, exercise and meditation), and, of those who tried, 88% thought that these methods improved seizures. Among STRESS (-) subjects, 25% had tried relaxation or stress reduction, and 71% thought that seizures improved. Although univariate analysis showed multiple associations with stress as a seizure precipitant, in the multivariable logistic regression, only the GAD-7 score was associated with STRESS (+) (OR = 1.18 [1.03-1.35], p = 0.017). Subjects who reported stress as a seizure precipitant were more likely to report an ability to self-predict seizures (p < 0.001). CONCLUSION: Stress-precipitated seizures are commonly reported by patients, may be associated with either acute stress or chronic stress, and are associated with higher scores on anxiety tests. Patients frequently use stress reduction methods to self-treat and report high success rates. A prospective, randomized trial of stress reduction for seizures is indicated.