Higher Validity, Lower Radiation: A New Ictal Single-Photon Emission Computed Tomography Framework.

OBJECTIVE: To assess whether arterial spin labeling perfusion images of healthy controls can enhance ictal single-photon emission computed tomography analysis and whether the acquisition of the interictal image can be omitted. METHODS: We developed 2 pipelines: The first uses ictal and interictal images and compares these to single-photon emission computed tomography and arterial spin labeling of healthy controls. The second pipeline uses only the ictal image and the analogous healthy controls. Both pipelines were compared to the gold standard analysis and evaluated on data of individuals with epilepsy who underwent ictal single-photon emission computed tomography imaging during presurgical evaluation between 2010 and 2022. Fifty healthy controls prospectively underwent arterial spin labeling imaging. The correspondence between the detected hyperperfusion and the postoperative resection cavity or the presumably affected lobe was assessed using Dice score and mean Euclidean distance. Additionally, the outcomes of the pipelines were automatically assigned to 1 of 5 concordance categories. RESULTS: Inclusion criteria were met by 43 individuals who underwent epilepsy surgery and by 73 non-surgical individuals with epilepsy. Compared to the gold standard analysis, both pipelines resulted in significantly higher Dice scores and lower mean distances (p < 0.05). The combination of both provided localizing results in 85/116 cases, compared to 54/116 generated by the current gold standard analysis and the ictal image alone produced localizing results in 60/116 (52%) cases. INTERPRETATION: We propose a new ictal single-photon emission computed tomography protocol; it finds relevantly more ictal hyperperfusion, and halves the radiation dose in about half of the individuals. ANN NEUROL 2024.

Implications for driving based on the risk of seizures after ischaemic stroke.

BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

Mortality of Epilepsy in Chinese Populations: A Comprehensive Review.

BACKGROUND: Premature mortality is a significant part of the epilepsy burden and may vary across populations, especially between high-income and lower- and middle-income countries. People with epilepsy in China are approximately a fifth of the global population with epilepsy. Previous studies were unlikely to represent the situation in China due to limitations in design, methods, sample size, follow-up time, and other inherent population heterogeneity. SUMMARY: By summarising the evidence on the mortality characteristics in Chinese populations with epilepsy in the last 6 decades, we found a median mortality rate of 14.7 (6.8-74.4)/1,000 person-years and a median standardised mortality ratio (SMR) of 4.4 (2.6-12.9) in population-based studies, and a median mortality rate of 12.3 (9.5-101.5)/1,000 person-years and a median SMR of 3.0 (1.5-5.1) in hospital-based studies. Vascular diseases, complications of diabetes, and accidental injuries were the leading causes of death. Risk factors for mortality were reported as older age, male, longer duration, and higher frequency of seizures. Case fatality ratios of status epilepticus in adults were higher than in children, and both increased with follow-up time. Mortality in people with symptomatic epilepsy was high and varied across different primary diseases. KEY MESSAGES: The highest mortality rate and sudden unexpected death in epilepsy (SUDEP) incidence were reported from the least developed areas in China. Accidental injuries were the most common causes of epilepsy-related deaths, while the incidence of SUDEP may be underestimated in Chinese populations. Further research is warranted to improve the understanding of premature mortality risk so that preventative measures can be introduced to improve the situation.

Grading objective diagnostic components in paroxysmal events: One-year follow-up at a tertiary epilepsy center.

OBJECTIVE: This study was undertaken to develop a model and perform a preliminary internal validation study of the Scale for Objective Diagnostic Components of Paroxysmal Events (STAMP). METHODS: We developed STAMP, which builds on the International League Against Epilepsy task force scale for functional seizures with additional categories for epileptic seizures and syncope. We included 200 consecutive referrals to a Dutch tertiary epilepsy center to evaluate seizurelike events. We recorded demographic and clinical data and collected the clinical evaluation at referral and after 3, 6, 9, and 12 months of follow-up. We ascertained the STAMP at each time point and evaluated factors predicting an improvement in STAMP grade during follow-up. RESULTS: Of the 200 referrals at baseline, 131 were classified as having epileptic seizures, 17 as functional seizures, and three as syncope, and 49 were unclassifiable. STAMP grade at baseline was 4 (absent) in 56 individuals, 3 (circumstantial) in 78, 2 (clinically established) in six, and 1 (documented) in 11. Over time, 62 cases STAMP grades improved, and 23 remained unclassifiable. A refinement of STAMP grade during follow-up was due to successful event recordings in 34 people (30 video-electroencephalographic [EEG] recordings, four tilt table testing), home videos or clinician-witnessed events in 13, and identification of interictal EEG or magnetic resonance imaging abnormalities in seven. An improved STAMP grade after 12 months of follow-up was significantly more likely in those with higher event frequency, unclassifiable events, longer event duration, and a shorter time since the first event and less likely in those with a history suggestive of seizures. SIGNIFICANCE: This epilepsy service evaluation underscores the crucial role of event recording in improving diagnostic certainty. STAMP may be used to monitor diagnostic performance over time but requires further validation.

Magnetic resonance imaging findings in Kenyans and South Africans with active convulsive epilepsy: An observational study.

OBJECTIVE: Focal epilepsy is common in low- and middle-income countries. The frequency and nature of possible underlying structural brain abnormalities have, however, not been fully assessed. METHODS: We evaluated the possible structural causes of epilepsy in 331 people with epilepsy (240 from Kenya and 91 from South Africa) identified from community surveys of active convulsive epilepsy. Magnetic resonance imaging (MRI) scans were acquired on 1.5-Tesla scanners to determine the frequency and nature of any underlying lesions. We estimated the prevalence of these abnormalities using Bayesian priors (from an earlier pilot study) and observed data (from this study). We used a mixed-effect modified Poisson regression approach with the site as a random effect to determine the clinical features associated with neuropathology. RESULTS: MRI abnormalities were found in 140 of 240 (modeled prevalence = 59%, 95% confidence interval [CI]: 53%-64%) of people with epilepsy in Kenya, and in 62 of 91 (modeled prevalence = 65%, 95% CI: 57%-73%) in South Africa, with a pooled modeled prevalence of 61% (95% CI: 56%-66%). Abnormalities were common in those with a history of adverse perinatal events (15/23 [65%, 95% CI: 43%-84%]), exposure to parasitic infections (83/120 [69%, 95% CI: 60%-77%]) and focal electroencephalographic features (97/142 [68%, 95% CI: 60%-76%]), but less frequent in individuals with generalized electroencephalographic features (44/99 [44%, 95% CI: 34%-55%]). Most abnormalities were potentially epileptogenic (167/202, 82%), of which mesial temporal sclerosis (43%) and gliosis (34%) were the most frequent. Abnormalities were associated with co-occurrence of generalized non-convulsive seizures (relative risk [RR] = 1.12, 95% CI: 1.04-1.25), lack of family history of seizures (RR = 0.91, 0.86-0.96), convulsive status epilepticus (RR = 1.14, 1.08-1.21), frequent seizures (RR = 1.12, 1.04-1.20), and reported use of anti-seizure medication (RR = 1.22, 1.18-1.26). SIGNIFICANCE: MRI identified pathologies are common in people with epilepsy in Kenya and South Africa. Mesial temporal sclerosis, the most common abnormality, may be amenable to surgical correction. MRI may have a diagnostic value in rural Africa, but future longitudinal studies should examine the prognostic role.

Neurological complications during the Omicron COVID-19 wave in China: A cohort study.

BACKGROUND AND PURPOSE: The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID-19) during the 2022 Omicron wave. METHODS AND ANALYSIS: The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID-19-related new-onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. RESULTS: In all, 790 people were enrolled, of whom 436 were positive for COVID-19. Ninety-nine had new onset COVID-related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID-specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. CONCLUSION: New-onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large-scale treatment trial of people with COVID-19 infection presenting with neurological disorders is still needed.

Identification of different MRI atrophy progression trajectories in epilepsy by subtype and stage inference.

Artificial intelligence (AI)-based tools are widely employed, but their use for diagnosis and prognosis of neurological disorders is still evolving. Here we analyse a cross-sectional multicentre structural MRI dataset of 696 people with epilepsy and 118 control subjects. We use an innovative machine-learning algorithm, Subtype and Stage Inference, to develop a novel data-driven disease taxonomy, whereby epilepsy subtypes correspond to distinct patterns of spatiotemporal progression of brain atrophy.In a discovery cohort of 814 individuals, we identify two subtypes common to focal and idiopathic generalized epilepsies, characterized by progression of grey matter atrophy driven by the cortex or the basal ganglia. A third subtype, only detected in focal epilepsies, was characterized by hippocampal atrophy. We corroborate external validity via an independent cohort of 254 people and confirm that the basal ganglia subtype is associated with the most severe epilepsy.Our findings suggest fundamental processes underlying the progression of epilepsy-related brain atrophy. We deliver a novel MRI- and AI-guided epilepsy taxonomy, which could be used for individualized prognostics and targeted therapeutics.

Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults.

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7-11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8-0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.

Attitudes and perceptions towards epilepsy in an onchocerciasis-endemic region of Tanzania: a mixed approach to determine the magnitude and driving factors.

BACKGROUND: Epilepsy remains a significant public health concern in Tanzania, with affected individuals enduring stigma, whether through actions or perceptions. Myths, misunderstandings, and misconceptions about epilepsy have persisted due to a multitude of factors. Here, we assessed attitudes and perceptions toward epilepsy in Mahenge. METHODS: A cross-sectional study utilising a mixed-methods approach was undertaken in eight villages in the Ulanga district of Mahenge, integrating a semi-structured questionnaire and focus group discussions (FGDs). The questionnaire involved 778 community members, and 15 FGDs were conducted (seven groups with people with epilepsy and eight without). Descriptive statistics, chi-square, and logistic regression were used for quantitative analysis, while we used NVivo version 14 for thematic analysis of qualitative data. RESULTS: Of 778 participants, over half were women (425, 54.6%) with a median age of 41 years (IQR: 30-55) and most had completed primary education (79.9%). The majority of participants were aware of epilepsy (96.8%), yet they displayed low knowledge (51%), negative attitudes (45.5%), and perceptions (42.1%) towards the disorder. A low level of understanding was significantly associated with negative attitudes (Adjusted Odds Ratio [AOR] = 1.89, 95%CI: 1.41-2.53) and perceptions (AOR = 3.22, 95%CI: 2.05-5.04) towards epilepsy. In the qualitative analysis, often hereditary factors and infections were named as causes of epilepsy, along with misconceptions involving witchcraft and divine punishment. There was also a misconception about the contagiousness of epilepsy. Traditional healers were often the initial point of treatment. Epilepsy-related stigma was evident, with individuals with epilepsy facing derogatory labels, social isolation, and barriers to education. Lastly, there was a lack of understanding regarding a possible association between epilepsy and onchocerciasis. CONCLUSIONS: Despite high awareness of epilepsy, there is insufficient understanding, negative attitudes, and perceptions, including misconceptions and stigma about this neurologic condition. Community-based education programmes are essential for promoting proper healthcare-seeking behaviour and dispelling myths.

Mood disorders in adults with epilepsy: a review of unrecognized facts and common misconceptions.

Epilepsy is one of the most common neurologic conditions. Its clinical manifestations are not restricted to seizures but often include cognitive disturbances and psychiatric disorders. Prospective population-based studies have shown that people with epilepsy have an increased risk of developing mood disorders, and people with a primary mood disorder have an increased risk of developing epilepsy. The existence of common pathogenic mechanisms in epilepsy and mood disorders may explain the bidirectional relation between these two conditions. Recognition of a personal and family psychiatric history at the time of evaluation of people for a seizure disorder is critical in the selection of antiseizure medications: those with mood-stabilizing properties (e.g., lamotrigine, oxcarbazepine) should be favoured as a first option in those with a positive history while those with negative psychotropic properties (e.g., levetiracetam, topiramate) avoided. While mood disorders may be clinically identical in people with epilepsy, they often present with atypical manifestations that do not meet ICD or DSM diagnostic criteria. Failure to treat mood disorders in epilepsy may have a negative impact, increasing suicide risk and iatrogenic effects of antiseizure medications and worsening quality of life. Treating mood disorders in epilepsy is identical to those with primary mood disorders. Yet, there is a common misconception that antidepressants have proconvulsant properties. Most antidepressants are safe when prescribed at therapeutic doses. The incidence of seizures is lower in people randomized to antidepressants than placebo in multicenter randomized placebo-controlled trials of people treated for a primary mood disorder. Thus, there is no excuse not to prescribe antidepressant medications to people with epilepsy.

Transcranial magnetic stimulation-evoked electroencephalography responses as biomarkers for epilepsy: A review of study design and outcomes.

Transcranial magnetic stimulation (TMS) with electroencephalography (EEG), that is TMS-EEG, may assist in managing epilepsy. We systematically reviewed the quality of reporting and findings in TMS-EEG studies on people with epilepsy and healthy controls, and on healthy individuals taking anti-seizure medication. We searched the Cochrane Library, Embase, PubMed and Web of Science databases for original TMS-EEG studies comparing people with epilepsy and healthy controls, and healthy subjects before and after taking anti-seizure medication. Studies should involve quantitative analyses of TMS-evoked EEG responses. We evaluated the reporting of study population characteristics and TMS-EEG protocols (TMS sessions and equipment, TMS trials and EEG protocol), assessed the variation between protocols, and recorded the main TMS-EEG findings. We identified 20 articles reporting 14 unique study populations and TMS methodologies. The median reporting rate for the group of people with epilepsy parameters was 3.5/7 studies and for the TMS parameters was 13/14 studies. TMS protocols varied between studies. Fifteen out of 28 anti-seizure medication trials in total were evaluated with time-domain analyses of single-pulse TMS-EEG data. Anti-seizure medication significantly increased N45, and decreased N100 and P180 component amplitudes but in marginal numbers (N45: 8/15, N100: 7/15, P180: 6/15). Eight articles compared people with epilepsy and controls using different analyses, thus limiting comparability. The reporting quality and methodological uniformity between studies evaluating TMS-EEG as an epilepsy biomarker is poor. The inconsistent findings question the validity of TMS-EEG as an epilepsy biomarker. To demonstrate TMS-EEG clinical applicability, methodology and reporting standards are required.

Somatic symptoms and related disorders in a large cohort of people with epilepsy: A cohort study.

OBJECTIVE: This study was undertaken to characterize somatic symptoms and related disorders (SSD) in epilepsy. METHODS: Adults with epilepsy under active follow-up at a tertiary epilepsy center were consecutively enrolled. The diagnosis of SSD was performed by an experienced psychologist based on the structured clinical interview for Statistical Manual of Mental Disorders, 5th edition. Detailed social/demographic data, epilepsy features, psychiatric features, life quality, disability, and economic burden were collected and compared between people with SSD and those without. Bodily distress syndrome checklist, Somatic Symptom Disorder-B Criteria Scale, Patient Health Questionnaire-9, and Generalized Anxiety Disorder seven-item scale (GAD-7) were used to evaluate SSD individuals' somatic symptoms, symptom-related psychological distress, and depressive and anxious symptoms. Quality of life and disability were assessed by Quality of Life in Epilepsy Inventory 31 (QOLIE-31) and World Health Organization Disability Assessment Schedule V.2.0 (WHO DAS 2.0). A risk prediction nomogram was generated using least absolute shrinkage and selection operator (LASSO) analysis and validated. RESULTS: One hundred fifty of 631 participants (24%) were diagnosed with SSD. In people with SSD, the top three most common somatic symptoms were memory impairment, headache, and dizziness (85%, 80%, and 78%, respectively), and multiple systems were involved in most (82%) people with SSD. Compared with people without SSD, those with SSD had lower QOLIE-31 total scores, and higher WHO DAS 2.0 scores and disease economic burdens. LASSO analysis suggested that a history of severe traumatic brain injury, hippocampal sclerosis, low seizure worry and medication effects scores on QOLIE-31, multiple systems affected by somatic symptoms, and a high GAD-7 score were risk factors of SSD. The nomogram was validated for good accuracy in the training and testing cohorts. SIGNIFICANCE: SSD are likely to be a common comorbidity in epilepsy and harm epilepsy prognosis. Our risk prediction nomogram was successfully developed but needs further validation in larger cohorts.

Cost-effectiveness of cenobamate for focal seizures in people with drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to estimate the cost-effectiveness of add-on cenobamate in the UK when used to treat drug-resistant focal seizures in adults who are not adequately controlled with at least two prior antiseizure medications, including at least one used adjunctively. METHODS: We estimated the cost per quality-adjusted life-year (QALY) for cenobamate compared to brivaracetam, eslicarbazepine, lacosamide, and perampanel in the UK National Health Service over a lifetime time horizon. We used a Markov cohort structure to determine response to treatment, using pooled data from three long-term studies of cenobamate. A network meta-analysis informed the likelihood of response to therapy with brivaracetam, eslicarbazepine, lacosamide, and perampanel relative to cenobamate. Once individuals discontinued treatment, they transitioned to subsequent treatment health states, including other antiseizure medicines, surgery, and vagus nerve stimulation. Costs included treatment, administration, routine monitoring, event management, and adverse events. Published evidence and expert opinion informed the likelihood of response to subsequent treatments, associated adverse events, and costs. Utility data were based on Short-Form six-dimension form utility. Discounting was applied at 3.5% per annum as per National Institute for Health and Care Excellence guidance. Uncertainty was explored through deterministic and probabilistic sensitivity analyses. RESULTS: In the base case, cenobamate led to cost savings of £51 967 (compared to brivaracetam), £21 080 (compared to eslicarbazepine), £33 619 (compared to lacosamide), and £28 296 (compared to perampanel) and increased QALYs of 1.047 (compared to brivaracetam), 0.598 (compared to eslicarbazepine), 0.776 (compared to lacosamide), and 0.703 (compared to perampanel) per individual over a lifetime time horizon. Cenobamate also dominated the four drugs across most sensitivity analyses. Differences were due to reduced seizure frequency with cenobamate relative to comparators. SIGNIFICANCE: Cenobamate improved QALYs and was less costly than brivaracetam, eslicarbazepine, lacosamide, and perampanel. Therefore, cenobamate may be considered as a cost-effective adjunctive antiseizure medication for people with drug-resistant focal seizures.

Verbal fluency functional magnetic resonance imaging detects anti-seizure effects and affective side effects of perampanel in people with focal epilepsy.

Perampanel, a noncompetitive antagonist of the postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping-derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in anti-seizure medication (ASM) regimen in-between. After commencing perampanel, individuals had higher task-related activations in left orbitofrontal cortex (OFC), fewer task-related activations in the subcortical regions including the left thalamus and left caudate, and lower task-related thalamocaudate and caudate-subtantial nigra connectivity. Decreased task-related connectivity is observed between the left OFC and precuneus and left medial frontal lobe. Our results highlight the brain regions associated with the beneficiary therapeutic effects on focal to bilateral tonic-clonic seizures (thalamus and caudate) but also the undesired affective side effects of perampanel with increased anger and aggression (OFC).

TMS-evoked EEG potentials demonstrate altered cortical excitability in migraine with aura.

Migraine is associated with altered sensory processing, that may be evident as changes in cortical responsivity due to altered excitability, especially in migraine with aura. Cortical excitability can be directly assessed by combining transcranial magnetic stimulation with electroencephalography (TMS-EEG). We measured TMS evoked potential (TEP) amplitude and response consistency as these measures have been linked to cortical excitability but were not yet reported in migraine.We recorded 64-channel EEG during single-pulse TMS on the vertex interictally in 10 people with migraine with aura and 10 healthy controls matched for age, sex and resting motor threshold. On average 160 pulses around resting motor threshold were delivered through a circular coil in clockwise and counterclockwise direction. Trial-averaged TEP responses, frequency spectra and phase clustering (over the entire scalp as well as in frontal, central and occipital midline electrode clusters) were compared between groups, including comparison to sham-stimulation evoked responses.Migraine and control groups had a similar distribution of TEP waveforms over the scalp. In migraine with aura, TEP responses showed reduced amplitude around the frontal and occipital N100 peaks. For the migraine and control groups, responses over the scalp were affected by current direction for the primary motor cortex, somatosensory cortex and sensory association areas, but not for frontal, central or occipital midline clusters.This study provides evidence of altered TEP responses in-between attacks in migraine with aura. Decreased TEP responses around the N100 peak may be indicative of reduced cortical GABA-mediated inhibition and expand observations on enhanced cortical excitability from earlier migraine studies using more indirect measurements.

Validation of the Georgian version of a Stigma Scale of Epilepsy.

INTRODUCTION: Stigma Scale of Epilepsy (SSE), initially developed in Brazil, is accepted worldwide as a sensitive tool for assessing epilepsy-related stigma. We adapted and validated a Georgian version of SSE. MATERIALS AND METHODS: The SSE originated in Brazil and was translated into Georgian by three independent experts through forward and backward translation. The final version was generated for validation after handling gross or conceptual inconsistencies between the source and the new format. We used Cronbach's alpha to assess the internal consistency of the Georgian version of SSE. To explore the construct of SSE subscales in the Georgian version, we used principal components and factor analysis. Varimax rotation was applied. The Kaiser-Meyer-Olkin Measure and Bartlett's test of sphericity were employed to assess the sampling adequacy. A probability <0.05 was considered statistically significant. RESULTS: 87 adults, 32 (37 %) with epilepsy and 55 (63 %) without epilepsy were enrolled. The overall mean score of SSE was 19.5 (SD 10.1; min. 2, max. 53), and the differences between people with [20.7 (SD 8.9; min. 2, max. 53)] and without epilepsy [17.5 (SD 10.4; min. 3, max. 42)] were not statistically significant. Cronbach's alpha for the overall sample was 0.854; for the epilepsy cohort it was 0.876, and for individuals without epilepsy 0.823, indicating good SSE internal consistency. Kaiser-Meyer-Olkin Measure was 0.705 and Bartlett's test of sphericity was 926.2 (df 276; p < 0.001), suggesting acceptable sample adequacy. DISCUSSION: The Georgian version of the SSE is a valid and reliable measurement tool for assessing epilepsy-related stigma determinants among the country's population.

Characterising people with focal drug-resistant epilepsy: A retrospective cohort study.

OBJECTIVES: To describe the demographics, clinical characteristics, drug treatment outcomes, healthcare resource utilization, and injuries among people with focal drug-resistant epilepsy (F-DRE) analysed separately for six European countries. METHODS: We used electronic medical record data from six European (Belgium, Spain, Italy, France, UK and Germany) primary care/specialist care databases to identify antiseizure medication (ASM) treatment-naïve people (aged ≥ 18 years at F-DRE diagnosis). They were followed from their epilepsy diagnosis until death, the date of last record available, or study end. We used descriptive analyses to characterise the F-DRE cohort, and results were reported by country. RESULTS: One-thousand-seventy individuals with F-DRE were included (mean age 52.5 years; 55.4 % female). The median follow-up time from the first diagnosis to the end of the follow-up was 95.5 months across all countries. The frequency of F-DRE diagnosis in 2021 ranged from 8.8 % in Italy to 18.2 % in Germany. Psychiatric disorders were the most common comorbidity across all countries. Frequently reported psychiatric disorders were depression (26.7 %) and anxiety (11.8 %). The median time from epilepsy diagnosis to the first ASM failure ranged from 5.9 (4.2-10.2) months in France to 12.6 (5.8-20.4) months in Spain. Levetiracetam and lamotrigine were the most commonly used ASM monotherapies in all countries. Consultation with a general practitioner is sought more frequently after F-DRE diagnosis than after epilepsy diagnosis, except in the UK. SIGNIFICANCE: No one ASM is optimal for all people with F-DRE, and the risks and benefits of the ASM must be considered. Comorbidities must be an integral part of the management strategy and drive the choice of drugs.

Prognosis of adults and children following a first unprovoked seizure.

BACKGROUND: Epilepsy is clinically defined as two or more unprovoked epileptic seizures more than 24 hours apart. Given that, a diagnosis of epilepsy can be associated with significant morbidity and mortality, it is imperative that clinicians (and people with seizures and their relatives) have access to accurate and reliable prognostic estimates, to guide clinical practice on the risks of developing further unprovoked seizures (and by definition, a diagnosis of epilepsy) following single unprovoked epileptic seizure. OBJECTIVES: 1. To provide an accurate estimate of the proportion of individuals going on to have further unprovoked seizures at subsequent time points following a single unprovoked epileptic seizure (or cluster of epileptic seizures within a 24-hour period, or a first episode of status epilepticus), of any seizure type (overall prognosis). 2. To evaluate the mortality rate following a first unprovoked epileptic seizure. SEARCH METHODS: We searched the following databases on 19 September 2019 and again on 30 March 2021, with no language restrictions. The Cochrane Register of Studies (CRS Web), MEDLINE Ovid (1946 to March 29, 2021), SCOPUS (1823 onwards), ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. In MEDLINE (Ovid) the coverage end date always lags a few days behind the search date. SELECTION CRITERIA: We included studies, both retrospective and prospective, of all age groups (except those in the neonatal period (< 1 month of age)), of people with a single unprovoked seizure, followed up for a minimum of six months, with no upper limit of follow-up, with the study end point being seizure recurrence, death, or loss to follow-up. To be included, studies must have included at least 30 participants. We excluded studies that involved people with seizures that occur as a result of an acute precipitant or provoking factor, or in close temporal proximity to an acute neurological insult, since these are not considered epileptic in aetiology (acute symptomatic seizures). We also excluded people with situational seizures, such as febrile convulsions. DATA COLLECTION AND ANALYSIS: Two review authors conducted the initial screening of titles and abstracts identified through the electronic searches, and removed non-relevant articles. We obtained the full-text articles of all remaining potentially relevant studies, or those whose relevance could not be determined from the abstract alone and two authors independently assessed for eligibility. All disagreements were resolved through discussion with no need to defer to a third review author. We extracted data from included studies using a data extraction form based on the checklist for critical appraisal and data extraction for systematicreviews of prediction modelling studies (CHARMS). Two review authors then appraised the included studies, using a standardised approach based on the quality in prognostic studies (QUIPS) tool, which was adapted for overall prognosis (seizure recurrence). We conducted a meta-analysis using Review Manager 2014, with a random-effects generic inverse variance meta-analysis model, which accounted for any between-study heterogeneity in the prognostic effect. We then summarised the meta-analysis by the pooled estimate (the average prognostic factor effect), its 95% confidence interval (CI), the estimates of I² and Tau² (heterogeneity), and a 95% prediction interval for the prognostic effect in a single population at three various time points, 6 months, 12 months and 24 months. Subgroup analysis was performed according to the ages of the cohorts included; studies involving all ages, studies that recruited adult only and those that were purely paediatric. MAIN RESULTS: Fifty-eight studies (involving 54 cohorts), with a total of 12,160 participants (median 147, range 31 to 1443), met the inclusion criteria for the review. Of the 58 studies, 26 studies were paediatric studies, 16 were adult and the remaining 16 studies were a combination of paediatric and adult populations. Most included studies had a cohort study design with two case-control studies and one nested case-control study. Thirty-two studies (29 cohorts) reported a prospective longitudinal design whilst 15 studies had a retrospective design whilst the remaining studies were randomised controlled trials. Nine of the studies included presented mortality data following a first unprovoked seizure. For a mortality study to be included, a proportional mortality ratio (PMR) or a standardised mortality ratio (SMR) had to be given at a specific time point following a first unprovoked seizure. To be included in the meta-analysis a study had to present clear seizure recurrence data at 6 months, 12 months or 24 months. Forty-six studies were included in the meta-analysis, of which 23 were paediatric, 13 were adult, and 10 were a combination of paediatric and adult populations. A meta-analysis was performed at three time points; six months, one year and two years for all ages combined, paediatric and adult studies, respectively. We found an estimated overall seizure recurrence of all included studies at six months of 27% (95% CI 24% to 31%), 36% (95% CI 33% to 40%) at one year and 43% (95% CI 37% to 44%) at two years, with slightly lower estimates for adult subgroup analysis and slightly higher estimates for paediatric subgroup analysis. It was not possible to provide a summary estimate of the risk of seizure recurrence beyond these time points as most of the included studies were of short follow-up and too few studies presented recurrence rates at a single time point beyond two years. The evidence presented was found to be of moderate certainty. AUTHORS' CONCLUSIONS: Despite the limitations of the data (moderate-certainty of evidence), mainly relating to clinical and methodological heterogeneity we have provided summary estimates for the likely risk of seizure recurrence at six months, one year and two years for both children and adults. This provides information that is likely to be useful for the clinician counselling patients (or their parents) on the probable risk of further seizures in the short-term whilst acknowledging the paucity of long-term recurrence data, particularly beyond 10 years.

Learning from the comorbidities of epilepsy.

PURPOSE OF REVIEW: Comorbidities are a common feature in epilepsy, but neither the entire spectrum nor the significance of such comorbidities has been fully explored. We review comorbidities associated with epilepsy and their associated burden, provide an overview of relationships, and discuss a new conceptualization of the comorbidities. RECENT FINDINGS: The epidemiology of the comorbidities of epilepsy and effects on health outcomes, healthcare use, and healthcare expenditures have been partly delineated. Distinct mechanisms of the associations have been suggested but not entirely ascertained. Movement from conceptualizing epilepsy as a condition to a symptom-complex has occurred. SUMMARY: Comorbidities are common among people with epilepsy and are associated with poorer clinical outcomes and quality of life, greater use of health resources, and increased expenditure. Becoming aware of the associated mechanisms and their uncertainty is central to understanding the relationships between epilepsy and comorbid health conditions, which have implications for diagnosis and screening, medical management, and surgical management. Conceptualizing comorbidities of epilepsy as precipitating factors and epilepsy as the symptom will improve the understanding of epilepsy and catalyze research and improvements in clinical practice.

Seizures after Ischemic Stroke: A Matched Multicenter Study.

OBJECTIVE: The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. METHODS: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. RESULTS: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. INTERPRETATION: Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy. ANN NEUROL 2021;90:808-820.