A textbook for every neurologist

Abstract

Neurologic paraneoplastic syndromes (NPSs) account for a tiny percentage of the complications seen in cancer patients, but they were the starting point for the interest of neurology in a discipline that would later be dubbed neuro-oncology. The possibility that not all neurologic lesions seen in cancer patients are due to metastases was first considered by Heinrich Oppenheim in 1888. However, the concept of the remote effect of cancer on the nervous system was first articulated by Derek Denny-Brown, when, in 1948, he reported two patients with lung carcinoma and sensory neuronopathy. The pioneers who further developed this field were mainly British neurologists: Peter Croft, Ronald Henson and Marcia Wilkinson. In the early 1960s these authors confirmed the association of cancer with sensory neuronopathy, and described other paraneoplastic diseases such as limbic encephalomyelitis and subacute cerebellar degeneration. Thanks to the interest of Lord Brain, then editor of the journal, most of the seminal papers were published in Brain . In 1965, Lord Brain and Raymond Adams provided the first clinical classification and pathological characterization of NPSs in their concluding chapter to the remarkable and now classic book edited by Lord Brain and Forbes Norris from San Francisco, The remote effect of cancer on the nervous system (1965). But the pathogenesis of these conditions remained mysterious for some time. Jerome Posner and his associates Francesc Grauss, Josep Dalmau and many others have contributed more than anyone else to the understanding of NPSs by identifying specific antibodies directed against onconeural antigens expressed by some tumours and the nervous system. These antibodies are able to slow tumour growth and even eradicate the cancerous lesion, but their role in the pathogenesis of NPSs has not been entirely elucidated. In Lambert–Eaton myasthenic syndrome (LEMS) the circulating antibodies, directed against voltage-gated calcium-channel protein, are clearly …