Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis

Abstract

SUMMARY Herpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral treatment is 70%, with most survivors suffering from permanent neurological sequelae. The use of intravenous acyclovir together with improved diagnostic technologies such as PCR and magnetic resonance imaging has resulted in a reduction in the mortality rate to close to 20%. However, 70% of surviving patients still do not recover complete neurological functions. Thus, there is an urgent need to develop more effective treatments for a better clinical outcome. It is well recognized that cerebral damage resulting from HSE is caused by viral replication together with an overzealous inflammatory response. Both of these processes constitute potential targets for the development of innovative therapies against HSE. In this review, we discuss recent progress in therapy that may be used to ameliorate the outcome of patients with HSE, with a particular emphasis on immunomodulatory agents. Ideally, the administration of adjunctive immunomodulatory drugs should be initiated during the rise of the inflammatory response, and its duration should be limited in time to reduce undesired effects. This critical time frame should be optimized by the identification of reliable biomarkers of inflammation.

The Golgi Apparatus May Be a Potential Therapeutic Target for Apoptosis-Related Neurological Diseases

“…Herpes simplex virus encephalitis (HSE) caused by HSV-1 infection is the most common sporadic encephalitis worldwide (Piret and Boivin, 2020). DeBiasi et al (2002) found apoptotic neurons and glial cells in the brain tissue sections of patients with acute HSE.…”

Dementia and cognitive impairment in adults as sequels of HSV-1-related encephalitis: a review

“…Among these, HSVs account for 50 to 75% of viral encephalitis, which consist of brain parenchyma inflammation associated with clinical evidence of neurologic dysfunctions, such as reduced consciousness, behavioral alterations, and impaired cognitive function. 3 The herpetic encephalitis (HSE) is responsible for a high mortality rate between patients who do not receive antiherpetic treatment and for over 70% of neurological sequelae in surviving patients. 3 Given the HSV-1 wide invasive potential of the CNS, it is able not only to agglomerate in the dorsal root nerve ganglia (DRG), but also to migrate to the cerebral cortex itself, including the orbitofrontal, insular, and mesial temporal lobe regions, specially affecting the hippocampus, 4 whose vulnerability to Alzheimer disease is substantial, as demonstrated in pioneer and recent studies.…”

“…3 The herpetic encephalitis (HSE) is responsible for a high mortality rate between patients who do not receive antiherpetic treatment and for over 70% of neurological sequelae in surviving patients. 3 Given the HSV-1 wide invasive potential of the CNS, it is able not only to agglomerate in the dorsal root nerve ganglia (DRG), but also to migrate to the cerebral cortex itself, including the orbitofrontal, insular, and mesial temporal lobe regions, specially affecting the hippocampus, 4 whose vulnerability to Alzheimer disease is substantial, as demonstrated in pioneer and recent studies. [5][6][7] Furthermore, evidence carried out with animal models prove that the area analogous to the human limbic cortex is commonly affected by encephalitis.…”

“…Among these, HSVs account for 50 to 75% of viral encephalitis, which consist of brain parenchyma inflammation associated with clinical evidence of neurologic dysfunctions, such as reduced consciousness, behavioral alterations, and impaired cognitive function. 3 The herpetic encephalitis (HSE) is responsible for a high mortality rate between patients who do not receive antiherpetic treatment and for over 70% of neurological sequelae in surviving patients. 3 …”

“… 3 The herpetic encephalitis (HSE) is responsible for a high mortality rate between patients who do not receive antiherpetic treatment and for over 70% of neurological sequelae in surviving patients. 3 …”