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Introduction Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. Methods The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0–2 vs. 3–6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. Results The trial was stopped prematurely for slow recruitment after 41 patients had been randomized, 21 of them treated with dexamethasone and 20 with placebo. No difference was observed in the primary endpoint. In the full analysis set (n = 19 in each group), 12 patients in each treatment arm achieved a mRS of 0–2. Similarly, we did not observe significant differences in the secondary endpoints (GOS, mRS, quality of life, neuropsychological testing). Conclusion GACHE being prematurely terminated demonstrated challenges encountered performing randomized, placebo-controlled trials in rare life threatening neurological diseases. Based upon our trial results the use of adjuvant steroids in addition to antiviral treatment remains experimental and is at the decision of the individual treating physician. Unfortunately, the small number of study participants does not allow firm conclusions. Trial registration EudraCT-Nr. 2005–003201-81.

Emerging and re-emerging viruses may cause meningitis, encephalitis, meningoencephalomyelitis, encephalitis, Guillian-Barré-like-syndromes as well as strokes. Most important viruses belong to the family of Adenoviridae, Arbovirus, Arenaviridae, Herpesviridae, Picornaviridae, Paramyxoviridae as well as Togaviridae. Clinical presentation usually consists of a biphasic presentation. Non-specific febrile illnesses may be accompanied by rash, headache, arthralgia and myalgia. Thereafter focal neurological signs may evolve. Diagnostic strategies for the detection of emerging and re-emerging viruses may be difficult due to the short viraemic period. Pitfalls in serology may be due to antibody crossreactivity. Arboviruses are transmitted by arthropods. Aedes mosquitos are one of the vectors for arboviruses like Chikungunya-virus, Dengue-virus, Japanese-Encephalitis-B-virus and West-Nile-virus. Since the last centuries Aedes mosquitos have spread from their naturally habitat in Africa to America as well as Europe. The arboviruses risk profile depend essentially on the occurrence, the activity of the respective vector, this may be the key to fight the disease and its spread. Due to global shifts in the ecological balance but also as a result of more or less successful control measures, some diseases have become rarer, others are more common. The viruses persist in the respective vector months to years; in ticks they may persist for years and in mosquitoes 1 to 4 months. In order to survive bad climatic conditions unscathed, the viruses partially overwinter in arthropods.

Nicht weil es schwer ist, wagen wir es nicht, sondern weil wir es nicht wagen, ist es schwer. Lucius AnnaeusSeneca (1-65 n. Chr.