Fast Treatment Can Reverse Progress of Newly Recognized Disease Anti-NMDA Receptor Encephalitis and its Related Tumor
LONDON, Oct. 12, 2008--The clinical features of 100 patients diagnosed with the recently discovered condition anti-NMDA-receptor encephalitis (ANRE) are reported in an Article early Online and in the December edition of The Lancet Neurology, written by Dr Josep Dalmau, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA, and colleagues. Further, they discuss how fast tumour removal and immunotherapy is associated with patients recovery.
NMDA receptors are ion channels with crucial roles in synaptic transmission and plasticity. Overactivity of these receptors, causing excitotoxicity, is a proposed underlying mechanism for epilepsy, dementia, and stroke, whereas low activity produces symptoms of schizophrenia. Dalmau and colleagues recently identified ANRE, which is associated with antibodies against the subunits that form NMDA receptors, and results in a characteristic neuropsychiatric syndrome. Whilst it mainly affects women (around 90% of cases), ANRE can also be found in men and children. The first patients identified were young women with ovarian tumours. The immune system in these patients produces antibodies in response to the tumour, which in turn leads to ANRE. The women presented with psychosis or memory problems, rapidly progressing to multiple serious neurological problems requiring intensive care; but after tumour removal and immunotherapy, patients can recover. The authors say*: “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.”
Of the 100 ANRE patients aged 5–76 years analysed, 91 were female. All had psychiatric symptoms or memory problems; 76 had seizures, 88 decreased consciousness; 86 involuntary movements frequently involving the face; 69 autonomic nervous system instability; and 66 hypoventilation. Of 98 patients tested for cancer, 58 had tumours—most commonly ovarian teratomas. Patients who had early tumour treatment along with immunotherapy had better outcome and fewer neurological relapses than the rest of the patients. Of the 100 patients, 75 recovered or had mil neurological deficits, while 25 had severe deficits or died. Patients’ improvement was associated with a decrease in anti-NMDA receptor antibodies. The researchers conclude that these antibodies reduced the numbers of cell-surface NMDA receptors and receptor clusters in the postsynaptic dendrites of the nervous system; this effect could be reversed by removing the antibodies.
They say: “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.”
In an accompanying Reflection and Reaction comment, Professor Angela Vincent, Department of Clinical Neurology, University of Oxford, UK, and Dr Christian Bien, University of Bonn, Germany, say: “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.”
Dr Josep Dalmau, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA. T) +1 215-746-4707
Reflection and Reaction Professor Angela Vincent, Department of Clinical Neurology, University of Oxford, UK. T) +44 (0) 1865 222321
josep.dalmau@uphs.upenn.edu
angela.vincent@imm.ox.ac.uk
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Posted: October 2008
