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In this study we sought to determine whether axonal damage in severe Guillain-Barré syndrome (GBS) was secondary to critical illness polyneuropathy (CIP) in the intensive care unit (ICU) by reviewing comorbidities in patients who had initial and follow-up electromyographic (EMG) studies. Patients were classified as demyelinating (EMG-D) or axonal (EMG-A) according to findings on the second EMG. A critical illness (CI) score, derived from components of the APACHE II score, assessed the severity of critical illness in the ICU. Forty-one patients were admitted to the ICU and had a follow-up EMG. Of these, 28 (68%) developed an EMG-A pattern. There was no difference in the timing of the second EMG (mean, 23 days) between the two groups. The mean CI score (10.7 for EMG-A vs. 9.2 for EMG-D, P = 0.47) and frequency of sepsis (89% vs. 77%, P = 0.36) were similar between the groups. Mean strength (0-100, Medical Research Council scale) and Hughes disability scores for the EMG-A group were significantly worse at admission, nadir, and discharge. EMG-A patients had significantly more days on the ventilator (25 vs. 11), in the ICU (26 vs. 15), and in the hospital (29 vs. 18). Sixty-eight percent of patients with GBS in the ICU developed axon loss, but this was not related to the usual precipitants of CIP. Muscle Nerve 39: 10-15, 2009. [ABSTRACT FROM AUTHOR]

Objective: To assess the frequency of additional causes of distal sensory polyneuropathy (DSP) in patients with diabetes mellitus (DM).Methods: Retrospective review of patients with DM and DSP during a 5 year period. A quantitative sensory score (QSS) was determined at the initial evaluation and extensive laboratory and EMG studies were performed. Patients with one or more potential causes for DSP were compared to those with DM alone.Results: Fifty five patients (53%) had potential additional causes for DSP. These included: neurotoxic medications (seven), alcohol abuse (six), and B12 deficiency and renal disease (four each). The most common laboratory abnormalities were: abnormally low levels of vitamin B6 (11) or B1 (10), monoclonal gammopathy (eight), and hypertriglyceridaemia (eight). Twenty six (25%) subjects had more than one additional cause. Nine (9%) had three or more demyelinating features on EMG. There was a trend toward a lower QSS score (p = 0.05) and reduced mean amplitude of the sensory potentials in those with additional causes. Those with additional causes more often had upper limb sensory symptoms (p = 0.001) and sensory findings (p = 0.003).Conclusion: There was a high frequency of additional sources of DSP in patients with DM. These patients more often had sensory symptoms and findings in the hands. Tests that may be useful in the evaluation of DSP in diabetic patients include measures of vitamins B1, B6, B12, serum triglycerides, and immunofixation. [ABSTRACT FROM AUTHOR]

Background: Tanezumab, a humanized anti-nerve growth factor antibody, was developed for the treatment of pain associated with osteoarthritis. Due to its mechanism of action, peripheral nerve safety was assessed in all clinical studies., Objectives: To summarize the neurological safety of intravenous (IV) and subcutaneous (SC) tanezumab versus placebo in patients with osteoarthritis., Methods: Data were pooled from 3389 patients across seven studies that investigated IV administration, and from 1840 patients across three studies that investigated SC administration. The treatment period of each study ranged from 16 to 24 weeks, and follow-up periods ranged from 8 to 24 weeks. Neurological safety evaluations focused on adverse events (AEs) of abnormal peripheral sensation (APS), neurologic examinations, and consultations., Results: Across datasets, the incidence of AEs of APS was higher in tanezumab groups versus placebo. Paresthesia and hypoesthesia were the most frequently reported AEs in tanezumab-treated patients, compared with placebo. In both datasets, most AEs were of mild severity, resolved, and rarely resulted in discontinuation. In all treatment groups in both IV and SC studies, over 90% of patients had no new or worsened neurological examination abnormalities at the last study visit. Across datasets, mononeuropathy was diagnosed more frequently in tanezumab groups compared with placebo. Polyneuropathy was diagnosed in ≤ 0.9% of patients in tanezumab and placebo groups., Conclusions: Tanezumab IV or SC had an increased incidence of AEs of APS, such as paresthesia and hypoesthesia, and diagnoses of mononeuropathy compared with placebo. However, tanezumab was not associated with generalized peripheral neuropathy., Gov Identifiers: NCT00733902, NCT00744471, NCT00830063, NCT00863304, NCT00863772, NCT01089725, NCT00985621, NCT02697773, and NCT02709486., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background and Objectives: To 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., Methods: Albuminocytologic 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%)., Results: In 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%)., Discussion: ACD 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., Classification of Evidence: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS., (© 2023 American Academy of Neurology.)

Background: This study aimed to determine the clinical and diagnostic factors associated with mechanical ventilation (MV) in Guillain-Barré syndrome (GBS) and to simplify the existing Erasmus GBS Respiratory Insufficiency Score (EGRIS) for predicting the risk of MV., Methods: Data from the first 1500 patients included in the prospective International GBS Outcome Study (IGOS) were used. Patients were included across five continents. Patients <6 years and patients from Bangladesh were excluded. Univariable logistic and multivariable Cox regression were used to determine which prespecified clinical and diagnostic characteristics were associated with MV and to predict the risk of MV at multiple time points during disease course., Results: 1133 (76%) patients met the study criteria. Independent predictors of MV were a shorter time from onset of weakness until admission, the presence of bulbar palsy and weakness of neck flexion and hip flexion. The modified EGRIS (mEGRIS) was based on these factors and accurately predicts the risk of MV with an area under the curve (AUC) of 0.84 (0.80-0.88). We internally validated the model within the full IGOS cohort and within separate regional subgroups, which showed AUC values of 0.83 (0.81-0.88) and 0.85 (0.72-0.98), respectively., Conclusions: The mEGRIS is a simple and accurate tool for predicting the risk of MV in GBS. Compared with the original model, the mEGRIS requires less information for predictions with equal accuracy, can be used to predict MV at multiple time points and is also applicable in less severely affected patients and GBS variants. Model performance was consistent across different regions., Competing Interests: Competing interests: BCJ received grants from Grifols, CSL-Behring, Annexon, Prinses Beatrix Spierfonds, Baxalta, Hansa Biopharma, Roche, Horizon 2000 and GBS-CIDP Foundation International and is on the Global Medical Advisory Board of the GBS CIDP Foundation International. BCJ received consultance fees from Roche for activities outside the current study. KCG provides consulting services for Annexon, Argenx, Janssen, Pfizer, Roche and UCB Pharma, and participates on date safety monitoring boards or advisory boards from Annexon, Argenx, Janssen, Immunopharma and Roche. MMD received grants from Alexion, Alnylam Pharmaceuticals, Amicus, Biomarin, Bristol-Myers Squibb, Catalyst, Corbus, CSL-Behring, FDA/OOPD, GlaxoSmithKline, Genentech, Grifols, Kezar, Mitsubishi Tanabe Pharma, MDA, NIH, Novartis, Octapharma, Orphazyme, Ra Pharma/UCB, Sanofi Genzyme, Sarepta Therapeutics, Shire Takeda, Spark Therapeutics, The Myositis Association, UCB Biopharma/RaPharma, Viromed/Healixmith & TMA; MMD received consult fees from Amazentis, ArgenX, Catalyst, Cello, Covance/Labcorp, CSL-Behring, EcoR1, Janssen, Kezar, Medlink, Momenta, NuFactor, Octapharma, RaPharma/UCB, Roivant Sciences Inc, Sanofi Genzyme, Shire Takeda, Scholar Rock, Spark Therapeutics, Abata/Third Rock, UCB Biopharma and UpToDate; MMD received payment or honoraria for lectures/presentations from AAN, AANEM, Medlink, SANAM2022, CATALYST, SPARK, OCTOPHARMA, CSL-Behring; MMD participated in the data safety monitoring boards of Covance/LabCorp DMC and advisory boards of Sanofi, Argenx, Takeda and Janssen. SK received grants and honoraria for speech from Teijin, Nihon Pharm and the Japan Blood Products Organization. YY received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Teijin and CSL Behring., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Infections play a key role in the development of Guillain-Barré syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale., Methods: We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with Campylobacter jejuni , hepatitis E virus, Mycoplasma pneumoniae , cytomegalovirus, and Epstein-Barr virus., Results: Serologic evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%), and Epstein-Barr virus in 7 (1%) patients. Evidence of more than 1 recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiologic subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni -positive patients were more severely affected, indicated by a lower Medical Research Council sum score at nadir ( p = 0.004) and a longer time to regain the ability to walk independently ( p = 0.005). The pure motor variant and axonal electrophysiologic subtype were more frequent in Asian compared with American or European C. jejuni -positive patients ( p < 0.001, resp. p = 0.001). Time to nadir was longer in the cytomegalovirus-positive patients ( p = 0.004)., Discussion: Across geographical regions, the distribution of infections was similar, but the association between infection and clinical phenotype differed. A mismatch between symptom reporting and serologic results and the high frequency of coinfections demonstrate the importance of broad serologic testing in identifying the most likely infectious trigger. The association between infections and outcome indicates their value for future prognostic models., (© 2022 American Academy of Neurology.)

Objective: This study aimed to validate the Erasmus Guillain-Barré Syndrome Respiratory Insufficiency Score in the International Guillain-Barré Syndrome Outcome Study cohort, and to improve its performance and region-specificity., Methods: We examined data from the first 1,500 included patients, aged ≥6 years and not ventilated prior to study entry. Patients with a clinical variant or mild symptoms were also included. Outcome was mechanical ventilation within the first week from study entry. Model performance was assessed regarding the discriminative ability (area under the receiver operating characteristic curve) and the calibration (observed vs predicted probability of mechanical ventilation), in the full cohort and in Europe/North America and Asia separately. We recalibrated the model to improve its performance and region-specificity., Results: In the group of 1,023 eligible patients (Europe/North America n = 842, Asia n = 104, other n = 77), 104 (10%) required mechanical ventilation within the first week from study entry. Area under the curve values were ≥0.80 for all validation subgroups. Mean observed proportions of mechanical ventilation were lower than predicted risks: full cohort 10% versus 21%, Europe/North America 9% versus 21%, and Asia 17% versus 23%. After recalibration, predicted risks for the full cohort and Europe/North America corresponded to observed proportions., Interpretation: This prospective, international cohort study validated the Erasmus Guillain-Barré Syndrome Respiratory Insufficiency Score, and showed that the model can be used in the full spectrum of Guillain-Barré syndrome patients. In addition, a more accurate, region-specific version of the model was developed for patients from Europe/North America. ANN NEUROL 2022;91:521-531., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To assess the long-term neurological safety of tanezumab, a monoclonal antibody against nerve growth factor., Methods: Patients with osteoarthritis of the hip or knee received stable doses of oral nonsteroidal anti-inflammatory drugs (NSAIDs) before study entry and during a ≤ 37-day screening period. Patients were randomized 1:1:1 to double-dummy tanezumab (2.5 mg or 5 mg, subcutaneous every 8 weeks) or oral NSAIDs (twice-daily) for 56 weeks, with a 24-week follow-up. Neurological safety evaluation focused on peripheral and sympathetic adverse events (AEs), neurologic examinations, and consultations with blinded, external diagnostic reviews., Results: During the treatment period, 6.2%, 9.0%, and 4.6% of patients experienced AEs of abnormal peripheral sensation (APS) in the tanezumab 2.5 mg, 5 mg, and NSAID groups, respectively. Hypoesthesia, paresthesia, and carpal tunnel syndrome were the most common AEs of APS. Clinically significant worsening on examination occurred in <1% in any treatment group at the last study assessment. Diagnoses following external neurological consultation included mononeuropathy (1.3%, 2.1%, and 1.0%), radiculopathy (0.9%, 0.4%, and 0.5%), and polyneuropathy (0.3%, 0.5%, and 0%) in tanezumab 2.5 mg, 5 mg, and NSAID groups, respectively. AEs potentially associated with sympathetic neuropathy were reported for 1.8%, 2.3%, and 2.9% of patients in the tanezumab 2.5 mg, 5 mg, and NSAID groups, respectively. No patient was diagnosed with sympathetic neuropathy., Conclusion: Tanezumab had an increased incidence of AEs of APS versus NSAID; these were typically mild/moderate in severity, resolved during the study, and rarely resulted in discontinuation. Tanezumab was not associated with peripheral neuropathy and did not adversely affect the sympathetic nervous system., Trial Registration: ClinicalTrials.gov Identifier NCT02528188 (https://clinicaltrials.gov/ct2/show/NCT02528188)., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: The clinical course and outcome of the Guillain-Barré 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., Methods: We 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., Results: For 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., Discussion: mEGOS 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 Evidence: This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS., Trial Registration Information: NCT01582763., (© 2021 American Academy of Neurology.)

Objective: To compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only., Methods: We selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis., Results: Of 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms., Conclusion: In patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS., Competing Interests: Competing interests: DRC is a consultant to Amgen, Annexon Biosciences, argenx SE, Biotest Pharmaceuticals, Boehringer Ingelheim, Cigna Health Management, CSL Behring, Grifols S.A., Neuropore, New Enterprise Associates, Octapharma AG, Passage Bio, Pfizer, Pharnext SAS, Polyneuron Pharmaceuticals, Sanofi-Aventis, Seattle Genetics and UCB Pharma. He is on Data Safety Monitoring Boards for Alnylam Pharmaceuticals, Anavex Life Sciences, PledPharma AB, Momenta Pharma, Hansa Medical AB and Mitsubishi Tanabe Pharma Corporation. He receives royalties for Technology Licensing from AstraZeneca Pharmaceuticals, LP, Genentech, Levicept, Seattle Genetics, Merrimack Pharmaceuticals, Disarm Therapeutics. RACH has consultancies with Hansa Biopharma, Immunic and Sanofi. PAvD has received honoraria for consulting, lectures and serving on steering committees from Octapharma, Kedrion, CSL Behring, Grifols and Hansa (all honoraria to departmental research fund) and received grants from the Prinses Beatrix Spierfonds, Sanquin Blood supply, Shire and Grifols for conducting clinical trials in GBS and CIDP. MPL is supported by the by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. KCG has consulting agreements with Annexon, Argenx and UCB Pharma. BCJ has received funding for research projects from Prinses Beatrix Spierfonds, Horizon 2020, GBS-CIDP Foundation International, Grifols, CSL Behring, Annexon and Hansa Biopharma. He is on the Medical Advisory Board for the GBS-CIDP Foundation International, and a member of the Inflammatory Neuropathy Consortium., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The objective of this study was to explore the extent of IV immunoglobulin (IVIG) treatment-related fluctuations (TRFs) by using home collection of daily grip strength in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to use that information to develop evidence-based treatment optimization strategies., Methods: This prospective observational study included 25 patients with well-defined CIDP. Participants recorded grip strength daily for 6 months. Disability and gait metrics were collected weekly. Serum immunoglobulin G levels were obtained at peak, trough, and midcycle IVIG intervals. Day-to-day grip strength changes <10% were considered random. To identify patients with TRFs, 3-day averaged grip strength was calculated on each consecutive day after an IVIG infusion. TRFs were defined as ≥10% 3-day averaged grip strength difference compared to the pre-IVIG baseline., Results: Participants successfully recorded grip strength on all but 9% of recordable days. Twelve patients (48%) were classified as low/no fluctuaters and 13 (52%) as frequent fluctuaters. In the frequent fluctuating group, grip strength improved over 1 week and thereafter was relatively stable until the third week after infusion. Grip strength was significantly correlated with measures of disability., Conclusions: Grip strength collection by patients at home is reliable, valid, and feasible. A change in grip strength by ≥10% is a useful, practical, and evidence-based approach that may be used to identify clinically meaningful TRFs. From these data, we propose a treatment optimization strategy for patients with CIDP on chronic IVIG that may be applied to routine clinic care during both face-to-face and virtual video or telephone patient encounters., Trial Registration Information: ClinicalTrials.gov Identifier: NCT02414490., (© 2021 American Academy of Neurology.)

Objective: To compare disease course in patients with Guillain-Barré syndrome (GBS) with a poor prognosis who were treated with one or with two intravenous immunoglobulin (IVIg) courses., Methods: From the International GBS Outcome Study, we selected patients whose modified Erasmus GBS Outcome Score at week 1 predicted a poor prognosis. We compared those treated with one IVIg course to those treated with two IVIg courses. The primary endpoint, the GBS disability scale at 4 weeks, was assessed with multivariable ordinal regression., Results: Of 237 eligible patients, 199 patients received a single IVIg course. Twenty patients received an 'early' second IVIg course (1-2 weeks after start of the first IVIg course) and 18 patients a 'late' second IVIg course (2-4 weeks after start of IVIg). At baseline and 1 week, those receiving two IVIg courses were more disabled than those receiving one course. Compared with the one course group, the adjusted OR for a better GBS disability score at 4 weeks was 0.70 (95%CI 0.16 to 3.04) for the early group and 0.66 (95%CI 0.18 to 2.50) for the late group. The secondary endpoints were not in favour of a second IVIg course., Conclusions: This observational study did not show better outcomes after a second IVIg course in GBS with poor prognosis. The study was limited by small numbers and baseline imbalances. Lack of improvement was likely an incentive to start a second IVIg course. A prospective randomised trial is needed to evaluate whether a second IVIg course improves outcome in GBS., Competing Interests: Competing interests: CV, BvdB, EV, HL, KB, SHS, ZI report no disclosures. DRC is a consultant for Acetylon, Alcobra Pharma, Alnylam Pharmaceuticals, Annexon Biosciences, Akros Pharma, Biotest Pharmaceuticals, Boehringer Ingelheim, Cigna HealthManagement, CSL Behring, DP Clinical, Grifols, Hansa Medical, Karos Pharmaceuticals, Neurocrine Biosciences, Novartis, Octapharma, Pharnext, Seattle Genetics, Sun Pharmaceuticals, and Syntimmune. He is on the data and safety monitoring board for Sanofi, Pledpharma, Pfizer, Johnson Roche, Sanofi Genzyme, Teva,TG Therapeutics and UCB. GC has received honoraria from CSL Behring. BCJ has received funding for research projects from Prinses Beatrix Spierfonds, Horizon 2020,GBS-CIDP Foundation International, Grifols, CSL Behring and Annexon. He is on the Medical Advisory Board for the GBS-CIDP Foundation International, and a member of the Inflammatory Neuropathy Consortium. RH has current consultancies with LFB and former consultancies with Novartis. PvD has received honoraria for consulting, lectures and serving on steering committees from Octapharma, Kedrion, CSL Behring, Grifols, and Hansa (all honoraria to departmental research fund), and is currently receiving grants from Prinses Beatrix Spierfonds, Sanquin Blood supply, Shire and Grifols. He is President Elect of the Peripheral Nerve Society, member of the Inflammatory Neuropathy Consortium, Medical Advisory Board for the GBS-CIDP Foundation International, editorial board for the Journal of the Neurological Sciences and Journal of Neuromuscular Diseases. He is PI of the RCT investigating the effect of methylprednisolone in GBS (MP/IVIg RCT in GBS) and the RCT investigating the effect of a second dose IVIg in GBS (SID-GBS study)., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Guillain-Barré syndrome is a heterogeneous disorder regarding the clinical presentation, electrophysiological subtype and outcome. Previous single country reports indicate that Guillain-Barré syndrome may differ among regions, but no systematic comparative studies have been conducted. Comparative studies are required to identify factors determining disease susceptibility, variation and prognosis, and to improve diagnostic criteria. The International Guillain-Barré Syndrome Outcome Study is a prospective, observational cohort study including all patients within the diagnostic spectrum, aiming to describe the heterogeneity of Guillain-Barré syndrome worldwide. The current study was based on the first 1000 inclusions with a follow-up of at least 1 year and confirmed the variation in clinical presentation, course and outcome between patients. The full clinical spectrum of Guillain-Barré syndrome was observed in patients from all countries participating in the International Guillain-Barré Syndrome Outcome Study, but the frequency of variants differed between regions. We compared three regions based on geography, income and previous reports of Guillain-Barré syndrome subtypes: 'Europe/Americas', 'Asia' (without Bangladesh), and 'Bangladesh'. We excluded 75 (8%) patients because of alternative diagnoses, protocol violations, or missing data. The predominant clinical variant was sensorimotor in Europe/Americas (n = 387/562, 69%) and Asia (n = 27/63, 43%), and pure motor in Bangladesh (n = 74/107, 69%). Miller Fisher syndrome and Miller Fisher-Guillain-Barré overlap syndrome were more common in Asia (n = 14/63, 22%) than in the other two regions (Europe/Americas: n = 64/562, 11%; Bangladesh: n = 1/107, 1%) (P < 0.001). The predominant electrophysiological subtype was demyelinating in all regions (Europe/Americas: n = 312/573, 55%; Asia: n = 29/65, 45%; Bangladesh: n = 38/94, 40%). The axonal subtype occurred more often in Bangladesh (n = 34/94, 36%) than in Europe/Americas (n = 33/573, 6%) and other Asian countries (n = 4/65, 6%) (P < 0.001). In all regions, patients with the axonal subtype were younger, had fewer sensory deficits, and showed a trend towards poorer recovery compared to patients with the demyelinating subtype. The proportion of patients able to walk unaided after 1 year varied between Asia (n = 31/34, 91%), Europe/Americas (n = 334/404, 83%) and Bangladesh (n = 67/97, 69%) (P = 0.003). A similar variation was seen for mortality, being higher in Bangladesh (n = 19/114, 17%) than in Europe/Americas (n = 23/486, 5%) and Asia (n = 1/45, 2%) (P < 0.001). This study showed that factors related to geography have a major influence on clinical phenotype, disease severity, electrophysiological subtype, and outcome of Guillain-Barré syndrome.

Introduction: We explored adherence to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) guidelines for the diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) by reviewing data from a specialty pharmacy database., Materials and Methods: Clinical and electrophysiologic data were reviewed for 65 consecutive patients treated with intravenous immunoglobulin (IVIG) for CIDP. Three neuromuscular neurologists independently classified cases according to EFNS/PNS criteria as (1) fulfilling CIDP criteria; (2) non-CIDP (neither clinical nor electrophysiologic criteria met); or (3) unknown (insufficient information)., Results: Patients were treated by 31 different community neurologists in 14 states. Only seven patients (11%) met clinical and electrodiagnostic CIDP criteria. The remainder (89%) did not have CIDP (49%) or were unknown (40%). IVIG mean induction dose was 1.25 g/kg, mean maintenance dose 0.79 g/kg, and mean interval between infusions was 23 days., Conclusions: Adherence to EFNS/PNS CIDP diagnostic and treatment guidelines in the general neurologic community was poor. Improved education and awareness of widely available CIDP guidelines are recommended.

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, multicenter 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 2 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 1,000 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 1,400 participants from 143 active centers 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 modeling, 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., (© 2017 Peripheral Nerve Society.)

Background and Purpose: There is increasing interest in using patient-reported outcome measures (PROMs) in clinical studies to capture individual changes over time. However, PROMs have also been criticized because they are entirely subjective. Our objective was to examine the relationship between a subjective PROM and an objective outcome tool in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and gammopathy-related polyneuropathy (MGUSP)., Methods: The Inflammatory Rasch-built Overall Disability Scale (I-RODS©, a multi-item scale that examines functionality) was completed by 137 patients with newly diagnosed (or relapsing) GBS (55), CIDP (59) and MGUSP (23) who were serially examined (GBS/CIDP, T0/T1/T3/T6/T12 months; MGUSP, T0/T3/T12). Possible association between the I-RODS findings and the vigorimeter scores, an objective linear instrument to assess grip strength, was examined., Results: A significant correlating trend was found between the I-RODS and grip strength scores for the overall group and in each illness, independently., Conclusion: The objectivity of patients' subjective report on their functional state based on a strong correlation between the I-RODS and grip strength in patients with GBS, CIDP and MGUSP has been demonstrated. These findings provide further support to use the I-RODS and grip strength in future clinical studies in these conditions., (© 2016 EAN.)

The "ability to walk" is considered a benchmark for good clinical recovery and prognosis, particularly in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, it has never been determined whether being "able to walk" represents general functionality. The purpose of this study was to examine whether the ability to walk outside independently reflects general functional improvement in patients with GBS, CIDP, and gammopathy-related neuropathy (MGUSP). A total of 137 patients with newly diagnosed (or relapsing) GBS (55), CIDP (59), and MGUSP (23) were serially examined (1-year). Predefined arbitrary cut-offs (so-called patients' Functional-Acceptable-Clinical-Thresholds [FACTs]) were taken at the 50th, 75th, and 90th percentile of the Inflammatory-Rasch-built-Overall-Disability-Scale (I-RODS(©) ). We determined the proportion of patients able to walk outside independently that reached the postulated cut-offs. A mean total of 85%, 39%, and 12% of all patients able to walk reached 50th, 75th, and 90th percentile thresholds, respectively. These findings were not neuropathy type related. Our findings show that assessing only one construct of functionality (e.g., walking ability) does not reflect the full scope of daily/social functional deficits perceived by patients. The ability to walk shows a patient is doing better, but not necessarily doing well. The I-RODS(©) bypasses these limitations., (© 2016 Peripheral Nerve Society.)

We performed a comparison between Neuropathy Impairment Scale-sensory (NISs) vs. the modified Inflammatory Neuropathy Cause and Treatment sensory scale (mISS), and NIS-motor vs. the Medical Research Council sum score in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and IgM monoclonal gammopathy of undetermined significance-related polyneuropathy (MGUSP). The ordinal data were subjected to Rasch analyses, creating Rasch-transformed (RT)-intervals for all measures. Comparison between measures was based on validity/reliability with an emphasis on responsiveness (using the patient's level of change related to the individually obtained varying SE for minimum clinically important difference). Eighty stable patients (GBS: 30, CIDP: 30, and MGUSP: 20) were assessed twice (entry: two observers; 2-4 weeks later: one observer), and 137 newly diagnosed or relapsing patients (GBS: 55, CIDP: 59, and IgM-MGUSP: 23) were serially examined with 12 months follow-up. Data modifications were needed to improve model fit for all measures. The sensory and motor scales demonstrated approximately equal and acceptable validity and reliability scores. Responsiveness scores were poor but slightly higher in RT-mISS compared to RT-NISs. Responsiveness was equal for the RT-motor scales, but higher in GBS compared to CIDP; responsiveness was poor in patients with MGUSP, suggesting a longer duration of follow-up in the latter group of patients., (© 2015 Peripheral Nerve Society.)

Clinical trials in multifocal motor neuropathy (MMN) have often used ordinal-based measures that may not accurately capture changes. We aimed to construct a disability interval outcome measure specifically for MMN using the Rasch model and to examine its clinimetric properties. A total of 146 preliminary activity and participation items were assessed twice (reliability studies) in 96 clinically stable MMN patients. These patients also assessed the ordinal-based overall disability sum score (construct, sample-dependent validity). The final Rasch-built overall disability scale for MMN (MMN-RODS(©) ) was serially applied in 26 patients with newly diagnosed or relapsing MMN, treated with intravenous immunoglobulin (IVIg) (1-year follow-up; responsiveness study). The magnitude of change for each patient was calculated using the minimum clinically important difference technique related to the individually obtained standard errors. A total of 121 items not fulfilling Rasch requirements were removed. The final 25-item MMN-RODS(©) fulfilled all Rasch model's expectations and showed acceptable reliability and validity including good discriminatory capacity. Most serially examined patients improved, but its magnitude was low, reflecting poor responsiveness. The constructed MMN-RODS(©) is a disease-specific, interval measure to detect activity limitations in patients with MMN and overcomes the shortcomings of ordinal scales. However, future clinimetric studies are needed to improve the MMN-RODS(©) 's responsiveness by longer observations and/or more rigorous treatment regimens., (© 2015 Peripheral Nerve Society.)

The Jamar dynamometer and Vigorimeter have been used to assess grip strength in immune-mediated neuropathies, but have never been compared to each other. Therefore, we performed a comparison study between these two devices in patients with immune-mediated neuropathies. Grip strength data were collected in 102 cross-sectional stable and 163 longitudinal (new diagnoses or changing condition) patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), gammopathy-related polyneuropathy (MGUSP), and multifocal motor neuropathy (MMN). Stable patients were assessed twice (validity/reliability studies). Longitudinal patients were assessed 3-5 times during 1 year. Responsiveness comparison between the two tools was examined using combined anchor-/distribution-based minimum clinically important difference (MCID) techniques. Patients were asked to indicate their preference for the Jamar or Vigorimeter. Both tools correlated highly with each other (ρ = 0.86, p < 0.0001) and showed good intra-class correlation coefficients (Jamar [Right/Left hands]: ICC 0.997/0.96; Vigori: ICC 0.95/0.98). Meaningful changes were comparable between the two instruments, being higher in GBS compared to CIDP patients. In MGUSP/MMN poor responsiveness was seen. Significant more patients preferred the Vigorimeter. In conclusion, validity, reliability, and responsiveness aspects were comparable between the Jamar dynamometer and Vigorimeter. However, based on patients' preference, the Vigorimeter is recommended in future studies in immune-mediated neuropathies., (© 2015 Peripheral Nerve Society.)

The objectives of this study were to provide an overview of the outcome measures (OMs) applied in clinical trials in multifocal motor neuropathy (MMN) and to determine the responsiveness of a core set of selected OMs as part of the peripheral neuropathy outcome measures standardization (PeriNomS) study. The following OMs were serially applied in 26 patients with newly diagnosed or relapsing MMN, receiving intravenous immunoglobulin (assessments: T0/T3/T12 months): 14 muscle pairs MRC (Medical Research Council) scale, the Neuropathy Impairment Scale motor-subset, a self-evaluation scale, grip strength, and MMN-RODS© (Rasch-built overall disability scale). All data, except the grip strength, were subjected to Rasch analyses before determining responsiveness. For grip strength, responsiveness was examined using a combined anchor- (SF-36 question-2) and distribution-based (½ × SD) minimum clinically important difference (MCID) techniques, determining the proportion of patients exceeding both the identified cut-offs. For the remaining scales, the magnitude of change for each patient on each scale was determined using the MCID related to the individual SE (responder definition: MCID-SE ≥ 1.96). Overall, a great assortment of measures has been used in MMN trials with different responsiveness definitions. For the selected OMs, responsiveness was poor and only seen in one fourth to one third of the patients, the grip strength being more responsive. Despite the efforts taken to standardize outcome assessment, further clinimetric responsiveness studies are needed in MMN., (© 2015 Peripheral Nerve Society.)

This study aimed to 'define responder' through the concept of minimum clinically important differences using the individually obtained standard errors (MCID-SE) and a heuristic 'external criterion' responsiveness method in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One hundred and fourteen newly diagnosed or relapsing patients (GBS: 55, CIDP: 59) were serially examined (1-year follow-up). The inflammatory Rasch-built overall disability scale (I-RODS), Rasch-transformed MRC sum score (RT-MRC), and Rasch-transformed modified-INCAT-sensory scale (RT-mISS) were assessed. Being-a-responder was defined as having a MCID-SE cut-off ≥1.96. Also, the correlations between patients' scores on each scale and the EuroQoL health-status 'thermometer' (external criterion) were determined (higher correlation indicated better responsiveness). In both diseases, the SEs showed a characteristic 'U'-shaped dynamic pattern across each scales' continuum. The number of patients showing a meaningful change were higher for the I-RODS > RT-MRC > RT-mISS and were in GBS higher than CIDP patients. The MCID-SE concept using Rasch-transformed data demonstrated an individual pattern of 'being-a-responder' in patients with immune-mediated neuropathies, and the findings were validated by the external criterion responsiveness method. The I-RODS showed greater responsiveness compared with the MRC and INCAT-sensory scales, and its use is therefore recommended in future trials in GBS and CIDP., (© 2015 Peripheral Nerve Society.)

Outcome measures are considered the most important tools to monitor patients' outcome in both clinical and research settings. Measuring the clinical state of patients is a fundamental part of our daily clinical practice and research that sometimes is taken for granted. In peripheral neuropathies, there are many scales available, but most of these are at the ordinal level. This paper will systematically address the types of scales available (being nominal, ordinal, interval, or ratio data-based) in terms of their strengths and weaknesses. The differences between classical test theory-based and modern test method-based outcome measures will be addressed with emphasis on Rasch methodology. Various steps will be highlighted as part of the evaluation and construction of outcome measures using the Rasch method, with the aim to increase the knowledge and utility of this technique. We argue that Rasch-built outcome measures should be used for future studies in neuromuscular disorders and their method of construction could be easily extrapolated to other neurological illnesses., (© 2015 Peripheral Nerve Society.)