A New Score for Sharp Discharges in the EEG Predicts Epilepsy

Purpose: A challenge in EEG interpretation is to correctly classify suspicious focal sharp activity as epileptiform or not. A predictive score was developed from morphologic features of the first focal sharp discharge, which can help in this decision. Methods: From a clinical standard EEG database, the authors identified 2,063 patients without a previous epilepsy diagnosis who had a focal sharp discharge in their EEG. Morphologic features (amplitude, area of slow wave, etc.) were extracted using an open source one-click algorithm in EEGLAB, masked to clinical classification. A score was developed from these features and validated with the clinical diagnosis of epilepsy over 2 to 6 years of follow-up. Independent external validation was performed in Kural long-term video-EEG monitoring dataset. Results: The score for the first focal sharp discharge had a moderate predictive performance for the clinical designation as the EEG being epileptiform (area under the receiver operating characteristics curve = 0.86). Best specificity was 91% and sensitivity 55%. The score also predicted a future epilepsy diagnosis (area under the receiver operating characteristics curve = 0.70). Best specificity was 86% and sensitivity 38%. Validation on the external dataset had an area under the receiver operating characteristics curve = 0.80. Clinical EEG identification of focal interictal epileptiform discharges had an area under the receiver operating characteristics curve = 0.73 for prediction of epilepsy. The score was based on amplitude, slope, difference from background, slow after-wave area, and age. Interrater reproducibility was high (ICC = 0.91). Conclusions: The designation of the first focal sharp discharge as epileptiform depends on reproducible morphologic features. Characteristic features were amplitude, slope, slow after-wave area, and difference from background. The score was predictive of future epilepsy. Halford semiquantitative scale had similar diagnostic performance but lower reproducibility.publishedVersio

International consensus guidance for management of myasthenia gravis

Altres ajuts: Supported by a grant from the Myasthenia Gravis Foundation of America (MGFA).To develop formal consensus-based guidance for the management of myasthenia gravis (MG). In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness methodology was used to develop consensus guidance statements. Definitions were developed for goals of treatment, minimal manifestations, remission, ocular MG, impending crisis, crisis, and refractory MG. An in-person panel meeting then determined 7 treatment topics to be addressed. Initial guidance statements were developed from literature summaries. Three rounds of anonymous e-mail votes were used to attain consensus on guidance statements modified on the basis of panel input. Guidance statements were developed for symptomatic and immunosuppressive treatments, IV immunoglobulin and plasma exchange, management of impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG associated with antibodies to muscle-specific tyrosine kinase, and MG in pregnancy. This is an international formal consensus of MG experts intended to be a guide for clinicians caring for patients with MG worldwide

Late Onset Myasthenia Gravis Is Associated with HLA DRB1*15:01 in the Norwegian Population

BACKGROUND: Acquired myasthenia gravis (MG) is a rare antibody-mediated autoimmune disease caused by impaired neuromuscular transmission, leading to abnormal muscle fatigability. The aetiology is complex, including genetic risk factors of the human leukocyte antigen (HLA) complex and unknown environmental factors. Although associations between the HLA complex and MG are well established, not all involved components of the HLA predisposition to this heterogeneous disease have been revealed. Well-powered and comprehensive HLA analyses of subgroups in MG are warranted, especially in late onset MG. METHODOLOGY/PRINCIPAL FINDINGS: This case-control association study is of a large population-based Norwegian cohort of 369 MG patients and 651 healthy controls. We performed comprehensive genotyping of four classical HLA loci (HLA-A, -B, -C and -DRB1) and showed that the DRB1*15:01 allele conferred the strongest risk in late onset MG (LOMG; onset ≥ 60 years) (OR 2.38, p(c)7.4 × 10(-5)). DRB1*13:01 was found to be a protective allele for both early onset MG (EOMG) and LOMG (OR 0.31, p(c) 4.71 × 10(-4)), a finding not previously described. No significant association was found to the DRB1*07:01 allele (p(nc) = 0.18) in a subset of nonthymomatous anti-titin antibody positive LOMG as reported by others. HLA-B*08 was mapped to give the strongest contribution to EOMG, supporting previous studies. CONCLUSION: The results from this study provide important new information concerning the susceptibility of HLA alleles in Caucasian MG, with highlights on DRB1*15:01 as being a major risk allele in LOMG

A New Score for Sharp Discharges in the EEG Predicts Epilepsy

Purpose: A challenge in EEG interpretation is to correctly classify suspicious focal sharp activity as epileptiform or not. A predictive score was developed from morphologic features of the first focal sharp discharge, which can help in this decision. Methods: From a clinical standard EEG database, the authors identified 2,063 patients without a previous epilepsy diagnosis who had a focal sharp discharge in their EEG. Morphologic features (amplitude, area of slow wave, etc.) were extracted using an open source one-click algorithm in EEGLAB, masked to clinical classification. A score was developed from these features and validated with the clinical diagnosis of epilepsy over 2 to 6 years of follow-up. Independent external validation was performed in Kural long-term video-EEG monitoring dataset. Results: The score for the first focal sharp discharge had a moderate predictive performance for the clinical designation as the EEG being epileptiform (area under the receiver operating characteristics curve = 0.86). Best specificity was 91% and sensitivity 55%. The score also predicted a future epilepsy diagnosis (area under the receiver operating characteristics curve = 0.70). Best specificity was 86% and sensitivity 38%. Validation on the external dataset had an area under the receiver operating characteristics curve = 0.80. Clinical EEG identification of focal interictal epileptiform discharges had an area under the receiver operating characteristics curve = 0.73 for prediction of epilepsy. The score was based on amplitude, slope, difference from background, slow after-wave area, and age. Interrater reproducibility was high (ICC = 0.91). Conclusions: The designation of the first focal sharp discharge as epileptiform depends on reproducible morphologic features. Characteristic features were amplitude, slope, slow after-wave area, and difference from background. The score was predictive of future epilepsy. Halford semiquantitative scale had similar diagnostic performance but lower reproducibility

Altered Cardiac Autonomic Regulation in Individuals with Myasthenia Gravis—A Systematic Review and Meta-Analysis

The aim of this systematic review with meta-analysis was to determine differences in cardiovascular autonomic parameters between patients with myasthenia gravis (MG) and healthy controls (HCs). Two reviewers searched four electronic databases, namely PubMed, Web of Science, EMBASE, and SCOPUS, from database inception to 7 July 2023 for studies investigating cardiovascular autonomic parameters in MG vs. HCs. A random-effects meta-analysis was performed to compute Hedges’ g ± 95% confidence intervals (CI). Out of a total of 2200 records, 8 observational studies with a sample size of 301 patients with MG and 454 HCs were included in the systematic review. Meta-analysis revealed lower values of expiration/inspiration ratio (g = −0.45, I2 = 74.7), baroreflex sensitivity (g = −0.56, 95%CI −0.80, −0.33; I2 = 0.3), percentage of adjacent NN intervals differing by more than 50 ms (g = −1.2, I2 = 82.8), square root of the mean of squared differences between successive beat intervals (g = −1.94, I2 = 95.1), mean of the standard deviations of all NN intervals (g = −0.83, 95%CI −1.37, −0.28; I2 = 55.5), and high frequency of HRV during tilt (g = −0.75, 95%CI −0.11, −0.39; I2 = 0). MG patients vs. HCs had higher systolic blood pressure (g = 0.39; I2 = 56.1), sympathovagal balance at rest/during tilt (LF/HF-RRIsupine, g = 0.44; I2 = 0; LF/HF-RRItilt, g = 0.86; I2 = 0; LF/HFtilt, g = 0.40; I2 = 0). As a group, MG patients have altered cardiac autonomic function, including decreased parasympathetic function, lower baroreflex sensitivity, and higher sympathovagal balance at rest and during orthostatic challenges

International consensus guidance for management of myasthenia gravis: Executive summary.

ObjectiveTo develop formal consensus-based guidance for the management of myasthenia gravis (MG).MethodsIn October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness methodology was used to develop consensus guidance statements. Definitions were developed for goals of treatment, minimal manifestations, remission, ocular MG, impending crisis, crisis, and refractory MG. An in-person panel meeting then determined 7 treatment topics to be addressed. Initial guidance statements were developed from literature summaries. Three rounds of anonymous e-mail votes were used to attain consensus on guidance statements modified on the basis of panel input.ResultsGuidance statements were developed for symptomatic and immunosuppressive treatments, IV immunoglobulin and plasma exchange, management of impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG associated with antibodies to muscle-specific tyrosine kinase, and MG in pregnancy.ConclusionThis is an international formal consensus of MG experts intended to be a guide for clinicians caring for patients with MG worldwide