INTRODUCTION/AIMS:The value of electrodiagnostic subtyping of Guillain-Barré syndrome (GBS) is still debated. This study aimed to determine the diagnostic yield, timing, and changes of the electrodiagnostic subtyping in patients with GBS in serial nerve conduction studies (NCS). METHODS:Data were extracted from the International GBS Outcome Study (IGOS) database. Serial NCS were available for 469 patients. For the serial NCS analysis, the intervals between the first and second study were defined as ≥ 7 and ≤ 42 days after onset of weakness. All NCS were classified according to the electrodiagnostic criteria sets of Hadden et al. and Rajabally et al. RESULTS:In NCS conducted within 3 days of onset of weakness, an axonal or demyelinating subtype could be demonstrated in 58.4% (Hadden) and 52.1% (Rajabally). NCS performed at a later timepoint demonstrated a similar yield of axonal and demyelinating subtypes. In patients with motor-sensory and motor GBS, the electrodiagnostic subtype changed on serial NCS in 37.8% (Hadden) and 44.7% (Rajabally). As the subtypes changed in multiple and opposite directions, the total proportion of axonal and demyelinating subtypes remained stable across time points. In patients with motor GBS, both axonal and demyelinating subtypes were found. DISCUSSION:This study demonstrates the highly dynamic disease course of GBS. The role of NCS remains to support the clinical diagnosis of GBS and should be performed as quickly as possible after onset of weakness. If these early NCS are non-diagnostic, repeating the study should be considered. Electrodiagnostic subtyping offers no additional value.

Guillain–Barré syndrome (GBS) is an acute immune-mediated polyneuropathy with a high disease impact, even after good clinical recovery. The Inflammatory Rasch-built Overall Disability Scale (I-RODS) is a Patient-Reported Outcome Measure (PROM) developed for patients with immune-mediated neuropathies that measures limitations in daily activities and social participation. It consists of 24 items, scored from 0–48. The present study aimed to validate the measurement properties of the I-RODS in patients with GBS included in the prospective International GBS Outcome Study (IGOS). The current study focussed on structural validity, cross-cultural validity, internal consistency, and construct validity of I-RODS using Rasch-based methods. The study was conducted in 1226 patients diagnosed with GBS with a median I-RODS score of 28 (IQR 10–41) 4 weeks after inclusion into IGOS. Rasch analyses revealed adequate internal consistency (PSI = 0.95; α = 0.98) and sufficient construct validity, indicated by strong correlations (R = − 0.91 to − 0.77). Targeting was acceptable, although there was a skew towards the floor (10.1

BACKGROUND AND AIM:IgM monoclonal gammopathy-associated polyneuropathy with(out) anti-myelin associated glycoprotein (±anti-MAG) is a rare immune-mediated disease that may cause severe limitations in daily activities and quality of life. The absence of a systematic comparison between patients with/without anti-MAG IgM polyneuropathy, no disease-specific functional metric, and lack of international consensus regarding assessment and treatment of these patients are factors obstructing future clinical trials. Therefore, it was decided to develop an interval Rasch-built activity/participation scale specifically for IgM polyneuropathy ±anti-MAG (IgM-RODS) and examine its clinimetric properties. METHODS:A pre-phase IgM-RODS questionnaire containing 146 activity/participation items, based on the WHO International Classification of Functioning, Disability and Health, was completed by participants (≥ 18 years) of the IMAGiNe observational registry that fulfilled international criteria for IgM-polyneuropathy ±anti-MAG. Data was subjected to Rasch analyses, and reliability/validity studies were performed as well. RESULTS:The pre-RODS data of 259 subjects (originating from 8 different countries) underwent quality assessment, and 244 remaining records were submitted to the Rasch model, evidencing the model's expectations. Based on requirements like exceeding fit residuals, misfit statistics, item bias, local dependency, and less face validity, we systematically removed items until the final 36-item IgM-RODS fulfilled all Rasch requirements and showed acceptable test-retest reliability, cross-cultural, construct and discriminant validity, and unidimensionality. Compared to the Inflammatory-RODS, the IgM-RODS showed lower standard errors across the metric, indicating greater sensitivity. INTERPRETATION:The 36-item IgM-RODS is a disease-specific interval measure suitable for detecting functional deficits in patients with IgM-polyneuropathy ±anti-MAG. Future studies are needed to determine its responsiveness.

ABSTRACTIntravenous immunoglobulin (IVIG) is an immunomodulatory therapy derived from pooled donor immunoglobulins and used for treatment of various autoimmune conditions. Here we report the diagnosis and management of IVIG‐induced chronic severe neutropenia with absolute neutrophil count <0.5×103/µL in a patient with multifocal motor neuropathy. Serial blood count showed a cyclical pattern of neutropenia: worsening 24–48 h post‐IVIG, then gradually improving before the next infusion. IVIG‐induced neutropenia is rare, with previous reports of predominantly mild transient neutropenia. Our case describes chronic severe neutropenia that developed years after starting IVIG. We summarize available evidence and management strategies for IVIG‐associated neutropenia.

BACKGROUND AND PURPOSE:Various electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. METHODS:From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. RESULTS:Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. CONCLUSIONS AND DISCUSSION:This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.

BACKGROUND AND PURPOSE:Chemotherapy-induced peripheral neuropathy (CIPN) is perceived differently by patients and physicians, complicating its assessment. Current recommendations advocate combining clinical and patient-reported outcomes measures, but this approach can be challenging in patient care. This multicenter European study aims to bridge the gap between patients' perceptions and neurological impairments by aligning both perspectives to improve treatment decision-making. METHODS:Data were pooled from two prospective studies of subjects (n = 372) with established CIPN. Patient and physician views regarding CIPN were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Total Neuropathy Scale-clinical version (TNSc) items, and the disease-specific quality of life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20) from the European Organization for Research and Treatment of Cancer (EORTC). To identify inherent neurotoxic severity patterns, we employed hierarchical cluster analysis optimized with k-means clustering and internally validated by discriminant functional analysis. RESULTS:Both NCI-CTCAE and TNSc demonstrated a significant difference in the distribution of severity grades in relation to QLQ-CIPN20 scores. However, a proportion of subjects with different neurotoxic severity grades exhibited overlapping QLQ-CIPN20 scores. We identified three distinct clusters classifying subjects as having severely impaired, intermediately impaired, and mildly impaired CIPN based on TNSc and QLQ-CIPN20 scores. No differences in demographics, cancer type distribution, or class of drug received were observed. CONCLUSIONS:Our results confirm the heterogeneity in CIPN perception between patients and physicians and identify three well-differentiated subgroups of patients delineated by degree of CIPN impairment based on scores derived from TNSc and QLQ-CIPN20. A more refined assessment of CIPN could potentially be achieved using the calculator tool derived from the cluster equations in this study. This tool, which facilitates individual patient classification, requires prospective validation.

International consensus on IgM ± anti‐MAG ± PNP (IgM PNP) is lacking. Despite increasing interest in clinical trials, validated disease‐specific measures are needed to adequately capture limitations and changes over time. The IMAGiNe (IgM ± anti‐myelin associated glycoprotein [MAG] peripheral neuropathy) study surges as an international collaboration to create a standardized registry of patients with IgM ± anti‐MAG PNP. The consortium, which currently consists of 11 institutions from 7 countries, presents here the IMAGiNe study design and protocol.

Objective: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, chronic autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensation. The ARISE study (NCT05327114) is a Phase 2/3 multicenter, double-blind, placebo-controlled, randomized withdrawal study evaluating the efficacy and safety of nipocalimab in adults with CIDP. Background: Nipocalimab is a fully human aglycosylated immunoglobulin (Ig)G1 monoclonal antibody (mAb) designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal Fc receptor. Nipocalimab is administered via intravenous infusion. Design/Methods: The study consists of the following periods: (1) Screening (≤4 weeks)/Run-in (≤12 weeks), which includes identification of patients with active CIDP; (2) Stage A (Open-label, 12 weeks), in which participants receive nipocalimab loading dose, then once every 2 weeks (q2w); (3) Stage B (Double-blind, placebo-controlled, ≤52 weeks), in which participants are randomized 1:1 to nipocalimab q2w versus placebo; (4) Open-label extension (variable duration), in which participants receive nipocalimab q2w. Key inclusion criteria include adults ≥18 years with CIDP, progressing/relapsing forms, confirmed by independent adjudication committee; CIDP disease activity score ≥3; and adjusted INCAT disability score 2–9. Patients with pure sensory CIDP or CISP, or other diagnoses that could better explain their clinical presentation are excluded. The primary endpoint is time to first occurrence of a relapse event in Stage B. Secondary efficacy endpoints include time to initial response to nipocalimab and percentage of nipocalimab responders in Stage A, and change from baseline in functional measures (e.g. grip strength, MRC sum score, etc.) in Stage B. Other secondary endpoints include safety/tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of nipocalimab. Results: The study is currently enrolling patients, targeting approximately 300 patients, with primary study completion date anticipated in 2026. Conclusions: This ongoing phase 2/3 study will assess the efficacy, safety, PK, and PD of nipocalimab in adults with CIDP. Disclosure: Dr. Ford has received personal compensation for serving as an employee of Janssen . Dr. Ford has stock in Janssen. Dr. Wong has received personal compensation for serving as an employee of Janssen Research & Development. Dr. Wong has received personal compensation for serving as an employee of Biogen. Dr. Wong has stock in Biogen. Dr. Youssef has received personal compensation for serving as an employee of Janssen. Dr. Youssef has stock in Janssen. Mr. Murray has received personal compensation for serving as an employee of Janssen. Dr. Lim has received personal compensation for serving as an employee of Johnson & Johnson. Dr. Lim has stock in Johnson & Johnson. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ArgenX, Belgium. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LFB, France. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche, Switzerland. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL Behring. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen, USA. The institution of Dr. Nobile-Orazio has received research support from Takeda/Shire. Ingemar Merkies has nothing to disclose. Dr. Cornblath has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Octapharma. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Cornblath has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Cornblath has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Grifols. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cigna. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Anavex. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hansa. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MPTP. Dr. Cornblath has received intellectual property interests from a discovery or technology relating to health care. Dr. Sun has received personal compensation for serving as an employee of Janssen.

The ProCID study evaluated the efficacy and safety of three doses of a 10

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. To summarize the neurological safety of intravenous (IV) and subcutaneous (SC) tanezumab versus placebo in patients with osteoarthritis. 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. 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

Electrodiagnostic (EDx) studies are helpful in diagnosing and subtyping of Guillain-Barré syndrome (GBS). Published criteria for differentiation into GBS subtypes focus on cutoff values, but other items receive less attention, although they may influence EDx subtyping: (a) extensiveness of EDx testing, (b) nerve-specific considerations, (c) distal compound muscle action potential (CMAP)-amplitude requirements, (d) criteria for conduction block and temporal dispersion. The aims of this study were to investigate how these aspects were approached by neuromuscular EDx experts in practice and how this was done in previously published EDx criteria for GBS. A completed questionnaire was returned by 24 (of 49) members of the electrophysiology expertise group from the International GBS Outcome Study. Six published EDx criteria for GBS subtyping were compared regarding these aspects. The indicated minimal number of motor nerves to study varied among respondents and tended to be more extensive in equivocal than normal studies. Respondents varied considerably regarding usage of compression sites for subtyping (median/wrist, ulnar/elbow, peroneal/fibular head): 29% used all variables from all sites, 13% excluded all sites, and 58% used only some sites and/or variables. Thirty-eight percent of respondents required a minimal distal CMAP amplitude to classify distal motor latency as demyelinating, and 58% did for motor conduction velocity. For proximal/distal CMAP-amplitude ratio and F-wave latency, a requisite minimal CMAP amplitude was more often required (79%). Also, the various published criteria sets showed differences on all items. Practical use of EDx criteria for subtyping GBS vary extensively across respondents, potentially lowering the reproducibility of GBS subtyping.

OBJECTIVE:To describe the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barré syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS). METHODS:Prospectively collected clinical and EDx data were available in 957 IGOS patients from 115 centers. Only the first EDx study was included in the current analysis. RESULTS:Median timing of the EDx study was 7 days (interquartile range 4-11) from symptom onset. Methodology varied between centers, countries and regions. Reference values from the responding 103 centers were derived locally in 49%, from publications in 37% and from a combination of these in the remaining 15%. Amplitude measurement in the EDx studies (baseline-to-peak or peak-to-peak) differed from the way this was done in the reference values, in 22% of motor and 39% of sensory conduction. There was marked variability in both motor and sensory reference values, although only a few outliers accounted for this. CONCLUSIONS:Our study showed extensive variation in the clinical practice of EDx in GBS patients among IGOS centers across the regions. SIGNIFICANCE:Besides EDx variation in GBS patients participating in IGOS, this diversity is likely to be present in other neuromuscular disorders and centers. This underlines the need for standardization of EDx in future multinational GBS studies.

Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy Department of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Center+, Maastricht, Netherlands Department of Neurology, John Hopkins University School of Medicine, Baltimore, Maryland, USA

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.