From Diagnosis to Satisfaction in Multiple Sclerosis: A Swiss Patient Survey Highlighting the Importance of the First Diagnostic Consultation

Background: An early treatment start with disease modifying therapies (DMT) and long-term adherence is crucial in the treatment of people with multiple sclerosis (PwMS) to prevent future disability. Objectives: To gain information on the diagnostic process, decision making, treatment start and adherence with regard to DMT as well as satisfaction in PwMS in Switzerland to optimize management of PwMS. Methods: A survey was conducted between June 2017 and March 2018 in six hospital-based MS centres and eight private practices in Switzerland. PwMS according to the 2010 McDonald criteria, aged 18–60 years, having a clinical isolated syndrome, relapsing remitting MS, or secondary progressive MS were eligible. The survey contained 40 questions, covering participants’ background and circumstances, treatment decisions, therapy start, treatment adherence, and satisfaction (EKNZ Req-2016-00701). Results: 212 questionnaires were returned for analysis. Of these, 125 (59.0%) were answered by patients treated by practice-based neurologists and 85 (40.1%) by patients treated in hospitals. That PwMS were satisfied overall with current medical care, that they were free of relapses and disease progression, and that they were able to live independently were the main goals of patients. Satisfaction was reflected by an early therapy start and a high adherence to DMT in our cohort. The treating neurologist played a major role in this regard. Furthermore, a satisfactory first diagnostic consultation (FDC) was crucial for successful long-term patient care positively influencing an early treatment start, longer duration of the initial therapy, as well as adherence to treatments and general satisfaction. Conclusion: The treating neurologist and especially a satisfactory FDC play a major role for the successful long-term treatment of PwMS. Detailed information on various aspects of the disease and time with the treating neurologist seems to be of major importance

Comparison of mRNA Vaccinations with BNT162b2 or mRNA-1273 in Anti-CD20-Treated Multiple Sclerosis Patients

Objective: Anti-CD20-treated patients are at risk of a reduced humoral immune response during the SARS-CoV-2 pandemic. Our aim was to compare the antibody response after two vaccinations with the mRNA vaccines BNT162b2 or mRNA-1273 in patients with multiple sclerosis. Methods: Data from the University Hospital of Bern and Cantonal Hospital of Lucerne were retrospectively collected from medical records and then analyzed. Anti-spike IgG serum titers were collected from both centers and were considered to be protective from a value of ≥100 AU/mL. Continuous variables were given as the mean and 95% confidence interval (95% CI); categorical variables were given as frequencies. A Mann–Whitney test and Fisher’s exact test as well as a multivariable linear regression analysis with anti-spike IgG (AU/mL) as the dependent variable were run using SPSS Statistic 25 (IBM Corp., Amonk, NY, USA). Results: A total of 74 patients were included; 41/74 (63.51%) were female patients and the mean age was 46.6 years (95% CI 43.4–49.9). Of these patients, 36/74 were vaccinated with BNT162b2 and 38/74 with mRNA-1273, following the national vaccination recommendation. In both vaccine groups, protective anti-spike IgG titers (≥100 AU/mL) were infrequently achieved (5/74: mRNA-1273 3/38; BNT162b2 2/36). Conclusions: In addition to a low rate of protective anti-spike IgG titers in both vaccine groups, we identified a drop in anti-spike IgG serum titers over time. This observation bears therapeutic consequences, as initial positive titers should be checked in case of an infection with the SARS-CoV-2 virus to identify patients who would benefit from an intravenous anti-spike IgG treatment against acute COVID-19

Multidimensional phenotyping of the post-COVID-19 syndrome: A Swiss survey study.

INTRODUCTION Post-COVID-19 syndrome affects approximately 10-25% of people after a COVID-19 infection, irrespective of initial COVID-19 severity. The aim of this project was to assess the clinical characteristics, course, and prognosis of post-COVID-19 syndrome using a systematic multidimensional approach. PATIENTS AND METHODS An online survey of people with suspected and confirmed COVID-19 and post-COVID-19 syndrome, distributed via Swiss COVID-19 support groups, social media, and our post-COVID-19 consultation, was performed. A total of 8 post-infectious domains were assessed with 120 questions. Data were collected from October 15 to December 12, 2021, and 309 participants were included. Analysis of clinical phenomenology of post-COVID-19 syndrome was performed using comparative statistics. RESULTS The three most prevalent post-COVID-19 symptoms in our survey cohort were fatigue (288/309, 93.2%), pain including headache (218/309, 70.6%), and sleep-wake disturbances (mainly insomnia and excessive daytime sleepiness, 145/309, 46.9%). Post-COVID-19 syndrome had an impact on work ability, as more than half of the respondents (168/268, 62.7%) reported an inability to work, which lasted on average 26.6 weeks (95% CI 23.5-29.6, range 1-94, n = 168). Quality of life measured by WHO-5 Well-being Index was overall low in respondents with post-COVID-19 syndrome (mean, 95% CI 9.1 [8.5-9.8], range 1-25, n = 239). CONCLUSION Fatigue, pain, and sleep-wake disturbances were the main symptoms of the post-COVID-19 syndrome in our cohort and had an impact on the quality of life and ability to work in a majority of patients. However, survey respondents reported a significant reduction in symptoms over 12 months. Post-COVID-19 syndrome remains a significant challenge. Further studies to characterize this syndrome and to explore therapeutic options are therefore urgently needed

Fatigue in Post-COVID-19 Syndrome: Clinical Phenomenology, Comorbidities and Association With Initial Course of COVID-19.

Introduction Post-COVID-19 syndrome affects approximately 10-25% of people suffering from COVID-19 infection, irrespective of initial COVID-19 severity. Fatigue is one of the major symptoms, occurring in 30-90% of people with post-COVID-19 syndrome. This study aims at describing factors associated with fatigue in people with Post-COVID-19 seen in our newly established Post-Covid clinic. Methods This retrospective single center study included 42 consecutive patients suffering from Post-COVID-19 syndrome treated at the Department of Neurology, University Hospital Bern, between 11/2020 and05/2021. Clinical phenomenology of Post-COVID-19 syndrome with a special focus on fatigue and risk factor identification was performed using Mann-Whitney U Test, Pearson Correlation, and Chi-Quadrat-Test. Results Fatigue (90.5%) was the most prevalent Post-COVID-19 symptom followed by depressive mood (52.4%) and sleep disturbance (47.6%). Fatigue was in mean severe (Fatigue severity scale (FSS) mean 5.5 points (95% Confidence interval (95CI) 5.1 - 5.9, range .9 - 6.9, n = 40), and it was unrelated to age, COVID-19 severity or sex. The only related factors with fatigue severity were daytime sleepiness and depressed mood. Conclusion Fatigue is the main symptom of the Post-COVID-19 syndrome in our cohort. Further studies describing this syndrome are needed to prepare the healthcare systems for the challenge of treating patients with Post-COVID-19 syndrome

Evaluation of diagnostic criteria and red flags of myelin oligodendrocyte glycoprotein encephalomyelitis in a clinical routine cohort.

AIMS Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been proposed to define "MOG encephalomyelitis" (MOG-EM), with published diagnostic and "red flag" criteria. We aimed to evaluate these criteria in a routine clinical setting. METHODS We retrospectively analyzed patients with borderline/positive MOG-IgG and applied the diagnostic and red flag criteria to determine likelihood of MOG-EM diagnosis. Para-/clinical parameters were described and analyzed with chi-square test. RESULTS In total, 37 patients fulfilled MOG-EM diagnostic criteria (female-to-male ratio: 1.6:1, median onset age: 28.0 years [IQR 18.5-40.5], n = 8 with pediatric onset). In 24/37, red flags were present, predominantly MOG-IgG at assay cutoff and/or MRI lesions suggestive of multiple sclerosis (MS). As proposed in the consensus criteria, these patients should rather be described as "possible" MOG-EM. Of these, we classified 13 patients as "unlikely" MOG-EM in the presence of the red flag "borderline MOG-IgG" with negative MOG-IgG retest or coincidence of ≥1 additional red flag. This group mainly consisted of patients diagnosed with MS (n = 11). Frequency of cerebrospinal fluid (CSF-)-specific oligoclonal bands (OCB) is significantly lower in definite vs possible and unlikely MOG-EM (P = .0005). CONCLUSION Evaluation of diagnostic and red flag criteria, MOG-IgG retesting (incl. change of assay), and CSF-specific OCB are relevant in clinical routine cohorts to differentiate MOG-EM from MS

Rebound After Fingolimod and a Single Daclizumab Injection in a Patient Retrospectively Diagnosed With NMO Spectrum Disorder—MRI Apparent Diffusion Coefficient Maps in Differential Diagnosis of Demyelinating CNS Disorders

Objective: Differential diagnosis of neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) or mimics can be challenging, especially in patients with atypical presentations and negative serostatus for aquaporin-4 antibodies (AQP4-Ab). This brief research report describes magnetic resonance imaging (MRI) findings focusing on quantitative apparent diffusion coefficient (ADC) histogram analysis as a potential tool to differentiate NMOSD from MS.Methods: Longitudinal MRI data obtained during routine clinical examinations were retrospectively analyzed in a patient with histologically determined cerebral NMOSD, a patient with an acute tumefactive MS lesion, and a patient with ischemic stroke. Histogram analyses of ADC maps were evaluated.Results: A patient diagnosed with MS experienced a severe rebound after fingolimod withdrawal and a single daclizumab injection. Cerebral NMOSD manifestation was confirmed by brain biopsy. However, the patient did not fulfill consensus criteria for NMOSD and was AQP4-Ab negative. Comparison of ADC histogram analyses of this patient with those from a patient with MS and one with ischemic stroke revealed differential ADC characteristics: namely a more pronounced and prolonged ADC leftward shift in inflammatory than in ischemic pathology, even more accentuated in NMOSD versus MS.Conclusion: ADC map histograms and ADC threshold values for different conditions may be useful for differentiation of large inflammatory brain lesions and further studies are merited

MINDS. Abundant water and varying C/O across the disk of Sz 98 as seen by JWST/MIRI

MIRI/MRS on board the JWST allows us to probe the inner regions of protoplanetary disks. Here we examine the disk around the classical T Tauri star Sz 98, which has an unusually large dust disk in the millimetre with a compact core. We focus on the H$_2$O emission through both its ro-vibrational and pure rotational emission. Furthermore, we compare our chemical findings with those obtained for the outer disk from Atacama Large Millimeter/submillimeter Array (ALMA) observations. In order to model the molecular features in the spectrum, the continuum was subtracted and LTE slab models were fitted. The spectrum was divided into different wavelength regions corresponding to H$_2$O lines of different excitation conditions, and the slab model fits were performed individually per region. We confidently detect CO, H$_2$O, OH, CO$_2$, and HCN in the emitting layers. The isotopologue H$^{18}_2$O is not detected. Additionally, no other organics, including C$_2$H$_2$, are detected. This indicates that the C/O ratio could be substantially below unity, in contrast with the outer disk. The H$_2$O emission traces a large radial disk surface region, as evidenced by the gradually changing excitation temperatures and emitting radii. The OH and CO$_2$ emission are relatively weak. It is likely that H$_2$O is not significantly photodissociated; either due to self-shielding against the stellar irradiation, or UV-shielding from small dust particles. The relative emitting strength of the different identified molecular features point towards UV-shielding of H$_2$O in the inner disk of Sz 98, with a thin layer of OH on top. The majority of the organic molecules are either hidden below the dust continuum, or not present. In general, the inferred composition points to a sub-solar C/O ratio (<0.5) in the inner disk, in contrast with the larger than unity C/O ratio in the gas in the outer disk found with ALMA.Comment: Submitted to A&A on May 25 2023. 18 pages, 11 figure

MINDS: The JWST MIRI Mid-INfrared Disk Survey

The study of protoplanetary disks has become increasingly important with the Kepler satellite finding that exoplanets are ubiquitous around stars in our galaxy and the discovery of enormous diversity in planetary system architectures and planet properties. High-resolution near-IR and ALMA images show strong evidence for ongoing planet formation in young disks. The JWST MIRI mid-INfrared Disk Survey (MINDS) aims to (1) investigate the chemical inventory in the terrestrial planet-forming zone across stellar spectral type, (2) follow the gas evolution into the disk dispersal stage, and (3) study the structure of protoplanetary and debris disks in the thermal mid-IR. The MINDS survey will thus build a bridge between the chemical inventory of disks and the properties of exoplanets. The survey comprises 52 targets (Herbig Ae stars, T Tauri stars, very low-mass stars and young debris disks). We primarily obtain MIRI/MRS spectra with high S/N (~100-500) covering the complete wavelength range from 4.9 to 27.9 {\mu}m. For a handful of selected targets we also obtain NIRSpec IFU high resolution spectroscopy (2.87-5.27 {\mu}m). We will search for signposts of planet formation in thermal emission of micron-sized dust - information complementary to near-IR scattered light emission from small dust grains and emission from large dust in the submillimeter wavelength domain. We will also study the spatial structure of disks in three key systems that have shown signposts for planet formation, TW Hya and HD 169142 using the MIRI coronagraph at 15.5 {\mu}m and 10.65 {\mu}m respectively and PDS70 using NIRCam imaging in the 1.87 {\mu}m narrow and the 4.8 {\mu}m medium band filter. ...Comment: accepted for publication in PAS

MINDS. The detection of 13^{13}CO2_{2} with JWST-MIRI indicates abundant CO2_{2} in a protoplanetary disk

We present JWST-MIRI MRS spectra of the protoplanetary disk around the low-mass T Tauri star GW Lup from the MIRI mid-INfrared Disk Survey (MINDS) GTO program. Emission from $^{12}$CO$_{2}$, $^{13}$CO$_{2}$, H$_{2}$O, HCN, C$_{2}$H$_{2}$, and OH is identified with $^{13}$CO$_{2}$ being detected for the first time in a protoplanetary disk. We characterize the chemical and physical conditions in the inner few au of the GW Lup disk using these molecules as probes. The spectral resolution of JWST-MIRI MRS paired with high signal-to-noise data is essential to identify these species and determine their column densities and temperatures. The $Q$-branches of these molecules, including those of hot-bands, are particularly sensitive to temperature and column density. We find that the $^{12}$CO$_{2}$ emission in the GW Lup disk is coming from optically thick emission at a temperature of $\sim$400 K. $^{13}$CO$_{2}$ is optically thinner and based on a lower temperature of $\sim$325 K, may be tracing deeper into the disk and/or a larger emitting radius than $^{12}$CO$_{2}$. The derived $N_{\rm{CO_{2}}}$/$N_{\rm{H_{2}O}}$ ratio is orders of magnitude higher than previously derived for GW Lup and other targets based on \textit{Spitzer}-IRS data. This high column density ratio may be due to an inner cavity with a radius in between the H$_{2}$O and CO$_{2}$ snowlines and/or an overall lower disk temperature. This paper demonstrates the unique ability of JWST to probe inner disk structures and chemistry through weak, previously unseen molecular features.Comment: 15 pages, 10 figures. Accepted to ApJ