Developing optimized physical activity interventions for drug-resistant epilepsy: Challenges and lessons learned from a remote exercise intervention pilot trial.

People with epilepsy (PWE) stand to benefit significantly from increasing their physical activity, but promotion of physical activity is difficult in any population; a challenge compounded by the unique barriers encountered by PWE, especially those with drug-resistant epilepsy (DRE). This study explores the feasibility of a remotely delivered, 12-week aerobic exercise program based on social cognitive theory principles in adults with DRE. This line of research is nested within the Multiphase Optimization Strategy (MOST), a framework that emphasizes iterative early pilot work (preparation phase research), followed by iterative optimization phase research. Ten participants were recruited, and four out of ten completed the study, resulting in 3.8 % recruitment from those preliminarily eligible by chart review, and 40 % retention. While acceptability was high among those who completed the study, recruitment, retention, and uptake were low. Three key related lessons learned emerged: 1) low appeal of an exercise intervention in our population of DRE 2) barriers related to comorbid mental health struggles, and 3) fear of seizures. How to best approach physical activity promotion in PWE, particularly DRE, will require a somewhat novel approach involving iterative pilot work and optimization before large scale efficacy trials and implementation can be achieved.

Quality of life during usual epilepsy care for anxiety or depression symptoms: Secondary patient-reported outcomes in a randomized trial of remote assessment methods.

BACKGROUND AND OBJECTIVES: Anxiety and depression are highly prevalent and impactful in epilepsy. American Academy of Neurology quality measures emphasize anxiety and depression screening and quality of life (QOL) measurement, yet usual epilepsy care QOL and anxiety/depression outcomes are poorly characterized. The main objective was to assess 6-month QOL, anxiety and depression during routine care among adults with epilepsy and baseline anxiety or depression symptoms; these were prespecified secondary outcomes within a pragmatic randomized trial of remote assessment methods. METHODS: Adults with anxiety or depression symptoms and no suicidal ideation were recruited from a tertiary epilepsy clinic via an electronic health record (EHR)-embedded process. Participants were randomized 1:1 to 6 month outcome collection via patient portal EHR questionnaires vs. telephone interview. This report focuses on an a priori secondary outcomes of the overall trial, focused on patient-reported health outcomes in the full sample. Quality of life, (primary health outcome), anxiety, and depression measures were collected at 3 and 6 months (Quality of Life in Epilepsy-10, QOLIE-10, Generalized Anxiety Disorder-7, Neurological Disorders Depression Inventory-Epilepsy). Change values and 95 % confidence intervals were calculated. In post-hoc exploratory analyses, patient-reported anxiety/depression management plans at baseline clinic visit and healthcare utilization were compared with EHR-documentation, and agreement was calculated using the kappa statistic. RESULTS: Overall, 30 participants (15 per group) were recruited and analyzed, of mean age 42.5 years, with 60 % women. Mean 6-month change in QOLIE-10 overall was 2.0(95 % CI -6.8, 10.9), and there were no significant differences in outcomes between the EHR and telephone groups. Mean anxiety and depression scores were stable across follow-up (all 95 % CI included zero). Outcomes were similar regardless of whether an anxiety or depression action plan was documented. During the baseline interview, most participants with clinic visit EHR documentation indicating action to address anxiety and/or depression reported not being offered a treatment(7 of 12 with action plan, 58 %), and there was poor agreement between patient report and EHR documentation (kappa=0.22). Healthcare utilization was high: 40 % had at least one hospitalization or emergency/urgent care visit reported and/or identified via EHR, but a third (4/12) failed to self-report an EHR-identified hospitalization/urgent visit. DISCUSSION: Over 6 months of usual care among adults with epilepsy and anxiety or depression symptoms, there was no significant average improvement in quality of life or anxiety/depression, suggesting a need for interventions to enhance routine neurology care and achieve quality of life improvement for this group.

Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Anticipatory anxiety of seizures in epilepsy: A common, complex, and underrecognized phenomenon?

The diagnosis of epilepsy is associated with loss of predictability, which invariably results in the fear of when and if future seizures will occur. For a subset of patients with epilepsy (PWE), there may be a pathological persistent fear of seizure occurrence, resulting in limitations to daily activities through avoidant behaviors. Paradoxically, the research of anticipatory anxiety of seizures (AAS; also referred to as seizure phobia) has been practically nonexistent and, not surprisingly, this condition remains underrecognized by clinicians. The available data are derived from three small case series of patients followed in tertiary epilepsy centers. In this study, we review the available data on the reported clinical manifestations of AAS in PWE, and of the potential role of variables associated with it, such as personal and family psychosocial and psychiatric history and epilepsy-related variables. In addition, we review the need for the creation of screening tools to identify patients at risk of AAS and discuss potential treatment strategies, which could be considered as part of the comprehensive management for PWE.

What is the role of screening instruments in the management of psychiatric comorbidities in epilepsy? Tools and practical tips for the most common comorbidities: Depression and anxiety.

Depression and anxiety are the most common psychiatric comorbidities in epilepsy and are known to increase healthcare utilization, the risk of refractory epilepsy, and anti-seizure medication intolerability. Despite this, depression and anxiety continue to be underrecognized and undertreated in people with epilepsy (PWE). Several barriers to the identification of depression and anxiety in PWE exist, including reliance on unstructured interviews rather than standardized, validated instruments. Moreover, there is a dearth of behavioral health providers to manage these comorbidities once identified. The use of validated screening instruments in epilepsy clinics can assist with both the identification of psychiatric symptoms and monitoring of treatment response by the epilepsy clinician for PWE with comorbid depression and/or anxiety. While screening instruments can identify psychiatric symptoms occurring within a specified time, they are not definitively diagnostic. Screeners can be time efficient tools to identify patients requiring further evaluation for diagnostic confirmation. This article reviews recent literature on the utility of depression and anxiety screening instruments in epilepsy care, including commonly used screening instruments, and provides solutions for potential barriers to clinical implementation. Validated depression and anxiety screening instruments can increase identification of depression and anxiety and guide epilepsy clinician management of these comorbidities which has the potential to positively impact patient care.

Interest and Satisfaction of Telemedicine Use Among Ambulatory Neurology Patients in Western North Carolina During the COVID-19 Pandemic.

Introduction: During the COVID-19 pandemic, care shifted from exclusively telemedicine to hybrid models with in-person, video, and telephone visits. We explored how patient satisfaction and visit preferences have changed by comparing in-person versus virtual visits (telephone and video) in an ambulatory neurology practice across three time points. Methods: Patients who completed a virtual visit in March 2020 (early-pandemic), May 2020 (mid-pandemic), and March 2021 (later-pandemic) were contacted. Patients were assessed for visit satisfaction and desire for future telemedicine. Univariate and multivariable logistic regression analysis was conducted to determine factors independently associated with video visit completion. Results: Four thousand seven hundred seventy-eight the number of ambulatory visits (n = 4,778) were performed (1,004 early; 1,265 mid; and 2,509 later); 1,724 patients (36%) assented to postvisit feedback; mean age 45.8 ± 24.4 years, 58% female, 79% white, and 56% with Medicare/Medicaid insurance. Patient satisfaction significantly increased (73% early, 79% mid, 81% later-pandemic, p = 0.008). Interest in telemedicine also increased for patients completing telephone visits (40% early, 50% mid, 59% later, p = 0.027) and video visits (52% early, 59% mid, 62% later, p = 0.035). Patients satisfied with telemedicine visits were younger (p < 0.001). White patients were more interested in future telemedicine (p = 0.037). Multivariable analysis showed that older patients (for each 1 year older), Black patients, and patients with Medicare/Medicaid were 2%, 45%, and 54% less likely to complete a video visit than telephone, respectively. Discussion: Patients, especially younger ones, have become more satisfied and more interested in hybrid care models during the COVID-19 pandemic. Barriers to conducting video visits persist for older, Black patients with Medicare or Medicaid insurance.

A single-center survey on physical activity barriers, behaviors and preferences in adults with epilepsy.

BACKGROUND: Improved understanding of physical activity barriersand preferences in people with epilepsyis needed to successfully design and perform larger, more robust effectivenesstrials. METHODS: Adult patients at a single tertiary epilepsy center between January and April 2020 were surveyed. The survey included a validated physical activity questionnaire (Physical Activity Scale for the Elderly) plus 15 items aimed to address 1) perceptions and beliefs regarding physical activity, 2) barriers to routine physical activity, and 3) willingness and ability to participate in a physical activity intervention and 4) current physical abilities, activities, and preferences. RESULTS: 95 participants with epilepsy (age 42 ± 16.2, 59 % female) completed the survey. Sixty-five participants (68.4 %) reported that they believe that physical activity could improve their seizure frequency. However, 40 % of those surveyed said their neurologist had never talked to them about physical activity. The most commonly reported barriers to physical activity were lack of time (24.7 %) and fear of having a seizure (19.7 %), while barriers to intervention participation included being unable to come to in-person sessions (53 % of those willing to participate),living far away (39.3 %), time constraints (28.6 %), and lack of transportation (21.4 %). CONCLUSION: Future physical activity studies in people with epilepsy should focus on using tailored interventions that accommodate their unique beliefs and barriers.

Integrated psychological care services within seizure settings: Key components and implementation factors among example services in four ILAE regions: A report by the ILAE Psychiatry Commission.

Mental health comorbidities are prevalent and problematic in patients with seizures but often suboptimally managed. To address common gaps in care, the Integrated Mental Health Care Pathways Task Force of the International League Against Epilepsy (ILAE) Psychiatry Commission was tasked with providing education and guidance on the integration of mental health management (e.g., screening, referral, treatment) into routine seizure care. This report aims to describe a variety of established services in this area, with a specific focus on psychological care models. Services were identified by members of the ILAE Psychiatry Commission and authors of psychological intervention trials in epilepsy. A total of eight services met inclusion criteria and agreed to be showcased. They include three pediatric and five adult services located across four distinct ILAE regions (Europe, North America, Africa, Asia Oceania). The report describes the core operations, known outcomes, and implementation factors (i.e., barriers and facilitators) of these services. The report concludes with a set of practical tips for building successful psychological care services within seizure settings, including the importance of having local champions, clearly defining the scope of the service, and establishing sustainable funding models. The breadth of exemplars demonstrates how models tailored to the local environment and resources can be implemented. This report is an initial step to disseminate information regarding integrated mental health care within seizure care settings. Future work is needed to systematically examine both psychological and pharmacological care models and to further establish the evidence base in this area, especially around clinical impact, and cost-effectiveness.

Cereset Research Standard Operating Procedures for Insomnia: A Randomized, Controlled Clinical Trial.

Background: Interventions for insomnia that also address autonomic dysfunction are needed. Objective: We evaluate Cereset Research™ Standard Operating Procedures (CR-SOP) in a pilot randomized, controlled trial. CR-SOP is a less operator-dependent, more generalizable innovation of HIRREM®, a noninvasive, closed-loop, allostatic, acoustic stimulation neurotechnology demonstrated to improve insomnia and autonomic function. Methods: Adults with Insomnia Severity Index (ISI) scores of ≥8 were randomized to receive ten sessions of CR-SOP, with tones linked to brainwaves (LB, intervention), or a sham condition of random tones not linked to brainwaves (NL, control). Measures were collected at enrollment and 0-14 days and 4-6 weeks post-allocated intervention. The primary outcome was differential change in ISI from baseline to 4-6 weeks post-intervention. Secondary self-report measures assessed sleep quality65 and behavioral outcomes. Ten-minute recordings of heart rate and blood pressure were collected to analyze autonomic function (heart rate variability [HRV] and baroreflex sensitivity). Results: Of 22 randomized, 20 participants completed the allocated condition. Intention to treat analysis of change from baseline to the 4-6 week outcome demonstrated mean ISI score reduction of 4.69 points among controls (SE 1.40). In the intervention group, there was an additional 2.58 point reduction in ISI score (SE 2.13; total reduction of 7.27, P = .24). Sleep quality and some measures of autonomic function improved significantly among the intervention group compared to control. Conclusions: This pilot study compared use of a standardized, allostatic, acoustic neurotechnology intervention with a sham, active control condition. The magnitude of change in insomnia severity was clinically relevant and similar to the findings in a prior, fully powered trial, but the differential improvement observed was not statistically significant. Significant improvements were demonstrated in sleep quality and some autonomic function measures.

Afraid to go out: Poor quality of life with phobic anxiety in a large cross-sectional adult epilepsy center sample.

PURPOSE: People with epilepsy (PWE) have unmet healthcare needs, especially in the context of mental health. Although the current literature has established increased incidence of anxiety and depression in PWE and their contribution to poor quality of life, little is known regarding the presence and impact of specific phobia and agoraphobia. Our aim was to assess factors associated with high phobic/agoraphobic symptoms in a large, single tertiary epilepsy center sample, and to assess their impact on quality of life. METHODS: In a diverse sample of 420 adults with epilepsy, cross-sectional association of demographic, epilepsy and cognitive factors with high phobic symptoms were assessed using multiple logistic regression. Symptoms were measured with the SCL-90R validated self-report subscale (T-score ≥ 60 considered high phobic symptom group). Multiple logistic regression modeling was used to assess for independent association of demographic and clinical variables with presence of high phobic symptoms, and multiple linear regression modeling was used to evaluate for independent cross-sectional associations with epilepsy-specific quality of life (QOLIE-89). RESULTS: Lower education (adjusted OR 3.38), non-White race/ethnicity (adjusted OR 2.34), and generalized anxiety symptoms (adjusted OR 1.91) were independently associated with high phobic/agoraphobic symptoms, all p < 0.005. Phobic/agoraphobic symptoms were independently associated with poor quality of life as were depression symptoms, older age, and non-White race/ethnicity. Generalized anxiety did not demonstrate a significant independent association with quality of life in the multivariable model. CONCLUSION: In this study sample, phobic/agoraphobic symptoms were independently associated with poor quality of life. Clinicians should consider using more global symptom screening instruments with particular attention to susceptible populations, as these impactful symptoms may be overlooked using generalized-anxiety focused screening paradigms.

Positive anxiety or depression screen despite ongoing antidepressant prescription in people with epilepsy: A large cross-sectional analysis.

Purpose: While antidepressants are recommended to manage anxiety or depression in epilepsy, limited effectiveness data exist in real-world epilepsy samples, and prior work indicated frequent positive screens despite antidepressant prescription. In response, this study evaluates factors associated with positive anxiety or depression screen during ongoing antidepressant prescription. Methods: Clinical and sociodemographic characteristics were collected among consecutive adult epilepsy clinic patients completing validated anxiety and depression instruments. The sample was divided by presence vs absence of existing antidepressant prescription at time of screening. Among those on an antidepressant, multivariable logistic regression was performed on pre-selected characteristics to evaluate for association with positive anxiety and/or depression screen. Pre-selected characteristics included: antidepressant dose, antidepressant prescriber specialty, antiseizure medications (number, potential psychotropic effects), seizure frequency, employment, visit no-shows, and medical insurance. Results: Of 563 people with epilepsy, 152 had evidence of antidepressant prescription at time of screening and 73/152(48%) had positive anxiety and/or depression screen. Multivariable modeling demonstrated low antidepressant dose and no-show visit(s) were associated with positive screens (adjusted OR 2.29, CI 1.00-5.48 and 3.11, 1.26-8.22 respectively). Conclusion: Low antidepressant dose and factors potentially associated with adherence (visit no-shows) may contribute to persistent anxiety and/or depression among epilepsy patients on an antidepressant.

Patient-reported outcomes via electronic health record portal versus telephone: a pragmatic randomized pilot trial of anxiety or depression symptoms in epilepsy.

Objective: To close gaps between research and clinical practice, tools are needed for efficient pragmatic trial recruitment and patient-reported outcome collection. The objective was to assess feasibility and process measures for patient-reported outcome collection in a randomized trial comparing electronic health record (EHR) patient portal questionnaires to telephone interview among adults with epilepsy and anxiety or depression symptoms. Materials and Methods: Recruitment for the randomized trial began at an epilepsy clinic visit, with EHR-embedded validated anxiety and depression instruments, followed by automated EHR-based research screening consent and eligibility assessment. Fully eligible individuals later completed telephone consent, enrollment, and randomization. Participants were randomized 1:1 to EHR portal versus telephone outcome assessment, and patient-reported and process outcomes were collected at 3 and 6 months, with primary outcome 6-month retention in EHR arm (feasibility target: ≥11 participants retained). Results: Participants (N = 30) were 60% women, 77% White/non-Hispanic, with mean age 42.5 years. Among 15 individuals randomized to EHR portal, 10 (67%, CI 41.7%-84.8%) met the 6-month retention endpoint, versus 100% (CI 79.6%-100%) in the telephone group (P = 0.04). EHR outcome collection at 6 months required 11.8 min less research staff time per participant than telephone (5.9, CI 3.3-7.7 vs 17.7, CI 14.1-20.2). Subsequent telephone contact after unsuccessful EHR attempts enabled near complete data collection and still saved staff time. Discussion: In this randomized study, EHR portal outcome assessment did not meet the retention feasibility target, but EHR method saved research staff time compared to telephone. Conclusion: While EHR portal outcome assessment was not feasible, hybrid EHR/telephone method was feasible and saved staff time.

Corrigendum: Patterned hippocampal stimulation facilitates memory in patients with a history of head impact and/or brain injury.

[This corrects the article DOI: 10.3389/fnhum.2022.933401.].

Suicide and Epilepsy.

PURPOSE OF REVIEW: Epilepsy has a bidirectional association with suicidality, and epilepsy patients are at much higher risk for suicide than the general population. This article reviews the recent literature on suicide risk factors, assessments, and management as they pertain specifically to suicidality in people with epilepsy, a population that requires unique considerations. RECENT FINDINGS: Risk factors for suicidality include younger age (independent of comorbid psychiatric disorders), poor social support, psychiatric comorbidity (depression, anxiety, obsessive-compulsive symptoms, and alcohol use), and epilepsy-related factors (more frequent seizures, temporal lobe epilepsy, and drug-resistant epilepsy). Most clinicians agree with the need for addressing suicidality; however, there is inconsistency in the approach to caring for these patients. An example neurology clinic-based approach is outlined. Although PWE are at risk for suicide and risk factors have been characterized, care gaps remain. Screening strategies may help close these gaps.