Causality in acute encephalitis: defining aetiologies

Abstract

Defining the causal relationship between a microbe and encephalitis is complex. Over 100 different infectious agents may cause encephalitis, often as one of the rarer manifestations of infection. The gold-standard techniques to detect causative infectious agents in encephalitis in life depend on the study of brain biopsy material; however, in most cases this is not possible. We present the UK perspective on aetiological case definitions for acute encephalitis and extend them to include immune-mediated causes. Expert opinion was primarily used and was supplemented by literature-based methods. Wide usage of these definitions will facilitate comparison between studies and result in a better understanding of the causes of this devastating condition. They provide a framework for regular review and updating as the knowledge base increases both clinically and through improvements in diagnostic methods. The importance of new and emerging pathogens as causes of encephalitis can be assessed against the principles laid out here.

Infectious and Autoantibody-Associated Encephalitis: Clinical Features and Long-term Outcome

“…1 Encephalitis was defined as an acute encephalopathy with $2 of the following: fever $38°C, seizures or focal neurologic signs, CSF pleocytosis ($5 white blood cells/µL) or elevated CSF neopterin (.30 nmol/ L), EEG consistent with encephalitis (presence of slowing in this study), or MRI findings suggestive of encephalitis. CSF neopterin, which is produced secondary to a-or g-interferon stimulation, was included as an alternative to CSF pleocytosis because it has been shown to be a useful marker of central nervous system (CNS) inflammation.…”

“…The final etiologic diagnosis was determined by stringent application of the consensus guidelines proposed by Granerod et al 1 Cases were classified as confirmed, probable, or possible. Confirmed cases had detection of the organism or autoantibody in CSF or brain.…”

“…Confirmed cases had detection of the organism or autoantibody in CSF or brain. 1 A probable diagnosis was based on serological evidence of acute infection or autoantibody, and a possible diagnosis was based on detection of the organism from a specimen sample outside the CNS, such as stool or nasopharyngeal aspirate. 1 As accepted in the literature, we used the term infection-associated encephalopathy rather than encephalitis to denote encephalitis related to influenza virus or rotavirus.…”

“…1 A probable diagnosis was based on serological evidence of acute infection or autoantibody, and a possible diagnosis was based on detection of the organism from a specimen sample outside the CNS, such as stool or nasopharyngeal aspirate. 1 As accepted in the literature, we used the term infection-associated encephalopathy rather than encephalitis to denote encephalitis related to influenza virus or rotavirus. [17][18][19] In cases with multiple etiologies (Supplemental Table 4), the agent with the strongest hierarchical association (confirmed .…”

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

“…The goldstandard technique to detect causative infectious agents in encephalitis is a study of brain biopsy material, 49 but this is not possible in most HCT recipients. The results of retrospective studies 14,38 and many case reports 36 have suggested the importance of demonstrating HHV-6 DNA in cerebrospinal fluid, 3 image in (c) was taken from Ogata et al 7 and images in (f-h) were taken from Ogata et al 41 and several guidelines recommend cerebrospinal PCR testing for the diagnosis of HHV-6 encephalitis.…”