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1.
Sci Rep ; 14(1): 4344, 2024 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-38383725

RESUMO

The purpose of this study was to demonstrate the performance of a fully automated, deep learning-based brain segmentation (DLS) method in healthy controls and in patients with neurodevelopmental disorders, SCN1A mutation, under eleven. The whole, cortical, and subcortical volumes of previously enrolled 21 participants, under 11 years of age, with a SCN1A mutation, and 42 healthy controls, were obtained using a DLS method, and compared to volumes measured by Freesurfer with manual correction. Additionally, the volumes which were calculated with the DLS method between the patients and the control group. The volumes of total brain gray and white matter using DLS method were consistent with that volume which were measured by Freesurfer with manual correction in healthy controls. Among 68 cortical parcellated volume analysis, the volumes of only 7 areas measured by DLS methods were significantly different from that measured by Freesurfer with manual correction, and the differences decreased with increasing age in the subgroup analysis. The subcortical volume measured by the DLS method was relatively smaller than that of the Freesurfer volume analysis. Further, the DLS method could perfectly detect the reduced volume identified by the Freesurfer software and manual correction in patients with SCN1A mutations, compared with healthy controls. In a pediatric population, this new, fully automated DLS method is compatible with the classic, volumetric analysis with Freesurfer software and manual correction, and it can also well detect brain morphological changes in children with a neurodevelopmental disorder.


Assuntos
Aprendizado Profundo , Humanos , Criança , Imageamento por Ressonância Magnética/métodos , Hipocampo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Software , Processamento de Imagem Assistida por Computador/métodos
2.
Front Neurol ; 14: 1209796, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37426442

RESUMO

Purpose: This study aimed to discover electrophysiologic markers correlated with clinical responses to vigabatrin-based treatment in infants with epileptic spasms (ES). Method: The study involved a descriptive analysis of ES patients from a single institution, as well as electroencephalogram (EEG) analyses of 40 samples and 20 age-matched healthy infants. EEG data were acquired during the interictal sleep state prior to the standard treatment. The weighted phase-lag index (wPLI) functional connectivity was explored across frequency and spatial domains, correlating these results with clinical features. Results: Infants with ES exhibited diffuse increases in delta and theta power, differing from healthy controls. For the wPLI analysis, ES subjects exhibited higher global connectivity compared to control subjects. Subjects who responded favorably to treatment were characterized by higher beta connectivity in the parieto-occipital regions, while those with poorer outcomes exhibited lower alpha connectivity in the frontal regions. Individuals with structural neuroimaging abnormalities exhibited correspondingly low functional connectivity, implying that ES patients who maintain adequate structural and functional integrity are more likely to respond favorably to vigabatrin-based treatments. Conclusion: This study highlights the potential utility of EEG functional connectivity analysis in predicting early response to treatments in infants with ES.

3.
Front Genet ; 13: 829558, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719373

RESUMO

The complex and evolving nature of clinical phenotypes have made genetically diagnosing pediatric patients with movement disorders difficult. Here, we describe this diverse complexity in the clinical and genetic features of a pediatric cohort examined by whole-exome sequencing (WES) and demonstrate the clinical benefit of WES as a diagnostic tool in a pediatric cohort. We evaluated 75 patients with diverse single or combined movement phenomenologies using WES. WES identified 42 variants in 37 genes (56.0%). The detection rate was highest in patients with dystonia (11/13, 84.6%), followed by ataxia (21/38, 55.3%), myoclonus (3/6, 50.0%), unspecified dyskinesia (1/4, 25.0%), tremor (1/1, 100%), respectively. Most genetically diagnosed patients (90.5%) were affected by other neurologic or systemic manifestations; congenital hypotonia (66.7%), and epilepsy (42.9%) were the most common phenotypes. The genetic diagnosis changed the clinical management for five patients (6.7%), including treatments targeting molecular abnormalities, and other systemic surveillance such as cancer screening. Early application of WES yields a high diagnostic rate in pediatric movement disorders, which can overcome the limitations of the traditional phenotype-driven strategies due to the diverse phenotypic and genetic complexity. Additionally, this early genetic diagnosis expands the patient's clinical spectrum and provides an opportunity for tailored treatment.

4.
Pediatr Int ; 64(1): e15200, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35770792

RESUMO

BACKGROUND: We describe the prevalence, thromboembolic risk factors, and neurologic outcomes in children with congenital heart disease (CHD) and arterial ischemic stroke (AIS). METHODS: We retrospectively analyzed the clinical data of children with CHD and AIS from 2000 to 2016. Demographics, procedural and postprocedural data, neuroimaging findings, details of antithrombotic treatment, and neurological status at last follow up were evaluated. RESULTS: Patients with cyanotic CHD accounted for 24 of 30 cases with AIS. The majority of AIS (70%) was procedure related, and the mean time from procedure to diagnosis of stroke was 9.7 (range, 1-30) days. At the time of AIS, 14 (46.7%) patients revealed coexistence of additional thromboembolic causes of AIS. Three patients (10.0%) experienced recurrent AIS and six patients (20.0%) were diagnosed with post-stroke epilepsy. The unfavorable outcomes were found in 13 patients (43.3%), including four deaths. The unfavorable outcome was significantly associated with the main branch involvement of middle cerebral artery (OR = 10.296, 95% CI = 1.335-79.439) and hemorrhagic transformation (OR = 16.264, 95% CI = 1.359-194.690). CONCLUSIONS: Additional thromboembolic risk factors such as systemic or cardiac thrombus, arrhythmia, and surgical procedures for cyanotic CHD were found in patients with CHD and AIS. The main branch involvement of middle cerebral artery and hemorrhagic transformation were significant predictors of unfavorable outcomes. Further studies are required to identify the target for stroke prevention and develop better prophylactic strategies to minimize AIS in patients with CHD.


Assuntos
Isquemia Encefálica , Cardiopatias Congênitas , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Criança , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Humanos , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
5.
Seizure ; 98: 95-100, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35462301

RESUMO

PURPOSE: To investigate the relationship between the anatomical features of schizencephaly and characteristics of epilepsy. METHODS: We retrospectively evaluated patients diagnosed with schizencephaly using brain magnetic resonance imaging. Seizure outcomes were evaluated as drug-resistant epilepsy and frequent seizures (more than once a month) during the previous year. Development of epilepsy, seizure outcomes, and clinical variables were compared according to the anatomical features of schizencephaly, such as cleft type, size, bilaterality, presence of cortical dysplasia, and temporal lobe involvement. RESULTS: Of the 76 patients with schizencephaly-related epilepsy, 28 (36.8%) had open lip clefts, and 13 (17.1%) had bilateral clefts. The development of epilepsy was related to a larger cleft size and the presence of cortical dysplasia. The patients with medium-to-large clefts were younger at seizure onset than those with small clefts (9.7±7.8 vs. 20.8±10.4 years). Among the 64 patients whose outcomes were evaluated, 31 (48.4%) had drug-resistant epilepsy, and 21 (32.8%) met our definition of frequent seizures. In the univariate analysis, open lip, larger clefts, and the presence of cortical dysplasia were associated with poor seizure outcomes. Even after adjustment for covariates, open lip clefts were significantly related to drug-resistant epilepsy (odds ratio=13.036, P=0.001) and frequent seizures (odds ratio=7.682, P=0.008). CONCLUSION: Open lip clefts were associated with poor seizure outcomes. Further, a larger cleft was related to an earlier development of epilepsy. The anatomical features of schizencephaly should be considered in the treatment of epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Malformações do Desenvolvimento Cortical , Esquizencefalia , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/etiologia , Eletroencefalografia , Epilepsia/complicações , Epilepsia/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Estudos Retrospectivos , Esquizencefalia/complicações , Esquizencefalia/diagnóstico por imagem , Convulsões/complicações , Convulsões/etiologia
6.
Medicine (Baltimore) ; 100(47): e27949, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34964776

RESUMO

ABSTRACT: FOXG1, located at chromosome 14q12, is critical for brain development, and patients with FOXG1 mutation exhibit developmental encephalopathy with high phenotypic variability, known as FOXG1 syndrome. Here, we report 3 cases of FOXG1 syndrome that presented with infantile hypotonia and microcephaly.A total of 145 children with developmental delay and/or hypotonia were evaluated by whole-exome sequencing (WES) in the pediatric neurology clinic and medical genetics center at Asan Medical Center Children's Hospital, from 2017 to 2019. Each FOXG1 mutation was confirmed by Sanger sequencing. The clinical findings of each patient with FOXG1 mutation were reviewed.WES identified de-novo, pathogenic, and heterozygous FOXG1 mutations in 3 of 145 patients in our patient cohort with developmental delay and/or hypotonia. The characteristics of brain magnetic resonance imaging (MRI) were reported as callosal anomaly, decrease in frontal volume, fornix thickening, and hypoplastic olfactory bulbs. A phenotype-genotype correlation was demonstrated as a patient with a novel missense mutation, c.761A > C (p.Tyr254Ser), in the forkhead domain had better outcome and milder brain abnormalities than the other 2 patients with truncating mutation in the Groucho binding domain site, c.958delC (p.Arg320Alafs), or N-terminal domain, c.506dup (p.Lys170GlnfsThe). Importantly, all 3 patients had hypoplastic olfactory bulbs on their brain MRI, which is a distinct and previously unrecognized feature of FOXG1 syndrome.This is the first report of FOXG1 syndrome in a Korean population; this condition accounts for 2% (3 of 145 patients) of our patient cohort with developmental delays and/or hypotonia. Our report contributes to understanding this extremely rare genetic condition in the clinical and genetic perspectives.


Assuntos
Fatores de Transcrição Forkhead/genética , Microcefalia , Hipotonia Muscular/diagnóstico , Proteínas do Tecido Nervoso/genética , Bulbo Olfatório/patologia , Eletroencefalografia , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Microcefalia/diagnóstico por imagem , Microcefalia/genética , Doença dos Neurônios Motores , Hipotonia Muscular/genética , Mutação/genética , Bulbo Olfatório/diagnóstico por imagem , Síndrome de Rett/patologia , Sequenciamento do Exoma
7.
Seizure ; 91: 325-331, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34274892

RESUMO

OBJECTIVES: This study aimed to explore the clinical and neuropsychological characteristics-cognition, behavior, parenting-related stress, and sleep-of children with epilepsy, attention-deficit/hyperactivity disorder (ADHD), or both. METHODS: We retrospectively reviewed the electronic medical records of 33 children with epilepsy and ADHD, 113 with epilepsy alone, and 294 with ADHD alone. The children were required to complete the Advanced Test of Attention (ATA), and their parents completed the ADHD Rating Scale (ARS), Child Behavior Checklist (CBCL), Children's Sleep Habits Questionnaire (CSHQ), Disruptive Behavior Disorder (DBD) Scale (DBD), Social Responsiveness Scale (SRS), and Parenting Stress Index-Short Form (PSI-SF). RESULTS: Auditory Commission Errors made during the ATA were higher in children with epilepsy and ADHD than in those with epilepsy alone. On the SRS, all the subscales except Social Awareness were significantly higher in children with epilepsy and ADHD or ADHD alone than in those with epilepsy alone. The Oppositional Defiant and Conduct Disorder subscales on DBD, Attention Problems, and Aggressive Behaviors on CBCL were significantly higher in children with both epilepsy and ADHD than in those with epilepsy alone. The Parent-Child Dysfunctional Interaction subscales on the PSI-SF were significantly greater in children with both epilepsy and ADHD than in those with epilepsy alone. The subscales on the CSHQ did not significantly differ between children with both epilepsy and ADHD and those with epilepsy alone. CONCLUSIONS: In children with epilepsy, comorbid ADHD was associated with negative effects on response inhibition, aggressive behavior, and parenting-related stress.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Epilepsia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Epilepsia/complicações , Epilepsia/epidemiologia , Humanos , Pais , Estudos Retrospectivos , Sono
8.
Cancers (Basel) ; 13(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205634

RESUMO

PURPOSE: To determine the prognostic indicators for hematopoietic stem cell transplantation (HSCT)-associated neurological complications, the clinical characteristics and brain magnetic resonance imaging (MRI) lesions in pediatric HSCT recipients were reviewed. METHODS: This retrospective study included 51 patients who had underwent a brain MRI due to newly developed neurological symptoms or infection signs during chemotherapy or HSCT. We reviewed the demographics, received treatments, treatment-related morbidities, laboratory findings and brain MRI findings, which were compared between good and poor neurologic outcome groups. RESULTS: Thirty-seven patients (72.5%) fully recovered from the neurologic deficits and fourteen (27.5%) persisted or aggravated. The children with an underlying malignant disease had significantly poorer neurological outcomes (p = 0.015). The neurologic complications associated with infection were more frequent in the poor outcome group (p = 0.038). In the neuroimaging findings, the extent of the white matter lesions was significantly higher in the poor outcome group, as was that of abnormal enhancement, ventriculomegaly, cortical change, deep gray matter abnormalities and cerebellar abnormalities. CONCLUSION: Most children with neurologic complications and neuroimaging abnormalities during HSCT had recovered. However, children with neurologic complications associated with infectious causes, malignant disease or severe brain MRI abnormalities should be more carefully monitored during HSCT.

10.
J Clin Med ; 10(3)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33499362

RESUMO

Seizures in infancy have highly variable courses and underlying etiologies. However, there are only a few long-term follow-up studies regarding infantile-onset epilepsy. Therefore, we aimed to describe the clinical courses, seizure outcomes, and risk factors of infantile-onset epilepsy followed up for more than 10 years in a tertiary center. METHODS: Data of the patients with epilepsy, diagnosed under the age of 12 months and followed up for more than 10 years, were retrieved from the electronic medical records of Asan Medical Center Children's Hospital. The patients' medical records were retrospectively reviewed, and clinical outcomes were assessed based on the duration of seizure freedom at the last follow-up. RESULTS: Of the 146 patients, 103 (70.5%) entered at least one remission, of whom epilepsy was resolved in 46 (31.5%). Forty-nine (33.6%) were found to be intractable at last contact. Delayed development, neurological deficits, and later onset (>3 months) were significantly associated with intractable epilepsies (p < 0.01). CONCLUSIONS: This study demonstrated that many patients with infantile-onset epilepsy can experience seizure remission. However, in some cases, early onset epilepsy was highly associated with various comorbidities and intractable seizures. Therefore, appropriate diagnosis and treatment are necessary to prevent further neuropsychiatric complications.

11.
J Epilepsy Res ; 11(2): 127-135, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35087721

RESUMO

BACKGROUND AND PURPOSE: This study was aimed to describe focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients. METHODS: A total of 82 SCN1A mutation-positive patients were reviewed retrospectively (39 boys and 43 girls). Seizure type and electroencephalography (EEG) findings were investigated according to the stage, disease onset, and steady state (after age 2 years). Long-term video EEG data were used to classify the seizure type. RESULTS: Focal seizures at onset and the steady state were found in 54.9% (45/82) and 90% (63/70) of patients, respectively. Afebrile focal seizures were an initial seizure in about one fourth of the patients (22/82, 26.8%). Of 48 seizures captured during long-term video EEG monitoring of 30 patients, 19 seizures were classified as focal onset (39.6%). Of the 19 focal seizures, 12 were either focal motor or focal non-motor seizures, and seven were focal onset bilateral tonic-clonic seizure. Focal epileptiform discharges were more frequent than generalized epileptiform discharges at seizure onset and during the clinical course on conventional EEG (3.7% vs. 0%, 52.9% vs. 32.9%, respectively). CONCLUSIONS: Our study provides a comprehensive description of focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients. Recognizing these features as defining the clinical spectrum of Dravet syndrome may lead to earlier genetic diagnosis and tailored management.

12.
Medicine (Baltimore) ; 99(51): e23864, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371171

RESUMO

ABSTRACT: Schaaf-Yang syndrome (SYS) is a recently identified disorder caused by a loss-of-function mutation in a maternally imprinted gene, MAGEL2, at 15q11.2q13. Due to its extreme rarity and wide range of clinical severity, clinical suspicion is difficult for a physician. In the current study, its frequency among the Korean pediatric patients with developmental delay (DD) or intellectual disability (ID) was assessed. As the first report of Korean patients with SYS, our study aims to increase the awareness of this condition among the physicians taking care of the pediatric patients with DD/ID and hypotonia.The patients diagnosed with SYS by whole-exome sequencing (WES) among the 460 Korean pediatric patients with DD/ID were included, and their clinical and molecular features were reviewed.Four patients (0.9%) were diagnosed with SYS. Profound DD (4 patients), multiple anomalies including joint contractures and facial dysmorphism (4 patients), generalized hypotonia (3 patients), and severe respiratory difficulty requiring mechanical ventilation (3 patients) were noted in most cases, similar to those in previous reports. Sleep apnea (2 patients), autistic features (2 patients), a high grade of gastroesophageal reflux (1 patient), and seizures (1 patient) were found as well. A total of 3 different truncating MAGEL2 mutations were identified. A previously-reported mutation, to be the most common one, c.1996dupC, was found in 2 patients. The other 2 mutations, c.2217delC and c.3449_3450delTT were novel mutations. As MAGEL2 is maternally imprinted, 2 patients had inherited the MAGEL2 mutation from their respective healthy fathers.SYS is an extremely rare cause of DD/ID. However, hypotonia, joint contractures, profound DD/ID and facial dysmorphism are the suggestive clinical features for SYS. As a maternally imprinted disorder, it should be reminded that SYS may be inherited in form of a mutation from a healthy father.


Assuntos
Síndrome de Prader-Willi/diagnóstico , Proteínas/análise , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Lactente , Masculino , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/genética , Síndrome de Prader-Willi/genética , Proteínas/genética , República da Coreia , Sequenciamento do Exoma/métodos
13.
J Clin Med ; 9(11)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233562

RESUMO

BACKGROUND: The aim of this study was to describe the application of whole exome sequencing (WES) in the accurate genetic diagnosis and personalized treatment of extremely rare neurogenetic disorders. METHODS: From 2017 to 2019, children with neurodevelopmental symptoms were evaluated using WES in the pediatric neurology clinic and medical genetics center. The clinical presentation, laboratory findings including the genetic results from WES, and diagnosis-based treatment and outcomes of the four patients are discussed. RESULTS: A total of 376 children with neurodevelopmental symptom were evaluated by WES, and four patients (1.1%) were diagnosed with treatable neurologic disorders. Patient 1 (Pt 1) showed global muscle hypotonia, dysmorphic facial features, and multiple anomalies beginning in the perinatal period. Pt 1 was diagnosed with congenital myasthenic syndrome 22 of PREPL deficiency. Pt 2 presented with hypotonia and developmental arrest and was diagnosed with autosomal recessive dopa-responsive dystonia due to TH deficiency. Pt 3, who suffered from intractable epilepsy and progressive cognitive decline, was diagnosed with epileptic encephalopathy 47 with a heterozygous FGF12 mutation. Pt 4 presented with motor delay and episodic ataxia and was diagnosed with episodic ataxia type II (heterozygous CACNA1A mutation). The patients' major neurologic symptoms were remarkably relieved with pyridostigmine (Pt 1), levodopa (Pt 2), sodium channel blocker (Pt 3), and acetazolamide (Pt 4), and most patients regained developmental milestones in the follow-up period (0.4 to 3 years). CONCLUSIONS: The early application of WES helps in the identification of extremely rare genetic diseases, for which effective treatment modalities exist. Ultimately, WES resulted in optimal clinical outcomes of affected patients.

14.
Front Neurosci ; 14: 711, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973422

RESUMO

Malformations of cortical development (MCD) is associated with a wide range of developmental delay and drug resistant epilepsy in children. By using resting-state functional magnetic resonance imaging (RS-fMRI) and event-related spectral perturbation (ERSP) of cortical electroencephalography (EEG) data, we tried to investigate the neural changes of spatiotemporal functional connectivity (FC) and fast oscillation (FO) dynamics in a rat model of methylazoxymethanol (MAM)-induced MCD. A total of 28 infant rats with prenatal exposure to MAM and those of age matched 28 controls with prenatal saline exposure were used. RS-fMRI were acquired at postnatal day 15 (P15) and 29 (P29), and correlation coefficient analysis of eleven region of interests (ROI) was done to find the differences of functional networks between four groups. Two hour-cortical EEGs were also recorded at P15 and P29 and the ERSP of gamma (30-80 Hz) and ripples (80-200 Hz) were analyzed. The rats with MCD showed significantly delayed development of superior colliculus-brainstem network compared to control rats at P15. In contrast to marked maturation of default mode network (DMN) in controls from P15 to P29, there was no clear development in MCD rats. The MCD rats showed significantly higher cortical gamma and ripples-ERSP at P15 and lower cortical ripples-ERSP at P29 than those of control rats. This study demonstrated delayed development of FC and altered cortical FO dynamics in rats with malformed brain. The results should be further investigated in terms of the epileptogenesis and cognitive dysfunction in patients with MCD.

15.
Psychiatry Investig ; 17(5): 412-416, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32295327

RESUMO

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of atomoxetine in Korean children and adolescents with epilepsy. METHODS: We retrospectively reviewed the electronic medical records of 105 children and adolescents with epilepsy treated with atomoxetine. Effectiveness was measured with the Clinical Global Impressions-Severity (CGI-S) and/or Clinical Global Impressions-Improvement (CGI-I) scales at baseline, and after 4 and 12 weeks. We defined response to atomoxetine as a CGI-I score less than three at week 12. Safety was evaluated at each visit, based on clinical assessment by a child and adolescent psychiatrist and reports from participants or their caregivers. RESULTS: In total participants (n=105), 33 (31.4%) showed a response to treatment: a significant decrease in CGI-S scale score was observed over 12 weeks of atomoxetine treatment. The most common adverse event (AE) was decreased appetite (n=16, 15.2%), and life-threatening AEs were not observed. Seizure aggravation due to atomoxetine was observed in 7.6% (n=8) of total participants, and one of them discontinued atomoxetine. CONCLUSION: Our results provide preliminary evidence of the effectiveness and safety of atomoxetine in children and adolescents with epilepsy.

16.
Medicine (Baltimore) ; 99(2): e18674, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914058

RESUMO

This study was to develop tablet personal computer-based cognitive training programs for children with developmental disabilities whose cognitive age is less than 4 years. Twelve cognitive training programs (named Injini) were designed comprising cognitive domains that included attention, visual and auditory perception, memory, executive function, language, and reasoning. In addition, programs related to learning experiences, such as self-regulation, role play, learning of number, and letter/shape concepts, comparison, classification, and pattern matching, were included. Six of 12 programs comprised approximately 10 levels for each program, with different difficulty levels. Other programs consisted of universal tasks that did not have a difficulty level. To ensure that the difficulty level was appropriate, we pre-tested the pilot version of Injini among 80 children with typical development aged 18 to 41 months. After modifying the pilot version, we developed the final version and tested it among 80 children with cognitive impairment whose cognitive age was 18 to 41 months. All children were assessed using the Bayley Scales of Infant and Toddler Development to determine their development and cognitive age. The difficulty level analyses in children with typical development revealed several inappropriate results wherein the success rate did not decrease with increase in level in some programs. After adjusting the difficulty level, the analyses in children with cognitive impairment demonstrated that the success rate gradually decreased with increasing level in all programs. Cognitive training programs for children with developmental disabilities were successfully developed.


Assuntos
Cognição , Computadores de Mão , Deficiências do Desenvolvimento/reabilitação , Aprendizagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes
17.
J Med Genet ; 57(2): 124-131, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31649052

RESUMO

BACKGROUND: Ambroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD. METHODS: ABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed. RESULTS: Enhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2-8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events. CONCLUSIONS: Long-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.


Assuntos
Ambroxol/administração & dosagem , Terapia de Reposição de Enzimas , Epilepsias Mioclônicas/tratamento farmacológico , Doença de Gaucher/tratamento farmacológico , Adolescente , Biomarcadores/sangue , Criança , Relação Dose-Resposta a Droga , Epilepsias Mioclônicas/sangue , Epilepsias Mioclônicas/patologia , Feminino , Doença de Gaucher/sangue , Doença de Gaucher/patologia , Glucosilceramidase/sangue , Humanos , Masculino
18.
Eur J Neurosci ; 50(12): 4018-4027, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31397941

RESUMO

Although steroids are suggested as the treatment of choice for infantile spasms, the mechanism of action is still unclear. Using a rat model of malformation of cortical development with refractory infantile spasms, we evaluated the efficacy of methylprednisolone on spasms susceptibility and behaviors. Additionally, we investigated the in vivo electrophysiological and neurochemical changes of the brain after methylprednisolone treatment. Infant rats with prenatal exposure of methylazoxymethanol at gestational day 15 were used. After a single dose of methylprednisolone or three different doses of methylprednisolone for 3 days, spasms were triggered by intraperitoneal injection of N-methyl-d-aspartic acid. In rats with 3 days of methylprednisolone pretreatment and their controls, behavioral testing was performed at postnatal day 15. In vivo magnetic resonance imaging was conducted at postnatal day 15 after 3 days of methylprednisolone treatment. The rats with single methylprednisolone pretreatment showed significantly delayed onset of spasms and multiple doses of methylprednisolone significantly suppressed the development of spasms in a dose-dependent manner. After multiple methylprednisolone pretreatment and a cluster of N-methyl-d-aspartic acid-induced spasms, the rats showed significantly increased freezing behaviors to conditioned stimuli. Glutamate-weighted chemical exchange saturation transfer revealed significant elevation of glutamate concentration in the cortices of the rats with multiple methylprednisolone pretreatments. Methylprednisolone pretreatment could attenuate N-methyl-d-aspartic acid-induced spasms with in vivo neurochemical and electrophysiological changes, which indicates this steroid's action on the brain and in epilepsy.


Assuntos
Encéfalo/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Metilprednisolona/farmacologia , N-Metilaspartato/farmacologia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Metilprednisolona/administração & dosagem , N-Metilaspartato/administração & dosagem , Neurogênese/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos
19.
Occup Ther Int ; 2019: 3026150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863242

RESUMO

BACKGROUND: Computers are used as a means of social communication, for work and other purposes. However, patients with spinal cord injuries may have a higher risk than normal individuals with musculoskeletal problems when using computers owing to their inability to control respective postures due to problems in motor and sensory functioning. OBJECTIVES: This study is aimed at identifying the effect of computer desk heights on musculoskeletal discomforts of the neck and upper extremities and EMG activities in patients with spinal cord (C6) and upper thoracic spinal cord injuries. METHODS: Participants of the present study were the patients diagnosed with ASIA A or B. The patients were divided into two groups according to their spinal cord injuries: C6 group and T2-T6 group. The level of the desk was set at 5 cm below the elbow, at the elbow level, and 5 cm above the elbow level. Electromyography was used to measure the duration of typing task EMG(%RVC) of the cervical erector spinae, upper trapezius, anterior deltoid, and wrist extensor. Subjective musculoskeletal discomfort (Borg-RPE) was measured at the end of the experiment. RESULTS: The two groups showed differences in terms of RPE corresponding to each level of the computer desk (p < .05). Postanalysis revealed the C6 group had decreased RPE as the level of computer desk increased, whereas the subjects in the T2-T6 group had decreased RPE values in accordance with the decreasing level of computer desk (p < .05). In EMG, both groups had no significant differences (p > .05). However, in terms of the interaction between the muscles and the level of computer desk in both groups, the differences in the interactions of the upper trapezius and wrist extensor with each level of the desk were found (p < .05). CONCLUSION: This study is meaningful in that it confirms computer work posture and preference of spinal cord-injured individuals.


Assuntos
Músculos do Dorso/fisiopatologia , Ergonomia , Decoração de Interiores e Mobiliário , Mialgia/fisiopatologia , Músculos do Pescoço/fisiopatologia , Adulto , Vértebras Cervicais/lesões , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Ocupacional , Postura Sentada , Traumatismos da Medula Espinal/fisiopatologia , Vértebras Torácicas/lesões , Extremidade Superior/fisiopatologia
20.
Pediatr Emerg Care ; 35(5): 341-346, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29768295

RESUMO

OBJECTIVES: This study aimed to investigate the clinical features and head magnetic resonance imaging (MRI) findings in children who presented to the emergency department with acute nontraumatic visual disturbance and to study related clinical factors for discovering positive lesions on head MRI. METHODS: We performed a retrospective study of 1-month to 15-year-old children who underwent head MRI as an evaluation for acute nontraumatic visual disturbance as a chief complaint in our pediatric emergency department between March 2010 and March 2015. The symptoms of visual disturbance were blurred vision, diplopia, loss of vision, and visual hallucination. Head MRI findings were considered positive when lesions could explain the symptoms. RESULTS: We identified 39 patients (25 with blurred vision, 9 with diplopia, 3 with loss of vision, and 2 with visual hallucination) with a mean age of 8.35 ± 4.06 years. Positive head MRI findings were identified in 13 patients (33.3%). Brain tumors were most common (53.8%), followed by optic nerve inflammations (23.1%), congenital brain lesions (15.4%), and hypertensive encephalopathy (7.7%). Compared with the negative head MRI group, the positive head MRI group showed significantly less transient visual disturbance (duration <1 hour to complete recovery) (P = 0.001), more limited eye movement (P = 0.003), and more pupillary abnormalities (P = 0.030). CONCLUSIONS: We suggest performing urgent head MRI in children with acute nontraumatic visual disturbance if the symptoms last longer than 1 hour without complete recovery and are accompanied by limited eye movement or pupillary abnormality.


Assuntos
Serviço Hospitalar de Emergência , Imageamento por Ressonância Magnética/métodos , Transtornos da Visão/diagnóstico por imagem , Doença Aguda , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Transtornos da Visão/etiologia
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