Background <p>Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is an autoimmune inflammatory disease of the central nervous system triggered by GFAP. Currently, the diagnosis is mainly based on the detection of autoantibodies that recognize GFAP in the cerebrospinal fluid. Its imaging manifestations are complex and variable. It is extremely necessary to enhance the understanding of this disease among radiologists and reduce the damage caused by invasive procedures.</p> Case presentation <p>We report a case of a 39-year-old female patient with lesions throughout the spinal cord. The patient presented with recurrent fever without obvious cause, and no obvious lesions were found in the lung CT examination. Two months later, she developed weakness of both lower limbs with neck and back pain. Contrast-enhanced MRI of the cervical and thoracic spinal cord demonstrated diffuse intramedullary punctate-to-linear and patchy enhancement, with associated leptomeningeal enhancement. GFAP-IgG was subsequently detected in the cerebrospinal fluid, confirming the diagnosis of GFAP-A. After intravenous methylprednisolone pulse therapy combined with immunoglobulin therapy, the lesion extent of the patient was significantly reduced.</p> Conclusions <p>The MRI manifestations of GFAP-A patients are complex. When there is a whole spinal cord lesion, acute infectious lesions should be considered, but GFAP-A should also be kept in mind. In cases where CSF antibody test results are negative or weakly positive, a diagnosis of GFAP-A can still be established when characteristic imaging manifestations are consistent with clinical symptoms. Follow-up observation by MRI examination is necessary to avoid recurrence when the dose of steroid hormones is reduced.</p>