Estimating the Magnitude of Genetic Factors by Calculating the Genetic Relative Risk of Stroke in First-Ever Lacunar Stroke Patients

BACKGROUND: Positive family history of stroke is an independent risk factor for lacunar stroke. However, the magnitude of familial aggregation of a certain disease is better evaluated by the genetic relative risk. This is calculated by dividing the prevalence of specific disease in family members of patients by the prevalence of this disease in the general population. In a cohort of lacunar stroke patients, who were subtyped clinically and radiologically, we determined the genetic relative risk of stroke. METHODS: By questionnaire and additional interview, we obtained a complete first-degree family history of stroke. The prevalence of stroke in first-degree relatives of these lacunar stroke patients was compared to the self-reported prevalence of stroke in a Dutch community based cohort of elderly volunteers. Secondly, the influence of proband characteristics and family composition on parental and sibling history of stroke were evaluated. PRINCIPAL FINDINGS: We collected data of 1066 first-degree relatives of 195 lacunar stroke patients. Strokes occurred in 13.5% of first-degree relatives. The genetic relative risk was 2.94 (95%CI 2.45-3.53) for overall first-degree relatives, 4.52 (95%CI 3.61-5.65) for patients' parents and 2.10 (95%CI 1.63-2.69) for patients' siblings. Age of proband and proband status for hypertension influenced the chance of having a parent with a history of stroke whereas the likelihood of having a concordant sibling increased with sibship size. CONCLUSIONS: We found an increased genetic relative risk of stroke in first-degree relatives of patients with lacunar stroke. Our data warrant further genomic research in this well-defined high risk population for stroke

A Comprehensive View on MRI Techniques for Imaging Blood-Brain Barrier Integrity

The blood-brain barrier (BBB) is the interface between the blood and brain tissue, which regulates the maintenance of homeostasis within the brain. Impaired BBB integrity is increasingly associated with various neurological diseases. To gain a better understanding of the underlying processes involved in BBB breakdown, magnetic resonance imaging (MRI) techniques are highly suitable for noninvasive BBB assessment. Commonly used MRI techniques to assess BBB integrity are dynamic contrast-enhanced and dynamic susceptibility contrast MRI, both relying on leakage of gadolinium-based contrast agents. A number of conceptually different methods exist that target other aspects of the BBB. These alternative techniques make use of endogenous markers, such as water and glucose, as contrast media. A comprehensive overview of currently available MRI techniques to assess the BBB condition is provided from a scientific point of view, including potential applications in disease. Improvements that are required to make these techniques clinically more easily applicable will also be discussed.</p

Novel neuronal surface autoantibodies in plasma of patients with depression and anxiety

Neuronal surface autoantibodies (NSAbs) against various antigens cause autoimmune encephalitis. Some of these antigens are also involved in the pathology of depression and anxiety. To study whether NSAbs are more common in plasma of individuals with depression and anxiety than in controls, and to investigate if NSAbs correlate with disease status, plasma samples of 819 individuals with a current diagnosis of depression and/or anxiety, 920 in remission and 492 individuals without these disorders were included in this study. Samples were tested by a combination of immunohistochemistry (IHC), staining on live rat hippocampus neurons and cell-based assay (CBA). By IHC, 50 (2.2%) samples showed immunoreactivity to rat brain tissue, with no significant differences between the aforementioned groups (22/819 vs 18/920 vs 11/492, P > 0.99). In addition, eight IHC positive samples were positive for NSAbs on live neurons (7/819 vs 0/920 vs 1/492, P = 0.006). The IHC-staining patterns of these eight samples were atypical for autoimmune encephalitis and accordingly, they tested negative for known NSAbs by CBA. No obvious difference in the clinical characteristics between individuals with or without NSAbs was observed. In conclusion, novel NSAbs were rare but predominately found in patients with current anxiety or depression indicating they might affect mental health in a small group of patients.info:eu-repo/semantics/publishedVersio

Combining gamma with Alpha and Beta power modulation for enhanced cortical mapping in patients with focal epilepsy

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of "eloquent" areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity (55-200 Hz) recorded with extraoperative electrocorticography (ECoG) during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha (8-12 Hz) and beta (15-25 Hz) bands could further improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy (age: 35.9 ± 9.1 years, range: 22-48, 8 females, 9 right handed) participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model (GLM) approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic (ROC) curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient's degree of attention to the stimulus. We show that diagnostic ability can be increased by 3-5% by combining gamma and alpha and by 7.5-11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy.info:eu-repo/semantics/publishedVersio

Antibodies Contributing to Focal Epilepsy Signs and Symptoms Score

Objective: Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology, and to create a score to preselect patients requiring testing. Methods: In this prospective, multicenter cohort study, adults with focal epilepsy of unknown etiology, without recognized AIE, were included, between December 2014 and December 2017, and followed for 1 year. Serum, and if available cerebrospinal fluid, were analyzed using different laboratory techniques. The ACES score was created using factors favoring an autoimmune etiology of seizures (AES), as determined by multivariate logistic regression. The model was externally validated and evaluated using the Concordance (C) statistic. Results: We included 582 patients, with median epilepsy duration of 8 years (interquartile range = 2–18)

Inter- and intraobserver agreement of seizure behavior scoring in the amygdala kindled rat

\u3cp\u3eIntroduction: The Racine scale is a 5-point seizure behavior scoring paradigm used in the amygdala kindled rat. Though this scale has been applied widely in experimental epilepsy research, studies of reproducibility are rare. The aim of the current study was, therefore, to assess its interobserver variability and intraobserver variability. Material and methods: A video database set was acquired in the course of amygdala kindling of 67 Wistar rats. Six blinded observers received scoring instructions and then viewed a set of 15 random videos (session #1). Next, each observer scored 379 to 1048 additional videos (session #2) and finally scored the same set of 15 videos again (session #3). Scores included the occurrence of seizures (yes or no), the total seizure time (start of stimulus until the absence of seizure behavior), and the highest Racine stage. Interobserver variability and intraobserver variability were assessed in and between sessions #1 and #3 using a 2-way mixed intraclass correlation or Cohen's kappa depending on the variable. Results: Interobserver agreement in session #1 was 0.664 for seizure occurrence, 0.861 for total seizure time, and 0.797 for the highest Racine stage. In session #3, interobserver agreement on seizure occurrence declined to 0.492, total seizure time declined to 0.625, and agreement for the highest Racine stage was 0.725. Interobserver agreement was scored insufficiently on focal R2 seizures in both sessions (0.287 and 0.182). Intraobserver agreement reached &gt;. 0.80 agreement for seizure occurrence, highest seizure score, and total seizure time in 3 out of 4 observers. Racine's scale stage 2 seizure scores were only 0.135 in one observer but 0.650, 0.810, and 0.635 in the other observers. Discussion and conclusion: Overall, interobserver agreement and intraobserver agreement in scoring with Racine's scale were adequate. However, because interobserver agreement declined after a period of individually scoring videos, we suggest periodic repetition of the standardized instruction in the course of evaluating videos in order to ensure reproducible results.\u3c/p\u3