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Background: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases affecting primarily proximal muscles. Major subtypes include dermatomyositis, polymyositis, inclusion body myositis, immune-mediated necrotizing myopathy and antisynthetase syndrome. Overexpression of sarcoplasmic myxovirus-resistance protein A (MxA) has been observed in muscle biopsy specimens of dermatomyositis but is rarely seen in other subtypes of IIM and other myopathies. Objective: We evaluate the expression of sarcoplasmic MxA and its diagnostic value in IIM and other myopathies. Methods: One hundred and thirty-eight muscle biopsy specimens with the diagnosis of IIM and other myopathies from 2011 to 2020 were reviewed and stained for MxA by immunohistochemistry. The difference of the expression of MxA between IIM and other myopathies was analyzed by Fisher's exact test, and the sensitivity and specificity of MxA immunohistochemistry in the diagnosis of IIM were assessed. Results: MxA protein was positive in 16/138 (11.6%) specimens. All 12 dermatomyositis specimens positive for MxA protein were positive in perifascicular area pattern. Only dermatomyositis specimens had a significantly higher percentage of positive sarcoplasmic MxA expression than specimens of other subtypes of IIM (p<0.001). Sarcoplasmic MxA expression for dermatomyositis diagnosis had a sensitivity of 46.15% (95% CI 26.59-66.63%) and a specificity of 94.44% (95% CI 81.34-99.32%) with the positive and negative likelihood ratio of 8.31 (95% CI 2.03-34.01) and 0.57 (95% CI 0.40-0.82), respectively. Conclusion: The MxA immunohistochemistry is highly specific for dermatomyositis and should be added to a routine inflammatory panel of muscle biopsy. MxA expression should be cautiously interpreted to avoid pitfalls.
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Nonketotic hyperglycinemia (NKH) is in most cases a fatal inborn error of metabolism which usually presents during the neonatal period as encephalopathy and refractory seizures. The reported congenital anomalies associated with NKH included corpus callosal agenesis, club foot, cleft palate, and congenital heart disease. Here, we report a newborn who presented with encephalopathy without overt seizures, cerebral venous sinus thrombosis, and cleft palate. Electroencephalography showed a burst suppression pattern, which suggests the etiology could be due to a metabolic or genetic disorder. The amino acid analysis of plasma and cerebrospinal fluid showed elevated glycine. Whole exome sequencing identified a heterozygous c.492C > G; p.Tyr164Ter variant in exon 4 of the GLDC gene inherited from the patient's father. Further long-read whole genome sequencing revealed an exon 1-2 deletion in the GLDC gene inherited from the patient's mother. Additional analyses revealed no pathogenic variants of the cleft palate-related genes. The cleft palate may be an associated congenital anomaly in NKH. Regarding cerebral venous sinus thrombosis, we found a heterozygous variant (p.Arg189Trp) of the PROC gene, which is a common cause of thrombophilia among Thai newborns. A neonate with NKH could present with severe encephalopathy without seizures. A close follow up for clinical changes and further next generation sequencing are crucial for definite diagnosis in neonates with encephalopathy of unclear cause.
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BACKGROUND: To study the associations of parenting styles and anxiety in Thai children and adolescents with tic disorders, comparing with healthy children and adolescents. METHODS: A cross-sectional study of children and adolescents aged between six and 18 years with tic disorders were enrolled. The control group comprised gender- and age-matched healthy children with no history of tic disorders. The Yale Global Tic Severity Scale was used to assess tics severity. All participants were evaluated for anxiety trait and state using the State-Trait Anxiety Inventory for Children (STAIC). The anxiety disorders were screened by using the Screen for Child Anxiety-Related Emotional Disorders questionnaire. Parenting styles were evaluated by the Parenting Styles and Dimensions Questionnaire. RESULTS: A total of 41 children with tic disorders and 41 children in the control group were enrolled. According to the STAIC, the anxiety state and trait scores were significantly higher in the tic disorders group than in the control group (median [interquartile range]: 28 [13 to 31] vs 8 [6 to 10], P≤0.001, and 31 [18 to 36] vs 8 [3 to 11], P≤0.001, respectively). Furthermore, anxiety disorder was more frequently found in children with tic disorders than in controls (58.5% vs 17.1%, P≤0.001). There was no significant correlation between anxiety symptoms, parenting styles, and the severity of tics. CONCLUSION: Anxiety is common in Thai children with tic disorders. Screening for anxiety in children and adolescents with tic disorders is essential, leading to early detection and providing proper management.
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Transtornos de Tique , Tiques , Criança , Humanos , Adolescente , Poder Familiar , Estudos Transversais , Transtornos de Tique/epidemiologia , Transtornos de Tique/psicologia , Ansiedade/epidemiologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologiaRESUMO
PURPOSE: To evaluate the effectiveness and tolerability of perampanel (PER) in real-world settings in patients between 1 month and 18 years of age with drug resistant epilepsy (DRE) waiting for epilepsy surgery. METHODS: In this multicenter study, patients between 1 month and 18 years of age with DRE treated with PER between January 2020 and June 2021 were selected. The study outcome was effectiveness of PER treatment reported as reduction in seizure frequency and seizure freedom rate. Effectiveness was assessed at 30, 60, 90, 120, 150 and 180 days after initiation of PER. Tolerability profiles were reported as adverse events according to the observations of the patients' family members and physician. RESULTS: Eighty-five patients treated with PER were included in the study. The mean initial dose and mean maximum dose of adjunctive PER was 2 mg/day and 5.8 mg/day, respectively. The mean seizure frequency (rate/week) was 41.3, 25.4, 18.9, 14.3, 11.2, 11.1 and 8.9 seizures at baseline, 30, 60, 90, 120, 150 and 180 days, respectively; the reduction in the mean seizure frequency at all timepoints was significant compared at the baseline (p<0.001). At 180 days, ≥75% seizure reduction was seen in 64.9% (37/57) of the patients and seizure freedom was achieved in 36.8% (21/57). Drowsiness, ataxia, and behavioral changes were the common adverse events observed, and these improved after the dose of PER was reduced. No discontinuation of PER was required due to side effects or intolerance. CONCLUSION: In real-world settings, PER is well tolerated and effective in seizure control in pediatric and adolescent patients with DRE.
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Epilepsia Resistente a Medicamentos , Epilepsia , Adolescente , Anticonvulsivantes/efeitos adversos , Criança , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/cirurgia , Quimioterapia Combinada , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Humanos , Nitrilas , Piridonas/efeitos adversos , Convulsões/tratamento farmacológico , Tailândia , Resultado do TratamentoRESUMO
BACKGROUND: Anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) is one of the most common types of autoimmune encephalitis. Most patients have no apparent immunologic triggers, which suggests a genetic predisposition. This study was conducted to identify human leukocyte antigen (HLA) class II alleles associated with anti-NMDARE in Thai children. METHODS: This case-control study enrolled patients younger than 18 years who were diagnosed with anti-NMDARE between January 2010 and December 2020. A "good outcome" was determined as a patient with a modified Rankin scale score of less than 2 at any follow-up visit. HLA genotypes were determined at four-digit alleles using reverse sequence-specific oligonucleotide probe hybridization. The HLA class II allele frequency in patients was compared with that in a database of 101 healthy control Thai children. RESULTS: Thirty-four patients were enrolled with a mean age of 12.8 ± 5.6 years (females 85.3%). The HLA-DRB1∗1502 allele frequency was significantly higher in patients than in controls (odds ratio, 2.32; 95% confidence interval, 1.11-4.8, P = 0.023). A good outcome was noted in 14 of 14 (100%) HLA-DRB1∗1502-positive patients (median time to a good outcome, 6 months) and 14 of 17 (82.3%) HLA-DRB1∗1502-negative patients (median time to a good outcome, 3 months). Two (11.8%) HLA-DRB1∗1502-positive patients had one relapse each, and six (35.3%) HLA-DRB1∗1502-negative patients had one to three relapses. CONCLUSIONS: HLA-DRB1∗1502 was significantly associated with anti-NMDARE in our patients. Most patients had good outcomes. HLA-DRB1∗1502-positive patients tended to require a longer time to achieve a good outcome but had less frequent relapses than HLA-DRB1∗1502-negative patients.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Cadeias HLA-DRB1/genética , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/genética , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Recidiva Local de Neoplasia , TailândiaRESUMO
Glucose transporter type-1 deficiency syndrome (Glut1 DS) is a rare disorder with various manifestations. Early diagnosis is crucial because treatment with the ketogenic diet can lead to clinical improvement. Here, we report the cases of two siblings with Glut1 DS and one of them presented with sleep disorder which is a rare and atypical manifestation of Glut1 DS. Patient 1 was a 3.5-year-old boy who presented with paroxysmal loss of tone and weakness of the whole body with unresponsiveness after waking up. He also had excessive daytime sleepiness, insomnia, and restless sleep. His other clinical findings included focal seizures, paroxysmal exercise-induced dyskinesia (PED), ataxia, mild global developmental delay, and hyperactivity. Patient 2 was a 5.5-year-old boy who presented with drug-resistant focal epilepsy, global developmental delay, paroxysmal dystonia, and ataxia. A novel heterozygous nonsense variant of SLC2A1, c.1177G > T (p.Glu393*), classified as a pathogenic variant, was identified in both patients, but not in their parents' blood. After treatment with the modified Atkins diet, their neurological functions significantly improved. In conclusion, we reported two siblings with variable phenotypes of Glut1 DS with a novel nonsense mutation. Although sleep disorder and daytime somnolence were the nonclassical manifestations of Glut1 DS, the diagnostic evaluation of possible Glut1 DS in patients presented with daytime sleepiness, particularly in cases with the cooccurrence of seizures or movement disorders should be considered.
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Erros Inatos do Metabolismo dos Carboidratos , Coreia , Dieta Cetogênica , Epilepsia , Transtornos do Sono-Vigília , Ataxia/etiologia , Ataxia/genética , Erros Inatos do Metabolismo dos Carboidratos/complicações , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/genética , Pré-Escolar , Coreia/genética , Epilepsia/genética , Transportador de Glucose Tipo 1/genética , Humanos , Masculino , Proteínas de Transporte de Monossacarídeos/deficiência , Mutação , Convulsões , Transtornos do Sono-Vigília/genéticaRESUMO
BACKGROUND: Children with refractory epilepsy (RE) are associated with increased mortality rate, nonfatal injuries, disability, and diminished quality of life. Biomarkers for the early prediction of RE is still an unmet need. METHODS: Eighteen children with RE and six age-matched unrelated controls were included in this study. Plasma samples were prefractionated by the optimized thermal treatment before proteomic analysis using 2DE-LC-MS/MS. Bioinformatic analysis was carried out using STRING protein network. Immunoassay of unprocessed plasma was applied to confirm changes of proteins of interest. P-value < 0.05 was considered statistically significant. RESULTS: Proteomic analysis (n = 6 each group) revealed nine differentially expressed proteins, i.e., haptoglobin, S100A9, serpin B1, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein C-II, alpha-1-acid glycoprotein 1 and 2, and transthyretin. Western immunoblotting confirmed haptoglobin upregulation in the RE group. STRING protein network predicted the inflammatory cytokines, i.e., interferon gamma (IFN-γ), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), play roles in pathophysiology in RE patients. Cytokine immunoassay (n = 24, 18 RE vs. 6 controls) exhibited plasma IFN-γ was upregulated in RE patients as compared to the healthy individuals (median [IQR]; 2.9 [2.9, 4.9] vs. 1.32 [0.8, 1.5] pg/mL, p = 0.0013), and plasma IL-1ß was significantly downregulated in patients (1.0 [0.2, 1.9] vs. 4.5 [1.9, 11.0] pg/mL, p = 0.01). TNF-α had no difference between groups. The results suggest that haptoglobin may be associated with oxidative brain damage, while IFN-γ and IL-1ß may be involved with neuroinflammation. CONCLUSIONS: Alterations in plasma haptoglobin, IFN-γ, and IL-1ß were associated with RE patients. Future studies using a combination of these candidate biomarkers may help predict the intractability of epilepsy in pediatric populations.
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Biomarcadores/sangue , Epilepsia Resistente a Medicamentos/sangue , Haptoglobinas/metabolismo , Interferon gama/sangue , Interleucina-1beta/sangue , Criança , Feminino , Humanos , Masculino , Proteômica/métodosRESUMO
BACKGROUND: Intracranial infectious aneurysms are rarely reported in children; in particular, they are very rare in infants. They are mostly related to infective endocarditis and are usually located in the anterior cerebral vasculature. A ruptured intracranial infectious aneurysm is a catastrophic event associated with high morbidity and mortality rates. CASE REPORT: An 8-month-old female infant presented with a prolonged fever without any organ-specific symptoms. Two weeks after admission, she had a high-grade fever with drowsiness; the cerebrospinal fluid (CSF) examination indicated meningitis. Despite treatments with empiric antibiotic and antiviral agents, both her condition and the repeated CSF profiles worsened. The ineffective medications were promptly changed to susceptible antibiotic after the CSF culture showed Pseudomonas aeruginosa. Three days after the diagnosis of meningitis, the patient suddenly developed seizures and alteration of consciousness. The computerized tomography and angiography (CT and CTA) of the brain demonstrated a diffuse subarachnoid hemorrhage (SAH) with intraventricular hemorrhage (IVH) and a lobulated fusiform aneurysm at the proximal basilar artery, suggestive of a ruptured basilar infectious aneurysm. Endovascular treatment was planned and a transarterial occlusion of the vertebrobasilar junction was performed in order to disrupt inflow of the aneurysm. After endovascular intervention, her clinical symptoms gradually improved and the patient was discharged after completing a 4-week course of antibiotics. At the 6-week follow-up, she was doing well without neurological deficit. CONCLUSION: To our knowledge, this is the first reported case of a ruptured basilar infectious aneurysm in an infant secondary to Pseudomonas meningitis, successfully treated with parent artery occlusion.
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Aneurisma Roto , Embolização Terapêutica , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Aneurisma Roto/terapia , Artéria Basilar , Angiografia Cerebral , Criança , Feminino , Humanos , Lactente , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgiaRESUMO
OBJECTIVE: We aim to identify prognostic factors for visual outcomes following a first episode of neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) in affected eyes. MATERIALS AND METHODS: This was a single-center, retrospective study. The study included 50 individuals who were diagnosed with NMOSD-ON (63 affected eyes) in a tertiary institution over a 12-year period. Data regarding any second, or higher, episodes of NMOSD-ON in each eye were not taken into consideration. Medical records of included individuals were reviewed. Demographic data, clinical and magnetic resonance imaging characteristics, and treatment outcomes were collected. Main outcome measures of the study were prognostic factors for good visual outcome (best-corrected visual acuity (BCVA) ≥ 20/200) following an initial episode of NMOSD-ON in affected eyes. RESULTS: Sixty-three affected eyes of 50 individuals (3 men and 47 women) were included. BCVA at nadir that was better than counting fingers (CF) (odds ratio 10.43, 95% confidence interval 1.04, 104.45, p = 0.046) and time from NMOSD-ON onset to intravenous methylprednisolone (IVMP), less than 21 days (odds ratio 10.73, 95% confidence interval 1.91, 60.01, p = 0.007), were significantly associated with good visual outcomes. CONCLUSION: BCVA at nadir that was better than CF and treatment with IVMP within 21 days of symptom onset were important prognostic factors of good visual outcomes following a first episode of NMOSD-ON in affected eyes.
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PURPOSE: To compare demographic data, clinical and radiological characteristics, treatment, and long-term visual outcomes between myelin oligodendrocyte glycoprotein autoantibody-positive optic neuritis (MOG-IgG + ON) and aquaporin-4 autoantibody-positive optic neuritis (AQP4-IgG + ON) in Thailand. PATIENTS AND METHODS: We included individuals who were diagnosed with either MOG-IgG + ON or AQP4-IgG + ON over an 11-year period. Demographic data, clinical and radiological characteristics at ON presentation, treatment, and long-term visual outcomes were retrospectively collected. RESULTS: There were 16 patients (28 eyes) and 43 patients (59 eyes) in the MOG-IgG + ON and AQP4-IgG + ON groups, respectively. AQP4-IgG + ON occurred predominantly in female patients whereas MOG-IgG + ON-affected female patients and male patients equally (p < 0.001). Prior or concurrent non-ON demyelinating events were more often observed at AQP4-IgG + ON onset (p < 0.001). At ON presentation, bilaterality and the presence of optic disc edema were predominantly found in the MOG-IgG + ON group (bilaterality: 80% vs 8%, MOG-IgG + ON vs AQP4-IgG + ON patients, respectively (p < 0.001); presence of optic disc edema: 92.3% vs 36.6%, MOG-IgG + ON- vs AQP4-IgG + ON-affected eyes, respectively (p < 0.001)). There was no statistically significant difference in age at ON onset, nadir visual acuity (VA), presence of pain, segmental enhancement, and total enhanced segments of the anterior visual pathways. At the last follow-up, immunosuppressive drugs were used more often in the AQP4-IgG + ON group (43.7% vs 74.4%, MOG-IgG + ON vs AQP4-IgG + ON, respectively; p < 0.027). Remarkably better final VA was achieved in MOG-IgG + ON-affected eyes (median: 0.0 vs 0.4 logMAR, MOG-IgG + ON- vs AQP4-IgG + ON-affected eyes, respectively; p < 0.001). CONCLUSION: Compared with AQP4-IgG + ON, MOG-IgG + ON tended to present with bilaterality and optic disc edema and demonstrated better visual outcomes.
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Epilepsy surgery is proven as a cost-effective treatment in developed countries, especially in adults with drug resistant epilepsy (DRE). This study is aimed to demonstrate the cost-effectiveness of epilepsy surgery in children and adolescents with DRE at three years compared with those who were eligible for surgery but received medical treatment. This study was conducted from January 2014 to December 2018. Clinical data were obtained from a retrospective chart review. Direct medical costs, including epilepsy surgery, inpatient and outpatient treatment were retrieved from the finance department. Direct non-medical costs were collected from the family interview. The effectiveness was determined by percent seizure reduction and quality of life assessed by EQ-5D scores. Decision tree analysis using TreeAge Pro® 2018 was deployed to determine the cost-effectiveness. Seventeen patients had epilepsy surgery and 19 were in the medical group. Seizure freedom was noted in 52% and 16% in the surgical and medical groups, respectively. Incremental cost-effectiveness ratio (ICER) was 743,040 THB (22,793 USD) per 1 QALY and 3302 THB (101 USD) per 1% seizure reduction. The study did not demonstrate cost-effectiveness of epilepsy surgery in the short term compared with Thailand's threshold (160,000 THB (4908 USD) per 1 QALY). Epilepsy surgery may be cost-effective if evaluated beyond three years.
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Análise Custo-Benefício , Epilepsia Resistente a Medicamentos/cirurgia , Custos de Cuidados de Saúde , Procedimentos Neurocirúrgicos/economia , Resultado do Tratamento , Adolescente , Anticonvulsivantes/economia , Anticonvulsivantes/uso terapêutico , Criança , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/economia , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/cirurgia , Feminino , Humanos , Masculino , Procedimentos Neurocirúrgicos/métodos , Qualidade de Vida , Estudos Retrospectivos , Centros de Atenção Terciária/economia , Atenção Terciária à Saúde/economia , TailândiaRESUMO
Congenital myasthenic syndromes (CMS) comprise a heterogeneous group of genetic disorders of the neuromuscular junction. Next generation sequencing has been increasingly used for molecular diagnosis in CMS patients. This study aimed to identify the disease-causing variants in Thai patients. We recruited patients with a diagnosis of CMS based on clinical and electrophysiologic findings, and whole exome sequencing was performed. Thirteen patients aged from 2 to 54 years (median: 8 years) from 12 families were enrolled. Variants were identified in 9 of 13 patients (69%). Five novel variants and two previously reported variant were found in the COLQ, RAPSN and CHRND gene. The previously reported c.393+1G>A splice site variant in the COLQ gene was found in a majority of patients. Five patients harbor the homozygous splice site c.393+1G>A variant, and two patients carry compound heterozygous c.393+1G>A, c.718-1G>T, and c.393+1G>A, c.865G>T (p.Gly289Ter) variants. The novel variants were also found in RAPSN (p.Cys251del, p.Arg282Cys) and CHRND (p.Met481del). Molecular diagnosis in CMS patients can guide treatment decisions and may be life changing, especially in patients with COLQ mutations.
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Síndromes Miastênicas Congênitas/diagnóstico , Síndromes Miastênicas Congênitas/genética , Síndromes Miastênicas Congênitas/fisiopatologia , Acetilcolinesterase/genética , Adolescente , Adulto , Criança , Pré-Escolar , Colágeno/genética , Estudos Transversais , Eletromiografia , Ácidos Graxos Dessaturases/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/genética , Linhagem , Receptores Colinérgicos/genética , Tailândia , Sequenciamento do Exoma , Adulto JovemRESUMO
BACKGROUND: Induction chemotherapy with carboplatin followed by radiotherapy has been used for many years for treating intracranial germ-cell tumors (IC-GCTs) in Thailand. The objective of this study was to assess treatment outcomes, focusing on survival and ototoxicity. METHODS: The outcomes of all patients with IC-GCT treated at Ramathibodi Hospital and the Prasat Neurological Institute between 2000 and 2017 were reviewed and analyzed, including all patient characteristics and treatment modalities. Five-year overall survival (OS) and event-free survival (EFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were compared using the log-rank test. RESULTS: Fifty-three patients age 1-14 years (median, 11 years) were included in this study. The median follow-up time was 63 months. The 5-year EFS and OS rates were 94.3% and 96.2% for all patients, respectively. No statistical difference in OS or EFS was observed between the data of recipients in the carboplatin-based and historical cisplatin-based therapies in our institutes. Concerning radiotherapy, omission of radiotherapy or focal irradiation results in worse long-term survival outcomes, but reduction in dose of radiotherapy to less than 40 Gy did not cause any negative impact on survival rates. Furthermore, carboplatin was associated with lower rates of hearing loss than cisplatin (5.7% vs 87.5%). CONCLUSIONS: Induction chemotherapy with carboplatin-based regimens was associated with excellent survival rates and low ototoxicity in patients with IC-GCT. Radiotherapy should be given to all patients with a minimal volume equivalent to whole-ventricular radiotherapy, during which doses of lower than 40 Gy can be effectively used.
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A high red cell distribution width (RDW) and low hemoglobin level increase the risk of arterial ischemic stroke (AIS), mostly in adults. The mechanisms related to AIS remain unknown. A total of 233 subjects (90 patients and 143 healthy controls [HC]) were enrolled. The mean(SD) age in patients and HC was 9.5(3.8) and 11.4(1.8) years, respectively. We found increased odds ratios (ORs) for large vessel and small vessel subtypes in patients without underlying diseases with a mean corpuscular volume (MCV) <80â¯fL (OR: 5.4, 95%CI 1.8-16.3 and 2.8, 95%CI 1.2-7.2), mean corpuscular hemoglobin levels <27â¯pg (OR: 2.9, 95%CI 1.0-6.7 and 2.6, 95%CI 1.0-6.7), and RDW >15% (OR: 5.5, 95%CI 1.3-24.5 and 2.7, 95%CI 1.0-7.3). RBC indices showed significant correlations with TM levels. Therefore, low MCV and MCH levels, and a high RDW were risk factors for AIS and associated with TM levels in this population.
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Eritrócitos/patologia , Acidente Vascular Cerebral/etiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Criança , Índices de Eritrócitos , Feminino , Hemoglobinas/análise , Humanos , MasculinoRESUMO
Medulloblastoma is the most common malignant brain tumor among children. Although molecular study has been included in the new classification, in developing countries with limited resources the previous Chang staging system is still used. Therefore, treatment with postoperative radiation and chemotherapy remains the standard treatment. One common complication after treatment is ototoxicity, mainly due to radiation and cisplatinum. We report a revised chemotherapy protocol, replacing cisplatinum with carboplatin in newly diagnosed medulloblastoma cases. All 23 patients in this study had high risk medulloblastoma. Mean (SD) age was 9.5⯱â¯3.1â¯years. The 5-year progression free survival (PFS), 5-year overall survival (OS), and 10-year OS were 41.8⯱â¯12.2%, 60.0⯱â¯11.2%, and 48.0⯱â¯14.0 respectively. Most patients had grade 3-4 hematologic toxicity. Twelve patients had hearing tests, with 11 patients having grade 0 and 1 patient having grade 1 according to the Brock criteria.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Etoposídeo/uso terapêutico , Meduloblastoma/tratamento farmacológico , Vincristina/uso terapêutico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Lactente , Vincristina/administração & dosagemRESUMO
BACKGROUND: Neurofeedback (NF) is an operant conditioning procedure that trains participants to self-regulate brain activity. NF is a promising treatment for attention-deficit/hyperactivity disorder (ADHD), but there have been only a few randomized controlled trials comparing the effectiveness of NF with medication with various NF protocols. The aim of this study was therefore to evaluate the effectiveness of unipolar electrode NF using theta/beta protocol compared with methylphenidate (MPH) for ADHD. METHODS: Children with newly diagnosed ADHD were randomly organized into NF and MPH groups. The NF group received 30 sessions of NF. Children in the MPH group were prescribed MPH for 12 weeks. Vanderbilt ADHD rating scales were completed by parents and teachers to evaluate ADHD symptoms before and after treatment. Student's t-test and Cohen's d were used to compare symptoms between groups and evaluate the effect size (ES) of each treatment, respectively. RESULTS: Forty children participated in the study. No differences in ADHD baseline symptoms were found between groups. After treatment, teachers reported significantly lower ADHD symptoms in the MPH group (P = 0.01), but there were no differences between groups on parent report (P = 0.55). MPH had a large ES (Cohen's d, 1.30-1.69), while NF had a moderate ES (Cohen's d, 0.49-0.68) for treatment of ADHD symptoms. CONCLUSION: Neurofeedback is a promising alternative treatment for ADHD in children who do not respond to or experience significant adverse effects from ADHD medication.
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Transtorno do Deficit de Atenção com Hiperatividade/terapia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Neurorretroalimentação/métodos , Criança , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Resultado do TratamentoRESUMO
BACKGROUND: Levetiracetam (LEV) is an antiepileptic drug which has good safety and efficacy in neonatal seizure (NS), a common incident in neonates with weight <1500â¯g. The pharmacokinetics for LEV in neonatal populations is yet to be clearly understood. In this study, we developed and validated a method for determination of LEV in plasma by liquid chromatography tandem mass spectrometry for the purpose of pharmacokinetic study. METHODS: Plasma LEV was spiked with Lamivudine as internal standard before extraction by C18 solid-phase extraction (SPE) cartridge. Chromatography was performed using isocratic elution with mobile phase A: B (10: 90) for 2.0â¯min with flow rate 0.4â¯mL/min. The mobile phase was composed of 0.1% formic acid in 10.0â¯mM ammonium acetate (A) and 100% methanol (B). The injection volume was 1.0⯵L and the total run time was 2.0â¯min. Multiple reaction monitoring (MRM) with electro spray in positive mode was used. The mass transition for LEV was 171.2/126.0 and 230.0/112.0 for IS with retention time of 0.73 and 0.72â¯min, respectively. RESULTS: A calibration curve range from 0.50-80.0⯵g/mL was obtained with a correlation coefficient >0.99 in the quadratic model. Precision and accuracy was within the acceptable range and the intra- and inter-day %CV for three concentrations of QCs were <10%. CONCLUSION: This method was reliable, accurate and applicable for LEV pharmacokinetic study in neonates with seizure.
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Cromatografia Líquida/métodos , Piracetam/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Estabilidade de Medicamentos , Feminino , Humanos , Recém-Nascido , Levetiracetam , Modelos Lineares , Masculino , Piracetam/sangue , Piracetam/química , Piracetam/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
GATAD2B gene is involved in chromatin modification and transcription activity. Loss-of-function mutations of GATAD2B have recently been defined to cause a recognizable syndrome with intellectual disability (ID). Human TPM3 gene encoding thin filament protein is associated with myopathies. Both genes are located on chromosome 1q21.3. We herein report an infant with feeding difficulty, developmental delay, hypotonia, and dysmorphic features including small palpebral fissures, telecanthus, sparse hair and eyebrow, cup-shaped ears, and clinodactyly. Karyotype was normal. Single nucleotide polymorphism array revealed a 1.06 Mb deletion of chromosome 1q21.3, which was confirmed to be de novo. The deleted region encompassed 35 genes, including three known disease-associated genes, namely GATAD2B, TPM3, and HAX1. We further identify and summarize seven additional patients with 1q21.3 microdeletion from literature review and clinical databases (DECIPHER, ISCA/ClinGen). Genomic location analysis of all eight patients revealed different breakpoints and no segmental duplication, indicating that non-homologous end joining is a likely mechanism underlying this particular microdeletion. This data suggests that 1q21.3 microdeletion is a recurrent microdeletion syndrome with distinguishable phenotypes, and loss of function of GATAD2B is the major contributor of the characteristic facies and ID. Additionally, the deletion of TPM3 warrants a risk of concomitant muscle disease in our patient. © 2017 Wiley Periodicals, Inc.
Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 1 , Fatores de Transcrição GATA/genética , Fenótipo , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Fácies , Feminino , Estudos de Associação Genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Proteínas Repressoras , SíndromeRESUMO
BACKGROUND: The analysis of fresh frozen muscle specimens is standard following routine muscle biopsy, but this service is not widely available in countries with limited medical facilities, such as Thailand. Nevertheless, immunohistochemistry (IHC) analysis is essential for the diagnosis of patients with a strong clinical suspicion of muscular dystrophy, in the absence of mutations detected by molecular genetics. As the successful labelling of sarcolemmal membrane-associated proteins in formalin-fixed and paraffin-embedded (FFPE) muscle sections using IHC staining has rarely been described, this study aimed to develop a reproducible IHC method for such an analysis. METHODS: Thirteen cases were studied from the files of the Department of Pathology, Mahidol University. Diagnoses included three Duchenne muscular dystrophy (DMD), one Becker muscular dystrophy (BMD), one dysferlinopathy, and several not-specified muscular dystrophies. IHC was performed on FFPE sections at different thicknesses (3 µm, 5 µm, and 8 µm) using the heat-mediated antigen retrieval method with citrate/EDTA buffer, followed by an overnight incubation with primary antibodies at room temperature. Antibodies against spectrin, dystrophin (rod domain, C-terminus, and N-terminus), dysferlin, sarcoglycans (α, ß, and γ), and ß-dystroglycan were used. Frozen sections were tested in parallel for comparative analysis. RESULTS: Antibodies labelling spectrin, dystrophin (rod domain and C-terminus), dysferlin, sarcoglycans (α, ß, and γ), and ß-dystroglycan clearly exhibited sarcolemmal staining in FFPE sections. However, staining of FFPE sections using the antibody directed against the N-terminus of dystrophin was unsuccessful. The absence of labeling for dystrophins and dysferlin in FFPE sections was documented in all three DMD patients and the dysferlinopathy patient. The BMD diagnosis could not be made using IHC in FFPE sections alone because of a lack of staining for the dystrophin N-terminus, indicating a limitation of this method. CONCLUSIONS: We developed a reliable and reproducible IHC technique using FFPE muscle. This could become a valuable tool for the diagnosis of some muscular dystrophies, dystrophinopathies, sarcoglycanopathies (LGMD2D, LGMD2E, and LGMD2C), and dysferlinopathy, especially in situations where the analysis of fresh frozen muscle samples is not routinely available.
Assuntos
Distroglicanas/metabolismo , Distrofina/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Musculares/metabolismo , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofias Musculares/diagnóstico , Sarcoglicanas/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Disferlina , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofias Musculares/metabolismo , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/metabolismo , Inclusão em Parafina , Reprodutibilidade dos Testes , Sarcoglicanopatias/diagnóstico , Sarcoglicanopatias/metabolismoRESUMO
Neurostimulation can be an alternative treatment for medically intractable epilepsy, especially when the resective surgery could not be performed. The author reported a case of 19-year-old, right-handed male patient who had a history of intractable epilepsy for 11 years after post viral encephalitis associated with status epilepticus. Following the failure of antiepileptic medications and then resective surgery, anterior thalamic deep brain stimulation (DBS) was performed. Indirect targeting of anterior thalamic nuclei could not be used because of asymmetric brain shift from prior multilobar resections. Direct targeting of anterior thalamic nuclei from MRI T1 sequence, Short Tau Inversion Recovery (STIR) sequence combined neurophysiological mapping by microelectrode recording were used as a technique for implantation of DBS electrodes. The stimulation was turned on with 145 Hz, pulse width 90 microseconds, 5 volts with cycling mode 1 minute "on" and 5 minutes "0ff". The antiepileptic medications continued the same as pre-operative state. Sixty percent seizure reduction was achieved in 24 months after surgery. There were no side effects of DBS during the follow-up period. Anterior thalamic DBS can be performed safely with satisfactory seizure outcomes. Direct targeting of anterior thalamic nuclei combination with microelectrode recording can be very helpful, especially when asymmetric basal ganglion structures were detected.