Fast Treatment Can Reverse Anti-NMDA-Receptor Encephalitis

Allison Gandey

October 20, 2008

October 20, 2008 – Tumor removal and immunotherapy can reverse anti-NMDA–receptor encephalitis, researchers show. Reporting in an early release published online October 11 in Lancet Neurology, investigators shed light on this recently discovered condition.

This syndrome has already become an essential consideration in the diagnosis of subacute or acute encephalopathies – particularly in young people – editorialists Prof. Angela Vincent, from the University of Oxford, in the UK, and Christian Bien, MD, from the University of Bonn, in Germany, point out in an accompanying Reflection and Reaction article.

"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," they note.

This is certainly an important development in the study of autoimmune encephalopathies.

"The clinical presentation of psychosislike symptoms, seizures, abnormal movements, and autonomic disturbances is highly characteristic of NMDA-receptor antibodies in both female and male patients," the editorialists write.

Recovery from this disorder is typically slow, and symptoms may recur – especially in patients with undetected or recurrent tumors and patients with no associated tumors.

Lead investigator Josep Dalmau, MD, from the University of Pennsylvania, in Philadelphia, and his team show that improvement was associated with a decrease in anti-NMDA–receptor antibodies.

The researchers suggest that these antibodies reduced the numbers of cell-surface NMDA receptors and receptor clusters in the postsynaptic dendrites of the nervous system. This effect, they say, could be reversed by removing the antibodies.

Essential New Consideration in Diagnosing Encephalopathies

Less than 2 years ago, this same group published an article on the new condition (Dalmau J et al. Ann Neurol. 2007;61:25-36). They reported on a series of 12 female patients with teratomas and a newly discovered antibody, which, although mainly paraneoplastic, identifies a potentially treatable disease in young people.

The women presented with psychosis or memory problems, rapidly progressing to multiple serious neurological problems requiring intensive care.

Now these same researchers report the clinical features of 100 female and male patients.

"This surprisingly rapid collection of so many patients suggests that the disorder is not rare," the editorialists note.

NMDA receptors are ion channels with key roles in synaptic transmission and plasticity. Overactivity of these receptors, causing excitotoxicity, is a proposed underlying mechanism for epilepsy, dementia, and stroke. Low activity of these same receptors can produce symptoms of schizophrenia.

Can Develop in About 40% of Patients Without Tumors

In about 40% of patients, anti-NMDA–receptor encephalitis can develop without the presence of a tumor. "We believe that some of these patients may have a microscopic tumor, but we also acknowledge that most have been followed for many months or years without developing a tumor," the researchers write.

Nevertheless, they note, given that the neurologic disease usually develops before the presence of a tumor is known, all patients with this disease should first be examined.

In this latest report, 91 of the 100 patients were female and:

  • All had psychiatric symptoms or memory problems.

  • 76 had seizures.

  • 88 experienced decreased consciousness.

  • 86 had involuntary movements frequently involving the face.

  • 69 experienced autonomic nervous system instability.

  • 66 had hypoventilation.

Of 98 patients tested for cancer, 58 had tumors – most commonly ovarian teratomas. Patients who had early tumor treatment along with immunotherapy had better outcome (P = .004) and fewer neurological relapses (P = .009).

Of the 100 patients, 75 recovered or had mild neurological deficits. A total of 25 had severe deficits or died.

Dr. Dalmau and his team conclude, "Future studies should clarify the best type and duration of immunotherapy, the role of prodromal events in triggering the immune response, and the molecular mechanisms involved in decreasing the number of NMDA receptors."

The study was funded by the National Institutes for Health, the University of Pennsylvania Institute for Translational Medicine, the Lankenau Institute for Medical Research, and the Foederer Foundation of the Children's Hospital of Philadelphia.

Lancet Neurol. Published online October 11, 2008. Abstract Abstract

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