Etiology Still Unclear in Many Cases of Childhood Encephalitis

By Will Boggs MD

May 05, 2020

NEW YORK (Reuters Health) - Viral, bacterial and autoimmune etiologies account for most cases of encephalitis in children, but more than four in 10 have no recognized cause, according to a new review of medical records.

"With 42% of our cases still not having a diagnosis as to cause, increasing testing might help us better understand the true incidence of these diseases in the pediatric population and help guide treatment," Dr. Kristy O. Murray of the National School of Tropical Medicine, at Baylor College of Medicine, and Texas Children's Hospital, in Houston, told Reuters Health by email.

There are more than 100 different recognized etiologies that can lead to encephalitis in children, and many of these differ with respect to geography and ecology.

Dr. Murray and colleagues examined the prevalence of infectious and noninfectious etiologies of encephalitis in their analysis of 231 children with encephalitis in the Texas Children's Hospital's database of medical records.

More than half of the patients (133/231, 58%) had an identified etiology of encephalitis, whereas the remaining 42% had no identified cause. Infectious etiologies accounted for 73 cases, and noninfectious or autoimmune etiologies accounted for 60 cases.

Among the infectious etiologies, viral causes were most common (51/73, 70%), and the most common viral cause was West Nile virus (12 cases). Less common viral causes included herpes simplex virus 1 (HSV-1; 10 cases), human herpesvirus 6 (HHV-6; four cases), and varicella zoster virus (three cases), the researchers report in Pediatrics.

Bacteria accounted for 19 cases of encephalitis, led by Bartonella henselae (the cause of cat scratch fever; seven cases) and followed by Streptococcus pneumoniae (five cases) and Rickettsia rickettsii (the cause of Rocky Mountain spotted fever; two cases).

Autoimmune and immune-mediated causes of encephalitis represented 45% of all patients with an identified etiology. The most frequently identified single cause in this group was anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (31 cases). Second most common was acute disseminated encephalomyelitis (ADEM; 18 cases).

There were nine deaths (4%) among these patients, five of which had unknown causes despite extensive testing. The other deaths were caused by the ameba Naegleria fowleri and the viruses enterovirus, HSV-1 and HHV-6, with the latter death occurring in the recipient of a medically complex bone marrow transplant.

The median time to diagnosis of causal agents varied widely, from two to six days for infectious causes to as long as 32.5 days for diseases associated with rarer autoimmune antibodies.

Male patients were more likely to present with infectious causes, whereas female patients were more likely to have autoimmune etiologies. The proportion of autoimmune cases relative to infectious cases increased with increasing age.

Compared with autoimmune encephalitis, infectious encephalitis was more likely to occur in immunocompromised patients and to be associated with abnormal brain MRI findings.

"Our most common causes of viral, bacterial, and autoimmune causes of encephalitis (West Nile, Bartonella, and anti-NMDAR, respectively) were also the ones that had lower testing rates compared to other traditional causes of encephalitis," Dr. Murray said. "These causes should also be included when working up a case of encephalitis in a child."

"Future research should be focused on pathogen discovery and investigating other autoimmune causes," she said.

SOURCE: Pediatrics, online May 1, 2020.