SEREEGA: Simulating Event-Related EEG Activity

Abstract Electroencephalography (EEG) is a popular method to monitor brain activity, but it can be difficult to evaluate EEG-based analysis methods because no ground-truth brain activity is available for comparison. Therefore, in order to test and evaluate such methods, researchers often use simulated EEG data instead of actual EEG recordings, ensuring that it is known beforehand which e ects are present in the data. As such, simulated data can be used, among other things, to assess or compare signal processing and machine learn-ing algorithms, to model EEG variabilities, and to design source reconstruction methods. In this paper, we present SEREEGA, short for Simulating Event-Related EEG Activity . SEREEGA is a MATLAB-based open-source toolbox dedicated to the generation of sim-ulated epochs of EEG data. It is modular and extensible, at initial release supporting ve different publicly available head models and capable of simulating multiple different types of signals mimicking brain activity. This paper presents the architecture and general work ow of this toolbox, as well as a simulated data set demonstrating some of its functions. Highlights Simulated EEG data has a known ground truth, which can be used to validate methods. We present a general-purpose open-source toolbox to simulate EEG data. It provides a single framework to simulate many different types of EEG recordings. It is modular, extensible, and already includes a number of head models and signals. It supports noise, oscillations, event-related potentials, connectivity, and more

VZV-associated acute retinal necrosis in a patient with MS treated with natalizumab

Natalizumab (NTZ) was the first approved humanized monoclonal antibody in highly active relapsing remitting MS (RRMS). Because of the mechanism of inhibiting the migration of immune cells through the blood-brain barrier into the CNS, NTZ is associated with an increased risk of progressive multifocal leukoencephalopathy (PML) by the John Cunningham virus (JCV). Infections with other neurotropic viruses are rarely reported. We present a case of rapid retinal necrosis induced by varicella zoster virus (VZV) in a patient with RRMS under long-term NTZ treatment

Evaluation of a dry EEG system for application of passive brain-computer interfaces in autonomous driving

© 2017 Zander, Andreessen, Berg, Bleuel, Pawlitzki, Zawallich, Krol and Gramann. We tested the applicability and signal quality of a 16 channel dry electroencephalography (EEG) system in a laboratory environment and in a car under controlled, realistic conditions. The aim of our investigation was an estimation how well a passive Brain-Computer Interface (pBCI) can work in an autonomous driving scenario. The evaluation considered speed and accuracy of self-applicability by an untrained person, quality of recorded EEG data, shifts of electrode positions on the head after driving-related movements, usability, and complexity of the system as such and wearing comfort over time. An experiment was conducted inside and outside of a stationary vehicle with running engine, air-conditioning, and muted radio. Signal quality was sufficient for standard EEG analysis in the time and frequency domain as well as for the use in pBCIs. While the influence of vehicle-induced interferences to data quality was insignificant, driving-related movements led to strong shifts in electrode positions. In general, the EEG system used allowed for a fast self-applicability of cap and electrodes. The assessed usability of the system was still acceptable while the wearing comfort decreased strongly over time due to friction and pressure to the head. Fromthese results we conclude that the evaluated system should provide the essential requirements for an application in an autonomous driving context. Nevertheless, further refinement is suggested to reduce shifts of the system due to body movements and increase the headset’s usability and wearing comfort

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature

Background: Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic progressive demyelinating disease. It is unclear if patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) should routinely be tested for MOG-IgG. Objective: To evaluate the frequency of MOG-IgG among patients classified as having PPMS or SPMS based on current diagnostic criteria. Methods: For this purpose, we retrospectively tested serum samples of 200 patients with PPMS or SPMS for MOG-IgG using cell-based assays. In addition, we performed a review of the entire English language literature on MOG-IgG published between 2011 and 2017. Results: None of 139 PPMS and 61 SPMS patients tested was positive for MOG-IgG. Based on a review of the literature, we identified 35 further MOG-IgG tests in patients with PPMS and 55 in patients with SPMS; the only reportedly positive sample was positive just at threshold level and was tested in a non-IgG-specific assay. In total, a single borderline positive result was observed among 290 tests. Conclusion: Our data suggest that MOG-IgG is absent or extremely rare among patients with PPMS or SPMS. Routine screening of patients with typical PPMS/SPMS for MOG-IgG seems not to be justified

Pain, depression and quality of life in adults with MOG-antibody associated disease

BACKGROUND AND PURPOSE: Myelin oligodendrocyte glycoprotein-antibody (MOG-ab)-associated disease (MOGAD) is an inflammatory autoimmune condition of the CNS. However, data on pain and depression have remained scarce. The aim of this study was to assess features of chronic pain and depression as well as their impact on health-related quality of life (hr-QoL) in MOGAD. METHODS: Patients with MOGAD were identified in the Neuromyelitis Optica Study Group (NEMOS) registry. Data were acquired by a questionnaire, including clinical, demographic, pain (PainDetect, Brief Pain Inventory - short form, McGill Pain Questionnaire - short form), depression (Beck Depression Inventory-II), and hr-QoL (Short Form-36 Health Survey) items. RESULTS: Twenty-two of 43 patients suffered from MOGAD-related pain (11 nociceptive, 8 definite neuropathic, 3 possible neuropathic) and 18 from depression. Patients with neuropathic pain had highest pain intensity and most profound ADL impairment. Fifteen patients reported spasticity-associated pain, including four with short-lasting painful tonic spasms. Later disease onset, profound physical impairment and depression were associated with chronic pain. Physical QoL was more affected in pain-sufferers (p<0.001) than in pain-free patients, being most severely reduced by neuropathic pain (p=0.016). Pain severity, visual impairment, and gait impairment independently predicted lower physical QoL. Depression was the only factor reducing mental QoL. Twelve patients received pain medication, still suffering from moderate pain (pain severity 4.6±2.3). Only four out of ten patients with moderate to severe depression took antidepressants. CONCLUSIONS: Being highly prevalent, pain and depression strongly affect QoL and ADL in MOGAD. Both conditions remain insufficiently controlled in real-life clinical practice

Pain, depression, and quality of life in neuromyelitis optica spectrum disorder: a cross-sectional study of 166 AQP4 antibody-seropositive patients

OBJECTIVES: To evaluate prevalence, clinical characteristics, and predictors of pain, depression, and their impact on the quality of life (QoL) in a large neuromyelitis optica spectrum disorder (NMOSD) cohort. METHODS: We included 166 patients with aquaporin-4–seropositive NMOSD from 13 tertiary referral centers. Patients received questionnaires on demographic and clinical characteristics, PainDetect, short form of Brief Pain Inventory, Beck Depression Inventory–II, and Short Form 36 Health Survey. RESULTS: One hundred twenty-five (75.3%) patients suffered from chronic NMOSD-associated pain. Of these, 65.9% had neuropathic pain, 68.8% reported spasticity-associated pain and 26.4% painful tonic spasms. Number of previous myelitis attacks (OR = 1.27, p = 0.018) and involved upper thoracic segments (OR = 1.31, p = 0.018) were the only predictive factors for chronic pain. The latter was specifically associated with spasticity-associated pain (OR = 1.36, p = 0.002). More than a third (39.8%) suffered from depression, which was moderate to severe in 51.5%. Pain severity (OR = 1.81, p < 0.001) and especially neuropathic character (OR = 3.44, p < 0.001) were associated with depression. Pain severity and walking impairment explained 53.9% of the physical QoL variability, while depression and walking impairment 39.7% of the mental QoL variability. No specific medication was given to 70.6% of patients with moderate or severe depression and 42.5% of those with neuropathic pain. Two-thirds (64.2%) of patients with symptomatic treatment still reported moderate to severe pain. CONCLUSIONS: Myelitis episodes involving upper thoracic segments are main drivers of pain in NMOSD. Although pain intensity was lower than in previous studies, pain and depression remain undertreated and strongly affect QoL. Interventional studies on targeted treatment strategies for pain are urgently needed in NMOSD

Costs and health-related quality of life in patients with NMO spectrum disorders and MOG-antibody-associated disease: CHANCE(NMO) study

OBJECTIVE: To evaluate costs and health-related quality of life (HRQoL) of neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD).MethodsIn this multicenter cross-sectional study, data on consumption of medical and non-medical resources and work ability were assessed via patient questionnaires. Costs were analyzed in EUR for 2018 from the societal perspective. HRQoL was captured by the EuroQoL EQ-5D-5L questionnaire. Clinical data were retrieved from the Neuromyelitis Optica Study Group (NEMOS) database. RESULTS: Two hundred twelve patients (80% women; median age 50 [19-83] years; median disease duration 7 [0-43] years; median Expanded Disability Status Scale [EDSS] 3.5 [0-8.5]; 66% Aquaporin-4 IgG, 22% MOG IgG positive, 12% double seronegative) were analyzed. The mean total annual per capita cost of illness accounted for EUR (Euro) 59 574 (95% CI 51 225 to 68 293; USD [United States dollars] 70 297, 95% CI 60 445 to 80 586), and the mean index value of the EQ-5D-5L was 0.693 (95% CI 0.65 to 0.73). The most important cost drivers were informal care costs (28% of total costs), indirect costs (23%) and drugs (16%), especially immunotherapeutics. Costs showed a positive correlation with disease severity (ρ=0.56, 95% CI 0.45 to 0.65); in the EDSS 6.5-8.5 subgroup the mean annual costs were EUR 129 687 (95% CI 101 946 to 160 336; USD 153 031, 95% CI 120 296 to 189 196). The HRQoL revealed a negative correlation to disease severity (ρ=-0.69, 95% CI -0.76 to -0.61); in the EDSS 6.5-8.5 subgroup the EQ-5D-5L mean index value was 0.195 (95% CI 0.13 to 0.28). Neither antibody status nor disease duration influenced the total annual costs or HRQoL. CONCLUSION: These German data from the era without approved preventive immunotherapies show enormous effects of the diseases on costs and quality of life. An early and cost-effective therapy should be provided to prevent long-term disability and preserve quality of life

Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis

'Myasthenia gravis' (MG) is an autoimmune disease in which immunoglobulin G (IgG) antibodies (Abs) bind to acetylcholine receptors (AChR) or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction. IgG crystallizable fragment (Fc)-mediated effector functions, such as antibody-dependent complement deposition, contribute to disease development and progression. Despite progress in understanding Ab-mediated disease mechanisms, immunotherapy of MG remained rather unspecific with corticosteroids and maintenance with immunosuppressants as first choice drugs for most patients. More specific therapeutic IgG Fc-based platforms that reduce serum half-life or effector functions of pathogenic MG-related Abs are currently being developed, tested in clinical trials or have recently been successfully translated into the clinic. In this review, we illustrate mechanisms of action and clinical efficacies of emerging Fc-mediated therapeutics such as neonatal Fc receptor (FcRn)-targeting agents. Furthermore, we evaluate prospects of therapies targeting classical Fc receptors that have shown promising therapeutic efficacy in other antibody-mediated conditions. Increased availability of Fc- and Fc receptor-targeting biologics might foster the development of personalized immunotherapies with the potential to induce sustained disease remission in patients with MG

Anatomically constrained tractography facilitates biologically plausible fiber reconstruction of the optic radiation in multiple sclerosis

Diffusion-weighted magnetic resonance imaging (dMRI) enables the microstructural characterization and reconstruction of white matter pathways in vivo non-invasively. However, dMRI only provides information on the orientation of potential fibers but not on their anatomical plausibility. To that end, recent methodological advances facilitate the effective use of anatomical priors in the process of fiber reconstruction, thus improving the accuracy of the results. Here, we investigated the potential of anatomically constrained tracking (ACT), a modular addition to the tractography software package MRtrix3, to accurately reconstruct the optic radiation, a commonly affected pathway in multiple sclerosis (MS). Diffusion MRI data were acquired from 28 MS patients and 22 age- and sex-matched healthy controls. For each participant, the optic radiation was segmented based on the fiber reconstruction obtained using ACT. When implementing ACT in MS, it proved essential to incorporate lesion maps to avoid incorrect reconstructions due to tissue-type misclassifications in lesional areas. The ACT-based results were compared with those obtained using two commonly used probabilistic fiber tracking procedures, based on FSL (FMRIB Software Library) and MRtrix3 without ACT. All three procedures enabled a reliable localization of the optic radiation in both MS patients and controls. However, for FSL and MRtrix3 without ACT it was necessary to place an additional waypoint halfway between the lateral geniculate nucleus and the primary visual cortex to filter out anatomically implausible tracks. In the case of ACT, the results with and without an additional waypoint were virtually identical, presumably because the employed anatomical constraints already prevented the occurrence of the most implausible tracks. Irrespective of the employed tractography procedure, increased diffusivity and decreased anisotropy were found in the optic radiation of the MS patients compared to the controls. Keywords: Magnetic resonance imaging, Multiple sclerosis, Fiber tracking, Probabilistic tractography, Diffusion MRI, Optic radiation, AC

Real-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials

Ocrelizumab is a B cell-depleting drug widely used in relapsing-remitting multiple sclerosis (RRMS) and primary-progressive MS. In RRMS, it is becoming increasingly apparent that accumulation of disability not only manifests as relapse-associated worsening (RAW) but also as progression independent of relapse activity (PIRA) throughout the disease course. This study's objective was to investigate the role of PIRA in RRMS patients treated with ocrelizumab. We performed a single-center, retrospective, cross-sectional study of clinical data acquired at a German tertiary multiple sclerosis referral center from 2018 to 2022. All patients with RRMS treated with ocrelizumab for at least six months and complete datasets were analyzed. Confirmed disability accumulation (CDA) was defined as a ≥ 12-week confirmed increase from the previous expanded disability status scale (EDSS) score of ≥ 1.0 if the previous EDSS was ≤  5.5 or a ≥ 0.5-point increase if the previous EDSS was > 5.5. PIRA was defined as CDA without relapse since the last EDSS measurement and at least for the preceding 12 weeks. RAW was defined as CDA in an interval of EDSS measurements with ≥ 1 relapses. Cox proportional hazard models were used to analyze the probability of developing PIRA depending on various factors, including disease duration, previous disease-modifying treatments (DMTs), and optical coherence tomography-assessed retinal degeneration parameters. 97 patients were included in the analysis. Mean follow-up time was 29 months (range 6 to 51 months). 23.5% developed CDA under ocrelizumab therapy (n = 23). Of those, the majority developed PIRA (87.0% of CDA, n = 20) rather than RAW (13.0% of CDA, n = 3). An exploratory investigation using Cox proportional hazards ratios revealed two possible factors associated with an increased probability of developing PIRA: a shorter disease duration prior to ocrelizumab (p = 0.02) and a lower number of previous DMTs prior to ocrelizumab (p = 0.04). Our data show that in ocrelizumab-treated RRMS patients, the main driver of disability accumulation is PIRA rather than RAW. Furthermore, these real-world data show remarkable consistency with data from phase 3 randomized controlled trials of ocrelizumab in RRMS, which may increase confidence in translating results from tightly controlled RCTs into the real-world clinical setting