Multifocal Motor Neuropathy With Negative Anti-GM1 Antibodies and Poor IVIG Response: A Case Report

Case Diagnosis: A 70-year-old male presents with progressive bilateral upper extremity weakness, diagnosed as multifocal motor neuropathy (MMN) via EMG with negative anti-GM1 antibodies and poor response to IVIG.

Case Description or Program Description: The patient experienced progressive bilateral upper extremity weakness over several months, without any associated neck or back pain. MRI of the brain and cervical spine showed chronic ischemic white matter changes and chronic infarcts, with no high-grade canal stenosis or spinal cord compression. EMG findings were consistent with MMN. The patient was treated with a 5-day IVIG course but showed minimal improvement in strength.

Setting: General Medical Floor

Assessment/Results: Laboratory tests revealed elevated ANA, anti-histone, anti-dsDNA, ESR, and CRP, while anti-GM1 antibodies were negative. Tests for Smith, RNP, SSA, SSB, and myelin-associated glycoprotein antibodies were negative. EMG/NCS showed intact sensory nerves but significant motor axonal loss and conduction blocks.

Discussion (relevance): MMN is an immune-mediated neuropathy characterized by progressive motor weakness without sensory loss. The presence of anti-GM1 antibodies is a common finding, detected in 40-50% of MMN cases. However, this case highlights MMN without anti-GM1 antibodies, which is less commonly reported.

Studies suggest that patients with negative anti-GM1 antibodies may have a poorer prognosis, with less response to IVIG and a more aggressive disease course. This patient’s lack of improvement with IVIG aligns with previous findings that IVIG non-responders often lack anti-GM1 antibodies. Furthermore, high complement activation by anti-GM1-positive MMN patients correlates with disease severity, which may suggest different pathogenic mechanisms in anti-GM1-negative cases.

The elevated ANA, anti-histone, and anti-dsDNA antibodies raise the question of a potential overlap between MMN and systemic autoimmunity, though prior studies have not established a strong link between MMN and ANA positivity.

Conclusions: This case underscores the poor prognostic implications of anti-GM1-negative MMN, particularly regarding IVIG response and disease progression. Further research is needed to explore alternative treatments for anti-GM1-negative MMN.