Glial fibrillary acid protein (GFAP) astrocytopathy

Case contribution: Dr Radhiana Hassan


  • A 22 years old man
  • No known medical illness, presented with bilateral lower limb weakness, LL>UL
  • Associated with blurring of vision
  • The symptoms progressively worsen over one week
  • Clinically muscle power of both upper and lower limbs were 2/5
  • Reflexes normal, treated as demyelinating disease, with IVIG and methylprednisolone
  • Referred to other hospital for expert opinion since his condition not improved
  • Subsequently diagnosed as GFAP demyelination disease (pending investigation result)
  • Patient shows good response to IV rituzimab, latest clinical examination shows muscle power of 4/5
MRI brain in axial planes

MRI findings:

  • Abnormal T2/FLAIR hyperintensity is seen in the white matter
  • Bilateral, almost symmetrical involvement, some confluent areas
  • Involvement of periventricular white matter, centrum semiovale, corpus callosum
  • The lesions show restricted diffusion, no enhancement
  • MRI spine done was normal (image not shown)
  • Optic nerves are also normal (images not show)
  • The changes show more extensive involvement on subsequent imaging, otherwise signal intensity remain the same
  • No enhancement and no change in restricted diffusion areas

Diagnosis: GFAP astrocytopathy (presumed diagnosis, awaiting final lab results)


  • GFAP astrocytopathy is a rare inflammatory CNS disorder
  • It tends to occur in middle-aged adults with slight female preponderance
  • It has broad neuropsychiatric and temporal spectrum clinical presentation
  • The pathophysiology is not well understood.
  • The key marker is GFAP antibody which has a higher positive predictive value when present in CSF rather than in the serum.
  • Co-existing NMDA receptor antibody, aquaphorin-4 antibody may also be present
  • MRI features include T2/FLAIR hyperintensity which is diffuse, confluent at periventricular white matter often extending to centrum semiovale, deeper brain structures and or brainstem.
  • It may also shows perivascular enhancement extending radially from the periventricular surface. Less characteristic is leptomeningeal or periependymal enhancement.
  • Optic nerve often normal on imaging.
  • MR angioram is also normal. No restricted diffusion on DWI and ADC.
  • Findings can also involve spinal cord.
  • A differential diagnosis for this case was acute demyelination lesions with restricted diffusion in MS; a new variant of MS lesion. However, the lesions do not show resolving restricted diffusion after treatment.
Author: radhianahassan