Abstract
A previously well 52-year-old-man developed insidious onset of imbalance resulting in falls over 2 years, particularly in low light settings. Additional symptoms included fluctuating horizontal diplopia, patchy sensory changes in the limbs, dysgeusia, postural light-headedness, and 10kg weight loss. Examination revealed a complex variable ophthalmoparesis, anisocoria with poorly reactive pupils, mild distal weakness, global areflexia, glove and stocking distribution reduction in pin-prick and temperature sensation, pseudoathetosis of the fingers, and positive Romberg’s test. Appendicular coordination with eyes open was preserved, alongside distal vibration and joint position sense. Unaided gait in daylight was normal. Nerve conduction studies revealed a sensory-predominant axonal neuropathy affecting upper more than lower limbs. MRI brain with gadolinium was unremarkable. Blood tests revealed a significant IgM kappa paraprotein (13g/L). Anti-ganglioside GQ1b IgG was negative, however anti-GQ1b IgM and anti-GD1b IgM were positive. Cold agglutinin antibodies were detected. A diagnosis of CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins, and disialosyl antibodies) was made. Bone marrow aspiration and trephine identified a population of abnormal medium-sized lymphocytes. MYD88 mutation lead to a diagnosis of Waldenstrom’s macroglobulinemia. A trial of intravenous immunoglobulin induction (2g/kg over 5 days) resulted in no symptomatic improvement. The patient underwent 6 cycles of rituximab-bendamustine chemotherapy with stabilisation of diplopia and sensory changes and improvement in balance. This case is a useful reminder of the features of CANOMAD, a rare paraproteinaemic neuropathy representing a chronic form of Miller-Fisher syndrome, and highlights the importance of assessing paraprotein and anti-ganglioside antibodies in patients presenting with atypical neuropathy.
