title: Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities.
abstract: 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.
authors.affiliation: Department of Neurology, INF 400 Kopfklinik, Heidelberg, Germany. uta_meyding-lamade@med.uni-heidelberg.de
authors.forename: Uta K
authors.initials: UK
authors.lastname: Meyding-Lamadé
authors.forename: Christoph
authors.initials: C
authors.lastname: Oberlinner
authors.forename: Philipp R
authors.initials: PR
authors.lastname: Rau
authors.forename: Sonja
authors.initials: S
authors.lastname: Seyfer
authors.forename: Sabine
authors.initials: S
authors.lastname: Heiland
authors.forename: Johann
authors.initials: J
authors.lastname: Sellner
authors.forename: Brigitte T
authors.initials: BT
authors.lastname: Wildemann
authors.forename: Wolfram R
authors.initials: WR
authors.lastname: Lamadé
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D018792:Encephalitis, Viral / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006561:Herpes Simplex / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008775:Methylprednisolone / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D005938:Glucocorticoids; D000212:Acyclovir; D008775:Methylprednisolone