October 30, 2019

Solid background for EURECA study

Early ICU admission and body control temperature, two possibilities to improve functional status in patients with HS Encephalitis


Infections with Herpes Simplex belong to the most common human diseases, and also the most frequent cause of acute encephalitis. Herpes Simplex Encephalitis (HSE) can lead to high mortality rates and severe functional disabilities.  Since the use of high-dose acyclovir (ACV) became the golden standard as an empiric treatment while recovering the results of PCR and brain MRI however, mortality rates in ICU have reduced by up to10%.

Nevertheless, 29% -43% of survivors still suffer from significant impairments. Some studies have focused on new, promising treatments, like vaccines, or antiviral targets, that might include cellular genes, but other perspectives to reduce negative outcomes have to be explored.

The ENCEPHALICA study group, led by P Jaquet, has proposed a large, multicentre, cohort retrospective study in 47 ICUs in France between 2007 and 2017, studying the relationship of admission factors with outcomes of HSE adult patients requiring ICU admission, in order to identify potentially modifiable factors.

Patients were included if their admission to ICU was related to a possible acute encephalitis, following a strict definition, and presented a positive CSF PCR for HSV DNA during hospitalisation. Missing data, LOS in ICU < 24h, multiple pathogen detection and initial admission in ICU in a foreign country were the main exclusion criteria.

The final study counted 256 patients with a Glasgow score of 9 and a body temperature of 38.7.

71% (185) of the patients had a poor outcome within the first 90 days, including 17% (44) deaths. Two neuro intensivists evaluated functional outcomes at ICU discharge and 90 days after discharge.

The study highlighted two modifiable factors that could have an impact on outcomes: indirect ICU admission, and elevated body temperature at admission, although the latter factor has not been confirmed in other studies.



The main limitation of this study is its retrospective design, and 90-day delay to evaluate outcomes, which might be too short.  Nevertheless, it proposes a sound target to improve patients’ outcomes through an early admission in ICU.

It represents the largest retrospective study on patients presenting HSE in France and gives a solid background to the next step, the EURECA study (EURopean study on acute Encephalitis in intensive CAre units) – the first prospective international study on outcomes of all-cause acute meningoencephalitis requiring ICU admission.



Early detection and ICU admission in patients suspected of HSE and management of high body temperature, might be new perspectives to explore in order to obtain a significantly better functional outcome.


This article review was prepared and submitted by Silvia Calvino Gunther from the N&AHP section, on behalf of Journal Review Club




1) Whitley R and Baines J., Clinical management of herpes simplex virus infections: past, present, and future. F1000Research 2018, 7(F1000 Faculty Rev):1726

2) P. Jaquet, E. de Montmollin, C. Dupuis et al. and ENCEPHALITICA study group, Functional outcomes in adult patients with herpes simplex encephalitis admitted to the ICU: a multicenter cohort study. Intensive Care Med (2019) 45: 1103-1111

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