Infection as a potential trigger in glial fibrillary acidic protein astrocytopathy: a case report and review of immunotherapeutic strategies.

purposeGlial fibrillary acidic protein astrocytopathy (GFAP-A) is a form of autoimmune encephalitis (AE) that commonly affects the central nervous system (CNS). The pathogenesis of GFAP-A remains unclear, with infection proposed as a potential trigger, often leading to a misdiagnosis as meningoencephalitis due to overlapping clinical manifestations. This study aims to reports a case of GFAP-A associated with Enterococcus faecium infection, summarize the clinical characteristics, treatment details, and prognostic outcomes of GFAP-IgG-positive patients with concurrent infections, and provide evidence for optimizing clinical diagnosis and treatment strategies.

methodsWe report a detailed case of an 81-year-old male GFAP-A patient with an E. faecium infection, with primary manifestations of drowsiness and seizures. We also retrospectively analyzed 4 additional GFAP-A patients with confirmed infections from our institution (2022–2024) and systematically reviewed 20 eligible cases from the literature (2016–2024). The inclusion criteria were: (1) GFAP-IgG positivity in CSF/ serum, (2) definitive evidence of infection, (3) complete clinical, imaging, treatment, prognostic and laboratory data available.

resultsA total of 25 patients (19 males, 6 females; median age 45 years, range 12–81 years) were included. The most common initial symptoms were fever (80%, 20/25) and headache (76%, 19/25), followed by altered consciousness (76%, 19/25), urinary dysfunction (68%, 17/25), weakness (56%, 14/25), ataxia (44%, 11/25), blurred vision (40%,10/25), neuropsychiatric abnormalities (40%, 10/25), seizures (36%, 9/25), respiratory dysfunction (32%, 8/25), and positive meningeal signs (8%, 2/25). Brain MRI was abnormal in 75% (18/24) of patients, with T2-FLAIR hyperintensity (42%, 10/24) being the most common finding, and classic periventricular enhancement in 12.5% (3/24). All patients were GFAP-IgG-positive in CSF, and 52% (13/25) were positive in serum. Treatment included anti-infective therapy (all 25 cases) plus immunotherapy (21/25 cases: intravenous immunoglobulin (IVIG) in 16, corticosteroids in 12, plasma exchange (PE) in 4, protein A immunoadsorption (PAIA) in 1). Prognostic outcomes: 10 patients (40%) achieved complete recovery, 11 (44%) had residual sequelae (urinary dysfunction in 5, cognitive impairment in 3, motor weakness in 2, behavioral abnormalities in 1), and 4 (16%) had unknown prognosis. The index case showed significant recovery after combined anti-infective (piperacillin-tazobactam + linezolid) and IVIG, with modified Rankin Scale (mRS) score improving from 5 to 2 at 1-month follow-up.

conclusionInfection is a potential trigger for GFAP-A, and differentiation from infectious meningoencephalitis is challenging. For patients presenting with meningoencephalitis accompanied by persistent disturbances of consciousness and seizures, GFAP reactive antibody testing of CSF and plasma is appropriate. In patients with GFAP-A, early and effective anti-infective and immunotherapies may help to prevent disease progression and improve the likelihood of full recovery. In severe cases, additional immunotherapies may be required.