Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children

Abstract

Importance: Acute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge.

Objective: To characterize neurological, psychological, and quality of life sequelae after MIS-C.

Design, setting, and participants: This cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023.

Exposure: Diagnosis of MIS-C.

Main outcomes and measures: A central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences.

Results: Sixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls.

Conclusions and relevance: In this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms.

Figure.. Parallel Line Plot Depicting Group Differences in Selected Outcome Measures

Scores on the National Institutes of Health (NIH) Cognition Toolbox (List Sort Working Memory) (A), Behavior Assessment Scale for Children, Third Edition (BASC-3; Internalizing Problems) (B), Pediatric Quality of Life Inventory (PedsQL) Generic (Self-report) (C), and PedsQL Generic (Parent-report) (D) for patients with multisystem inflammatory syndrome in children (MIS-C) are plotted along the dark blue line in sequential order. Vertical light blue lines reflect difference between case and matched control, where available. Solid orange line reflects test mean or historical normative mean if not standardized. Dotted orange line indicates 1 SD worse than the mean; for BASC-3 internalizing problems, the dotted line indicates the test defined at-risk threshold. In the box plots, lines within boxes denote medians, ends of boxes denote IQRs, error bars extend to the farthest point within 1.5 IQR of the quartiles, and circles denote outliers.