Immunotherapy And Quick Action Key To Fighting Anti-NMDA-receptor Encephalitis Tumor

Editor's Choice
Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience;  Schizophrenia;  Epilepsy
Article Date: 17 Oct 2008 - 0:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

An article published early online and in the December edition of The Lancet Neurology describes the clinical features of 100 patients who were diagnosed with the newly discovered anti-NMDA-receptor encephalitis (ANRE). Dr Josep Dalmau (Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA) and colleagues also note that patient recovery is improved by early tumor removal in combination with immunotherapy.

Synaptic transmission and plasticity rely on ion channels called NMDA receptors (N-methyl-D-aspartic acid). Epilepsy, dementia, and stroke are associated with the excitotoxicity that is caused by overactivity of these receptors, and schizophrenia symptoms are associated with low activity of the receptors. According to Dalmau and colleagues, their recently identified ANRE is a condition that leads to neuropsychiatric syndrome because of antibodies against the subunits that form NMDA receptors.

Although 90% of ANRE cases are in women and the first identified patients were young women with ovarian tumors, the condition can also develop in men and children. ANRE occurred in the ovarian tumor patients when the immune system made antibodies in response to the tumor. This caused the women to have psychosis or memory problems, which quickly led to several serious neurological problems that required intensive care. Recovery is possible, however, after the tumor is removed and the patient receives immunotherapy. In conversation with the media, the authors note that, "ANRE can also, in about 40% of patients, develop without the presence of a tumour. We believe that some of these patients may have a microscopic tumour, but we also acknowledge that most have been followed for many months or years without developing a tumour. Nevertheless, given that the neurologic disease usually develops before the presence of a tumour is known, all patients with this disease should first be examined for a tumour."

Dalmau and colleagues studied 100 ANRE patients (91 female and 9 male) ranging from five to 76 years of age. Each patient had psychiatric symptoms or memory problems. Of the 100, 76 had seizures, 88 had decreased consciousness, 86 suffered from involuntary movements (usually of the face), 69 had autonomic nervous system instability, and 66 had hypoventilation (inadequate breathing). Ninety-eight patients were tested for cancer and 58 presented with tumors, mostly ovarian teratomas. Better outcomes and fewer neurological relapses were noted in patients who had early tumor treatment in combination with immunotherapy. Although 25% of the patients had severe deficits or died, three quarters of them recovered or only had mild neurological deficits. Overall, improvements were associated with a reduction in anti-NMDA receptor antibodies.

Ultimately, the researchers say the anti-NMDA receptor antibodies decreased the numbers of cell-surface NMDA receptors and receptor clusters in the postsynaptic dendrites of the nervous system - an effect that, by removing the antibodies, could be reversed. "A well-defined set of clinical characteristics are associated with anti-NMDA-receptor encephalitis. The pathogenesis of the disorder seems to be mediated by antibodies," conclude the researchers.

Professor Angela Vincent (Department of Clinical Neurology, University of Oxford, UK) and Dr Christian Bien (University of Bonn, Germany) write in an accompanying reflection and reaction that, "The clinical presentation of psychosis-like symptoms, seizures, abnormal movements, and autonomic disturbances is highly characteristic of NMDA-receptor antibodies in both female and male patients. This syndrome has already become an essential consideration in the diagnosis of subacute or acute encephalopathies, particularly in young people, and one should expect the clinical phenotype to expand further as more cases are reported. This is certainly an important development in the study of autoimmune encephalopathies."

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies
Josep Dalmau, Amy J Gleichman, Ethan G Hughes, Jeffrey E Rossi, Xiaoyu Peng, Meizan Lai, Scott K Dessain, Myrna R Rosenfeld, Rita Balice-Gordon, David R Lynch
The Lancet Neurology (2008).
DOI:10.1016/S1474-4422(08)70224-2
Click Here to View Journal Website

Written by: Peter M Crosta
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today