Small vessel childhood primary angiitis of the central nervous system with positive anti-glial fibrillary acidic protein antibodies: a case report and review of literature.

BACKGROUND: Small vessel childhood primary angiitis of the central nervous system (SV-cPACNS) is a rare disease characterized by inflammation within small vessels such as arterioles or capillaries. CASE PRESENTATION: We report a case of SV-cPACNS in an 8-year-old boy confirmed by brain biopsy. This patient was also incidentally found to have anti-glial fibrillary acidic protein (GFAP) antibodies in the cerebrospinal fluid (CSF) but had no evidence of antibody-mediated disease on brain biopsy. A literature review highlighted the rarity of SV-cPACNS and found no prior reports of CSF GFAP-associated SV-cPACNS in the pediatric age group. CONCLUSION: We present the first case of biopsy proven SV-cPACNS vasculitis associated with an incidental finding of CSF GFAP antibodies. The GFAP antibodies are likely a clinically insignificant bystander in this case and possibly in other diseases with CNS inflammation. Further research is needed to determine the clinical significance of newer CSF autoantibodies such as anti-GFAP before they are used for medical decision-making in pediatrics.

Safety and Immunogenicity of SARS-CoV-2 Vaccination in Children with a History of MIS-C

Background. Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare sequela that typically develops 2-6 weeks after SARS-CoV-2 infection. According to CDC recommendations, children who recover from MIS-C should be vaccinated 90 days after diagnosis, but safety and immunogenicity data are lacking. Our aim was to evaluate the safety and immunogenicity of one dose of the BNT162b2 vaccine in children with a history of MIS-C. Methods. We conducted a longitudinal study of children with MIS-C admitted to Monroe Carell Jr. Children's Hospital at Vanderbilt from 7/11/2020 to 3/23/2022. Children were eligible if they met CDC's MIS-C criteria and had blood collected before and after SARS-CoV-2 vaccination. Clinical data were obtained from medical records and injection site and systemic reactions were recorded for a week following SARS-CoV-2 vaccination via memory aids. IgG against SARS-CoV-2 nucleocapsid (N), spike receptor-binding domain (RBD), and spike extracellular domain (ECD)was detected using an enzyme-linked immunosorbent assay. The first anti-RBD and anti-ECD levels prevaccination and post vaccination were compared using the paired-samples t-test. Results. Seven children were included, of whom five were male and five were non-Hispanic White. The first blood sample was collected 3-44 days following admission. The median age at admission was 15.8 years (IQR, 10.5-14.7 years), and the median time from admission to vaccination was 7 months (IQR, 6-8 months). Five children each had injection site or systemic reactions (Figure 1);the majority were mild or moderate and occurred within 2 days of vaccination. Children were followed for a median of 5.6 months (4.3-6.2 months) postvaccination;none developed MIS-C recurrence. Following vaccination, mean anti-RBD and anti-ECD levels increased by 2.0 (1.2-2.9;p < 0.001) and 1.9 (1.2-2.6;p < 0.001) absorbance units, respectively (Figure 2). A sensitivity analysis excluding children with antibody evidence of reinfection (increase in anti-N level >= 0.5) showed similar results. Conclusion. SARS-CoV-2 vaccination is safe and immunogenic in children with a history of MIS-C, with no documented recurrence of MIS-C-like illness. Further studies are needed to determine the optimal timing, safety, and immunogenicity of vaccination following MIS-C.

Identification of Early Features to Differentiate Hospitalized Children Admitted for Suspected MIS-C from Alternative Diagnoses

Background. Multi-system inflammatory syndrome in children (MIS-C) is a rare consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MIS-C shares features with common infectious and inflammatory syndromes and differentiation early in the course is difficult. Identification of early features specific to MIS-C may lead to faster diagnosis and treatment. We aimed to determine clinical, laboratory, and cardiac features distinguishing MIS-C patients within the first 24 hours of admission to the hospital from those who present with similar features but ultimately diagnosed with an alternative etiology. Methods. We performed retrospective chart reviews of children (0-20 years) who were admitted to Vanderbilt Children's Hospital and evaluated under our institutional MIS-C algorithm between June 10, 2020-April 8, 2021. Subjects were identified by review of infectious disease (ID) consults during the study period as all children with possible MIS-C require an ID consult per our institutional algorithm. Clinical, lab, and cardiac characteristics were compared between children with and without MIS-C. The diagnosis of MIS-C was determined by the treating team and available consultants. P-values were calculated using two-sample t-tests allowing unequal variances for continuous and Pearson's chi-squared test for categorical variables, alpha set at < 0.05. Results. There were 128 children admitted with concern for MIS-C. Of these, 45 (35.2%) were diagnosed with MIS-C and 83 (64.8%) were not. Patients with MIS-C had significantly higher rates of SARS-CoV-2 exposure, hypotension, conjunctival injection, abdominal pain, and abnormal cardiac exam (Table 1). Laboratory evaluation showed that patients with MIS-C had lower platelet count, lymphocyte count and sodium level, with higher c-reactive protein, fibrinogen, B-type natriuretic peptide, and neutrophil percentage (Table 2). Patients with MIS-C also had lower ejection fraction and were more likely to have abnormal electrocardiogram. Conclusion. We identified early features that differed between patients with MIS-C from those without. Development of a diagnostic prediction model based on these early distinguishing features is currently in progress.

Comparison of Demographics and Clinical Characteristics of Multisystem Inflammatory Syndrome in Children and Kawasaki Disease

Background. Multisystem inflammatory syndrome in children (MIS-C) is an illness associated with recent SARS-CoV-2 infection or exposure. Kawasaki disease (KD), a vasculitis with an unknown etiology, has overlapping clinical presentation with MIS-C, making it difficult to clinicians for distinguish between them. Therefore, we aimed to compare demographic, laboratory, and clinical characteristics between MIS-C and KD in hospitalized children in Nashville, TN. Methods. We conducted a single-center retrospective chart review for hospitalized children under 18 years who met American Heart Association criteria for KD and were treated with intravenous immunoglobulin from May 2000 to December 2019, and children meeting the CDC criteria for MIS-C from July 2020 to May 2021. Data ion for patients' demographics, clinical presentation, laboratory values and imaging results was performed. Pearson's chi-squared test for categorical variables and Wilcoxon rank sum test for continuous variables, with alpha=5%, were used to compare groups. Results. A total of 603 KD and 52 MIS-C hospitalized patients were included. Children with MIS-C were older than those with KD. A higher frequency of male sex was noted in both groups, with no significant differences in race and ethnicity (Table). MIS-C children frequently presented with symptoms similar to KD (63.5% rash, 55.8% conjunctivitis, 28.9% mucous membrane changes);however, only one MIS-C patient met criteria for complete KD (Figure). Both MIS-C and KD children presented with elevated CRP and ESR, but the median value of CRP in MIS-C children was significantly higher (Table). In addition, white cell count was lower in MIS-C children, which is primarily driven by the lower absolute lymphocyte count in this group (0.9 vs 2.7, p< 0.001), and echocardiography was more likely to be abnormal at presentation compared to KD (Table). Conclusion. MIS-C and KD present similarly in children;however, age, laboratory and echocardiography findings can help differentiate between them. Different laboratory values suggest different pathophysiology and inflammatory mediators behind these two illnesses, warranting further research.