ABSTRACT
Paraneoplastic neurological syndromes belong to the most enigmatic and fascinating disorders. Their remarkable clinical spectrum ranges from sensory neuronopathy to cerebellar degeneration or limbic encephalitis. We retrace the clinical and pathological description of a forgotten case published by Hermann Oppenheim in 1888, which to our knowledge represents the first report of a paraneoplastic neurological syndrome. The young Oppenheim used thorough observation and good clinical judgment to suggest a causal link between the seemingly mere association of an underlying malignancy and a neurological syndrome, decades before Denny-Brown's identification of sensory neuronopathy in 1948 and a century before the discovery of "anti-Hu" antibodies. Oppenheim anticipated that scientific progress was required to prove this link, and he indicated his finding as "a pointer for future observers." In this way, he leaves the reader with the fascinating question of which observations during our current neurology practice could be the next "pointers" in medical research.
Subject(s)
Paraneoplastic Syndromes, Nervous System/history , Female , Germany , History, 19th Century , History, 20th Century , HumansABSTRACT
Paraneoplastic neurological syndrome (PNS) may affect any part of the nervous system and muscles. PNS is a rare disorder caused by the remote effects of cancer and is considered to be immune-mediated. Since the 1980s, several specific onco-neural antibodies and T-cell responses against onco-neural molecules have been reported, as shown in the historical review in this article. Immunoresponses to cancer are considered to cross-react with self-antigens in the nervous system or muscle. The presence of such onco-neural antibodies is a useful diagnostic marker for PNS and occult cancer. Despite sustained efforts to elucidate the effects of such antibodies on neuron, only a few onco-neural antibodies have been identified as primary effectors of neurological symptoms. However the absence of these antibodies does not exclude a PNS. In some instances, these antibodies can be detected in cancer patients without PNS. PNS diagnosis requires excluding many other complications of cancer and mimics of other neurological diseases as differential diagnoses. Recently, an international panel of experts provided useful diagnostic criteria for PNS. These criteria are based on well-characterized onco-neural antibodies and specific neurological syndromes. Probable cases of PNS are strongly advised to undergo early antitumor therapy and immunotherapy to prevent progressive neuronal death. As the symptoms of PNS often appear before the diagnosis of malignant cancer, repeated searches for occult cancer are recommended, if the tumor has not yet been found. Further studies are required to clarify the exact mechanisms underlying neuronal damage in PNS, which may lead to the development of more rational therapies and greater understanding of immunology in the nervous system.
