Paraneoplastic myeloneuropathies: Clinical, oncologic and serologic accompaniments

Objective: To test the hypothesis that myeloneuropathy is a presenting phenotype of paraneoplastic neurological syndromes, we retrospectively reviewed clinical, radiological and serological features of 32 patients with concomitant paraneoplastic spinal cord and peripheral nervous system involvements.

Methods: Observational study investigating patients with myeloneuropathy and underlying cancer and/or onconeural antibody seropositivity.

Results: Among 32 paraneoplastic myeloneuropathy patients, twenty (63%) were women with median age 61 years (range 27-84 years). Twenty-six patients (81%) had classified onconeural antibodies (amphiphysin, n=8; ANNA1 [anti-Hu] n=5; CRMP5 [anti-CV2], n=6; PCA1 [anti-Yo], n=1; PCA2, n=2; KLHL11, n=1; and combinations thereof: ANNA1/CRMP5, n=1; ANNA1/amphiphysin, n=1; ANNA3/CRMP5, n=1). Cancer was confirmed in twenty-five cases (onconeural antibodies, n=19; unclassified antibodies, n=3; no antibodies, n=3). Paraneoplastic myeloneuropathies had asymmetric paresthesias (84%), neuropathic pain (78%), subacute onset (72%) sensory ataxia (69%), bladder dysfunction (69%), and unintentional weight loss >15 pound (63%). Neurological examination demonstrated concomitant distal or asymmetric hyporeflexia and hyperreflexia (81%), impaired vibration and proprioception (69%), Babinski response (68%), and asymmetric weakness (66%). MRI showed longitudinally-extensive (45%), tract-specific spinal-cord T2-hyperintensities (39%) and lumbar nerve root enhancement (38%). Ten of twenty-eight (36%) were unable to ambulate independently at last follow-up (median: 24 months, range 5-133 months). Combined oncologic and immunologic therapy had more favorable modified Rankin scores at post-treatment follow-up compared to those receiving either oncologic or immunologic therapy alone (2 [range 1 to 4] vs 4 [range 2 to 6] p<0.001).

Conclusions: Paraneoplastic etiologies should be considered in the evaluation of subacute myeloneuropathies. Recognition of key characteristics of paraneoplastic myeloneuropathy may facilitate in early tumor diagnosis and initiation of immunosuppressive treatment.