Encephalitis ll: Pathophysiology

Encephalitis is inflammation of the brain parenchyma caused by direct viral invasion or immune-mediated mechanisms triggered by infections or tumors. Both processes lead to neuronal injury, disrupted neurotransmission, and diverse neurological symptoms, often with overlapping clinical and pathological features.

Autoimmune Encephalitis

In autoimmune encephalitis, antibodies target neuronal antigens on cell surfaces, synapses, or within neurons. A key example is anti-NMDAR encephalitis, which can happen after HSV-1 infection or in association with ovarian teratomas. These antibodies bind the GluN1 subunit, causing receptor internalization and NMDAR hypofunction. This disrupts glutamate signaling, producing neuropsychiatric and cognitive symptoms without excitotoxic damage.

Viral Entry into the CNS

Neurotropic viruses enter the central nervous system (CNS) through multiple routes. Hematogenous spread allows passage across the blood–brain or blood–CSF barriers. Some viruses enter via the olfactory nerve through the cribriform plate, while others travel retrogradely along peripheral nerves, as in rabies and HSV. Once inside, they spread through synaptic connections or cerebrospinal fluid (CSF).

Early Pathological Changes

After entry, viruses infect neurons or glial cells, causing dysfunction and metabolic disruption. This activates microglia and astrocytes, leading to lymphocytic infiltration, vascular congestion, and cerebral edema. Gray matter is commonly affected, though white matter involvement may also be involved.

Regional Tropism and Pathology

Certain viruses target specific regions; HSV-1 preferentially affects the limbic system. Common features include inflammation, neuronal degeneration, edema, and raised intracranial pressure, with necrosis or hemorrhage in severe cases.