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Encephalitis and meningoencephalitis: chasing the culprit
SCHIBLER, Manuel, et al.
SCHIBLER, Manuel, et al . Encephalitis and meningoencephalitis: chasing the culprit. Clinical Microbiology and Infection , 2019, vol. 25, no. 4, p. 406-407
DOI : 10.1016/j.cmi.2019.01.013 PMID : 30703529
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Editorial
Encephalitis and meningoencephalitis: chasing the culprit
Acute encephalitis, or meningoencephalitis if there is concom- itant meningeal inflammation, refers to a complex syndrome caused by brain inflammation resulting from various processes.
Although relatively rare, its consequences, including neurological sequelae and even death, can be devastating. Pinpointing its aeti- ology is a constant diagnostic challenge, as approximately half of cases remain of undetermined origin [1]. Infections represent thefirst cause of central nervous system inflammation, and signif- icant advances in microbiological diagnostics have been achieved in recent years, mainly through the implementation of sensitive and specific molecular tests that can be run in various biological compartments, including the cerebrospinalfluid. Autoimmunity is increasingly considered as an alternative differential diagnosis leading to encephalitis, and specialized laboratories offer more and more testing for highly specific autoantibodies, which can be screened for in serum as well as in cerebrospinal fluid, to further enhance specificity. Despite these recent developments, the diagnostic gap remains sizeable. An important diagnostic lim- itation rests in the nature of the clinical specimen that is most often analysed, namely the cerebrospinal fluid. Although ideal for investigating meningitis, it is only a suboptimal surrogate for what is happening deep within the brain parenchyma, which is the most relevant sample to analyse, at least regarding infectious encephalitis. However, because of its invasive character, brain bi- opsy is only rarely performed. Furthermore, the timing of path- ogen detection might also play against us. Indeed, some brain injuries can result from the immune response to a pathogen that has already disappeared.
Thefirst two reviews of this theme issue ofClinical Microbi- ology and Infection[2],[3]describe the numerous bugs infecting the central nervous system, and how to detect them using appro- priate microbiological tools. Thefirst one focuses on those that are ubiquitous or found in Europe, while the second attempts an over- view of the main infectious causes of encephalitis and meningo- encephalitis outside Europe, in the returning traveller, with emphasis on their geographic distribution. In these two reviews, useful central nervous system magnetic resonance imagingfind- ings, which can sometimes orientate to the underlying aetiology of encephalitis, are also discussed. The third review[4]offers a thorough overview of the contribution of unbiased high- throughput sequencing to expanding the list of viral neuropatho- gens, which might not be detected using conventional microbio- logical assays.
To complement the diagnostic approach, the fourth review[5]
discusses the main autoimmune causes of encephalitis,
highlighting the recent‘antibody breakthrough’, which dramati- cally enhances the diagnostic accuracy of autoimmune encephali- tis. This review also highlights the complexity of this topic, because an infection-triggered autoimmune mechanism has been proposed in patients presenting with encephalitis. As for in- fectious encephalitis, brain magnetic resonance imaging can be of great complementary diagnostic value, and specificfindings are emphasized. The added value of positron emission tomography computed tomography in the setting of autoimmune encephalitis, is also discussed.
In summary, the aim of the current theme issue is to compile the currently available diagnostic tools enabling the rapid and accurate identification of encephalitis and meningoencephalitis aetiology.
Since differentiating between infectious and autoimmune enceph- alitis on a clinical basis is challenging[6], paraclinical tools are necessary, such as molecular diagnostics, serological tests looking for an immune response to a microorganism or for autoantibodies, as well as the aforementioned imaging techniques. Efficient team- work between specialists in charge of a patient presenting with en- cephalitis or meningoencephalitis is of important diagnostic and therapeutic value. Such a collaboration should include an infectious diseases specialist and neuro-immunologist in order to tackle the challenges of diagnostic strategies and appropriate therapeutics, according to the culprit. Opposite approaches are in play: either empiric or tailored antimicrobial treatment, versus immuosuppres- sive therapy. Furthermore, even in the absence of therapeutic con- sequences, identifying the cause of (meningo-)encephalitis may allow for prognosis evaluation. Finally, basic research in thefield of brain inflammation should be promoted tofill the aetiological gap of this clinically important entity.
Transparency declaration
The authors have no conflicts of interest to declare. No external funding was received to write this review.
References
[1]Venkatesan A. Epidemiology and outcomes of acute encephalitis. Curr Opin Neurol 2015;28:277e82.
[2]Schibler M, Eperon G, Kenfak A, Lascano A, Vargas MI, Stahl JP. Diagnostic tools to tackle infectious causes of encephalitis and meningoencephalitis in immuno- competent adults in Europe. Clin Microbiol Infect 2019;25:408.
[3]Kenfak A, Eperon G, Schibler M, Lamoth F, Vargas MI, Stahl JP. Diagnostic approach to encephalitis and meningoencephalitis in adult returning travellers.
Clin Microbiol Infect 2019;25:430.
Contents lists available atScienceDirect
Clinical Microbiology and Infection
j o u r n a l h o m e p a g e : w w w . c l i n i c a l m i c r o b i o l o g y a n d i n f e c t i o n . c o m Clinical Microbiology and Infection 25 (2019) 406e407
https://doi.org/10.1016/j.cmi.2019.01.013
1198-743X/©2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
[4]Zanella M-C, Lenggenhager L, Schrenzel J, Cordey S, Kaiser L. High-throughput sequencing for the aetiologic identification of viral encephalitis, meningoen- cephalitis, and meningitis. A narrative review and clinical appraisal. Clin Micro- biol Infect 2019;25:415.
[5]Lascano AM, Vargas MI, Lalive PH. Diagnostic tools for immune causes of en- cephalitis. Clin Microbiol Infect 2019;25:424.
[6]Wagner JN, Kalev O, Sonnberger M, Krehan I, von Oertzen TJ. Evaluation of clin- ical and paraclinicalfindings for the differential diagnosis of autoimmune and infectious encephalitis. Front Neurol 2018;9:434.
M. Schibler* Infectious Diseases Division and Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland M.C. Zanella Infectious Diseases Division, Geneva University Hospitals, Geneva, Switzerland
L. Kaiser Infectious Diseases Division, Laboratory of Virology, and Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland P.H. Lalive Neurology Division, Geneva University Hospitals, Geneva, Switzerland
* Corresponding author.
E-mail address:manuel.schibler@hcuge.ch(M. Schibler).
6 December 2018 Available online 29 January 2019 Editor: L. Leibovici
Editorial / Clinical Microbiology and Infection 25 (2019) 406e407 407
