Objective: Several autoimmune CNS inflammatory diseases, including autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorders (AQP4-IgG+ NMOSD) often presented initially with similar infectious meningitis-like symptoms. However, it was not easy to differentiate them at disease onset without antibody detection. The present study aimed to compare the clinical, immunological and radiological features among the three diseases. Methods: In our single-center cohorts, 9 A-GFAP-A, 17 MOGAD and 11 AQP4-IgG+ NMOSD patients mimicking infectious meningitis as initial symptoms were retrospectively included. The autoantibodies were detected with cell-based assays. The clinical, immunological and radiological characteristics of the three groups were summarized. Results: AQP4-IgG+ NMOSD patients were statistically more often in men (10, 90.9%, P=0.003). Tremor was predominated in A-GFAP-A (4, 44.4%) over MOGAD (1, 5.9%, P= 0.034) and never found in AQP4-IgG+NMOSD (0, P=0.026). The Modified Rankin Score (mRS) at the clinical nadir of diseases was lower in AQP4-IgG+NMOSD (2.2 [IQR, 1-3]) compared to A-GFAP-A (3.7 [IQR, 3-5], P=0.04). On CSF examination, white blood cell count (WBC) was higher in A-GFAP-A (median, 272×106/L [range, 0-1600]) compared to AQP4-IgG+NMOSD (median, 12×106/L [range, 0-48], P=0.049). Significant increase in CSF protein (1490.7±871.2 mg/L), lactic acid (3.43±0.81 mmol/L), IgG (130.9±60.4 mg/L), IgM (8.6±6.1mg/L) and IgA (23.0±11.4mg/L) levels in A-GFAP-A was found compared to MOGAD (CSF protein: 606.7±379.4 mg/L, P<0.001; lactic acid: 2.15 ± 0.62mmol/L, P<0.001; IgG: 77.9±71.3 mg/L, P=0.043; IgM, 2.7±2.9mg/L, P=0.002; IgA, 11.3±12.1mg/L, P=0.012) and AQP4-IgG+NMOSD (CSF protein: 441.8±178.0 mg/L, P<0.001; lactic acid: 2.40 ± 0.66 mmol/L, P=0.003; IgG, 53.2±30.3 mg/L, P=0.01; IgM, 2.1±3.9mg/L, P=0.003; IgA, 5.2±5.0mg/L, P=0.001). Over half of the A-GFAP-A patients (5/8, 62.5%) showed small (<2 cm), symmetrical lesions in ganglia and thalamus (5/8, 62.5%), but never in MOGAD (0%, P=0.001) and AQP4-IgG+NMOSD (0%, P=0.026). Diffuse meningeal enhancement was common in A-GFAP-A (8, 88.9%) compared to MOGAD (5, 29.4%, P=0.011) and AQP4-IgG+NMOSD (1/6, 16.7%, P=0.011). Acute disseminated encephalomyelitis (ADEM) -like lesions occurred frequently in MOGAD (6/16, 37.5%) but never in A-GFAP-A and AQP4-IgG+NMOSD (P=0.02). Conclusion: Our study demonstrated that several signs including the symptom of tremor, a more severe disease course, higher CSF immunological profiles and ganglia bilateral symmetrical lesions, diffuse meningeal enhancement were distinct features in A-GFAP-A, and ADEM-like lesions occurred only in MOGAD mimicking infectious meningitis as initial symptoms, providing possible clinical implications for patient differential diagnosis.