Ophthalmic and Systemic Factors of Acute Nonarteritic Anterior Ischemic Optic Neuropathy in the Quark207 Treatment Trial.

PURPOSE: We describe the baseline ophthalmic and cardiovascular risk factors across countries, race, and sex for the Quark207 treatment trial for acute nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Prospective, randomized controlled clinical trial. PARTICIPANTS: Adults 50 to 80 years of age with acute NAION recruited from 80 sites across 8 countries. MAIN OUTCOME MEASURES: Ophthalmic features of NAION and cardiovascular risk factors. METHODS: We evaluated demographics and clinical and ophthalmologic data, including best-corrected visual acuity (BCVA) and average visual field total deviation (TD), in affected eyes and cup-to-disc ratio in fellow eyes at enrollment. We report the prevalence (mean and standard devition, and median and interquartile range [IQR]) of ophthalmic features and cardiovascular risk factors, stratified by country, race, and sex. We corrected for multiple comparisons using Dunn's test with Bonferroni correction for continuous variables and chi-square testing with Holm-Bonferroni correction for categorical variables. RESULTS: The study enrolled 500 men and 229 women with a median age of 60 and 61 years (P = 0.027), respectively. Participants were predominantly White (n = 570) and Asian (n = 149). The study eye BCVA was 71 characters (IQR, 53-84 characters; approximately 0.4 logarithm of the minimum angle of resolution), and the TD was -16.5 dB (IQR, -22.2 to -12.6 dB) for stimulus III and -15.7 dB (IQR, -20.8 to -10.9 dB) for stimulus V. The vertical and horizontal cup-to-disc ratio was 0.1 (IQR, 0.1-0.3) for unaffected fellow eyes. The prevalence of cardiovascular risk factors varied among countries. The most notable differences were in the baseline comorbidities and ophthalmologic features, which differed between Asian and White races. Men and women differed with respect to a few clinically meaningful features. CONCLUSIONS: The cardiovascular risk factors in the NAION cohort varied among the 7 countries, race, and sex, but were not typically more prevalent than in the general population. Ophthalmic features, typical of NAION, generally were consistent across countries, race, and sex, except for worse BCVA and TD in China. Men have a frequency of NAION twice that of women. Having a small cup-to-disc ratio in the fellow eye was the most prevalent risk factor across all demographics. This study suggests that factors, not yet identified, may contribute to the development of NAION. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Health care disparities in morbidity and mortality in adults with acute and remote status epilepticus: A national study.

OBJECTIVE: Although disparities have been described in epilepsy care, their contribution to status epilepticus (SE) and associated outcomes remains understudied. METHODS: We used the 2010-2019 National Inpatient Sample to identify SE hospitalizations using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM codes. SE prevalence was stratified by demographics. Logistic regression was used to assess factors associated with electroencephalographic (EEG) monitoring, intubation, tracheostomy, gastrostomy, and mortality. RESULTS: There were 486 861 SE hospitalizations (2010-2019), primarily at urban teaching hospitals (71.3%). SE prevalence per 10 000 admissions was 27.3 for non-Hispanic (NH)-Blacks, 16.1 for NH-Others, 15.8 for Hispanics, and 13.7 for NH-Whites (p < .01). SE prevalence was higher in the lowest (18.7) compared to highest income quartile (18.7 vs. 14, p < .01). Older age was associated with intubation, tracheostomy, gastrostomy, and in-hospital mortality. Those ≥80 years old had the highest odds of intubation (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.43-1.58), tracheostomy (OR = 2, 95% CI = 1.75-2.27), gastrostomy (OR = 3.37, 95% CI = 2.97-3.83), and in-hospital mortality (OR = 6.51, 95% CI = 5.95-7.13). Minority populations (NH-Black, NH-Other, and Hispanic) had higher odds of tracheostomy and gastrostomy compared to NH-White populations. NH-Black people had the highest odds of tracheostomy (OR = 1.7, 95% CI = 1.57-1.86) and gastrostomy (OR = 1.78, 95% CI = 1.65-1.92). The odds of receiving EEG monitoring rose progressively with higher income quartile (OR = 1.47, 95% CI = 1.34-1.62 for the highest income quartile) and was higher for those in urban teaching compared to rural hospitals (OR = 12.72, 95% CI = 8.92-18.14). Odds of mortality were lower (compared to NH-Whites) in NH-Blacks (OR = .71, 95% CI = .67-.75), Hispanics (OR = .82, 95% CI = .76-.89), and those in the highest income quartiles (OR = .9, 95% CI = .84-.97). SIGNIFICANCE: Disparities exist in SE prevalence, tracheostomy, and gastrostomy utilization across age, race/ethnicity, and income. Older age and lower income are also associated with mortality. Access to EEG monitoring is modulated by income and urban teaching hospital status. Older adults, racial/ethnic minorities, and populations of lower income or rural location may represent vulnerable populations meriting increased attention to improve health outcomes and reduce disparities.

Elevated phase amplitude coupling as a depression biomarker in epilepsy.

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.

Health equity integrated epilepsy care and research: A narrative review.

BACKGROUND: With the unanimous approval of the Intersectoral Global Action Plan on epilepsy and other neurological disorders by the World Health Organization in May 2022, there are strong imperatives to work towards equitable neurological care. AIMS: Using epilepsy as an entry point to other neurologic conditions, we discuss disparities faced by marginalized groups including racial/ethnic minorities, Americans living in rural communities, and Americans with low socioeconomic status. MATERIALS AND METHODS: The National Institute on Minority Health Disparities Research Framework (NIMHD) was used to conduct a narrative review through a health equity lens to create an adapted framework for epilepsy and propose approaches to working towards equitable epilepsy and neurological care. RESULTS: In this narrative review, we identified priority populations (racial and ethnic minority, rural-residing, and low socioeconomic status persons with epilepsy) and outcomes (likelihood to see a neurologist, be prescribed antiseizure medications, undergo epilepsy surgery, and be hospitalized) to explore disparities in epilepsy and guide our focused literature search using PubMed. In an adapted NIMHD framework, we examined individual, interpersonal, community, and societal level contributors to health disparities across five domains: (1) behavioral, (2) physical/built environment, (3) sociocultural, (4) environment, and (5) healthcare system. We take a health equity approach to propose initiatives that target modifiable factors that impact disparities and advocate for sustainable change for priority populations. DISCUSSION: To improve equity, healthcare providers and relevant societal stakeholders can advocate for improved care coordination, referrals for epilepsy surgery, access to care, health informatics interventions, and education (i.e., to providers, patients, and communities). More broadly, stakeholders can advocate for reforms in medical education, and in the American health insurance landscape. CONCLUSIONS: Equitable healthcare should be a priority in neurological care.

Latent class analysis of eHealth behaviors among adults with epilepsy.

OBJECTIVE: The objective of this study was to determine the proportions of uptake and factors associated with electronic health (eHealth) behaviors among adults with epilepsy. METHODS: The 2013, 2015, and 2017 National Health Interview Surveys were analyzed. We assessed the proportions of use of five domains of eHealth in those with epilepsy: looked up health information on the internet, filled a prescription on the internet, scheduled a medical appointment on the internet, communicated with a health care provider via email, and used chat groups to learn about health topics. Multivariate logistic regressions were conducted to identify factors associated with any eHealth behaviors among those with active epilepsy. Latent class analysis was performed to identify underlying patterns of eHealth activity. Survey participants were classified into three discrete classes: (1) frequent, (2) infrequent, and (3) nonusers of eHealth. Multinomial logistic regression was performed to identify factors associated with frequency of eHealth use. RESULTS: There were 1770 adults with epilepsy, of whom 65.87% had at least one eHealth behavior in the prior year. By domain, 62.61% looked up health information on the internet, 15.81% filled a prescription on the internet, 14.95% scheduled a medical appointment on the internet, 17.20% communicated with a health care provider via email, and 8.27% used chat groups to learn about health topics. Among those with active epilepsy, female sex, more frequent computer usage, and internet usage were associated with any eHealth behavior. Female sex and frequent computer use were associated with frequent eHealth use as compared to nonusers. SIGNIFICANCE: A majority of persons with epilepsy were found to use at least one form of eHealth. Various technological and demographic factors were associated with eHealth behaviors. Individuals with lower eHealth behaviors should be provided with targeted interventions that address barriers to the adoption of these technologies.

Medical and surgical treatment of epilepsy in older adults: A national survey.

OBJECTIVE: There are no clinical guidelines dedicated to the treatment of epilepsy in older adults. We investigated physician opinion and practice regarding the treatment of people with epilepsy aged 65 years or older. We also sought to study how our opinion and practice varied between geriatricians, general neurologists, and epilepsy neurologists (i.e., epileptologists). METHODS: We initially piloted our survey to measure test-retest reliability. Once finalized, we disseminated the survey via two rounds of facsimiles, and then conventional mail, to eligible individuals listed in a national directory of Canadian physicians. We used descriptive statistics such as stacked bar charts and tables to illustrate our findings. RESULTS: One hundred forty-four physicians (104 general neurologists, 25 geriatricians, and 15 epileptologists) answered our survey in its entirety (overall response rate of 13.2%). Levetiracetam and lamotrigine were the preferred antiseizure medications (ASMs) to treat older adults with epilepsy. Two thirds of epileptologists and almost half of general neurologists would consider prescribing lacosamide in >50% of people aged >65 years; only one geriatrician was of the same opinion. More than 40% of general neurologists and geriatricians erroneously believed that none of the ASMs mentioned in our survey was previously studied in randomized controlled trials specific to the treatment of epilepsy in older adults. Epileptologists were more likely as compared to general neurologists and geriatricians to recommend epilepsy surgery (e.g., 66.6% vs. 22.9%-37.5% among older adults). SIGNIFICANCE: Therapeutic decisions for older adults with epilepsy are heterogeneous between physician groups and sometimes misalign with available clinical evidence. Our surveyed physicians differed in their approach to ASM choice as well as perception of surgery in older adults with epilepsy. These findings likely reflect the lack of clinical guidelines dedicated to this population and the deficient implementation of best practices.

Scoping review and expert-based consensus recommendations for assessment and management of psychogenic non-epileptic (functional) seizures (PNES) in children: A report from the Pediatric Psychiatric Issues Task Force of the International League Against Epilepsy.

Limited guidance exists regarding the assessment and management of psychogenic non-epileptic seizures (PNES) in children. Our aim was to develop consensus-based recommendations to fill this gap. The members of the International League Against Epilepsy (ILAE) Task Force on Pediatric Psychiatric Issues conducted a scoping review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SR) standards. This was supplemented with a Delphi process sent to pediatric PNES experts. Consensus was defined as ≥80% agreement. The systematic search identified 77 studies, the majority (55%) of which were retrospective (only one randomized clinical trial). The primary means of PNES identification was video electroencephalography (vEEG) in 84% of studies. Better outcome was associated with access to counseling/psychological intervention. Children with PNES have more frequent psychiatric disorders than controls. The Delphi resulted in 22 recommendations: Assessment-There was consensus on the importance of (1) taking a comprehensive developmental history; (2) obtaining a description of the events; (3) asking about potential stressors; (4) the need to use vEEG if available parent, self, and school reports and video recordings can contribute to a "probable" diagnosis; and (5) that invasive provocation techniques or deceit should not be employed. Management-There was consensus about the (1) need for a professional with expertise in epilepsy to remain involved for a period after PNES diagnosis; (2) provision of appropriate educational materials to the child and caregivers; and (3) that the decision on treatment modality for PNES in children should consider the child's age, cognitive ability, and family factors. Comorbidities-There was consensus that all children with PNES should be screened for mental health and neurodevelopmental difficulties. Recommendations to facilitate the assessment and management of PNES in children were developed. Future directions to fill knowledge gaps were proposed.

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.

In-hospital outcomes in patients with and without epilepsy diagnosed with COVID-19-A cohort study.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with mortality in persons with comorbidities. The aim of this study was to evaluate in-hospital outcomes in patients with COVID-19 with and without epilepsy. METHODS: We conducted a retrospective study of patients with COVID-19 admitted to a multicenter health system between March 15, 2020, and May 17, 2021. Patients with epilepsy were identified using a validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM case definition. Logistic regression models and Kaplan-Meier analyses were conducted for mortality and non-routine discharges (i.e., not discharged home). An ordinary least-squares regression model was fitted for length of stay (LOS). RESULTS: We identified 9833 people with COVID-19 including 334 with epilepsy. On univariate analysis, people with epilepsy had significantly higher ventilator use (37.70% vs 14.30%, p < .001), intensive care unit (ICU) admissions (39.20% vs 17.70%, p < .001) mortality rate (29.60% vs 19.90%, p < .001), and longer LOS (12 days vs 7 days, p < .001). and fewer were discharged home (29.64% vs 57.37%, p < .001). On multivariate analysis, only non-routine discharge (adjusted odds ratio [aOR] 2.70, 95% confidence interval [CI] 2.00-3.70; p < .001) and LOS (32.50% longer, 95% CI 22.20%-43.60%; p < .001) were significantly different. Factors associated with higher odds of mortality in epilepsy were older age (aOR 1.05, 95% CI 1.03-1.08; p < .001), ventilator support (aOR 7.18, 95% CI 3.12-16.48; p < .001), and higher Charlson comorbidity index (CCI) (aOR 1.18, 95% CI 1.04-1.34; p = .010). In epilepsy, admissions between August and December 2020 or January and May 2021 were associated with a lower odds of non-routine discharge and decreased LOS compared to admissions between March and July 2020, but this difference was not statistically significant. SIGNIFICANCE: People with COVID-19 who had epilepsy had a higher odds of non-routine discharge and longer LOS but not higher mortality. Older age (≥65), ventilator use, and higher CCI were associated with COVID-19 mortality in epilepsy. This suggests that older adults with epilepsy and multimorbidity are more vulnerable than those without and should be monitored closely in the setting of COVID-19.

Palliative care referral across the disease trajectory in high-grade glioma.

PURPOSE: Adults with high-grade glioma (HGG), WHO grade III or IV, have substantial palliative care needs. Our aim was to determine occurrence, timing, and factors associated with palliative care consultation (PCC) in HGG at one large academic institution. METHODS: HGG patients receiving care between 08/1/2011 and 01/23/2020 were identified retrospectively from a multi-center healthcare system cancer registry. Patients were stratified by any PCC (yes/no), and timing of initial PCC by disease phase: diagnosis (before radiation), during initial treatment (first-line chemotherapy/radiation), second-line treatment(s), or end-of-life (after last chemotherapy). RESULTS: Of 621 HGG patients, 134 (21.58%) received PCC with the vast majority occurring during hospital admission [111 (82.84%)]. Of the 134, 14 (10.45%) were referred during the diagnostic phase; 35 (26.12%) during initial treatment; 20 (14.93%) during second-line treatment; and 65 (48.51%) during end of life. In multivariable logistic regression, only higher Charlson Comorbidity Index was associated with greater odds of PCC [OR 1.3 (95% CI 1.2-1.4), p < 0.01]; but not age or histopathology. Patients who received PCC prior to end of life had longer survival from diagnosis than those referred during end of life [16.5 (8, 24) months vs. 11 (4, 17); p < 0.01]. CONCLUSION: A minority of HGG patients ever received PCC, which primarily occurred in the inpatient setting, and nearly half during the end-of-life phase. Thus, only about one in ten patients in the entire cohort potentially received the benefits of earlier PCC despite earlier referral having an association with longer survival. Further studies should elucidate barriers and facilitators to early PCC in HGG.

Depression readmission risk is elevated in multiple sclerosis compared to other chronic illnesses.

OBJECTIVE: Assess readmissions for depression or suicide attempt (SA) after MS admission versus other chronic inflammatory illnesses. METHODS: This retrospective cohort study identified MS, asthma, rheumatoid arthritis (RA), depression, and SA in the 2013 National Readmissions Database by International Classification of Diseases codes. Index admissions (MS, n = 7698; asthma, n = 93,590; RA, n = 3685) and depression or SA readmission rates were analyzed. Hazard ratios (HRs) estimated 1-year depression/SA readmission hazard, comparing MS to asthma or RA, adjusting for age, sex, psychiatric comorbidity, substance abuse, tobacco use, income, and index hospitalization characteristics. RESULTS: MS had more baseline depression (24.7%) versus asthma (15.6%) and RA (14.6%). Ninety-day depression readmission rate was higher in MS (0.5%) than asthma (0.3%) and RA (0.03%). Depression readmission HR was higher after MS admission versus asthma (HR = 1.37, 95% confidence interval (CI) = 1.00-1.86, p = 0.0485) and RA (HR = 4.68, 95% CI = 1.60-13.62, p = 0.0047). HR was not different for SA readmission across groups. Depression readmission HR was more than double in MS patients with psychiatric disease or substance abuse versus RA or asthma patients with either comorbidity. CONCLUSION: Depression readmission risk after MS hospitalization was elevated versus asthma/RA. Substance use and baseline psychiatric comorbidity were more strongly associated with depression readmission in MS patients.

The worldwide epilepsy treatment gap: A systematic review and recommendations for revised definitions - A report from the ILAE Epidemiology Commission.

OBJECTIVE: In order to more appropriately apply and understand the "epilepsy treatment gap" (ETG) concept in current health systems, revised conceptual and operational definitions of ETG are timely and necessary. This article therefore systematically reviews worldwide studies of the ETG, distinguishing high-, middle-, and low-income regions, and provides recommendations for an updated International League Against Epilepsy (ILAE) definition of ETG. METHODS: A systematic review of the ETG was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The search was conducted from January 1990 to July 2019, in the online databases of Ovid MEDLINE and Embase. Identified abstracts were reviewed in duplicate and data independently extracted using a standard proforma. Data describing treatment gap information including both diagnostic and therapeutic aspects of access to epilepsy treatment were recorded. Descriptive statistics are presented. RESULTS: The treatment gap reported in the 45 distinctive populations represented 33 countries. Treatment gap definitions varied widely. The reported ETGs ranged broadly from 5.6% in Norway to 100% in parts of Tibet, Togo, and Uganda. The wide range of reported ETGs was multifactorial in origin including true differences in the availability and utilization of health care among study populations, variations in operational definitions of the epilepsy treatment gap, and methodological differences in sampling and identifying representative epilepsy cases in populations. Significance and recommendations For the ETG to be a useful metric to compare levels of unmet epilepsy care across different countries and regions, a standardized definition must be adapted, recognizing some of the limitations of the current definitions. Our proposed definition takes into account the lack of effective health care insurance, the diagnostic gap, the therapeutic gap, quality-of-care, and other unmet health care needs."

What is a clinical practice guideline? A roadmap to their development. Special report from the Guidelines Task Force of the International League Against Epilepsy.

Clinical practice guidelines (CPGs) are statements that provide evidence-based recommendations aimed at optimizing patient care. However, many other documents are often published as "guidelines" when they are not; these documents, although also important in clinical practice, are usually not systematically produced following rigorous processes linking the evidence to the recommendations. Specifically, the International League Against Epilepsy (ILAE) guideline development toolkit aims to ensure that high-quality CPGs are developed to fill knowledge gaps and optimize the management of epilepsy. In addition to adhering to key methodological processes, guideline developers need to consider that effective CPGs should lead to improvements in clinical processes of care and health care outcomes. This requires monitoring the effectiveness of epilepsy-related CPGs and interventions to remove the barriers to epilepsy CPG implementation. This article provides an overview of what distinguishes quality CPGs from other documents and discusses their benefits and limitations. We summarize the recently revised ILAE CPG development process and elaborate on the barriers and facilitators to guideline dissemination, implementation, and adaptation.

Epilepsy-related stigma and attitudes: Systematic review of screening instruments and interventions - Report by the International League Against Epilepsy Task Force on Stigma in Epilepsy.

OBJECTIVE: This is a systematic review aimed at summarizing the evidence related to instruments that have been developed to measure stigma or attitudes toward epilepsy and on stigma-reducing interventions. METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. A broad literature search (1985-2019) was performed in 13 databases. Articles were included if they described the development and testing of psychometric properties of an epilepsy-related stigma or attitude scale or stigma-reducing interventions. Two reviewers independently screened abstracts, reviewed full-text articles, and extracted data. Basic descriptive statistics are reported. RESULTS: We identified 4234 abstracts, of which 893 were reviewed as full-text articles. Of these, 38 met inclusion criteria for an instrument development study and 30 as a stigma-reduction intervention study. Most instruments were initially developed using well-established methods and were tested in relatively large samples. Most intervention studies involved educational programs for adults with pre- and post-evaluations of attitudes toward people with epilepsy. Intervention studies often failed to use standardized instruments to quantify stigmatizing attitudes, were generally underpowered, and often found no evidence of benefit or the benefit was not sustained. Six intervention studies with stigma as the primary outcome had fewer design flaws and showed benefit. Very few or no instruments were validated for regional languages or culture, and there were very few interventions tested in some regions. SIGNIFICANCE: Investigators in regions without instruments should consider translating and further developing existing instruments rather than initiating the development of new instruments. Very few stigma-reduction intervention studies for epilepsy have been conducted, study methodology in general was poor, and standardized instruments were rarely used to measure outcomes. To accelerate the development of effective epilepsy stigma-reduction interventions, a paradigm shift from disease-specific, siloed trials to collaborative, cross-disciplinary platforms based upon unified theories of stigma transcending individual conditions will be needed.

Systematic review of frequency of felt and enacted stigma in epilepsy and determining factors and attitudes toward persons living with epilepsy-Report from the International League Against Epilepsy Task Force on Stigma in Epilepsy.

OBJECTIVE: To review the evidence of felt and enacted stigma and attitudes toward persons living with epilepsy, and their determining factors. METHODS: Thirteen databases were searched (1985-2019). Abstracts were reviewed in duplicate and data were independently extracted using a standardized form. Studies were characterized using descriptive analysis by whether they addressed "felt" or "enacted" stigma and "attitudes" toward persons living with epilepsy. RESULTS: Of 4234 abstracts, 132 met eligibility criteria and addressed either felt or enacted stigma and 210 attitudes toward epilepsy. Stigma frequency ranged broadly between regions. Factors associated with enacted stigma included low level of knowledge about epilepsy, lower educational level, lower socioeconomic status, rural areas living, and religious grouping. Negative stereotypes were often internalized by persons with epilepsy, who saw themselves as having an "undesirable difference" and so anticipated being treated differently. Felt stigma was associated with increased risk of psychological difficulties and impaired quality of life. Felt stigma was linked to higher seizure frequency, recency of seizures, younger age at epilepsy onset or longer duration, lower educational level, poorer knowledge about epilepsy, and younger age. An important finding was the potential contribution of epilepsy terminology to the production of stigma. Negative attitudes toward those with epilepsy were described in 100% of included studies, and originated in any population group (students, teachers, healthcare professionals, general public, and those living with epilepsy). Better attitudes were generally noted in those of younger age or higher educational status. SIGNIFICANCE: Whatever the specific beliefs about epilepsy, implications for felt and enacted stigma show considerable commonality worldwide. Although some studies show improvement in attitudes toward those living with epilepsy over time, much work remains to be done to improve attitudes and understand the true occurrence of discrimination against persons with epilepsy.

Neurostimulation in people with drug-resistant epilepsy: Systematic review and meta-analysis from the ILAE Surgical Therapies Commission.

OBJECTIVE: Summarize the current evidence on efficacy and tolerability of vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) through a systematic review and meta-analysis. METHODS: We followed the Preferred Reporting Items of Systematic reviews and Meta-Analyses reporting standards and searched Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. We included published randomized controlled trials (RCTs) and their corresponding open-label extension studies, as well as prospective case series, with ≥20 participants (excluding studies limited to children). Our primary outcome was the mean (or median, when unavailable) percentage decrease in frequency, as compared to baseline, of all epileptic seizures at last follow-up. Secondary outcomes included the proportion of treatment responders and proportion with seizure freedom. RESULTS: We identified 30 eligible studies, six of which were RCTs. At long-term follow-up (mean 1.3 years), five observational studies for VNS reported a pooled mean percentage decrease in seizure frequency of 34.7% (95% confidence interval [CI]: -5.1, 74.5). In the open-label extension studies for RNS, the median seizure reduction was 53%, 66%, and 75% at 2, 5, and 9 years of follow-up, respectively. For DBS, the median reduction was 56%, 65%, and 75% at 2, 5, and 7 years, respectively. The proportion of individuals with seizure freedom at last follow-up increased significantly over time for DBS and RNS, whereas a positive trend was observed for VNS. Quality of life was improved in all modalities. The most common complications included hoarseness, and cough and throat pain for VNS and implant site pain, headache, and dysesthesia for DBS and RNS. SIGNIFICANCE: Neurostimulation modalities are an effective treatment option for drug-resistant epilepsy, with improving outcomes over time and few major complications. Seizure-reduction rates among the three therapies were similar during the initial blinded phase. Recent long-term follow-up studies are encouraging for RNS and DBS but are lacking for VNS.

Timing of referral to evaluate for epilepsy surgery: Expert Consensus Recommendations from the Surgical Therapies Commission of the International League Against Epilepsy.

Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines.

Small fiber neuropathy associated with SARS-CoV-2 infection.

INTRODUCTION/AIMS: The development and persistence of neurological symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is referred to as "long-haul" syndrome. We aimed to determine whether small fiber neuropathy (SFN) was associated with SARS-CoV-2 infection. METHODS: We retrospectively studied the clinical features and outcomes of patients who were referred to us between May 2020 and May 2021 for painful paresthesia and numbness that developed during or after SARS-CoV-2 infection and who had nerve conduction studies showing no evidence of a large fiber polyneuropathy. RESULTS: We identified 13 patients, Eight women and five men with age ranging from 38-67 y. Follow-up duration ranged from 8 to 12 mo. All patients developed new-onset paresthesias within 2 mo following SARS-CoV-2 infection, with an acute onset in seven and co-existing autonomic symptoms in seven. Three patients had pre-existing but controlled neuropathy risk factors. Skin biopsy confirmed SFN in six, all of whom showed both neuropathy symptoms and signs, and two also showed autonomic dysfunction by autonomic function testing (AFT). Of the remaining seven patients who had normal skin biopsies, six showed no clinical neuropathy signs and one exhibited signs and had abnormal AFT. Two patients with markedly reduced intraepidermal nerve fiber densities and one with normal skin biopsy had severe and moderate coronavirus disease 2019 (COVID-19); the remainder experienced mild COVID-19 symptoms. Nine patients received symptomatic neuropathy treatment with paresthesias controlled in seven (77.8%). DISCUSSION: Our findings suggest that symptoms of SFN may develop during or shortly after COVID-19. SFN may underlie the paresthesias associated with long-haul post-COVID-19 symptoms.

EEG Patterns and Outcomes After Hypoxic Brain Injury: A Systematic Review and Meta-analysis.

Electroencephalography (EEG) is used to prognosticate recovery in comatose patients with hypoxic ischemic brain injury (HIBI) secondary to cardiac arrest. We sought to determine the prognostic use of specific EEG patterns for predicting disability and death following HIBI secondary to cardiac arrest. This systematic review searched Medline, Embase, and Cochrane Central up to January 2020. We included original research involving prospective and retrospective cohort studies relating specific EEG patterns to disability and death in comatose adult patients suffering HIBI post cardiac arrest requiring admission to an intensive care setting. We evaluated study quality using the Quality of Diagnostic Accuracy Studies 2 tool. Descriptive statistics were used to summarize study, patient, and EEG characteristics. We pooled study-level estimates of sensitivity and specificity for EEG patterns defined a priori using a random effect bivariate and univariate meta-analysis when appropriate. Funnel plots were used to assess publication bias. Of 5191 abstracts, 333 were reviewed in full text, of which 57 were included in the systematic review and 32 in meta-analyses. No reported EEG pattern was found to be invariably associated with death or disability across all studies. Pooled specificities of status epilepticus, burst suppression, and electrocerebral silence were high (92-99%), but sensitivities were low (6-39%) when predicting a composite outcome of disability and death. Study quality varied depending on domain; patient flow and timing performed was well conducted in all, whereas EEG interpretation was retrospective in 17 of 39 studies. Accounting for variable study quality, EEG demonstrates high specificity with a low risk of false negative outcome attribution for disability and death when status epilepticus, burst suppression, or electrocerebral silence is detected. Increased use of standardized cross-study protocols and definitions of EEG patterns are required to better evaluate the prognostic use of EEG for comatose patients with HIBI following cardiac arrest.

Correlations Between Physician and Hospital Stroke Thrombectomy Volumes and Outcomes: A Nationwide Analysis.

Background and Purpose: Despite the Joint Commission's certification requirement of ≥15 stroke thrombectomy (ST) cases per center and proceduralist annually, the relationship between ST case volumes and outcomes is uncertain. We sought to determine whether a proceduralist or hospital volume threshold exists that is associated with better outcomes among Medicare beneficiaries. Methods: Retrospective cohort study using validated International Classification of Diseases, Tenth Revision, Clinical Modification codes to identify admissions with acute ischemic stroke and treatment with ST. We used de-identified, national 100% inpatient Medicare data sets from January 1, 2016, to December 31, 2017 for US individuals aged ≥65 years. We calculated total procedures by proceduralist and hospital. We performed adjusted logistic regression of total cases as a predictor of inpatient mortality, good outcome (defined by dichotomized discharge disposition of inpatient rehabilitation or better), and 30-day readmission. We adjusted for sex, age, Charlson Comorbidity Index, availability of neurocritical care, teaching hospital status, socioeconomic status, 2-year stroke volume, and urban versus rural hospital location. We dichotomized case numbers incrementally to determine a volume threshold for better outcomes. Results: Thirteen thousand three hundred thirty-five patients were treated with ST by 2754 proceduralists at 641 hospitals. For every 10 more proceduralist cases, patients had 4% lower adjusted odds of inpatient mortality (adjusted odds ratio, 0.96 [95% CI, 0.95­0.98], P<0.0001) and 3% greater adjusted odds of good outcome (adjusted odds ratio, 1.03 [95% CI, 1.02­1.04], P<0.0001). For every 10 more hospital cases, patients had 2% lower odds of inpatient mortality (adjusted odds ratio, 0.98 [95% CI, 0.98­0.99], P=0.0003) and 2% greater odds of good outcome (adjusted odds ratio, 1.02 [95% CI, 1.01­1.02], P<0.0001). With increasing volumes, there were higher odds of better outcomes. Conclusions: Nationally, higher proceduralist and hospital ST case volumes were associated with reduced inpatient mortality and better outcome. These data support volume requirements in guidelines for ST training and certification.