Transiently elevated anti-CRMP-5 autoantibodies in two patients with myelitis without underlying malignancy

• Anti-CRMP-5 autoantibody is associated with various neurologic conditions, including chorea, optic neuritis, cranial neuropathy, cerebellar ataxia, myelopathy, and myasthenic syndromes. • Anti-CRMP-5 Ab neurologic disease is highly suspicious for underlying malignancy (80–90 %), particularly SCLC and thymoma. • Transient elevation is unusual; titers often remain elevated after neurologic symptoms resolve. • It remains unclear whether anti-CRMP-5 Ab is a pathogenic, incidental, or false positive finding in these cases. Collapsin response-mediator protein 5 (CRMP-5) is a cytoplasmic regulator of neurite outgrowth. Antibodies against CRMP-5 are associated with various neurologic diseases, including myelitis. Underlying malignancy is present in 70 – 90 % of patients with CRMP-5 autoimmunity. We present two patients with myelitis and transiently elevated anti-CRMP-5 without evidence of malignancy and discuss the relevance of the antibody in these cases. 1. A 44-year-old male presented with symptoms of subacute thoracic myelitis and was found to have a persistently enhancing cord lesion on MRI. Serum anti-CRMP-5 antibody levels were initially elevated but absent on subsequent testing. Three whole-body PET scans during a three-year follow-up failed to uncover a malignancy. Neurologic condition improved on steroids. 2. A 65-year-old female presented with symptoms of a cervical myelitis followed by left facial weakness. MRI demonstrated multiple brain and spinal cord lesions as well as evidence of cranial neuritis, which persisted despite pulse steroid courses. Elevated serum anti-CRMP-5 was noted nine months after symptom onset. Malignancy workup failed to identify neoplasm and anti-CRMP-5 level subsequently seroreverted. Clinical and radiographic improvement occurred over several years of follow-up. CRMP-5 autoantibody is a marker for paraneoplastic autoimmune neurologic syndromes. However, these two cases illustrate the uncertainty regarding its significance, as anti-CRMP-5 was only transiently elevated and not associated with an underlying malignancy. The possibilities that anti-CRMP-5 autoantibodies were an incidental or false-positive finding are discussed.