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Abstract Post-traumatic epilepsy is the architype of acquired epilepsies, wherein a brain insult initiates an epileptogenic process culminating in an unprovoked seizure after weeks, months or years. Identifying biomarkers of such process is a prerequisite for developing and implementing targeted therapies aimed at preventing the development of epilepsy. Currently, there are no validated electrophysiological biomarkers of post-traumatic epileptogenesis. Experimental EEG studies using the lateral fluid percussion injury model have identified three candidate biomarkers of post-traumatic epileptogenesis: pathological high-frequency oscillations (HFOs, 80–300 Hz); repetitive HFOs and spikes (rHFOSs); and reduction in sleep spindle duration and dominant frequency at the transition from stage III to rapid eye movement sleep. EEG studies in humans have yielded conflicting data; recent evidence suggests that epileptiform abnormalities detected acutely after traumatic brain injury carry a significantly increased risk of subsequent epilepsy. Well-designed studies are required to validate these promising findings, and ultimately establish whether there are post-traumatic electrophysiological features which can guide the development of 'antiepileptogenic' therapies. [ABSTRACT FROM AUTHOR]

Gender differences in the incidence and clinical course of acquired and “cryptogenic” epilepsy are reviewed based on a literature search. We emphasized incidence and population-based studies because they are best suited to assess the effect of gender on susceptibility and clinical evolution of these epilepsies and may control for potential confounding factors. However, such studies were only available for a few acquired etiologies. These included tumor, prenatal and perinatal brain insults, cerebrovascular disease, infection, trauma, neurodegenerative disease, and autoimmune disorders. None of these acquired causes has been consistently shown to affect women or men to a greater or lesser degree, although some of the literature is contradictory or inadequate. There is almost no literature that addresses the effect of gender on the clinical course of epilepsy associated with these acquired causes. In addition, most studies of acquired causes do not take into account the incidence of the cause in the population with or without associated epilepsy. In children, “cryptogenic” epilepsy (non-syndromic and without causative MRI lesion) does not appear to have a gender preference and gender does not seem to affect the likelihood of remission. As further population-based studies of the etiology and clinical course of epilepsy are undertaken, it may be worthwhile to more specifically define the role of gender. [ABSTRACT FROM AUTHOR]

Abstract: With almost 100years of clinical experience, antiepileptic drugs (AEDs) remain the mainstay of epilepsy treatment. They suppress epileptic seizures by acting on a variety of mechanisms and molecular targets involved in the regulation of neuronal excitability. These include inhibitory-GABAergic and excitatory-glutamatergic neurotransmission, as well as ion (sodium and calcium) conductance through voltage-gated channels. On the other hand, accruing evidence indicates that these mechanisms and targets are also implicated in the regulation of mood and behavior, which may explain why each AED is associated with specific psychotropic effects. These effects, however, cannot be explained solely on the basis of the known mode of action of each AED, and other mechanisms or targets are likely to be implicated. In this article, we review positive and negative effects of AEDs on mood and behavior, discuss putative underlying mechanisms, and highlight knowledge gaps which should be addressed in future studies. This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”. [Copyright &y& Elsevier]

• Oculomotor tasks can be used as sensitive and objective measures of cerebral function in epilepsy. • Adults with drug-resistant focal epilepsy exhibited slow antisaccade processing speed, impaired inhibition, and poor visuospatial accuracy. • Processing speed slowing is marked in patients with left hemispheric epilepsy and those with temporal lobe epilepsy. Using objective oculomotor measures, we aimed to: (1) compare oculomotor performance in patients with drug-resistant focal epilepsy to healthy controls, and (2) investigate the differential impact of epileptogenic focus laterality and location on oculomotor performance. We recruited 51 adults with drug-resistant focal epilepsy from the Comprehensive Epilepsy Programs of two tertiary hospitals and 31 healthy controls to perform prosaccade and antisaccade tasks. Oculomotor variables of interest were latency, visuospatial accuracy, and antisaccade error rate. Linear mixed models were performed to compare interactions between groups (epilepsy, control) and oculomotor tasks, and between epilepsy subgroups and oculomotor tasks for each oculomotor variable. Compared to healthy controls, patients with drug-resistant focal epilepsy exhibited longer antisaccade latencies (mean difference = 42.8 ms, P = 0.001), poorer spatial accuracy for both prosaccade (mean difference = 0.4°, P = 0.002), and antisaccade tasks (mean difference = 2.1°, P < 0.001), and more antisaccade errors (mean difference = 12.6%, P < 0.001). In the epilepsy subgroup analysis, left-hemispheric epilepsy patients exhibited longer antisaccade latencies compared to controls (mean difference = 52.2 ms, P = 0.003), while right-hemispheric epilepsy was the most spatially inaccurate compared to controls (mean difference = 2.5°, P = 0.003). The temporal lobe epilepsy subgroup displayed longer antisaccade latencies compared to controls (mean difference = 47.6 ms, P = 0.005). Patients with drug-resistant focal epilepsy exhibit poor inhibitory control as evidenced by a high percentage of antisaccade errors, slower cognitive processing speed, and impaired visuospatial accuracy on oculomotor tasks. Patients with left-hemispheric epilepsy and temporal lobe epilepsy have markedly impaired processing speed. Overall, oculomotor tasks can be a useful tool to objectively quantify cerebral dysfunction in drug-resistant focal epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Epilepsy is a chronic disorder with complex effects on social, vocational, physical, and psychological well-being. Patient-oriented research has demonstrated that recurrent seizures have a strong adverse effect on health-related quality of life, but also that seizure rate in persons with pharmacoresistant epilepsy has only a modest correlation with quality of life. Although treatment side effects have received limited attention in epilepsy research, available evidence indicates that adverse medication effects may explain more variance in quality of life than any other clinical variable in persons with pharmacoresistant epilepsy. Furthermore, systematic screening for adverse effects has been shown to be associated with significant reduction in subjective toxicity and improvement in quality of life. There has been only limited research on the relative contribution of specific adverse effects to impaired health-related quality of life. The relative importance of reduction of medication burden after resective epilepsy surgery or vagal nerve stimulation has similarly received sparse attention. Existing deficiencies in the available published research present challenges and opportunities to perform further investigations to define and improve best clinical practices in epilepsy care. [Copyright &y& Elsevier]

Abstract: Growing evidence indicates that fast oscillations (>80Hz) can be recorded interictally in the scalp EEG of patients with epilepsy, and that they may point to the seizure-onset zone. However, mechanisms underpinning the emergence of scalp fast oscillations, and whether they differ from those of interictal epileptic discharges (IEDs), are yet to be understood. The visibility of cortical electric activity on scalp EEG recordings is dependent on two factors: the characteristics of the cortical generator and the background level. We studied this issue using scalp EEG recordings and detailed simulations, with a finite element model including 8million elements and 8 different tissues. We observed an almost linear relationship between the amplitude of scalp electric potential and the extent of the generator on the cortex. However, this relationship is subject to substantial variability, with variations in factors greater than 3 occurring simply by changing the location on the cortex of generators of fixed extent. In addition, we showed that the background power in scalp EEG recordings decreases at higher frequency bands, being inversely proportional to a power of 2.5 of the frequency. In the specific case of fast oscillations, they can be detected within the lower noise level of the ripple band (80–200Hz) even though their median amplitude on scalp EEG recordings is more than 10 times smaller than IEDs and consistent with cortical generators of approximately 1cm2. In conclusion, the physics governing the propagation of electrical activity from the brain to the scalp are consistent with the hypothesis that scalp fast oscillations and intracranial high-frequency oscillations (HFOs, 80–500Hz) are expressions of common generators. Given the potential role of HFOs as biomarkers in epilepsy, the possibility to obtain some of the associated information from scalp EEG is of high clinical significance. [Copyright &y& Elsevier]

• This study evaluated the role of antiseizure medications and other factors in the occurrence of intrauterine foetal deaths in Australian pregnant women with epilepsy. • Exposure to at least some antiseizure medications may be associated with risk of intrauterine foetal death. • Non-pharmacological factors, such as prior lost pregnancies and parental history malformations, are however more relevant to intrauterine foetal death occurrence. To assess the role of antiseizure medication (ASM) regimens and other factors in relation to the occurrence of intrauterine foetal death (IUFD) in pregnant women with epilepsy (WWE) enrolled in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (APR). IUFDs occurred in 70 (3.01 %) of 2,323 prospective pregnancies from WWE with known outcomes in the APR. Factors associated with IUFD occurrence included older maternal age, enrolment in the APR at an earlier stage of pregnancy, history of pregnancies which did not result in livebirths, parental history of foetal malformations, and maternal use of carbamazepine, lamotrigine or ethosuximide. Individual ASM dosages were not associated with IUFD occurrence. Relative to no exposure, the risk of IUFD increased with the increasing number of ASMs used in combination (2 ASMs: relative risk, RR = 5.45 [95 % CI: 0.73–41.80]; 3 ASMs: RR = 10.70 [95 % CI: 1.27–90.17]), >3 ASMs: RR = 10.70 [95 % CI: 1.27–90.17]), but this finding was attenuated after adjusting for other factors implicated in IUFD occurrence. Several ASM pairs were associated with an increased risk of IUFD relative to no exposure, but these associations were lost after accounting for confounders. Although it is possible that prenatal ASM exposure may increase the risk of IUFD, other non-pharmacological factors are more relevant to the occurrence to IUFD in pregnant WWE. [ABSTRACT FROM AUTHOR]

• Medical professionals are given questionnaires on the use of automated EEG based seizure detection tools. • The questionnaires focus on clinical utility, sentiment, requirements and barriers. • Minimum sensitivity required is 80% in seizure detection. • Respondents are receptive to the use of automated EEG based seizure detection tools. • Barriers for usage include lack of availability, training and the black box nature of these tools. Diagnosing and managing seizures presents substantial challenges for clinicians caring for patients with epilepsy. Although machine learning (ML) has been proposed for automated seizure detection using EEG data, there is little evidence of these technologies being broadly adopted in clinical practice. Moreover, there is a noticeable lack of surveys investigating this topic from the perspective of medical practitioners, which limits the understanding of the obstacles for the development of effective automated seizure detection. Besides the issue of generalisability and replicability seen in a small amount of studies, obstacles to the adoption of automated seizure detection remain largely unknown. To understand the obstacles preventing the application of seizure detection tools in clinical practice, we conducted a survey targeting medical professionals involved in the management of epilepsy. Our study aimed to gather insights on various factors such as the clinical utility, professional sentiment, benchmark requirements, and perceived barriers associated with the use of automated seizure detection tools. Our key findings are: I) The minimum acceptable sensitivity reported by most of our respondents (80%) seems achievable based on studies reported from most currently available ML-based EEG seizure detection algorithms, but replication studies often fail to meet this minimum. II) Respondents are receptive to the adoption of ML seizure detection tools and willing to spend time in training. III) The top three barriers for usage of such tools in clinical practice are related to availability, lack of training, and the blackbox nature of ML algorithms. Based on our findings, we developed a guide that can serve as a basis for developing ML-based seizure detection tools that meet the requirements of medical professionals, and foster the integration of these tools into clinical practice. [ABSTRACT FROM AUTHOR]

• This study assessed changes over 24 years in antiseizure medications (ASMs) used by women with epilepsy (WWE) enrolled in the Australian Pregnancy Register (APR). • The use of valproate and carbamazepine decreased progressively, that of lamotrigine plateaued, that of levetiracetam increased progressively, and that of topiramate first increased and then dropped again. • There has been a decrease in serious foetal malformations (e.g., spina bifida), with a tendency for more trivial ones to increase. • There has been an increase in rates of seizure freedom both before and during pregnancy. To trace (i) changes in Australian Pregnancy Register (APR) records concerning antiseizure medications (ASMs) prescribed for women with epilepsy (WWE) over the course of 24 years and correlate the changes with (ii) rates of occurrence of pregnancies involving foetal malformations, (iii) the body organs involved in the malformations, and (iv) freedom from epileptic seizures. Use of valproate and carbamazepine decreased progressively, use of lamotrigine remained relatively static, and the use of levetiracetam increased progressively, whereas the use of topiramate first increased and then fell again, associated with a temporary increase in malformation-associated pregnancy rate. More serious malformations, such as spina bifida, became less frequent, whereas more trivial ones tended to increase, whereas epileptic seizure freedom rates improved. The increasing use of newer ASMs in pregnant women has been associated with overall advantages in relation to the frequency and severity of foetal malformation and with advantages in relation to freedom from epileptic seizures. [ABSTRACT FROM AUTHOR]

• Prenatal exposure to valproate appears to be associated with non-specific organ teratogenicity. • Carbamazepine, topiramate, and zonisamide may instead have organ specific teratogenicity. • There is an increased hazard of fetal malformation if conception is facilitated by assisted fertilisation.. To investigate in the Australian Pregnancy Register of Antiepileptic Drugs patterns of fetal malformation associated with intrauterine exposure to particular currently available antiseizure medications taken by women with epilepsy. There was statistically significant evidence (P < 0.05) of an increased hazard of fetal malformation associated with exposure to valproate, carbamazepine, topiramate, zonisamide, and with conception after assisted fertilization, but a reduced hazard in the offspring of women who continued to smoke during pregnancy. Valproate exposure was associated with malformations in a wide range of organs and organ systems, carbamazepine and topiramate with hydronephrosis, topiramate also with hypospadias, zonisamide with spina bifida and assisted fertilization with heart and great vessel maldevelopment. Prenatal valproate exposure appears to interfere with the development of many if not all, fetal tissues. It seems likely that prenatal exposure to carbamazepine and topiramate, and possibly exposure to zonisamide, but also some process related to in vitro fertilization, may more selectively affect the normal development of particular fetal tissues or organs. [ABSTRACT FROM AUTHOR]

• We studied existing disorders in adults with a new diagnosis of epilepsy/seizures. • Forty percent of patients had a positive history, and 8 % reported >1 disorder. • Psychiatric (18%) and substance use (16%) disorders were most common. • Psychiatric and substance use disorders were most reported in those ≤65 years old. • Pre-existing health conditions were common and affected all age groups. People with epilepsy have a higher prevalence of medical and psychiatric comorbidities compared to the general population. Comorbidities are associated with poor epilepsy outcomes, and there have been recommendations for screening and early identification to improve clinical management. Data from 'First Seizure Clinics' (FSCs) with expert epileptological review can inform about disorders already present at the point of diagnosis of epilepsy or unprovoked seizures. Here, we aimed to describe pre-existing conditions with a focus on psychiatric, substance use, cardiac, neurological, and cancer health domains. We included 1383 adults who received a new diagnosis of epilepsy or unprovoked seizures at Austin Hospital (AH) or Royal Melbourne Hospital (RMH) (Australia) FSCs from 2000 to 2010. Data were audited from FSC records, primarily detailed interviews undertaken by epileptologists. Logistic regression examined age distribution and other risk factors. The median age at FSC presentation was 37 years (IQR 26–53, range 18–94). Pre-existing conditions were reported by 40 %; from 32 % in the youngest group (18–30 years) to 53 % in the oldest (65+ years). Psychiatric (18 %) and substance use (16 %) disorders were most common, with higher prevalence among patients 18 to 65 years of age compared to those older than 65 years (p < 0.001). Cardiac, neurological, or cancer conditions were reported by 3–6 %, most often amongst those older than 65 years (p < 0.01). Eight percent (n = 112) reported disorders in >1 health domain. The commonest combination was a psychiatric condition with substance use disorder. Of the sixty-two patients reporting this combination, 61 were ≤65 years of age. Pre-existing health conditions are present in a substantial proportion of patients diagnosed with epilepsy or unprovoked seizures. Disorders are highest amongst elders, but one-third of younger adults also reported positive histories. These are predominantly psychiatric and/or substance use disorders, conditions strongly associated with poor outcomes in the general population. These findings inform post-diagnosis planning and management, as well as research examining post-diagnostic outcomes and associations between comorbidities and epilepsy. [ABSTRACT FROM AUTHOR]

Malformations of cortical development (MCDs) are common causes of drug-resistant epilepsy. The mechanisms underlying the associated epileptogenesis and ictogenesis remain poorly elucidated. EEG can help in understanding these mechanisms. We systematically reviewed studies reporting scalp or intracranial EEG features of MCDs to characterise interictal and seizure-onset EEG patterns across different MCD types. We conducted a systematic review in accordance with PRISMA guidelines. MEDLINE, PubMed, and Cochrane databases were searched for studies describing interictal and seizure-onset EEG patterns in MCD patients. A classification framework was implemented to group EEG features into 20 predefined patterns, comprising nine interictal (five, scalp EEG; four, intracranial EEG) and 11 seizure-onset (five, scalp EEG; six, intracranial EEG) patterns. Logistic regression was used to estimate the odds ratios (OR) of each seizure-onset pattern being associated with specific MCD types. Our search yielded 1682 studies, of which 27 comprising 936 MCD patients were included. Of the nine interictal EEG patterns, five (three, scalp EEG; two, intracranial EEG) were detected in ≥2 MCD types, while four (rhythmic epileptiform discharges type 1 and type 2 on scalp EEG; repetitive bursting spikes and sporadic spikes on intracranial EEG) were seen only in focal cortical dysplasia (FCD). Of the 11 seizure-onset patterns, eight (three, scalp EEG; five, intracranial EEG) were found in ≥2 MCD types, whereas three were observed only in FCD (suppression on scalp EEG; delta brush on intracranial EEG) or tuberous sclerosis complex (TSC; focal fast wave on scalp EEG). Among scalp EEG seizure-onset patterns, paroxysmal fast activity (OR = 0.13; 95% CI: 0.03–0.53; p = 0.024) and repetitive epileptiform discharges (OR = 0.18; 95% CI: 0.05–0.61; p = 0.036) were less likely to occur in TSC than FCD. Among intracranial EEG seizure-onset patterns, low-voltage fast activity was more likely to be detected in heterotopia (OR = 19.3; 95% CI: 6.22–60.1; p < 0.001), polymicrogyria (OR = 6.70; 95% CI: 2.25–20.0; p = 0.004) and TSC (OR = 4.27; 95% CI: 1.88–9.70; p = 0.005) than FCD. Different MCD types can share similar interictal or seizure-onset EEG patterns, reflecting common underlying biological mechanisms. However, selected EEG patterns appear to point to distinct MCD types, suggesting certain differences in their neuronal networks. [ABSTRACT FROM AUTHOR]

• Women with epilepsy have an increased risk of fetal malformation in their next pregnancy if their previous pregnancy resulted in a malformation. • They seem predisposed to having babies with malformations in consecutive pregnancies. • These women tend to have genetic generalized epilepsies. • Valproate exposure does not fully account for their vulnerability to teratogenesis. To utilize data from the Australian Register of Antiepileptic Drugs in Pregnancy (APR) to determine the hazard of fetal malformation in the subsequent pregnancy or pregnancies in women with epilepsy following a pregnancy associated with a fetal malformation, and to identify factors relevant to the hazard. There was a 7.4% initial pregnancy fetal malformation rate. The subsequent pregnancy malformation rate was 4.2% if there was no initial pregnancy malformation, but 21.2% if there was an initial pregnancy malformation (O.R. = 6.1448, 95% C.I. 2.3396, 16.1386). For pregnancies where antiseizure medication (ASM) therapy was unchanged between pregnancies (N = 196), the initial pregnancy malformation rate was 10.2%, but 30.0% in the subsequent pregnancy if there was a malformation in the initial pregnancy, and 2.35% if there was none (O.R. = 17.7857, 95% C.I. 4.4847, 70.5361). A cohort comprising 24% of the women with fetal malformations in their initial pregnancies seemed to be intrinsically vulnerable to fetal malformation during successive pregnancies: when their seizure disorder type had been recorded all had genetic generalized epilepsies, compared with a 45.8% generalized epilepsy rate in women with initial but not subsequent pregnancy malformations (P = 0.0121). If fetal malformation had occurred in an initial ASM-treated pregnancy there was a significantly increased hazard of fetal malformation in the subsequent pregnancy, particularly if the woman involved had a genetic generalized epilepsy. [ABSTRACT FROM AUTHOR]

• Desirable outcome defined as seizure-free pregnancy and healthy baby. • Factors influencing desirable outcome examined. • From the Australian Register 46% of pregnancies achieved this result. • Seizure freedom for 12 months pre-pregnancy was statistically significant. • Valproate reduction was carried out in 15 per cent of pregnancies. • Levetiracetam replacement may be the most effective monotherapy as reported. To investigate possible factors that influenced whether pregnancy in women with epilepsy resulted in the desirable outcome of a live-born non-malformed infant and a mother whose pregnancy had been seizure free. The desirable outcome, as defined, occurred in 46.3% of unselected pregnancies in the database of the Australian Register of Antiepileptic Drugs in Pregnancy (APR). The only factor investigated that had a statistically significant (P < 0.05) effect, increasing the chance of such a desirable outcome, was freedom from seizures in the pre-pregnancy year. However, anti-seizure medication (ASM) doses, particularly valproate doses, had been reduced prior to 15.6% of the pregnancies, and this may have concealed factors that otherwise may have adversely affected the desirable outcome rate. Analysis of data for monotherapy with the more commonly used ASMs appears to suggest that employing levetiracetam at the outset of antiseizure therapy may offer a better chance of a desirable outcome to future pregnancies than monotherapy with other ASMs, but this finding is not confirmed statistically. In pregnancies where valproate use has already been minimized, seizure control throughout the pre-pregnancy year was associated with the best chance of a desirable outcome, as defined above. In most Australian women starting therapy for epilepsy initiating treatment with levetiracetam monotherapy may offer the best chance of such a desirable outcome to a future pregnancy, yet to be confirmed. [ABSTRACT FROM AUTHOR]

• Failure to achieve seizure control commoner in focal epilepsy. • More focal seizures were uncontrolled for a year or more before conception. • Younger age, generalized epilepsy showed lesser risk of seizures. • Risk of convulsive seizures commoner in generalized epilepsy. • Changing valproate before conception does not lead to seizure worsening. To examine factors contributing to failure to achieve full seizure control during pregnancy in women with anti-seizure medication (ASM) treated generalized epilepsy compared with focal epilepsy. Full seizure control was not attained in 51.4% of 1223 pregnancies of women with focal epilepsies in the Australian Pregnancy Register, and in 38.7% of 1026 pregnancies in women with generalized epilepsy (P < 0.05). For convulsive seizures only, the corresponding figures of 20.8% and 22.9% were reasonably similar. Where seizures had occurred in the pre-pregnancy year, 82.5% of the focal epilepsy pregnancies were seizure affected, and 70.1% of the generalized epilepsy ones (P < 0.05). Where the pre-pregnancy year was seizure free, the corresponding figures were 22.6% and 16.4% (P < 0.05), a roughly four-fold lower rate. Maternal age, epilepsy onset age, and epilepsy duration also differed between the focal and generalized epilepsy pregnancies. Multivariate regression analysis showed that generalized epilepsy and younger maternal age were associated with statistically significant decreased risks of seizure-affected pregnancy, and having seizure-affected pre-pregnancy years with an increased risk. However, for convulsive seizures only, the risk of seizure-affected pregnancy appeared increased in generalized epilepsy. The risk of seizure-affected pregnancy appears lower in women with generalized epilepsy, independently of pre-pregnancy seizure control, itself a major determinant of the risk. The risk of having only convulsive seizures in pregnancy was not lower in generalized epilepsy than in focal epilepsy. ASM therapy seemed less effective in controlling focal than generalized epileptic seizures during pregnancy. [ABSTRACT FROM AUTHOR]

• The COVID-19 and Epilepsy (COV-E) global surveys were launched in Brazil during the first wave of the pandemic. • People with epilepsy reported worsening seizure control, psychosocial stress, and impaired mental health. • There were difficulties in obtaining drug supplies because of canceled appointments. • Discussion of risk, including SUDEP, was infrequent even before the pandemic. • The surveys remain open to enable new participants to enter data providing insights as the pandemic evolves. 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. 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 those of their caregivers. We also evaluated the impact of COVID-19 on the care delivered to people with epilepsy by healthcare workers. 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 May 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. 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 canceled 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. 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. [ABSTRACT FROM AUTHOR]

• Psychiatric comorbidities are common among older adults admitted for VEM. • PNES is not as frequently diagnosed in older adults compared to younger adults. • Risk factors for PNES in younger adults are also applicable to older adults. • Older adults presenting for VEM had more cognitive impairment than younger adults. To compare the clinical, psychiatric, and cognitive characteristics of older with younger patients presenting to a video-EEG monitoring (VEM) unit. This was a retrospective case–control study involving patients admitted for VEM over a two-year period (from April 2018 to April 2020) at two comprehensive epilepsy units. Patients were categorized into an older (≥60 years) and a younger (<60 years) group. Younger patients were individually matched to older adults to form a matched younger group. Diagnosis was determined by a consensus opinion of epileptologists, neurologists, and neuropsychiatrists. The main diagnostic categories were epilepsy, psychogenic nonepileptic seizures (PNES), and 'other' diagnosis (non-diagnostic and other nonepileptic diagnoses). Clinical psychiatric diagnoses were obtained from neuropsychiatric reports. Objective cognitive function was measured with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Subjective cognitive function was assessed using the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) cognitive subscales. Five-hundred and thirty three patients (71 older, 462 younger) aged 16–91 years were admitted to the VEM unit during the study period. There was a diagnosis of focal epilepsy in 55% of the older group and 48% of the younger group, generalized epilepsy in 3% of the older group and 10% of the younger group, and 'other' in 32% of the older group and 19% of the younger group. Ten percent (2 males and 5 females) of the older group were diagnosed with PNES compared to 22% of the younger group (p = 0.016). A depressive disorder was diagnosed in 34% of the older group and 24% of the younger group (p = 0.20). An anxiety disorder was diagnosed in 15% of the older group and 25% of the younger group (p = 0.15). Mild neurocognitive disorder was more common in the older group (34%) compared to the matched younger group (34% vs 3%, p < 0.001). The older group had lower mean NUCOG scores compared to the matched younger group (79.49 vs 87.73, p = <0.001). There was no evidence for a relationship between mean NUCOG score and overall subjective cognitive difficulties for the older group (r = 0.03, p = 0.83). Among older adults, those diagnosed with PNES had more experiences of childhood trauma. Measures of dissociation, depression, or general anxiety did not differ between PNES and non-PNES diagnoses in the older group. Psychiatric comorbidities are common among older adults admitted for VEM. The psychological impact of epilepsy and risk factors for PNES seen in younger patients are also applicable in the older group. The older group demonstrated more cognitive impairments than the younger group, although these were usually unrecognized by individuals. Older adults admitted to VEM will benefit from psychiatric and neuropsychological input to ensure a comprehensive care approach to evaluation and management. [ABSTRACT FROM AUTHOR]

• The COVID-19 and Epilepsy (COV-E) global surveys were launched in May 2020. • UK respondents (n = 463) report changes in seizure frequency, mental health, and sleep. • Discussion of risk, including of SUDEP, was infrequent even before the pandemic. • COVID-19 is having far-reaching consequences on people with epilepsy. • Our study exemplifies the importance of delivering optimal care to mitigate risk. The COVID-19 pandemic has caused global anguish unparalleled in recent times. As cases rise, increased pressure on health services, combined with severe disruption to people's everyday lives, can adversely affect individuals living with chronic illnesses, including people with epilepsy. Stressors related to disruption to healthcare, finances, mental well-being, relationships, schooling, physical activity, and increased isolation could increase seizures and impair epilepsy self-management. We aim to understand the impact that COVID-19 has had on the health and well-being of people with epilepsy focusing on exposure to increased risk of seizures, associated comorbidity, and mortality. We designed two online surveys with one addressing people with epilepsy directly and the second for caregivers to report on behalf of a person with epilepsy. The survey is ongoing and has yielded 463 UK-based responses by the end of September 2020. Forty percent of respondents reported health changes during the pandemic (n = 185). Respondents cited a change in seizures (19%, n = 88), mental health difficulties (34%, n = 161), and sleep disruption (26%, n = 121) as the main reasons. Thirteen percent found it difficult to take medication on time. A third had difficulty accessing medical services (n = 154), with 8% having had an appointment canceled (n = 39). Only a small proportion reported having had discussions about epilepsy-related risks, such as safety precautions (16%, n = 74); mental health (29%, n = 134); sleep (30%, n = 140); and Sudden Unexpected Death in Epilepsy (SUDEP; 15%, n = 69) in the previous 12 months. These findings suggest that people with epilepsy are currently experiencing health changes, coupled with inadequate access to services. Also, there seems to be a history of poor risk communication in the months preceding the pandemic. As the UK witnesses a second COVID-19 wave, those involved in healthcare delivery must ensure optimal care is provided for people with chronic conditions, such as epilepsy, to ensure that avoidable morbidity and mortality is prevented during the pandemic, and beyond. [ABSTRACT FROM AUTHOR]

• Psychiatric symptomatology and AED adverse events are closely related. • Female sex and AED-polytherapy are associated with self-reported AED-adverse events. • Physical-adverse events and number of AEDs may differentiate epilepsy from PNES. • People with PNES endorse more physical-adverse events despite receiving fewer AEDs. Adverse events (AEs) related to antiepileptic drugs (AEDs) may interfere with adequate dosing and patient adherence, leading to suboptimal seizure control, and relatedly, increased injuries, hospitalizations, and mortality. This study investigated the clinicodemographic factors associated with AEs related to AEDs as reported by the Liverpool Adverse Events Profile (LAEP), and explored the ability of LAEP to discriminate between epilepsy and psychogenic nonepileptic seizures (PNES). We hypothesized that female sex, mood disorders, AED-polytherapy, duration, and severity of epilepsy are associated with increased endorsement of AEs related to AEDs, and that endorsement of AEs related to AEDs would significantly differ between epilepsy and PNES patients. We prospectively enrolled adult patients admitted to two inpatient video-electroencephalogram monitoring units. Clinicodemographic variables and psychometric measures of depression, anxiety, and cognitive function were recorded. Patient-reported AE endorsement was obtained using the LAEP, which was reduced to four latent domains using exploratory structural equation modeling. General linear models identified variables associated with each domain. Logistic regression determined the ability of LAEP scores to differentiate between epilepsy and PNES. 311 patients met inclusion criteria. Mean age was 38 years and 56% of patients were female. Network analysis demonstrated strong relationships between depression and anxiety with physical, sleep, psychiatric, and dermatological AE endorsement. Depression, female sex, and AED polytherapy were associated with greater AE endorsement. Epilepsy, compared to PNES, was associated with lower AE endorsement. Fewer prescribed AEDs and greater reported physical AE endorsement were associated with PNES diagnosis. There is a strong relationship between patient-reported AEs and psychiatric symptomatology. Those with PNES paradoxically endorse greater physical AEs despite receiving fewer AEDs. Patients who endorse AEs in clinical practice should be screened for comorbid depression or anxiety and treated accordingly. [ABSTRACT FROM AUTHOR]

• The 'appropriate' folic acid dose for pregnant women with epilepsy is debated. • No relationship noted between folate dose and protection against birth defects. • High-dose folic acid may not reduce risk of AED-induced anatomical teratogenesis. • Future studies may determine if high-dose folate may reduce behavioural teratogenesis. To determine whether there is a relationship between folic acid dose and the degree of protection against valproate-associated and other antiepileptic drug (AED)-associated fetal structural malformations in women with AED-treated epilepsy. Statistical analysis of data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy involving 2104 folic acid-treated pregnancies in women with epilepsy. Multiple variable logistic regression failed to demonstrate any statistically significant effect of folic acid dosage in reducing overall fetal malformation rates in women taking folic acid either before and during pregnancy (P = 0.640) or during early pregnancy only (P = 0.801), and in reducing spina bifida occurrence rates (P = 0.409). In the present state of knowledge, it would seem misguided to hope that a folic acid dose of 5 mg/day taken before and during pregnancy would protect against the occurrence of valproate-associated and other AED-associated fetal structural malformations. Future studies are required to determine whether high-dose periconceptional folate use may decrease the risk of other valproate-associated adverse fetal outcomes, including impaired post-natal neurobehavioral development. [ABSTRACT FROM AUTHOR]

Seizure-induced cardiorespiratory and autonomic dysfunction has long been recognized, and growing evidence points to its implication in sudden unexpected death in epilepsy (SUDEP). However, a comprehensive understanding of cardiorespiratory function in the preictal, ictal, and postictal periods are lacking. We examined continuous cardiorespiratory and autonomic function in 157 seizures (18 convulsive and 139 nonconvulsive) from 70 consecutive patients who had a seizure captured on concurrent video-encephalogram (EEG) monitoring and polysomnography between February 1, 2012 and May 31, 2017. Heart and respiratory rates, heart rate variability (HRV), and oxygen saturation were assessed across four distinct periods: baseline (120 s), preictal (60 s), ictal, and postictal (300 s). Heart and respiratory rates were further followed for up to 60 min after seizure termination to assess return to baseline. Ictal tachycardia occurred during both convulsive and nonconvulsive seizures, but the maximum rate was higher for convulsive seizures (mean: 138.8 beats/min, 95% confidence interval (CI): 125.3–152.4) compared with nonconvulsive seizures (mean: 105.4 beats/min, 95% CI: 101.2–109.6; p < 0.001). Convulsive seizures were associated with a lower ictal minimum respiratory rate (mean: 0 breaths/min, 95% CI: 0–0) compared with nonconvulsive seizures (mean: 11.0 breaths/min, 95% CI: 9.5–12.6; p < 0.001). Ictal obstructive apnea was associated with convulsive compared with nonconvulsive seizures. The low-frequency (LF) power band of ictal HRV was higher among convulsive seizures than nonconvulsive seizures (ratio of means (ROM): 2.97, 95% CI: 1.34–6.60; p = 0.008). Postictal tachycardia was substantially prolonged, characterized by a longer return to baseline for convulsive seizures (median: 60.0 min, interquartile range (IQR): 46.5–60.0) than nonconvulsive seizures (median: 0.26 min, IQR: 0.008–0.9; p < 0.001). For postictal hyperventilation, the return to baseline was longer in convulsive seizures (median: 25.3 min, IQR: 8.1–60) than nonconvulsive seizures (median: 1.0 min, IQR: 0.07–3.2; p < 0.001). The LF power band of postictal HRV was lower in convulsive seizures than nonconvulsive seizures (ROM: 0.33, 95% CI: 0.11–0.96; p = 0.043). Convulsive seizures with postictal generalized EEG suppression (PGES; n = 12) were associated with lower postictal heart and respiratory rate, and increased HRV, compared with those without (n = 6). Profound cardiorespiratory and autonomic dysfunction associated with convulsive seizures may explain why these seizures carry the greatest risk of SUDEP. • Convulsive and nonconvulsive seizures alter cardiorespiratory function. • Cardiorespiratory function is substantially altered in convulsive seizures. • Ictal apnea duration was longer in convulsive seizures, and commonly obstructive. • Convulsive seizures have prolonged postictal tachycardia and hyperventilation. [ABSTRACT FROM AUTHOR]