Incidence and determinants of seizures in multiple sclerosis: a meta-analysis of randomised clinical trials.

BACKGROUND: Seizures are reported to be more prevalent in individuals with multiple sclerosis (MS) compared with the general population. Existing data predominantly originate from population-based studies, which introduce variability in methodologies and are vulnerable to selection and reporting biases. METHODS: This meta-analysis aims to assess the incidence of seizures in patients participating in randomised clinical trials and to identify potential contributing factors. Data were extracted from 60 articles published from 1993 to 2022. The pooled effect size, representing the incidence rate of seizure events, was estimated using a random-effect model. Metaregression was employed to explore factors influencing the pooled effect size. RESULTS: The meta-analysis included data from 53 535 patients and 120 seizure events in a median follow-up of 2 years. The pooled incidence rate of seizures was 68.0 per 100 000 patient-years, significantly higher than the general population rate of 34.6. Generalised tonic-clonic seizures were the most common type reported, although there was a high risk of misclassification for focal seizures with secondary generalisation. Disease progression, longer disease duration, higher disability levels and lower brain volume were associated with a higher incidence of seizures. Particularly, sphingosine-1-phosphate receptor (S1PR) modulators exhibited a 2.45-fold increased risk of seizures compared with placebo or comparators, with a risk difference of 20.5 events per 100 000 patient-years. CONCLUSIONS: Patients with MS face a nearly twofold higher seizure risk compared with the general population. This risk appears to be associated not only with disease burden but also with S1PR modulators. Our findings underscore epilepsy as a significant comorbidity in MS and emphasise the necessity for further research into its triggers, preventive measures and treatment strategies.

Impact of a free medication intervention on seizure recurrence and anxious and depressive symptoms in people living with epilepsy in the Republic of Guinea.

BACKGROUND AND OBJECTIVE: Of ~5 million people living with epilepsy (PLWE) in Sub-Saharan Africa, roughly one-third experience depression and over one third experience anxiety. In Guinea, these issues may be compounded by fewer available resources, such as appropriate anti-seizure medications (ASMs). We aim to quantify seizure frequency, anxiety and depression in PLWE in Guinea, before and after a free ASM intervention and neurologist's consultation. METHODS: Guinean participants >12 years old with ≥2 unprovoked seizure were prospectively recruited. As part of a broader interview, participants reported prior 30-day seizure frequency and screened for depression (PHQ-9) (range 0-27 points) and anxiety (GAD-7) (range 0-21 points) with re-evaluation at 90 days. RESULTS: Of 148 participants enrolled (mean age = 27.3 years, range 12-72; 45% female), 62% were currently taking ASMs. For the 30 days pre-enrolment, average seizure frequency was 3.2 (95%CI 2.3, 4.2); 28% of participants were seizure-free. ASM regimens were modified for 95% of participants, mostly initiating levetiracetam (n = 115, 80% of modifications). 90-day study retention was 76% (n = 113) among whom 87% reported full adherence to the ASM. After 90 days, the average seizure frequency over the prior 30 days was 1.5 (95%CI 0.5, 2.6), significantly lower than at baseline (p = 0.002). 66% were seizure-free. At baseline, average PHQ-9 score was 21.2 (95%CI [20.2, 22.2]), indicating severe depressive symptoms. Average GAD-7 score was 16.5 [15.6, 17.4], indicating severe anxious symptoms. At 90-days, average PHQ-9 score was 17.5[16.4, 18.5] and significantly lower than baseline (p < 0.001). Average GAD-7 score was 14.4 [13.6, 15.3] and significantly lower than baseline (p = 0.002). Seizure frequency was not correlated with PHQ-9 nor GAD-7 scores at baseline but was at 90 days for both PHQ-9 (r = 0.24, p = 0.01) and GAD-7 (r = 0.22, p = 0.02) scores. The prevalence of suicidal ideation dropped from 67% to 47% of participants (p = 0.004). DISCUSSION: ASM management has dual importance for PLWE in resource-limited settings, improving both seizure control and mental health.

Very high epilepsy prevalence in rural Southern Rwanda: The underestimated burden of epilepsy in sub-Saharan Africa.

OBJECTIVES: Up to 85% of people living with epilepsy (PwE) reside in low-and middle-income countries. In sub-Saharan Africa, the lifetime prevalence of epilepsy is 16 per 1000 persons. In Northern rural Rwanda, a 47.7 per 1000 prevalence has been reported. As variations in prevalence across geographical areas have been observed, we studied the prevalence in Southern rural Rwanda using the same robust methodology as applied in the North. METHODS: We conducted a three-stage, cross-sectional, door-to-door survey in two rural villages in Southern Rwanda from June 2022 to April 2023. First, trained enumerators administered the validated Limoges questionnaire for epilepsy screening. Second, neurologists examined the persons who had screened positively to confirm the epilepsy diagnosis. Third, cases with an inconclusive assessment were separately reexamined by two neurologists to reevaluate the diagnosis. RESULTS: Enumerators screened 1745 persons (54.4% female, mean age: 24 ± 19.3 years), of whom 304 (17.4%) screened positive. Epilepsy diagnosis was confirmed in 133 (52.6% female, mean age: 30 ± 18.2 years) and active epilepsy in 130 persons. Lifetime epilepsy prevalence was 76.2 per 1000 (95% CI: 64.2-89.7‰). The highest age-specific rate occurred in the 29-49 age group. No gender-specific differences were noted. In 22.6% of the PwE, only non-convulsive seizures occurred. The treatment gap was 92.2%, including a diagnosis gap of 79.4%. CONCLUSION: We demonstrated a very high epilepsy prevalence in Southern rural Rwanda, with over 20% of cases having only non-convulsive seizures, which are often underdiagnosed in rural Africa. In line with previous Rwandan reports, we reiterate the high burden of the disease in the country. Geographic variation in prevalence throughout Africa may result from differences in risk and aetiological factors. Case-control studies are underway to understand such differences and propose adapted health policies for epilepsy prevention.

First unprovoked seizures among soldiers recruited to the Israeli Defense Forces during 10 consecutive years: A population-based study.

OBJECTIVE: The management of patients after a first unprovoked seizure (FUS) can benefit from stratification of the average 50% risk for further seizures. We characterized subjects with FUSs, out of a large generally healthy homogenous population of soldiers recruited by law to the Israeli Defense Forces, to investigate the role of the type of service, as a trigger burden surrogate, in the risk for additional seizures. METHODS: Soldiers recruited between 2005 and 2014, who experienced an FUS during their service, were identified from military records. Subjects with a history of epilepsy or lack of documentation of FUS characteristics were excluded from the study. Data on demographics and military service and medical details were extracted for the eligible soldiers. RESULTS: Of 816 252 newly recruited soldiers, representing 2 138 000 person-years, 346 had an FUS, indicating an incidence rate of 16.2 per 100 000 person-years. The FUS incidence rate was higher in combat versus noncombat male and female soldiers (p < .0001). Most subjects (75.7%) were prescribed antiseizure medications (ASMs), and 29.2% had additional seizures after the FUS. Service in combat units, abnormal magnetic resonance imaging, and being prescribed ASMs were correlated with a lower risk of having multiple seizures (95% confidence interval [CI] = .48-.97, .09-.86, .15-.28, respectively). On multivariate analysis, service in combat units (odds ratio [OR] = .48 for seizure recurrence, 95% CI = .26-.88) and taking medications (OR = .46, 95% CI = .24-.9) independently predicted not having additional seizures. SIGNIFICANCE: FUS incidence rate was higher in combat soldiers, but they had a twofold lower risk of additional seizures than noncombat soldiers, emphasizing the value of strenuous triggers as negative predictors for developing epilepsy. This suggests a shift in the perception of epilepsy from a "yes or no" condition to a continuous trend of predisposition to seizures, warranting changes in the ways etiologies of epilepsy are weighted and treatments are delivered.

Psychological precursors of epileptic seizures.

Psychological stress is the most commonly self-reported precursor of epileptic seizures. However, retrospective and prospective studies remain inconclusive in this regard. Here, we explored whether seizures would be preceded by significant changes in reported stressors or resource utilization. This study is based on high-frequency time series through daily online completion of personalized questionnaires of 9-24 items in epilepsy outpatients and compared responses 1-14 days before seizures with interictal time series. Fourteen patients (79% women, age = 23-64 years) completed daily questionnaires over a period of 87-898 days (median = 277 days = 9.2 months). A total of 4560 fully completed daily questionnaires were analyzed, 685 of which included reported seizure events. Statistically significant changes in preictal compared to interictal dynamics were found in 11 of 14 patients (79%) across 41 items (22% of all 187 items). In seven of 14 patients (50%), seizures were preceded by a significant mean increase of stressors and/or a significant mean decrease of resource utilization. This exploratory analysis of long-term prospective individual patient data on specific stressors and personal coping strategies generates the hypothesis that medium-term changes in psychological well-being may precede the occurrence of epileptic seizures in some patients.

Characterizing emergency department and inpatient health care utilization after seizure-related hospitalization: A retrospective cohort study.

OBJECTIVE: Seizure care is a significant driver of health care costs in both emergency department (ED) and inpatient settings, but the majority of studies have focused on inpatient admissions as the only metric of health care utilization. This study aims to better characterize ED and inpatient encounters among patients with seizure to inform care and policy. METHODS: Using statewide administrative data from the Healthcare Cost and Utilization Project State Inpatient Databases and State Emergency Department Databases from Florida and New York, we identified patients with a seizure-related index hospitalization between January 1, 2016, and December 31, 2018. Among this cohort, we examined the incidence and characteristics of subsequent acute care visits in the ED and inpatient settings for 365 days after initial hospital discharge. RESULTS: A total of 54 456 patients had an eligible seizure-related hospitalization. Patients were 49% female, predominantly White (64%) and non-Hispanic (84%), and used a public primary payer (68%). There were 36 838 (68%) patients with at least one acute care visit in the year following discharge. Overall, patients had a median of 2 (interquartile [IQR] = 1-5) subsequent acute care visits and the median time to first acute care visit was 53 days (IQR = 15-138). Of the 154 369 subsequent acute care visits, 97 399 (63%) were ED-only visits, 56 970 (37%) were readmissions, and 37 176 (24%) were seizure-related. There were 18 786 patients (35%) with four or more acute care visits over 365 days of follow-up. Patients with four or more visits contributed 84% of acute care visits and 78% of costs after initial hospitalization. SIGNIFICANCE: The majority of patients hospitalized for seizure return to the ED or hospital at least once in the year after discharge. A small portion of patients account for the majority of ED and inpatient visits as well as health care costs associated with this population, identifying a subgroup of patients who may benefit from improved inpatient and outpatient management.

EEG microstates show different features in focal epilepsy and psychogenic nonepileptic seizures.

OBJECTIVE: Electroencephalography (EEG) microstate analysis seeks to cluster the scalp's electric field into semistable topographical EEG activity maps at different time points. Our study aimed to investigate the features of EEG microstates in subjects with focal epilepsy and psychogenic nonepileptic seizures (PNES). METHODS: We included 62 adult subjects with focal epilepsy or PNES who received video-EEG monitoring at the epilepsy monitoring unit. The subjects (mean age = 42.8 ± 21.2 years) were distributed equally between epilepsy and PNES groups. We extracted microstates from a 4.4 ± 1.0-min, 21-channel resting-state EEG. We excluded subjects with interictal epileptiform discharges during resting-state EEGs. After preprocessing, we derived five main EEG microstates-MS1 to MS5-for the full frequency band (1-30 Hz) and frequency subbands (delta, 1-4 Hz; theta, 4-8 Hz; alpha, 8-12 Hz; beta, 12-30 Hz), using the MATLAB-based EEGLAB toolkit. Statistical features of microstates (duration, occurrence, contribution, global field power [GFP]) were compared between the groups, using logistic regression corrected for age and sex. RESULTS: We detected no differences in microstate parameters in the full frequency band. We found a longer duration (delta: B = -7.680, p = .046; theta: B = -16.200, p = .043) and a higher contribution (delta: B = -7.414, p = .035; theta: B = -7.509, p = .031) of MS4 in lower frequency bands in the epilepsy group. The PNES group showed a higher occurrence of MS5 in the delta subband (B = 3.283, p = .032). In the theta subband, a higher GFP of MS1 was associated with the PNES group (B = 5.674, p = .025), whereas a higher GFP of MS2 was associated with the epilepsy group (B = -6.579, p = .026). SIGNIFICANCE: Microstate features show differences between patients with focal epilepsy and PNES. EEG microstates could be a promising parameter, helping to understand changes in brain dynamics in subjects with epilepsy, and should be explored as a potential biomarker.

Transient postictal dysphagia in older adults with focal structural epilepsy.

OBJECTIVE: Seizures can cause transient neurological symptoms, such as hemiparesis and aphasia. However, temporary swallowing changes leading to postictal dysphagia have not been previously described. Therefore, this study evaluated the presence of swallowing disorders following seizure. In addition, dysphagia severity and duration of any recovery from dysphagic symptoms were investigated. METHODS: The local clinical database of all fiberoptic endoscopic evaluation of swallowing (FEES) examinations performed from 2008 to 2019 was screened for patients diagnosed with seizures, but excluding patients with intensive care unit admission or intubation >24 h. Patient charts were evaluated to identify preexisting dysphagia or potential concurrent medical causes for dysphagia, including hyponatremia, increased intracranial pressure, sepsis, or other encephalopathies associated with infections, or other possible causes at the time of admission. Patients receiving >.5 defined daily doses of benzodiazepines or neuroleptics were also excluded. Age, sex, seizure semiology and etiology, comorbidities, concurrent pneumonia, and dysphagia course during hospitalization were evaluated as predictors of the occurrence of dysphagia or its potential duration. RESULTS: We identified 41 patients with dysphagia following a seizure, without evidence of any concurrent cause of swallowing dysfunction. These patients all presented with focal structural epilepsy, they had a mean age of 79 ± 11.3 years (range = 44-95 years), and 21 were women. The mean Elixhauser Comorbidity Score was 4.8. Hospital-acquired pneumonia was detected in 21 patients (51.2%). FEES diagnosed mild and severe dysphagia in 21 (51.2%) and 20 (48.8%) patients, respectively. Dysphagia improved significantly (p = .001) during hospitalization, persisting for an average of 3.9 days (median = 3 days, SD = 2.07 days, range = 1-8 days). SIGNIFICANCE: Dysphagia is a potential transient neurological deficit following seizure. Our findings suggest that older patients, with focal structural epilepsy, are at risk for postictal dysphagia. Further studies are needed to ascertain the prevalence, complications, and predictors of postictal dysphagia. Dysphagia screening may improve early detection in patients with relevant risk factors, as well as reduce the occurrence of aspiration pneumonia.

The risk of unprovoked seizure occurrence after status epilepticus in adults.

OBJECTIVE: Status epilepticus (SE) may lead to long-term consequences. This study evaluated the risk and predictors of seizure occurrence after SE, with a focus on SE due to acute symptomatic etiologies. METHODS: Prospectively collected data about adults surviving a first non-hypoxic SE were reviewed. The outcome was the occurrence of unprovoked seizures during the follow-up. Kaplan-Meier survival curve analysis and log-rank test were used to analyze the time to seizure occurrence and determine the statistical significance between etiological groups. Three subcategories within acute etiology were considered according to the presence of the following: (1) structural lesion (acute-primary); (2) brain involvement during systemic disorders (acute-secondary); and (3) drug or alcohol intoxication/withdrawal (acute-toxic). Cox proportional hazards model was adopted to estimate hazard ratios (HRs) with the 95% confidence intervals (CIs). RESULTS: Two hundreds fifty-seven individuals were included. Fifty-four subjects (21.0%) developed seizures after a median of 9.9 (interquartile range 4.3-21.7) months after SE. The estimated 1-, 2-, and 5-year rates of seizure occurrence according to acute SE etiologies were 19.4%, 23.4%, and 30.1%, respectively, for acute-primary central nervous system (CNS) pathology; 2.2%, 2.2%, and 8.7%, respectively, for acute-secondary CNS pathology; and 0%, 9.1%, and 9.1%, respectively, for acute-toxic causes. Five-year rates of seizure occurrence for non-acute SE causes were 33.9% for remote, 65.7% for progressive, and 25.9% for unknown etiologies. In multivariate Cox regression model, progressive etiology (adjusted HR [adjHR] 2.27, 95% CI 1.12-4.58), SE with prominent motor phenomena evolving in non-convulsive SE (adjHR 3.17, 95% CI 1.38-7.25), and non-convulsive SE (adjHR 2.38, 95% CI 1.16-4.90) were independently associated with higher hazards of unprovoked seizures. Older people (adjHR .98, 95% CI .96-.99) and people with SE due to acute-secondary CNS pathology (adjHR .18, 95% CI .04-.82) were at decreased risk of seizure occurrence. SIGNIFICANCE: SE carries a risk of subsequent seizures. Both the underlying cause and epileptogenic effects of SE are likely to contribute.

Over- and underreporting of seizures: How big is the problem?

OBJECTIVE: Clinical decisions on managing epilepsy patients rely on patient accuracy regarding seizure reporting. Studies have noted disparities between patient-reported seizures and electroencephalographic (EEG) findings during video-EEG monitoring periods, chiefly highlighting underreporting of seizures, a well-recognized phenomenon. However, seizure overreporting is a significant problem discussed within the literature, although not in such a large cohort. Our aim is to quantify the over- and underreporting of seizures in a large cohort of ambulatory EEG patients. METHODS: We performed a retrospective data analysis on 3407 patients referred to a diagnostic service for ambulatory video-EEG between 2020 and 2022. Both patient-reported events and events discovered on review of the video-EEG were analyzed and classified as epileptic, psychogenic (typically clinical motor events, without accompanying EEG change), or noncorrelated events (NCEs; without perceivable clinical or EEG change). Events were analyzed by state of arousal and indication for referral. Subgroup analysis was performed in patients with focal and generalized epilepsies. RESULTS: A total of 21 024 events were recorded by 3407 patients. Fifty-eight percent of reported events were NCEs, whereas 27% of all events were epileptic. Sixty-four percent of epileptic seizures were not reported by the patient but discovered by the clinical service on review of the recording. NCEs were in the highest proportion in the awake and drowsy arousal states and were the most common event type for the majority of referral indications. Subgroup analysis found a significantly higher proportion of NCEs in the patients with focal epilepsy (23%) compared to generalized epilepsy (10%; p < .001, chi-squared proportion test). SIGNIFICANCE: Our results reaffirm the phenomenon of underreporting and highlight the prevalence of overreporting. Overreporting likely represents irrelevant symptoms or electrographic discharges not represented on scalp electrodes, identification of which has important clinical relevance. Future studies should analyze events by risk factors to elucidate relationships clinicians can use and investigate the etiology of NCEs.

Prevalence of epileptiform electroencephalographic abnormalities in people without a history of seizures: A systematic review and meta-analysis.

Abnormal patterns identified on electroencephalogram (EEG) are one of the primary diagnostic tests for epilepsy. However, epidemiological studies have established that both benign and epileptiform abnormalities (EAs) occur on the EEG of nonepileptic, seizure-free people as well. The reported rates of EAs in nonepileptic, seizure-free populations vary, and the true prevalence is unknown. The primary objective of this systematic review and meta-analysis was to estimate the overall prevalence of EAs in the EEG of people without a history of seizures. Secondary aims were to characterize (1) the cortical localization of focal abnormalities, (2) the proportion of findings that occurred during standard EEG stimulation protocols, and (3) the persistence and implications of abnormalities at follow-up. A comprehensive electronic search of six bibliographic databases was completed: Embase, MEDLINE, PsycInfo, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register for Controlled Trials, and Web of Science. No search date restrictions were applied. Overall effect size was calculated using a generalized linear mixed-effects model. Fifty-three studies, totaling 73 990 individuals, met our inclusion criteria. The overall point prevalence of EAs was 1.74% (95% confidence interval [CI] = 1.13-2.67). Due to the risk of bias in the literature, especially from participant selection, we believe this to be an overestimate of the true prevalence. Prevalence of EAs was greater in children (2.45%, 95% CI = 1.41-4.21) and the elderly (5.96%, 95% CI = 1.39-22.13) compared with adults (.93%, 95% CI = .48-1.80). Reports of developing epilepsy after an EA-positive EEG were rare. The likelihood of subsequent positive findings on follow-up EEG may be as high as 50%. Our study has limitations in that males were overrepresented in the study samples, there is substantial heterogeneity among studies, and many studies provided insufficient detail about their exclusion criteria. Nonetheless, our estimates provide benchmark data for future studies examining EAs in clinical populations, particularly behavioral and psychiatric populations.

Gabapentinoids in Ireland 2010 to 2020: An observational study of trends in gabapentinoid prescribing, law enforcement drug seizures and postmortem toxicology.

AIMS: We explored trends in gabapentinoid prescribing, drug seizures and postmortem toxicology using a national pharmacy claims database, law enforcement drug seizures data and a population-based postmortem toxicology database. METHODS: Gabapentinoid prescribing rates per 100 000 eligible population (2010-2020), annual number of drug seizures involving gabapentinoids (2012-2020) and gabapentinoid detection (positive) rates per 100 postmortem toxicology case (2013-2020) were calculated. Negative binomial regression models were used to evaluate longitudinal trends for gabapentin and pregabalin separately. RESULTS: Gabapentin (adjusted rate ratio [RR] 1.06, 95% confidence interval [CI] 1.05-1.06, P < .001) and pregabalin (adjusted RR 1.08, 95% CI 1.08-1.09, P < .001) prescribing increased annually, with higher rates of pregabalin (vs. gabapentin) observed every year. Drug seizures involving pregabalin also increased over time (RR 1.54 95% CI 1.25-1.90, P < .0001). Of the 26 317 postmortem toxicology cases, 0.92% tested positive for gabapentin, and 6.37% for pregabalin. Detection rates increased for both gabapentin (RR 1.28, 95% CI 1.11-1.48, P < .001) and pregabalin (RR 1.13, 95% CI 1.11-1.48, P < .001) between 2013 and 2020. A total of 1901 cases (7.2%) tested positive for heroin/methadone; this sub-group had a higher detection rate for pregabalin (n = 528, 27.8%) and gabapentin (n = 41, 2.2%) over the study period, with a high burden of codetections for pregabalin with benzodiazepines (peaking at 37.3% in 2018), and pregabalin with prescription opioids (peaking at 28.9% in 2020). CONCLUSION: This study raises concerns regarding the wide availability of pregabalin in Ireland, including a growing illicit supply, and the potential for serious harm arising from poly drug use involving pregabalin among people who use heroin or methadone.

Neurological manifestations of COVID-19 in adults and children.

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

Socioeconomic status in adulthood of children with and without a history of seizures: A retrospective cohort study.

OBJECTIVE: Compare adulthood socioeconomic status for children with and without a history of seizures. METHODS: Retrospective cohort study using Aberdeen Children of the Nineteen Fifties (ACONF) data comprising children born 1950-1956 attending primary school 1962-1964, with follow-up data collected in 2001. Adulthood socioeconomic status was based on registrar general measure of occupational social class and categorised as high or low. We adjusted for potentially confounding variables including childhood socioeconomic status, behavioural issues (Rutter A/B scores), biological sex, school test scores, educational attainment, parental engagement with education, peer-status in school, and alcohol use in adulthood. A multivariate binary logistic regression was performed to estimate the adjusted association between children with a history of seizures of any type (for example febrile seizures, or provoked seizures of any other etiology or seizures in the context of epilepsy) or severity and adult socioeconomic status. Multiple imputation using the Monte-Carlo-Markov-Chain method accounted for missing data. RESULTS: Pooled estimates (N = 2,208) comparing children with a history of seizures (n = 81) and children without a history of seizures (n = 2,127) found no differences between these cohorts in terms of adulthood socioeconomic status in both unadjusted (Odds Ratio (OR) 1.45 [95 % CI 0.71-2.96], p = 0.31) and adjusted (1.02 [0.46, 2.24], p = 0.96) analyses. Compared to males, females were at increased odds of having a lower socioeconomic status in adulthood (1.56 [1.13-2.17], p = 0.01).Compared to those with low educational attainment, those with moderate (0.32 [0.21, 0.48], p < 0.001) and high (0.12 [0.07, 0.20], p < 0.001) educational attainment were at reduced odds of having a lower socioeconomic status in adulthood. CONCLUSION: Cognitive problems in childhood (using educational attainment and scores on primary school tests proxy markers for cognition) rather than a history of seizures per se, were associated with lower SES in a population of adults born 1950-56 in Aberdeen. This relationship may be different depending on the time in history and nation/region of study. Given the changes in health, education and social support in the management of children with seizures over time, it would be of interest to investigate outcomes in a contemporary cohort. Such studies should ideally have validated diagnoses of seizures, details on seizure characteristics such as seizure type and severity, and a large sample size using national data.

Clinical characteristics of patients with refractory non-epileptic seizures.

OBJECTIVES: This incidence of non-epileptic seizures (NES) is estimated at 1-35 per 100,000 population. While many patients achieve remission, a significant fraction of patients have a poor prognosis despite optimal interventions. This study reports on the characteristics of patients with refractory NES diagnosed and treated at a comprehensive epilepsy centre. METHODS: A retrospective review of admissions to the Epilepsy Monitoring Unit identified patients diagnosed with NES over a 6-year period. Patients with refractory NES were identified through review of medical files. A diagnosis of refractory NES was assigned when patients experienced ongoing NES at least 1 year after diagnostic video-EEG monitoring. Data pertaining to predisposing, precipitating and perpetuating factors was collected on all patients and a comparative analysis was conducted between refractory and non-refractory cases. RESULTS: 66 patients with NES were identified, 35% were deemed refractory. There was no significant difference amongst predisposing factors between the groups. Psychosocial adversity and a clear precipitant proximate to the onset of NES were significantly more common in the refractory cohort. Unemployment at time of diagnosis was a significant perpetuating factor associated with poor outcome. CONCLUSION: This study provides insight into the features associated with refractory NES and may serve to improve prognostication and management in this disabling condition.

The crosstalk between epilepsy and dementia: A systematic review and meta-analysis.

BACKGROUND: Epilepsy and dementia are bidirectional. The purpose of this review was to investigate the epidemiological characteristics of and to identify the risk factors for epilepsy in patients with dementia and dementia in patients with epilepsy. METHODS: We retrieved the PubMed, Embase, Cochrane and Web of Science databases through January 2023. Two individuals screened the articles, extracted the data, and used a random effects model to pool the estimates and 95% confidence intervals (CIs). RESULTS: From 3475 citations, 25 articles were included. The prevalence of seizures/epilepsy was 4% among dementia patients and 3% among Alzheimer's disease (AD) patients. For vascular dementia, Lewy body dementia, and frontotemporal dementia, the pooled period prevalence of seizures/epilepsy was 6%, 3%, and 2%, respectively. Baseline early-onset AD was associated with the highest risk of 5-year epilepsy (pooled hazard ratios: 4.06; 95% CI: 3.25-5.08). Dementia patients had a 2.29-fold greater risk of seizures/epilepsy than non-dementia patients (95% CI: 1.37-3.83). Moreover, for baseline epilepsy, the pooled prevalence of dementia was 17% (95% CI: 10-25%), and that of AD was 15% (95% CI: 9-21%). The pooled results suggested that epilepsy is associated with a greater risk of dementia (risk ratio: 2.83, 95% CI: 1.64-4.88). CONCLUSIONS: There are still gaps in epidemiology regarding the correlation between dementia types and epilepsy, vascular risk factors, and the impact of antiseizure medication or cognitive improvement drugs on epilepsy and AD comorbidity.

Epilepsy monitoring unit practices and safety among NAEC epilepsy centers: A census survey.

OBJECTIVE: An epilepsy monitoring unit (EMU) is a specialized unit designed for capturing and characterizing seizures and other paroxysmal events with continuous video electroencephalography (vEEG). Nearly 260 epilepsy centers in the United States are accredited by the National Association of Epilepsy Centers (NAEC) based on adherence to specific clinical standards to improve epilepsy care, safety, and quality. This study examines EMU staffing, safety practices, and reported outcomes. METHOD: We analyzed NAEC annual report data and results from a supplemental survey specific to EMU practices reported in 2019 from 341 pediatric or adult center directors. Data on staffing, resources, safety practices and complications were collated with epilepsy center characteristics. We summarized using frequency (percentage) for categorical variables and median (inter-quartile range) for continuous variables. We used chi-square or Fisher's exact tests to compare staff responsibilities. RESULTS: The supplemental survey response rate was 100%. Spell classification (39%) and phase 1 testing (28%) were the most common goals of the 91,069 reported admissions. The goal ratio of EEG technologist to beds of 1:4 was the most common during the day (68%) and off-hours (43%). Compared to residents and fellows, advanced practice providers served more roles in the EMU at level 3 or pediatric-only centers. Status epilepticus (SE) was the most common reported complication (1.6% of admissions), while cardiac arrest occurred in 0.1% of admissions. SIGNIFICANCE: EMU staffing and safety practices vary across US epilepsy centers. Reported complications in EMUs are rare but could be further reduced, such as with more effective treatment or prevention of SE. These findings have potential implications for improving EMU safety and quality care.

Insomnia in epilepsy is associated with nocturnal seizures and anxiety.

PURPOSE: The purpose of this study was to identify the factors associated with insomnia in patients with epilepsy (PWE) and provide evidence for clinical prevention and treatment. METHODS: PWE who visited our epilepsy clinic from December 2021 to December 2022 were enrolled in our study. All participants completed the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Based on their ISI scores, they were categorized into two groups: PWE with insomnia (ISI score ≥ 10) and PWE without insomnia (ISI score < 10). Univariate analysis and stepwise logistic regression analysis were conducted to identify the factors associated with insomnia in PWE. RESULTS: A total of 196 Chinese PWE were recruited in this study(men, 39.8 %). Of these, 39 PWE(19.9 %) had insomnia.The incidence of nocturnal seizures (43.6 %vs19.7 %), depression (46.2 %vs9.6 %), anxiety (59.0 %vs11.5 %), and excessive daytime sleepiness(EDS,28.2 %vs5.7 %) in PWE with insomnia were significantly higher than in those without insomnia(all p＜0.01). Univariate regression analysis showed that seizures greater than or equal to once per month, nocturnal seizures, anxiety, depression, and EDS may associate with insomnia in PWE(all p＜0.05). Stepwise logistic regression analysis demonstrated that nocturnal seizures (OR = 2.611,95 % CI 1.040-6.478, P = 0.038) and anxiety (mild OR = 4.830,95 %CI 1.741-13.186, P = 0.002;moderate OR = 24.239,95 %CI 4.719-183.935, P＜0.001; severe OR = 37.653,95 %CI 4.931-782.741, P = 0.002) were independently associated with insomnia in PWE. CONCLUSION: PWE with insomnia are more likely to experience depression and EDS. Nocturnal seizures and anxiety are identified as independent factors associated with insomnia in PWE. Furthermore, Anxiety has a greater impact on insomnia in PWE and the likelihood of insomnia has increased significantly with the aggravation of anxiety levels.

Hypertension and other vascular risk factors in patients with functional seizures.

OBJECTIVE: Recent literature has suggested that functional seizures are associated with an elevated risk for vascular disease and mortality. We investigated the prevalence of risk factors for vascular disease in patients who were admitted to the epilepsy monitoring unit. METHODS: Patients who were admitted to the epilepsy monitoring unit and received a definitive diagnosis of either functional seizures or epilepsy were identified. Data collected included demographic, clinical characteristics, medication list, comorbidities, and scheduled blood pressure measurements that occurred every 12 h during the admission. The mean blood pressures were calculated and if they were above the American College of Cardiology and the American Heart Association guideline cutoff of 130/80 mm Hg or the patient had a documented history of hypertension the patient was counted as having the condition. A multiple logistic regression model was developed to evaluate the independent association of the patient's diagnosis (i.e., epilepsy or functional seizures) and vascular risk factors that controlled for the number of blood pressure measurements, age, sex, and if the patient was taking antihypertensive medications. RESULTS: 270 patients were included in this study of which 147 patients had epilepsy and 123 had functional seizures. Among those with functional seizures, 57.72 % had either a history of hypertension or a mean blood pressure above 130/80 compared to 38.78 % of those with epilepsy (p = 0.0022). In addition, 30.89 % of functional seizures patients had hyperlipidemia and 63.41 % were obese. The logistic regression model indicated that functional seizures were independently associated with high blood pressure (OR: 2.47, 95 % CI 1.10-5.69), hyperlipidemia (OR: 3.38, 95 % CI 1.35-8.86), and obesity (OR: 4.25, 95 % CI 2.22-8.36) compared to those with epilepsy. There was no significant difference in the prevalence of diabetes (OR: 0.81, 95 % CI 0.24-2.77) or current tobacco use (OR: 1.04, 95 % CI 0.48-2.25) between the groups. SIGNIFICANCE: Patients with functional seizures had an elevated prevalence of several vascular risk factors. These findings may partially account for complications associated with functional seizures and have implications related to their pathophysiology.

Time-course of drug-related psychiatric and behavioral treatment-emergent adverse events during brivaracetam treatment in adults with focal-onset seizures.

OBJECTIVE: We previously analyzed data from three phase lll trials of adjunctive brivaracetam (BRV) in adults showing that the incidence and prevalence of drug-related central nervous system treatment-emergent adverse events (TEAEs) quickly peaked and decreased over several weeks following BRV treatment initiation. However, that analysis did not assess psychiatric and behavioral side effects which can occur with antiseizure medication (ASM) treatment. Here, we investigate the time-course of psychiatric and behavioral TEAEs by week of BRV treatment and how these TEAEs were managed. METHODS: Data were pooled from three trials (N01252 [NCT00490035]; N01253 [NCT00464269]; N01358 [NCT01261325]) in adult patients (≥16 years of age) with focal-onset seizures receiving BRV adjunctive therapy. This post hoc analysis reports data on the incidence and prevalence of drug-related psychiatric or behavioral TEAEs over time in patients who received BRV doses of 50-200 mg/day (without titration) or placebo (PBO) during the 12-week treatment period. A logistic regression model was used to determine if psychiatric or behavioral comorbid conditions were predictors for drug-related psychiatric or behavioral TEAEs, or BRV discontinuation due to psychiatric or behavioral TEAEs. RESULTS: A total of 803 patients received BRV 50-200 mg/day, and 459 patients received PBO. Drug-related psychiatric or behavioral TEAEs were reported by 11.0 % of patients during adjunctive BRV treatment (PBO: 4.8 %) with onset early after BRV initiation (median time to onset of first drug-related psychiatric or behavioral TEAE: 15 days). Incidence peaked at week 1 and decreased over the first 4 weeks following BRV initiation. Prevalence peaked at week 4 and then remained stable between weeks 5-12. In an analysis excluding patients on concomitant levetiracetam (BRV: n = 744; PBO: n = 422), the incidence of drug-related psychiatric or behavioral TEAEs was similar to the incidence in the overall population. The most common drug-related psychiatric or behavioral TEAEs were irritability, insomnia, depression, and anxiety. Only 2 % of patients discontinued BRV due to psychiatric or behavioral TEAEs (PBO: 1.3 %), while most patients on BRV who reported drug-related psychiatric or behavioral TEAEs did not require a change in dose (84.1 %; PBO: 63.6 %). A history of psychiatric or behavioral comorbid conditions (not ongoing at BRV initiation) was not associated with an increased likelihood of drug-related psychiatric or behavioral TEAEs, or BRV discontinuation due to psychiatric or behavioral TEAEs. Ongoing psychiatric or behavioral comorbid conditions at BRV initiation increased the likelihood of drug-related psychiatric or behavioral TEAEs, but not the likelihood of BRV discontinuation due to psychiatric or behavioral TEAEs. CONCLUSIONS: Drug-related psychiatric and behavioral TEAEs occurred early during BRV treatment, and most patients did not require a change in BRV dose. These data can help guide clinician monitoring and patient expectations after starting BRV.