Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome

Abstract

IMPORTANCE Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. OBJECTIVE To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. SETTING, DESIGN, AND PARTICIPANTS Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. EXPOSURES Severe acute respiratory syndrome coronavirus 2. MAIN OUTCOMES AND MEASURES Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. RESULTS Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-tolymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. CONCLUSIONS AND RELEVANCE In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

6-month multidisciplinary follow-up and outcomes of patients with paediatric inflammatory multisystem syndrome (PIMS-TS) at a UK tertiary paediatric hospital: a retrospective cohort study

“…Neurological findings have also been reported commonly in other PIMS-TS cohorts. 16,17 In our cohort, persistence of subtle findings, which were only noticeable on detailed neurological exams, did not correlate with neurological functional impairment (median Expanded Disability Status Scale score 0 at 6 months). Although 98% of patients had resumed full-time education by 6 months, formal neuropsychology testing was not done and the long-term cognitive effects of PIMS-TS require attention given the high frequency of neurological involvement at presentation.…”

COVID-19 and the Pediatric Nervous System: Global Collaboration to Meet a Global Need

“…A recent case series of nearly 1700 hospitalized patients with COVID-19 under the age of 21 reported that 22% had neurologic manifestations. In this series, half of the patients with life-threatening neurologic manifestations had MIS-C [ 5 ].…”

Multisystem Inflammatory Syndrome in Children and COVID-19 Infections

“…Patients had an average of four organ systems involved with the most effected being the gastrointestinal, cardiovascular, hematologic, mucocutaneous, and respiratory systems ( Feldstein et al, 2020 ). Approximately 22% of MIS-C patients experience neurological manifestations, such as seizure, stroke, and encephalopathy ( LaRovere et al, 2021 ). The CDC has defined MIS-C using a specific set of criteria as listed in Figure 2 ( CDC, 2021b ).…”

“…In general, MIS-C is associated with increased interleukin (IL) levels for IL-6, neutrophils, troponin, brain natriuretic peptide, C-reactive protein, increased sedimentation rates, and altered T cell counts ( Ahmed et al, 2020 ; Cattalini et al, 2021 ; Feldstein et al, 2020 ; Rowley, 2020 ; Soma et al, 2021 ). Initial research points to children who present with higher neutrophil to lymphocyte ratios tended to experience more life-threatening neurological conditions ( LaRovere et al, 2021 ). It should be noted that there are no specific set of biomarkers that have been validated for MIS-C, however.…”

“…Cardiovascular complications, for example, may first be identified by the school nurse as new activity intolerance. Additionally, school nurses may recognize cognitive, developmental, and social changes, which could indicate ongoing neurological concerns ( LaRovere et al, 2021 ). Students with ongoing health concerns may benefit from a 504 plan.…”