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.

Authors' Contributions 1.JF -Substantial contributions to acquisition, analysis and interpretation of data, drafting the work, final approval of the version to be published and agreement to be accountable for all aspects of the work. 2.AO -Substantial contributions to the conception and design of the work, analysis and interpretation of data, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 3.TP -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 4.SW -Substantial contributions to the conception and design of the work, analysis and interpretation of data, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 5.AL -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 6.NL -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 7.AB -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 8.RP -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 9.LK -Substantial revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 10.SG -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 11.IP -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 12.IQ -Substantial contributions to revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable for all aspects of the work. 13.RJ -Substantial contributions to the conception and design of the work, revising it critically for important intellectual content, final approval of the version to be published and agreement to be accountable ...

Selumetinib has promising antitumor activity in children with LGG. Rash and mucositis were the most common DLTs.

A B S T R A C T PurposeA phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent malignant glioma (MG) and intrinsic brainstem glioma (BSG). Patients and MethodsEligible patients received two doses of BVZ intravenously (10 mg/kg) 2 weeks apart and then BVZ plus CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included diffusion weighted and T1 dynamic contrastenhanced permeability imaging, BVZ pharmacokinetics, and estimation of vascular endothelial growth factor receptor 2 (VEGFR-2) phosphorylation in peripheral blood mononuclear cells (PBMC) after single-agent BVZ. ResultsThirty-one evaluable patients received a median of two courses of BVZ plus 1 to 19). No sustained responses were observed in either stratum. Median time to progression for all 34 eligible patients enrolled was 127 days for MG and 71 days for BSG. Progression-free survival rates at 6 months were 41.8% and 9.7% for MG and BSG, respectively. Toxicities related to BVZ included grade 1 to 3 fatigue in seven patients, grade 1 to 2 hypertension in seven patients, grade 1 CNS hemorrhage in four patients, and grade 4 CNS ischemia in two patients. The mean diffusion ratio decreased after two doses of BVZ in patients with MG only. Vascular permeability parameters did not change significantly after therapy in either stratum. Inhibition of VEGFR-2 phosphorylation in PBMC was detected in eight of 11 patients after BVZ exposure. ConclusionBVZ plus CPT-11 was well-tolerated but had minimal efficacy in children with recurrent malignant glioma and brainstem glioma.