Background and ObjectivesTo investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the... Show moreBackground and ObjectivesTo investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study.MethodsAlbuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/μL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%).ResultsIn 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25–0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27–0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/μL in 1,005 patients (83%), 5–49 cells/μL in 200 patients (16%), and ≥50 cells/μL in 13 patients (1%).DiscussionACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/μL, is compatible with GBS after a thorough exclusion of alternative diagnoses. Show less
Hiele, K. van der; Egmond, E.E.A. van; Gorp, D.A.M. van; Jongen, P.J.; Reneman, M.F.; Klink, J.J.L. van der; ... ; Visser, L.H. 2022
Previous research discovered a protective effect of higher conscientiousness against a 3-year deterioration in employment status in persons with multiple sclerosis (pwMS). To replicate these... Show morePrevious research discovered a protective effect of higher conscientiousness against a 3-year deterioration in employment status in persons with multiple sclerosis (pwMS). To replicate these findings, we used data from a multicentre prospective cohort study where 145 employed pwMS completed questionnaires, neurological and neuropsychological examinations at baseline and after 3 years. A 3-year deterioration in employment status was reported in 31.0%. We observed no differences in personality, demographics or clinical characteristics between pwMS with deteriorated or stable employment status. These null findings may be partly explained by the classification of deteriorated employment status, which does not reflect Dutch labour conditions. Show less
Egmond, E.E.A. van; Hiele, K. van der; Gorp, D.A.M. van; Jongen, P.J.; Klink, J.J.L. van der; Reneman, M.F.; ... ; Visser, L.H. 2022
Background Symptoms of anxiety and depression affect the daily life of people with multiple sclerosis (MS). This study examined work difficulties and their relationship with anxiety, depression and... Show moreBackground Symptoms of anxiety and depression affect the daily life of people with multiple sclerosis (MS). This study examined work difficulties and their relationship with anxiety, depression and coping style in people with MS. Methods 219 employed people with MS (median age = 43 years, 79% female) completed questionnaires on anxiety, depression, coping style, demographics and work difficulties, and underwent a neurological examination. Two regression analyses were performed with work difficulties as the dependent variable and either anxiety or depression as continuous independent variables. Coping style, age, gender, educational level, MS-related disability and disease duration were added as additional predictors, as well as interaction terms between coping style and either symptoms of depression or anxiety. Results A significant model was found (F-(10,F-205) = 13.14, p < 0.001, R-2 = 0.39) in which anxiety, emotion- and avoidance-oriented coping and MS-related disability were positively related to work difficulties. The analysis of depression resulted in a significant model (F-(10,F-205) = 14.98, p < 0.001, R-2 = 0.42) in which depression, emotion- and avoidance-oriented coping and MS-related disability were positively related to work difficulties. None of the interaction effects were significant. Conclusions Work difficulties were positively related to anxiety, depression, emotion- and avoidance-oriented coping and MS-related disability in workers with MS. Show less
Background and ObjectivesThe clinical course and outcome of the Guillain-Barre syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data... Show moreBackground and ObjectivesThe clinical course and outcome of the Guillain-Barre syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity.MethodsWe used prospective data from the first 1,500 patients included in IGOS, aged >= 6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors.ResultsFor validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort.DiscussionmEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, also in countries outside the Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America.Classification of EvidenceThis study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS. Show less
Ballegooijen, H. van; Hiele, K. van der; Enzinger, C.; Voer, G. de; Visser, L.H. 2022
Purpose This study aimed to identify mental health, physical health, demographic and disease characteristics relating to work productivity in people with multiple sclerosis (MS). Methods In this... Show morePurpose This study aimed to identify mental health, physical health, demographic and disease characteristics relating to work productivity in people with multiple sclerosis (MS). Methods In this cross-sectional study, 236 employed people with MS (median age = 42 years, 78.8% female) underwent neurological and neuropsychological assessments. Additionally, they completed questionnaires inquiring about work productivity (presenteeism: reduced productivity while working, and absenteeism: loss of productivity due to absence from work), mental and physical health, demographic and disease characteristics. Multiple linear and logistic regression analyses were performed with presenteeism and absenteeism as dependent variables, respectively. Results A model with mental and physical health factors significantly predicted presenteeism F(11,202) = 11.33, p < 0.001, R-2 = 0.38; a higher cognitive (p < 0.001) and physical impact (p = 0.042) of fatigue were associated with more presenteeism. A model with only mental health factors significantly predicted absenteeism; chi(2)(11)=37.72, p < 0.001, with R-2 = 0.27 (Nagelkerke) and R-2 = 0.16 (Cox and Snell). Specifically, we observed that more symptoms of depression (p = 0.041) and a higher cognitive impact of fatigue (p = 0.011) were significantly associated with more absenteeism. Conclusions In people with MS, both cognitive and physical impact of fatigue are positively related to presenteeism, while symptoms of depression and cognitive impact of fatigue are positively related to absenteeism. Show less
In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barre syndrome (GBS), have... Show moreIn the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barre syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies.The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization.Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12-22).Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not. Show less
Hiele, K. van der; Gorp, D.A.M. van; Egmond, E.E.A. van; Jongen, P.J.; Reneman, M.F.; Klink, J.J.L. van der; ... ; Visser, L.H. 2021
Background: Multiple sclerosis (MS) poses a major threat to sustainable employability. Identifying conditions and factors that promote work participation is of great importance. Our objective was... Show moreBackground: Multiple sclerosis (MS) poses a major threat to sustainable employability. Identifying conditions and factors that promote work participation is of great importance. Our objective was to explore the contribution of personality traits in explaining occupational functioning in MS. Methods: 241 participants with relapsing-remitting MS (78% female, median age: 42.0 years, median EDSS: 2.0) and 60 healthy controls (70% female, median age: 45.0 years) underwent neuropsychological and neurological examinations and completed questionnaires. Multivariate logistic and linear regression analyses were conducted to examine relations between personality traits and self-reported occupational functioning, while accounting for known correlates. Results: Personality traits were not associated with self-reported occupational functioning when correcting for known correlates. A higher impact of fatigue (B = -0.05, p = .005 and B = -0.04, p = .009) and depression (B = -0.22, p = .008 and B = -0.21, p = .01) were associated with no paid job (R2 = 0.13) and considering to reduce work hours (R2 = 0.12). A higher impact of fatigue (B = -0.05, p = .008, beta = 0.46, p = .001 and beta = -0.36, p = .001) was associated with absenteeism from work (R2 = 0.15), more presenteeism (R2 = 0.35) and lower work ability (R2 = 0.25). A higher impact of fatigue (beta = 0.46, p = .001) and anxiety (beta = 0.25, p = .001) were associated with more work difficulties (R2 = 0.54). Conclusion: Personality traits did not explain additional variance in self-reported occupational functioning in persons with relapsing-remitting MS with mild disability. The impact of fatigue was the main and most consistent correlate of occupational functioning, often combined with depression or anxiety. Total explained variance of the Show less
Hiele, K. van der; Gorp, D.A.M. van; Egmond, E.E.A. van; Jongen, P.J.; Reneman, M.F.; Van der Klink, J.; ... ; Visser, L.H. 2021
Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients... Show moreBackground Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome.Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of >= 6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis.Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1.4 (95% CI 0.6-3.3; p=0.45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation).Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Show less
Hiele, K. van der; Egmond, E.E.A. van; Jongen, P.J.; Klink, J.J.L. van der; Beenakker, E.A.C.; Eijk, J.J.J. van; ... ; Visser, L.H. 2020
Background: Recent studies report deficits in social cognition in individuals with multiple sclerosis (MS). Social cognitive skills such as empathy are important for adequate social and... Show moreBackground: Recent studies report deficits in social cognition in individuals with multiple sclerosis (MS). Social cognitive skills such as empathy are important for adequate social and occupational functioning. Our objectives are: (1) to examine whether empathy differs between individuals with MS and healthy controls, (2) to examine relations between empathy and cognitive, psychological and occupational functioning. Methods: 278 individuals with MS (relapsing-remitting subtype) and 128 healthy controls from the MS@Work study participated in this investigation. The participants completed questionnaires about demographics, cognitive, psychological and occupational functioning, and underwent neurological and neuropsychological examinations. Mann-Whitney U-tests were used to examine group differences in empathy. Pearson and Spearman rank correlation analyses were used to examine relations between empathy and the other measures. Results: Empathy did not differ between individuals with MS and healthy controls. In individuals with MS, higher empathy was correlated with a higher educational level (X-2(df) = 13.2(2), p = 0.001), better verbal learning (r = 0.20, p = 0.001), less symptoms of depression (r=-0.21, p = 0.001), higher extraversion (r = 0.25, p <= 0.001), agreeableness (r = 0.55, p <= 0.001) and conscientiousness ( r = 0.27, p <= 0.001) and better occupational functioning in terms of work scheduling and output demands (r = 0.23, p = 0.002) and less cognitive/psychological work barriers (r = -0.21, p = 0.001). In healthy controls, higher empathy was correlated with less symptoms of depression (r = -0.34, p <= 0.001), less fatigue (r = -0.37, p <= 0.001), higher agreeableness (r = 0.59, p <= 0.001) and better occupational functioning in terms of work ability as compared to lifetime best (r = 0.28, p = 0.001) and less cognitive/psychological work barriers (r = -0.34, p <= 0.001). Empathy did not differ between unemployed and employed individuals with MS or healthy controls. Conclusion: Empathy did not differ between individuals with MS and healthy controls. Within both investigated groups, higher empathy was weakly to moderately correlated with less symptoms of depression, higher agreeableness and better occupational functioning. We also found unique correlations for empathy within the investigated groups. Longitudinal studies are needed to further examine social cognition in relation to cognitive, psychological and occupational functioning in both individuals with MS and healthy controls. It would be particularly interesting to concurrently examine changes in the brain network involved with social cognition. Show less
Dongen, L. van; Westerik, B.; Hiele, K. van der; Visser, L.H.; Schoonheim, M.M.; Douw, L.; ... ; Hulst, H.E. 2019
ObjectiveTo define the current treatment practice of Guillain-Barre syndrome (GBS).MethodsThe study was based on prospective observational data from the first 1,300 patients included in the... Show moreObjectiveTo define the current treatment practice of Guillain-Barre syndrome (GBS).MethodsThe 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.ResultsWe 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.ConclusionsIn 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. Show less
Gorp, D.A.M. van; Hiele, K. van der; Middelkoop, H.A.M.; Visser, L.H. 2019
Background: Cognitive dysfunction is increasingly being recognized as an important limiting factor in work participation in patients with multiple sclerosis. This literature review provides a... Show moreBackground: Cognitive dysfunction is increasingly being recognized as an important limiting factor in work participation in patients with multiple sclerosis. This literature review provides a description, synthesis and interpretation of the existing literature and identifies gaps in current knowledge.Methods: Papers published between 1970 and April 2017 were included. Clinical trials, randomized controlled trials or observational quantitative studies in which data on cognitive factors associated with employment, work functioning or work-related problems were reported. Papers were manually double checked by two blinded reviewers.Results: A total of 41 papers were included of which 4 described prospective, longitudinal studies. The majority of studies reported positive associations between cognitive functioning and work outcomes (38/41 studies; 93%). Positive associations were found between work outcomes and global cognitive functioning (8/9 studies; 89%), language (8/17 studies; 47%), processing speed/ working memory (23/26 studies; 88%),new learning and memory (12/22 studies; 55%), executive functioning (10/17; 59%), intelligence (1/6; 17%) and self-reported cognitive functioning (14/15; 93%). None of the reviewed studies found a relation between visuospatial processing and work outcomes (0/8; 0%). Models including cognitive measures as well as demographic (age, education), neurological (disability, fine motor coordination, disease course), and psychological variables (depression, personality, fatigue) best predicted work outcomes.Conclusion: By conducting this review we found ample evidence that objective cognitive functioning (specifically processing speed/ working memory and executive functioning) and self-reported cognitive functioning are important independent associates of work outcomes and these factors should be addressed by healthcare professionals. Future research could benefit from a focus on longitudinal changes in cognition and its relation to work outcomes. Show less
Hiele, K. van der; Gorp, D.A.M. van; Heerings, M.A.P.; Jongen, P.J.; Van der Klink, J.J.L.; Beenakker, E.A.C.; ... ; Visser, L.H. 2019
