Association of first antiseizure medication with acute health care utilization in a cohort of adults with newly diagnosed epilepsy.

OBJECTIVE: Epilepsy is primarily treated with antiseizure medications (ASMs). The recommendations for first ASM in newly diagnosed epilepsy are inconsistently followed, and we sought to examine whether nonrecommended first ASM was associated with acute care utilization. METHODS: We conducted a retrospective cohort study of adults (≥18 years old) with newly diagnosed epilepsy (identified using validated epilepsy/convulsion International Classification of Diseases, Clinical Modification codes) in 2015-2019, sampled from Marketscan's Commercial and Medicare Databases. Exposure of interest was receipt of a non-guideline-recommended ASM, and the primary outcome was acute care utilization (an emergency department visit or hospitalization after the first ASM claim). Descriptive statistics characterized covariates, and multivariable negative binominal regression models were built adjusting for age, sex, Elixhauser Comorbidity Index, comorbid neurologic disease (e.g., stroke), and ASM polypharmacy. RESULTS: Approximately 14 681 people with new epilepsy were prescribed an ASM within 1 year. The three most prescribed medications were levetiracetam (54%, n = 7912), gabapentin (10%, n = 1462), and topiramate (7%, n = 1022). Approximately 4% (n = 648) were prescribed an ASM that should be avoided, and ~74% of people with new epilepsy had an acute care visit during the follow-up period. Mean number of acute care visits during follow-up was 3.34 for "recommended" ASMs and 4.42 for ASMs that "should be avoided." Prescription of a recommended/neutral ASM as compared to an ASM that should be avoided was associated with reduced likelihood of acute care utilization (incidence rate ratio [IRR] = .85, 95% confidence interval [CI] = .77-.94). The recommended/neutral category of ASMs was not statistically significantly associated with seizure- or epilepsy-specific acute care utilization (IRR = .93, 95% CI = .79-1.09). SIGNIFICANCE: Adults with new epilepsy are frequent users of acute care. There remain a proportion of persons with epilepsy prescribed ASMs that guidelines suggest avoiding, and these ASMs are associated with increased likelihood of emergency department visit or hospitalization. These findings reinforce the importance of optimizing the choice of first ASM in epilepsy.

Consensus-based recommendations for the diagnosis and treatment of anxiety and depression in children and adolescents with epilepsy: A report from the Psychiatric Pediatric Issues Task Force of the International League Against Epilepsy.

The Psychiatric Pediatric Issues Task Force of the International League Against Epilepsy (ILAE) aimed to develop recommendations for the diagnosis and treatment of anxiety and depression in children and adolescents with epilepsy. The Task Force conducted a systematic review and identified two studies that assessed the accuracy of four screening measures for depression and anxiety symptoms compared with a psychiatric interview. Nine studies met the eligibility criteria for treatment of anxiety and depressive disorders or symptoms. The risk of bias and certainty of evidence were assessed. The evidence generated by this review followed by consensus where evidence was missing generated 47 recommendations. Those with a high level of agreement (≥80%) are summarized. Diagnosis: (1) Universal screening for anxiety and depression is recommended. Closer surveillance is recommended for children after 12 years, at higher risk (e.g., suicide-related behavior), with subthreshold symptoms, and experiencing seizure worsening or therapeutic modifications. (2) Multiple sources of ascertainment and a formal screening are recommended. Clinical interviews are recommended whenever possible. The healthcare provider must always explain that symptom recognition is essential to optimize treatment outcomes and reduce morbidity. (3) Questioning about the relationship between symptoms of anxiety or depression with seizure worsening/control and behavioral adverse effects of antiseizure medications is recommended. Treatment: (1) An individualized treatment plan is recommended. (2) For mild depression, active monitoring must be considered. (3) Referral to a mental health care provider must be considered for moderate to severe depression and anxiety. (4) Clinical care pathways must be developed. (5) Psychosocial interventions must be tailored and age-appropriate. (6) Healthcare providers must monitor children with epilepsy who are prescribed antidepressants, considering symptoms and functioning that may not improve simultaneously. (7) Caregiver education is essential to ensure treatment adherence. (8) A shared-care model involving all healthcare providers is recommended for children and adolescents with epilepsy and mental health disorders. We identified clinical decisions in the management of depression and anxiety that lack solid evidence and provide consensus-based guidance to address the care of children and adolescents with epilepsy.

The impact of COVID-19 on people with epilepsy: Global results from the coronavirus and epilepsy study.

OBJECTIVE: To characterize the experience of people with epilepsy and aligned healthcare workers (HCWs) during the first 18 months of the COVID-19 pandemic and compare experiences in high-income countries (HICs) with non-HICs. METHODS: Separate surveys for people with epilepsy and HCWs were distributed online in April 2020. Responses were collected to September 2021. Data were collected for COVID-19 infections, the effect of COVID-related restrictions, access to specialist help for epilepsy (people with epilepsy), and the impact of the pandemic on work productivity (HCWs). The frequency of responses for non-HICs and HICs were compared using non-parametric Chi-square tests. RESULTS: Two thousand one hundred and  five individuals with epilepsy from 53 countries and 392 HCWs from 26 countries provided data. The same proportion of people with epilepsy in non-HICs and HICs reported COVID-19 infection (7%). Those in HICs were more likely to report that COVID-19 measures had affected their health (32% vs. 23%; p < 0.001). There was no difference between non-HICs and HICs in the proportion who reported difficulty in obtaining help for epilepsy. HCWs in non-HICs were more likely to report COVID-19 infection than those in HICs (18% vs 6%; p = 0.001) and that their clinical work had been affected by concerns about contracting COVID-19, lack of personal protective equipment, and the impact of the pandemic on mental health (all p < 0.001). Compared to pre-pandemic practices, there was a significant shift to remote consultations in both non-HICs and HICs (p < 0.001). SIGNIFICANCE: While the frequency of COVID-19 infection was relatively low in these data from early in the pandemic, our findings suggest broader health consequences and an increased psychosocial burden, particularly among HCWs in non-HICs. Planning for future pandemics should prioritize mental healthcare alongside ensuring access to essential epilepsy services and expanding and enhancing access to remote consultations. PLAIN LANGUAGE SUMMARY: We asked people with epilepsy about the effects of COVID-19 on their health and healthcare. We wanted to compare responses from people in high-income countries and other countries. We found that people in high-income countries and other countries had similar levels of difficulty in getting help for their epilepsy. People in high-income countries were more likely to say that their general health had been affected. Healthcare workers in non-high-income settings were more likely to have contracted COVID-19 and have the care they deliver affected by the pandemic. Across all settings, COVID-19 associated with a large shift to remote consultations.

Multipsychiatric Comorbidity in People With Epilepsy Compared With People Without Epilepsy: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Persons with epilepsy (PwE) have a higher risk of developing psychiatric comorbidities compared with the general population. There is limited knowledge about the prevalence of multiple psychiatric conditions in PwE. We summarize the current evidence on the prevalence of multipsychiatric comorbidities in PwE compared with persons without epilepsy. METHODS: A systematic review of multipsychiatric comorbidities in PwE compared with persons without epilepsy was performed, and the results were reported using the Preferred Reporting Items of Systematic Reviews and Meta-analyses reporting standards. The search was conducted from January 1945 to June 2023 in Ovid MEDLINE. Embase, and PsycINFO, using the search terms related to "epilepsy," "psychiatric comorbidity," and "multimorbidity," combined with psychiatric disorders. Abstracts were reviewed in duplicate, and data were independently extracted using standard proforma. Data describing multipsychiatric comorbidities in PwE compared with persons without epilepsy were recorded. Descriptive statistics and, when feasible, meta-analyses are presented. The risk of bias of the studies was assessed using the Newcastle-Ottawa Scale and the International League Against Epilepsy tool. RESULTS: A total of 12,841 records were identified from the systematic database search, and 15 studies met the eligibility criteria. All included studies were deemed high-quality in risk of bias according to both tools. The prevalence of multipsychiatric comorbidity was greater in persons with compared with those without epilepsy. The pooled prevalence of concomitant depression and anxiety disorder in PwE in 2 population-based studies was 15 of 163 (9.2%), which was significantly higher than 250 of 10,551 (2.4%) in patients without epilepsy (odds ratio [OR] 3.7, 95% CI 2.1-6.5, p-value <0.001, I2 = 0%, Cochran Q p-value for heterogeneity = 0.84). In 2 hospital-based studies, the prevalence of concomitant depression and attention-deficit/hyperactivity disorder in PwE (14/97, 14.4%) was significantly higher than in patients without epilepsy (5/126, 3.9%), with an OR 5.2 (95% CI 1.8-15.0, p-value = 0.002, I2 = 0%, Cochran Q p-value for heterogeneity = 0.79). DISCUSSION: PwE experience elevated levels of multipsychiatric comorbidity compared with those without epilepsy. However, very few studies have empirically evaluated the extent of multipsychiatric comorbidity in PwE compared with persons without epilepsy nor their associations and consequences to prognosis in PwE.

A knowledge synthesis of health research reporting standards relevant to epilepsy surgery.

OBJECTIVE: Numerous studies have examined epilepsy surgery outcomes, yet the variability in the level of detail reported hampers our ability to apply these findings broadly across patient groups. Established reporting standards in other clinical research fields enhance the quality and generalizability of results, ensuring that the insights gained from studying these surgeries can benefit future patients effectively. This study aims to assess current reporting standards for epilepsy surgery research and identify potential gaps and areas for enhancement. METHODS: The Enhancing the Quality and Transparency of Health Research (EQUATOR) repository was accessed from inception to April 27, 2023, yielding 561 available reporting standards. Reporting standards were manually reviewed in duplicate independently for applicability to epilepsy and/or neurosurgery research. The reporting standards had to cover the following aspects in human studies: (1) reporting standards for epilepsy/epilepsy surgery and (2) reporting standards for neurosurgery. Disagreements were resolved by a third author. The top five neurosurgery, neurology, and medicine journals were also identified through Google Scholar's citation index and examined to determine the relevant reporting standards they recommended and whether those were registered with EQUATOR. RESULTS: Of the 561 EQUATOR reporting standards, 181 were pertinent to epilepsy surgery. One was related to epilepsy, six were specific to surgical research, and nine were related to neurological/neurosurgical research. The remaining 165 reporting standards were applicable to research across various disciplines and included but were not limited to CONSORT (Consolidated Standards of Reporting Trails), STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). None of these required reporting factors associated with epilepsy surgery outcomes, such as duration of epilepsy or magnetic resonance imaging findings. SIGNIFICANCE: Reporting standards specific to epilepsy surgery are lacking, reflecting a gap in standards that may affect the quality of publications. Improving this gap with a set of specific reporting standards would ensure that epilepsy surgery studies are more transparent and rigorous in their design.

Disparities in Teleneurology Use in Medicaid Beneficiaries With Epilepsy by Practice Setting: Promoting Health Equity in Academic Centers.

BACKGROUND AND OBJECTIVES: Medicaid beneficiaries in many American academic medical centers can receive care in a separate facility than those not covered by Medicaid. We aimed to identify possible disparities in care by evaluating the association between facility type (integrated faculty practice or Medicaid-only outpatient clinic) and telehealth utilization in people with epilepsy. METHODS: We performed retrospective analyses using structured data from the Mount Sinai Health System electronic medical record data from January 2003 to August 2021. We identified people of all ages with epilepsy who were followed by an epileptologist after January 3, 2018, using a validated ICD-9-CM/10-CM coded case definition. We evaluated associations between practice setting and telehealth utilization, an outcome measure that captures the evolving delivery of neurologic care in a post-coronavirus disease 2019 era, using multivariable logistic regression. RESULTS: We identified 4,586 people with epilepsy seen by an epileptologist, including Medicaid beneficiaries in the Medicaid outpatient clinic (N = 387), Medicaid beneficiaries in the faculty practice after integration (N = 723), and non-Medicaid beneficiaries (N = 3,476). Patients not insured by Medicaid were significantly older (average age 40 years vs 29 in persons seen in Medicaid-only outpatient clinic and 28.5 in persons insured with Medicaid seen in faculty practice [p < 0.0001]). Medicaid beneficiaries were more likely to have drug-resistant epilepsy (DRE), with 51.94% of people seen in Medicaid-only outpatient clinic, 41.63% of Medicaid beneficiaries seen in faculty practice, and 37.2% of non-Medicaid beneficiaries having DRE (p < 0.0001). Medicaid outpatient clinic patients were less likely to have telehealth visits (phone or video); 81.65% of patients in the Medicaid outpatient clinic having no telehealth visits vs 71.78% of Medicaid beneficiaries in the faculty practice and 70.89% of non-Medicaid beneficiaries (p < 0.0001). In an adjusted logistic regression analysis, Medicaid beneficiaries had lower odds (0.61; 95% CI 0.46-0.81) of using teleneurology compared with all patients seen in faculty practice (p = 0.0005). DISCUSSION: Compared with the Medicaid-only outpatient clinic, we found higher telehealth utilization in the integrated faculty practice with no difference by insurance status (Medicaid vs other). Integrated care may be associated with better health care delivery in people with epilepsy; thus, future research should examine its impact on other epilepsy-related outcomes.

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.

Neuropsychiatric complications of coronavirus disease 2019: Mount Sinai Health System cohort study.

OBJECTIVE: To describe the frequency of neuropsychiatric complications among hospitalized patients with coronavirus disease 2019 (COVID-19) and their association with pre-existing comorbidities and clinical outcomes. METHODS: We retrospectively identified all patients hospitalized with COVID-19 within a large multicenter New York City health system between March 15, 2020 and May 17, 2021 and randomly selected a representative cohort for detailed chart review. Clinical data, including the occurrence of neuropsychiatric complications (categorized as either altered mental status [AMS] or other neuropsychiatric complications) and in-hospital mortality, were extracted using an electronic medical record database and individual chart review. Associations between neuropsychiatric complications, comorbidities, laboratory findings, and in-hospital mortality were assessed using multivariate logistic regression. RESULTS: Our study cohort consisted of 974 patients, the majority were admitted during the first wave of the pandemic. Patients were treated with anticoagulation (88.4%), glucocorticoids (24.8%), and remdesivir (10.5%); 18.6% experienced severe COVID-19 pneumonia (evidenced by ventilator requirement). Neuropsychiatric complications occurred in 58.8% of patients; 39.8% experienced AMS; and 19.0% experienced at least one other complication (seizures in 1.4%, ischemic stroke in 1.6%, hemorrhagic stroke in 1.0%) or symptom (headache in 11.4%, anxiety in 6.8%, ataxia in 6.3%). Higher odds of mortality, which occurred in 22.0%, were associated with AMS, ventilator support, increasing age, and higher serum inflammatory marker levels. Anticoagulant therapy was associated with lower odds of mortality and AMS. CONCLUSION: Neuropsychiatric complications of COVID-19, especially AMS, were common, varied, and associated with in-hospital mortality in a diverse multicenter cohort at an epicenter of the COVID-19 pandemic.

Provider Experience With the Use of Ketamine for Refractory Status Epilepticus.

OBJECTIVE: Refractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an emerging RSE treatment, but optimal dosing and timing are unknown. We studied provider attitudes and practices regarding the use of ketamine for RSE. METHODS: A literature review informed the creation of the survey, developed by professionals in epilepsy, pharmacy, and neurocritical care. The survey was distributed to members of the Critical Care EEG Monitoring and Research Consortium, Neurocritical Care Society, American Academy of Neurology Synapse community, American Epilepsy Society, and the Canadian League Against Epilepsy. Descriptive statistics were calculated. RESULTS: There were 109 respondents. First-line agents for RSE were midazolam (53%), propofol (42%), pentobarbital (2%), and ketamine (1%). Reasons for ketamine use included failure of midazolam/propofol to control seizures (81%) or hypotension on another anesthetic (35%). Perceived contraindications included hypertension (37%), elevated intracranial pressure (24%), and heart failure (18%). Perceived benefits included decreased use of vasopressors (53%) and more rapid RSE control when used adjunctively (49%). Routine ketamine users often treated more than 10 RSE cases per year, worked as intensivists or at academic institutions. Of the respondents, 59% found ketamine useful for RSE and 94% were interested in learning more about its use. CONCLUSIONS: Although most participants found ketamine helpful for RSE, it is mainly used as a second-line agent adjunctively with midazolam or propofol. Perceived ketamine benefits included decreased need for hemodynamic support and more rapid seizure control when used in conjunction with other anesthetics. Perceived contraindications centered on cardiac and intracranial pressure concerns.

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.

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.

Older adults with epilepsy and COVID-19: Outcomes in a multi-hospital health system.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with high rates of mortality and morbidity in older adults, especially those with pre-existing conditions. There is little work investigating how neurological conditions affect older adults with COVID-19. We aimed to compare in-hospital outcomes, including mortality, in older adults with and without epilepsy. METHODS: This retrospective study in a large multicenter New York health system included consecutive older patients (age ≥65 years) either with or without epilepsy who were admitted with COVID-19 between 3/2020-5/2021. Epilepsy was identified using a validated International Classification of Disease (ICD) and antiseizure medicationbased case definition. Univariate comparisons were calculated using Chi-square, Fisher's exact, Mann-Whitney U, or Student's t-tests. Multivariable logistic regression models were generated to examine factors associated with mortality, discharge disposition and length of stay (LOS). RESULTS: We identified 5384 older adults admitted with COVID-19 of whom 173 (3.21 %) had epilepsy. Mean age was significantly lower in those with (75.44, standard deviation (SD): 7.23) compared to those without epilepsy (77.98, SD: 8.68, p = 0.007). Older adults with epilepsy were more likely to be ventilated (35.84 % vs. 16.18 %, p < 0.001), less likely to be discharged home (21.39 % vs. 43.12 %, p < 0.001), had longer median LOS (13 days vs. 8 days, p < 0.001), and had higher in-hospital death (35.84 % vs. 28.29 %, p = 0.030) compared to those without epilepsy. Epilepsy in older adults was associated with increased odds of in-hospital death (adjusted odds ratio (aOR), 1.55; 95 % CI 1.12-2.14, p = 0.032), non-routine discharge disposition (aOR, 3.34; 95 % CI 2.21-5.03, p < 0.001), and longer LOS (46.46 % 95 % CI 34 %-59 %, p < 0.001). CONCLUSIONS: In models that adjusted for multiple confounders including comorbidity and age, our study found that epilepsy was still associated with higher in-hospital mortality, longer LOS and worse discharge dispositions in older adults with COVID-19 higher in-hospital mortality, longer LOS and worse discharge dispositions in older adults with COVID-19. This work reinforces that epilepsy is a risk factor for worse outcomes in older adults admitted with COVID-19. Timely identification and treatment of COVID-19 in epilepsy may improve outcomes in older people with epilepsy.

Responsive Neurostimulation for People With Drug-Resistant Epilepsy and Autism Spectrum Disorder.

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System. METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis. RESULTS: Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a >50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction >90%). For the super responders, two of the four patients had the device implanted for >2 years. The response rate was 70% for those in whom the device was implanted for >2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported. CONCLUSIONS: Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD-DRE.

Variation in US acute ischemic stroke treatment by hospital regions: limited endovascular access despite evidence.

BACKGROUND: Although national organizations recognize the importance of regionalized acute ischemic stroke (AIS) care, data informing expansion are sparse. We assessed real-world regional variation in emergent AIS treatment, including growth in revascularization therapies and stroke center certification. We hypothesized that we would observe overall growth in revascularization therapy utilization, but observed differences would vary greatly regionally. METHODS: A retrospective cross-sectional analysis was carried out of de-identified national inpatient Medicare Fee-for-Service datasets from 2016 to 2019. We identified AIS admissions and treatment with thrombolysis and endovascular thrombectomy (ET) with International Classification of Diseases, 10th Revision, Clinical Modification codes. We grouped hospitals in Dartmouth Atlas of Healthcare Hospital Referral Regions (HRR) and calculated hospital, demographic, and acute stroke treatment characteristics for each HRR. We calculated the percent of hospitals with stroke certification and AIS cases treated with thrombolysis or ET per HRR. RESULTS: There were 957 958 AIS admissions. Relative mean (SD) growth in percent of AIS admissions receiving revascularization therapy per HRR from 2016 to 2019 was 13.4 (31.7)% (IQR -6.1-31.7%) for thrombolysis and 28.0 (72.0)% (IQR 0-56.0%) for ET. The proportion of HRRs with decreased or no difference in ET utilization was 38.9% and the proportion of HRRs with decreased or no difference in thrombolysis utilization was 32.7%. Mean (SD) stroke center certification proportion across HRRs was 45.3 (31.5)% and this varied widely (IQR 18.3-73.4%). CONCLUSIONS: Overall growth in AIS treatment has been modest and, within HRRs, growth in AIS treatment and the proportion of centers with stroke certification varies dramatically.

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.

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.

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.

Sensitivity and specificity of alternative screening methods for systematic reviews using text mining tools.

OBJECTIVES: To evaluate the impact of text mining (TM) on the sensitivity and specificity of title and abstract screening strategies for systematic reviews (SRs). STUDY DESIGN AND SETTING: Twenty reviewers each evaluated a 500-citation set. We compared five screening methods: conventional double screen (CDS), single screen, double screen with TM, combined double screen and single screen with TM, and single screen with TM. Rayyan, Abstrackr, and SWIFT-Review were used for each TM method. The results of a published SR were used as the reference standard. RESULTS: The mean sensitivity and specificity achieved by CDS were 97.0% (95% confidence interval [CI]: 94.7, 99.3) and 95.0% (95% CI: 93.0, 97.1). When compared with single screen, CDS provided a greater sensitivity without a decrease in specificity. Rayyan, Abstrackr, and SWIFT-Review identified all relevant studies. Specificity was often higher for TM-assisted methods than that for CDS, although with mean differences of only one-to-two percentage points. For every 500 citations not requiring manual screening, 216 minutes (95% CI: 169, 264) could be saved. CONCLUSION: TM-assisted screening methods resulted in similar sensitivity and modestly improved specificity as compared to CDS. The time saved with TM makes this a promising new tool for SR.

Recapitulation of pathophysiological features of AD in SARS-CoV-2-infected subjects.

Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition in some patients with post-acute sequelae of SARS-CoV-2 (PASC). To evaluate neuropathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Brodmann area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimer's disease (AD), and SARS-CoV-2-infected AD individuals compared to age- and gender-matched neurological cases. Here, we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2-infected AD individuals. Distribution of microglial changes reflected by the increase in Iba-1 reveals nodular morphological alterations in SARS-CoV-2-infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help in informing decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.