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1.
Ann Neurol ; 95(4): 700-705, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38411340

RESUMEN

Reported rates of Epstein-Barr virus (EBV) seropositivity in children meeting multiple sclerosis (MS) diagnostic criteria are considerably lower than those reported in adult-onset MS, putting in question a requisite role for EBV in MS development. As prior work preceded recognition of myelin oligodendrocyte glycoprotein-associated disease (MOGAD), we assessed viral serologies in 251 children with incident demyelination and prospectively ascertained diagnoses. When MOGAD was serologically accounted for, the prevalence of EBV infection among MS children exceeded 90%, whereas remote EBV infection was not associated with MOGAD risk. Together, these findings substantiate EBV's role across the MS spectrum, and support distinct pathobiological mechanisms in MS versus MOGAD. ANN NEUROL 2024;95:700-705.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Esclerosis Múltiple , Adulto , Niño , Humanos , Autoanticuerpos , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Glicoproteína Mielina-Oligodendrócito
2.
Dev Med Child Neurol ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491729

RESUMEN

AIM: To characterize the presenting features and outcomes in children with seronegative autoimmune encephalitis, and to evaluate whether scores at nadir for the Modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) or its paediatric-specific modification (ped-CASE) are predictive of outcomes. METHOD: This observational study included children younger than 18 years of age with seronegative autoimmune encephalitis. Demographics and clinical data were collected. The mRS and CASE/ped-CASE scores were used to evaluate disease severity. Descriptive statistics and logistic regression were used for data analysis and to evaluate associations between scale scores and outcomes. RESULTS: Sixty-three children were included (39 [62%] females, median age 7 years, interquartile range [IQR] 4 years 1 months-11 years 6 months), with follow-up available for 56 out of 63 patients (median follow-up 12.2 months, IQR 13.4-17.8). The most frequent presenting neurological manifestation was encephalopathy (81%). Median CASE/ped-CASE and mRS scores at nadir were 12.0 (IQR 7.0-17.0) and 1.0 (IQR 0-2.0) respectively. Thirty-three patients (59%) had persistent neurological deficits at follow-up. Both scoring systems suggested good functional recovery (mRS score ≤2, 95%; CASE/ped-CASE score <5, 91%). CASE/ped-CASE score was more likely than mRS to distinguish children with worse outcomes. INTERPRETATION: Children with seronegative autoimmune encephalitis are likely to have neurological deficits at follow-up. CASE/ped-CASE is more likely to distinguish children with worse outcomes than MRS.

3.
Can J Neurol Sci ; 51(1): 40-49, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36597285

RESUMEN

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.


Asunto(s)
COVID-19 , Niño Hospitalizado , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , Niño , COVID-19/complicaciones , SARS-CoV-2 , Hospitalización , Fiebre/epidemiología , Fiebre/etiología , Cefalea/epidemiología , Cefalea/etiología , Síndrome
4.
J Pediatr ; 253: 55-62.e4, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36115622

RESUMEN

OBJECTIVES: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central , Infecciones por Enterovirus , Mielitis , Enfermedades Neuromusculares , Niño , Humanos , Mielitis/diagnóstico , Mielitis/terapia , Enfermedades Neuromusculares/diagnóstico , Enfermedades Neuromusculares/terapia , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/terapia , Estudios Retrospectivos , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/terapia
5.
Infection ; 51(3): 737-741, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36038707

RESUMEN

PURPOSE: The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection. METHODS: Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome. RESULTS: Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home. CONCLUSION: Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge.


Asunto(s)
COVID-19 , Humanos , Niño , SARS-CoV-2 , Canadá , Progresión de la Enfermedad , Oxígeno
6.
Mult Scler ; 28(14): 2253-2262, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35946086

RESUMEN

BACKGROUND: In children, multiple sclerosis (MS) is the ultimate diagnosis in only 1/5 to 1/3 of cases after a first episode of central nervous system (CNS) demyelination. As the visual pathway is frequently affected in MS and other CNS demyelinating disorders (DDs), structural retinal imaging such as optical coherence tomography (OCT) can be used to differentiate MS. OBJECTIVE: This study aimed to investigate the utility of machine learning (ML) based on OCT features to identify distinct structural retinal features in children with DDs. METHODS: This study included 512 eyes from 187 (neyes = 374) children with demyelinating diseases and 69 (neyes = 138) controls. Input features of the analysis comprised of 24 auto-segmented OCT features. RESULTS: Random Forest classifier with recursive feature elimination yielded the highest predictive values and identified DDs with 75% and MS with 80% accuracy, while multiclass distinction between MS and monophasic DD was performed with 64% accuracy. A set of eight retinal features were identified as the most important features in this classification. CONCLUSION: This study demonstrates that ML based on OCT features can be used to support a diagnosis of MS in children.


Asunto(s)
Esclerosis Múltiple , Tomografía de Coherencia Óptica , Humanos , Niño , Esclerosis Múltiple/diagnóstico por imagen , Aprendizaje Automático , Retina/diagnóstico por imagen , Vías Visuales
7.
CMAJ ; 194(14): E513-E523, 2022 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-35410860

RESUMEN

BACKGROUND: SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time. METHODS: We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement. RESULTS: Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 µg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%). INTERPRETATION: We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.


Asunto(s)
COVID-19 , Enfermedades del Tejido Conjuntivo , COVID-19/complicaciones , COVID-19/epidemiología , Canadá/epidemiología , Niño , Preescolar , Estudios de Cohortes , Ferritinas , Humanos , Masculino , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica
8.
Pediatr Blood Cancer ; 69(9): e29793, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35689507

RESUMEN

INTRODUCTION: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited. METHODS: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes. RESULTS: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage. CONCLUSION: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.


Asunto(s)
COVID-19 , Trombosis , COVID-19/complicaciones , Niño , Niño Hospitalizado , Síndrome de Liberación de Citoquinas , Hemorragia/epidemiología , Hemorragia/etiología , Humanos , Sistema de Registros , Estudios Retrospectivos , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica , Trombosis/epidemiología , Trombosis/etiología
9.
Dev Med Child Neurol ; 64(8): 1008-1016, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35108406

RESUMEN

AIM: To evaluate clinical and imaging features in patients with acute necrotizing encephalopathy of childhood (ANEC) to identify predictors of RANBP2 mutations, influenza association, and long-term outcomes. METHOD: A retrospective chart review in patients with ANEC (2012-2020) seen at a tertiary pediatric center was performed. Children were included if they had acute inflammatory lesions in the basal ganglia and pons. Variables included presenting features, imaging characteristics, RANBP2 gene testing, nasopharyngeal swab findings, therapies, and long-term outcomes. RESULTS: Twenty patients were included (average age at presentation 3y 6mo, interquartile range  3y 7mo, SD  2y 8mo; 14 females, six males). Three of the 20 experienced recurrences; one of the 20 died. Ten patients were influenza positive. Seven patients were RANBP2 mutation positive. A higher likelihood of hemorrhage was observed in patients who were influenza positive compared to influenza negative (p=0.048). Patients with influenza had a higher degree of thalamic hemorrhage (2, p=0.035) and greater extent of diffusion restriction (3, p=0.035) in semiquantitive analysis. INTERPRETATION: Children with ANEC who are positive for influenza are more likely to have hemorrhage and greater thalamic swelling. RANBP2 status was predictive of relapse but not predictive of overall outcome.


Asunto(s)
Encefalitis , Gripe Humana , Leucoencefalitis Hemorrágica Aguda , Chaperonas Moleculares , Proteínas de Complejo Poro Nuclear , Enfermedad Aguda , Niño , Encefalitis/genética , Femenino , Humanos , Gripe Humana/complicaciones , Gripe Humana/genética , Leucoencefalitis Hemorrágica Aguda/genética , Masculino , Chaperonas Moleculares/genética , Mutación , Proteínas de Complejo Poro Nuclear/genética , Estudios Retrospectivos
10.
Eur J Pediatr ; 181(6): 2535-2539, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35217918

RESUMEN

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)).    Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: • A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. • For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: • One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. • Infants had half the odds of older children of having severe or critical disease.


Asunto(s)
COVID-19 , Adolescente , COVID-19/terapia , Niño , Preescolar , Estudios de Cohortes , Hospitalización , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad
11.
Dev Med Child Neurol ; 62(3): 390-395, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31468511

RESUMEN

The aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol. MOG antibody testing was performed following standardized cell-based methods. Median clinical follow-up after rituximab induction was 2 years (IQR 1y 7mo-2y 10mo). The relapse rate in the first 12 months posttreatment was 0 (IQR 0-0). After rituximab, two patients relapsed during B-cell suppression and four showed clinical or radiological disease recurrences at B-cell reconstitution. Mild-to-moderate infusion related adverse events occurred in two patients. Leukopenia developed in seven patients and serum immunoglobulin suppression in five patients with no significant age effect on the risk of their development. None developed severe life-threatening events. Rituximab-induced B-cell suppression was associated with absence of relapses in 10 patients who were MOG-positive with recurrent disease. Rituximab was well tolerated. The most frequent adverse effects were hypogammaglobulinemia and leukopenia. We recommend monitoring of complete blood counts and immunoglobulins in this population. WHAT THIS PAPER ADDS: Rituximab appears to control disease in most anti-myelin oligodendrocyte glycoprotein-positive patients with relapsing neuroinflammatory disease. Rituximab was associated with transitory, mild-to-moderate infusion-related effects. Half of patients treated with rituximab developed leukopenia or hypogammaglobulinemia. No opportunistic infections were observed.


Asunto(s)
Antiinflamatorios/uso terapéutico , Enfermedades Autoinmunes Desmielinizantes SNC/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Glicoproteína Mielina-Oligodendrócito/inmunología , Rituximab/uso terapéutico , Adolescente , Autoanticuerpos/sangre , Niño , Enfermedades Autoinmunes Desmielinizantes SNC/sangre , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Femenino , Humanos , Inflamación/sangre , Inflamación/inmunología , Masculino , Resultado del Tratamiento
12.
Pediatr Blood Cancer ; 66(8): e27776, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31033188

RESUMEN

BACKGROUND: Treatment of opsoclonus-myoclonus syndrome (OMS) has historically involved corticosteroids and intravenous immunoglobulin (IVIG) for a duration of 6-12 months or longer. This study evaluated whether a brief upfront immunomodulatory therapy protocol with rituximab reduces the duration of OMS therapy without adversely affecting OMS outcomes. PROCEDURE: Retrospective chart review was performed for consecutive children diagnosed with OMS from 2006 to 2019 at The Hospital for Sick Children (Toronto, Canada). Children treated within 3 months of diagnosis with a treatment protocol involving pulse methylprednisolone (3-5 days, followed by an oral steroid taper), IVIG and/or plasma exchange, and rituximab (protocol group, n = 7) were compared to a historical group treated primarily with prednisone and IVIG (n = 8). RESULTS: The duration of corticosteroid treatment was shorter in the protocol (median 4.5 [range 3-12] months) compared to that in the historical group (median 21.5 [range 6-70] months, P = .005), and subjects in the protocol group received fewer cycles of IVIG (median 1 [range 0-7] cycle vs 7 [range 1-70] cycles, P = .01). The proportion of children with OMS relapse was similar between the protocol and historic groups (2/6 vs 5/8, P = .59). OMS symptom rating scales at 12-month follow-up were similar in the protocol group (median 2.5, range 0-3) compared to that in the historical group (median 1, range 0-7; P = .66). CONCLUSIONS: An upfront immunomodulatory therapy protocol with rituximab permits reduction in the duration of corticosteroid and IVIG therapy without a detrimental effect on OMS outcomes. Future studies with longer follow-up will have to determine whether neurocognitive and psychosocial outcomes are improved by this approach.


Asunto(s)
Inmunomodulación , Inmunoterapia/métodos , Recurrencia Local de Neoplasia/terapia , Síndrome de Opsoclonía-Mioclonía/terapia , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Síndrome de Opsoclonía-Mioclonía/inmunología , Síndrome de Opsoclonía-Mioclonía/patología , Pronóstico , Estudios Retrospectivos
13.
Mult Scler ; 22(3): 385-8, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26199356

RESUMEN

Epstein-Barr virus (EBV) infection is associated with increased multiple sclerosis (MS) risk. Recently, cytomegalovirus (CMV) infection has been proposed as a protective factor against MS development. We determined EBV, herpes simplex virus, varicella-zoster virus and CMV seroprevalence in 247 prospectively followed children with acquired demyelinating syndromes (ADS). Remote EBV infection was more common in children with MS than those with monophasic ADS while CMV infection was more common in children with monophasic ADS. Children displaying evidence of remote EBV without CMV infection were at highest risk of subsequent MS diagnosis. Viral infection repertoire detected at ADS provides important prognostic information.


Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Enfermedades Desmielinizantes/virología , Infecciones por Virus de Epstein-Barr/epidemiología , Esclerosis Múltiple/virología , Anticuerpos Antivirales/sangre , Varicela/complicaciones , Varicela/epidemiología , Niño , Estudios de Cohortes , Infecciones por Citomegalovirus/complicaciones , Ensayo de Inmunoadsorción Enzimática , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Herpes Simple/complicaciones , Herpes Simple/epidemiología , Humanos , Inmunoglobulina G/sangre , Masculino , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Estudios Seroepidemiológicos
14.
PLoS Pathog ; 8(2): e1002523, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22319451

RESUMEN

The eukaryotic cytoskeleton is essential for structural support and intracellular transport, and is therefore a common target of animal pathogens. However, no phytopathogenic effector has yet been demonstrated to specifically target the plant cytoskeleton. Here we show that the Pseudomonas syringae type III secreted effector HopZ1a interacts with tubulin and polymerized microtubules. We demonstrate that HopZ1a is an acetyltransferase activated by the eukaryotic co-factor phytic acid. Activated HopZ1a acetylates itself and tubulin. The conserved autoacetylation site of the YopJ / HopZ superfamily, K289, plays a critical role in both the avirulence and virulence function of HopZ1a. Furthermore, HopZ1a requires its acetyltransferase activity to cause a dramatic decrease in Arabidopsis thaliana microtubule networks, disrupt the plant secretory pathway and suppress cell wall-mediated defense. Together, this study supports the hypothesis that HopZ1a promotes virulence through cytoskeletal and secretory disruption.


Asunto(s)
Acetiltransferasas/metabolismo , Arabidopsis/microbiología , Proteínas de la Membrana Bacteriana Externa/metabolismo , Citoesqueleto/metabolismo , Microtúbulos/metabolismo , Pseudomonas syringae/patogenicidad , Acetilación , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/inmunología , Proteínas de Arabidopsis/metabolismo , Línea Celular , Células HEK293 , Humanos , Ácido Fítico/metabolismo , Enfermedades de las Plantas/microbiología , Pseudomonas syringae/enzimología , Pseudomonas syringae/genética , Tubulina (Proteína)/metabolismo
15.
J Child Neurol ; 39(3-4): 129-134, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38544431

RESUMEN

INTRODUCTION: Little is known about the longitudinal trajectory of brain growth in children with opsoclonus-myoclonus ataxia syndrome. We performed a longitudinal evaluation of brain volumes in pediatric opsoclonus-myoclonus ataxia syndrome patients compared with age- and sex-matched healthy children. PATIENTS AND METHODS: This longitudinal case-control study included brain magnetic resonance imaging (MRI) scans from consecutive pediatric opsoclonus-myoclonus ataxia syndrome patients (2009-2020) and age- and sex-matched healthy control children. FreeSurfer analysis provided automatic volumetry of the brain. Paired t tests were performed on the curvature of growth trajectories, with Bonferroni correction. RESULTS: A total of 14 opsoclonus-myoclonus ataxia syndrome patients (12 female) and 474 healthy control children (406 female) were included. Curvature of the growth trajectories of the cerebral white and gray matter, cerebellar white and gray matter, and brainstem differed significantly between opsoclonus-myoclonus ataxia syndrome patients and healthy control children (cerebral white matter, P = .01; cerebral gray matter, P = .01; cerebellar white matter, P < .001; cerebellar gray matter, P = .049; brainstem, P < .01). DISCUSSION/CONCLUSION: We found abnormal brain maturation in the supratentorial brain, brainstem, and cerebellum in children with opsoclonus-myoclonus ataxia syndrome.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Síndrome de Opsoclonía-Mioclonía , Humanos , Femenino , Masculino , Estudios Longitudinales , Síndrome de Opsoclonía-Mioclonía/diagnóstico por imagen , Síndrome de Opsoclonía-Mioclonía/patología , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Niño , Estudios de Casos y Controles , Preescolar , Adolescente , Tamaño de los Órganos
16.
Annu Rev Pathol ; 17: 141-158, 2022 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-34637338

RESUMEN

Recent years have seen growing attention to inflammatory and infectious disorders of the spinal cord, not only due to the discovery of autoantibody-mediated disorders of the spinal cord [e.g., aquaporin-4 immunoglobulin G (IgG) antibodies and myelin oligodendrocyte glycoprotein IgG antibodies], but also due to the emergence of clusters of infection-related myelopathy, now known as acute flaccid myelitis. We review the spectrum of infection-related myelopathies and outline a nosological classification system based on association with infection. We describe the epidemiology and definitions of myelopathies, with a discussion of clinical presentation and neuroimaging features, and then turn to specific discussion of myelopathies due to direct pathogen invasion and those considered to be post- or parainfectious.


Asunto(s)
Mielitis , Enfermedades de la Médula Espinal , Autoanticuerpos , Humanos , Mielitis/complicaciones , Neuroimagen , Enfermedades de la Médula Espinal/complicaciones
17.
BMJ Paediatr Open ; 6(1)2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-36053578

RESUMEN

OBJECTIVE: To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. DESIGN: Multicentre retrospective cohort study. SETTING: 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. PATIENTS: Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). MAIN OUTCOME MEASURE: Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. RESULTS: We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45-9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. CONCLUSION: We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.


Asunto(s)
COVID-19 , Adolescente , COVID-19/complicaciones , COVID-19/diagnóstico , Prueba de COVID-19 , Niño , Niño Hospitalizado , Preescolar , Humanos , Lactante , Obesidad/epidemiología , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2/genética , Síndrome de Respuesta Inflamatoria Sistémica
18.
Mult Scler Relat Disord ; 56: 103286, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34627003

RESUMEN

BACKGROUND: Despite better characterization of the spectrum of MOG-IgG-associated disorders (MOGAD) in children, the role of infection in its pathophysiology remains unclear. The goal of this study was to evaluate if public health measures put in place to prevent the spread of SARS-CoV-2 in March 2020 in Ontario (Canada) have been associated with a change in the incidence of MOGAD and other neuroinflammatory disorders in children. METHODOLOGY: We reviewed a single-centre cohort of children referred for a suspicion of neuroinflammatory disorder between January 2015 and March 2021. Age, date, sex, diagnosis, MOG-IgG antibodies status and detected pathogens at presentation were identified. Comparative statistical analysis was performed based on diagnosis between years and seasons using Pearson's Chi-squared test or Fisher's exact test for categorical variables and using ANOVA or Kruskal-Wallis test for continuous variables, as appropriate. We compared the post-lockdown period (March 17th, 2020, to March 31st, 2021) to previous calendar years (2015 to 2019) alone and to previous calendar years and the pre-lockdown 2020 period (January 1st, 2020, to March 16th, 2020). A p-value of < 0.05 was considered significant. Post-hoc pairwise comparisons between the post-lockdown period and previous years were performed on significant results. A false discovery rate adjustment with an adjusted p-value (q-value) < 0.05 was computed. We hypothesized that the number of new MOGAD would be significantly lower in the post-lockdown period compared to previous years due to decreased regional pathogen transmission. RESULTS: Among 491 referred cases, we identified 415 new cases of neuroinflammatory disorder between January 2015 and March 2021. The number of new neuroinflammatory disorder diagnoses did not change between years. We noted significantly fewer new MOGAD diagnoses in 2020 compared to previous years, with no MOGAD patients presenting in 2020 after the spring lockdown (q=0.0009). In addition, there were significantly fewer parainfectious neuroinflammatory cases (q=0.04) and pathogen detected (q=0.04) in the post-lockdown period. The number of new multiple sclerosis (MS) and aquaporin-4 neuromyelitis optica spectrum disorders (AQP4-NMOSD) cases remained stable despite the lockdown (q=0.185 and 0.693 respectively). INTERPRETATION: Enhanced population-based infection control strategies may have a role in modulating the incidence of MOGAD and parainfectious neuroinflammatory disorders, but not MS or AQP4-NMOSD.


Asunto(s)
COVID-19 , Control de Enfermedades Transmisibles , Enfermedades Neuroinflamatorias/epidemiología , Acuaporina 4 , Autoanticuerpos , COVID-19/prevención & control , Niño , Humanos , Inmunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica/epidemiología , Ontario/epidemiología , Salud Pública
19.
Lancet Child Adolesc Health ; 4(11): 828-836, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33068549

RESUMEN

BACKGROUND: Acute flaccid myelitis (AFM) is characterised by rapid onset of limb weakness with spinal cord grey-matter abnormalities on MRI scan. We aimed to assess whether detection of enterovirus in respiratory or other specimens can help predict prognosis in children with AFM. METHODS: In this nationwide, longitudinal study, we evaluated the significance of detection of enterovirus in any sample in predicting outcomes in a cohort of Canadian children younger than 18 years presenting with AFM to tertiary paediatric hospitals in Canada in 2014 and 2018. All patients fulfilled the 2015 US Centers for Disease Control and Prevention case definition for definite AFM or probable AFM. Clinical data, laboratory findings, treatment, and neuroimaging results were collected (follow up period up to 5 years). We assessed neurological function and motor outcomes using Kurtzke's Expanded Disability Status Scale (EDSS) and a Weakest Limb Score. FINDINGS: 58 children with AFM (median age 5·1 years, IQR 3·8-8·3) were identified across five of Canada's ten provinces and three territories. 25 (43%) children had enterovirus detected in at least one specimen: 16 (64%) with EV-D68, two (8%) with EV-A71, two (8%) with coxsackievirus, 10 (40%) with untyped enterovirus. Children who were enterovirus positive were more likely than those that were negative to have had quadriparesis (12 [48%] of 25 vs four [13%] of 30; p=0·028), bulbar weakness (11 [44%] of 25 vs two [7%] of 30; p=0·028), bowel or bladder dysfunction (14 [56%] of 25 vs seven [23%] of 30; p=0·040), cardiovascular instability (nine [36%] of 25 vs one [3%] of 30; p=0·028), and were more likely to require intensive care unit admission (13 [52%] of 25 vs 5 [17%] of 30; p=0·028). On MRI, most children who were enterovirus positive showed brainstem pontine lesions (14 [61%] of 23), while other MRI parameters did not correlate with enterovirus status. Median EDSS of enterovirus positive (EV+) and enterovirus negative (EV-) groups was significantly different at all timepoints: baseline (EDSS 8·5, IQR 4·1-9·5 vs EDSS 4·0, IQR 3·0-6·0; p=0·0067), 3 months (EDSS 4·0, IQR 3·0-7·4 vs EDSS 3·0, IQR 1·5-4·3; p=0·0067), 6 months (EDSS 3·5, IQR 3·0-7·0 vs EDSS 3·0, IQR 1·0-4·0; p=0·029), and 12 months (EDSS 3·0, IQR 3·0-6·9 vs EDSS 2·5 IQR 0·3-3·0; p=0·0067). Kaplan-Meier survival analysis of a subgroup of patients showed significantly poorer motor recovery among children who tested positive for enterovirus than for those who tested negative (p=0·037). INTERPRETATION: Detection of enterovirus in specimens from non-sterile sites at presentation correlated with more severe acute motor weakness, worse overall outcomes and poorer trajectory for motor recovery. These results have implications for rehabilitation planning as well as counselling of families of children with these disorders. The findings of this study support the need for early testing for enterovirus in non-CNS sites in all cases of AFM. FUNDING: None.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central , Enterovirus/aislamiento & purificación , Debilidad Muscular , Mielitis , Enfermedades Neuromusculares , Médula Espinal/diagnóstico por imagen , Canadá/epidemiología , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/epidemiología , Enfermedades Virales del Sistema Nervioso Central/microbiología , Enfermedades Virales del Sistema Nervioso Central/terapia , Preescolar , Enterovirus/clasificación , Femenino , Hospitales Pediátricos/estadística & datos numéricos , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Destreza Motora , Debilidad Muscular/diagnóstico , Debilidad Muscular/etiología , Debilidad Muscular/rehabilitación , Mielitis/diagnóstico , Mielitis/epidemiología , Mielitis/microbiología , Mielitis/terapia , Enfermedades Neuromusculares/diagnóstico , Enfermedades Neuromusculares/epidemiología , Enfermedades Neuromusculares/microbiología , Enfermedades Neuromusculares/terapia , Evaluación de Resultado en la Atención de Salud , Pronóstico , Recuperación de la Función
20.
Methods Mol Biol ; 510: 73-81, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19009254

RESUMEN

HCV infection provides a classic example of the phenomenon of quasispecies. Because several lines of investigation support the contribution of quasispecies to HCV's capacity to maintain a persistent infection, adequate characterization of the quasispecies is important. The hypervariable region 1 (HVR1) of the E2 glycoprotein has been particularly well studied in this regard. We present here a rapid method for characterizing the HVR1 quasispecies, based on in vitro coupled transcription/translation of the amplicons, followed by mass spectrometry of the resulting peptide mix.


Asunto(s)
Hepacivirus/clasificación , Hepacivirus/genética , Biosíntesis de Proteínas , Proteínas del Envoltorio Viral/biosíntesis , Proteínas del Envoltorio Viral/química , Proteínas Virales/biosíntesis , Proteínas Virales/química , Secuencia de Aminoácidos , Animales , Genotipo , Magnetismo , Espectrometría de Masas , Datos de Secuencia Molecular , Péptidos/análisis , Péptidos/química , Péptidos/aislamiento & purificación , Péptidos/metabolismo , Conejos , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/aislamiento & purificación , Proteínas Virales/genética , Proteínas Virales/aislamiento & purificación
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