Case Presentation: A 20 year old female with a history of childhood seizures, major depressive disorder, and post-traumatic stress disorder was evaluated for acute onset of bizarre behavior, confusion and disorganized thoughts for the past three days. Her initial psychiatric exam was notable for labile mood, psychomotor agitation and paranoia, but otherwise neurologic examination was unrevealing. She was admitted to the psychiatric unit and initiated on antipsychotic medications. She then became nonverbal, akathisic and her symptoms worsened despite adjustment of medications. She then developed possible neuroleptic malignant syndrome (NMS), which resolved with benzodiazepines and discontinuation of all antipsychotics. However, she subsequently developed catatonic posturing and convulsive status epilepticus. In addition, she had intermittent tachycardia and fevers deemed as autonomic instability. Brain imaging and extensive evaluation for acute infection, lupus and toxic metabolic etiologies were unrevealing. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis and was later found to have N-methyl D-aspartate receptor (NMDAR) antibodies. She was initially treated with intravenous immunoglobulin and high dose methylprednisolone without significant improvement. She was then treated with rituximab, after which her mentation and speech improved. Computed tomography (CT) of the chest, abdomen, and pelvis did not demonstrate primary malignancy, and specifically, pelvic imaging did not show ovarian teratoma. However, whole body PET-CT did show evidence of myositis ossificans of the bilateral gluteal regions.
Discussion: Initial clinical presentation of anti-NMDAR encephalitis, especially the neuropsychiatric symptomatic phase, allows for a wide differential diagnosis. It may be characterized as (1) primary psychiatric (acute psychosis, schizophrenia spectrum disorders, malignant catatonia), (2) toxic metabolic (intoxication/withdrawal, NMS, serotonin syndrome), (3) infectious (HSV/EBV encephalitis, mycoplasma pneumoniae), (4) neurologic (autoimmune or paraneoplastic encephalitis, stroke, acute disseminated encephalomyelitis) and (5) rheumatologic (CNS-lupus associated encephalopathy). Establishing an anti-NMDAR encephalitis diagnosis is especially crucial to monitor for relapses and rule out underlying malignancy. In particular, it has been associated with ovarian teratomas, the removal of which has been associated with better prognosis. In rare cases, as in this patient, heterotopic calcification such as myositis ossificans has been reported as a complication of encephalitis.
Conclusions: Although only recently described and its incidence is unknown, anti-NMDAR encephalitis is becoming more frequently reported, suggesting it was likely significantly underdiagnosed in the past. Acute onset psychosis, especially in a young, previously healthy individual, should necessitate the consideration of anti-NMDAR encephalitis, as early treatment has been associated with better outcomes and shorter hospital stays. Furthermore, its association with infectious encephalitis, underlying malignancy, and ovarian teratomas may alter management.