Severe fever with thrombocytopenia syndrome-associated encephalopathy/encephalitis

Abstract

Objectives: Severe fever with thrombocytopenia syndrome (SFTS) virus has a variety of central nervous system (CNS) manifestations. However, there are limited data regarding SFTS-associated encephalopathy/encephalitis (SFTSAE) and its mechanism. Methods: All patients with confirmed SFTS who underwent cerebrospinal fluid (CSF) examination due to suspected acute encephalopathy were enrolled in three referral hospitals between January 2013 and October 2016. Real-time RT-PCR for SFTS virus and chemokine/cytokines levels from blood and CSF were analysed. Results: Of 41 patients with confirmed SFTS by RT-PCR for SFTS virus using blood samples, 14 (34%) underwent CSF examination due to suspected SFTSAE. All 14 patients with SFTSE revealed normal protein and glucose levels in CSF, and CSF pleocytosis was uncommon (29%, 4/14). Of the eight patients whose CSF was available for further analysis, six (75%) yielded positive results for SFTS virus. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) level in CSF were significantly higher than those in serum (geometric mean 1889 pg/mL in CSF versus 264 pg/mL in serum for MCP-1, p ¼ 0.01, and geometric mean 340 pg/mL in CSF versus 71 pg/mL in serum for IL-8, p ¼ 0.004). Conclusions: The CNS manifestation of SFTS as acute encephalopathy/encephalitis is a common complication of SFTS. Although meningeal inflammation was infrequent in patients with SFTSAE, SFTS virus was frequently detected in CSF with elevated MCP-1 and IL-8. These findings indicate that possible direct invasion of the CNS by SFTS virus with the associated elevated cytokine levels in CSF may play an important role in the pathogenesis of SFTSAE.

Monocyte Chemoattractant Protein (MCP)-1 in Rotavirus-Associated White Matter Injury in Newborns

“…In fact, overexpression of MCP-1 in the CNS clearly has an important role in viral encephalitis through the recruitment of monocytes, facilitating virus invasion into the brain. 18,19 However, similar results with our study, that is, only increased chemokines including MCP-1 without virus invasion, have been reported in other viralassociated encephalopathies. 20,21 In our R þ Wþ cases, rotavirus might not function in the CNS directly because neither pleocytosis nor virus was detected in the CSF.…”

Detection of viral RNA in diverse body fluids in an SFTS patient with encephalopathy, gastrointestinal bleeding and pneumonia: a case report and literature review

“…Most risk factors for encephalopathy were consistent with the aforementioned factors related to poor prognosis. In addition, Park et al reported that CSF analysis exhibited glucose and protein levels within the normal range, an increase in cell count in the CSF was not remarkable, and the SFTSV genome was positive in 75% of cases [13]. These findings, along with the findings in this study, may be an important piece of information to advance our understanding of the pathophysiological mechanisms of encephalopathy in SFTS patients.…”

“…Patients with SFTS are prone to develop encephalopathy [12,13]. Cui et al reported that 19% of patients with SFTS developed encephalopathy, and of these, the mortality rate was 44.7% [12].…”

Case Report: Use of Plasma Exchange Followed by Convalescent Plasma Therapy in a Critically Ill Patient with Severe Fever and Thrombocytopenia Syndrome–Associated Encephalopathy: Cytokine/Chemokine Concentrations, Viral Loads, and Antibody Responses

“…We started PE from hospital day (HD) 1 and performed it a total of four times for about 120 minutes per session using a Cobe spectra (Terumo BCT, Lakewood, CO) because approximately 60-70% of the substances present in plasma are removed for each 1-1.5 plasma volumes exchanged, and more than 90% of substances can be removed when PE is performed more than three times. 5 We analyzed 18 cytokines and chemokines in his serum, as described previously, 6 and the levels of interferon (IFN)-α and inducible protein (IP)-10 significantly decreased after the start of PE ( Figure 1 and Supplemental Figure 1). However, even after the fourth PE, when the level of IP-10 was further reduced from 6,427.8 pg/mL (HD 1) to 5,040.73 pg/mL (HD 3), the patient's consciousness had deteriorated further to GCS score 9 and there was no change in serum viral load ( Figure 1).…”