Study Evaluating the Predictive Value of the Terminal Latency Index (TLI) for Treatment Response in Patients With Anti-MAG Neuropathy

N/ANot Yet RecruitingNCT07794137

Centre Hospitalier Universitaire de Nice100 enrolled

Overview

"Anti-myelin-associated glycoprotein (anti-MAG) neuropathy is a rare dysimmune peripheral neuropathy, most commonly associated with an IgM monoclonal gammopathy. Its course is generally slow but may lead to significant functional disability. Despite therapeutic advances, including rituximab, intravenous immunoglobulins (IVIg), immunochemotherapy, and more recently Bruton tyrosine kinase inhibitors (BTKi), treatment response remains highly variable between patients. The Terminal Latency Index (TLI), an electrophysiological parameter reflecting distal demyelination, is a recognized diagnostic marker of anti-MAG neuropathy. However, its potential role as a predictive biomarker of treatment response remains insufficiently studied. Identifying a simple, reproducible, and readily available biomarker that could predict treatment response would be of major clinical importance for personalized patient management and optimization of therapeutic strategies. This monocentric retrospective study will analyze clinical, biological, and electrophysiological data from patients with anti-MAG neuropathy followed at Nice University Hospital (CHU de Nice) to assess the predictive value of baseline TLI for clinical response 12 months after treatment initiation."

Study Type

OBSERVATIONAL

Enrollment

100

Conditions

Anti-MAG Neuropathy Peripheral Nervous System Disease Anti-Myelin-Associated Glycoprotein Antibodie

Interventions

Electroneuromyography (ENMG) and Terminal Latency Index (TLI) AssessmentDIAGNOSTIC_TEST

This monocentric retrospective observational study will include 100 patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy followed at Nice University Hospital (CHU de Nice). No additional intervention or modification of routine clinical care will be performed. Clinical, biological, therapeutic, and electrophysiological data will be retrospectively collected from medical records and available archives. Routinely performed electroneuromyography (ENMG) data will be analyzed, with particular emphasis on the Terminal Latency Index (TLI), calculated from available electrophysiological parameters according to the standard formula. The predictive value of baseline TLI for clinical response to treatment at 12 months will be assessed. Treatments received as part of routine care, including rituximab, IVIg, immunochemotherapy, and Bruton tyrosine kinase inhibitors (BTKi), will be recorded. No treatment will be assigned or modified by the study. Data will be pseudonymized and ente

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Documented anti-MAG IgM polyneuropathy: positive anti-MAG antibodies, associated with an IgM monoclonal gammopathy, and a compatible clinical phenotype. * Complete and interpretable baseline ENMG assessment: an initial electroneuromyography (ENMG) examination allowing reliable calculation of the TLI in at least two motor nerves among the right median, ulnar, and common fibular nerves. * The examination must include the distal motor latency, proximal motor conduction velocity, and compound muscle action potential (CMAP). * Treatment with at least one established therapeutic strategy: treatment initiated at the center, including intravenous immunoglobulins (IVIg), rituximab, immunochemotherapy, Bruton tyrosine kinase inhibitors (BTKi), and/or symptomatic treatment. * Available functional clinical assessment: a documented INCAT disability score at two predefined time points: baseline (before treatment initiation) and 12 months (±2 months) after treatment initiation. * Consent to participate in the study. Exclusion Criteria: * Peripheral neuropathy associated with an IgM monoclonal gammopathy, with strictly negative anti-MAG antibody testing or no available anti-MAG antibody measurement. * Incomplete or uninterpretable ENMG data preventing accurate calculation of the TLI for the nerves of interest (median and ulnar nerves). * Absence of a formally documented INCAT score at baseline or within the 12-month assessment window.

Outcomes

Primary Outcomes

Favorable Clinical Response at 12 Months (≥1-Point Decrease in INCAT Score)

Clinical response at 12 months, defined as a reduction of at least 1 point in the INCAT disability score from baseline. This outcome will be used to assess the predictive value of the baseline Terminal Latency Index (TLI) for treatment response in patients with anti-MAG neuropathy.

Time frame: 12 months after treatment initiation

Secondary Outcomes

Predictive performance of TLI according to treatment strategy

Assessment of the predictive performance of baseline TLI for clinical response at 12 months, stratified according to the treatment strategy received.

Time frame: 12 months after treatment initiation.

Correlation between TLI, anti-MAG antibody titer, and INCAT score evolution

Assessment of the association between baseline TLI, quantitative anti-MAG antibody titer, and change in the INCAT disability score from baseline to 12 months.

Time frame: Baseline to 12 months after treatment initiation

Optimal TLI threshold for predicting treatment response

Determination of the optimal baseline TLI threshold for predicting clinical response at 12 months using Receiver Operating Characteristic (ROC) curve analysis and the Youden index