IgM Anti MAG± Peripheral Neuropathy (IMAGiNe) Study Protocol: An international, observational, prospective registry of patients with IgM M-protein Peripheral Neuropathies

Background: 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. Aims: Functional outcome measures will be constructed at the level of impairment, as well as activity and participation. We aim to describe the natural history of the cohort, the role of anti-MAG antibodies, the presence of clinical subtypes and potential biomarkers. Methods: The IMAGiNe study is a prospective, observational cohort study with a 3 years follow-up. At each assessment, researchers collect clinical data and subjects complete a list of pre-selected outcome measures. Among these, the 'Pre-Rasch-built Overall Disability Scale (Pre-RODS)' questionnaire will be submitted to Rasch analysis to assess classic and modern clinimetric requirements. Results: The final measures will include the IgM-PNP-specific RODS and Ataxia Rating Scale (IgM-PNP-ARS). Descriptions of the disease course, clinical heterogeneity, treatment regimes, variations in laboratory values and antibody titers, will help reach consensus on diagnosis and follow-up strategies. Conclusion: The constructed interval scales will be cross-culturally valid and suitable for use in future clinical trials and daily practice. The ultimate goals are to improve functional individualized assessment, reach international consensus, and lay the foundations for successful designs in future studies.