Zabeen Mahuwala1, Vishakhadatta Mathur Kumaraswamy2, Mangayarkarasi Thandampallayam Ajjeya3, Saniya Pervin3
1Neurology, University of Kentucky, KY Clinic Neurology Department, 2University of Kentucky, 3Neurology, University of Kentucky
Background:
Anti- myelin associated glycoprotein (MAG) neuropathy constitutes 5% of CIDP like presentation and is a disabling paraproteinemic neuropathy with variable response to treatment.
Design/Methods:
69-year-old male with eleven-year history of tingling in the hands and then feet presented with worsening dexterity and numbness in 2012. Examination showed distal wasting, weakness of toe and ankle movements, length dependent pan sensory loss, and plantar flexion, wide-based gait and absent reflexes. Nerve conduction studies (NCS) showed primary demyelinating length dependent polyneuropathy. Work up revealed IgM monoclonal gammopathy and anti MAG antibody titer of 66,000. He was diagnosed with Waldenstrom Macroglobulinemia (WM). Initial treatment with IVIg showed minimal response. Symptoms stabilized on Rituximab between 2013 and 2016 and treatment was temporarily stopped. In January 2020 due to re-emergence of symptoms, Rituximab was restarted. But he continued to worsen. Repeat NCS/EMG in 2021 did not show improvement. Ibrutinib was started in April 2022 due to electroclinical worsening of neuropathy, but he has not had a clinical response. His IgM gammopathy has resolved although his kappa/lambda ratio and anti-MAG titer remain elevated. We plan on repeat NCS/EMG and ultrasound of the peripheral nerve for further characterization and assessment of the neuropathy.
Results:
Rituximab, currently the most commonly prescribed treatment for anti-MAG neuropathy, provides benefit in less than 50% of patients. Smaller studies show efficacy of Ibrutinib in anti-MAG antibody neuropathy. Our patient tolerated Ibrutinib but failed to show clinical improvement. Anti-MAG antibody titers do not correlate with severity of disease or with paraprotein levels, and the mechanism of action of Ibrutinib in anti-MAG neuropathy is not well understood. The lymphoplasmacytes producing anti-MAG antibodies may have a survival advantage, explaining refractoriness of anti-MAG neuropathy to treatment.
Conclusions:
Larger studies are needed to understand the efficacy of Ibrutinib. Drugs targeting anti-MAG antibodies and lymphoplasmacytes need to be developed.