The CV2/CRMP5 antibody is a type of neuronal intracellular antigen antibody which can participate in the production of antigen-specific CD8⁺ T lymphocytes leading to neuronal damage and rapid and widespread cell death.  The clinical manifestations of CV2 antibody related paraneoplastic neurological syndrome (PNS) are varied and include limbic encephalitis, chorea, ocular manifestation, cerebellar ataxia, myelopathy, and peripheral neuropathy. Peripheral neuropathies associated with CV2/CRMP5 antibodies are mostly mixed axonal and demyelinating peripheral neuropathies. Most of CV2/CRMP5 antibody-associated PNS are associated with SCLC and thymoma, but have been reported also in breast cancer, lymphoma, renal carcinoma, colon cancer, testicular tumor, uterine sarcoma, prostate cancer, undifferentiated carcinoma, thyroid cancer, squamous cell carcinoma of tongue, and adenocarcinoma of the lung. Some studies have also found that 22% of patients with CV2/CRMP5 antibody-associated PNS do not have tumors at time of diagnosis. 

A 76-year-old Caucasian man with history of cervical spine surgery after a car accident 25 years ago, was later diagnosed with multiple myeloma after he presented with L2 vertebral body pathologic fracture treated with palliative radiation therapy followed by multiple cycles of chemotherapy including daratumumab, lenalidomide, bortezomib, and dexamethasone.  Patient was referred to neurology clinic for further evaluation of a recent onset numbness and tingling in his distal extremities. Nerve conduction study of bilateral lower extremity showed mixed demyelinating axonal motor neuropathy with unobtainable response from sensory nerves.  Initial blood work-up for neuropathy including vitamin B12, thiamine, Hgb A1C, Asialo-GM1 antibodies, anti MAG antibody and paraneoplastic antibody panel was unremarkable except for an elevated anti-CV2 antibody. 

Peripheral neuropathies associated with CV2 are mostly mixed axonal and demyelinating peripheral neuropathies and reported in different types of cancer. To the best of our knowledge, this is the first case of anti CV2 antibody associated peripheral neuropathy in a patient with multiple myeloma