Infectious and Autoimmune Causes of Encephalitis in Children

Abstract

BACKGROUND AND OBJECTIVES: Encephalitis can result in neurologic morbidity and mortality in children. Newly recognized infectious and noninfectious causes of encephalitis have become increasingly important over the past decade. METHODS:We retrospectively reviewed medical records from pediatric patients in Houston diagnosed with encephalitis in both an urban and rural catchment area between 2010 and 2017. We conducted an investigation to understand the etiology, clinical characteristics, and diagnostic testing practices in this population. RESULTS:We evaluated 231 patients who met the case definition of encephalitis, among which 42% had no recognized etiology. Among those with an identified etiology, the most common were infectious (73; 31%), including viral (n = 51; 22%), with the most frequent being West Nile virus (WNV; n = 12), and bacterial (n = 19; 8%), with the most frequent being Bartonella henselae (n = 7). Among cases of autoimmune encephalitis (n = 60; 26%), the most frequent cause was anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (n = 31). Autoimmune causes were seen more commonly in female (P , .01) patients. Testing for herpes simplex virus and enterovirus was nearly universal; testing for anti-NMDAR encephalitis, WNV, and Bartonella was less common.CONCLUSIONS: WNV was the most common infectious cause of encephalitis in our pediatric population despite lower testing frequency for WNV than herpes simplex virus or enterovirus. Increasing testing for anti-NMDAR encephalitis resulted in frequent identification of cases. Increased awareness and testing for WNV and Bartonella would likely result in more identified causes of pediatric encephalitis. Earlier etiologic diagnosis of encephalitides may lead to improve clinical outcomes.WHAT'S KNOWN ON THIS SUBJECT: Pediatric encephalitides are often severe and lack an identified etiology. Newly recognized viruses and autoimmune causes are considered to be important, but no large recent studies have been conducted to assess their exact role in children. WHAT THIS STUDY ADDS:We found more encephalitides caused by West Nile virus, Bartonella, and autoimmune disease, despite these conditions being tested for less frequently. Testing for these conditions will improve our understanding of etiology and pathogenesis and may improve patient outcomes.

Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections

“…We describe application of metagenomics in the diagnosis of pediatric CNS infections that included all consenting subjects meeting enrollment criteria rather than only a referred subset. As described in previous studies, an infectious etiology was not identified for most subjects with suspected CNS infection [ 5 ]. A putative organism was isolated from CSF in 25 (35.7%) subjects, and, of these, mNGS of the CSF samples identified a pathogen in 20 (28.6%) subjects ( Table 3 ).…”

Search for Viral Infections in Cerebrospinal Fluid From Patients With Autoimmune Encephalitis

“…However, our study could have underestimated the prevalence of AE, as patients were required to have increased CSF pleocytosis and/or elevated protein to be diagnosed with encephalitis, and some AE cases have been observed without these findings [ 42 ]. The International Encephalitis Consortium has published guidelines for the identification of encephalitis that might decrease this bias using a combination approach specifically designed to include autoimmune causes [ 43 ], and some recent studies using these less strict criteria reported an AE proportion as high as 26% among all encephalitis cases [ 4 ].…”

“…Autoimmune encephalitis (AE), which is characterized by the presence of antineuronal or antiglial antibodies, has been reported to constitute 4.2% and 7.9% of all encephalitis cases in the United States and the United Kingdom, respectively [ 1 , 2 ]. However, some studies reported a markedly higher percentage [ 2 , 3 ] among pediatric patients [ 4 ]. Autoantibodies in AE are classified into 2 main categories: antibodies against neuronal cell surface and against intracellular antigens [ 5 ].…”

Pediatric Anti-N-methyl-D-aspartate Receptor Encephalitis Mimicking Glutaric Aciduria Type 1: A Case Report

“…Encephalitis is a potentially lethal neurologic disease wherein inflammation of brain parenchyma leads to neurologic dysfunction (8). Although infectious agents are the main cause of encephalitis, cases of autoimmune encephalitis are increasingly being reported (8,9). Since Dalmau et al (10) described anti-NMDAR encephalitis in 2007, epidemiologic studies have implicated anti-NMDAR encephalitis as a predominant cause of autoimmune encephalitis, second only to demyelinating acute encephalitis (9).…”