RESUMO
OBJECTIVES: There is lack of evidence-based information on the use and timing of endotracheal intubation (ETI) in children with prehospital status epilepticus (SE). METHODS: The aim of this study was to investigate ETI use, timing, risk factors, and outcomes in children presenting to a single-center children's emergency (CE) with prehospital SE, over a 5-year period. RESULTS: A total of 118 events involving children presenting to CE with ongoing prehospital SE were included, and 39% (46/118) of the events required ETI. The most common indication for ETI was respiratory depression. The median time to intubation after arrival at CE was 20.0 minutes (1-155 minutes). Risk factors associated with ETI use include the administration of more than 2 benzodiazepines (26.1% vs 4.2%, P < 0.001) and the use of second- or third-line antiepileptic therapy ( P < 0.001). The use of more than 2 doses of benzodiazepines was found in 12.7% (15/118) of the patients. In patients who received excessive benzodiazepines, 87% (13/15) of them required intubation. CONCLUSIONS: Excessive use of benzodiazepine was found to be a main risk factor for ETI in patients with prehospital SE. Avoidance of the excessive use of benzodiazepines and adhering to clinical management guidelines may reduce the risk for ETI in the CE. The best approach to airway management in children with prehospital SE is lacking and urgently needed.
Assuntos
Anticonvulsivantes , Benzodiazepinas , Serviços Médicos de Emergência , Intubação Intratraqueal , Estado Epiléptico , Humanos , Benzodiazepinas/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/uso terapêutico , Estado Epiléptico/tratamento farmacológico , Masculino , Feminino , Fatores de Risco , Pré-Escolar , Criança , Lactente , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/efeitos adversos , Estudos Retrospectivos , AdolescenteRESUMO
Purpose/Aim: Acute movement disorder is an uncommon presenting symptom in patients with diabetes mellitus. We report a 20-year-old lady with poorly controlled type 1 diabetes, who presented with acute hemichorea and was found to have two rare diabetes-related central nervous complications of diabetic striatopathy and severe moyamoya disease (MMD).Materials and methods: She was treated with aggressive glycemic control; clonazepam and tetrabenazine as well as aspirin stroke prophylaxis for her MMD with resolution of her chorea 3 months later. She subsequently underwent cerebral revascularization surgery for her MMD.Results: This case highlights the possible differentials of acute chorea in diabetic patients and explores the pathophysiological mechanisms that may underlie both conditions in patients with type 1 diabetes.Conclusion: We recommend performing both magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) brain for comprehensive evaluation of diabetic patients with new onset chorea. Prompt and accurate diagnosis is crucial as it guides prognostication and treatment strategies.
Assuntos
Encéfalo/diagnóstico por imagem , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Transtornos dos Movimentos/diagnóstico por imagem , Doença de Moyamoya/diagnóstico por imagem , Angiografia , Encéfalo/patologia , Complicações do Diabetes/diagnóstico por imagem , Complicações do Diabetes/patologia , Diabetes Mellitus Tipo 1/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Transtornos dos Movimentos/complicações , Transtornos dos Movimentos/patologia , Doença de Moyamoya/complicações , Doença de Moyamoya/patologia , Adulto JovemRESUMO
BACKGROUND: Neurological complications with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant have been reported in adults; however, there are little data in the pediatric population. We aimed to report on the prevalence and clinical characteristics of children with neurological symptoms during the SARS-CoV-2 omicron wave. METHODS: This was a single-center, retrospective cohort review of children (<18 years old) hospitalized for SARS-CoV-2 infection from December 2, 2021, to June 30, 2022. RESULTS: During the study period, 455 children (mean age 4.8 years, range 0.67 to 18, male 58.9%) were hospitalized with SARS-CoV-2 infection. A total of 108 (23.7%) children experienced neurological symptoms; most common were seizures (62.0%), headaches (32.4%) and giddiness (14.8%). Seizures included febrile seizures (64.1%), acute symptomatic seizures (17.9%), and breakthrough seizures in known epileptics (17.9%). Children with neurological manifestations were older (7.3 vs 4.0 years, P < 0.00001), more likely to have underlying epilepsy (9.3% vs 1.2%, P = 0.0002) or neurodevelopmental disorders (17.6% vs 1.7%, P < 0.00001), and presented earlier in their illness (2.1 vs 2.8 days, P < 0.00001), compared with those without neurological manifestations. Neurological symptoms fully resolved in all but one patient at discharge. There were no mortalities and no difference in duration of hospitalization (3.1 vs 3.7 days, P = 0.5) between the groups. CONCLUSIONS: One in four hospitalized children with SARS-CoV-2 infection when omicron variant was dominant experienced mild neurological symptoms. Overall risk factors for neurological symptoms associated with SARS-CoV-2 included older age, pre-existing febrile seizures/epilepsy and neurodevelopmental disorders.
Assuntos
COVID-19 , Epilepsia , Convulsões Febris , Criança , Adulto , Masculino , Humanos , Lactente , Pré-Escolar , Adolescente , COVID-19/complicações , SARS-CoV-2 , Criança Hospitalizada , Singapura/epidemiologia , Estudos Retrospectivos , Epilepsia/epidemiologia , Epilepsia/etiologiaRESUMO
Moderate to hyper-expansion of trinucleotide repeats at the FRAXA and FRAXE fragile sites, with or without concurrent hypermethylation, has been associated with intellectual disability and other conditions. Unlike molecular diagnosis of FMR1 CGG repeat expansions in FRAXA, current detection of AFF2 CCG repeat expansions in FRAXE relies on low-throughput and otherwise inefficient techniques combining Southern blot analysis and PCR. A novel triplet-primed PCR assay was developed for simultaneous screening for trinucleotide repeat expansions at the FRAXA and FRAXE fragile sites, and was validated using archived clinical samples of known FMR1 and AFF2 genotypes. Population samples and FRAXE-affected samples were sequenced for the evaluation of variations in the AFF2 CCG repeat structure. The duplex assay accurately identified expansions at the FMR1 and AFF2 trinucleotide repeat loci. On Sanger sequencing of the AFF2 CCG repeat, the single-nucleotide polymorphism variant rs868914124(C) that effectively adds two CCG repeats at the 5'-end, was enriched in the Malay population and with short repeats (<11 CCGs), and was present in all six expanded AFF2 alleles of this study. All expanded AFF2 alleles contained multiple non-CCG interruptions toward the 5'-end of the repeat. A sensitive, robust, and rapid assay has been developed for the simultaneous detection of expansion mutations at the FMR1 and AFF2 trinucleotide repeat loci, simplifying screening for FRAXA- and FRAXE-associated disorders.
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Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Proteínas Nucleares/genética , Expansão das Repetições de Trinucleotídeos , Alelos , Eletroforese Capilar , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: With better medical care, patients with Duchenne muscular dystrophy (DMD) now live longer but face more complex medical and social needs. This study described the perceptions of DMD patients and their families of disease-specific palliative care services in Singapore. MATERIALS AND METHODS: A multicentre, cross-sectional study involving DMD patients and their families was carried out. Structured questionnaires were administered to them to collect data on their understanding of palliative care, health services accessed and desired by them and quality of life. RESULTS: A total of 30 pairs of DMD patients and their caregivers responded. Most patients were >13 years old (70%) and non-ambulant (86%). Most of them and their families (70%) were also not aware of palliative care and support services that were available to them in Singapore. Additionally, they perceived greater financial assistance and better transport services as resources that could better meet their care needs. The presence of scoliosis and need for ventilatory support were associated with lower quality of life in patients. CONCLUSION: There is a need to improve awareness and provision of palliative care services for DMD patients in Singapore where discussion of end-of-life care is often considered taboo. Prevention and correction of scoliosis and provision of appropriate ventilatory support may improve quality of life in DMD patients.
Assuntos
Acessibilidade aos Serviços de Saúde , Distrofia Muscular de Duchenne/terapia , Cuidados Paliativos , Adolescente , Adulto , Cuidadores , Criança , Estudos Transversais , Humanos , Masculino , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/psicologia , Qualidade de Vida , Singapura , Inquéritos e Questionários , Adulto JovemRESUMO
The VARS2 gene encodes a mitochondrial valyl-transfer RNA synthetase which is used in mitochondrial translation. To date, several patients with VARS2 pathogenic variants have been described in the literature. These patients have features of lactic acidosis with encephalomyopathy. We present a case of an infant with lactic acidosis, failure to thrive, and severe primary pulmonary hypertension who was found to be a compound heterozygote for two novel VARS2 variants (c.1940C>T, p.(Thr647Met) and c.2318G>A, p.(Arg773Gln)). The patient was treated with vitamin supplements and a carbohydrate-restricted diet. The lactic acidosis and failure to thrive resolved, and he showed good growth and development. Functional studies and molecular analysis employed a yeast model system and the VAS1 gene (yeast homolog of VARS2). VAS1 genes harboring either one of two mutations corresponding to the two novel variants in the VARS2 gene, exhibited partially reduced function in haploid yeast strains. A combination of both VAS1 variant alleles in a diploid yeast cell exhibited a more significant decrease in oxidative metabolism-dependent growth and in the oxygen consumption rate (reminiscent of the patient who carries two mutant VARS2 alleles). Our results demonstrate the pathogenicity of the biallellic novel VARS2 variants. KEY MESSAGES: ⢠A case of an infant who is a compound heterozygote for two novel VARS2 variants. ⢠This infant displayed lactic acidosis, failure to thrive, and pulmonary hypertension. ⢠Treatment of the patient with a carbohydrate-restricted diet resulted in good growth and development. ⢠Studies with the homologous yeast VAS1 gene showed reduced function of corresponding single mutant in haploid yeast strains. ⢠A combination of both VAS1 variant alleles in diploid yeast exhibited a more significant decrease in function, thereby confirming the pathogenicity of the biallellic novel VARS2 variants.
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Insuficiência de Crescimento/genética , Insuficiência de Crescimento/metabolismo , Antígenos HLA/genética , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Valina-tRNA Ligase/genética , Alelos , Sequência de Aminoácidos , Heterozigoto , Humanos , Lactente , Masculino , Mutação/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Análise de Sequência de DNARESUMO
BACKGROUND: Urea cycle disorders are secondary to defects in the system converting ammonia into urea, causing accumulation of ammonia and other byproducts which are neurotoxic. Ornithine transcarbamylase deficiency is the most common of the urea cycle disorders and frequently presents with coma or seizures during hyperammonemia. However, seizures can also occur without metabolic decompensation. CASE PRESENTATION: We describe a 23-year-old Chinese woman with urea cycle disorder who presented with confusion due to focal seizures arising from the left frontotemporal region. Interestingly, her ammonia levels remained normal during the seizures. Neuroimaging showed bilateral mesial temporal sclerosis. Her seizures were successfully controlled with two anti-epileptic medications. CONCLUSIONS: This case adds evidence of the predisposition of the temporal lobe to injury in urea cycle disorder. Urea cycle disorder can lead to mesial temporal sclerosis which leads to increased susceptibility of patients to seizures regardless of their metabolic state.
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Epilepsias Parciais/diagnóstico , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Distúrbios Congênitos do Ciclo da Ureia/diagnóstico , Eletroencefalografia , Epilepsias Parciais/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Esclerose/complicações , Esclerose/diagnóstico por imagem , Distúrbios Congênitos do Ciclo da Ureia/complicações , Adulto JovemAssuntos
Hidrocefalia , Transiluminação , Humanos , Hidrocefalia/diagnóstico por imagem , Lactente , CrânioRESUMO
BACKGROUND: Leigh syndrome, French-Canadian type is unique to patients from a genetic isolate in the Saguenay-Lac-Saint-Jean region of Québec. It has also been recently described in 10 patients with LRPPRC mutation outside of Québec. It is an autosomal recessive genetic disorder with fatal metabolic crisis and severe neurological morbidity in infancy caused by LRPPRC mutation. METHODS AND RESULTS: The authors report a boy with a novel LRPPRC compound heterozygous missense mutations c.3130C>T, c.3430C>T, and c.4078G>A found on whole-exome sequencing which correlated with isolated cytochrome c-oxidase deficiency found in skeletal muscle. CONCLUSION: LRPPRC mutation is a rare cause of cytochrome c-oxidase-deficient form of Leigh syndrome outside of Québec. Our patient broadens the spectrum of phenotypes of Leigh syndrome, French-Canadian type. LRPPRC mutation should be considered in children with early childhood neurodegenerative disorder, even in the absence of metabolic crisis. Early evaluation with whole-exome sequencing is useful for early diagnosis and for genetic counseling.