Clinical Characteristics and Follow-Up of Seizures in Children With Anti-NMDAR Encephalitis

Objective: To analyze the seizure characteristics of children with anti-NMDAR encephalitis.Methods: This was a retrospective analysis of 50 children with anti-NMDAR encephalitis between July 1, 2013, and July 1, 2019.Results: Fifty children with anti-NMDAR encephalitis were included in this study, of which 34 (68.0%) had seizures. During the follow-up, three patients with anti-NMDAR encephalitis secondary to herpes simplex virus encephalitis had persistent seizures. The average duration of seizures in the remaining patients was 14.6 days (range 1–47 days). Compared to patients without seizures, those with seizures were more likely to experience consciousness disturbances (p = 0.008) and epileptic form discharge on electroencephalograms (p = 0.002). The Glasgow coma scale scores (p = 0.014), and Rankin scale scores (p = 0.019) were also different. The cranial MRI findings of children were reviewed, and clinical characteristics were compared between children without cranial lesions and those with lesions in the limbic system and neocortex. Compared to children in the non-lesion group, children with lesions in the limbic system and neocortex had a higher incidence of status epilepticus. Further, children in the limbic system and neocortical lesions groups were more likely to be taking anti-seizure medications (ASMs) and receive second-line drugs.Conclusion: Long-term oral ASMs are not recommended for most children with anti-NMDAR encephalitis. Children with involvement of the limbic system and neocortex are prone to status epilepticus, and sequelae of epilepsy may remain when the neocortex is involved.

271. US Hospitalizations and 60-Day Readmission Rates Associated with Herpes Simplex Virus Encephalitis

Background Herpes Simplex encephalitis (HSE) is the most common cause of encephalitis hospitalizations with a known etiology. However, it remains a challenge to capture a comprehensive and robust understanding of the disease, particularly for long term outcomes after acute diagnosis and treatment. In particular, there is a growing body of literature showing increased concern for recurrent encephalopathic disease several weeks after initial HSE recovery. We sought to describe and analyze features associated with all cause readmissions and encephalopathy associated readmissions amongst HSE cases. Methods HSE hospitalizations and 60-day rehospitalizations were assessed in a retrospective cohort using linked hospitalizations from the Healthcare Utilization Project (HCUP) National Readmission Database (NRD) from 2010 through 2017. Risk factors for all-cause readmissions and encephalopathy associated readmissions were assessed with a weighted logistic regression model. Results There were 10,272 HSE cases in the United States between 2010 and 2017, resulting in a national rate of 4.95 per 100,000 hospitalizations. A total of 23.7% were readmitted at least once within 60-days. Patients that were readmitted were older (mean age 62.4 vs. 57.9, p< 0.0001), had a greater number of procedures at the index hospitalization (aOR 1.03, p< 0.0001) and have a higher Charlson comorbidity score (aOR 1.11, p< 0.0001). Amongst those readmitted, 465 (16.5%) had an encephalopathy related diagnosis. Over eight years, the prevalence of encephalopathy associated readmissions increased from 0.12 to 0.20 (figure 1). Encephalopathy specific readmissions were found to be associated with greater age (mean age 6.9 vs. 61.7, p = 0.004) and findings of cerebral edema at index hospitalization (aOR 2.16, p < 0.0001). Most Common Diagnosis Groups Listed at the 60-Day Readmission Conclusion HSE 60-day readmissions are relatively common, particularly among older and sicker individuals. Readmissions were often associated with new neurological symptoms concerning for either recurrent or new encephalopathic events. Early signs and symptoms of neurological disease at index were correlated with encephalopathic specific readmissions. Disclosures Rodrigo Hasbun, MD, MPH, Biofire (Speaker’s Bureau) Rodrigo Hasbun, MD, MPH, Biofire (Individual(s) Involved: Self): Consultant, Research Grant or Support

Quercus acuta Thunb. (Fagaceae) and Its Component, Isoquercitrin, Inhibit HSV-1 Replication by Suppressing Virus-Induced ROS Production and NF-κB Activation

HSV-1 is a neurotropic virus that replicates lytically during acute infection and establishes latency in peripheral neurons. Currently, the clinically approved compounds for the prevention of HSV-1 infection include acyclovir and penciclovir; however, long-term use of the drug is associated with serious side effects, and drug-resistant strains often appear. Therefore, it is important to find a safe and novel antiviral agent for HSV-1 infection. Quercus acuta Thunb. (Fagaceae) (QA) is widely distributed as an ornamental and dietary plant in Korea, Taiwan, China, and Japan. Thus far, the effects of QA extract and its active ingredients are known to have antioxidant, antibacterial, and anti-inflammatory activity, but studies of possible antiviral effects have not been reported. We studied the antiviral effects and molecular mechanism of QA after HSV-1 infection at the cellular level. We confirmed that QA suppresses ROS expression after HSV-1 infection and also suppresses inflammatory cytokine expression through inhibition of NF-кB activity. In addition, we found that QA increases the phosphorylation activity of IRF3 through induction of TBK1 activity during HSV-1 infection. QA exhibits an antiviral effect, and we confirmed through UPLC-DAD-mass spectrometer (MS)/MS analysis that it contains five main components: catechin, chlorogenic acid, fraxin, isoquercitrin, and taxifolin. Of these, isoquercitrin was confirmed to exhibit an antiviral effect on SK-N-SH cells through ICP27 inhibition. Overall, our results suggest that QA is a novel inhibitor with antiviral effects against HSV-1 infection and may be used specifically to prevent and treat of herpes simplex virus encephalitis infection.

A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis

Herpes simplex virus 1 (HSV-1) is responsible for herpes simplex virus encephalitis (HSE), associated with a 70% mortality rate in the absence of treatment. Despite intravenous treatment with acyclovir, mortality remains significant, highlighting the need for new anti-herpetic agents. Herein, we describe a novel neurovirulent recombinant HSV-1 (rHSV-1), expressing the fluorescent tdTomato and Gaussia luciferase (Gluc) enzyme, generated by the Clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9) system. The Gluc activity measured in the cell culture supernatant was correlated (P = 0.0001) with infectious particles, allowing in vitro monitoring of viral replication kinetics. A significant correlation was also found between brain viral titers and Gluc activity in plasma (R2 = 0.8510, P < 0.0001) collected from BALB/c mice infected intranasally with rHSV-1. Furthermore, evaluation of valacyclovir (VACV) treatment of HSE could also be performed by analyzing Gluc activity in mouse plasma samples. Finally, it was also possible to study rHSV-1 dissemination and additionally to estimate brain viral titers by in vivo imaging system (IVIS). The new rHSV-1 with reporter proteins is not only as a powerful tool for in vitro and in vivo antiviral screening, but can also be used for studying different aspects of HSE pathogenesis.