Does the herpes virus persist in the brain after encephalitis?

 

An 8 year old girl with cerebral palsy with spastic quadriparesis was admitted with the history of fever, seizures and altered sensorium. This was her MRI brain (seen above)with cystic encephalomalacia and fresh diffusion restriction in bilateral basal ganglia. Her CSF had 7 lymphocytes, elevated proteins and PCR for Herpes was positive with 4000 copies/ml.

In her neonatal period also she had been diagnosed with viral encephalitis and had been treated with acyclovir for presumed herpes infection on the basis of diffusion restriction of bilateral temporal lobes, which is seen the the MRI below. Despite treatment she had been left with significant neurological deficit and had become essentially bedridden.

There have been reports of herpes reactivation several years after an initial encephalitis. In fact it is believed that the virus often remains in a latent state in some tissues in the brain such as the ependymal lining of the ventricles even after treatment with standard doses of acyclovir.

In fact 70% of cases of HSV encephalitis is considered due to reactivation of the virus, though primary infections are more common in children.

During the latent period only the "Latency Associated Transcript" (LAT)of the virus is coded in the neurons. This also interestingly enhances neuronal survival by inhibiting apoptosis. During periods of immune depression such as infections or fever or even trauma, the virus is reactivated and enters the lytic cycle and starts actively damaging neutrons. https://doi.org/10.3389/fncel.2019.00046

There are also cases which have documented a progressive downhill neurological disease due to herpes encephalitis. It is also implicated in certain neurodegenerative disorders such as Alzheimers disease and multiple sclerosis. It is proposed that multiple mild HSV infections involving the brain may result in the same pathology noted in Alzheimers disease.

Acyclovir inhibits active viral replication. It has been suggested that viruses which are not actively replicating may continue to survive in the brain. Various suggestions including longer duration of treatment with acyclovir and repeated courses have ben suggested to overcome the problem of relapsing or chronic HSV brain disease.