What is subcortical gliosis?

Subcortical Gliosis: Definition and Clinical Significance

Subcortical gliosis is a non-neoplastic reaction characterized by hypertrophy and/or proliferation of astrocytes in the subcortical white matter of the brain, which can occur as a response to various forms of injury or as part of certain neurodegenerative conditions. 1, 2

Pathological Features

• Subcortical gliosis presents as prominent fibrillary astrocytosis primarily in the subcortical white matter and may extend to the subpial and deep layers of the overlying cerebral cortex 3, 4
• It is characterized by reactive astrocytes that show morphological properties of an active process, often detected through glial fibrillary acidic protein (GFAP) immunostaining 5
• The condition may be accompanied by mild cortical neuronal loss but typically without significant myelin loss 3, 4
• Subcortical gliosis can be a surrogate marker for cortical scarring resulting from microinfarcts 1

Types and Causes

• Reactive gliosis: Occurs in response to parenchymal injury, inflammation, or altered microenvironmental conditions 2
• Progressive subcortical gliosis (PSG): Can occur as:
  • Familial form with autosomal dominant inheritance 3, 6
  • Sporadic late-onset form 4
• Secondary gliosis: May develop following:
  • Ischemic injury or infarction 1, 5
  • Infectious processes 1
  • Focal cortical dysplasia (FCD) type III 1
  • Incomplete ischemic injury 1

Imaging Characteristics

• On MRI, subcortical gliosis may appear as:
  • Abnormal signal intensities in subcortical white matter 1
  • In focal cortical dysplasia, it can present as a radially oriented and funnel-shaped high T2/FLAIR signal intensity in the subcortical white matter pointing to the ipsilateral ventricle (known as "transmantle sign") 1
  • White matter changes that may be prominent on both MRI and CT imaging 6
• In neonatal brains, gliotic areas may show hypointense T2 and hyperintense T1 signal 1

Clinical Significance

• Subcortical gliosis can be associated with various neurological conditions:
  • Frontotemporal dementia clinical syndrome 6
  • Amyotrophic lateral sclerosis (ALS) 5
  • Vascular cognitive impairment 1
  • Epilepsy when associated with focal cortical dysplasia 1
• Progressive forms may present with:
  • Personality changes and social dysfunction 3, 6
  • Memory impairment and progressive dementia 3, 4
  • In later stages: verbal stereotypy, decreased speech output, and extrapyramidal signs 3

Histopathological Assessment

• For optimal investigation of white matter lesions with gliosis, immunohistochemistry using primary antibodies to:
  • Myelin oligodendrocyte glycoprotein
  • Phosphorylated neurofilament
  • Glial markers
  • Ubiquitin and amyloid precursor protein (APP) 1
• Quantitative assessment of neuronal loss and astrogliosis may be performed in research settings 1
• Differentiation from other conditions is important, as subcortical gliosis lacks amyloid deposits and neuronal cytoskeletal inclusions seen in other neurodegenerative disorders 3, 4

Differential Diagnosis

• Low-grade tumors such as gangliogliomas 1
• Oligodendrocytosis 1
• Mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) 1
• Alzheimer's disease (clinically may be misdiagnosed) 4
• Various forms of heterotopia (collections of neurons in abnormal locations) 1