A 32 year old gentleman, presenting initially with a ‘dragging’ foot, rapidly progressed to become paraplegic within a year. Here, a case summary is presented initially, followed by the differential diagnosis for the clinical presentation. Investigations primarily showed combined central and peripheral demyelination which could have been secondary to the anti-CRMP5 antibodies found in his serum. Such antibodies are highly associated with malignancy and, as a consequence, our patient was extensively investigated for an occult neoplasm (which was not found). While the central and peripheral demyelination may have been secondary to an antibody-mediated paraneoplastic syndrome, other differentials such as autoimmune combined demyelination must also be considered.