RESUMO
BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.
Assuntos
COVID-19/complicações , Doenças do Sistema Nervoso/epidemiologia , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Doença Aguda , Adolescente , Encefalopatias/epidemiologia , Encefalopatias/etiologia , COVID-19/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Cefaleia/epidemiologia , Cefaleia/etiologia , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Modelos Logísticos , Masculino , Doenças do Sistema Nervoso/etiologia , Prevalência , Fatores de Risco , América do Sul/epidemiologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: To define the incidence and characteristics of influenza-associated neurologic complications in a cohort of children hospitalized at a tertiary care pediatric hospital with laboratory-confirmed influenza and to identify associated clinical, epidemiologic, and virologic factors. STUDY DESIGN: This was an historical cohort study of children aged 0.5-18.0 years old hospitalized between 2010 and 2017 with laboratory-confirmed influenza. Children with immune compromise or a positive test due to recent receipt of live virus vaccine or recently resolved illness were excluded. Influenza-associated neurologic complications were defined as new-onset neurologic signs/symptoms during acute influenza illness without another clear etiology. RESULTS: At least 1 influenza-associated neurologic complication was identified in 10.8% (95% CI 9.1-12.6%, n = 131 of 1217) of hospitalizations with laboratory-confirmed influenza. Seizures (n = 97) and encephalopathy (n = 44) were the most commonly identified influenza-associated neurologic complications, although an additional 20 hospitalizations had other influenza-associated neurologic complications. Hospitalizations with influenza-associated neurologic complications were similar in age and influenza type (A/B) to those without. Children with a pre-existing neurologic diagnosis (n = 326) had a greater proportion of influenza-associated neurologic complications compared with those without (22.7% vs 6.4%, P < .001). Presence of a pre-existing neurologic diagnosis (aOR 4.6, P < .001), lack of seasonal influenza vaccination (aOR 1.6, P = .020), and age ≤5 years (aOR 1.6, P = .017) were independently associated with influenza-associated neurologic complications. CONCLUSIONS: Influenza-associated neurologic complications are common in children hospitalized with influenza, particularly those with pre-existing neurologic diagnoses. A better understanding of the epidemiology and factors associated with influenza-associated neurologic complications will direct future investigation into potential neuropathologic mechanisms and mitigating strategies. Vaccination is recommended and may help prevent influenza-associated neurologic complications in children.
Assuntos
Hospitalização/estatística & dados numéricos , Influenza Humana/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Incidência , Lactente , Masculino , Doenças do Sistema Nervoso/etiologia , Estudos RetrospectivosRESUMO
Multisystem inflammatory syndrome in children (MIS-C) is characterized by fever and multiorgan system dysfunction. Neurologic complications of MIS-C are not well described. We present 4 patients with MIS-C who had intracranial hypertension and discuss the unique management considerations when this occurs concurrently with significant myocardial dysfunction.
Assuntos
COVID-19/complicações , Hipertensão Intracraniana/etiologia , Pressão Intracraniana/fisiologia , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/complicações , Adolescente , COVID-19/epidemiologia , Criança , Feminino , Humanos , Hipertensão Intracraniana/fisiopatologia , Masculino , Pandemias , Síndrome de Resposta Inflamatória Sistêmica/epidemiologiaRESUMO
Acute flaccid myelitis (AFM) is a rare condition associated with spinal cord gray matter abnormalities and frequent persistent motor deficits in the limbs. We present our experience with the diagnosis, management, and outcomes of affected children in 2014 and 2016, emphasizing features that should trigger early consideration of AFM. Early viral testing may increase the rate of detecting associated viruses.
Assuntos
Viroses do Sistema Nervoso Central/diagnóstico , Viroses do Sistema Nervoso Central/terapia , Mielite/diagnóstico , Mielite/terapia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/terapia , Encéfalo/diagnóstico por imagem , Viroses do Sistema Nervoso Central/virologia , Criança , Pré-Escolar , DNA Viral , Erros de Diagnóstico/estatística & dados numéricos , Enterovirus/genética , Enterovirus/isolamento & purificação , Feminino , Fluoxetina/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Imageamento por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Mielite/virologia , Doenças Neuromusculares/virologia , Troca Plasmática , Reação em Cadeia da Polimerase , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medula Espinal/diagnóstico por imagemRESUMO
OBJECTIVE: To characterize the incidence and clinical characteristics of neurotoxicity in the month following CTL019 infusion in children and young adults, to define the relationship between neurotoxicity and cytokine release syndrome (CRS), and to identify predictive biomarkers for development of neurotoxicity following CTL019 infusion. METHODS: We analyzed data on 51 subjects, 4 to 22 years old, who received CTL019, a chimeric antigen receptor-modified T-cell therapy against CD19, between January 1, 2010 and December 1, 2015 through a safety/feasibility clinical trial (NCT01626495) at our institution. We recorded incidence of significant neurotoxicity (encephalopathy, seizures, and focal deficits) and CRS, and compared serum cytokine levels in the first month postinfusion between subjects who did and did not develop neurotoxicity. RESULTS: Neurotoxicity occurred in 23 of 51 subjects (45%, 95% confidence interval = 31-60%) and was positively associated with higher CRS grade (p < 0.0001) but was not associated with demographic characteristics or prior oncologic treatment history. Serum interleukin (IL)-2, IL-15, soluble IL-4, and hepatocyte growth factor concentrations were higher in subjects with neurotoxicity than those with isolated CRS. Differences in peak levels of select cytokines including IL-12 and soluble tumor necrosis factor receptor-1 within the first 3 days were seen in subjects with neurotoxicity. INTERPRETATION: Neurotoxicity is common after CTL019 infusion in children and young adults, and is associated with higher CRS grade. Differences in serum cytokine profiles between subjects with neurotoxicity and those with isolated CRS suggest unique pathophysiological mechanisms. Serum cytokine profiles in the first 3 days postinfusion may help identify children and young adults at risk for neurotoxicity, and may provide a foundation for investigation into potential mitigation strategies. Ann Neurol 2018;84:537-546.
Assuntos
Antígenos CD19/metabolismo , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/metabolismo , Receptores de Antígenos de Linfócitos T/administração & dosagem , Receptores de Antígenos de Linfócitos T/metabolismo , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Citocinas/metabolismo , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
Subtle differences in neuronal microanatomy may be coded in individuals with genetic susceptibility for neuropsychiatric disorders. Genetic susceptibility is a significant risk factor in the development of anxiety disorders, including post-traumatic stress disorder (PTSD). Pavlovian fear conditioning has been proposed to model key aspects of PTSD. According to this theory, PTSD begins with the formation of a traumatic memory which connects relevant environmental stimuli to significant threats to life. The lateral amygdala (LA) is considered to be a key network hub for the establishment of Pavlovian fear conditioning. Substantial research has also linked the LA to PTSD. Here we used a genetic mouse model of fear susceptibility (F-S) and resistance (F-R) to investigate the dendritic and spine structure of principal neurons located in the LA. F-S and F-R lines were bi-directionally selected based on divergent levels of contextual and cued conditioned freezing in response to fear-evoking footshocks. We examined LA principal neuron dendritic and spine morphology in the offspring of experimentally naive F-S and F-R mice. We found differences in the spatial distribution of dendritic branch points across the length of the dendrite tree, with a significant increase in branch points at more distal locations in the F-S compared with F-R line. These results suggest a genetic predisposition toward differences in fear memory strength associated with a dendritic branch point organization of principal neurons in the LA. These micro-anatomical differences in neuron structure in a genetic mouse model of fear susceptibility and resistance provide important insights into the cellular mechanisms of pathophysiology underlying genetic predispositions to anxiety and PTSD.