# IgG-NR2B--A Potentially Valuable Biomarker in the Management of Refractory Anti-NMDAR Encephalitis
## 2 Case Report
She was also noted to have brief episodes of tonic-clonic seizure activity necessitating critical anesthesiologist care. Acute respiratory failure led to emergent endotracheal intubation, including mechanical ventilation. Intravenous continuous anesthetic therapy with thiopental was administered for sedation, as well as for the treatment of refractory status epilepticus. A CT chest-abdomen-pelvis scan was requested for further evaluation, and in the right ovary a smaller-sized solid cystic mass-like lesion, more akin to a dermatoid cyst, was found (Figure 3). Figure 3: CT examination of the small pelvis, with a dermatoid cyst (yellow box) found in the region of the right ovary. Figure 2: EEG findings of generalized PSW complexes. \begin{table}
\begin{tabular}{l c c c c c c c c c c c c c c c c c c c c c c c c c} \hline \hline  & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** & **Day** \\  & **1** & **7** & **10** & **16** & **22** & **33** & **39** & **47** & **53** & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & \\ \hline CSF Proteins (g/L) & 1.43 & ND & 0.55 & ND & 0.42 & ND & 0.25 & ND & ND & CSF Proteins (g/L) & ND & 0.33 & 0.37 & ND & ND & ND & ND & 1.06 & ND & ND & ND \\ CSF Abumin (g/L) & 0.808 & ND & 0.212 & ND & 0.118 & ND & 0.105 & ND & ND & CSF Abumin (g/L) & ND & 0.11 & 0.115 & ND & ND & ND & ND & 0.594 & ND & ND \\ CSF Mononuclear & 723 & ND & 533 & ND & 76 & ND & 14 & ND & ND & ND & CSF Mononuclear & ND & 7 & 28 & ND & ND & ND & 0 & ND & ND \\ CSF Polynuclear /uL & 2 & ND & 4 & ND & 0 & ND & 1 & ND & ND & CSF Polynuclear /uL & ND & 0 & 127 & ND & ND &  
While there was no response to the first-line immunotherapy, second-line immunotherapy with rituximab (375 mg/m\({}^{2}\)/every two weeks for two cycles) was initiated, and this immunotherapy included the use of cyclophosphamide (after 2 months, a monthly dose of 750 mg/m\({}^{2}\) was used). The patient also underwent a laparoscopic right-overay cystectomy. After tumor removal, the histological findings revealed a mature ovarian teratoma. Hematoxylin-eosin (HE) staining revealed a characteristic spectrum of elements, including stratified squamous epithelium and cutaneous adnexal structures (sweat glands and pilosebaceous units with hair follicles and sebaceous glands) and fat tissue accompanied by neuroglial cells (Figure 4). Subsequent immunohistochemical staining showed an expression of the NR2B subunits of NMDARs in different structures of the teratoma, including the neuroglial cells (Figure 5). No sustained improvement occurred after the initiation of either first- or second-line immunotherapies or after tumor removal (her GCS score was 3, her mRS score was 5). Our patient progressed into a state of unresponsiveness within 86 days. The control EEG recording showed a unique electrographic pattern with \"extreme delta-brush\". There was an increased level of CSF anti-NMDAR antibodies with monocytosis (28). Due to excessive intrathecal antibody production with unsuccessful recovery from standard immunotherapy, we realized that these therapeutic strategies were insufficient in our patient. After the failure of the first- and second-line immunotherapies, an intrathecal application of methotrexate (15 mg weekly during the first two weeks, followed by a weekly dose of 10 mg), along with dexamethasone (20 mg), was carried out for 4 weeks. CSF and blood samples were collected before each intrathecal injection for the identification of anti-NMDAR antibodies (Table 4). After the second application of methotrexate (MTX) and dexamethasone (DXM),  
Figure 4: Histological appearance of mature ovarian teratoma composed of different structures—stratified squamous epithelium, cutaneous adnexal structures (sweat glands, pilosebaceous units with hair follicles and sebaceous glands), fat tissue, and neuroglial cells.