Case Presentation: A 32-year-old female was admitted after a seizure. Brain MRI was unremarkable and lumbar puncture yielded 133 white blood cells with 100% lymphocytes. Within a few days, refractory seizures occurred. Due to suspected autoimmune encephalitis, plasma exchange and high-dose steroids were started. Cerebral spinal fluid (CSF) studies returned with IgG antibody levels for NMDA receptors being significantly elevated. CT imaging revealed a 4.1 cm lesion associated with the right ovary, and subsequent ultrasound confirmed a right ovarian mass and also a lesion in the left ovary. She underwent bilateral salpingo-oophorectomy. Pathology results demonstrated bilateral teratomas. Intravenous immunoglobulin (IVIG) therapy was initiated for five days after a full course of plasma exchange. Rituximab and then cyclophosphamide were initiated after minimal clinical improvement. With ongoing encephalopathy, electroconvulsive therapy (ECT) was performed for six days, and amantadine was also trialed. She improved minimally over the next 3-4 weeks. IVIG treatments were then resumed weekly along with tramadol for dyskinesias. Bortezomib was started, and ECT was resumed. PET scan was performed to look for any occult tumors and found an active left thyroid nodule; biopsy showed papillary thyroid carcinoma, and total thyroidectomy was performed. Over the next several weeks, the patient slowly recovered and finally discharged after more than three months of hospitalization.
Discussion: This is a challenging case of anti-NMDA receptor encephalitis that comprehensively summarizes numerous interventions and medications that may need to be considered in order to treat this disease and its associated symptoms. This is an autoimmune disease caused by IgG antibodies that attack the NR1 subunit of NMDA receptors in the brain [1]. This disease can have a wide range of neurologic and psychiatric symptoms to include autonomic instability, seizures, dyskinesias, cognitive dysfunction, catatonia, hallucinations, and agitation [2]. Prodromal symptoms such as gastrointestinal or viral symptoms may precede the development of this disease. Work-up frequently includes a lumbar puncture, and CSF abnormalities that may be present include lymphocytosis, mild to normal protein level, and oligoclonal bands. The diagnosis can be confirmed with positive serum or CSF antibodies for the NMDA receptor. Imaging typically consists of a brain MRI, although this can frequently be normal [3]. First-line therapies are focused on immunosuppression, and includes steroids, IVIG, and plasma exchange [4]. Second- and third-line therapies may include rituximab, cyclophosphamide, and bortezomib [5]. Importantly, tumors are common, particularly ovarian tumors, in these patients, and removal is typically needed. The presence of other tumors, including those of the thyroid, has also been described, but their association with this disease is still unclear [6]. Equally important, the symptoms must be treated as well, and this may include therapies such as ECT and amantadine for catatonia [7], and tramadol for dyskinesias [8].
Conclusions: Anti-NMDA receptor encephalitis management is focused on immunosuppression while simultaneously providing supportive cares and treating any tumor or malignancy. Hospitalists should be aware that this disease sometimes requires numerous interventions and medications for treatment. Some of the facts related to this case may have been changed to protect the identity of the patient.