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1.
J Infect Chemother ; 2021 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-33583741

RESUMEN

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.

2.
Artículo en Inglés | MEDLINE | ID: mdl-33448517

RESUMEN

Long-term use of benzodiazepines (BZD) is not recommended for the treatment of anxiety disorders. Cognitive behavioral therapy (CBT) is an effective treatment option for discontinuation of BZD in patients with anxiety disorders. This systematic review and meta-analysis sought to clarify whether CBT is effective for discontinuing BZD anxiolytics in patients with anxiety disorders. This study was preregistered with PROSPERO (registration number: CRD42019125263). A literature search of major electronic databases was conducted in December 2018. Three randomized controlled trials were included in this review, and meta-analyses were performed. The proportion of discontinuing BZD anxiolytics was significantly higher in the CBT plus gradual tapering group than in the gradual tapering alone group, both in the short term (3 months after allocation; number needed to treat: 3.2, 95% confidence interval [CI]: 2.1 to 7.1; risk ratio: 1.96, 95%CI: 1.29 to 2.98, P = 0.002, three studies) and long term (6 to 12 months after allocation; number needed to treat: 2.8, 95%CI: 1.9 to 5.3; risk ratio: 2.16, 95%CI: 1.41 to 3.32, P = 0.0004, three studies). CBT may be effective for discontinuing BZD anxiolytics, both in the short term and in the long term after the allocation. Further studies with larger sample sizes are necessary to draw definitive conclusions regarding the efficacy and safety of CBT for discontinuing BZD anxiolytics in patients with anxiety disorders.

4.
J Neuroimmunol ; 352: 577475, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33454554

RESUMEN

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.

5.
Indian J Pediatr ; 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33400135

RESUMEN

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.

6.
Seizure ; 85: 6-11, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33360040

RESUMEN

PURPOSE: We aimed to study the efficacy of adrenocorticotropic hormone (ACTH) treatment on infantile spasms with different aetiologies. In particular, we were interested in patients with structural-acquired aetiology. METHODS: Patients with infantile spasms, who were treated with ACTH, were divided into three groups based on the aetiologies: unknown aetiology with normal development (unknown-normal), structural-acquired, and combined-congenital aetiologies that included genetic, metabolic, structural-congenital, or unknown aetiology with developmental delay. RESULTS: Of the 107 patients included (58 males, 49 females), 25 patients had unknown-normal aetiology [median age at onset 5 months, standard deviation (SD) 3.12, range 2-16 months]; 20 patients had structural-acquired aetiology (median age at onset 6.5 months, SD 3.85 months, range 4-17 months); and 62 patients had combined-congenital aetiologies (median age at onset 5 months, SD 2.73 months, range 2-16 months). The efficacy of ACTH was 64.0 %, 65 %, and 30.6 % in the unknown-normal aetiology, structural-acquired aetiology, and combined-congenital aetiologies, respectively (p < 0.01). Multivariate analysis showed a statistically significant higher efficacy in the unknown-normal aetiology [Odds ratio (OR) 4.63, 95 % confidence interval (CI) 1.60-13.30] and structural-acquired aetiology (OR 3.41, 95 % CI 1.01-11.50) compared to that in the combined-congenital aetiologies. CONCLUSION: Infantile spasms with structural-acquired aetiology had greater response to ACTH treatment than those with combined-congenital aetiologies. The efficacy of standard therapy of infantile spasms should be considered based on aetiology.

7.
J Pharmacol Sci ; 145(1): 155-165, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33357774

RESUMEN

In this study, among neurovascular unit (NVU) cells, we focused on pericyte reactivity in mice subjected to controlled cortical impact (CCI) to understand how traumatic brain injury (TBI) causes uncoordinated crosstalk in the NVU and alters neuronal activity. Histological analyses of brain pericytes, microglia and astrocytes were performed for up to 28 days after CCI in the injured ipsilateral hippocampus. To evaluate altered neuronal activity caused by CCI, we measured seizure susceptibility to a sub-threshold dose of pilocarpine on postoperative day 7, 14, 21 and 28. Platelet-derived growth factor receptor (PDGFR) ß immunoreactivity in pericytes significantly increased from 1 h to 4 days after CCI. The expression of Iba1 and GFAP, as markers of microglia and astrocytes, respectively, increased from 4 to 28 days after CCI. The severity of seizure induced by pilocarpine gradually increased, becoming significant at 28 days after CCI. Then, we treated CCI mice with an inhibitor of PDGFR signaling, imatinib, during the postoperative day 0-4 period. Imatinib lowered seizure susceptibility to pilocarpine and suppressed microglial activation in the injured hippocampus at postoperative day 28. These findings indicate that brain pericytes with rapidly increased PDGFRß expression may drive TBI-induced dysregulation of NVU function and brain hyperexcitability.

8.
J Clin Med ; 9(11)2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33228144

RESUMEN

Although migraines are common in children and adolescents, they have a robustly negative impact on the quality of life of individuals and their families. The current treatment guidelines outline the behavioral and lifestyle interventions to correct common causative factors, such as negative emotional states, lack of exercise and sleep, and obesity; however, the evidence of their effectiveness is insufficient. To create a plan for disseminating optimal pediatric headache education, we reviewed the current evidence for factors correlated with migraine. We assessed three triggers or risk factors for migraines in children and adolescents: stress, sleep poverty, and alimentation (including diet and obesity). While there is a gradual uptick in research supporting the association between migraine, stress, and sleep, the evidence for diet-related migraines is very limited. Unless obvious dietary triggers are defined, clinicians should counsel patients to eat a balanced diet and avoid skipping meals rather than randomly limiting certain foods. We concluded that there is not enough evidence to establish a headache education plan regarding behavioral and lifestyle interventions. Clinicians should advise patients to avoid certain triggers, such as stress and sleep disorders, and make a few conservative dietary changes.

9.
Am J Med Genet A ; 2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33251766

RESUMEN

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.

11.
Jpn J Infect Dis ; 73(6): 443-446, 2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-32611972

RESUMEN

Low blood levels of vitamin D have been reported in children who have frequent respiratory tract infections. We measured serum concentrations of 25-hydroxy (OH) vitamin D in Japanese infants under 3 months of age who had respiratory syncytial virus (RSV) infection. Serum levels of 25-OH vitamin D in the 10 infants, excluding those with underlying diseases, were between < 4 and 29.8 ng/mL. In 8 out of 10 subjects (80.0%), serum 25-OH vitamin D levels were lower than 20 ng/mL. There was no statistically significant association between the levels of 25-OH vitamin D and age, duration of admission, respiratory severity score, white blood cell count, blood gas levels, and N-terminal pro-natriuretic peptide levels. Levels of serum 25-OH vitamin D in children who required hospitalization owing to RSV infection were low, indicating deficiency. These results suggest that vitamin D deficiency affects the susceptibility to RSV infection, but not the severity of the infection.

13.
J Child Neurol ; 35(10): 667-673, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32476572

RESUMEN

BACKGROUND: Migraines are a broad spectrum of disorders classified by the type of aura with some requiring attentive treatment. Vasoconstrictors, including triptans, should be avoided in the acute phase of migraines with brainstem aura, in hemiplegic migraine, and in retinal migraine. This study investigated the characteristics and burden of these migraines. METHODS: Medical charts of 278 Japanese pediatric patients with migraines were retrospectively reviewed. Migraine burden of migraines with brainstem aura, hemiplegic migraines, and retinal migraine was assessed using the Headache Impact Test-6™ (HIT-6) and the Pediatric Migraine Disability Assessment scale (PedMIDAS). RESULTS: Of 278 patients screened, 12 (4.3%) patients with migraines with brainstem aura (n = 5), hemiplegic migraines (n = 2), and retinal migraine (n = 5) were enrolled in the study. All patients had migraine with/without typical aura, whereas some patients had coexisting migraine with another type of headache (chronic tension-type headache in 3 patients, and 1 each with frequent episodic tension-type headache, headache owing to medication overuse, and chronic migraine). Migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients with coexisting headaches had higher HIT-6 or PedMIDAS scores, whereas migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients without coexisting headache did not show high HIT-6 or PedMIDAS scores. CONCLUSION: All migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients experienced migraine with or without typical aura, and some patients having other coexisting headaches also had high PedMIDAS and HIT-6 scores. PedMIDAS and HIT-6 should not be considered diagnostic indicators of migraines with brainstem aura, hemiplegic migraines, or retinal migraine. In clinical practice for headaches in children, careful history taking and proactive assessment of the aura are needed for accurate diagnosis of migraines with brainstem aura, hemiplegic migraines, and retinal migraine.

15.
Brain Dev ; 42(7): 523-528, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32336482

RESUMEN

BACKGROUND: Riboflavin may prevent migraine episodes; however, there is limited evidence of its effectiveness in pediatric populations. This study investigated the effectiveness of riboflavin and clinical predictors of response in children with migraines. METHODS: We retrospectively reviewed data from 68 Japanese children with migraines, of whom 52 also exhibited another type of headache. Patients received 10 or 40 mg/day of riboflavin. We evaluated the average migraine frequency per month as a baseline and after 3 months of riboflavin therapy to determine the effectiveness and clinical predictors of response. RESULTS: The frequency of migraine episodes was significantly lower at 3 months than at baseline (median, [interquartile range], 5.2 (3-7) vs. 4.0 (2-5); p < 0.01). Twenty-five patients (36.7%) showed 50% or greater reduction in episode frequency (responders), while 18 (26.5%) showed a 25%-50% reduction. We compared responders (n = 25) and non-responders (n = 43) and found no significant differences in sex, familial history, riboflavin dose, migraine type (i.e., presence or absence of aura), age at headache onset, or age at consultation. However, non-responders were more likely to have co-morbid non-migraine headaches (odds ratio, 4.11; 95% confidence interval [CI], 1.27-13.33; p = 0.02); this variable was also significant in a multivariate analysis (adjusted odds ratio, 3.8; 95% CI, 1.16-12.6; p = 0.03). Of the co-morbid headache types, only tension headaches were significant (odds ratio, 0.176; 95% CI, 0.04-0.73; p = 0.013). No adverse effects of riboflavin were identified. CONCLUSIONS: Low-dose riboflavin is safe and modestly effective for migraines in children. It may be especially beneficial for children without other co-morbid headache types.

16.
Neuropediatrics ; 51(2): 154-159, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31935762

RESUMEN

Some studies have shown that sedative antihistamines prolong febrile seizure duration. Although the collective evidence is still mixed, the Japanese Society of Child Neurology released guidelines in 2015 that contraindicated the use of sedative antihistamines in patients with febrile seizure. Focused on addressing limitations of previous studies, we conducted a cross-sectional study to evaluate the relationship between febrile seizure duration and the use of sedative antihistamines. Data were collected from patients who visited St. Luke's International Hospital due to febrile seizure between August 2013 and February 2016. Patients were divided into groups based on their prescribed medications: sedative antihistamine, nonsedative antihistamine, and no antihistamine. Seizure duration was the primary outcome and was examined using multivariate analyses. Of the 426 patients included, sedative antihistamines were administered to 24 patients. The median seizure duration was approximately 3 minutes in all three groups. There was no statistical difference in the bivariate (p = 0.422) or multivariate analyses (p = 0.544). Our results do not support the relationship between sedative antihistamine use and prolonged duration of febrile seizure. These results suggest that the use of antihistamines may be considered for patients with past history of febrile seizure, when appropriate.

17.
J Child Neurol ; 35(3): 208-214, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31709864

RESUMEN

OBJECTIVE: The present study aimed to determine whether granzymes are implicated in the pathogenesis of infection-associated acute encephalopathy (AE). METHODS: We investigated granzyme and cytokine levels in the cerebrospinal fluid of patients with acute encephalopathy or complex febrile seizures (cFS). A total of 24 acute encephalopathy patients and 22 complex febrile seizures patients were included in the present study. Levels of granzymes A and B were measured using enzyme-linked immunosorbent assay, and levels of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), interleukin 1ß (IL-1ß), IL-1 receptor antagonist (IL-1RA), IL-4, IL-6, IL-8, and IL-10 were assessed using the Bio-Plex suspension array system. RESULTS: Cerebrospinal fluid levels of granzyme A were significantly higher, and those of TNF-α and IL-1RA were significantly lower in the AE group than in the cFS group; however, no significant differences in the levels of granzyme B, IFN-γ, IL-1ß, IL-4, IL-6, IL-8, and IL-10 were observed between the 2 groups. In addition, no significant differences in granzyme A, granzyme B, or cytokine levels were observed between acute encephalopathy patients with and those without neurologic sequelae. CONCLUSIONS: Our findings indicate the involvement of granzyme A in the pathogenesis of acute encephalopathy.

19.
J Infect Chemother ; 26(4): 393-396, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31879187

RESUMEN

We report a first case of respiratory syncytial virus (RSV) infection-associated encephalopathy in which RS virus was detected in the patient's intratracheal aspiration and cerebrospinal fluid despite negative rapid test results of the nasal swab. The patient's findings and clinical course coincided with those of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) with severe subsequent sequelae. Our case indicates that clinicians should consider RSV infection when patients have AESD with unknown etiology.

20.
Neuroscience ; 422: 12-20, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31705893

RESUMEN

Oncostatin M (OSM) is a cytokine of the interleukin (IL)-6 family members. It induces blood-brain barrier (BBB) dysfunction by activating Janus-activated kinase (JAK) and signal transducer and activator of transcription (STAT) 3 pathways in brain endothelial cells. Brain pericytes located around microvessels are one of the BBB constituents. Pericytes work as a boundary surface between the blood circulation and brain parenchyma, and their functions are altered under pathophysiological conditions, leading to BBB dysregulation. However, it remains unknown whether pericytes are associated with OSM-induced BBB dysfunction. We demonstrated that pericyte exposure to OSM (100 ng/mL) elevated phosphorylation of STAT3, a main OSM signaling pathway, and that pericytes expressed OSM receptors (OSMRs) including OSMRß and glycoprotein 130. These results suggest that pericytes are able to respond to OSM. To determine the effects of OSM-reactive pericytes on BBB functions, rat brain endothelial cell (RBEC) monolayers were cultured with OSM-treated pericytes. The presence of pericytes exposed to 100 ng/mL of OSM for 48 h aggravated both the elevated permeability to sodium fluorescein and the lowered transendothelial electrical resistance which were induced by OSM in RBECs. This OSM-reactive pericyte-induced aggravation of lowered RBEC barrier function was reversed by ruxolitinib, a JAK inhibitor. These findings suggest that activated JAK/STAT3 signaling in pericytes contributes to OSM-produced BBB breakdown. Thus, OSM-reactive pericytes may have to be considered a characteristic machinery in the formation and progression of BBB breakdown under pathological conditions associated with increased OSM levels.


Asunto(s)
Barrera Hematoencefálica/fisiopatología , Quinasas Janus/metabolismo , Oncostatina M/farmacología , Oncostatina M/fisiología , Factor de Transcripción STAT3/metabolismo , Animales , Receptor gp130 de Citocinas/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Oncostatina M/antagonistas & inhibidores , Subunidad beta del Receptor de Oncostatina M/metabolismo , Pericitos/efectos de los fármacos , Pericitos/metabolismo , Fosforilación/efectos de los fármacos , Cultivo Primario de Células , Pirazoles/farmacología , Ratas , Transducción de Señal
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