Mazen M. Dimachkie

Key terms describing the activity status and clinical outcomes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) lack standardized definitions. To address the need for uniform definitions, we sought to develop formal consensus-based terminology to define key aspects pertinent to the management of CIDP. In April 2025, the GBS|CIDP Foundation International convened a Task Force of 17 international CIDP experts, 2 guest experts from related specialties, and 3 patient representatives. Task Force panels iteratively reviewed, discussed, and voted on proposed definitions for No Evidence of Disease Activity, Relapse, Response, Refractory, Remission, and Residual Symptoms. Relevant literature was reviewed to inform each definition. A modified Delphi approach was used to achieve consensus, defined as a median rating ≥7 on a 9-point scale with ≥80% agreement. Voting included 17 content experts and 3 patient representatives. Guest experts provided nonvoting input. Composite metrics incorporating disability, strength impairment, and patient perception were determined to provide the most sensitive and specific assessment of clinical change in CIDP. Using commonly used clinical outcome measures, including minimally clinically important differences where available, unique definitions were developed for each clinical term. Definitions for No Evidence of Disease Activity, Relapse, Response (minimal, partial, and optimal), Refractory, Remission, and Residual Symptoms were iteratively refined to integrate patient-reported experiences, standardized disability scores, and objective measures of strength impairment, ensuring that each term captured a multidimensional view of disease status. The development of consensus-based definitions for key clinical terms in CIDP addresses a longstanding gap in standardizing the assessment of disease activity and treatment outcomes. By combining patient-reported experiences with objective disability and strength measures, the Task Force created comprehensive definitions reflecting the patient experience. The iterative Delphi process ensured broad expert agreement while allowing patient perspectives to inform the terminology. These standardized definitions may improve consistent evaluations in clinical practice, facilitate communication among healthcare providers, and support more robust design and interpretation of clinical trials. Furthermore, the incorporation of composite metrics sensitive to meaningful clinical changes may enhance the ability to detect treatment effects and disease progression, ultimately promoting more precise and patient-centered management of CIDP.

This series reports 3 unrelated individuals with features of neurofibromatosis type 1 (NF1) and/or schwannomatosis (SWN) in whom variants of uncertain significance (VUSs) were resolved through RNA testing and tissue analysis, highlighting the clinical impact of these tests. Each patient's genetic testing identified a VUS that could have explained their clinical presentation. Because diagnostic criteria were not met, we performed VUS resolution. For patient 1, we conducted tissue analysis and RNA-based Sanger sequencing. For patients 2 and 3, RNA-based Sanger sequencing was pursued. Tissue analysis and RNA testing reclassified the NF1 c.8050 + 93A>T VUS in patient 1 as pathogenic, confirming diagnosis of NF1. RNA testing of the NF2 c.448-5T>C VUS in patient 2 reclassified the variant as likely benign, ruling out diagnosis of germline neurofibromatosis type 2 (NF2). RNA testing of the SPRED1 c.377-13T>A VUS in patient 3 reclassified the variant as likely benign, ruling out diagnosis of germline Legius syndrome. Because diagnostic criteria for NF1 and SWN include genetic testing, resolving VUSs in those who do not meet criteria is crucial for clinical care. In this article, we report 3 cases in which RNA testing and tissue analysis clarified pathogenicity of VUSs, thereby affecting clinical care, and in one case providing a definitive diagnosis.

Introduction Muscle and skin involvement are well defined in dermatomyositis but other symptoms contribute significantly to the disease burden and their treatment is not well characterized. This post hoc analysis of ProDERM assessed the effect of intravenous immunoglobulin (IVIg) treatment on other manifestations of dermatomyositis beyond muscular and cutaneous involvement. Methods ProDERM was a randomized, placebo-controlled study. For weeks 0–16, patients with dermatomyositis received 2.0 g/kg IVIg (Octagam, 10%) or placebo every 4 weeks. Eligible patients entered the open-label extension, where all received IVIg to week 40. Pulmonary, skeletal, constitutional, gastrointestinal, and cardiovascular disease activity was assessed using the myositis disease activity assessment tool, comprising a visual analog scale (VAS; 0–10 cm) and myositis intention-to-treat activity index. Results Of 95 patients enrolled, 47 received IVIg and 48 received placebo to week 16. At baseline, 37.9% of patients experienced pulmonary, 64.2% experienced skeletal, 76.8% experienced constitutional, 33.7% experienced gastrointestinal, and 15.8% experienced cardiovascular involvement (VAS > 0.5). Among these patients, for those on IVIg, the following mean VAS scores decreased from baseline to week 16: pulmonary (37.7%; P = 0.001), skeletal (52.6%; P < 0.001), constitutional (44.4%; P < 0.001), and gastrointestinal (49.2%; P = 0.005). No corresponding improvement was seen with placebo except for constitutional VAS. With IVIg, the proportions of patients with arthritis (36.2 to 17.8%; P = 0.01), arthralgia (68.1 to 0.0%; P < 0.001), and fatigue (68.1 to 3.3%; P = 0.008) decreased from baseline to week 16. In the combined cohort, the proportions of patients with dysphonia (20.0 to 8.1%; P = 0.04), arthralgia (66.3 to 39.8%; P < 0.001), weight loss (10.5 to 3.4%; P = 0.04), fatigue (75.8 to 50.0%; P < 0.001), and dysphagia (40.0 to 18.4%; P < 0.001) decreased from baseline to week 40. Conclusion IVIg was effective in treating pulmonary, skeletal, constitutional, and gastrointestinal manifestations of dermatomyositis. We advocate exploring IVIg as treatment for dermatomyositis, beyond muscle and skin manifestations. Trial Registration ClinicalTrials. gov identifier, NCT02728752.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

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.

Objectives: To evaluate the validity, reliability, responsiveness and meaningful change threshold of the Inclusion Body Myositis (IBM) Functional Rating Scale (FRS).Methods: Data from a large 20-month multicentre, randomised, double-blind, placebo-controlled trial in IBM were used. Convergent validity was tested using Spearman correlation with other health outcomes. Discriminant (known groups) validity was assessed using standardised effect sizes (SES). Internal consistency was tested using Cronbach’s alpha. Intrarater reliability in stable patients and equivalence of face-to-face and telephone administration were tested using intraclass correlation coefficients (ICCs) and Bland-Altman plots. Responsiveness was assessed using standardised response mean (SRM). A receiver operator characteristic (ROC) curve anchor-based approach was used to determine clinically meaningful IBMFRS change.Results: Among the 150 patients, mean (SD) IBMFRS total score was 27.4 (4.6). Convergent validity was supported by medium to large correlations (r_smodulus: 0.42–0.79) and discriminant validity by moderate to large group differences (SES=0.51–1.59). Internal consistency was adequate (overall Cronbach’s alpha: 0.79). Test–retest reliability (ICCs=0.84–0.87) and reliability of telephone versus face-to-face administration (ICCs=0.93–0.95) were excellent, with Bland-Altman plots showing good agreement. Responsiveness in the worsened group defined by various external constructs was large at both 12 (SRM=−0.76 to −1.49) and 20 months (SRM=−1.12 to −1.57). In ROC curve analysis, a drop in at least two IBMFRS total score points was shown to represent a meaningful decline.Conclusions: When administered by trained raters, the IBMFRS is a reliable, valid and responsive tool that can be used to evaluate the impact of IBM and its treatment on physical function, with a 2-point reduction representing meaningful decline.Trial registration number: NCT02753530.