Update on paraneoplastic syndromes

Abstract

This review discusses the varied clinical spectrum of neurologic paraneoplastic disorders, describes recent advances in our understanding of autoimmunity in these disorders, and outlines a practical clinical approach to patient management. Paraneoplastic disorders may affect any part of the central or peripheral nervous system. Although relatively uncommon, these disorders are a significant cause of severe and permanent neurologic disability. Syndromes such as limbic encephalitis or opsoclonus-myoclonus should always raise suspicion of a paraneoplastic condition, but any paraneoplastic syndrome can also occur in patients without a neoplasm. Most neurologic paraneoplastic disorders are thought to be caused by an autoimmune reaction directed against ‘onconeural’ antigens expressed by neurons and tumor cells. Some syndromes such as Lambert–Eaton myasthenic syndrome and neuromyotonia are clearly mediated by autoantibodies. Much less is known about the immunopathogenesis of syndromes that affect the central nervous system, although a growing body of evidence implicates cellular immune effectors in causing neuronal injury. Many patients have circulating antineuronal antibodies, which can be useful in identifying a neurologic disorder as paraneoplastic and in finding the associated neoplasm. Early diagnosis of the neurologic disorder and prompt initiation of tumor treatment probably increase the likelihood of neurologic improvement. Neurologists must be able to recognize the clinical manifestations of neurologic paraneoplastic disorders, and to distinguish them from other causes of neurologic dysfunction in cancer patients. Early diagnosis of paraneoplastic syndromes maximizes the likelihood of a favorable oncologic and neurologic outcome.