Paraneoplastic Myeloneuropathies: characterization of a distinguishable phenotype and clinical outcomes (4933)

Objective: To describe a distinguishable clinical phenotype of paraneoplastic myeloneuropathies. Background: There is limited data to suggest that myeloneuropathies exist within the spectrum of classical paraneoplastic syndromes. Design/Methods: We analyzed patients with clinical/radiographic/electrodiagnostic evidence of co-occurring myelopathy and peripheral neuropathy seropositive for onconeural autoantibodies, and/or a diagnosis of cancer within 5 years of symptom onset. Comparison to historical cohort of copper-deficiency myeloneuropathies was performed. Results: Among thirty-two patients with paraneoplastic myeloneuropathy, twenty-six had detectable onconeural antibodies (Amphiphysin, 8; ANNA-1/anti-Hu, 6; CRMP-5, 5; PCA-1/anti-Yo, 2; PCA-2, 1; Kelch-like-Protein-11, 1; combinations thereof: ANNA-1 and CRMP-5, 1; ANNA-1 and Amphiphysin, 1; ANNA-3 and CRMP-5,1). Among these, twenty-two had underlying malignancy (small-cell lung cancer, 10), and four had lung nodules/masses (not evaluated further). Six patients had malignancies without classified onconeural antibodies (unclassified neural-autoantibodies, 3). Weight loss (>10 lbs, 63%), bowel/bladder dysfunction (69%) and gastrointestinal dysmotility (46%) were common presenting symptoms. The majority of neuropathies were non-length dependent (88%), asymmetric (69%), and presented with dysesthesia at onset (63%). A considerable proportion had polyradicular localization (56%). Co-existing upper and lower motor neuron involvement was documented on initial examination in 81%. However, 56% initially received an alternative diagnosis. Inflammatory CSF was noted in 82% (median nucleated-cell count, 13 cell/mm3 [range 0–74]). Tract-specific changes on cervical/thoracic MRI were seen in 9/29(31%) patients. In comparison to copper-deficiency myeloneuropathy (n=11), asymmetric sensory presentations, subacute progression, anorexia/weight loss, dysautonomia, taste/smell alterations, inflammatory CSF and gadolinium enhancement of spinal cord or lumbosacral roots were significantly more frequent in paraneoplastic myeloneuropathies (p Conclusions: A paraneoplastic etiology should be considered in the differential of subacute, progressive myeloneuropathy. Onconeural antibody evaluation and malignancy screening among these cases may aid in diagnosis of occult malignancy. Disclosure: Dr. Shah has nothing to disclose. Dr. Vazquez Do Campo has nothing to disclose. Dr. Pittock has received personal compensation from Alexion, Grifols, Euroimmun, MedImmune/Viela Bio Dr. Pittock has received research support from Alexion, Grifols, Euroimmun, MedImmune/Viela BioDr. McKeon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Grifols, Medimmune, and Euroimmun. Dr. McKeon has received royalty, license fees, or contractual rights payments from Pending patents: MAP1B, Kelch-like-protein 11, GFAP and MAP1B. Dr. McKeon has received research support from Medimmune, Euroimmun but has not received personal compensation.. Dr. Kumar has nothing to disclose. Dr. Flanagan has received research support from Medimmune/Viela Bio.Dr. Klein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Honorarium received from Ackea; Consulting for Pfizer, Stealth Pharmaceutical. No personal compensation received.. Dr. Dubey has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulted for UCB and Astellas. All compensation for consulting activities is paid directly to Mayo Clinic.. Dr. Dubey has received research support from Research support from Grifols and Center of Multiple Sclerosis and Autoimmune Neurology, Center for Clinical and Translational Science. Patent pending for KLHL11 as a marker of neurological autoimmunity..