Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities

J Neurovirol. 2003 Feb;9(1):118-25. doi: 10.1080/13550280390173373.


Despite early antiviral treatment, herpes simples virus encephalitis (HSVE) still remains a life-threatening sporadic disease with high mortality and morbidity. In patients and in experimental disease, chronic progressive magnetic resonance imaging (MRI) abnormalities have been found even after antiviral therapy. Secondary autoimmune-mediated and not directly virus-mediated mechanisms might play a key role for the outcome of disease. This study aimed to evaluate a possible beneficial effect of a therapy of acyclovir and corticosteroids versus acyclovir only. In a mouse model of HSVE (intranasal inoculation with 10(5) pfu [plaque-forming units] of HSV-1 strain F), a long-term MRI study was realized. Cranial MRI was performed serially at days 2, 7, 14, 21, 60, and 180 in different therapy groups: 1, saline; 2, acyclovir; 3, acyclovir, subsequently methylprednisolone; 4, sham-infected with saline. Brain viral load peaked at day 7 to decline thereafter to a low baseline value. Viral load in group 1 was significantly higher than in animals with antiviral therapy. In group 4, no viral DNA was detectable. Viral load did not differ significantly between acyclovir and acyclovir/corticosteroid-treated groups, suggesting that the use of corticosteroids in addition to acyclovir does not increase viral burden. MRI findings in untreated and acyclovir-treated animals revealed chronic progressive changes. In contrast, there was a significant reduction of the severity of long-term MRI abnormalities in acyclovir/corticosteroid-treated animals. With respect to abnormal MRI findings, this study demonstrates a clear beneficial effect of an acyclovir and corticosteroid therapy without influencing brain viral load.

MeSH terms

  • Acyclovir / pharmacology*
  • Animals
  • Antiviral Agents / pharmacology*
  • Drug Therapy, Combination
  • Encephalitis, Viral / drug therapy*
  • Encephalitis, Viral / pathology
  • Female
  • Glucocorticoids / pharmacology*
  • Herpes Simplex / drug therapy*
  • Herpes Simplex / pathology
  • Magnetic Resonance Imaging
  • Methylprednisolone / pharmacology*
  • Mice
  • Mice, Inbred Strains
  • Viral Load


  • Antiviral Agents
  • Glucocorticoids
  • Acyclovir
  • Methylprednisolone