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1.
Med Sci Monit ; 27: e928374, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33388740

RESUMO

BACKGROUND Although influenza primarily affects the respiratory system, it can cause severe neurological complications, especially in younger children, but knowledge about the early indicators of acute necrotizing encephalopathy (ANE) is limited. The main purpose of this article is to summarize the clinical characteristics, diagnosis, and treatment of neurological complications of influenza in children, and to identify factors associated with ANE. MATERIAL AND METHODS This was a retrospective study of children with confirmed influenza with neurological complications treated between 01/2014 and 12/2019 at Guangzhou Women and Children's Medical Center. A receiver operating characteristics curve analysis was performed to determine the prognostic value of selected variables. RESULTS Sixty-three children with IAE (n=33) and ANE (n=30) were included. Compared with the IAE group, the ANE group showed higher proportions of fever and acute disturbance of consciousness, higher alanine aminotransferase, higher aspartate aminotransferase, higher creatinine kinase, higher procalcitonin, higher cerebrospinal fluid (CSF) protein, and lower CSF white blood cells (all P<0.05). The areas under the curve (AUCs) for procalcitonin and CSF proteins, used to differentiate IAE and ANE, were 0.790 and 0.736, respectively. The sensitivity and specificity of PCT >4.25 ng/ml to predict ANE were 73.3% and 100.0%, respectively. The sensitivity and specificity of CSF protein >0.48 g/L to predict ANE were 76.7% and 69.7%, respectively. Thirteen (43.3%) children with ANE and none with IAE died (P<0.0001). CONCLUSIONS High levels of CSF protein and serum procalcitonin might be used as early indicators for ANE. All children admitted with neurological findings, especially during the influenza season, should be evaluated for influenza-related neurological complications.

2.
J Neuroimmunol ; 352: 577479, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33486307

RESUMO

OBJECTIVE: To study the clinical features of children diagnosed with anti-NMDAR encephalitis in southern China. METHODS: Clinical data of children diagnosed with anti-NMDAR encephalitis from October 2014 to June 2020 from one national regional medical center were analyzed. Neurological disability was assessed by modified Rankin Scale (mRS) throughout the course of disease. RESULTS: 111 children (M/F = 49/62; mean onset age = 6.8 y) with anti-NMDAR encephalitis were involved. Prodromal events occurred in 34.2% of patients with infectious events being the most common. Seizure was the most common initial symptom, though movement disorder served as the most common event throughout the course of disease. 9.9% of patients had overlapped with other neuronal autoantibodies. Electroencephalogram showed abnormalities with slow wave (100.0%), epileptic discharge (31.5%) and delta brush (8.1%) respectively. 41.4% of patients had abnormal brain MRI, with focal lesions being the most common. None patients had tumor. 80.9% of patients had good response to first line therapy (steroid plus immunoglobulin), while 14 patients accepted second-line therapy (Rituximab) and all had a good response. Boys were significantly more likely to need more course of steroid. 13.8% of patients relapsed. 2 male patients died. mRS score was significantly improved after treatment. 51.4% of patients had a full recovery and 81.7% had mRS score ≤ 2. The median mRS score of boys after treatment was higher than that of girls. Non-infectious prodromal event, past medical history, perivascular lesions in brain MRI, hospital stay, initial mRS score higher than 3, and RTX treatment were independent risk factors associated with poor prognosis, defined as mRS score > 2. CONCLUSION: Of pediatric anti-NMDAR encephalitis in southern China: median onset age around 7 years; girls more common; boys might have poor outcome than girls; seizure or movement disorder respectively being most common onset or course symptom; a few overlapped with other neuronal autoantibodies; rare combined with tumor; most had a good response to immunotherapy and a good prognosis; relapse rate relatively high; fatality rate relatively low; some risk factors associated with poor prognosis.

4.
World J Clin Cases ; 8(2): 382-389, 2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-32047789

RESUMO

BACKGROUND: Influenza in children is a major cause of morbidity and mortality worldwide. Nervous system diseases are a factor relating to increased mortality rate. However, reports of how these underlying diseases contribute to the death of children with influenza are rare. CASE SUMMARY: A 4-year-old-girl developed type A influenza-related encephalopathy (IAE) with seizures, acute disorder of consciousness, and intracranial hypertension (cerebrospinal fluid pressure: 250 mmH2O), and the Dandy-Walker variant was found by her first magnetic resonance imaging (MRI) when admission. Three days later, she suddenly presented anisocoria, acute pulmonary edema, and coma, and the later MRI found that she had compressed brainstem, oblongata "Z-like folding", and swelling bilateral basal ganglia. After admission, the patient were tested for routine and special biomarkers and underwent neuroimaging and neuroelectrophysiology examinations as well as Oseltamivir and intravenous immunogloblin treatments. When predicting that unstable intracranial structures detected by MRI might have disastrous consequences in the progression of IAE, she was transferred into the pediatric intensive care unit and underwent continuous assessment of clinical condition while she did not have instability of basic vital signs; at the same time, her parents were fully informed about the risk and prognosis. Although she was ultimately dead from brain stem failure, the parents expressed understanding and did not trigger a doctor-patient conflict. CONCLUSION: In case of finding an unstable intracranial structure, intensive care should be given to IAE patient and their clinical condition should be monitored continuously.

6.
BMC Neurol ; 19(1): 320, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830942

RESUMO

BACKGROUND: X-linked agammaglobulinaemia (XLA) is a rare inherited primary immunodeficiency disease characterized by the B cell developmental defect, caused by mutations in the gene coding for Bruton's tyrosine kinase (BTK), which may cause serious recurrent infections. The diagnosis of XLA is sometimes challenging because a few number of patients have higher levels of serum immunoglobulins than expected. In this study, we reported an atypical case with recurrent meningitis, delayed diagnosis with XLA by genetic analysis at the second episode of meningitis at the age of 8 years. CASE REPORT: An 8-year-old Chinese boy presented with fever, dizziness and recurrent vomiting for 3 days. The cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) results were suggestive of bacterial meningoencephalitis, despite the negative gram staining and cultures of the CSF. The patient was treated with broad-spectrum antibiotics and responded well to the treatment. He had history of another episode of acute pneumococci meningitis 4 years before. The respective level of Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM) was 4.85 g/L, 0.93 g/L and 0.1 g/L at 1st episode, whereas 1.9 g/L, 0.27 g/L and 0 g/L at second episode. The B lymphocytes were 0.21 and 0.06% of peripheral blood lymphocytes at first and second episode respectively. Sequencing of the BTK coding regions showed that the patient had a point mutation in the intron 14, hemizyous c.1349 + 5G > A, while his mother had a heterozygous mutation. It was a splice site mutation predicted to lead to exon skipping and cause a truncated BTK protein. CONCLUSION: Immunity function should be routinely checked in patients with severe intracranial bacterial infection. Absence of B cells even with normal level of serum immunoglobulin suggests the possibility of XLA, although this happens only in rare instances. Mutational analysis of BTK gene is crucial for accurate diagnosis to atypical patients with XLA.


Assuntos
Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Encefalite Infecciosa/genética , Tirosina Quinase da Agamaglobulinemia/genética , Agamaglobulinemia/genética , Criança , Análise Mutacional de DNA , Diagnóstico Tardio , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Masculino , Mutação
7.
Int J Mol Med ; 44(2): 759-767, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173167

RESUMO

Enterovirus 71 (EV71) accounts for the majority of hand, foot and mouth disease­related deaths due to fatal neurological complications. EV71 structural viral protein 1 (VP1) promotes viral replication by inducing autophagy in neuron cells, but the effect of VP1 on myelin cells is unclear. The present study aimed to investigate the role and mechanism of VP1 in autophagy of mouse Schwann cells. An EV71 VP1­expressing vector (pEGFP­C3­VP1) was generated and transfected into mouse Schwann cells. Transmission electron microscopy and western blot analysis for microtubule­associated protein 1 light chain 3 α (LC3) II (an autophagy marker) were used to assess autophagy. Reverse transcription­quantitative PCR and immunofluorescence were performed to determine the expression of peripheral myelin protein 22 (PMP22). Small interfering RNA against PMP22 was used to investigate the role of PMP22 in mouse Schwann cell autophagy. Salubrinal [a selective endoplasmic reticulum (ER) stress inhibitor] was used to determine whether PMP22 expression was affected by ER stress. The present results indicated that VP1 promoted mouse Schwann cell autophagy. Overexpression of VP1 upregulated PMP22. PMP22 deficiency downregulated LC3II and thus inhibited autophagy. Furthermore, PMP22 expression was significantly suppressed by salubrinal. In conclusion, VP1 promoted mouse Schwann cell autophagy through upregulation of ER stress­mediated PMP22 expression. Therefore, the VP1/ER stress/PMP22 autophagy axis may be a potential therapeutic target for EV71 infection­induced fatal neuronal damage.


Assuntos
Enterovirus Humano A/fisiologia , Infecções por Enterovirus/metabolismo , Proteínas da Mielina/metabolismo , Células de Schwann/virologia , Proteínas Estruturais Virais/metabolismo , Animais , Autofagia , Linhagem Celular , Estresse do Retículo Endoplasmático , Infecções por Enterovirus/virologia , Humanos , Camundongos , Células de Schwann/metabolismo , Células de Schwann/patologia
8.
BMC Infect Dis ; 17(1): 153, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28212620

RESUMO

BACKGROUND: Enterovirus 71 (EV-A71) shows a potential of rapid death, but the natural history of the infection is poorly known. This study aimed to examine the natural history of EV-A71 infection. METHODS: This was a prospective longitudinal observational study performed between January 1st and October 31st, 2012, at three hospitals in Guangdong, China. Subjects with positive EV-A71 RNA laboratory test results were included. Disease progression was documented with MRI, autopsies, and follow-up. Symptoms/signs with potential association with risk of death were analyzed. RESULTS: Among the 288 patients, neurologic symptoms and signs were observed (emotional movement disorders, dyskinesia, involuntary movements, autonomic dysfunction, and disturbance of consciousness). Some of them occurred as initial symptoms. Myoclonic jerks/tremors were observed among >50% of the patients; nearly 40% of patients presented fatigue and 25% were with vomiting. Twenty-eight patients (9.7%) presented poor peripheral perfusion within 53.4 ± 26.1 h; 23 patients (8.0%) presented pulmonary edema and/or hemorrhage within 62.9 ± 28.6 h. Seventeen (5.9%) patients were in a coma. Seven (2.4%) patients died within 62.9 ± 28.6 h. Seventy-seven survivors underwent head and spinal cord MRI and 37.7% (29/77) showed abnormalities. Two fatal cases showed neuronal necrosis, softening, perivascular cuffing, colloid, and neuronophagia phenomenon in the brainstem. CONCLUSIONS: Patients with EV-A71 infection showed high complexity of symptoms and onset timing. Death risk may be indicated by autokinetic eyeball, eyeball ataxia, severe coma, respiratory rhythm abnormality, absent pharyngeal reflex, ultrahyperpyrexia, excessive tachycardia, pulmonary edema and/or hemorrhage, and refractory shock and ataxic respiration. Early assessment of these symptoms/signs is important for proper management.


Assuntos
Encefalite Viral/diagnóstico , Enterovirus Humano A/patogenicidade , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/virologia , Hemorragia/diagnóstico , Edema Pulmonar/diagnóstico , Transtornos Respiratórios/diagnóstico , Autopsia , Criança , Pré-Escolar , China/epidemiologia , Coma , Surtos de Doenças , Progressão da Doença , Encefalite Viral/mortalidade , Encefalite Viral/fisiopatologia , Enterovirus Humano A/isolamento & purificação , Infecções por Enterovirus/mortalidade , Infecções por Enterovirus/fisiopatologia , Feminino , Hemorragia/mortalidade , Hemorragia/fisiopatologia , Humanos , Lactente , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Estudos Prospectivos , Edema Pulmonar/mortalidade , Edema Pulmonar/fisiopatologia , Transtornos Respiratórios/mortalidade , Transtornos Respiratórios/fisiopatologia , Taxa Respiratória/fisiologia
9.
Neurotox Res ; 31(2): 204-217, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27848175

RESUMO

Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD. EV71 capsid proteins VP1, VP2, VP3, or VP4 did not induce apoptosis of brainstem neurons. Interestingly, we found VP1-activated endoplasmic reticulum (ER) stress and autophagy could promote Ecto-CRT upregulation, but ER stress or autophagy alone was not sufficient to induce CRT exposure. Furthermore, we demonstrated that VP1-induced autophagy activation was mediated by ER stress. Meaningfully, we found dexamethasone treatment could attenuate Ecto-CRT upregulation by alleviating VP1-induced ER stress. Altogether, these findings identify VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications.


Assuntos
Calreticulina/metabolismo , Proteínas do Capsídeo/toxicidade , Dexametasona/farmacologia , Estresse do Retículo Endoplasmático/fisiologia , Neurônios/fisiologia , Fagocitose/fisiologia , Proteínas Estruturais Virais/toxicidade , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiopatologia , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Humanos , Masculino , Fagocitose/efeitos dos fármacos , Ratos , Regulação para Cima
10.
Brain Dev ; 38(10): 915-927, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27591118

RESUMO

OBJECTIVE: To describe clinical features of reversible splenial lesion syndrome (RESLES) in children. METHODS: Retrospectively analyzed clinical features of RESLES in children and compared differences between severe and non-severe group, classified by clinical global impression-scale; summarized clinical features of children with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) from case series. RESULTS: 16 episodes of RESLES occurring in 15 Chinese children were analyzed, with 13 episodes having MERS and 3 episodes with epilepsy. 10 episodes were associated with various pathogens including rotavirus (n=5), adenovirus (n=1), influenza A (n=1), mycoplasma (n=2), and jejunum campylobacter (n=1). The common neurological symptoms included seizure, behavioral changes, altered consciousness and motor deterioration. The lesions of splenium of corpus callosum (SCC), extra-SCC (n=2) or extra-CC (n=1) showed T2-weight and FLAIR hyper-intensity, with the corresponding reduced diffusion. All had complete resolution of radiological changes except 1 episode with small residual. 8 episodes had EEG abnormalities, while elevated white blood count, increased hs-CRP, and hyponatremia were commonly revealed. 7 episodes were given steroid plus therapy, while 3 episodes were treated with antiepileptic drugs. Compared with non-severe group, the number of patients with altered consciousness, EEG abnormalities, motor deterioration, or extra-SCC lesions in severe group was significantly increased. The patients in severe group tended to need longer hospital stay interval. No case caused neurological sequelae, except 1 patient in severe group with recurrent episode and extra-CC lesions having intellectual disability (ID). Five pediatric MERS case series were summarized, including 67 episodes (40 male and 27 female; age ranging 10 m∼13y) from 65 patients, with 33 episodes in Japan, 27 in China, and 7 in Caucasian Australian children, and all patients have a good prognosis except 1 patient with ID (current study). CONCLUSION: Although RESLES in children tend to be a good outcome, the prognosis of patient in severe group, especially with extra-CC lesions, might have neurological sequelae.


Assuntos
Encefalopatias/diagnóstico , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/epidemiologia , Encefalopatias/fisiopatologia , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndrome
11.
Bing Du Xue Bao ; 32(6): 752-7, 2016 11.
Artigo em Chinês | MEDLINE | ID: mdl-30004648

RESUMO

We investigated the infection and molecular-epidemiologic characteristics of human astrovirus (HAstV) of hospitalized infants in Kunming City from the year 2013 to 2014.Infection and genotype of HAstV of 63 samples of diarrheal feces and 42 controls were analyzed by reverse transcription-polymerase chain reaction(RT-PCR).The complete genome sequence of a HAstV strain was amplified and sequenced. The positive rate of HAstV in 63 feces samples was 41.27%(26/63).The main circulating genotype of HAstV was HAstV1.Only 1sample was positive for HAstV in 42controls(2.38%).A complete genome sequence of the HAstV strain was identified as HAstV1 by phylogenetic analyses. These data provide an important theoretical basis for the control of viral diarrhea in infants in Kunming City.


Assuntos
Infecções por Astroviridae/virologia , Mamastrovirus/genética , Mamastrovirus/isolamento & purificação , Infecções por Astroviridae/epidemiologia , Infecções por Astroviridae/terapia , China/epidemiologia , Diarreia/epidemiologia , Diarreia/terapia , Diarreia/virologia , Fezes/virologia , Feminino , Genótipo , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Mamastrovirus/classificação , Epidemiologia Molecular , Filogenia
13.
Zhonghua Er Bi Yan Hou Ke Za Zhi ; 39(11): 648-53, 2004 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-15835813

RESUMO

OBJECTIVE: To explore the clinic and audiological characteristics of auditory neuropathy in children. METHODS: Between 2002 and 2004, ninety-eight cases with the severe abnormal results of ABR and the normal results of DPOAE were enrolled in the study group. The mean patient age was 9 months, with a range of 1 month to 5 years. According to the evaluation of pediatric neurologist, the high-risk factors of psychomotor development retardation were statistically analyzed whether the cases were accompanied by psychomotor development retardation or not. The cases with abnormal results of ABR and DPOAE and without abnormal conductive function were selected as the cochlea lesion group. Some same age children without hearing loss were subjected as normal control group. RESULTS: The psychomotor development retardation was performed in 83.67% of cases. Hypercholesterolemia of newborn was the common high-risk factor of psychomotor development retardation (43.88% ). Severe abnormal results of ABR were occurred in 66. 07% of ears. Prolonged latency of wave I - V ABR and acoustic stapedius reflex were observed in few cases. The DPOAE amplitudes at intermediate and high frequencies were normal or slightly descending. Occurring rate of DPOAE at intermediate and high frequencies was the same as in normal control group. CONCLUSIONS: Hypercholesterolemia of newborn is the most common cause of auditory neuropathy. The auditory test results are various in children with auditory neuropathy. This character is different from it in adults.


Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva/fisiopatologia , Emissões Otoacústicas Espontâneas/fisiologia , Audiometria de Tons Puros , Pré-Escolar , Humanos , Lactente
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