International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763

Cross-Sectional and Longitudinal MRI Brain Scans Reveal Accelerated Brain Aging in Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. By combining longitudinal MRI-based brain morphometry and brain age estimation using machine learning, we tested the hypothesis that MS patients have higher brain age relative to chronological age than healthy controls (HC) and that longitudinal rate of brain aging in MS patients is associated with clinical course and severity. Seventy-six MS patients [71% females, mean age 34.8 years (range 21–49) at inclusion] were examined with brain MRI at three time points with a mean total follow up period of 4.4 years (±0.4 years). We used additional cross-sectional MRI data from 235 HC for case-control comparison. We applied a machine learning model trained on an independent set of 3,208 HC to estimate individual brain age and to calculate the difference between estimated and chronological age, termed brain age gap (BAG). We also assessed the longitudinal change rate in BAG in individuals with MS. MS patients showed significantly higher BAG (4.4 ± 6.6 years) compared to HC (Cohen's D = 0.69, p = 4.0 × 10−6). Longitudinal estimates of BAG in MS patients showed high reliability and suggested an accelerated rate of brain aging corresponding to an annual increase of 0.41 (SE = 0.15) years compared to chronological aging (p = 0.008). Multiple regression analyses revealed higher rate of brain aging in patients with more brain atrophy (Cohen's D = 0.86, p = 4.3 × 10−15) and increased white matter lesion load (WMLL) (Cohen's D = 0.55, p = 0.015). On average, patients with MS had significantly higher BAG compared to HC. Progressive brain aging in patients with MS was related to brain atrophy and increased WMLL. No significant clinical associations were found in our sample, future studies are warranted on this matter. Brain age estimation is a promising method for evaluation of subtle brain changes in MS, which is important for predicting clinical outcome and guide choice of intervention

Creating a learning space: Using experiential learning and creativity in the teaching and learning of social pedagogy

This reflective account has been co-developed, produced and written by students and the teaching staff on the BA Hons Social Pedagogy, Advocacy, and Participation degree at the University of Central Lancashire. The account focuses on the use of experiential and creative teaching methods utilised on the course and how this enhances the understanding and application of social pedagogy. The article critically analyses the link between how the social pedagogical theories, concepts and methods are taught and the advancement of the student and lecturer understanding of this field of study. In developing this reflective account, the current student cohort and lecturers were given the opportunity to participate in a collaborative reflection across all years of the course. They discussed their own learning journey and how this has shaped development of creativity within their practice. During the discussions around the use of blended, experiential learning and creativity, three key themes emerged: (1) the importance of the environment on creativity and learning; (2) the importance of relationships, creativity and learning; and (3) Haltung, psychological safety and creativity. In the reflections on what they have learned so far, the students and lecturers hope to inspire other education providers to use creative and experiential teaching methods within their courses. The authors feel that the reflective account contains useful information around the learning that has taken place over the last three years of this course being taugh

Impact of treatment on cellular immunophenotype in MS: a cross-sectional study

OBJECTIVE: To establish cytometry profiles associated with disease stages and immunotherapy in MS. METHODS: Demographic/clinical data and peripheral blood samples were collected from 227 patients with MS and 82 sex- and age-matched healthy controls (HCs) enrolled in a cross-sectional study at 4 European MS centers (Spain, Italy, Germany, and Norway). Flow cytometry of isolated peripheral blood mononuclear cells was performed in each center using specifically prepared antibody-cocktail Lyotubes; data analysis was centralized at the Genoa center. Differences in immune cell subsets were assessed between groups of untreated patients with relapsing-remitting or progressive MS (RRMS or PMS) and HCs and between groups of patients with RRMS taking 6 commonly used disease-modifying drugs. RESULTS: In untreated patients with MS, significantly higher frequencies of Th17 cells in the RRMS population compared with HC and lower frequencies of B-memory/B-regulatory cells as well as higher percentages of B-mature cells in patients with PMS compared with HCs emerged. Overall, the greatest deviation in immunophenotype in MS was observed by treatment rather than disease course, with the strongest impact found in fingolimod-treated patients. Fingolimod induced a decrease in total CD4(+) T cells and in B-mature and B-memory cells and increases in CD4(+) and CD8(+) T-regulatory and B-regulatory cells. CONCLUSIONS: Our highly standardized, multisite cytomics data provide further understanding of treatment impact on MS immunophenotype and could pave the way toward monitoring immune cells to help clinical management of MS individuals

Are all prognostic factors in parotid gland carcinoma well recognized?

The aim of his study was to assess the treatment results and prognostic factors in patients with parotid gland carcinoma. The material consisted of 109 patients treated surgically, with or without complementary radiotherapy, between 1978 and 2008 (follow-up at least 5-years). 5-year overall and disease-specific survival were observed in 57.0% of the patients and 5-year disease-free survival was achieved in 50.0%. Univariate analysis including ten clinical and pathological features to assess their prognostic value was done. Parapharyngeal space invasion, facial nerve palsy, and high grade of tumor malignancy were the factors with the highest influence on the treatment results, because their presence decreased the chance for recovery 9.8, 9.7, and 8.2 times, respectively. Histologically positive cervical lymph nodes and extraparenchymal extension were the other factors connected with poor prognosis (prognosis worse 6.7 and 5.4 times, respectively). Clinically positive cervical lymph nodes, positive/uncertain microscopic margin, involvement of the deep lobe, or the whole gland increased the risk of treatment failure 3.4, 3.1, and 2.8, respectively. The age ≥60 years and male gender were statistically significant factors, correlated with poor prognosis and decreased chance for recovery 2.4 and 2.6 times. T-status and clinical stage had important influence on 5-year disease-free survival rate because there were significant differences in the treatment results between individual stages. Multivariate analysis proved that the independent prognostic value, among anatomic structures involved by the neoplasm, had mandible, facial nerve, and skin infiltration. Among tumor-related factors, T-stage and grade had the statistically significant influence on treatment results, and stage and lymph nodes metastases among clinical and pathological features. These results confirm the value of actually used TNM classification (2002). Although the parapharyngeal space invasion is a factor, which seems to have a significant, poor prognostic value, it was not included in this classification

Prognostic value of single-subject grey matter networks in early multiple sclerosis

The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict five-year EDSS progression in patients with relapsing-remitting MS (RRMS). We hypothesized that network measures, derived from magnetic resonance imaging (MRI), outperform conventional MRI measurements at identifying patients at risk of developing disability progression. This longitudinal, multicentre study within the Magnetic Resonance Imaging in MS (MAGNIMS) network included 406 patients with RRMS (mean age = 35.7 ± 9.1 years) followed up for five years (mean follow-up = 5.0 ± 0.6 years). Expanded Disability Status Scale (EDSS) was determined to track disability accumulation. A group of 153 healthy subjects (mean age = 35.0 ± 10.1 years) with longitudinal MRI served as controls. All subjects underwent MRI at baseline and again one year after baseline. Grey matter (GM) atrophy over one year and white matter (WM) lesion load were determined. A single-subject brain network was reconstructed from T1-weighted scans based on GM atrophy measures derived from a statistical parameter mapping (SPM)-based segmentation pipeline. Key topological measures, including network degree, global efficiency and transitivity, were calculated at single-subject level to quantify network properties related to EDSS progression. Areas under receiver operator characteristic (ROC) curves were constructed for GM atrophy, WM lesion load and the network measures, and comparisons between ROC curves were conducted. The applied network analyses differentiated patients with RRMS who experience EDSS progression over five years through lower values for network degree [H(2)=30.0, p<0.001] and global efficiency [H(2)=31.3, p<0.001] from healthy controls but also from patients without progression. For transitivity, the comparisons showed no difference between the groups (H(2)= 1.5, p=0.474). Most notably, changes in network degree and global efficiency were detected independent of disease activity in the first year. The described network reorganization in patients experiencing EDSS progression was evident in the absence of GM atrophy. Network degree and global efficiency measurements demonstrated superiority of network measures in the ROC analyses over GM atrophy and WM lesion load in predicting EDSS worsening (all p-values < 0.05). Our findings provide evidence that GM network reorganization over one year discloses relevant information about subsequent clinical worsening in RRMS. Early GM restructuring towards lower network efficiency predicts disability accumulation and outperforms conventional MRI predictors

Current treatment practice of Guillain-Barré syndrome

Objective: To define the current treatment practice of Guillain-Barré syndrome (GBS). Methods: The study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account. Results: We excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE. Conclusions: In current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.publishedVersio