Paraneoplastic Neurologic Syndromes—An Update on Current Understanding and Future Perspectives

Abstract

Paraneoplastic neurological syndromes (PNS) are remote effects of tumors on the nervous system. They can strike at single or at multiple sites of the central nervous system (CNS) and the peripheral nervous system, and often appear before the detection of cancer. PNS can be disabling and debilitating and may be either an additional burden to cancer or the cause of death. The PNS Euronetwork group has collected a series of approximately 1,000 patients in several European centers. This study is the largest systematic series of patients with PNS and, for the first time, can answer questions about the most frequent PNS, their detailed symptoms, associated antibodies, and the types of underlying tumors. The clinical course and laboratory findings for many PNS suggest an autoimmune pathogenesis; however, research into this heterogeneous immunological relationship has been evolving over recent decades. The classic syndromes are antigen-target-oriented syndromes such as myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and ion channel-mediated diseases. Onconeuronal antibodies constitute a large group of PNS, characterized by the appearance of specific antibodies, defined clinical signs and often an association with specific tumors. In recent years, a new group of antibodies directed at surface antigens as receptors has been identified. Finally, there is a long list of ‘other’ PNS, which are evident to clinicians but which have no pathogenetic explanation. Examples include the mild terminal neuropathies and sarcopenia in cancer patients. In addition to the emerging classification based on pathophysiology, other new syndromes and symptoms have appeared, including apnea in brainstem encephalitis, a neuropsychiatric spectrum of limbic encephalitis, and increased knowledge about LEMS. Two important aspects warrant attention: some PNS respond to therapy and not all paraneoplastic-like syndromes are tumor related. This view is based on the current understanding of immune pathogenesis and on the enlarged spectrum of PNS.