뇌염 II: 병태생리학

Neurotropic viruses enter the CNS through multiple routes including hematogenous spread across the blood-brain barrier, the olfactory nerve via the cribriform plate, and retrograde travel along peripheral nerves. Once inside, viruses spread through synaptic connections or cerebrospinal fluid, infecting neurons and glial cells that disrupt normal brain function.

HSV-1 exhibits regional tropism, preferentially targeting the limbic system, particularly the inferior and medial temporal lobes. This selective affinity reflects viral preference for specific receptor-rich brain regions where neuronal receptors that viruses bind to are highly concentrated, determining the pattern of infection.

After viral infection, microglia and astrocytes activate, triggering perivascular lymphocytic infiltration, capillary congestion, and cerebral edema. Gray matter is commonly affected due to its higher density of neuronal receptors, though white matter involvement may also occur, leading to increased intracranial pressure and neurological complications.

In autoimmune encephalitis, antibodies target neuronal antigens on cell surfaces, synapses, or within neurons, disrupting neural signaling. For example, anti-NMDAR encephalitis antibodies bind the GluN1 subunit, causing receptor internalization and NMDAR hypofunction, which disrupts glutamate signaling and produces neuropsychiatric and cognitive symptoms.

Anti-NMDAR encephalitis can develop after HSV-1 infection or in association with ovarian teratomas, triggering an immune response. The immune system produces antibodies targeting NMDARs, disrupting glutamate signaling without causing excitotoxic damage, resulting in distinct neuropsychiatric and cognitive symptoms in affected patients.

Gray matter is more frequently affected than white matter in viral encephalitis because it contains a higher density of neuronal receptors that viruses preferentially bind to. This regional variation in receptor distribution determines viral tropism and the pattern of neuronal infection throughout the brain.

Viral encephalitis involves direct pathogen invasion causing neuronal dysfunction, inflammation, and lymphocytic infiltration, while autoimmune encephalitis features antibody-mediated attacks on neuronal antigens disrupting neural signaling. Both pathways lead to neuronal injury and neurological symptoms, though through distinct mechanisms and inflammatory cascades.