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An exploratory analysis from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray for acute treatment of seizure clusters assessed the use of a second dose up to 24 hours after the initial dose and effectiveness in potentially reducing the number of seizures.Seizures and doses were recorded in diaries.Of 175 patients enrolled, 163 received ≥1 dose of diazepam nasal spray and were included in the safety population; those patients received a total of 4390 doses for a total of 3853 seizure clusters. Less than half of these patients used a second dose a least once during the study (79 patients [48.5%]), with a total of 485 second doses for seizure clusters (12.6% of all seizure clusters). Among these 79 patients, 33 (41.8%) used only one second dose during the study (range: 1-82). The proportion of seizure clusters treated with a second dose over time was consistently low across 24 h: 0-4 h, 152 (3.9%); 4-6 h, 72 (1.9%); 6-8 h, 39 (1.0%); 8-12 h, 55 (1.4%); 12-16 h, 42 (1.1%); 16-20 h, 42 (1.1%); 20-24 h, 83 (2.2%). Rates of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs occurring within 1 day of a second dose were low (15.2% and 5.1%, respectively).Patients with epilepsy may experience seizure clusters lasting up to 24 hours, and little is known about the effectiveness of rescue therapies for that duration. The current labeling of the US Food and Drug Administration (FDA)-approved outpatient treatments for seizure clusters (rectal diazepam, intranasal midazolam, and diazepam nasal spray) allows for a second dose, if needed, for control. These findings support the safety profile of second doses, and the low use supports the effectiveness of diazepam nasal spray across 24 hours.

Background and ObjectivesTo explore efficacy/safety of natalizumab, a humanized monoclonal anti–α4-integrin antibody, as adjunctive therapy in adults with drug-resistant focal epilepsy.MethodsParticipants with ≥6 seizures during the 6-week baseline period were randomized 1:1 to receive natalizumab 300 mg IV or placebo every 4 weeks for 24 weeks. Primary efficacy outcome was change from baseline in log-transformed seizure frequency, with a predefined threshold for therapeutic success of 31% relative reduction in seizure frequency over the placebo group. Countable seizure types were focal aware with motor signs, focal impaired awareness, and focal to bilateral tonic-clonic. Secondary efficacy endpoints/safety were also assessed.ResultsOf 32 and 34 participants dosed in the natalizumab 300 mg and placebo groups, 30 (94%) and 31 (91%) completed the placebo-controlled treatment period, respectively (one participant was randomized to receive natalizumab but not dosed due to IV complications). Estimated relative change in seizure frequency of natalizumab over placebo was −14.4% (95% confidence interval [CI] –46.1%–36.1%; p = 0.51). The proportion of participants with ≥50% reduction from baseline in seizure frequency was 31.3% for natalizumab and 17.6% for placebo (odds ratio 2.09, 95% CI 0.64–6.85; p = 0.22). Adverse events were reported in 24 (75%) and 22 (65%) participants receiving natalizumab vs placebo.DiscussionAlthough the threshold to demonstrate efficacy was not met, there were no unexpected safety findings and further exploration of possible anti-inflammatory therapies for drug-resistant epilepsy is warranted.Trial Registration InformationThe ClinicalTrials.gov registration number is NCT03283371.Classification of EvidenceThis study provides Class I evidence that IV natalizumab every 4 weeks, compared to placebo, did not significantly change seizure frequency in adults with drug-resistant epilepsy. The study lacked the precision to exclude an important effect of natalizumab.

Background Previous studies of racial differences in Alzheimer disease (AD) presentation have not included Native Hawaiians and Pacific Islanders (NHPI). Objective To explore the presentation of AD and mild cognitive impairment (MCI) in NHPI. Method We conducted a retrospective review of patient records from Hawaii with a diagnosis of unspecified AD or MCI from September 2000 to September 2019. Variables of interest included age at diagnosis, gender, race, marital status, insurance, comorbidities, and scores on the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). Results We reviewed the medical records of 598 patients, including 224 Asians, 202 Whites, 87 NHPI, and 85 Other. AD was more dominant than MCI across all of the groups, with the highest percentage in NHPI. Among the mean ages of diagnosis, NHPI were the youngest. Across all groups, a higher proportion of women than men had AD, with the highest female prevalence among NHPI. Hypertension, hyperlipidemia, and type II diabetes were highest among NHPI compared with the other groups. Of individuals with MMSE/MoCA scores, there were significant variations in scores by racial group. The mean MMSE/MoCA score was highest among Whites and lowest among NHPI. Conclusion Compared with other racial groups, NHPI have a higher proportion of AD than MCI at diagnosis, are diagnosed at a younger age, have a higher female prevalence, have more comorbidities that may contribute to AD/MCI onset, and present with lower MMSE scores.

Alprazolam administered via the Staccato® breath-actuated device is delivered into the deep lung for rapid systemic exposure and is a potential therapy for rapid epileptic seizure termination (REST). We conducted an inpatient study (ENGAGE-E-001 [NCT03478982]) in patients with stereotypic seizure episodes with prolonged or repetitive seizures to determine whether Staccato alprazolam rapidly terminates seizures in a small observed population after administration under direct supervision.Adult patients with established diagnosis of focal and/or generalized epilepsy with a documented history of seizure episodes with a predictable pattern were enrolled. They were randomized 1:1:1 to double-blind treatment of a single seizure event with one dose of Staccato alprazolam 1.0 mg or 2.0 mg, or Staccato placebo in an inpatient unit. The primary end point of the study was the proportion of responders in each treatment group achieving seizure activity cessation within 2 min after administration of study drug and no recurrence of seizure activity within 2 h.A total of 273 patients were screened, and 116 randomized patients received treatment with the study drug in the double-blind part. The proportion of treated patients who were responders was 65.8% for each of Staccato alprazolam 1.0 mg (n = 38; p = .0392) and 2.0 mg (n = 38; p = .0392), compared with 42.5% for Staccato placebo (n = 40). Staccato alprazolam was well tolerated when administered as a single dose of 1.0 or 2.0 mg: cough and somnolence were the most common adverse events (AEs) (both 14.5%), followed by dysgeusia (13.2%). AEs were mostly mild or moderate in intensity; there were no treatment-related serious AEs.Both 1.0 mg and 2.0 mg doses of Staccato alprazolam demonstrated efficacy in rapidly terminating seizures in an inpatient setting and were well tolerated. The next step is a Phase 3 confirmatory study to demonstrate efficacy and safety of Staccato alprazolam for rapid cessation of seizures in an outpatient setting.

Clinical trials for calcitonin gene-related peptide (CGRP) inhibitors excluded the concomitant use of onabotulinumtoxinA; thus, there is a lack of efficacy and safety data of the combined therapies. Our study aims to examine the effectiveness of CGRP inhibitors with onabotulinumtoxinA by evaluating migraine reductions in headache days and severity. Seventeen patients with chronic migraines were identified who had a partial or poor response to onabotulinumtoxinA, and were placed on dual therapy with a CGRP inhibitor. Patients’ initial headache days and severity ratings were compared to final values taken 1–6 months after adding the CGRP inhibitor to their treatment regime. Comparisons between headache days and severity ratings prior to and during dual treatment were performed utilizing the Kruskal–Wallis test. The significance was set at p

Objective Need for rescue therapy differs among patients with seizure clusters. Diazepam nasal spray is approved to treat seizure clusters in patients with epilepsy ≥6 years of age. This analysis used interim data from a phase 3 safety study to assess safety profile and effectiveness of diazepam nasal spray using average number of doses/month as a proxy measurement. Methods This phase 3, open‐label, repeat‐dose, safety study of diazepam nasal spray enrolled patients (6‐65 years) with epilepsy and need of benzodiazepine rescue. Patients were stratified by average number of doses/month (5, very‐high frequency). Safety was evaluated based on treatment‐emergent adverse events (TEAEs), assessed nasal irritation, and olfaction. The proportion of treatments given as a second dose was used as an exploratory proxy for effectiveness. Results Of 175 enrolled patients (data cutoff, October 31, 2019), 158 received ≥1 dose of diazepam nasal spray. Frequency of use was moderate in 43.7% of patients, high in 50.6% of patients, and very high in 5.7% of patients. Patients treated 3397 seizure episodes (moderate frequency, 14.2%; high frequency, 59.9%; very high frequency, 25.8%). Nasal discomfort was the most common treatment‐related TEAE in all groups. No notable changes in nasal irritation or olfaction were observed. Second doses represented only 2.5%, 7.5%, and 17.2% of all doses in the moderate‐, high‐, and very‐high‐frequency groups, respectively. Overall retention rate was 82.9%, without an observed relationship to frequency of use. Significance Frequency of dosing diazepam nasal spray had little impact on the safety/tolerability profile across a range of 5 doses/month. Effectiveness was suggested for all dosing frequencies by the high proportion of seizure clusters not treated with a second dose. These results support the utility, safety profile, and effectiveness of diazepam nasal spray across frequencies of seizure cluster burden.

Objective Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. Methods A long‐term, phase 3, open‐label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. Results Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6–65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no‐benzodiazepine group. Findings were similar in a sub‐analysis of patients who were (n = 44) or were not (n = 75) taking clobazam. Significance This analysis of patients from a long‐term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub‐analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.

OBJECTIVE: A survey was implemented for early assessment of pandemic-related practice processes and quality improvement (QI). BACKGROUND: In response to the public health measures in Hawaii to curtail the coronavirus 2019 pandemic, Hawaii Pacific Neuroscience (HPN) adapted their patient care to ensure continuity of neurological treatment. METHODS: The telephone survey was conducted on patients seen at HPN during the period of April 22, 2020-May 18, 2020 to address four areas related to patients' outpatient experience: delivery of care, general well-being, experience with telemedicine, and disease-specific questions. RESULTS: A total of 928 patients were contacted of which 429 (46.2%) patients responded and 367 (85.5%) agreed to participate. A total of 133 patients with migraine and 234 patients with other neurological conditions provided responses. Our migraine patients' survey responses suggest that their well-being was disproportionately negatively affected by the pandemic. Survey respondents with migraine were significantly more likely than their non-migraine peers to report worsening anxiety and sleep problems [62/132 (47.0%) vs. 78/234 (33.3%), χ2 = 6.64, p = 0.010, and 64/132 (48.5%) vs. 73/234 (31.2%), χ2 = 10.77, p = 0.001]; migraine patients also reported worsening of depression as a result of the pandemic more than patients with other diagnoses, though this was not statistically significant [44/132 (33.3%) vs. 57/234 (24.4%), χ2 = 3.40, p = 0.065]. In regard to access to healthcare, significantly more migraine patients reported running out of medications than those with other diagnoses [20/133 (15.0%) vs. 18/234 (7.7%), χ2 = 4.93, p = 0.026]. More avoided seeking medical help for new health problems because of the pandemic [30/133 (22.6%) vs. 30/234 (12.8%), χ2 = 5.88, p = 0.015]. Migraine patients were also significantly impacted economically by the pandemic; 43/132 (32.4%) of migraine patients reported losing their jobs as the result of the pandemic versus 34/234 (14.5%) of their peers (χ2 = 11.20, p

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

Introduction: Given that the success of vaccines against coronavirus disease 2019 (COVID-19) relies on herd immunity, identifying patients at risk for vaccine hesitancy is imperative—particularly for those at high risk for severe COVID-19 (i.e., minorities and patients with neurological disorders). Methods: Among patients from a large neuroscience institute in Hawaii, vaccine hesitancy was investigated in relation to over 30 sociodemographic variables and medical comorbidities, via a telephone quality improvement survey conducted between 23 January 2021 and 13 February 2021. Results: Vaccine willingness (n = 363) was 81.3%. Univariate analysis identified that the odds of vaccine acceptance reduced for patients who do not regard COVID-19 as a severe illness, are of younger age, have a lower Charlson Comorbidity Index, use illicit drugs, or carry Medicaid insurance. Multivariable logistic regression identified the best predictors of vaccine hesitancy to be: social media use to obtain COVID-19 information, concerns regarding vaccine safety, self-perception of a preexisting medical condition contraindicated with vaccination, not having received the annual influenza vaccine, having some high school education only, being a current smoker, and not having a prior cerebrovascular accident. Unique amongst males, a conservative political view strongly predicted vaccine hesitancy. Specifically for Asians, a higher body mass index, while for Native Hawaiians and other Pacific Islanders (NHPI), a positive depression screen, both reduced the odds of vaccine acceptance. Conclusion: Upon identifying the variables associated with vaccine hesitancy amongst patients with neurological disorders, our clinic is now able to efficiently provide ancillary COVID-19 education to sub-populations at risk for vaccine hesitancy. While our results may be limited to the sub-population of patients with neurological disorders, the findings nonetheless provide valuable insight to understanding vaccine hesitancy.

INTRODUCTION Against the backdrop of the diverse minority-majority state of Hawaii, this study seeks to better characterize associations between idiopathic intracranial hypertension (IIH) with sociodemographic variables and medical comorbidities. METHODS A retrospective case-control study was conducted by utilizing 54 IIH patients and 216 age-, sex-, and race-matched controls, 216 unmatched controls, and 63 age-, sex-, and race-matched migraine patients. RESULTS Relative to controls, IIH were 25 years younger (p 40 kg/m2; OR: 6.10), recent weight gain (OR: 11.66), current smoker (OR: 2.48), hypertensive (OR: 3.08), and peripheral vascular disease (OR: 16.42). Odds of IIH were reduced (p

We read with interest the recent paper by Fonseca et al. (1) in which they reported the effects of the COVID-19 pandemic on their Epilepsy clinic's patients in Spain who were assessed through a telephonic survey during the first month of confinement (16 March 2020 - 17 April 2020). Their work provides important insight into the impact of the pandemic on persons with Epilepsy, particularly in major outbreak areas.

Tolerance is a known consideration for maintenance use of benzodiazepines and other antiseizure drugs; however, clinical experience suggests that tolerance may not be anticipated with long-term intermittent use of benzodiazepines as rescue therapy. Diazepam nasal spray (Valtoco®) is a proprietary intranasal formulation approved for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Reported here are exploratory analyses investigating whether there was evidence of development of tolerance in an interim analysis of a long-term, phase 3, open-label safety study of diazepam nasal spray.Patients and care partners were trained to administer 5, 10, 15, or 20 mg of diazepam nasal spray (age- and weight-based dosing), with a second dose administered 4-12 hours later if needed. A series of analyses were performed to assess evidence of tolerance using 2 equal, adjacent time periods and data for each patient to compare the proportion of events for which second doses of diazepam nasal spray (as a proxy for effectiveness) were administered in period 1 compared with period 2.A total of 175 patients were enrolled at interim cutoff, and 158 were treated with diazepam nasal spray for 3370 seizure-cluster events. For 73.4% of patients, duration of exposure to diazepam nasal spray was ≥12 months. A total of 191 analyses were conducted; the proportion of analyses in which second doses in period 2 were lower than in period 1 was 72.8%. Only 5 analyses showed nominally statistically significant changes (P 0.05); this is fewer than expected by chance, and these differences were not directionally consistent. There was no safety signal with continued use.These analyses found no statistical evidence of tolerance with the use of diazepam nasal spray over time based on use of a second dose in an initial period of the study compared with a subsequent period for each patient. These results are in agreement with prior studies of benzodiazepine rescue therapy.

Introduction: Alzheimer's disease (AD) has no effective treatment, nor does its “precursor” mild cognitive impairment (MCI). Methods: This is a nine-month, randomized, open, pilot trial. We are using four dietary changes and twelve supplements to slow progression of dementia in patients with MCI. Patients were randomly assigned to the diet-plus-supplement intervention group (1) or to the supplement intervention group (2). Supplementary cobalamin, folate, and S-adenosylmethionine (SAM) may reduce secretase/amyloid production. Antioxidants coenzyme Q10, ascorbates, gamma-tocopherol, and extracts of ginkgo biloba and centella asiatica were used. Zinc, copper, manganese, and selenium support endogenous antioxidant enzymes. Dietary interventions include berries, walnuts, decreasing dietary advanced glycation endproduct intake, and limiting saturated fatty acids to seven percent of calories. Results: In this small pilot study, it was surprising that participants in the supplement-only group improved more than in the supplement-plus-diet group. The Mini Mental State Examination (MMSE) was administered at baseline and every 3 months. While 9.6% of MCI patients normally degenerate to dementia each year, over nine months, participants in the supplement-only group had an average improvement in the MMSE of 10 points (out of 30 points). At the end of the intervention, average score was 29 out of 30 points, indicating a normal cognitive state. In the food-plus-supplement group no degeneration was seen, although improvement was also not seen. Conclusions: This multifaceted nutritional intervention had a positive impact by slowing the progression of dementia and reducing the risk of Alzheimer’s disease. A larger, multicenter trial is needed to confirm these results.

Purpose This exploratory study compared the semiology of psychogenic nonepileptic seizures (PNES) between a diverse group of patients in the state of Hawaii. This study may expand understanding of PNES across different ethnocultural and gender groups. Methods A retrospective chart review of patients admitted to our Epilepsy Monitoring Unit (EMU) over a 4-year period was performed to compare semiology in different ethnic groups and gender. Results A total of 139 patients were included in this study, 37% (n = 51) with PNES, 34% (n = 47) with epilepsy only, and 29% (n = 41) with other non-PNES, nonepilepsy diagnosis. The number of Asians with PNES were found to differ when compared with the patients with epilepsy and the patients with non-PNES, nonepilepsy diagnosis. A positive trend was found in the number of Native Hawaiians and Caucasians with PNES in comparison with patients with non-PNES, nonepilepsy diagnosis. In addition, three semiology of PNES in Native Hawaiians were found to differ in comparison with other ethnic groups with PNES: rhythmic motor, mixed semiology, and nonepileptic aura. There is a significant difference in all motor manifestation between males and females in Native Hawaiians. Between patients with PNES, patients with epilepsy, and patients with non-PNES, nonepilepsy diagnosis, significant correlation was found in psychiatric disorders including posttraumatic stress disorder (PTSD), anxiety, and any psychiatric disorder. Conclusion This cross-cultural study found significant differences in the expression of PNES across key ethnoracial groups for the Islands of Hawaii. These findings have implications to the diagnosis and treatment of PNES for Native Hawaiians and other Pacific Islanders in the United States.

Objectives Currently, predicting and preventing idiopathic normal pressure hydrocephalus (iNPH) remains challenging, especially for patients without a history of cerebrovascular disease. By exploring the role of cardiovascular and psychiatric history, demographics, and socioeconomic status in iNPH, will provide better direction for elucidating the etiology or addressing healthcare inequalities. Patients and methods To investigate iNPH with respect to the selected risk factors, we conducted a retrospective case-control study from a neuroscience institute in Hawaii with a patient pool of 25,843. After excluding patients with a history of cerebrovascular disease, we identified 29 cases which meet the American-European guidelines for iNPH diagnosis. Meanwhile, 116 controls matched to age, sex, and race were also randomly selected. Results Median age at diagnosis was 83 (IQR: 74–88), with cases estimated 22 years older than controls (95 % CI: 14.00–29.00; p = 0.0000001). Patients with iNPH were more likely to be White (OR 4.01, 95 % CI: 1.59–10.11; p = 0.0042) and less likely Native Hawaiian and other Pacific Islander (OR 0.010, 95 % CI: 0.00−0.78; p = 0.014). Median household income was $2874 (95 % CI: 0.000089–6905; p = 0.088) greater amongst iNPH cases. Effect size amongst cardiovascular risk factors was not found statistically significant (i.e., body mass index, hyperlipidemia, type 2 diabetes mellitus, hypertension, coronary artery disease or prior myocardial infarction history, peripheral vascular disease, smoking status, congestive heart failure, atrial fibrillation/flutter, and history of prosthetic valve replacement). However, iNPH patients were more likely to have a history of alcohol use disorder (OR 8.29, 95 % CI: 0.99-453.87; p = 0.050) and history of a psychiatric disorder (OR 2.48; 95 % CI: 1.08–5.68; p = 0.029). Odds ratio for autoimmune disorder, thyroid disorder, glaucoma, and seizures did not reach statistical significance. Conclusion Patient race (i.e., White; Native Hawaiian or other Pacific Islander) was found associated with iNPH development. Meanwhile, after excluding those with cerebrovascular disease, cardiovascular risk factors were not found associated with iNPH. Lastly, iNPH cases were more inclined to have a history of alcohol use disorder and prior psychiatric disorder. Overall, this data reveals that a racial disparity exists amongst iNPH, as well as highlights the role of various cardiovascular and psychiatric risk factors, which can potentially provide direction in etiology elucidation.

The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) is a psychological testing tool used to measure psychological and personality constructs. The MMPI-2 has proven helpful in identifying individuals with nonepileptic events/nonepileptic seizures. However, the MMPI-2 has had some updates that enhanced its original scales. The aim of this article was to test the utility of updated MMPI-2 scales in predicting the likelihood of non-epileptic seizures in individuals admitted to an EEG video monitoring unit. We compared sensitivity, specificity, and likelihood ratios of traditional MMPI-2 Clinical Scales against more homogenous MMPI-2 Harris-Lingoes subscales and the newer Restructured Clinical (RC) scales. Our results showed that the Restructured Scales did not show significant improvement over the original Clinical scales. However, one Harris-Lingoes subscale (HL4 of Clinical Scale 3) did show improved predictive utility over the original Clinical scales as well as over the newer Restructured Clinical scales. Our study suggests that the predictive utility of the MMPI-2 can be improved using already existing scales. This is particularly useful for those practitioners who are not invested in switching over to the newly developed MMPI-2 Restructured Form (MMPI-2 RF).

Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.

Objective An estimated 24% of patients referred to epilepsy clinics actually have nonepileptic seizures. Various procedures have been used to precipitate nonepileptic events. The goal of this study was to use hypnosis in seizure provocation and differentiation between epileptic and nonepileptic seizure events. Methods Fifty study participants were enrolled from the Via Christi Comprehensive Epilepsy Center’s video/electroencephalography unit. Patients underwent the Hypnotic Induction Profile (HIP) to assess susceptibility to hypnosis. After completion of the HIP, participants underwent hypnosis by a physician trained to do so. They received a hypnotic suggestion to have a seizure. All seizure-like events were classified as either an epileptic, nonepileptic, or undetermined event based on whether or not the patient had abnormal EEG activity during the event. Results Of the 50 participants enrolled, 3 withdrew consent, resulting in 47 participants. Seven (15%) participants failed to have an event of any type and were classified as undetermined. Sixteen (34%) participants were classified as having epileptic seizure events, and 24 (51%) participants had nonepileptic events. Most participants were Caucasian (87%), female (57%), and unemployed (55%). HIP scores ranged from 0 to 10. Participants classified with nonepileptic scores had higher mean HIP scores (8.08, SD 2.483) than those diagnosed with epileptic seizures [5.94, SD 3.492, t (25) = 2.126, P = 0.044]. The sensitivity of eliciting a nonepileptic event during hypnosis was only 0.46, but the specificity was 0.88. Conclusion Hypnosis may be considered as a method of seizure provocation. Events provoked by hypnotic suggestion were more likely than not to be nonepileptic events. However, the current study has moderate specificity and poor sensitivity. Seizures could not be induced in patients who did not also have spontaneous seizures. Additional methodologies for seizure provocation need to be explored.

As the elderly represent the most rapidly growing population in the United States, it is critical that physicians are capable of managing their chronic illnesses, including epilepsy. Optimal treatment of epilepsy integrates an understanding of health-related quality of life (HRQOL), yet limited information is available to guide HRQOL issues among the elderly. This study found that seniors with epilepsy do not have poorer HRQOL compared with general epilepsy populations. However, when compared with general populations without epilepsy, seniors with epilepsy report a significantly lower HRQOL across all domains. Multiple factors may uniquely affect HRQOL among elderly populations with epilepsy: aging, comorbid conditions, and epilepsy variables. However, to our knowledge, no one instrument addresses all of these aspects. The development of HRQOL instruments specifically for an elderly population with epilepsy may be useful and needed.

As individuals directly impacted by their experience of epilepsy and others’ responses to it, epilepsy patients’ opinions about education and awareness issues are needed. A community-based participatory approach was used to develop a survey of public and patient attitudes and perceptions about epilepsy, which was administered to persons with epilepsy. The majority of the 165 respondents (34% response rate) indicated they perceive misperceptions and stigma related to epilepsy in the general public, which they thought could be ameliorated through educational interventions. Respondents indicated potential avenues of educational intervention for the general public as well as for those with epilepsy, with recommended content and intervention type depending on target audience. The community-based participatory research process and the patients’ perceptions gathered through the resulting survey indicate potential activities for overcoming stigma and increasing education and awareness related to epilepsy. 2007 Elsevier Inc. All rights reserved.

Complementary and alternative medicine (CAM) is recognized to be commonly used by patients, yet there have been few studies regarding the scope of CAM use by patients with epilepsy. This study assessed usage and perceptions of CAM by patients with epilepsy in the midwest of the United States. A 25-item survey was administered to adult patients with epilepsy, and data were collected from 228 patients. The survey collected demographics, specific CAM usage, adverse effects of CAM therapy, and perceptions of the effectiveness of CAM. Thirty-nine percent reported using CAM; 25% reported using CAM specifically for their epilepsy. Prayer/spirituality was the most commonly used form of CAM (46%), followed by "mega" vitamins (25%), chiropractic care (24%), and stress management (16%). CAM use is common among midwestern patients with epilepsy, although the pattern of use may be slightly different than in other regions of the United States and elsewhere.

Objective: To characterize the cognitive deficits in children with gelastic seizures and hypothalamic hamartoma and investigate the relationship of seizure severity to cognitive abilities. Methods: Eight children with gelastic seizures and hypothalamic hamartoma completed a neuropsychological battery of standardized and age-normed tests, including the Woodcock–Johnson Psycho-Educational Battery–Revised: Tests of Cognitive Ability, Peabody Picture Vocabulary Test-III , and initial-letter word fluency measure. Results: All children displayed cognitive deficits, ranging from mild to severe. Gelastic/complex partial seizure severity was correlated with broad cognitive ability standard scores ( r = −0.79; r 2 = 0.63; (F[1,6] = 10.28; p = 0.018]. Frequency of gelastic/complex partial seizures was also correlated with broad cognitive ability standard scores ( r = −0.72; r 2 = 0.52; F[1,6] = 6.44; p = 0.044). Significant intracognitive standard score differences were found, with relative weaknesses in long-term retrieval (mean = 64.1; SD = 13.3) and processing speed (mean = 67.7; SD = 21.6) and a relative strength in visual processing (mean = 97.6; SD = 12.8). Performance in visual processing differed from performance in long-term retrieval ( p = 0.009) and processing speed ( p = 0.029). Conclusion: These findings are consistent with cognitive functions and affective/emotional states associated with conduction pathways of the hypothalamus involving cortical association areas and amygdala and hippocampal formation. These abnormalities can account for the prominent deficit found in integrating information in the processing of memories.

The risk of dose-dependent seizures is a safety issue with bupropion hydrochloride. To evaluate the presence of specific electroencephalographic (EEG) waveforms, 210 adult subjects taking stable doses of bupropion hydrochloride were recruited to undergo 2 EEGs in a prospective, single-center cohort study. The occurrence of spike waves, sharp waves, and focal slowing was recorded and assessed with a continuation ratio logit model for polytomous responses. This model showed that there was a relationship between sex and the incidence of these waveforms, such that the odds of female subjects having sharp waves was increased by a factor of 2.53 (P = 0.05) when compared with male subjects and controlled for both age and dose. Similarly, female subjects were 2.45 (P = 0.09) times more likely than males to have focal slowing on EEG. Overall, 19.8% (39/197) of this representative population was found to have abnormal, asymptomatic EEG findings. The presence of these waveforms in individuals taking a medication known to lower the seizure threshold may be a risk factor for developing seizures.

Using amalgamated Behavioral Risk Factor Surveillance System (BRFSS) data from nine states in 2006, this study examined the differences in demographics, health conditions, health behaviors, and quality of life among persons with active epilepsy (PWAE) and persons with a lifetime prevalence of epilepsy (PWLE), compared with persons without epilepsy (PWOE). Frequencies for PWAE, PWLE, and PWOE by selected health behaviors, health conditions, quality of life, and demographic variables were produced. Differences between persons with and without epilepsy were analyzed. Results indicated smoking and unemployment rates were significantly higher among PWLE/PWAE than among PWOE. PWLE/PWAE were also less likely than PWOE to report advanced educational attainment, and more likely to report suffering physical, mental, or emotional limitations that affected their activities in some way. Hispanics were less likely to report a lifetime or active prevalence of epilepsy than people without epilepsy. PWLE/PWAE report several differences in demographics, health conditions, health behaviors, and quality of life compared to people without epilepsy.

Obesity and lack of physical activity are an increasing problem. In addition to common barriers to physical activity, people with epilepsy also face fear of exercise-induced seizures, medication side effects, and, often, confusing advice regarding the safety of exercise. To explore barriers faced by people with epilepsy, we mailed a survey to 412 adult patients with epilepsy from an epilepsy center in Kansas. Survey items assessed patients’ exercise habits, attitudes regarding exercise, and barriers to exercise. Forty-seven percent completed the survey. Most respondents reported that they did exercise, though most did so 3 or fewer days per week and at light intensity. Respondents who reported seizures as a barrier to exercise did not exercise with less frequency or intensity than those who did not report seizures as a barrier, but these respondents reported greater fear of seizures. Patient-specific education about the benefits of exercise needs to be initiated by physicians.

Objective Concerns have been raised about the safety of switching from a branded antiepileptic drug (AED) to a generic AED. The goal of the study described here was to understand patients’ experiences with generic AEDs in the Midwestern United States. Methods A one-page, six-item survey was mailed to 356 patients to determine patients’ awareness of the existence and their usage of generic AEDs. Results Twenty-eight percent (27.8%) of respondents (N = 179) reported breakthrough seizures they believed were a direct result of the switch from a brand to a generic AED, and 33.7% reported side effects due to the switch. Thirty-one percent (31.2%) returned to a brand-name AED as a result. Sixty-nine percent (68.8%) reported being unaware that some pharmacies switch to generic AEDs without a patient’s or physician’s consent, and 78.7% expressed concern over this. Conclusion A significant percentage of patients reported that generic AEDs were responsible for breakthrough seizures and increased side effects. A significant percentage of patients also reported switching back to a brand-name AED and expressed concern over pharmacies switching to generic AEDs without a patient’s or physician’s consent.

Objective To determine if applying chilled solution to exposed cerebral cortex can reduce interictal epileptiform activities in patients during surgery. Methods Electrocorticography was used to record the epileptiform activity of 12 patients (ages 18–53) undergoing cortical mapping and resection surgery. Interictal spikes were counted at baseline and compared with spikes after applying room temperature and chilled Lactated Ringer's or normal saline solution. Results Cortical irrigation with 150-cm 3 , chilled (4°C) normal saline solution reduced the mean number of interictal spikes from 11.46 to 4.87 spikes per minute ( p =0.04). There was no significant reduction in the epileptic spike frequency when room temperature normal saline was used. Conclusion The application of chilled solution directly to the cortex can reduce interictal epileptiform activities, suggesting that seizure potential can be suppressed to avoid evoked seizures during intraoperative surgery.

Summary: Purpose: Hypothalamic hamartomas (HHs) have been associated with uncontrolled seizures, and aggressive therapy including surgery is often recommended. However, some patients, particularly those with other findings associated with Pallister-Hall syndrome (PHS), have a more benign course. Methods: Thirty-seven of 40 PHS patients and 16 of 16 patients with isolated HH had a lesion confirmed on magnetic resonance imaging (MRI). Records for all patients were reviewed for the following information: presence of seizures, age at seizure onset, seizure type, seizure frequency, number of antiepileptic medications (AEDs) at the time of evaluation, past AEDs, MRI characteristics of the HH, presence of endocrine dysfunction, and presence of developmental and behavioral problems. Results: All isolated HH patients had a history of seizures, compared with 13 of 40 PHS patients (all PHS patients with seizures had hamartomas). In isolated HH, seizures started earlier in life, occurred more frequently, and were harder to control than those in patients with PHS. Isolated HH patients were more likely to have behavioral and developmental problems than were PHS patients. The T2 signal of the hamartoma was isointense to gray matter in the majority of PHS patients, but showed a significant increase in all but one patient with isolated HH. Conclusions: Patients with isolated HH have a distinct clinical phenotype, showing more severe seizures and neurologic dysfunction, HH showing increased T2 signal, and are more likely to have precocious puberty. In contrast, PHS patients usually have well-controlled seizures and other endocrine disturbances than precocious puberty. Patients with HH with or without seizures should be evaluated carefully for other clinical manifestations of PHS, particularly before surgery is considered.

To assess aggression and psychiatric comorbidity in a sample of children with hypothalamic hamartomas and gelastic seizures and to assess psychiatric diagnoses in siblings of study subjects.Children with a clinical history of gelastic seizures and hypothalamic hamartomas (n = 12; age range 3-14 years) had diagnoses confirmed by video-EEG and head magnetic resonance imaging. Structured interviews were administered, including the Diagnostic Interview for Children and Adolescents-Revised Parent Form (DICA-R-P), the Test of Broad Cognitive Abilities, and the Vitiello Aggression Scale. Parents were interviewed with the DICA-R-P about each subject and a sibling closest in age without seizures and hypothalamic hamartomas. Patients were seen from 1998 to 2000.Children with gelastic seizures and hypothalamic hamartomas displayed a statistically significant increase in comorbid psychiatric conditions, including oppositional defiant disorder (83.3%) and attention-deficit/hyperactivity disorder (75%). They also exhibited high rates of conduct disorder (33.3%), speech retardation/learning impairment (33.3%), and anxiety and mood disorders (16.7%). Significant rates of aggression were noted, with 58% of the seizure patients meeting criteria for the affective subtype of aggression and 30.5% having the predatory aggression subtype. Affective aggression was significantly more common (p.05). Unaffected siblings demonstrated low rates of psychiatric pathology on semistructured parental interview and no aggression as measured by the Vitiello Aggression Scale.Children with hypothalamic hamartomas and gelastic seizures had high rates of psychiatric comorbidity and aggression. Parents reported that healthy siblings had very low rates of psychiatric pathology and aggression.

Summary: Purpose: To examine the relationship between frequency of complex partial (CPS) and secondarily generalized tonic-clonic seizures (sGTCS) on hippocampal volume (HV) and temporal lobe metabolism. Methods: We performed volumetric magnetic resonance imaging (MRI) and positron emission tomography with 18fluorodeoxyglucose (18FDG-PET) in 32 patients with epilepsy. Temporal lobe foci were localized by ictal video-EEG. Results: We did not find any association between CPS frequency or lifetime number of sGTCS and HV or metabolism ipsilateral to electroencephalographic focus. Conclusion: The progress of metabolic or pathologic abnormalities of temporal lobe epilepsy may not be altered by adequate seizure control. The presence of an epileptic focus might be associated with progressive neuronal injury even in clinically well-controlled patients.

Intravascular lymphomatosis (IL) is a rare variant of non-Hodgkin's lymphoma with an unusual predilection for the central nervous system (CNS). Most cases are not diagnosed until postmortem because of variable clinical presentation and nonspecific laboratory findings. Neuroimaging findings vary widely and range from diffuse involvement of the deep white matter to infarct-like lesions. Cerebral magnetic resonance imaging (MRI) may show parenchymal and meningeal gadolinium enhancement. The authors describe brain MRI findings of linear, punctate, and patchy enhancement suggestive of CNS IL in two patients confirmed by brain biopsy/histologic studies. High index of clinical suspicion and careful interpretation of MRI (including gadolinium contrast studies) may contribute to premortem diagnosis and early intervention of this often-missed disease.

Nonpolio enteroviral encephalitis usually presents as a diffuse, generalized encephalitis. Focal cerebral involvement by nonpolioviruses is uncommon, and neuroradiologic studies in these cases are usually normal. The authors present a case of a 5-year-old male with an acute encephalitic illness and bilateral lesions of the hippocampi on magnetic resonance imaging. Enteroviral nucleic acids were detected in the cerebrospinal fluid by the reverse transcription polymerase chain reaction. The findings suggest that enteroviral infection should be considered in the differential diagnosis of acute bilateral hippocampal encephalitis in patients in whom polymerase chain reaction fails to demonstrate the presence of herpes simplex virus.

To investigate the effect of vigabatrin (VGB; gamma-vinyl gamma-aminobutyric acid [GABA]), a selective irreversible GABA-transaminase inhibitor, on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF) measured with 18F-fluorodeoxyglucose (FDG) PET and 15O water PET.Antiepileptic drugs (AEDs) reduce CMRGlc to varying degrees. Phenobarbital causes a mean decrease of 30 to 40%. Phenytoin, carbamazepine (CBZ), and valproate (VPA) cause milder reductions in CMRGlc. The combination of VPA with CBZ results in a greater decrease than either drug alone. The effect of novel AEDs on both CBF and CMRGlc has not been studied extensively.Fourteen patients with refractory complex partial seizures on CBZ monotherapy for 4 weeks were included in the study. All patients had baseline 18F-FDG and 15O water PET studies followed by double-blind randomization to placebo (PLC) or VGB while on continuous CBZ treatment. PET scans were repeated after an interval of 2 months on target dose of VGB (50 mg/kg) or PLC. Quantitative PET data analysis was performed using a region of interest template. Significance was tested with the Wilcoxon rank sum test.No statistically significant difference in age, duration of epilepsy, or CBZ levels was observed in the two patient groups. VGB reduced global CMRGlc by 8.1+/-6.5% and global CBF by 13.1+/-10.4%. The change in CMRGlc was different in patients taking VGB compared with those on PLC (p0.04). VGB patients showed regional decreases in both CMRGlc and CBF, particularly in temporal lobes. CSF total GABA increased in the VGB patient group (1.48+/-1.06 versus 4.03+/-4.19 nm/mL). The increase differed from the PLC group (p0.03). We found a strong relation between decreased total CSF GABA and increased CMRGlc in the VGB patient group (R2 = 0.82, p0.01).Vigabatrin (VGB) causes mild reductions in both cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMRGlc) in contrast to other drugs such as barbiturates, which are direct agonists at the gamma-aminobutyric acid-benzodiazepine receptor complex. Conventional AEDs depress CBF and CMRGlc to a greater degree than does VGB. The relatively mild reduction could be due to pre- as well as postsynaptic effects or a use-dependent mechanism.

The American Academy of Neurology (AAN), representing over 20,000 neurologists and neuroscience professionals, has taken an active interest in the clinical, ethical, and policy considerations concerning the coverage of anticonvulsant drugs for people with epilepsy. The AAN has developed evidence-based guidelines that strongly support complete physician autonomy in determining the appropriate use of anticonvulsants for the patients with epilepsy. Based on this evidence, the AAN has adopted the following principles concerning coverage of anticonvulsants for adults and children with epilepsy. The Food and Drug Administration has allowed for significant differences between name-brand and generic drugs. This variation can be highly problematic for patients with epilepsy. Even minor differences in the composition of generic and name-brand anticonvulsant drugs for the treatment of epilepsy can result in breakthrough seizures.