Rasmussen encephalitis is a rare, progressive, and severe inflammatory disease of the brain that typically affects one cerebral hemisphere, predominantly in children. Microglia play a central role in the immunopathogenesis of this condition, mediating both the inflammatory response and the cytotoxic mechanisms that lead to progressive neuronal loss and cortical atrophy[@varadkar2014].
Microglia are the resident immune cells of the central nervous system and serve as the primary mediators of neuroinflammation in Rasmussen encephalitis. Their activation and interactions with T-cells drive the characteristic progressive neurological decline seen in this condition[@bien2002].
Rasmussen encephalitis is an immune-mediated disease characterized by a focal inflammatory process that progressively destroys one cerebral hemisphere. The pathogenesis involves a complex interplay between microglia, CD8+ cytotoxic T-cells, and neurons[@granata2003].
CD8+ T-cell mediated cytotoxicity:
CD8+ T-cells recognize neuronal antigens presented on MHC-I molecules
Cytotoxic T-cells release granzyme and perforin leading to apoptotic neuronal death
The attack predominantly targets pyramidal neurons in the affected cortex
Microglia serve as antigen-presenting cells that activate the T-cell response
Microglial activation:
Activated microglia express increased levels of MHC-I and MHC-II
Microglia produce pro-inflammatory cytokines including IL-1β, TNF-α, and IL-6
Chronically activated microglia create a self-perpetuating inflammatory cycle
Microglial proliferation correlates with disease progression[@gupta2004]
Neuroimaging Correlates
PET imaging shows increased microglial activation in the affected hemisphere
TSPO binding is elevated in active inflammatory regions
Longitudinal PET demonstrates progressive involvement correlating with clinical decline[@chen2012]
Clinical Features
Treatment Approaches
Immunotherapy: Corticosteroids, IVIG, cyclophosphamide may slow progression
Anti-epileptic drugs: Control seizures but do not halt disease progression
Hemispherectomy: Surgical disconnection of affected hemisphere (only curative option)
Emerging therapies: T-cell targeted treatments under investigation[@loring2020]
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Pathway Diagram
The following diagram shows the key molecular relationships involving Microglia in Rasmussen Encephalitis discovered through SciDEX knowledge graph analysis: