From the Guidelines
HSV-1 encephalitis reaches the brain primarily through retrograde transport of the virus along nerve axons, particularly via the trigeminal nerve or olfactory pathway, as well as through hematogenous spread, although the former is more common. The pathogenesis of Herpes Simplex Virus type 1 (HSV-1) encephalitis involves the virus's ability to infect and replicate within neural tissue, leading to inflammation and tissue damage in the brain. Key aspects of this process include:
- Initial infection or reactivation of latent HSV-1 in the trigeminal ganglia 1
- Retrograde transport of the virus along nerve axons to the brain, especially affecting the temporal lobes
- Hematogenous spread, where the virus travels through the bloodstream to cross the blood-brain barrier, though this is less common
- The virus's neurotropic nature, which explains its affinity for neural tissue
- Its ability to remain latent in sensory ganglia, allowing for periodic reactivation throughout a person's lifetime This neuronal transport mechanism explains why HSV-1 encephalitis typically affects specific regions of the brain, particularly the temporal and frontal lobes, rather than causing diffuse brain infection. In terms of management, immunocompromised patients with encephalitis caused by HSV-1 should be treated with intravenous aciclovir (10 mg/kg three times daily) for at least 21 days, and reassessed with a CSF PCR assay; following this long term oral treatment should be considered until the CD4 cell count is >200 106/L 1. The geographical risk factors associated with viral CNS infections, including HSV-1 encephalitis, highlight the importance of close liaison with regional and national tropical and infectious diseases units, and national specialist diagnostic laboratories when deciding on appropriate investigations 1.
From the Research
Pathogenesis of Herpes Simplex Virus type 1 (HSV-1) Encephalitis
The pathogenesis of HSV-1 encephalitis involves several key steps:
- Viral replication: HSV-1 replicates in the brain, leading to cerebral damage 2, 3.
- Inflammatory response: An overzealous inflammatory response contributes to the cerebral damage and neurological sequelae 2, 4.
- Disruption of tissue integrity: HSV-1 infection disrupts tissue integrity, neuronal function, and cellular transcriptomes in the brain 4.
- Activation of immune pathways: The infection activates immune pathways, including tumour necrosis factor activation, which may contribute to the damage caused by the infection 4.
Key Factors in the Development of Encephalitis
Several factors contribute to the development of encephalitis:
- Viral entry: HSV-1 gains access to the brain stem and subsequently brain ependymal cells, leading to infection of the brain parenchyma 3.
- Microglial response: Microglial cells play a crucial role in the resistance to HSV-1 infection in the central nervous system (CNS) during the early stages of infection 3.
- Cerebral lateral ventricle enlargement: Enlargement of the cerebral lateral ventricle is a major cause of mortality in mice and may also occur in a subpopulation of human HSV encephalitic patients 3.
Consequences of Infection
The consequences of HSV-1 encephalitis can be severe:
- High mortality rate: The mortality rate for untreated HSV-1 encephalitis is high, ranging from 30% to 70% 2, 5.
- Neurological sequelae: Most survivors of HSV-1 encephalitis experience permanent neurological sequelae, including cognitive impairment, personality changes, and seizures 2, 6.
- Chronic complications: Chronic complications, such as autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor, can occur in some patients 6.