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1.
Brain Dev ; 45(9): 479-486, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37263884

RESUMO

BACKGROUND: Pericytes play a role in the maintenance of the blood-brain barrier and neuroinflammation, attracting attention as to whether they are also involved in the pathogenesis of epilepsy.This study aimed to explore the relationship between West syndrome and pericytes. METHODS: Eighteen Japanese pediatric West syndrome patients and nine controls aged 2 years or younger were retrospectively enrolled in this study. We assessed theserumlevels of pericyte markers, serum PDGFRß (platelet-derived growth factor receptorß),CD13 (aminopeptidase N), and 27 cytokines in 17 pediatric patients with West syndrome and the control group. RESULTS: Patients with West syndrome exhibited significantly increased CD13 and decreased PDGFRß levels, compared with controls but not serum cytokine levels. These values did not differ significantly between symptomatic and idiopathic West syndrome. CONCLUSION: Pericytes might be implicated in the pathogenesis of West syndrome.


Assuntos
Pericitos , Espasmos Infantis , Criança , Humanos , Pericitos/metabolismo , Pericitos/patologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Estudos Retrospectivos , Espasmos Infantis/metabolismo , Antígenos CD13
2.
Int J Mol Sci ; 24(9)2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37176049

RESUMO

The role of neuroinflammation in the pathophysiology of migraines is increasingly being recognized, and cytokines, which are important endogenous substances involved in immune and inflammatory responses, have also received attention. This review examines the current literature on neuroinflammation in the pathogenesis of migraine. Elevated TNF-α, IL-1ß, and IL-6 levels have been identified in non-invasive mouse models with cortical spreading depolarization (CSD). Various mouse models to induce migraine attack-like symptoms also demonstrated elevated inflammatory cytokines and findings suggesting differences between episodic and chronic migraines and between males and females. While studies on human blood during migraine attacks have reported no change in TNF-α levels and often inconsistent results for IL-1ß and IL-6 levels, serial analysis of cytokines in jugular venous blood during migraine attacks revealed consistently increased IL-1ß, IL-6, and TNF-α. In a study on the interictal period, researchers reported higher levels of TNF-α and IL-6 compared to controls and no change regarding IL-1ß levels. Saliva-based tests suggest that IL-1ß might be useful in discriminating against migraine. Patients with migraine may benefit from a cytokine perspective on the pathogenesis of migraine, as there have been several encouraging reports suggesting new therapeutic avenues.


Assuntos
Citocinas , Transtornos de Enxaqueca , Masculino , Camundongos , Feminino , Animais , Humanos , Fator de Necrose Tumoral alfa , Interleucina-6 , Doenças Neuroinflamatórias , Transtornos de Enxaqueca/etiologia
3.
Cureus ; 15(2): e34536, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36874330

RESUMO

Pediatric mastocytosis is a relatively rare disorder and most commonly occurs as isolated cutaneous lesions. Although autism spectrum disorders have been reported to be associated with mastocytosis, no clear association between mastocytosis and motor and intellectual delay has been reported with the exception of the case that detected de novo monoallelic mutations in the GNB1 gene. Herein, we describe the case of a Japanese male pediatric patient aged two years and six months who had cutaneous mastocytosis accompanied by motor and intellectual delay without the presence of GNB1 mutation.

4.
Cureus ; 14(11): e31138, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36479407

RESUMO

Bacterial meningitis in infants is a life-threatening illness that survives significant neurological sequelae that remain in survivors. The current diagnostic gold standard for meningitis is bacterial isolation from culture or molecular diagnostics in the cerebrospinal fluid. The decision for antibiotics therapy before bacterial detection is made on microscopic and biochemical findings in the cerebrospinal fluid, however, some patient shows no microscopic finding and pleocytosis at the initial cerebrospinal fluid analysis. Herein, we report a case of late-onset group B Streptococcus serotype Ib meningitis that could be introduced with timelier antibiotic therapy even in the absence of pleocytosis without the detection of bacteria on smear at the initial CSF analysis.

5.
J Clin Med ; 11(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36294363

RESUMO

(1) Background: Almost 100% of children are initially infected by respiratory syncytial virus (RSV) by the age of 2 years, with 30% to 40% of children developing lower respiratory tract infections, of which 1% to 3% become severe. The severity of RSV-induced disease correlates with the influx of leukocytes, which leads to damage of the airways. We hence performed an immunological study based on the assumption that a chemokine/interleukin imbalance affects respiratory disorders caused by bronchiolitis and severe pneumonia. (2) Methods: The subjects were 19 infants without any underlying diseases, who developed respiratory symptoms owing to RSV infection. The subjects were stratified by their symptom severity, and chemokine and interleukin levels in their serum and tracheal aspirate fluid (TAF) were measured. (3) Results: The data of TAF, which were only obtained from subjects with severe symptoms, indicated that levels of inflammatory interleukins were much lower than the levels of chemokines. Three out of 6 subjects with severe symptoms showed below detectable levels of IL-6. TNF-α and IFN-γ levels were also lower than those of chemokines. The main increased CCL chemokines were CCL21 and CCL25, and the main increased CXCL chemokines were CXCL5, 8, 10, 12, and CX3CL1 in the lower respiratory region. Multiple regression analysis demonstrated that serum CX3CL1 and IL-6 levels were most strongly associated with symptom severity. This is the first report to date demonstrating that serum CX3CL1 level is associated with the severity of RSV infection. (4) Conclusions: Our results demonstrated that specific chemokines and the imbalance of cytokines are suspected to be associated with aggravated symptoms of RSV infection.

6.
J Clin Med ; 11(2)2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35054141

RESUMO

Neuroinflammation has been implicated in the pathogenesis of West syndrome (WS). Inflammatory cytokines, including interleukin-1ß(IL-1ß), have been reported to be associated with epilepsy. However, the assessment of cytokine changes in humans is not always simple or deterministic. This study aimed to elucidate the immunological mechanism of WS. We examined the intracellular cytokine profiles of peripheral blood cells collected from 13 patients with WS, using flow cytometry, and measured their serum cytokine levels. These were compared with those of 10 age-matched controls. We found that the WS group had significantly higher percentages of inter IL-1ß, interleukin-1 receptor antagonist (IL-1RA)-positive monocytes, and interferon gamma (IFN-γ) in their CD8+ T cells than the control group. Interestingly, the group with sequelae revealed significantly lower levels of intracellular IFN-γ and IL-6 in their CD8+ T and CD4+ T cells, respectively, than the group without sequelae. There was no correlation between the ratios of positive cells and the serum levels of a particular cytokine in the WS patients. These cytokines in the peripheral immune cells might be involved in the neuroinflammation of WS, even in the absence of infectious or immune disease. Overall, an immunological approach using flow cytometry analysis might be useful for immunological studies of epilepsy.

7.
J Clin Med ; 10(17)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34501321

RESUMO

The roles of cytokines in the cerebrospinal fluid (CSF) of patients with acute encephalopathy remain unclear and controversial. In this study, the profiles of 26 cytokines and others were determined in 17 children with infection-associated neurological complications. Interleukin (IL)-12 levels were found to be high in a few of the patients. A comparison of the IL-12 levels in the CSF of patients demonstrated that IL-12 (p70) is almost always increased in those with encephalopathy. Levels of IL-12 in the CSF were highly correlated with the levels of PDGF-bb and IL-RA. IL-12 levels were found to be weakly correlated with IFN-γ levels, and strongly correlated with VEGF levels. These results demonstrate that IL-12 levels may affect the clinical symptoms of pediatric patients with encephalopathy.

8.
Glob Pediatr Health ; 8: 2333794X211044114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527765

RESUMO

We investigated 22 cases of patients with myocarditis during respiratory syncytial virus (RSV) infection by a questionnaire survey, and performed a literature search to clarify their characteristics. The age distribution was divided into 2 groups, that is, 1 group comprised of patients younger than 4-years old and the other comprised patients older than 15 years. ECG demonstrated disturbance of the conduction system (AV block) in 7 out of 18 patients (38.8%), myocardial damage (ST-T change) in 9 out of 18 patients (50.0%), and tachycardia in 3 out of 18 patients (16.6%). Echocardiography displayed a robust decrease in left-heart function in 12 out of 14 patients. The outcome was 2 deaths, 1 pacemaker placement, 4 patients with mild sequel. Our data suggest that RSV myocarditis caused by RSV infection can be divided into 3 different pathophysiologies, characterized by disturbance of the conduction system, myocardial damage, and increase of autonomy.

9.
Nutrients ; 13(8)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34444772

RESUMO

Riboflavin, a water-soluble member of the B-vitamin family, plays a vital role in producing energy in mitochondria and reducing inflammation and oxidative stress. Migraine pathogenesis includes neuroinflammation, oxidative stress, and mitochondrial dysfunction. Therefore, riboflavin is increasingly being recognized for its preventive effects on migraines. However, there is no concrete evidence supporting its use because the link between riboflavin and migraines and the underlying mechanisms remains obscure. This review explored the current experimental and clinical evidence of conditions involved in migraine pathogenesis and discussed the role of riboflavin in inhibiting these conditions. Experimental research has demonstrated elevated levels of various oxidative stress markers and pro-inflammatory cytokines in migraines, and riboflavin's role in reducing these marker levels. Furthermore, clinical research in migraineurs showed increased marker levels and observed riboflavin's effectiveness in reducing migraines. These findings suggest that inflammation and oxidative stress are associated with migraine pathogenesis, and riboflavin may have neuroprotective effects through its clinically useful anti-inflammatory and anti-oxidative stress properties. Riboflavin's safety and efficacy suggests its usefulness in migraine prophylaxis; however, insufficient evidence necessitates further study.


Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Riboflavina/uso terapêutico , Animais , Humanos , Inflamação , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Vitaminas/uso terapêutico
10.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445635

RESUMO

Currently, migraine is treated mainly by targeting calcitonin gene-related peptides, although the efficacy of this method is limited and new treatment strategies are desired. Neuroinflammation has been implicated in the pathogenesis of migraine. In patients with migraine, peripheral levels of pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α, are known to be increased. Additionally, animal models of headache have demonstrated that immunological responses associated with cytokines are involved in the pathogenesis of migraine. Furthermore, these inflammatory mediators might alter the function of tight junctions in brain vascular endothelial cells in animal models, but not in human patients. Based on clinical findings showing elevated IL-1ß, and experimental findings involving IL-1ß and both the peripheral trigeminal ganglion and central trigeminal vascular pathways, regulation of the Il-1ß/IL-1 receptor type 1 axis might lead to new treatments for migraine. However, the integrity of the blood-brain barrier is not expected to be affected during attacks in patients with migraine.


Assuntos
Barreira Hematoencefálica/patologia , Encéfalo/patologia , Permeabilidade da Membrana Celular , Inflamação/complicações , Transtornos de Enxaqueca/patologia , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/imunologia , Humanos , Transtornos de Enxaqueca/etiologia
12.
Biomedicines ; 9(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209145

RESUMO

Pericytes are a component of the blood-brain barrier (BBB) neurovascular unit, in which they play a crucial role in BBB integrity and are also implicated in neuroinflammation. The association between pericytes, BBB dysfunction, and the pathophysiology of epilepsy has been investigated, and links between epilepsy and pericytes have been identified. Here, we review current knowledge about the role of pericytes in epilepsy. Clinical evidence has shown an accumulation of pericytes with altered morphology in the cerebral vascular territories of patients with intractable epilepsy. In vitro, proinflammatory cytokines, including IL-1ß, TNFα, and IL-6, cause morphological changes in human-derived pericytes, where IL-6 leads to cell damage. Experimental studies using epileptic animal models have shown that cerebrovascular pericytes undergo redistribution and remodeling, potentially contributing to BBB permeability. These series of pericyte-related modifications are promoted by proinflammatory cytokines, of which the most pronounced alterations are caused by IL-1ß, a cytokine involved in the pathogenesis of epilepsy. Furthermore, the pericyte-glial scarring process in leaky capillaries was detected in the hippocampus during seizure progression. In addition, pericytes respond more sensitively to proinflammatory cytokines than microglia and can also activate microglia. Thus, pericytes may function as sensors of the inflammatory response. Finally, both in vitro and in vivo studies have highlighted the potential of pericytes as a therapeutic target for seizure disorders.

13.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208064

RESUMO

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a unique catastrophic epilepsy syndrome, and the development of drug-resistant epilepsy (DRE) is inevitable. Recently, anakinra, an interleukin-1 receptor antagonist (IL-1RA), has been increasingly used to treat DRE due to its potent anticonvulsant activity. We here summarized its effects in 38 patients (32 patients with FIRES and six with DRE). Of the 22 patients with FIRES, 16 (73%) had at least short-term seizure control 1 week after starting anakinra, while the remaining six suspected anakinra-refractory cases were male and had poor prognoses. Due to the small sample size, an explanation for anakinra refractoriness was not evident. In all DRE patients, seizures disappeared or improved, and cognitive function improved in five of the six patients following treatment. Patients showed no serious side effects, although drug reactions with eosinophilia and systemic symptoms, cytopenia, and infections were observed. Thus, anakinra has led to a marked improvement in some cases, and functional deficiency of IL-1RA was indicated, supporting a direct mechanism for its therapeutic effect. This review first discusses the effectiveness of anakinra for intractable epileptic syndromes. Anakinra could become a new tool for intractable epilepsy treatment. However, it does not currently have a solid evidence base.


Assuntos
Encéfalo/patologia , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Inflamação/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Humanos , Inflamação/patologia , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem
15.
Int J Mol Sci ; 22(9)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922369

RESUMO

Accumulating evidence has demonstrated that the pathogenesis of epilepsy is linked to neuroinflammation and cerebrovascular dysfunction. Peripheral immune cell invasion into the brain, along with these responses, is implicitly involved in epilepsy. This review explored the current literature on the association between the peripheral and central nervous systems in the pathogenesis of epilepsy, and highlights novel research directions for therapeutic interventions targeting these reactions. Previous experimental and human studies have demonstrated the activation of the innate and adaptive immune responses in the brain. The time required for monocytes (responsible for innate immunity) and T cells (involved in acquired immunity) to invade the central nervous system after a seizure varies. Moreover, the time between the leakage associated with blood-brain barrier (BBB) failure and the infiltration of these cells varies. This suggests that cell infiltration is not merely a secondary disruptive event associated with BBB failure, but also a non-disruptive event facilitated by various mediators produced by the neurovascular unit consisting of neurons, perivascular astrocytes, microglia, pericytes, and endothelial cells. Moreover, genetic manipulation has enabled the differentiation between peripheral monocytes and resident microglia, which was previously considered difficult. Thus, the evidence suggests that peripheral monocytes may contribute to the pathogenesis of seizures.


Assuntos
Astrócitos/patologia , Barreira Hematoencefálica/patologia , Encéfalo/patologia , Epilepsia/patologia , Leucócitos/patologia , Animais , Astrócitos/imunologia , Barreira Hematoencefálica/imunologia , Encéfalo/imunologia , Epilepsia/imunologia , Humanos , Leucócitos/imunologia
16.
J Infect Chemother ; 27(6): 840-844, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33583741

RESUMO

INTRODUCTION: To clarify the pathology of children with acute encephalopathy and other neurological disorders, the involvement of high-mobility group box 1 (HMGB1), which is a representative of danger-associated molecular patterns, and angiogenesis-related growth factors were investigated. PATIENTS AND METHODS: Participants were 12 children with acute encephalopathy (influenza, rotavirus, and others), 7 with bacterial meningitis, and 6 with epilepsy disease (West syndrome). Twenty-four patients with non-central nervous system (CNS) infections as a control group were admitted to our hospital. We examined the levels of HMGB1, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and other cytokines in the serum and cerebrospinal fluid (CSF) of the subjects. RESULTS: Serum and CSF HMGB1 levels were significantly higher in the encephalopathy and meningitis groups than in the West syndrome and control groups. CSF HMGB1 levels correlated with those of interleukin-6 and -8. CSF HMGB1 and VEGF levels were correlated, and PDGF showed a positive relationship. CONCLUSION: HMGB1 and angiogenesis-related growth factors appear to play pivotal roles in the pathophysiology of CNS infections.


Assuntos
Encefalopatias , Infecções do Sistema Nervoso Central , Proteína HMGB1/metabolismo , Influenza Humana , Criança , Proteína HMGB1/sangue , Proteína HMGB1/líquido cefalorraquidiano , Humanos , Fator A de Crescimento do Endotélio Vascular
17.
J Neuroimmunol ; 352: 577475, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33454554

RESUMO

In this study, we assessed circulating immune cells and plasma cytokine levels in 15 pediatric patients with drug-resistant epilepsy (DRE). DRE patients had a significantly higher percentage of CD14+ monocytes positive for IL-1ß, IL-1 receptor antagonist, IL-6, and TNF-α than controls. Significantly higher intracellular levels of IFN-γ in CD4+ T cells and NK cells were also found in DRE patients. The level of IL-1ß+ CD14+ monocytes correlated with seizure frequency, and intracellular levels of IFN-γ in NKT-like cells were negatively correlated with the duration of epilepsy. Peripheral immune cells might be involved in the pathogenesis of DRE.


Assuntos
Epilepsia Resistente a Medicamentos/imunologia , Interleucina-1beta/imunologia , Monócitos/imunologia , Convulsões/imunologia , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/sangue , Feminino , Humanos , Lactente , Interferon gama/sangue , Interferon gama/imunologia , Interleucina-1beta/sangue , Masculino , Células T Matadoras Naturais/imunologia , Convulsões/sangue
18.
J Clin Med ; 10(1)2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401551

RESUMO

Complementary and integrative medicines (CIMs) are increasingly used as a preventive antimigraine therapy. In this review, we aimed to summarize the evidence for the efficacy and safety of eight CIMs (riboflavin, coenzyme Q10, magnesium, melatonin, polyunsaturated fatty acids, and combination therapy of feverfew, vitamin D, and ginkgolide B) in pediatric migraine prevention. The level of evidence for riboflavin was relatively high; it was investigated by many studies with five/seven studies demonstrating its efficacy. Five studies investigated the use of melatonin, with one reporting negative results. There was insufficient evidence on the effectiveness of coenzyme Q10, magnesium, and polyunsaturated fatty acids. Combination therapy showed positive potential; however, reports on the individual antimigraine effects of the CIMs were lacking. A definitive conclusion was not reached regarding the specific integrative drugs clinicians should choose for pediatric migraines, owing to low-quality evidence and a limited number of studies. Integrative medications are becoming more common for pediatric migraine prevention as they do not produce serious side effects, and underlying research data suggest their efficacy in preventing migraine. Additional studies are warranted to confirm the role of CIMs in treating patients with migraines.

19.
Indian J Pediatr ; 88(9): 879-884, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33400135

RESUMO

OBJECTIVE: To clarify the pathogenesis of sudden unexpected natural death (SUD) as well as biomarkers to differentiate the underlying diseases, by performing cytokine analysis in the acute phase of pediatric patients in whom viral infection led to SUD. METHODS: An acute phase cytokine analysis of pediatric patients in whom viral infection led to SUD was performed, and the data obtained were compared with those from SUD patients not associated with viral infections. Subjects included 4 boys aged 1-16 mo who died of cardiopulmonary arrest associated with viral infections. The causative viruses were identified as enterovirus, parainfluenza virus, respiratory syncytial virus, and rotavirus. The 4 other infants/children (aged 2-12 mo) died of non-infectious episodes, i.e., 1, 2, and 1 died of drowning, falling, and a traffic accident, respectively. Cerebrospinal fluid samples (CSF) of the subjects were collected during cardiopulmonary resuscitation or within 24 h of the events. RESULTS: The infection-induced sudden death group showed elevated CSF levels of inflammatory cytokines and chemokines. No increase was observed in interleukin-10 levels. Furthermore, in the infection-induced sudden death group, platelet-derived growth factor levels correlated with inflammatory cytokine levels. CONCLUSIONS: Infection-associated SUD may be differentiated from noninfectious SUD by measuring the levels of acute phase-inflammatory cytokines and chemokines at the onset of SUD.


Assuntos
Citocinas , Fator de Crescimento Derivado de Plaquetas , Viroses , Criança , Morte Súbita , Humanos , Lactente , Masculino , Fator de Crescimento Derivado de Plaquetas/líquido cefalorraquidiano , Vírus Sinciciais Respiratórios
20.
Am J Med Genet A ; 185(2): 579-583, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33251766

RESUMO

Several patients with beta-propeller protein-associated neurodegeneration (BPAN)/static encephalopathy with neurodegeneration in adulthood have been reported to present Rett syndrome (RTT)-like features. This report presents an individual with BPAN showing clinical features of RTT. Psychomotor delay and epilepsy onset were noted at 1 year, and regression began at 4 years. Screening of the methyl-CpG binding protein 2 (MECP2) did not show variants. At 22 years, basal ganglia iron deposits were found on magnetic resonance imaging (MRI), and the WD-domain repeat 45 gene (WDR45) variant was identified. Review of the literature showed that BPAN with RTT-like features is associated with more epileptic seizures and less deceleration of head growth, breathing irregularities, and cold extremities than classic RTT with MECP2 variants. These clinical presentations may provide clues for differentiating between these two disorders. However, both WDR45 and MECP2 should be screened in patients presenting a clinical picture of RTT without specific MRI findings of BPAN.


Assuntos
Encefalopatias/genética , Proteínas de Transporte/genética , Proteína 2 de Ligação a Metil-CpG/genética , Síndrome de Rett/genética , Adolescente , Adulto , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Encefalopatias/complicações , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Criança , Pré-Escolar , Epilepsia Parcial Complexa/complicações , Epilepsia Parcial Complexa/diagnóstico por imagem , Epilepsia Parcial Complexa/genética , Epilepsia Parcial Complexa/patologia , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Ferro , Distúrbios do Metabolismo do Ferro/complicações , Distúrbios do Metabolismo do Ferro/diagnóstico por imagem , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/patologia , Imageamento por Ressonância Magnética , Síndrome de Rett/complicações , Síndrome de Rett/diagnóstico por imagem , Síndrome de Rett/patologia , Adulto Jovem
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