Anti–N-methyl-D-aspartate Receptor Encephalitis

Abstract

Anti–N-methyl-d-aspartate (anti-NMDA) receptor encephalitis is a treatable paraneo-plastic disorder predominantly affecting young women. It is characterized by a combination of psychotic encephalopathy, seizures, and abnormal movements of the trunk and face, particularly in the form of jaw dystonia. Enhanced awareness of the typical presentation can increase the index of suspicion and facilitate initiation of appropriate treatment. A previously healthy 26-year-old African American woman presented to the emergency department after an acute episode of psychotic behavior in which she was described as becoming abruptly agitated and restless. Over the next few days, she developed seizures and sustained impairment of consciousness for which she required intubation and intensive care monitoring. She showed intermittent agitation with screaming and crying spells. Electroencephalography revealed bilateral independent temporal epileptiform discharges, which prompted treatment with phenytoin. On neurological examination, she was awake but unresponsive to verbal or noxious stimulation. Several episodes of jaw-opening dystonia, paroxysmal opisthotonus, and catatonic postures were observed (Figure 1A and B, video [http://www.archneurol.com]). Figure 1 Jaw-opening dystonia (A) and opisthotonic posture (B) are observed. C, A fluid-attenuated inversion recovery sequence of an axial brain magnetic resonance image shows symmetric hyperintensities in the cerebellar hemispheres (arrows). Analysis of cerebrospinal fluid showed lymphocytic pleocytosis (white blood cell count, 200/µL), with normal glucose and protein levels. Results from cytology, Gram stain, cultures, and polymerase chain reaction for herpes simplex virus, varicella zoster virus, Epstein-Barr virus, and West Nile virus in cerebrospinal fluid were negative. Brain magnetic resonance imaging disclosed hyperintensities in both cerebellar hemispheres (Figure 1C). Results for human immunodeficiency virus, rapid plasma reagin, serum cultures, autoimmune panel, and thyroid-stimulating hormone, free thyroxine, folic acid, and B12 levels were within normal limits. Results from the following paraneoplastic antibody tests were negative: antineuronal nuclear, cytoplasmatic Purkinje cell, amphiphysin, collapsing-response mediator protein type 5, calcium channel, acetylcholine receptor ganglionic neuronal, antiglial nuclear, and voltage-gated potassium channel. Using human embryonic kidney 293 cells transfected with NR1/NR2 heteromers,1 antibodies against NMDA receptors were found in cerebrospinal fluid (serial dilutions; titer, 1:160) and serum (titer, 1:40). Although initial pelvic computed tomographic and ultrasonographic results were unrevealing, a pelvic magnetic resonance image demonstrated a right 9-mm ovarian mass (Figure 2A), which proved to be a teratoma on histopathological analysis (Figure 2B). Surgical teratoma excision and intravenous methylprednisolone sodium succinate led to noticeable improvement in function over the next few days. Five weeks after this treatment, the patient had returned to work. Figure 2 Imaging and histopathological findings. A, A T1-weighted magnetic resonance image of the pelvis shows a 9-mm high-signal mass in the right ovary, suggestive of a small teratoma (arrow). B, Hematoxylin-eosin staining of the ovarian mass demonstrates typical ...