Spectrum of Clinical and Imaging Features of Children With GFAP Astrocytopathy

Neurol Neuroimmunol Neuroinflamm. 2025 Jan;12(1):e200327. doi: 10.1212/NXI.0000000000200327. Epub 2024 Nov 20.

Abstract

Background and objectives: Glial fibrillary acidic protein (GFAP) antibodies (abs) have been described primarily in adults with a spectrum of autoimmune-mediated diseases. In children, data on clinical and neuroradiologic features of children with autoimmune GFAP astrocytopathy are limited. The aim of this study was to describe the clinical and radiologic features in children with GFAP-ab-associated diseases.

Methods: We retrospectively recruited children from 13 clinical centers between 2020 and 2023 who (1) tested positive for GFAP-ab in serum and/or CSF and (2) of whom a complete clinical and MRI data set was available.

Results: We identified and included 15 children (5 girls, 10 boys). The median age at onset was 9.9 years (range: 2-16 years). All children presented with features of AE or meningitis, acute cerebellitis, or transverse myelitis. CSF pleocytosis was common (13/15, median 245 cells/μL), and 13 (87%) of 15 harbored GFAP-abs in their CSF, 8 (53%) of whom did not have detectable GFAP-abs in their serum. MRI was abnormal in 15 (100%) of 15 children: Specific patterns included confluent lesions in the pons or caudate nucleus (11/15; 73%), peri-aqueductal regions (13/15; 87%), and spinal cord (6/10; 60%). 12 children had a favorable outcome (mRS score of </= 1). Two patients died in the acute phase or during follow-up.

Discussion: GFAP-ab-associated diseases encompass a wide spectrum of clinical presentation associated with a particular set of MRI features clearly distinct to other antibody-mediated diseases or MOGAD. We recommend that testing for GFAP-abs in serum and CSF be included in the workup of children with AE, particularly if brainstem involvement occurs.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Astrocytes / pathology
  • Autoantibodies* / blood
  • Autoantibodies* / cerebrospinal fluid
  • Autoimmune Diseases of the Nervous System / blood
  • Autoimmune Diseases of the Nervous System / cerebrospinal fluid
  • Autoimmune Diseases of the Nervous System / diagnosis
  • Autoimmune Diseases of the Nervous System / diagnostic imaging
  • Autoimmune Diseases of the Nervous System / immunology
  • Child
  • Child, Preschool
  • Female
  • Glial Fibrillary Acidic Protein* / blood
  • Glial Fibrillary Acidic Protein* / cerebrospinal fluid
  • Glial Fibrillary Acidic Protein* / immunology
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Retrospective Studies

Substances

  • Glial Fibrillary Acidic Protein
  • GFAP protein, human
  • Autoantibodies