The patient, a 33-year-old man, was hospitalized with complaints of headache, fever, unresponsiveness, irritability, and neck pain. The patient was reported to have lost 35 kg during the last 2 years (Figure 1). Twenty days before admission, the patient experienced persistent acute headaches, primarily in the front of the ear, temporal and posterior occipital part of the right side, without any distinct cause. These headaches were mainly characterized by unbearable distending pain, occasionally accompanied by dull, tingling, throbbing pain, which led to prolonged insomnia. Moreover, the patient experienced loss of appetite, but without nausea, vomiting, fever, diplopia, limb movement disorder, chest tightness, or shortness of breath. Eighteen days before admission, the patient sought medical help to manage the headaches. At that time, brain computed tomography (CT) scans were normal and the patient was given analgesic drugs, including rotundine (60 mg, orally three times per day), which relieved the headaches for 4 h and partly ameliorated the insomnia. Gradually, the degree of the headaches reduced, only occurring three to four times a day for approximately 4 h. However, 3 days before admission, the patient developed a low-grade fever when a headache occurred, accompanied by irritability and neck pain. Brain MRI was normal, but chest CT images revealed that the upper lobe of both lungs had lesions secondary to tuberculosis, and the left pleura was thickened and had encapsulated effusion (Figures 2A,B). The patient had no history of chronic disease, smoked for 20 years (10 cigarettes per day), occasionally drank a small amount of alcohol, and denied to have a family history of genetic disease. At admission, the patient was irritable and unresponsive, and upon examination, verbal reduction (unable to express full sentences), mild loss of comprehension, decreased calculation ability, and poor spatial learning and memory were confirmed. The eyeballs were in place on both sides, and horizontal nystagmus to the right was observed. The patient also showed signs of meningeal irritation, with nuchal rigidity (neck flexion angle of approximately 5 ), positive bilateral Kernig's sign, and negative Brucella's sign. According to the Clinical Assessment Scale in AIE (CASE), modified Rankin scale (mRS), Glasgow coma scale, mini-mental state examination (MMSE), and the Montreal Cognitive Assessment Test (MoCA) the patient scored 6, 3, 13 (E3M4V6), 9, and 8, respectively.
Laboratory tests showed that the erythrocyte sedimentation rate was 56 mm/h, and serum blood cell counts and C reactive protein levels were within normal range. Lumbar puncture showed an increased opening pressure, and cerebrospinal fluid (CSF) analysis revealed elevated white blood cell (WBC) count and protein levels (Table 1). Based on these findings, the initial clinical diagnosis of possible viral meningoencephalitis was achieved. The patient was treated empirically with intravenous acyclovir 10 mg/kg three times per day. However, his health status continued to gradually worsen, with the highest body temperature reaching 39 C, with confusion, occasional nonsense, and partial third cranial nerve palsy, on day 3 (Figure 1). The CASE and mRS scores were 13 and 4. Furthermore, CSF and serum analyses revealed the presence of anti-NMDAR antibody IgG, determined by cell-based assay (CBA) and tissue-based assay (TBA). The result of tuberculin-purified protein derivative (PPD) skin test was positive (++), and that of the T-SPOT.TB assay was positive. CSF was positive for the MTB complex DNA assay; however, the modified acid-fast staining and metagenomic next-generation sequencing (mNGS) result was negative. Moreover, MRI showed nodules and ring enhancement in the right lateral ventricle, left temporal and left cerebellar hemisphere, abnormal signal foci were observed in the right temporal lobe and basal ganglia, as well as enhancement of the pia mater of the right frontotemporal area (Figures 2C,D). Furthermore, the patient was negative for anti-MBP, anti-AQP4, anti-MOG, anti-GFAP, and anti-GQ1b IgGs, and neuron antibodies in serum and CSF. Tumor markers, blood cultures, and autoantibodies associated with other autoimmune diseases were also negative. Moreover, color Doppler ultrasound of lymphatic, reproductive, urinary, and digestive systems, and of the heart were all normal. The lungs were also normal as per bronchoscopy analysis.
Diagnosis of tuberculosis meningoencephalitis combined with anti-NMDAR encephalitis was achieved, and a standard antituberculosis regimen (rifampicin 0.45 g/day, ethambutol 0.75 g/day, isoniazid 0.6 g/day, and pyrazinamide 1.5 g/day) and intravenous 1,000 mg/d glucocorticoid pulse therapy (halved every 3 days, and switched to oral after 12 days) was initiated. Thereafter, the consciousness status of the patient and irritability gradually improved, and the head and neck pain was substantially ameliorated. On day 8, despite the health improvements noticed, the comprehension, calculation ability, spatial learning, and memory impairments remained unchanged, and depression manifestations appeared. The pain symptoms disappeared, but neck resistance increased to 15 C. On day 13, a lumbar puncture was performed with intrathecal isoniazid (0.1 g) and dexamethasone (5 mg). CSF analysis revealed evident improvements (Table 1), and the comprehension, mood, verbal reduction, and partial oculomotor nerve palsy showed some improvements. The neck flexion angle of 25  remained. The CASE and mRS scores were 6 and 3. The patient was discharged with an oral standard antituberculosis regimen combined with prednisone (60 mg/day) for 2 weeks, which was tapered to 50 mg/day until the following medical examination.
After 1 month of follow-up, the patient had gained 8 kg without any discomfort. Physical examination showed only right ptosis and diplopia. Moreover, the CASE, MMSE, MoCA, and mRS scores were 3, 29, 27, and 1, respectively. The CSF anti-NMDAR antibody titer remained unchanged. Noteworthily, the serum anti-NMDAR antibody titer, and protein and WBC of CSF were significantly reduced (Table 1). Brain MRI revealed significant shrinkage of the primary nodules. Nevertheless, the lesion in the right basal ganglia was larger than before, new lesions appeared in the right pontine and right-sided temporal lobe, and the right frontotemporal leptomeninges showed more evident enhancement than before (Figures 2E,F). The patient continued to receive the antituberculosis treatment regimen along with regular tapered prednisone. Additional evaluations revealed that the patient was still experiencing mild visual acuity decline in the right eye but without impact on his daily life, and the ptosis and memory disorders disappeared without further complaints. Physical examination remarkably improved after 3 months of discharge. The CASE and mRS scores were 2 and 1. The lesions on the CT chest and brain MRI (Figure 2G) showed evident improvements.