A Can of Worms - Video

An extended ganglioside antibody panel was obtained that showed asialo GM1, GM2, and GD1a antibodies. In light of these results and the chronicity of his presentation, CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein agglutination, and disialosyl antibodies) was diagnosed. He was treated with monthly IVIG, oral prednisone, and later rituximab. Ocular motility improved, although at one year of follow up he continues to have diplopia from 25 PD of esodeviation. The temporal association of his symptoms and recent nephrectomy for renal cell carcinoma was initially concerning for an infectious or neoplastic process, but neuroimaging and CSF cytology were normal. Miller-Fisher syndrome was then suspected, but serum GQ1b antibodies, which are present in over 80% of patients with Miller-Fisher syndrome (Ito 2008), were absent. Furthermore, he experienced no clinical improvement over the subsequent three months, which is unusual as the natural history of Miller-Fisher syndrome is for symptoms to peak after one week, plateau for two weeks, and resolve by three months (Mori 2001). The progressive nature of his diplopia and ophthalmoparesis prompted additional testing leading to the correct diagnosis. First described in 1985, CANOMAD is a chronic, often relapsing autoimmune polyneuropathy characterized by prominent ophthalmoparesis. Antibodies against multiple disialosyl-containing gangliosides, including GQ1b, may be present (Willison 2001). The typical neuro-ophthalmic presentation is diffuse, progressive ophthalmoparesis, though there are case reports of optic neuropathy in CANOMAD (Sanvito 2011). The literature is limited to a handful of case reports and case series totaling some 65 patients, and there is no known association with malignancy or recent surgery. The recognition of this rare clinical syndrome had implications for this patient's treatment, as there are reports of success with both IVIG (Attarian 2010) and rituximab (Delmont 2010).