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

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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 105 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.

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Authors and Affiliations

  1. Department of Neurology, INF 400 Kopfklinik, 69120, Heidelberg, Germany

    Uta K. Meyding-Lamadé, Christoph Oberlinner, Philipp R. Rau, Sonja Seyfer, Johann Sellner & Brigitte T. Wildemann

  2. Division of Neuroradiology, INF 400 Kopfklinik, Heidelberg, Germany

    Sabine Heiland

  3. Department of Surgery, INF 110, Heidelberg, Germany

    Wolfram R. Lamadé

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  1. Uta K. Meyding-Lamadé
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  2. Christoph Oberlinner
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  3. Philipp R. Rau
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  4. Sonja Seyfer
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  5. Sabine Heiland
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  6. Johann Sellner
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  7. Brigitte T. Wildemann
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  8. Wolfram R. Lamadé
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Correspondence to Uta K. Meyding-Lamadé.

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Meyding-Lamadé, U.K., Oberlinner, C., Rau, P.R. et al. Experimental herpes simplex virus encephalitis: A combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities. Journal of NeuroVirology 9, 118–125 (2003). https://doi.org/10.1080/13550280390173373

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  • DOI: https://doi.org/10.1080/13550280390173373

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