Learning difficulties often not documented in newly diagnosed focal epilepsy.

OBJECTIVE: A previous investigation of people with newly diagnosed focal epilepsy participating in the Human Epilepsy Project 1 (HEP1) revealed an association between learning difficulties and structural brain differences, suggesting an underlying relationship prior to seizure onset. To investigate physicians' practices of documentation learning difficulties during clinical encounters, we conducted a review of initial epileptologist encounter notes from HEP1 participants who self-reported early life learning difficulties separately as part of study enrollment. METHODS: HEP1 enrolled 67 North American participants between June 2012 and November 2017 who self-reported one or more difficulties with learning (i.e., having repeated grade, receiving learning support/remediation, and/or formal diagnosis of a learning disability) prior to epilepsy diagnosis as part of the study enrollment. The epileptologist's initial encounter note was then reviewed in detail for each of these participants. Documentation of learning issues and specific diagnoses of learning disabilities was compared to participant characteristics. Regression analysis was used to test for any independent associations between participant characteristics and physician documentation of learning difficulties. RESULTS: There were significant independent relationships between age, sex, and physician documentation of learning difficulties. On average, participants ages 22 and younger were 12.12 times more likely to have their learning difficulties documented compared to those 23 years and older (95 % CI: 2.226 to 66.02, p = 0.004). Additionally, male participants had 7.2 times greater odds of having their learning difficulty documented compared to female participants (95 % CI: 1.538 to 33.717, p = 0.012). There were no significant independent associations between race, language, employment, or geographical region. SIGNIFICANCE: These findings highlight disparities in physician documentation for people with newly diagnosed focal epilepsy and a history of learning difficulties. In the HEP1 cohort, physicians were more likely to document learning difficulties in males and in younger individuals. Systematic practice standards are important for reducing healthcare disparities across populations, improving clinical care to individuals, as well as enabling more accurate retrospective study of clinical phenomenon.

Testing the diagnostic accuracy of common questions for seizure diagnosis: Challenges and future directions.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of common interview questions used to distinguish a diagnosis of epilepsy from seizure mimics including non-epileptic seizures (NES), migraine, and syncope. METHODS: 200 outpatients were recruited with an established diagnosis of focal epilepsy (n = 50), NES (n = 50), migraine (n = 50), and syncope (n = 50). Patients completed an eight-item, yes-or-no online questionnaire about symptoms related to their events. Sensitivity and specificity were calculated. Using a weighted scoring for the questions alone with baseline characteristics, the overall questionnaire was tested for diagnostic accuracy. RESULTS: Of individual questions, the most sensitive one asked if events are sudden in onset (98 % sensitive for epilepsy (95 % CI: 89 %, 100 %)). The least sensitive question asked if events are stereotyped (46 % sensitive for epilepsy (95 % CI: 32 %, 60 %)). Overall, three of the eight questions showed an association with epilepsy as opposed to mimics. These included questions about "sudden onset" (OR 10.76, 95 % CI: (1.66, 449.21) p = 0.0047), "duration < 5 min" (OR 3.34, 95 % CI: (1.62, 6.89), p = 0.0008), and "duration not > 30 min" (OR 4.44, 95 % CI: (1.94, 11.05), p = <0.0001). When individual seizure mimics were compared to epilepsy, differences in responses were most notable between the epilepsy and migraine patients. Syncope and NES were most similar in responses to epilepsy. The overall weighted questionnaire incorporating patient age and sex produced an area under the ROC curve of 0.80 (95 % CI: 0.74, 0.87)). CONCLUSION: In this study, we examined the ability of common interview questions used by physicians to distinguish between epilepsy and prevalent epilepsy mimics, specifically NES, migraines, and syncope. Using a weighted scoring system for questions, and including age and sex, produced a sensitive and specific predictive model for the diagnosis of epilepsy. In contrast to many prior studies which evaluated either a large number of questions or used methods with difficult practical application, our study is unique in that we tested a small number of easy-to-understand "yes" or "no" questions that can be implemented in most clinical settings by non-specialists.

Engagement in online cognitive testing with the Cogstate brief battery among a multinational cohort of people with focal epilepsy.

OBJECTIVE: The Human Epilepsy Project (HEP) is a large multinational cohort study of people with newly diagnosed and treated focal epilepsy. HEP utilized the Cogstate Brief Battery (CBB) as a self-directed online assessment to examine cognitive outcomes in study participants. The CBB has previously been validated in healthy individuals and people with various brain disorders, but its use in adults participating in HEP has not been assessed. In this study, we describe how the CBB was used in the HEP cohort and assess factors associated with test completion among study participants. METHODS: Enrollment data for HEP included 408 participants with comprehensive enrollment records, of whom 249 completed CBB assessments. HEP enrolled cognitively normal-range participants between the ages of 12 and 60 from June 29, 2012, to November 7, 2017, with newly diagnosed focal epilepsy and within 4 months of initial treatment. Baseline participant characteristics were analyzed, including demographics, pre-treatment seizure histories, MRI abnormalities, and the presence of any learning difficulties while in school, including formal learning disability diagnoses, repeated grades, and remediation. HEP participant characteristics for those who completed CBB testing were compared to those who did not using multiple logistic regression. RESULTS: The analysis of HEP participants who completed CBB testing showed that, after controlling for other factors, male participants were more likely to engage in testing (OR 2.14, 95 % CI 1.29 to 3.5, p < 0.01), Black subjects were less likely (OR 0.45, 95 % CI 0.22 to 0.9, p = 0.02), primary English speakers were more likely (OR 3.1, 95 % CI 1.21 to 7.96, p = 0.02), and those with a history of learning challenges were less likely (OR 0.69, 95 % CI 0.49 to 0.97, p = 0.03). There were no significant associations between completing CBB testing and age, employment (employed or student vs not), education (higher education vs not), diagnostic delay, pre-diagnostic seizure burden, or initial seizure semiology (motor vs non-motor). SIGNIFICANCE: The findings from this study highlight factors associated with the application of remote and unsupervised assessments of cognition in a prospective cohort of adults with focal epilepsy. These factors can be considered when interpreting performance on the CBB in HEP, as well as assisting the design of future studies that use similar approaches.

Later onset focal epilepsy with roots in childhood: Evidence from early learning difficulty and brain volumes in the Human Epilepsy Project.

OBJECTIVE: Visual assessment of magnetic resonance imaging (MRI) from the Human Epilepsy Project 1 (HEP1) found 18% of participants had atrophic brain changes relative to age without known etiology. Here, we identify the underlying factors related to brain volume differences in people with focal epilepsy enrolled in HEP1. METHODS: Enrollment data for participants with complete records and brain MRIs were analyzed, including 391 participants aged 12-60 years. HEP1 excluded developmental or cognitive delay with intelligence quotient <70, and participants reported any formal learning disability diagnoses, repeated grades, and remediation. Prediagnostic seizures were quantified by semiology, frequency, and duration. T1-weighted brain MRIs were analyzed using Sequence Adaptive Multimodal Segmentation (FreeSurfer v7.2), from which a brain tissue volume to intracranial volume ratio was derived and compared to clinically relevant participant characteristics. RESULTS: Brain tissue volume changes observable on visual analyses were quantified, and a brain tissue volume to intracranial volume ratio was derived to compare with clinically relevant variables. Learning difficulties were associated with decreased brain tissue volume to intracranial volume, with a ratio reduction of .005 for each learning difficulty reported (95% confidence interval [CI] = -.007 to -.002, p = .0003). Each 10-year increase in age at MRI was associated with a ratio reduction of .006 (95% CI = -.007 to -.005, p < .0001). For male participants, the ratio was .011 less than for female participants (95% CI = -.014 to -.007, p < .0001). There were no effects from seizures, employment, education, seizure semiology, or temporal lobe electroencephalographic abnormalities. SIGNIFICANCE: This study shows lower brain tissue volume to intracranial volume in people with newly treated focal epilepsy and learning difficulties, suggesting developmental factors are an important marker of brain pathology related to neuroanatomical changes in focal epilepsy. Like the general population, there were also independent associations between brain volume, age, and sex in the study population.

Evaluation and Treatment of Seizures and Epilepsy During the COVID-19 Pandemic.

PURPOSE OF REVIEW: Seizures, including status epilepticus, have been reported in association with acute COVID-19 infection. People with epilepsy (PWE) have suffered from seizure exacerbations during the pandemic. This article reviews the data for clinical and electrographic seizures associated with COVID-19, technical EEG considerations for reducing risk of transmission, and factors contributing to seizure exacerbations in PWE as well as strategies to address this issue. RECENT FINDINGS: An increasing number of studies of larger cohorts, accounting for a variety of variables and often utilizing EEG with standardized terminology, are assessing the prevalence of seizures in hospitalized patients with acute COVID-19 infections, and gaining insight into the prevalence of seizures and their effect on outcomes. Additionally, recent studies are evaluating the effect of the pandemic on PWE, barriers faced, and the usefulness of telehealth. Although there is still much to learn regarding COVID-19, current studies help in assessing the risk of seizures, guiding EEG utilization, and optimizing the use of telehealth during the pandemic.

The language of seizure identification: A qualitative investigation.

OBJECTIVE: Clinical history taking is often the most important factor in seizure recognition and the diagnosis of epilepsy. Apart from subspecialist evaluation, patients frequently present for initial evaluation of seizures in emergency departments, urgent care clinics, and primary care clinics. We utilized qualitative methods to assess the current approaches and language used by both subspecialist and non-specialist physicians when interviewing adult patients with suspected seizures to create a clinical tool to aid in seizure diagnosis. METHODS: We carried out semi- structured interviews with 10 physicians spanning a range of specialties, practice locations, and clinical experience. This included epilepsy specialists and non-specialists in fields where evaluation of new-onset seizures is common: emergency medicine, internal medicine, and family medicine. Thematic analysis was used to develop a "Seizure Identifier" questionnaire, which was subsequently reviewed by five independent experts for content and face validity. RESULTS: Our analysis revealed that across specialties and practice settings, physicians have a structured approach in evaluating patients who present with suspected seizures. Five key characteristics important for identifying seizures emerged across interviews: sudden-onset unprovoked symptoms, short-lasting symptoms, strange or difficult-to-describe symptoms, highly stereotyped symptoms, and postictal symptoms. After independent review, these were translated into an eight-question "Seizure Identifier" tool. SIGNIFICANCE: This study highlights important concepts for clinical practice regarding seizure identification. Using themes from our analysis, we were able to create a tool that may aid non-specialists in the approach to history taking for adult patients who present with suspected seizures and may help improve time to subspecialist evaluation. Importantly, this tool can be tested in future research for improving seizure recognition and improving timely epilepsy diagnosis.

Diagnostic Delay in Epilepsy: the Scope of the Problem.

PURPOSE OF REVIEW: Diagnostic delay is an increasingly recognized issue in epilepsy. At the same time, there is a clear disparity between public awareness of epilepsy and that of other public health issues. A contributing factor for this seems to be a lack of studies testing interventions designed to improve seizure recognition. In this review, we summarize the main findings from recent studies investigating diagnostic delay in epilepsy, highlighting causes, consequences, and potential interventions in future research that may improve quality of care in this population. RECENT FINDINGS: Building on prior evidence, diagnostic delay in patients with new-onset focal epilepsy has been identified as an important problem for patients with epilepsy. Such delay in diagnosis can lead to delayed treatment and potentially preventable morbidity and mortality including motor vehicle accidents. Nonmotor seizure semiology appears to be a major contributor for delay; such seizures are largely unrecognized when patients present to emergency departments for care. Improving recognition and diagnosis of recurrent nonmotor seizures in emergency departments represents a significant opportunity for improving time to diagnosis, particularly when patients present following a first lifetime motor seizure and meet diagnostic criteria for epilepsy. Diagnostic delay in epilepsy is a significant public health issue and recent studies have highlighted potential areas for intervention.

Continuous EEG findings in patients with COVID-19 infection admitted to a New York academic hospital system.

OBJECTIVE: There is evidence for central nervous system complications of coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Encephalopathy caused by or arising from seizures, especially nonconvulsive seizures (NCS), often requires electroencephalography (EEG) monitoring for diagnosis. The prevalence of seizures and other EEG abnormalities among COVID-19-infected patients is unknown. METHODS: Medical records and EEG studies of patients hospitalized with confirmed COVID-19 infections over a 2-month period at a single US academic health system (four hospitals) were reviewed to describe the distribution of EEG findings including epileptiform abnormalities (seizures, periodic discharges, or nonperiodic epileptiform discharges). Factors including demographics, remote and acute brain injury, prior history of epilepsy, preceding seizures, critical illness severity scores, and interleukin 6 (IL-6) levels were compared to EEG findings to identify predictors of epileptiform EEG abnormalities. RESULTS: Of 111 patients monitored, most were male (71%), middle-aged or older (median age 64 years), admitted to an intensive care unit (ICU; 77%), and comatose (70%). Excluding 11 patients monitored after cardiac arrest, the most frequent EEG finding was moderate generalized slowing (57%), but epileptiform findings were observed in 30% and seizures in 7% (4% with NCS). Three patients with EEG seizures did not have epilepsy or evidence of acute or remote brain injury, although all had clinical seizures prior to EEG. Only having epilepsy (odds ratio [OR] 5.4, 95% confidence interval [CI] 1.4-21) or seizure(s) prior to EEG (OR 4.8, 95% CI 1.7-13) was independently associated with epileptiform EEG findings. SIGNIFICANCE: Our study supports growing evidence that COVID-19 can affect the central nervous system, although seizures are unlikely a common cause of encephalopathy. Seizures and epileptiform activity on EEG occurred infrequently, and having a history of epilepsy or seizure(s) prior to EEG testing was predictive of epileptiform findings. This has important implications for triaging EEG testing in this population.

Focal nonmotor versus motor seizures: The impact on diagnostic delay in focal epilepsy.

OBJECTIVE: To test the hypothesis that people with focal epilepsy experience diagnostic delays that may be associated with preventable morbidity, particularly when seizures have only nonmotor symptoms, we compared time to diagnosis, injuries, and motor vehicle accidents (MVAs) in people with focal nonmotor versus focal seizures with motor involvement at epilepsy onset. METHODS: This retrospective study analyzed the enrollment data from the Human Epilepsy Project, which enrolled participants between 2012 and 2017 across 34 sites in the USA, Canada, Europe, and Australia, within 4 months of treatment for focal epilepsy. A total of 447 participants were grouped by initial seizure semiology (focal nonmotor or focal with motor involvement) to compare time to diagnosis and prediagnostic injuries including MVAs. RESULTS: Demographic characteristics were similar between groups. There were 246 participants (55%) with nonmotor seizures and 201 participants (45%) with motor seizures at epilepsy onset. Median time to diagnosis from first seizure was 10 times longer in patients with nonmotor seizures compared to motor seizures at onset (P < .001). The number and severity of injuries were similar between groups. However, 82.6% of MVAs occurred in patients with undiagnosed nonmotor seizures. SIGNIFICANCE: This study identifies reasons for delayed diagnosis and consequences of delay in patients with new onset focal epilepsy, highlighting a treatment gap that is particularly significant in patients who experience nonmotor seizures at epilepsy onset.

Improving epilepsy diagnosis across the lifespan: approaches and innovations.

Epilepsy diagnosis is often delayed or inaccurate, exposing people to ongoing seizures and their substantial consequences until effective treatment is initiated. Important factors contributing to this problem include delayed recognition of seizure symptoms by patients and eyewitnesses; cultural, geographical, and financial barriers to seeking health care; and missed or delayed diagnosis by health-care providers. Epilepsy diagnosis involves several steps. The first step is recognition of epileptic seizures; next is classification of epilepsy type and whether an epilepsy syndrome is present; finally, the underlying epilepsy-associated comorbidities and potential causes must be identified, which differ across the lifespan. Clinical history, elicited from patients and eyewitnesses, is a fundamental component of the diagnostic pathway. Recent technological advances, including smartphone videography and genetic testing, are increasingly used in routine practice. Innovations in technology, such as artificial intelligence, could provide new possibilities for directly and indirectly detecting epilepsy and might make valuable contributions to diagnostic algorithms in the future.

Long-term seizure diary tracking habits in clinical studies: Evidence from the Human Epilepsy Project.

OBJECTIVE: To characterize seizure tracking patterns of people with focal epilepsy using electronic seizure diary entries, and to assess for risk factors associated with poor tracking. METHODS: We analyzed electronic seizure diary data from 410 participants with newly diagnosed focal epilepsy in the Human Epilepsy Project 1 (HEP1). Each participant was expected to record data each day during the study, regardless of seizure occurrence. The primary outcome of this post-hoc analysis was whether each participant properly tracked a seizure diary entry each day during their study participation. Using finite mixture modeling, we grouped patient tracking trajectories into data-driven clusters. Once defined, we used multinomial modeling to test for independent risk factors of tracking group membership. RESULTS: Using over up to three years of daily seizure diary data per subject, we found four distinct seizure tracking groups: consistent, frequent at study onset, occasional, and rare. Participants in the consistent tracking group tracked a median of 92% (interquartile range, IQR: 82%, 99%) of expected days, compared to 47% (IQR:34%, 60%) in the frequent at study onset group, 37% (IQR: 26%, 49%) in the occasional group, and 9% (IQR: 3%, 15%) in the rare group. In multivariable analysis, consistent trackers had lower rates of seizure days per tracked year during their study participation, compared to other groups. SIGNIFICANCE: Future efforts need to focus on improving seizure diary tracking adherence to improve quality of outcome data, particularly in those with higher seizure burden. In addition, accounting for missing data when using seizure diary data as a primary outcome is important in research trials. If not properly accounted for, total seizure burden may be underestimated and biased, skewing results of clinical trials.

Unrecognized Focal Nonmotor Seizures in Adolescents Presenting to Emergency Departments.

BACKGROUND AND OBJECTIVES: Many adolescents with undiagnosed focal epilepsy seek evaluation in emergency departments (EDs). Accurate history-taking is essential to prompt diagnosis and treatment. In this study, we investigated ED recognition of motor vs nonmotor seizures and its effect on management and treatment of focal epilepsy in adolescents. METHODS: This was a retrospective analysis of enrollment data from the Human Epilepsy Project (HEP), an international multi-institutional study that collected data from 34 sites between 2012 and 2017. Participants were 12 years or older, neurotypical, and within 4 months of treatment initiation for focal epilepsy. We used HEP enrollment medical records to review participants' initial diagnosis and management. RESULTS: A total of 83 adolescents were enrolled between 12 and 18 years. Fifty-eight (70%) presented to an ED before diagnosis of epilepsy. Although most ED presentations were for motor seizures (n = 52; 90%), many patients had a history of nonmotor seizures (20/52 or 38%). Adolescents with initial nonmotor seizures were less likely to present to EDs (26/44 or 59% vs 32/39 or 82%, p = 0.02), and nonmotor seizures were less likely to be correctly identified (2/6 or 33% vs 42/52 or 81%, p = 0.008). A history of initial nonmotor seizures was not recognized in any adolescent who presented for a first-lifetime motor seizure. As a result, initiation of treatment and admission from the ED was not more likely for these adolescents who met the definition of epilepsy compared with those with no seizure history. This lack of nonmotor seizure history recognition in the ED was greater than that observed in the adult group (0% vs 23%, p = 0.03) and occurred in both pediatric and nonpediatric ED settings. DISCUSSION: Our study supports growing evidence that nonmotor seizures are often undiagnosed, with many individuals coming to attention only after conversion to motor seizures. We found this treatment gap is exacerbated in the adolescent population. Our study highlights a critical need for physicians to inquire about the symptoms of nonmotor seizures, even when the presenting seizure is motor. Future interventions should focus on improving nonmotor seizure recognition for this population in EDs.

Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations.

Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation. Many patients referred for surgical evaluation may benefit from ASM optimization; both ASM and surgical treatment should be individualized. Based on previous clinical studies and the authors' clinical experience with cenobamate, a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate. We recommend a cenobamate trial and ASM optimization in parallel with presurgical evaluations. Cenobamate can be started before phase two monitoring, especially in patients who are found to be suboptimal surgery candidates. As neurostimulation therapies are generally palliative, we recommend trying cenobamate before vagus nerve stimulation (VNS), deep brain stimulation, or responsive neurostimulation (RNS). In surgically remediable cases (mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), cenobamate use should not delay imminent surgery; however, a patient may decide to defer or even cancel surgery should they achieve sustained seizure freedom with cenobamate. This decision should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, potential surgical risks (mortality and morbidity), and likely surgical outcome. The addition of cenobamate after unsuccessful surgery or palliative neuromodulation may also be associated with better outcomes.

Impact of Seizures While Driving Prior to Diagnosis in People With Focal Epilepsy: Motor Vehicle Accidents and Time to Diagnosis.

OBJECTIVES: To identify the type, frequency, and consequences of seizures while driving (SzWD) in people with epilepsy before diagnosis. METHODS: We performed a retrospective cohort study using the Human Epilepsy Project (HEP) to identify prediagnostic SzWD. Clinical descriptions from seizure diaries and medical records were used to classify seizure types and frequencies, time to diagnosis, and SzWD outcomes. Data were modeled using multiple logistic regression to assess for factors independently associated with SzWD. RESULTS: 32 prediagnostic SzWD were reported among 23/447 (5.1%) participants. Of them, 7 (30.4%) had more than 1. Six participants (26.1%) experienced SzWD as their first lifetime seizure. Most SzWD were focal with impaired awareness (n = 27, 84.4%). Of participants who had motor vehicle accidents (MVAs), 6 (42.9%) had no recollection. SzWD led to hospitalization in 11 people. The median time from first seizure to first SzWD was 304 days (IQR = 0-4,056 days). The median time between first SzWD and diagnosis was 64 days (IQR = 10-176.5 days). Employment was associated with a 3.95-fold increased risk of SzWD (95% CI 1.2-13.2, p = 0.03), and nonmotor seizures were associated with a 4.79-fold increased risk (95% CI 1.3-17.6, p = 0.02). DISCUSSION: This study identifies the consequences of seizure-related MVAs and hospitalizations people experience before epilepsy diagnosis. This highlights the need for further research aimed at improving seizure awareness and improving time to diagnosis.

Improving Seizure Frequency Documentation and Classification.

Background and Objectives: Accurate and reliable seizure data are essential for evaluating treatment strategies and tracking the quality of care in epilepsy clinics. This quality improvement project aimed to increase seizure documentation (i.e., documentation of seizure frequency from 80% to 100%, date of last seizure from 35% to 50%, and International League Against Epilepsy (ILAE) seizure classification from 35% to at least 50%) over 6 months. Methods: We surveyed 7 epileptologists to determine their perceived seizure frequency, ILAE classification, and date of last seizure documentation habits. Baseline data were collected weekly from September to December 2021. Subsequently, we implemented a newly created flowsheet in our Electronic Health Record (EHR) based on the Epilepsy Learning Healthcare System (ELHS) Case Report Forms to increase seizure documentation in a standardized way. Two epileptologists tested this flowsheet tool in their epilepsy clinics between February 2022 and July 2022. Data were collected weekly and compared with documentation from other epileptologists within the same group. Results: Epileptologists at our center believed they documented seizure frequency for 84%-87% of clinic visits, which aligned with baseline data collection, showing they recorded seizure frequency for 83% of clinic visits. Epileptologists believed they documented ILAE classification for 47%-52% of clinic visits, and baseline data showed this was documented in 33% of clinic visits. They also reported documenting the date of the last seizure for 52%-63% of clinic visits, but this occurred in only 35% of clinic visits. After implementing the new flowsheet, documentation increased to nearly 100% for all fields being completed by the providers who tested the flowsheet. Discussion: We demonstrated that by implementing an easy-to-use standardized EHR documentation tool, our documentation of critical metrics, as defined by the ELHS, improved dramatically. This shows that simple and practical interventions can substantially improve clinically meaningful documentation.

Impaired wake-promoting mechanisms in ghrelin receptor-deficient mice.

Ghrelin receptors are expressed by key components of the arousal system. Exogenous ghrelin induces behavioral activation, promotes wakefulness and stimulates eating. We hypothesized that ghrelin-sensitive mechanisms play a role in the arousal system. To test this, we investigated the responsiveness of ghrelin receptor knockout (KO) mice to two natural wake-promoting stimuli. Additionally, we assessed the integrity of their homeostatic sleep-promoting system using sleep deprivation. There was no significant difference in the spontaneous sleep-wake activity between ghrelin receptor KO and wild-type (WT) mice. WT mice mounted robust arousal responses to a novel environment and food deprivation. Wakefulness increased for 6 h after cage change accompanied by increases in body temperature and locomotor activity. Ghrelin receptor KO mice completely lacked the wake and body temperature responses to new environment. When subjected to 48 h food deprivation, WT mice showed marked increases in their waking time during the dark periods of both days. Ghrelin receptor KO mice failed to mount an arousal response on the first night and wake increases were attenuated on the second day. The responsiveness to sleep deprivation did not differ between the two genotypes. These results indicate that the ghrelin-receptive mechanisms play an essential role in the function of the arousal system but not in homeostatic sleep-promoting mechanisms.

Treatment gaps in epilepsy.

Over 50 million people around the world have epilepsy, and yet, epilepsy recognition and access to care are ongoing issues. Nearly 80% of people with epilepsy live in low-and middle-income countries and face the greatest barriers to quality care. However, there are substantial disparities in care within different communities in high-income countries as well. Across the world, under-recognition of seizures continues to be an issue, leading to diagnostic and treatment delays. This stems from issues surrounding stigma, public education, basic access to care, as well as healthcare worker education. In different regions, people may face language barriers, economic barriers, and technological barriers to timely diagnosis and treatment. Even once diagnosed, people with epilepsy often face gaps in optimal seizure control with the use of antiseizure medications. Additionally, nearly one-third of people with epilepsy may be candidates for epilepsy surgery, and many either do not have access to surgical centers or are not referred for surgical evaluation. Even those who do often experience delays in care. The purpose of this review is to highlight barriers to care for people with epilepsy, including issues surrounding seizure recognition, diagnosis of epilepsy, and the initiation and optimization of treatment.

Standardization of seizure response times and data collection in an epilepsy monitoring unit.

OBJECTIVE: We sought to improve seizure response times in the epilepsy monitoring unit, improve the accuracy and reliability of seizure response time data collection, and develop a standardized and automated approach for seizure response data collection in the EMU. METHODS: We used Quality Improvement (QI) methodology to understand the EMU workflow involved in responding to seizures (a process map); to create a theory of change that stated the desired aim, potential drivers/barriers and interventions (i.e., key driver diagram) and perform iterative interventions to address some of the drivers plan-do-study-act (PDSA) cycles. We performed three PDSA cycles with a focus on improving the seizure alert system in our EMU. Adjustments were made to the methodology as it became clear that this was a systems issue, and our project would need to focus on improving the system rather than iteratively improving a functioning (stable) system. RESULTS: Over a 6-month period, 252 seizure response times were recorded and analyzed. We performed 3 interventions. The first was initiating twice monthly meetings with nursing and EEG techs to discuss the project and provide feedback on response times. The second was the implementation of a new Hill-Rom seizure alert system to reduce alert times and automate data tracking. The third was implementing a new alert deactivation system to reduce variability in the data. Following these 3 interventions, variation, and data collection methods were improved while also maintaining improvements in seizure response times. SIGNIFICANCE: We identified and implemented an alert system in our EMU which led to more efficient and accurate data collection while maintaining improved response times that resulted from the first intervention. This lays the groundwork for future QI initiatives and has created a framework for standardizing seizure response time recording and data collection that can be replicated at other centers with similar infrastructure, personnel and workflows.

Prospective multisite cohort study of patient-reported outcomes in adults with new-onset seizures.

OBJECTIVE: New-onset seizures affect up to 10% of people over their lifetime, however, their health economic impact has not been well-studied. This prospective multicenter study will collect patient-reported outcome measures (PROMs) from adults with new-onset seizures seen in six Seizure Clinics across Melbourne, Australia and The University of Colorado, USA. METHODS: Approximately 450 eligible patients will be enrolled in the study at or following their initial attendance to Seizure Clinics at the study hospitals. Inclusion criteria for the study group are those with new-onset acute symptomatic seizures, new-onset unprovoked seizures, and new-onset epilepsy. Inclusion criteria for the three comparator groups are those with noncardiac syncope, those with psychogenic nonepileptic seizures, as well as published PROMs data from the Australian general population. Exclusion criteria are those aged less than 18 years, those with a preexisting epilepsy diagnosis, and those with intellectual disabilities or other impairments which would preclude them from comprehending and completing the questionnaires. Patients will complete eight online questionnaires regarding the effect that their seizures (or seizure mimics) have had on various aspects of their life. These questionnaires will be readministered at 6 and 12 months. Patients with new-diagnosis epilepsy will also be asked to share the reasons why they have accepted or declined antiseizure medications. ANALYSIS: Primary outcome measures will be quality of life, work productivity, informal care needs, and mood, at baseline compared to 6 and 12 months later for those with new-onset seizures and comparing these outcomes to those in the three comparator groups. Secondary outcomes include mapping of QoLIE-31 to the EQ-5D-5L in epilepsy, modelling indirect costs of new-onset seizures, and exploring why patients may or may not wish to take antiseizure medications. SIGNIFICANCE: These data will form an evidence-base for future studies that examine the effectiveness of various healthcare interventions for new-onset seizure patients. ETHICS AND DISSEMINATION: This study is approved by the Alfred Health Human Research Ethics Committee (SERP: 52 538, Alfred HREC: 307/19), the Austin Health Human Research Ethics Committee (HREC/59148/Austin-2019), and the Colorado Multiple Institutional Review Board (COMIRB) (COMIRB #20-3028). ANZCTR TRIAL REGISTRATION NUMBER: ACTRN12621000908831.