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Anti–NMDA-Receptor Encephalitis and Demyelinating Syndromes

Summary and Comment |
March 17, 2014

Anti–NMDA-Receptor Encephalitis and Demyelinating Syndromes

  1. Robert T. Naismith, MD

Clinicians should consider antibody testing in certain cases of encephalitis, neuromyelitis optica, acute disseminated encephalomyelitis, and brainstem encephalitis.

  1. Robert T. Naismith, MD

Anti–N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a treatable autoimmune disease with immunoglobulin G antibodies directed at the GluN1 receptor subunit. Symptoms may include seizures, altered consciousness, memory loss, sleep dysfunction, fever, hypoventilation, confusion, psychosis, depression, autonomic disorders, dystonia, and dyskinesias. Patients often present with a normal brain magnetic resonance imaging (MRI) scan or with transient, mild, or nonspecific MRI abnormalities. This case series includes 23 patients from a cohort of 691 with NMDAR encephalitis who presented with MRI T2 lesions and signs consistent with demyelination either at the same time as the encephalitis or before or afterward. Demyelinating syndromes were categorizable as acute disseminated encephalomyelitis (ADEM), NMO-spectrum disorder (NMOSD), or a brainstem/bulbar/multifocal syndrome.

Twelve patients presented with the two conditions separately. Four patients with NMOSD and aquaporin-4 (AQP4) positivity developed NMDAR encephalitis 11 to 80 months later, and one patient without AQP4 antibodies developed NMOSD 1 month after recovering from NMDAR encephalitis. Three patients with brainstem syndromes and four with a multifocal demyelinating episode presented with NMDAR encephalitis either 3 to 36 months before or 22 to 96 months after the demyelinating episode. Eleven patients presented with NMDAR encephalitis and demyelinating episodes concurrently, manifested as MRI T2 lesions, mainly infratentorially and within the spinal cord, along with cranial neuropathies, ataxia, and hemiparesis. Of these 11 patients, 5 had AQP4 antibodies and 2 had MOG antibodies. Among all 23 patients, episodes were treated with glucocorticoids, intravenous immunoglobulin, or plasma exchange, sometimes requiring multiple acute treatments for clinical improvement. Among control patients, antibody cross-reactivity was minimal: One of 50 NMDAR encephalitis patients had AQP4 antibodies and one of 56 NMO patients had MOG antibodies. None of 30 patients with typical MS had NMDAR or AQP4 antibodies.

Comment

This is an important description of a cohort of patients who have antibody-mediated disease that causes multiple, distinct neurological disorders. MOG antibodies are not commercially available, but patients with NMO, ADEM, or NMDAR encephalitis should be tested for the other disorders if indicated by their MRI scan or clinical presentation. In certain situations, diagnosing someone with NMO may have long-term treatment implications to prevent an additional disabling relapse (NEJM JW Neurol May 29 2012).

Note to readers: At the time NEJM JW reviewed this paper, its publisher noted it was not in final form and that subsequent changes might be made.

  • Disclosures for Robert T. Naismith, MD at time of publication Consultant / Advisory board Acorda Therapeutics; Biogen Idec; EMD Serono; Genzyme; Questcor Speaker's bureau Acorda Therapeutics; Bayer Healthcare; Biogen Idec; Genzyme Grant / research support NIH; Acorda Therapeutics; National Multiple Sclerosis Society Leadership positions in professional societies Consortium of MS Centers (Speaker); National Multiple Sclerosis Society (Local Chair of Clinical Advisory Committee; Program Services Committee, Research Advocate, and Research Champion)

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