Medical and surgical treatment of epilepsy in older adults: A national survey.

OBJECTIVE: There are no clinical guidelines dedicated to the treatment of epilepsy in older adults. We investigated physician opinion and practice regarding the treatment of people with epilepsy aged 65 years or older. We also sought to study how our opinion and practice varied between geriatricians, general neurologists, and epilepsy neurologists (i.e., epileptologists). METHODS: We initially piloted our survey to measure test-retest reliability. Once finalized, we disseminated the survey via two rounds of facsimiles, and then conventional mail, to eligible individuals listed in a national directory of Canadian physicians. We used descriptive statistics such as stacked bar charts and tables to illustrate our findings. RESULTS: One hundred forty-four physicians (104 general neurologists, 25 geriatricians, and 15 epileptologists) answered our survey in its entirety (overall response rate of 13.2%). Levetiracetam and lamotrigine were the preferred antiseizure medications (ASMs) to treat older adults with epilepsy. Two thirds of epileptologists and almost half of general neurologists would consider prescribing lacosamide in >50% of people aged >65 years; only one geriatrician was of the same opinion. More than 40% of general neurologists and geriatricians erroneously believed that none of the ASMs mentioned in our survey was previously studied in randomized controlled trials specific to the treatment of epilepsy in older adults. Epileptologists were more likely as compared to general neurologists and geriatricians to recommend epilepsy surgery (e.g., 66.6% vs. 22.9%-37.5% among older adults). SIGNIFICANCE: Therapeutic decisions for older adults with epilepsy are heterogeneous between physician groups and sometimes misalign with available clinical evidence. Our surveyed physicians differed in their approach to ASM choice as well as perception of surgery in older adults with epilepsy. These findings likely reflect the lack of clinical guidelines dedicated to this population and the deficient implementation of best practices.

Non-contrast CT markers of intracerebral hematoma expansion: a reliability study.

OBJECTIVES: We evaluated whether clinicians agree in the detection of non-contrast CT markers of intracerebral hemorrhage (ICH) expansion. METHODS: From our local dataset, we randomly sampled 60 patients diagnosed with spontaneous ICH. Fifteen physicians and trainees (Stroke Neurology, Interventional and Diagnostic Neuroradiology) were trained to identify six density (Barras density, black hole, blend, hypodensity, fluid level, swirl) and three shape (Barras shape, island, satellite) expansion markers, using standardized definitions. Thirteen raters performed a second assessment. Inter- and intra-rater agreement were measured using Gwet's AC1, with a coefficient > 0.60 indicating substantial to almost perfect agreement. RESULTS: Almost perfect inter-rater agreement was observed for the swirl (0.85, 95% CI: 0.78-0.90) and fluid level (0.84, 95% CI: 0.76-0.90) markers, while the hypodensity (0.67, 95% CI: 0.56-0.76) and blend (0.62, 95% CI: 0.51-0.71) markers showed substantial agreement. Inter-rater agreement was otherwise moderate, and comparable between density and shape markers. Inter-rater agreement was lower for the three markers that require the rater to identify one specific axial slice (Barras density, Barras shape, island: 0.46, 95% CI: 0.40-0.52 versus others: 0.60, 95% CI: 0.56-0.63). Inter-observer agreement did not differ when stratified for raters' experience, hematoma location, volume, or anticoagulation status. Intra-rater agreement was substantial to almost perfect for all but the black hole marker. CONCLUSION: In a large sample of raters with different backgrounds and expertise levels, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement. KEY POINTS: • In a sample of 15 raters and 60 patients, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement (Gwet's AC1> 0.60). • Intra-rater agreement was substantial to almost perfect for eight of nine hematoma expansion markers. • Only the blend, fluid level, and swirl markers achieved substantial to almost perfect agreement across all three measures of reliability (inter-rater agreement, intra-rater agreement, agreement with the results of a reference reading).

Risk of Cancer Following an Ischemic Stroke in the Canadian Longitudinal Study on Aging.

BACKGROUND: Stroke survivors may be at higher risk of incident cancer, although the magnitude and the period at risk remain unclear. We conducted a retrospective cohort study to compare the risk of cancer in stroke survivors to that of the general population. METHODS: The Canadian Longitudinal Study on Aging is a large population-based cohort of individuals aged 45-85 years when recruited (2011-2015). We used data from the comprehensive subgroup (n = 30,097) to build a retrospective cohort with individual exact matching for age (1:4 ratio). We used Cox proportional hazards models to estimate hazard ratios of new cancer diagnosis with and without a prior stroke. RESULTS: We respectively included 920 and 3,680 individuals in the stroke and non-stroke groups. We observed a higher incidence of cancer in the first year after stroke that declined afterward (p-value = 0.030). The hazard of new cancer diagnosis after stroke was significantly increased (hazard ratio: 2.36; 95% CI: 1.21, 4.61; p-value = 0.012) as compared to age-matched non-stroke participants after adjustments. The most frequent primary cancers in the first year after stroke were prostate (n = 8, 57.1%) and melanoma (n = 2, 14.3%). CONCLUSIONS: The hazard of new cancer diagnosis in the first year after an ischemic stroke is about 2.4 times higher as compared to age-matched individuals without stroke after adjustments. Surveillance bias may explain a portion of post-stroke cancer diagnoses although a selection bias of healthier participants likely led to an underestimation of post-stroke cancer risk. Prospective studies are needed to confirm the potentially pressing need to screen for post-stroke cancer.

The Impact of Stroke Public Awareness Campaigns Differs Between Sociodemographic Groups.

BACKGROUND: Prehospital delays are a major obstacle to timely reperfusion therapy in acute ischemic stroke. Stroke sign recognition, however, remains poor in the community. We present an analysis of repeated surveys to assess the impact of Face, Arm, Speech, Time (FAST) public awareness campaigns on stroke knowledge. METHODS: Four cross-sectional surveys were conducted between July 2016 and January 2019 in the province of Quebec, Canada (n = 2,451). Knowledge of FAST stroke signs (face drooping, arm weakness and speech difficulties) was assessed with open-ended questions. A bilingual English/French FAST public awareness campaign preceded survey waves 1-3 and two campaigns preceded wave 4. We used multivariable ordinal regression models weighted for age and sex to assess FAST stroke sign knowledge. RESULTS: We observed an overall significant improvement of 26% in FAST stroke sign knowledge between survey waves 1 and 4 (odds ratio [OR] = 1.26; 95% CI: 1.02, 1.55; p = 0.035). After the last campaign, however, 30.5% (95% CI: 27.5, 33.6) of people were still unable to name a single FAST sign. Factors associated with worse performance were male sex (OR = 0.68; 95% CI: 0.53, 0.86; p = 0.002) and retirement (OR = 0.54; 95% CI: 0.35, 0.83; p = 0.005). People with lower household income and education had a tendency towards worse stroke sign knowledge and were significantly less aware of the FAST campaigns. CONCLUSIONS: Knowledge of FAST stroke signs in the general population improved after multiple public awareness campaigns, although it remained low overall. Future FAST campaigns should especially target men, retired people and individuals with a lower socioeconomic status.

Computer-assisted analysis of routine EEG to identify hidden biomarkers of epilepsy: A systematic review.

Background: Computational analysis of routine electroencephalogram (rEEG) could improve the accuracy of epilepsy diagnosis. We aim to systematically assess the diagnostic performances of computed biomarkers for epilepsy in individuals undergoing rEEG. Methods: We searched MEDLINE, EMBASE, EBM reviews, IEEE Explore and the grey literature for studies published between January 1961 and December 2022. We included studies reporting a computational method to diagnose epilepsy based on rEEG without relying on the identification of interictal epileptiform discharges or seizures. Diagnosis of epilepsy as per a treating physician was the reference standard. We assessed the risk of bias using an adapted QUADAS-2 tool. Results: We screened 10 166 studies, and 37 were included. The sample size ranged from 8 to 192 (mean=54). The computed biomarkers were based on linear (43%), non-linear (27%), connectivity (38%), and convolutional neural networks (10%) models. The risk of bias was high or unclear in all studies, more commonly from spectrum effect and data leakage. Diagnostic accuracy ranged between 64% and 100%. We observed high methodological heterogeneity, preventing pooling of accuracy measures. Conclusion: The current literature provides insufficient evidence to reliably assess the diagnostic yield of computational analysis of rEEG. Significance: We provide guidelines regarding patient selection, reference standard, algorithms, and performance validation.

Impact of bilingual face, arm, speech, time (FAST) public awareness campaigns on emergency medical services (EMS) activation in a large Canadian metropolitan area.

BACKGROUND AND AIMS: Face, arm, speech, time (FAST) public awareness campaigns improve stroke recognition in the general population. Whether this translates into improved emergency medical services (EMS) activation remains unclear. We assessed the association of five consecutive FAST campaigns with EMS calls for suspected strokes in a large urban area of Quebec, Canada. METHODS: We conducted an observational study to assess data collected between June 2015 and December 2019 by the public EMS agency covering the cities of Laval and Montreal (Quebec, Canada). Five FAST campaigns were held over this period (mean duration: 9 weeks). We compared daily EMS calls before and after all FAST campaigns (2015 vs 2019) with t tests and Mann-Whitney U tests. We used single-group, univariate interrupted time series to measure changes in daily EMS calls for suspected strokes following each FAST campaign (stroke categories: any, symptom onset < 5 h, Cincinnati Prehospital Stroke Scale [CPSS] 3/3). Calls for headache served as negative control. RESULTS: After five FAST campaigns, mean daily EMS calls increased by 28% (p < 0.001) for any suspected stroke and by 61% (p < 0.001) for stroke with symptom onset < 5 h, compared to 10.1% for headache (p = 0.012). Significant increases in daily EMS calls were observed after three campaigns (highest OR = 1.26; 95% CI 1.11, 1.43; p < 0.001). There were no significant changes in calls after individual campaigns for suspected stroke with symptom onset < 5 h, or suspected stroke with CPSS 3/3. CONCLUSIONS: We observed an inconsistent impact of individual FAST campaigns on EMS calls for any suspected stroke, and did not observe significant EMS call changes after individual campaigns for acute (< 5 h) and severe (CPSS 3/3) strokes. These results may help stakeholders identify potential benefits and limitations of public awareness campaigns using the FAST acronym.

RéSUMé: CONTEXTE ET OBJECTIFS: Les campagnes de sensibilisation du public Face, Arm, Speech, Time (FAST) améliorent la reconnaissance des AVC dans la population générale. Si cette amélioration de la reconnaissance des AVC se traduit par une amélioration de l'activation des services médicaux d'urgence (SMU) est encore inconnu. Nous avons évalué l'association de cinq campagnes FAST consécutives avec des appels SMU pour suspicion d'AVC dans une grande zone urbaine du Québec, au Canada. MéTHODES: Nous avons mené une étude observationnelle pour évaluer les données recueillies entre juin 2015 et décembre 2019 par l'agence publique EMS couvrant les villes de Laval et de Montréal (Québec, Canada). Cinq campagnes FAST ont été organisées sur cette période (durée moyenne : 9 semaines). Nous avons comparé les appels SMU quotidiens avant et après toutes les campagnes FAST (2015 vs 2019) avec les tests t et les tests U de Mann-Whitney. Nous avons utilisé des séries temporelles interrompues univariées à groupe unique pour mesurer les changements dans les appels quotidiens aux SMU pour des suspicions d'AVC après chaque campagne FAST (catégories d'AVC : tout, début des symptômes < 5 heures, Cincinnati Prehospital Stroke Scale [CPSS] 3/3). Les appels pour maux de tête ont servi de contrôle négatif. RéSULTATS: Après cinq campagnes FAST, le nombre moyen d'appels quotidiens aux SMU a augmenté de 28 % (p < 0,001) pour toute suspicion d'AVC et de 61 % (p < 0,001) pour les AVC avec une apparition des symptômes < 5 heures, contre 10,1 % pour les céphalées (p = 0,012). Des augmentations significatives des appels quotidiens aux SMU ont été observées après trois campagnes (OR le plus élevé = 1,26 ; IC à 95 % : 1,11, 1,43 ; p < 0,001). Il n'y a pas eu de changements significatifs dans les appels après les campagnes individuelles pour les suspicions d'AVC avec une apparition des symptômes < 5 heures, ou les suspicions d'AVC avec CPSS 3/3. CONCLUSIONS: Nous avons observé un impact irrégulier des campagnes FAST individuelles sur les appels aux SMU pour toute suspicion d'AVC, et nous n'avons pas observé de changements significatifs dans les appels aux SMU après les campagnes individuelles pour les AVC aigus (< 5 h) et sévères (CPSS 3/3). Ces résultats peuvent aider les parties prenantes à identifier les avantages et les limites potentielles des campagnes de sensibilisation du public utilisant l'acronyme FAST.

Computer-assisted analysis of routine electroencephalogram to identify hidden biomarkers of epilepsy: protocol for a systematic review.

INTRODUCTION: The diagnosis of epilepsy frequently relies on the visual interpretation of the electroencephalogram (EEG) by a neurologist. The hallmark of epilepsy on EEG is the interictal epileptiform discharge (IED). This marker lacks sensitivity: it is only captured in a small percentage of 30 min routine EEGs in patients with epilepsy. In the past three decades, there has been growing interest in the use of computational methods to analyse the EEG without relying on the detection of IEDs, but none have made it to the clinical practice. We aim to review the diagnostic accuracy of quantitative methods applied to ambulatory EEG analysis to guide the diagnosis and management of epilepsy. METHODS AND ANALYSIS: The protocol complies with the recommendations for systematic reviews of diagnostic test accuracy by Cochrane. We will search MEDLINE, EMBASE, EBM reviews, IEEE Explore along with grey literature for articles, conference papers and conference abstracts published after 1961. We will include observational studies that present a computational method to analyse the EEG for the diagnosis of epilepsy in adults or children without relying on the identification of IEDs or seizures. The reference standard is the diagnosis of epilepsy by a physician. We will report the estimated pooled sensitivity and specificity, and receiver operating characteristic area under the curve (ROC AUC) for each marker. If possible, we will perform a meta-analysis of the sensitivity and specificity and ROC AUC for each individual marker. We will assess the risk of bias using an adapted QUADAS-2 tool. We will also describe the algorithms used for signal processing, feature extraction and predictive modelling, and comment on the reproducibility of the different studies. ETHICS AND DISSEMINATION: Ethical approval was not required. Findings will be disseminated through peer-reviewed publication and presented at conferences related to this field. PROSPERO REGISTRATION NUMBER: CRD42022292261.

Inter-rater reliability of risk of bias tools for non-randomized studies.

PURPOSE: There is limited knowledge on the reliability of risk of bias (ROB) tools for assessing internal validity in systematic reviews of exposure and frequency studies. We aimed to identify and then compare the inter-rater reliability (IRR) of six commonly used tools for frequency (Loney scale, Gyorkos checklist, American Academy of Neurology [AAN] tool) and exposure (Newcastle-Ottawa scale, SIGN50 checklist, AAN tool) studies. METHODS: Six raters independently assessed the ROB of 30 frequency and 30 exposure studies using the three respective ROB tools. Articles were rated as low, intermediate, or high ROB. We calculated an intraclass correlation coefficient (ICC) for each tool and category of ROB tool. We compared the IRR between ROB tools and tool type by inspection of overlapping ICC 95% CIs and by comparing their coefficients after transformation to Fisher's Z values. We assessed the criterion validity of the AAN ROB tools by calculating an ICC for each rater in comparison with the original ratings from the AAN. RESULTS: All individual ROB tools had an IRR in the substantial range or higher (ICC point estimates between 0.61 and 0.80). The IRR was almost perfect (ICC point estimate > 0.80) for the AAN frequency tool and the SIGN50 checklist. All tools were comparable in IRR, except for the AAN frequency tool which had a significantly higher ICC than the Gyorkos checklist (p = 0.021) and trended towards a higher ICC when compared to the Loney scale (p = 0.085). When examined by category of ROB tool, scales, and checklists had a substantial IRR, whereas the AAN tools had an almost perfect IRR. For the criterion validity of the AAN ROB tools, the average agreement between our raters and the original AAN ratings was moderate. CONCLUSION: All tools had substantial IRRs except for the AAN frequency tool and the SIGN50 checklist, which both had an almost perfect IRR. The AAN ROB tools were the only category of ROB tools to demonstrate an almost perfect IRR. This category of ROB tools had fewer and simpler criteria. Overall, parsimonious tools with clear instructions, such as those from the AAN, may provide more reliable ROB assessments.

Phenotypes associated with genetic determinants of type I interferon regulation in the UK Biobank: a protocol.

Background: Type I interferons are cytokines involved in innate immunity against viruses. Genetic disorders of type I interferon regulation are associated with a range of autoimmune and cerebrovascular phenotypes. Carriers of pathogenic variants involved in genetic disorders of type I interferons are generally considered asymptomatic. Preliminary data suggests, however, that genetically determined dysregulation of type I interferon responses is associated with autoimmunity, and may also be relevant to sporadic cerebrovascular disease and dementia. We aim to determine whether functional variants in genes involved in type I interferon regulation and signalling are associated with the risk of autoimmunity, stroke, and dementia in a population cohort. Methods: We will perform a hypothesis-driven candidate pathway association study of type I interferon-related genes using rare variants in the UK Biobank (UKB). We will manually curate type I interferon regulation and signalling genes from a literature review and Gene Ontology, followed by clinical and functional filtering. Variants of interest will be included based on pre-defined clinical relevance and functional annotations (using LOFTEE, M-CAP and a minor allele frequency <0.1%). The association of variants with 15 clinical and three neuroradiological phenotypes will be assessed with a rare variant genetic risk score and gene-level tests, using a Bonferroni-corrected p-value threshold from the number of genetic units and phenotypes tested. We will explore the association of significant genetic units with 196 additional health-related outcomes to help interpret their relevance and explore the clinical spectrum of genetic perturbations of type I interferon. Ethics and dissemination: The UKB has received ethical approval from the North West Multicentre Research Ethics Committee, and all participants provided written informed consent at recruitment. This research will be conducted using the UKB Resource under application number 93160. We expect to disseminate our results in a peer-reviewed journal and at an international cardiovascular conference.

Frequency and predictors of occult cancer in ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: The optimal approach for cancer screening after an ischemic stroke remains unclear. AIMS: We sought to summarize the existing evidence regarding the frequency and predictors of cancer after an ischemic stroke. SUMMARY OF REVIEW: We searched seven databases from January 1980 to September 2019 for articles reporting malignant tumors and myeloproliferative neoplasms diagnosed after an ischemic stroke (PROSPERO protocol: CRD42019132455). We screened 15,400 records and included 51 articles. The pooled cumulative incidence of cancer within one year after an ischemic stroke was 13.6 per thousand (95% confidence interval [CI], 5.6-24.8), higher in studies focusing on cryptogenic stroke (62.0 per thousand; 95% CI, 13.6-139.3 vs 9.6 per thousand; 95% CI, 4.0-17.3; p = 0.02) and those reporting cancer screening (39.2 per thousand; 95% CI, 16.4-70.6 vs 7.2 per thousand; 95% CI, 2.5-14.1; p = 0.003). Incidence of cancer after stroke was generally higher compared to people without stroke. Most cases were diagnosed within the first few months after stroke. Several predictors of cancer were identified, namely older age, smoking, and involvement of multiple vascular territories as well as elevated C-reactive protein and d-dimers. CONCLUSIONS: The frequency of incident cancer after an ischemic stroke is low, but higher in cryptogenic stroke and after cancer screening. Several predictors may increase the yield of cancer screening after an ischemic stroke. The pooled incidence of post-stroke cancer is likely underestimated, and larger studies with systematic assessment of cancer after stroke are needed to produce more precise and valid estimates.

Acute carotid stenting in patients undergoing thrombectomy: a systematic review and meta-analysis.

BACKGROUND: The benefit of acute carotid stenting compared with no acute stenting on clinical outcomes among patients with tandem lesions (TL) undergoing endovascular thrombectomy (EVT) remains unknown. METHODS: We conducted a a systematic review and meta-analysis of studies comparing acute carotid stenting versus no stenting among TL patients undergoing EVT with regards to 90 day modified Rankin Scale (mRS) score, symptomatic intracerebral hemorrhage (sICH), and mortality. Four reviewers screened citations for eligibility and two assessed retained studies for risk of bias and data extraction. A random effects model was used for the synthesis of aggregated data. RESULTS: 21 studies (n=1635 patients) were identified for the systematic review; 19 were cohort studies, 1 was a post-hoc analysis of an EVT trial, and 1 was a pilot randomized controlled trial. 16 studies were included in the meta-analysis. Acute stenting was associated with a favorable 90 day mRS score: OR 1.43 (95% CI 1.07, 1.91). No significant heterogeneity between studies was found for this outcome (I2=17.0%; χ2=18.07, p=0.26). There were no statistically significant differences for 3 month mortality (OR 0.80 (95% CI 0.50, 1.28)) or sICH (OR 1.41 (95% CI 0.91, 2.19)). CONCLUSIONS: This meta-analysis suggests that among TL patients undergoing EVT, acute carotid stenting is associated with a greater likelihood of favorable outcome at 90 days compared with no stenting.

Incidence and Prevalence of Drug-Resistant Epilepsy: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the incidence and prevalence of drug-resistant epilepsy (DRE) as well as its predictors and correlates, we conducted a systematic review and meta-analysis of observational studies. METHODS: Our protocol was registered with PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology reporting standards were followed. We searched MEDLINE, Embase, and Web of Science. We used a double arcsine transformation and random-effects models to perform our meta-analyses. We performed random-effects meta-regressions using study-level data. RESULTS: Our search strategy identified 10,794 abstracts. Of these, 103 articles met our eligibility criteria. There was high interstudy heterogeneity and risk of bias. The cumulative incidence of DRE was 25.0% (95% confidence interval [CI]: 16.8-34.3) in child studies but 14.6% (95% CI: 8.8-21.6) in adult/mixed age studies. The prevalence of DRE was 13.7% (95% CI: 9.2-19.0) in population/community-based populations but 36.3% (95% CI: 30.4-42.4) in clinic-based cohorts. Meta-regression confirmed that the prevalence of DRE was higher in clinic-based populations and in focal epilepsy. Multiple predictors and correlates of DRE were identified. The most reported of these were having a neurologic deficit, an abnormal EEG, and symptomatic epilepsy. The most reported genetic predictors of DRE were polymorphisms of the ABCB1 gene. CONCLUSIONS: Our observations provide a basis for estimating the incidence and prevalence of DRE, which vary between populations. We identified numerous putative DRE predictors and correlates. These findings are important to plan epilepsy services, including epilepsy surgery, a crucial treatment option for people with disabling seizures and DRE.