Anti-Hu Associated Paraneoplastic Encephalomyelitis
Abstract & Commentary
Source: Graus F, et al. Anti-hu-associated paraneoplastic encephalomyelitis: Analysis of 200 patients. Brain. 2001;124: 1138-1148.
Two European groups studying paraneoplastic syndromes, one headed by Frances Graus in Barcelona and the other by Jean Yves Delattre in Paris, studied 200 patients suffering from paraneoplastic encephalomyelitis associated with high titers (> 1:1000) of the anti-Hu (ANNA-1) paraneoplastic antibody. They reviewed the clinical findings to "identify patient-, tumor- and treatment-related characteristics associated with neurologic disability and survival." They found, as have previous investigators, that the paraneoplastic disease was devastating. Clinical symptoms of sensory neuropathy, cerebellar degeneration, cortical encephalitis, brainstem encephalitis, sensory motor neuropathy, and dysautonomia either singly or in combination marked the syndrome. The neurologic syndrome preceded identification of the tumor in 85% of the patients, and at diagnosis, more than half were disabled by the neurologic disorder. In those who died, 60% died a neurologic death. Only in 5% of patients were the clinical symptoms, usually those of sensory neuropathy, mild and indolent. The cancer was usually small-cell lung cancer and, in almost all instances, the associated cancer contained the Hu antigen. In those few that did not, sampling error may be responsible because at times only a minority of cells express the antigen.
Two factors of clinical importance loom large: The first is that the milder the clinical symptomatology, the longer the delay in finding the tumor. The second is that only tumor treatment appears to affect the course of the neurologic disease. Graus and colleagues were unable to adduce evidence that immunotherapy significantly ameliorated the neurologic syndrome.
This paper gives the neurologist enough information to identify the anti-Hu syndromes and manage them appropriately. The only difference between these European data and similar data from the United States is the percentage of women suffering from small-cell lung cancer. In Spain, women represent 15% of the small-cell lung cancer population and in France, 33%. At Memorial Sloan-Kettering Cancer Center, more than 50% of newly diagnosed small-cell lung cancers are in women. This is important because among patients with small-cell lung cancer, women are far more likely to develop a paraneoplastic syndrome than are men. With the data from this paper and serum for anti-Hu antibodies, the neurologist can make an early diagnosis of even mild sensory or sensorimotor neuropathy, cerebellar ataxia, or limbic encephalitis as having a paraneoplastic etiology. As this paper indicates, the only even partially effective treatment is early identification and eradication of the cancer, while the patient is still neurologically independent. (Author’s note: Graus et al kindly dedicated their paper to me. I am flattered, but I wish I had written it rather than inspired it.) —Jerome B. Posner