A 24-year-old woman is brought to the office by her roommate due to behavioral changes. After taking a few days off work to recover from flu-like symptoms a month ago, the patient started to feel anxious about getting fired. Despite repeated reassurance from her boss, she continued to fixate on losing her job and had difficulty sleeping. More recently, she became convinced that her employer was trying to harm her and stopped going to work. The patient has been increasingly forgetful over the past week and was briefly unable to recognize well-known friends that came to visit her. Earlier today, her roommate noticed the patient staring blankly and smacking her lips rhythmically for about a minute while they watched television. An incidental, 2-cm, right-sided ovarian teratoma was visualized on ultrasound 2 months ago; the patient is scheduled for surgical resection next month. She has no other medical or psychiatric history. Temperature is 38 C (100.4 F), blood pressure is 167/86 mm Hg, pulse is 122/min, and respirations are 14/min. The patient is fully oriented, although easily distracted. The left hand is clenched, and the left wrist is held in sustained flexion. Mild rigidity is noted in the upper extremities. Deep tendon reflexes are 3+ throughout, and her gait is normal. She appears to be responding to internal stimuli and mumbles to herself during the examination. Which of the following is the most likely diagnosis?
This patient's psychiatric symptoms (eg, anxiety, psychosis, insomnia), autonomic instability (eg, hyperthermia, hypertension, tachycardia), cognitive impairment, rigidity, hyperreflexia, dystonia, and focal seizure after a flu-like prodrome in the setting of known ovarian teratoma strongly suggest anti-NMDA receptor (anti-NMDAR) encephalitis. This form of autoimmune encephalitis tends to present as a multistage syndrome with characteristic features. Anti-NMDAR encephalitis has a median age of onset of 21; it is 4 times more common in women, of whom >50% have an associated ovarian teratoma, as seen in this patient.
The clinical diagnosis can be confirmed by the presence of cerebrospinal fluid antibodies to the GluN1 subunit of the NMDAR. Because of the association with tumors, patients with anti-NMDAR encephalitis should undergo imaging. If applicable, prompt tumor removal has been associated with better outcomes. Regardless of the presence of a tumor, immunosuppressive treatment is the cornerstone of therapy. Recovery is often slow, but 4 of 5 patients recover with minimal sequelae within 2 years.
(Choice A) Aseptic meningitis typically presents with headache, fever, and photophobia. Meningitis, unlike encephalitis, classically presents with normal cognitive function, unlike the altered mental status seen in this patient.
(Choices C and E) Although both brief psychotic disorder and schizophreniform disorder are associated with psychosis (eg, hallucinations, delusions) and mild cognitive dysfunction (eg, disorganization), neither would explain this patient's neurologic symptoms (eg, focal seizure, rigidity, dystonia, hyperreflexia) or autonomic dysfunction. Brief psychotic disorder is diagnosed when psychotic symptoms are present for >1 day but <1 month, whereas schizophreniform disorder is diagnosed when symptoms have persisted for >1 month but <6 months.
(Choice D) Huntington disease presents with an insidious onset of chorea, abnormal eye movements, and psychiatric symptoms. Cognitive impairment is a core feature but usually develops later in the disease course. This patient's rapid symptom onset, history of ovarian teratoma, autonomic instability, and absence of characteristic choreiform movements make autoimmune encephalitis more likely.
Educational objective:
Anti-NMDA receptor encephalitis is an autoimmune encephalitis syndrome characterized by psychiatric symptoms (eg, anxiety, psychosis), cognitive dysfunction (eg, memory impairment), seizure, autonomic instability, dystonia, and rigidity. It occurs most commonly in young women (median age of 21) and is associated with ovarian teratoma in >50% of cases.