Acute Fulminant Cerebral Edema: A Newly Recognized Phenotype in Children With Suspected Encephalitis

Preetha Krishnan; Orit A Glenn; Michael C Samuel; Heather Sheriff; Audrey Foster-Barber; James J Sejvar; Arup Roy-Burman; Debra A Wadford; Christopher P Preas; Jay H Tureen; Carol A Glaser

doi:10.1093/jpids/piaa063

Acute Fulminant Cerebral Edema: A Newly Recognized Phenotype in Children With Suspected Encephalitis

J Pediatric Infect Dis Soc. 2021 Apr 3;10(3):289-294. doi: 10.1093/jpids/piaa063.

Authors

Affiliations

¹ Pediatric Critical Care Medicine, Randall Children's Hospital, Portland, Oregon, USA.
² Department of Radiology, University of California-San Francisco, San Francisco, California, USA.
³ California Department of Public Health, Richmond, California, USA.
⁴ Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, California, USA.
⁵ Department of Neurology, Benioff Children's Hospital, University of California-San Francisco, San Francisco, California, USA.
⁶ Division of High Consequence Pathogens and Pathology, National Center for Emerging Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁷ Univeristy of California-San Francisco, San Francisco, California, USA.
⁸ Department of Pediatrics, University of California-San Francisco, San Francisco, California, USA.
⁹ Pediatric Infectious Diseases, Kaiser Permanente, Oakland, California, USA.

PMID: 32667036
DOI: 10.1093/jpids/piaa063

Abstract

Background: Encephalitis is a severe neurological syndrome associated with significant morbidity and mortality. The California Encephalitis Project (CEP) enrolled patients for more than a decade. A subset of patients with acute and fulminant cerebral edema was noted.

Methods: All pediatric encephalitis patients with cerebral edema referred to the CEP between 1998 and 2012 were reviewed. A case definition was developed for acute fulminant cerebral edema (AFCE) that included the CEP case definition for encephalitis and progression to diffuse cerebral edema on neuroimaging and/or autopsy, and no other recognized etiology for cerebral edema (eg, organic, metabolic, toxin). Prodromic features, demographic and laboratory data, neuroimaging, and outcomes were compared with non-AFCE encephalitis cases.

Results: Of 1955 pediatric cases referred to the CEP, 30 (1.5%) patients met the AFCE case definition. The median age for AFCE and non-AFCE cases was similar: 8.2 years (1-18 years) and 8.0 years (0.5-18 years), respectively. Asian-Pacific Islanders comprised a larger proportion of AFCE cases (44%) compared with non-AFCE cases (14%, P < .01). AFCE cases often had a prodrome of high fever, vomiting, and profound headache. Mortality among AFCE patients was significantly higher than among non-AFCE patients (80% vs 13%, P < .01). A confirmed etiology was identified in only 2 cases (enterovirus, human herpes virus type 6), while 10 others had evidence of a respiratory pathogen.Thirty pediatric patients referred to the California Encephalitis Project with a unique, and often fatal, form of encephalitis are reported. Demographic and clinical characteristics, possible etiologies and a proposed case definition for acute fulminant cerebral edema (AFCE) are described.

Conclusions: AFCE is a recently recognized phenotype of encephalitis with a high mortality. AFCE may be triggered by common pediatric infections. Here, we propose a case definition.

Keywords: California Encephalitis Project; acute fulminant cerebral edema; encephalitis; pediatrics.

© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

MeSH terms

Brain Edema* / etiology
Child
Encephalitis* / diagnosis
Enterovirus Infections*
Humans
Neuroimaging
Phenotype