Anti-MAG-associated neuropathy: a case report and literature review

Anti-myelin-associated glycoprotein (MAG) neuropathy is an uncommon IgM-mediated autoimmune demyelinating peripheral neuropathy, which is prone to misdiagnosis due to overlapping clinical manifestations with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Serum anti-MAG IgM ≥ 1:1000 is widely accepted as the standard diagnostic cut-off value clinically, while cases with low-titer positive results remain poorly summarized. We report one low-titer MAG-antibody-positive case receiving individualized low-dose rituximab to supplement clinical evidence for this disease.

A 65-year-old male patient presented with progressive numbness and limb unsteadiness lasting for 5 months. Neurological examination identified predominantly distal lower limb weakness and prominent deep sensory ataxia. Pre-treatment INCAT disability score was 4 and decreased to 2 one month after intervention. Serum anti-MAG IgM was positive at 1:320; all nodal/paranodal antibodies including NF155, CNTN1, Caspr1 and pan-neurofascin tested negative. Immunofixation electrophoresis demonstrated an IgM-λ monoclonal gammopathy, with serum free κ/λ light chain within normal reference ranges. Cerebrospinal fluid (CSF) protein was markedly elevated. Nerve conduction study (NCS) performed prior to medication revealed diffuse distal-predominant demyelination combined with axonal injury. The patient failed high-dose methylprednisolone pulse therapy, then received split low-dose rituximab (100 mg on Day 1, 500 mg on Day 2). One-month follow-up showed antibody titer dropped to 1:100 and obvious clinical improvement; incident hyperthyroidism was detected during hospitalization. Bone marrow biopsy excluded B-cell proliferative disorders.

Low-titer anti-MAG IgM combined with typical clinical, electrophysiological and serological findings can confirm MAG neuropathy. Individualized low-dose rituximab achieves satisfactory efficacy for elderly patients complicated with underlying cerebrovascular disorders in early disease stage. Concurrent new-onset autoimmune hyperthyroidism is a rare clinical coincidence in this disease, requiring long-term follow-up observation.