Refractory Anti-NMDA Receptor Encephalitis Improved with Bilateral Salpingo-Oophorectomy

Alyssa Jackson, Rachel Billingsly, Kristin Olson, Miguel Yerena, Lauren Stogner, Shefali Hegde, MD, Rizwan Hassan, DO, Taylor Wallace, MD, Alex LaFever, MD, David Spiegel, MD

Anti-NMDA Receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis, characterized by antibodies directed at the NR1 subunit of NMDA receptors. Decreased NMDA signaling is thought to be the cause of the characteristic neuropsychiatric features. It is a paraneoplastic syndrome, most commonly associated with ovarian teratomas. The disease course involves a viral-like prodrome phase that rapidly progresses to psychiatric symptomatology within weeks to months of onset ranging from deficits in memory, speech, and cognition, to seizure, autonomic dysfunction, altered mental status, and disorganized movements. Prompt diagnosis and treatment is vital as 20% of patients develop focal deficits or die from the resultant encephalitis, with another 10% relapsing within 1-2 years. This novel case report describes a refractory case where empiric bilateral oophorectomy, with subsequent negative pathology, led to symptom resolution.

This was a case of a 32-year-old female with a past medical history of HSV and no past psychiatric history that presented after a witnessed tonic-clonic seizure. UDS was positive for cannabis and cocaine, initially concerning for substance-induced delirium, but with sustained confusion and agitation. Lumbar puncture revealed a mild lymphocytic pleocytosis. CSF studies were positive for anti-NMDA receptor antibodies. A malignancy work-up was negative. She received a course of IVIG and steroids, PLEX and steroids, and then rituximab with only modest improvement. Whole body PET scan was considered, but logistically difficult to obtain due to need for transportation to another facility and ongoing agitation requiring physical restraints. Diagnostic laparoscopy was unremarkable, and a right salpingo-oophorectomy was performed; the pathology report was negative for micro-teratoma. With only minimal symptomatic improvement after nearly 2 weeks, she returned to the OR for an empiric left salpingo-oophorectomy, which was also negative for micro-teratoma. Despite negative ovarian pathology, she demonstrated clinical improvement 2 days later and was discharged to long-term rehab shortly after.

As in this case of refractory anti-NMDAR encephalitis, it is important to exhaust all non-invasive approaches to treatment prior to oophorectomy. Although controversial, bilateral salpingo-oophorectomy should be considered in patients with severe and treatment refractory anti-NMDA encephalitis despite negative imaging. There have been similar cases of anti-NMDA receptor encephalitis described in the literature which have shown improvement after oophorectomy despite negative pathology.