# IgG-NR2B--A Potentially Valuable Biomarker in the Management of Refractory Anti-NMDAR Encephalitis
## 2 Case Report  
A 25-year-old female with no prior serious issues in her medical or psychiatric history was admitted to a local infectious department for severe headache, nausea, and a fever (body temperature of 39.0 \({}^{\circ}\)C) which lasted for 4 days. Because of her headache, photophobia, phenophobia, and neck stiffness, acute meningitis was considered for the patient. We carried out computed tomography (CT) of the brain, as well as a brain magnetic resonance imaging (MRI) scan, with negative findings for any acute process. Initial laboratory studies, including a comprehensive metabolic panel and electroencephalogram (EEG), were unremarkable. After a few days, she began to develop psychiatric symptoms (she was confused, aggressive, and somnolent). She underwent a diagnostic lumbar puncture with a routine cerebrospinal fluid (CSF) examination (Table 2), with normal glucose findings \begin{table}
\begin{tabular}{l l l l} \hline \hline
**Treatment** & **Dose/Unit/Frequency** & **Route of Administration** & **Duration** \\ \hline
**First-line immunotherapy** & & & \\ Methylprednisolon & 1 g daily & Intravenous & 3–5 days \\ Immunoglobulin & 2 g/kg over 5 days & Intravenous & 5 days \\  & (400 mg/kg/Day) & Intravenous & 5–7 cycles \\ Plasma exchange & 1 session every other day & Intravenous & 4 weeks \\
**Second-line immunotherapy** & & & 3–6 months \\ Rituximab & 375 mg/m\({}^{2}\)/weekly & Intravenous infusion & Monthly depending on clinical response \\ Cyclophosphamide & 750 mg/m\({}^{2}\)/monthly & Intravenous infusion & 3–6 months \\  & Initially—4 mg/kg & & \\ Tocilizumab & Increase to 8 mg/kg (depending & Intravenous infusion & Monthly depending on clinical response \\  & on clinical response) & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Therapeutic strategies based on observational studies and clinical experience. (2.49 mmol/L) being noted, but she had an elevated protein expression (1.43 g/L) with monocytosis (723/ mL). Due to the patient's psychiatric symptoms and the results of the routine biochemical CSF examination, herpes simplex virus (HSV) encephalitis was also considered, and Acylovir (with a treatment dose of 5 g) was used as the first-line treatment option. However, a CSF polymerase chain reaction (PCR) assay was negative for HSV and also for other neurotrophic viruses (Table 3). After six days, the patient became increasingly somnolent and verbally unresponsive. A physical neurological examination revealed somnolence, orofacial dyskinesia, and spastic tetrapedia with generalized tonic-clonic seizure. She was transferred to the neurological intensive care unit (ICU) and underwent other examinations. Control brain MRI showed an abnormal focal brainstem lesion. FLAIR- and T2-weighted MRI showed that the lesion was pontine hyperintense and non-enhancing after the administration of gadolinium chelating agents. It also did not display restricted diffusion (Figure 1). Longer-range EEG monitoring (Figure 2) showed an epileptogenic pattern with generalized positive sharp waves (PSWs). However, after parenteral antiepileptic drugs (AEDs) were administered (levetiracetam, sodium valproate, and clobazam), the EEG results became worse, and supportive EEG findings confirmed convulsive status epilepticus. A semi-quantitative method was applied to detect the presence of anti-NMDAR antibodies in the serum and CSF, with a positive result (Table 4). After the diagnosis of anti-NMDAR encephalitis was confirmed, first-line immunotherapy including intravenous methylprednisolone (1 g daily for 5 days), two cycles of intravenous immunoglobulin (0.4 g/kg/day for 5 days during the first cycle and 2 g/kg/day for 3 days during the second cycle, with a distance of 6 weeks), and plasma exchange (one session every other day for two cycles) was administered, though this did not yield an adequate response. Using the Glasgow coma scale (GCS) to evaluate loss of consciousness, we found that she had a score of 4-5 with autonomic dysfunction (hypotension + tachycardia) and central hypoventilation.