Epilepsy, comorbid conditions in Canadian children: Analysis of cross-sectional data from cycle 3 of the national longitudinal study of children and youth

Purpose: The purpose of this study was to analyze national survey data to provide estimates of prevalence of epilepsy and associated developmental disabilities and comorbid conditions. Methods: We analyzed data from Cycle 3 of Canada\u27s National Longitudinal Survey of Children and Youth. The NLSCY captured, socio-demographic information, as well as age, sex, education, ethnicity, household income, chronic health related conditions from birth to 15 years old. The main survey question intended to identify epilepsy , cerebral palsy , intellectual disability , learning disability , and emotional and nervous difficulties in the population of children surveyed. Prevalence was based on the national cross-sectional sample and used 1000 bootstrap weights to account for survey design factors. Results: Cycle 3 of the NLSCY had the largest number of patients with diagnosed epilepsy. Prevalence figures (n/1000) for epilepsy and cerebral palsy (EPI-CP), epilepsy and intellectual disability (EPI-ID), epilepsy and learning disability (EPI-LD), and epilepsy and emotional nervous difficulties (EPI-EMO- NERV) were 1.1, 1.17, 2.58 and 1.34 respectively. Amongst children with epilepsy, 43.17% reported the presence of one or more of the above comorbid conditions. Conclusion: These results provide an initial prevalence estimate of comorbid conditions with epilepsy in Canadian children. In a high proportion of children with epilepsy, the PMK had reported at least one comorbid disorder. These findings carry implications for health care utilization and long-term outcomes. We discuss methodological aspects related to the ascertainment of epilepsy in both surveys, and to the validity and implications of our findings

Epilepsy, comorbid conditions in Canadian children: Analysis of cross-sectional data from cycle 3 of the national longitudinal study of children and youth

Purpose: The purpose of this study was to analyze national survey data to provide estimates of prevalence of epilepsy and associated developmental disabilities and comorbid conditions. Methods: We analyzed data from Cycle 3 of Canada\u27s National Longitudinal Survey of Children and Youth. The NLSCY captured, socio-demographic information, as well as age, sex, education, ethnicity, household income, chronic health related conditions from birth to 15 years old. The main survey question intended to identify epilepsy , cerebral palsy , intellectual disability , learning disability , and emotional and nervous difficulties in the population of children surveyed. Prevalence was based on the national cross-sectional sample and used 1000 bootstrap weights to account for survey design factors. Results: Cycle 3 of the NLSCY had the largest number of patients with diagnosed epilepsy. Prevalence figures (n/1000) for epilepsy and cerebral palsy (EPI-CP), epilepsy and intellectual disability (EPI-ID), epilepsy and learning disability (EPI-LD), and epilepsy and emotional nervous difficulties (EPI-EMO- NERV) were 1.1, 1.17, 2.58 and 1.34 respectively. Amongst children with epilepsy, 43.17% reported the presence of one or more of the above comorbid conditions. Conclusion: These results provide an initial prevalence estimate of comorbid conditions with epilepsy in Canadian children. In a high proportion of children with epilepsy, the PMK had reported at least one comorbid disorder. These findings carry implications for health care utilization and long-term outcomes. We discuss methodological aspects related to the ascertainment of epilepsy in both surveys, and to the validity and implications of our findings

Epilepsy Risk Following Bariatric Surgery for Weight Loss

Background and objectives: A previous study reported finding that epilepsy risk is elevated following bariatric surgery for weight loss; however, this association has not been adequately explored. Our objectives were to (1) estimate the risk of epilepsy following bariatric surgery for weight loss relative to a non-surgical cohort of patients with an obesity diagnosis, and (2) identify epilepsy risk factors among bariatric surgery recipients. Methods: We conducted a population-based retrospective cohort study using linked health administrative databases in Ontario, Canada. Participants were accrued between July 1, 2010, and December 31, 2016, and followed until December 31, 2019. All Ontario residents 18 years of age and older who had bariatric surgery during the accrual period were eligible for inclusion in our exposed cohort. Patients hospitalized with a diagnosis of obesity and who did not have bariatric surgery during the accrual period were eligible for inclusion in our unexposed cohort. We excluded patients with a history of seizures, epilepsy, various seizure or epilepsy risk factors, psychiatric disorders, or drug or alcohol abuse/dependence. In our primary analysis, we used inverse probability of treatment weighting to control for confounding. A marginal Cox proportional hazards model was then used to estimate the risk of epilepsy associated with bariatric surgery. A Cox model was also used to identify epilepsy risk factors among exposed participants. Results: The final sample included 16,958 exposed participants and 622,514 unexposed participants. Following inverse probability of treatment weighting, the estimated rates of epilepsy were 50.1 and 34.1 per 100,000 person-years among those who did and did not have bariatric surgery, respectively. The hazard ratio for developing epilepsy after bariatric surgery was 1.45 (95% CI=1.35, 1.56). Among participants who received bariatric surgery, stroke during follow-up increased epilepsy risk (HR=14.03, 95% CI=4.26, 46.25). Discussion: In this study, we found that patients with a history of bariatric surgery were at increased risk of developing epilepsy. These findings suggest that epilepsy is a long-term risk associated with bariatric surgery for weight loss

Long Term outcomes after NORSE: Treatment with Vagus Nerve Stimulation

New-onset refractory status epilepticus (NORSE) is associated with high mortality, therapy resistant epilepsy (TRE) and poor cognitive and functional outcomes. Some patients develop multifocal TRE, for whom surgery with a curative intention, is not an option. In these patients, Vagus Nerve Stimulation (VNS) is performed as a palliative treatment. We report the long-term outcomes regarding seizure frequency, functional and cognitive outcome, and effectiveness of VNS in two patients with TRE as a consequence of NORSE. In the first patient with cryptogenic NORSE, VNS implantation occurred during the acute stage, probably contributing to the cessation of her status epilepticus. However, in the long-term follow-up, the patient persisted with daily multifocal seizures. In the second patient, VNS implantation was delayed to manage his epilepsy when the NORSE, ultimately due to autoimmune encephalitis, had resolved. During long-term follow-up, no reduction in seizure frequency was achieved. The current evidence supporting the use of VNS in patients with TRE after NORSE warrants further investigation

The risk of new-onset epilepsy and refractory epilepsy in older adult stroke survivors

Research Summary: Key Findings Stroke is a common cause of epilepsy in older adults, but little is known about stroke-related epilepsy or its outcomes in this population. 1.1% of older adult stroke survivors developed epilepsy in this study, of whom 12.9% developed refractory epilepsy, indicating that this population is particularly responsive to treatment. Over 85% of deaths in this population are not due to stroke or epilepsy.https://ir.lib.uwo.ca/neuruprojectsummaries/1000/thumbnail.jp

Quantitative relaxometry and diffusion MRI for lateralization in MTS and non-MTS temporal lobe epilepsy.

We developed novel methodology for investigating the use of quantitative relaxometry (T1 and T2) and diffusion tensor imaging (DTI) for lateralization in temporal lobe epilepsy. Patients with mesial temporal sclerosis confirmed by pathology (N=8) and non-MTS unilateral temporal lobe epilepsy (N=6) were compared against healthy controls (N=19) using voxel-based analysis restricted to the anterior temporal lobes, and laterality indices for each MRI metric (T1, T2, fractional anisotropy (FA), mean diffusivity, axial and radial diffusivities) were computed based on the proportion of significant voxels on each side. The diffusivity metrics were the most lateralizing MRI metrics in MTS and non-MTS subsets, with significant differences also seen with FA, T1 and T2. Patient-specific multi-modal laterality indices were also computed and were shown to clearly separate the left-onset and right-onset patients. Marked differences between left-onset and right-onset patients were also observed, with left-onset patients exhibiting stronger laterality indices. Finally, neocortical abnormalities were found to be more common in the non-MTS patients. These preliminary results on a small sample size support the further investigation of quantitative MRI and multi-modal image analysis in clinical determination of seizure onset. The presence of more neocortical abnormalities in the non-MTS group suggests a role in seizure onset or propagation and motivates the investigation of more sensitive histopathological analysis to detect and delineate potentially subtle neocortical pathology

Registration of in-vivo to ex-vivo MRI of surgically resected specimens: A pipeline for histology to in-vivo registration.

BACKGROUND: Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to develop and evaluate a protocol for deformable image registration of in-vivo to ex-vivo resected brain specimen MRI. This protocol, in conjunction with our previous work on ex-vivo to histology registration, completes a registration pipeline for histology to in-vivo MRI, enabling voxel-based validation of novel and existing MRI techniques with histopathology. NEW METHOD: A combination of image-based and landmark-based 3D registration was used to register in-vivo MRI and the ex-vivo MRI from patients (N=10) undergoing epilepsy surgery. Target registration error (TRE) was used to assess accuracy and the added benefit of deformable registration. RESULTS: A mean TRE of 1.35±0.11 and 1.41±0.33mm was found for neocortical and hippocampal specimens respectively. Statistical analysis confirmed that the deformable registration significantly improved the registration accuracy for both specimens. COMPARISON WITH EXISTING METHODS: Image registration of surgically resected brain specimens is a unique application which presents numerous technical challenges and that have not been fully addressed in previous literature. Our computed TRE are comparable to previous attempts tackling similar applications, as registering in-vivo MRI to whole brain or serial histology. CONCLUSION: The presented registration pipeline finds dense and accurate spatial correspondence between in-vivo MRI and histology and allows for the spatially local and quantitative assessment of pathological correlates in MRI

Magnetic resonance imaging and histology correlation in the neocortex in temporal lobe epilepsy.

OBJECTIVE: To investigate the histopathological correlates of quantitative relaxometry and diffusion tensor imaging (DTI) and to determine their efficacy in epileptogenic lesion detection for preoperative evaluation of focal epilepsy. METHODS: We correlated quantitative relaxometry and DTI with histological features of neuronal density and morphology in 55 regions of the temporal lobe neocortex, selected from 13 patients who underwent epilepsy surgery. We made use of a validated nonrigid image registration protocol to obtain accurate correspondences between in vivo magnetic resonance imaging and histology images. RESULTS: We found T1 to be a predictor of neuronal density in the neocortical gray matter (GM) using linear mixed effects models with random effects for subjects. Fractional anisotropy (FA) was a predictor of neuronal density of large-caliber neurons only (pyramidal cells, layers 3 and 5). Comparing multivariate to univariate mixed effects models with nested variables demonstrated that employing T1 and FA together provided a significantly better fit than T1 or FA alone in predicting density of large-caliber neurons. Correlations with clinical variables revealed significant positive correlations between neuronal density and age (rs  = 0.726, pfwe  = 0.021). This study is the first to relate in vivo T1 and FA values to the proportion of neurons in GM. INTERPRETATION: Our results suggest that quantitative T1 mapping and DTI may have a role in preoperative evaluation of focal epilepsy and can be extended to identify GM pathology in a variety of neurological disorders

Canadian epilepsy priority-setting partnership: Toward a new national research agenda

Background: Health research agendas are often set by researchers or by industry and may not reflect the needs and priorities of end users. This priority-setting partnership (PSP) for epilepsy was undertaken to identify the most pressing unanswered questions about epilepsy and seizures from the perspective of people with epilepsy (PWE) and their care providers. Methods: Using the methodology developed by the James Lind Alliance (JLA), evidence uncertainties were gathered via online surveys from stakeholders across Canada. Submissions were formed into summary questions and checked against existing evidence to determine if they were true uncertainties. Verified uncertainties were then ranked by patients, caregivers, and healthcare providers and a final workshop was held to reach a consensus on the top 10 priorities. Results: The final top 10 list reflects the priority areas of focus for research as identified by the Canadian epilepsy community, including genetic markers for diagnosis and treatment, concerns about living with the long-term effects of epilepsy, and addressing knowledge gaps in etiology and treatment approaches. Conclusion: This project represents the first systematic evidence of patient- and clinician-centered research priorities for epilepsy. The results of this priority-setting exercise provide an opportunity for researchers and funding agencies to align their agendas with the values and needs of the epilepsy community in order to improve clinical outcomes and quality of life (QOL) for PWE