Impact of the COVID-19 pandemic on people with epilepsy: Findings from the US arm of the COV-E study

Objectives: As part of the COVID-19 and Epilepsy (COV-E) global study, we aimed to understand the impact of COVID-19 on the medical care and well-being of people with epilepsy (PWE) in the United States, based on their perspectives and those of their caregivers. Methods: Separate surveys designed for PWE and their caregivers were circulated from April 2020 to July 2021; modifications in March 2021 included a question about COVID-19 vaccination status. Results: We received 788 responses, 71% from PWE (n = 559) and 29% (n = 229) from caregivers of persons with epilepsy. A third (n = 308) of respondents reported a change in their health or in the health of the person they care for. Twenty-seven percent (n = 210) reported issues related to worsening mental health. Of respondents taking ASMs (n = 769), 10% (n = 78) reported difficulty taking medications on time, mostly due to stress causing forgetfulness. Less than half of respondents received counseling on mental health and stress. Less than half of the PWE reported having discussions with their healthcare providers about sleep, ASMs, and potential side effects, while a larger proportion of caregivers (81%) reported having had discussions with their healthcare providers on the same topics. More PWE and caregivers reported that COVID-19-related measures caused adverse impact on their health in the post-vaccine period than during the pre-vaccine period, citing mental health issues as the primary reason. Significance: Our findings indicate that the impact of the COVID-19 pandemic in the US on PWE is multifaceted. Apart from the increased risk of poor COVID-19 outcomes, the pandemic has also had negative effects on mental health and self-management. Healthcare providers must be vigilant for increased emotional distress in PWE during the pandemic and consider the importance of effective counseling to diminish risks related to exacerbated treatment gaps

Outcomes of COVID-19 patients treated with continuous positive airway pressure outside ICU

Aim We aim at characterizing a large population of Coronavirus 19 (COVID-19) patients with moderate-to-severe hypoxemic acute respiratory failure (ARF) receiving CPAP outside intensive care unit (ICU), and ascertaining whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. Methods In this retrospective, multicentre cohort study, we included COVID-19 adult patients, treated with CPAP outside ICU for hypoxemic ARF from March 1 st to April 15th, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay (LOS), and 60- day in-hospital mortality. Results The study includes 537 patients with a median age of 69 (IQR, 60-76) years. Males were 391 (73%). According to predefined CPAP therapeutic goal, 397 (74%) patients were included in full treatment subgroup, and 140 (26%) in the do-not intubate (DNI) subgroup. Median CPAP duration was 4 (IQR, 1-8) days, while hospital LOS 16 (IQR, 9-27) days. Sixty-day in-hospital mortality was overall 34% (95%CI, 0.304-0.384), and 21% (95%CI, 0.169-0.249) and 73% (95%CI, 0.648-0.787) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95%CI, 0.345-0.488) for 180 (45%) CPAP failures requiring intubation, while 2% (95%CI, 0.008- 0.035) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality [HR, 1.093 (95%CI, 1.010-1.184)]. Conclusions We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures

Impact of the COVID-19 pandemic on people with epilepsy: findings from the Brazilian arm of the COV-E study

The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures. Objectives: As part of the COVID-19 and Epilepsy (COV-E) global study, we ascertained the effects of COVID-19 on people with epilepsy in Brazil, based on their perspectives and their perspectives those of those of their caregivers. We also evaluated the impact of COVID-19 on the care delivered to people with epilepsy by healthcare workers. Methods: We designed separate online surveys for people with epilepsy and their caregivers. A further survey for healthcare workers contained additional assessments of changes to working patterns, productivity, and concerns for those with epilepsy under their care. The Brazilian arm of COV-E initially collected data from April to November 2020 during the country's first wave. We also examined national data to identify the Brazilian states with the highest COVID-19 incidence and related mortality. Lastly, we applied this geographic grouping to our data to explore whether local disease burden played a direct role in difficulties faced by people with epilepsy. Results: Two hundred and forty-one people returned the survey, 20% were individuals with epilepsy (n = 48); 22% were caregivers (n = 53) and 58% were healthcare workers (n = 140). Just under half (43%) of people with epilepsy reported health changes during the pandemic, including worsening seizure control, with specific issues related to stress and impaired mental health. Of respondents prescribed antiseizure medication, 11% reported difficulty taking medication on time due to problems acquiring prescriptions and delayed or cancelled medical appointments. Only a small proportion of respondents reported discussing significant epilepsy-related risks in the previous 12 months. Analysis of national COVID-19 data showed a higher disease burden in the states of Sao Paulo and Rio de Janeiro compared to Brazil as a whole. There were, however, no geographic differences observed in survey responses despite variability in the incidence of COVID-19. Conclusion: Our findings suggest that Brazilians with epilepsy have been adversely affected by COVID-19 by factors beyond infection or mortality. Mental health issues and the importance of optimal communication are critical during these difficult times. Healthcare services need to find nuanced approaches and learn from shared international experiences to provide optimal care for people with epilepsy as the direct burden of COVID-19 improves in some countries. In contrast, others face resurgent waves of the pandemic

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia

Identifying mutations in epilepsy genes: Impact on treatment selection

The last decade saw impressive advances not only in the discovery of gene mutations causing epilepsy, but also in unraveling the molecular mechanisms underlying the clinical manifestations of the disease. Increasing evidence is emerging that understanding these mechanisms is relevant for selection of the most appropriate treatment in the affected individual(s). The present article discusses the therapeutic implications of epilepsy causing variants affecting a broad range of targets, from ion channels to genes controlling cellular metabolism and cell signaling pathways. Identification of a precise genetic etiology can direct physicians to (i) prescribe treatments that correct specific metabolic defects (e.g., the ketogenic diet for GLUT1 deficiency, or pyridoxine for pyridoxine-dependent epilepsies); (ii) avoid antiepileptic drugs (AEDs) that can aggravate the pathogenic defect (e.g., sodium channel blocking drugs in SCN1A-related Dravet syndrome), or (iii) select AEDs that counteract the functional disturbance caused by the gene mutation (e.g., sodium channel blockers for epilepsies due to gain-of-function SCN8A mutations). In some instances, different pathogenic variants of the same gene can have opposite functional effects, which determines whether certain treatments can be beneficial or deleterious (e.g., gain-of-function versus loss-of-function variants in SCN2A determine whether sodium channel blockers improve or worsen seizure control). There are also cases where functional disturbances caused by the gene defect may not be corrected by existing AEDs, but can be countered by medications already available in the market for other indications (e.g., memantine has been used to treat the epileptic encephalopathy caused by a specific gain-of-function GRIN2A mutation), thus making 'drug repurposing' a valuable tool for personalized epilepsy therapies. As our understanding of pathogenic mechanisms improve, opportunities arise for development of treatments targeting the specific gene defect or its consequences. Everolimus, an mTOR inhibitor approved for the treatment of focal seizures associated with tuberous sclerosis complex, is an example of a medication targeting the etiological mechanisms of the disease. Several treatments aimed at correcting specific pathogenic defects responsible for rare genetic epilepsies are currently in development, and range from traditional small molecules to novel approaches involving peptides, antisense oligonucleotides, and gene therapy

The role of genetic factors in the aetiology of focal epilepsy and in the outcomes of epilepsy treatment

© 2017 Dr. Piero Cesare PeruccaEpilepsy is one of the most common neurological disorders, affecting people of all ages, races, social classes, and nationalities. It is characterised by an enduring predisposition to generate epileptic seizures, and by the neurobiological, cognitive, psychological and social consequences of this condition. The aetiology of epilepsy has long been regarded as ‘unknown’ in about two-thirds of cases. However, evidence mainly from the past two decades has allowed to establish that many epilepsies initially considered to be of unknown cause have in fact a genetic basis. The importance of genetics in epilepsy is not limited to aetiology, and growing interest exists on the genetic contributions to epilepsy treatment outcomes. The overarching aim of this thesis was to investigate and characterise the role of genetic factors in determining the aetiology of focal epilepsies and influencing outcomes of epilepsy treatment. Firstly, I ascertained the extent to which newly diagnosed non-lesional mesial temporal lobe epilepsy (MTLE) actually represents familial MTLE (FMTLE). By directly assessing relatives of patients presenting to a First Seizure Clinic with non-lesional MTLE, the familial syndrome of FMTLE was found to account for about one-fifth of new diagnoses of non-lesional MTLE. Secondly, I examined the diagnostic yield and management implications of genetic testing in the routine clinical care of focal epilepsies. By applying whole exome sequencing (WES) with targeted gene analysis on patients with non-lesional focal epilepsy in whom a genetic aetiology was suspected, pathogenic or likely pathogenic variants were detected in one-eighth of cases. In an individual with drug-resistant epilepsy, the genetic finding altered clinical management, resulting in complete seizure control. Thirdly, I evaluated whether genetic factors influence seizure outcome after surgery for drug-resistant MTLE. Using a multicentre case-control WES study design, no definitive evidence for genetic influences on postsurgical outcome was found. However, a signal emerged for surgical failures, as a group, being enriched for individuals with deleterious variants in established epilepsy genes. Lastly, I investigated the genetic underpinnings of neural tube defects (NTDs) resulting from prenatal exposure to valproic acid (VPA). Adopting a family-based WES study design, two rare variants possibly conferring a substantial risk of VPA-associated NTDs were identified in the planar cell polarity genes CELSR1 and SCRIB. However, this interpretation remains speculative due to sample size limitations. Clearly, genetics has an important role in the aetiology of focal epilepsy. The results of this thesis also substantiate the excitement around the potential for genetics to improve outcomes of epilepsy treatment

Widespread EEG Changes Precede Focal Seizures

<div><p>The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal), and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline). Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma) and high-frequency bands (ripples and fast ripples). At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development), but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures.</p></div