Distal acquired demyelinating symmetric neuropathy associated with colorectal adenocarcinoma: Should it be termed paraneoplastic?

DISTAL ACQUIRED DEMYELINATING SYMMETRIC NEUROPATHY ASSOCIATED WITH COLORECTAL ADENOCARCINOMA: SHOULD IT BE TERMED PARANEOPLASTIC? In their study, Croft et al. described chronic, relapsing neuropathy with characteristics of chronic inflammatory demyelinating polyneuropathy (CIDP) in patients with occult malignancies but without tumor infiltration of the nerves. Paraneoplastic neurological syndromes (PNS) may have features of subacute sensory neuronopathy or primary demyelinating neuropathies, either Guillain– Barr e syndrome or CIDP. Antibodies generated against tumor antigens cross-react with nerve proteins; the responses of host tissues may become independent from the original antigenic trigger. Ayyappan et al. described a 78-year-old diabetic woman with a 4-month history of hand and great toe numbness and weakness, distal impairment of touch perception, and absent tendon reflexes. Motor examination and gait were normal. Evaluation revealed eosinophilia, positive immunofluorescence assay for myelin-associated glycoprotein (MAG), and increased antinuclear antibody (ANA) titer. Nerve conduction studies showed prolonged motor latencies and increased temporal dispersion of compound motor action potentials (CMAPs), consistent with distal-predominant demyelinating sensorimotor neuropathy (DADS). The clinical hallmarks of DADS are distal sensory and motor disturbances. Within 1 month, the patient underwent sigmoidoscopy for abdominal symptoms and laparoscopic resection of colon adenocarcinoma. On follow-up, 8 months after tumor removal, the patient showed dramatic clinical and electrophysiological improvement and had a negative assay for anti-MAG IgM antibody. We recently encountered a similar patient. At age 53, this man was admitted to our ward after a 2-month history of acroparesthesias. On admission, there was universal areflexia, distal muscle weakness (3/5 on the Medical Research Council scale), loss of touch and vibration perception, and elevated cerebrospinal fluid protein (140 mg/dl, normal< 45). Electrophysiology revealed low-amplitude CMAPs with dispersed shape, absent Fwaves in fibular and tibial nerves, and slowed conduction velocity, consistent with length-dependent demyelination. Sural nerve biopsy revealed axonal loss and segmental demyelination. He received monthly intravenous immunoglobulin (IVIg, 1 g/kg) for 42 months, with brief improvement of strength after each course. Thereafter, the weakness worsened in all 4 limbs and became progressively unresponsive to immunotherapy. Further trials with pulse steroids and plasmapheresis combined with IVIg had no effect. Ten months later, after a finding of an elevated carcinoembryonic antigen titer (100 ng/ dl, normal< 5), total body computed tomography revealed a sigmoid colon adenocarcinoma. A monoclonal IgG-lamba was detected in the serum. The patient underwent radical hemicolectomy followed by chemotheraphy with leucovorin and 5-fluorouracil. He died 12 months after discovery of the cancer. Ayyappan et al. concluded in their patient that DADS neuropathy was a PNS related to a tumor-associated immune response. The immune response enhanced the anti-MAG antibody positivity, which was considered to be the pathogenic antibody; removal of the cancer, and possibly of the antigen, would allow clinical and electrophysiological recovery. DADS neuropathy usually responds poorly and slowly to immunomodulating treatments. Antoine et al. and others described CIDP associated with monoclonal gammopathy of undetermined significance (MGUS) preceding overt manifestations of cancer by years. Among our cohort of IgM MGUS patients with anti-MAG antibody, solid cancers, either colorectal or urothelial, were found in 13%, but the relationship with MGUS remained unclear. Interestingly, in the Ayyappan et al. patient, the ANA was positive with a nuclear speckled pattern. Tschernatsch et al. compared ANA-positive and ANAnegative patients with paraneoplastic neuropathy (PN) and found that ANA-positive/antineural-antibody–negative cases were associated with a better clinical prognosis. We are reluctant to consider the subacute DADS reported by Ayyappan et al. as paraneoplastic; the association could be coincidental, and the mechanism by which the recovery arose remains unclear. We agree with Ayyappan et al. that an 18-month period of observation is not sufficient to exclude cancer recurrence. In our patient, extensive screening for onconeural VC 2016 Wiley Periodicals, Inc.