A 28-year-old man was brought to a local hospital in April 2021 because of the secondarily generalized epileptic-seizure, which presented itself with a sudden loss of consciousness, staring eyes, and stiffness of the limbs and convulsions. The various symptoms lasted for several minutes and terminated before reaching the hospital, and the patient was unable to recall the onset of this seizure. The patient had only one epileptic episode. The type of seizure was considered as focal impaired awareness with motor onset seizure. For the past one week, he suffered from headache and dizziness, but his medical history was unremarkable. Magnetic Resonance Imaging (MRI) of the brain showed significant hyperintensity of the cortical and subcortical of the left frontal lobe ( Figures 1A-C ). Thereafter, lumbar puncture was performed two days later, which revealed an increased intracranial pressure (250mmH2O), high protein levels (1.28 g/L) and increased accumulation of cells (610 white blood cells/mm3), but normal glucose and chloride levels. During hospitalization, the patient occasionally suffered with fever with a temperature of around 38.5 C. He was initially diagnosed with meningoencephalitis. Therefore, he was administered empirical intravenous (IV) anti-viral (acyclovir, 500mg/d, Q8h) and antibiotic (ceftriaxone sodium, 2000mg/d) therapy, and the above symptoms were gradually alleviated. After one week, the patient developed blurred vision in the right eye, which deteriorated markedly with binocular vision loss after 10 days and continued to worsen continuously over the following month. Repeated brain MRI showed enlarged lesion involving the left frontal, orbital gyrus and bilateral optic nerve with substantial contrast enhancement ( Figures 1D-F ). Hence, he was transferred to our tertiary care center for further diagnosis. Neurological examination revealed binocular vision loss with only light perception, and lateral visual field was impaired ( Supplementary Figures 2A, B ). Muscle weakness, sensory nervous system, cerebellar functions, Babinski sign and meningeal irritation signs were observed to be in the normal range.
Electroencephalograph (EEG) revealed a small amount of scattered slow waves. Repeated lumbar puncture depicted lower white blood cell count (11 cells/mm3) and protein (0.51 g/L) level. Anti-HHV-7 IgM and IgG antibodies were detected in both the serum and cerebrospinal fluid (CSF). CSF testing for HHV-7 RNA by next generation sequencing (NGS) metagenomics and polymerase chain reaction (PCR) yielded positive result. All other CSF tests for the neurotropic viruses and other bacteria displayed negative results. Upon search for anti-neural antibodies (to anti-NMDAR, anti-LGI1, anti-CASPR2, anti-AMPAR, anti-GABABR, anti-DPPX, and anti-mGLuR5), NMDAR antibodies (1:10) were found positive in the patient's CSF by cell-based assay (CBA) (Euroimmun, Lubeck, Germany) ( Figure 2A ). We also used CBA (Euroimmun, Lubeck, Germany) to detect CNS demyelinating antibodies (AQP4, MOG, GFAP), MOG antibodies were found positive in CSF (1:32) ( Figure 2B ) and the serum (1:10) ( Figure 2C ), whereas both AQP4 antibody (not shown) and GFAP antibody ( Figure 2D ) were negative. Besides, we found a weak fluorescence response in the TBA detection, which indicated that the disease was immunological in nature ( Supplementary Figures 1A, B ). The various tests conducted for the paraneoplastic antibodies, rheumatological autoantibodies, blood routine examination, biochemistry, tumor markers, thyroid profile, mycobacteria, treponema pallidum, human cytomegalovirus, and viral serological were all found to be negative ( Supplementary Table 1 ). NGS metagenomics tests, TBA tests, and CBA tests for anti-neural antibodies and CNS demyelinating antibodies also were performed at the Center for Precision Medicine, West China Hospital, Sichuan University. Study methods are provided in the  Supplementary Material .