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1.
Ann Neurol ; 90(6): 983-987, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34564866

RESUMO

Younger adults with epilepsy have an increased mortality. Some deaths are seizure-related, for example, sudden unexpected death in epilepsy (SUDEP), whereas others, for example, suicide, have multiple causes, including adverse effects of the treatment on mood. In this retrospective population-based study of all Danish persons with epilepsy aged 18 to 49 years during 2007 to 2009 we evaluated the risk of death from seizures and suicide. SUDEP comprised 82.7% of all seizure-related death. Younger adults with epilepsy had an 8.3-fold increased risk of death from seizure-related causes compared with suicide. This underpins the importance of effective seizure control in preventing premature death. ANN NEUROL 2021;90:983-987.


Assuntos
Epilepsia/mortalidade , Convulsões/mortalidade , Morte Súbita Inesperada na Epilepsia , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
2.
Pediatr Res ; 91(4): 879-887, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33790412

RESUMO

BACKGROUND: Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle. METHODS: We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls. RESULTS: Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally. CONCLUSIONS: Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure. IMPACT: It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure.


Assuntos
Síndrome Nefrótica , Substância Branca , Adolescente , Anisotropia , Encéfalo , Criança , Imagem de Tensor de Difusão/métodos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Síndrome Nefrótica/diagnóstico por imagem , Síndrome Nefrótica/tratamento farmacológico , Fascículo Uncinado , Substância Branca/diagnóstico por imagem
3.
Dev Med Child Neurol ; 64(6): 715-722, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34927722

RESUMO

AIM: To investigate reasons for the declining prevalence of cerebral palsy (CP) in children born at term in Denmark by evaluating obstetric and neonatal factors associated with CP, and their changes over time. METHOD: In this cohort study, we included 987 495 children (504 600 [51.1%] males and 482 895 [48.9%] females) born after 37 completed gestational weeks during birth years 1997 to 2013. Risk ratios of CP for each factor were calculated with log-binominal regression analyses. Significant factors were evaluated concerning their development in prevalence over time. RESULTS: In the antenatal period, there were significant associations with an increased risk of CP and high maternal body mass index (BMI), smoking during pregnancy, nulliparity, male sex, gestational age, and low birthweight. In the study period, fewer females smoked during pregnancy and fewer children were born post-term, dropping from 22.6% to 11.4% and 9.4% to 2.5% respectively. Conversely, the proportion of females with high BMI increased. Most significant risk factors were found in the neonatal period, with an increase in children with diagnosed birth defects and children admitted to neonatal care. INTERPRETATION: Reasons for the declining prevalence of CP appear to be multifactorial and likely include the decline in maternal smoking and children born post-term along with centralization and advances in neonatal treatment.


Assuntos
Paralisia Cerebral , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/etiologia , Criança , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Prevalência , Fatores de Risco
4.
Eur J Pediatr ; 181(4): 1547-1555, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35059826

RESUMO

Chronic diseases in children can impact their parents; this may be overlooked in a clinical setting. Our aim was to investigate associations of chronic diseases in children with their parents' employment, health care utilization, mental health, and mortality. In a matched cohort study using nationwide and population-based data in Denmark, we included parents to children (< 18 years) with acute disseminated encephalomyelitis, multiple sclerosis, type 1 diabetes, inflammatory bowel disease, and rheumatoid arthritis/juvenile idiopathic arthritis during 2008-2015. The reference group was parents to unaffected children. Outcomes were parental employment (early retirement, cash benefits, income), health care utilization (e.g., general practitioner, or hospital visits), mental health (visits to psychiatry/psychology clinics, antidepressant drug redemptions), and mortality. We included 13,769 parents with a chronically ill child and 138,606 control parents. Annual income was unaffected for two-parent families after the child's disease onset, but two-parent families had increased hazard of early retirement of 25% (95% CI = 1.01-1.54; p = 0.04). Parents with a chronically ill child had (a) increased rate of antidepressant drug redemptions or psychology/psychiatry visits (hazard ratio 1.37; 95% CI = 1.28-1.46 at 1-year follow-up); (b) increased health care utilization, with an increased marginal mean in primary care of 1% (95% CI = 1.00-1.02; p = 0.005), hospital-affiliated visits of 19% (95% CI = 1.14-1.24; p < 0.0001), and hospital admissions of 14% (95% CI = 1.09-1.20; p < 0.0001); and (c) 69% increased mortality hazard (95% CI = 1.30-2.18; p < 0.0001) in parents younger than 50 years with no comorbidities, albeit small in absolute numbers. CONCLUSION: Pediatric chronic diseases were negatively associated with parental employment, mental health, and mortality, and increased health care utilization. WHAT IS KNOWN: • Studies on the impact of pediatric chronic diseases on parental health are qualitative. • Knowledge is unavailable regarding the impact on parental work, health care utilization, and mortality. WHAT IS NEW: • Among 13,769 parents with a chronically ill child and 138,606 control parents, parents with a chronically ill child had 37% increased antidepressant drug redemptions, and these parents <50 years without comorbidities had 69% increased mortality hazard. • Medical doctors should consider the parental health condition and societal challenges related to having child with a chronic disease.


Assuntos
Saúde Mental , Pais , Criança , Doença Crônica , Estudos de Coortes , Dinamarca/epidemiologia , Emprego , Humanos , Pais/psicologia
5.
Acta Paediatr ; 111(2): 323-335, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34655503

RESUMO

AIM: Children with dyskinetic cerebral palsy (CP) are often severely affected and effective treatment is difficult, due to different underlying disease mechanisms. Comprehensive systematic movement disorder evaluations were carried out on patients with this disorder. METHODS: Patients born from 1995 to 2007 were identified from the Danish Cerebral Palsy Register and referrals to the neuropaediatric centre, Rigshospitalet, Copenhagen. They were classified by gross motor function, manual functional ability, communication ability, dystonia and spasticity. Electromyography was carried out on the upper and lower limbs. Magnetic resonance imaging scans were revised, and aetiological searches for underlying genetic disorders were performed. RESULTS: We investigated 25 patients with dyskinetic CP at a mean age of 11.7 years. Dystonia, spasticity and rigidity were found in the upper limbs of 21, four and six children, respectively, and in the lower limbs of 18, 18 and three children. The mean total Burke-Fahn-Marsden score for dystonia was 45.02, and the mean Disability Impairment Scale level was 38% for dystonia and 13% for choreoathetosis. Sustained electromyography activity was observed in 20/25 children. Stretching increased electromyography activity more in children with spasticity. There were 10 re-classifications. CONCLUSION: The children had heterogenic characteristics, and 40% were reclassified after systematic movement disorder evaluation.


Assuntos
Paralisia Cerebral , Distonia , Transtornos dos Movimentos , Paralisia Cerebral/complicações , Paralisia Cerebral/diagnóstico , Criança , Eletromiografia , Humanos , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/etiologia , Índice de Gravidade de Doença
6.
Epilepsia ; 62(10): 2405-2415, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34418071

RESUMO

OBJECTIVE: Persons with epilepsy have an increased mortality including a high risk of sudden unexplained death (SUD), also referred to as sudden unexpected death in epilepsy (SUDEP). We aimed to evaluate the risk of SUDEP in comparison to other causes of death and the risk of SUD in persons with and without epilepsy. METHODS: We undertook a retrospective population-based cohort study of all Danish citizens with and without epilepsy aged 1-49 years during 2007-2009. All deaths in the population were evaluated, and all cases of SUD identified. Primary causes of death in persons with epilepsy were evaluated independently by three neurologists and one neuropediatrician, using the unified SUDEP criteria. RESULTS: The three most frequent causes of death in persons with epilepsy were cancer (2.38 per 1000 person-years), SUDEP (1.65 per 1000 person-years), and pneumonia (1.09 per 1000 person-years) compared with cancer (.17 per 1000 person-years), accident-related deaths (.14 per 1000 person-years), and cardiovascular disease (.09 per 1000 person-years) in persons without epilepsy. Considering definite, definite plus, and probable cases, the SUDEP incidence was .27 per 1000 person-years (95% confidence interval [CI] = .11-.64) in children aged 1-17 years and 1.21 per 1000 person-years (95% CI = .96-1.51) in adults aged 18-49 years. Adjusted for age and sex, persons with epilepsy younger than 50 years had a 10.8-fold (95% CI = 9.97-11.64, p < .0001) increased all-cause mortality and a 34.4-fold (95% CI = 23.57-50.28, p < .0001) increased risk of SUD compared with persons without epilepsy. SUDEP accounted for 23.3% of all SUD. SIGNIFICANCE: This nationwide study of all deaths in persons with epilepsy younger than 50 years found a lower SUDEP risk in children compared with adults, and that epilepsy was a major risk factor for SUD in the background population. This underlines the importance of addressing risk factors for SUDEP to prevent premature death.


Assuntos
Epilepsia , Morte Súbita Inesperada na Epilepsia , Adulto , Criança , Estudos de Coortes , Morte Súbita/epidemiologia , Morte Súbita/etiologia , Dinamarca/epidemiologia , Epilepsia/complicações , Humanos , Estudos Retrospectivos , Fatores de Risco
7.
Epilepsy Behav ; 111: 107330, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32759075

RESUMO

PURPOSE: The purpose of the study was to explore the impact of timing and test specificity of cognitive outcome measures after pediatric epilepsy surgery. METHODS: A consecutive national cohort of 114 children with medically resistant epilepsy having had resective epilepsy surgery were screened for children tested with a complete age-appropriate Wechsler Intelligence test at two or three time-points. This provided 43 children for analyses. Composite subscale scores were assessed in comparison to index and intelligence quotient (IQ) scores. RESULTS: We found a main effect of time in seizure-free children for full-scale IQ (FSIQ); F(2, 42) = 6.49 with higher T2 measures compared with T1 (MDiff = 5.46, p = .006). There was a difference in FSIQ scores between seizure-free and nonseizure-free children at T2; M = 7.31, 95% confidence interval (CI) [0.05 to 14.57], t(38) = 2.04, p = .049, favoring seizure-free children. A statistical difference between composite scale scores and index scores was found with medium to large effect. The correlation of medical treatment (anti-epileptic drug (AED)) change and score differences in FSIQ outcome was significant (p = .041), with less AED correlated with a higher FSIQ. All children with left-temporal surgery had a stable or improved verbal comprehension composite subscale score outcome at T2 regardless of seizure status. CONCLUSION: Our results correspond to some longitudinal studies with outcome measures >2 years, in contrast to short-term studies ≤2 years with a stable outcome. Our study supports the fact that the specificity of the used tests and the timing of assessments after pediatric epilepsy surgery are essential factors for the clinical validity of outcome measures. However, there are further needs of extensive longitudinal studies to provide a better understanding of life-long cognitive development and impact after childhood epilepsy surgery.


Assuntos
Cognição/fisiologia , Epilepsia Resistente a Medicamentos/psicologia , Epilepsia Resistente a Medicamentos/cirurgia , Cuidados Pós-Operatórios/psicologia , Cuidados Pós-Operatórios/tendências , Adolescente , Criança , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Estudos de Coortes , Epilepsia Resistente a Medicamentos/diagnóstico , Feminino , Humanos , Testes de Inteligência , Estudos Longitudinais , Masculino , Resultado do Tratamento
8.
Genet Med ; 21(2): 398-408, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30093711

RESUMO

PURPOSE: To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants. RESULTS: The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign. CONCLUSION: Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.


Assuntos
Epilepsia/genética , Proteínas Ativadoras de GTPase/genética , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Síndrome de Brugada/genética , Síndrome de Brugada/mortalidade , Síndrome de Brugada/fisiopatologia , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Epilepsia/complicações , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Mutação INDEL/genética , Lactente , Recém-Nascido , Mutação com Perda de Função/genética , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Complexos Multiproteicos/genética , Linhagem , Convulsões/complicações , Convulsões/epidemiologia , Convulsões/genética , Convulsões/fisiopatologia , Transdução de Sinais/genética
11.
Mult Scler ; 25(6): 783-791, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29770725

RESUMO

BACKGROUND: Infections are suspected environmental triggers for multiple sclerosis (MS). The relationship between the timing and cumulative number of childhood infections regarding pediatric MS risk is uninvestigated. OBJECTIVES: To investigate whether childhood infections contribute to pediatric MS. METHODS: A nationwide nested case-control study with detailed MS case ascertainment including chart review was undertaken. For each MS case, we selected five control children using density sampling from the entire Danish population, matching controls to children with MS by sex and birthdate. We analyzed data with the cumulative number of childhood infections as exposure and MS as outcome. Hazard ratios (HRs) including 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS: We identified 212 children with MS and 1,060 controls. Median age at MS onset was 15.3 years (range: 7.6-17.8 years); 72% were girls. Each infection during the preceding 3 years increased the hazard for MS by 11% (95% CI = 1.01-1.22, p = 0.04); having 5+ infections compared with 0-4 infections in the preceding 3 years doubled the hazard for MS (HR: 2.18; 95% CI = 1.12-4.30, p = 0.02). CONCLUSION: Children with MS appeared to have more infections in the 3 years preceding MS clinical onset; accordingly, immune response to infections may influence MS pathogenesis.


Assuntos
Infecções/epidemiologia , Esclerose Múltipla/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adolescente , Estudos de Casos e Controles , Criança , Dinamarca/epidemiologia , Feminino , Humanos , Infecções/complicações , Masculino , Esclerose Múltipla/etiologia , Risco
12.
Acta Paediatr ; 108(10): 1850-1856, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30933377

RESUMO

AIM: We aimed at describing clinical findings in children with dyskinetic as compared to bilateral spastic cerebral palsy (CP). METHODS: Data were extracted from the Danish nationwide CP register. Participants were born in 1999-2007 and were 5-6 years at ascertainment. RESULTS: The total number of CP cases was 1165 of which 92 had dyskinetic and 540 bilateral spastic CP. Prevalence of dyskinetic CP was 0.16 per 1000 live births. In participants with dyskinetic compared to bilateral spastic CP, there was more frequently an Apgar level less than five at five minutes (22.7% vs. 11.2%) and neonatal seizures (43.5% vs. 28.5%), but less respiratory deficiency, hyperbilirubinaemia and sepsis. Impairment based on gross motor function classification was more severe in dyskinetic CP (level III-V 90.0% vs. 66.0%). In dyskinetic CP, there was a high rate of reduced developmental quotient (68.1%), visual impairment (39.3%) and epilepsy (51.6%). Basal ganglia lesions were more prevalent in dyskinetic compared to bilateral spastic CP (27.7% vs. 12.8%). CONCLUSION: Cases of dyskinetic CP had overlapping clinical features with cases of bilateral spastic CP, but differed significantly in several perinatal risk factors. The children with dyskinetic CP had experienced more peri- or neonatal adverse events, and neurodevelopmental impairment was severe.


Assuntos
Paralisia Cerebral/epidemiologia , Sistema de Registros , Paralisia Cerebral/complicações , Paralisia Cerebral/diagnóstico por imagem , Criança , Pré-Escolar , Dinamarca/epidemiologia , Epilepsia/etiologia , Feminino , Humanos , Recém-Nascido , Masculino , Neuroimagem , Gravidez , Prevalência
13.
Mult Scler ; 24(8): 1077-1086, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28608742

RESUMO

BACKGROUND: The incidence of acquired demyelinating syndromes (ADS) including multiple sclerosis (MS) has never been investigated in a Danish pediatric population. OBJECTIVES: We estimated the nationwide age- and sex-specific incidence of pediatric ADS including MS. METHODS: Data were sourced from the Danish Multiple Sclerosis Registry, providing cases of pediatric MS for 1977-2015, and the National Patient Register, providing cases of ADS during 2008-2015. All medical records were reviewed to validate the register-based diagnoses. RESULTS: We identified 364 cases of pediatric MS occurring during 1977-2015 (incidence rate = 0.79 per 100,000 person-years). MS was exceptionally rare before puberty, but the incidence rose considerably from 9 years in girls and 11 years in boys. The female-to-male ratio was 2.5; the median age at onset was 16 years (range = 7-17 years). The MS incidence rate was relatively stable through the study period. During 2008-2015, we identified 219 ADS cases. The incidence was 2.29 per 100,000 person-years with considerable differences in the age peaks for the separate ADS. CONCLUSION: The incidence rates of MS and other ADS in Denmark were higher than those reported for some other European countries. Referral bias and classification differences may account for this disparity, in particular the age-intervals and the definition of onset.


Assuntos
Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/epidemiologia , Esclerose Múltipla/epidemiologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Sistema de Registros
14.
Pediatr Res ; 83(4): 804-812, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29252981

RESUMO

BackgroundPerinatal exposure to glucocorticoids and elevated endogenous glucocorticoid levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid treatment during childhood on brain volumes.MethodsA total of 30 children and adolescents with rheumatic or nephrotic disease previously treated with glucocorticoids and 30 controls matched on age, sex, and parent education underwent magnetic resonance imaging (MRI) of the brain. Total cortical gray and white matter, brain, intracranial volume, and total cortical thickness and surface area were derived from MRI scans.ResultsPatients had significantly smaller gray and white matter and total brain volumes relative to healthy controls. Brain volume differences disappeared when accounting for intracranial volume, as patients had relatively smaller intracranial volumes. Group differences were mainly driven by the children with rheumatic disease. Total cortical thickness and cortical surface area did not significantly differ between groups. We found no significant associations between glucocorticoid-treatment variables and volumetric measures.ConclusionObserved smaller total brain, cortical gray, and white matter volumes in children and adolescents previously treated with glucocorticoids compared with that in healthy controls may reflect both developmental and degenerative processes. Prospective longitudinal studies are warranted to clarify whether findings are related to treatment or disease.


Assuntos
Encéfalo/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Nefropatias/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Substância Branca/patologia , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Masculino , Síndrome Nefrótica/tratamento farmacológico , Reconhecimento Automatizado de Padrão
15.
Dev Med Child Neurol ; 60(11): 1123-1131, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29744874

RESUMO

AIM: The International Paediatric Multiple Sclerosis Study Group (IPMSSG) has proposed criteria for acute disseminated encephalomyelitis (ADEM) not evaluated in clinical practice. Our objective was to assess epidemiological implications of the IPMSSG criteria for ADEM in a cohort study using prospectively collected data. METHOD: We identified all diagnosed cases of ADEM in Denmark between 2008 and 2015 from the Danish National Patient Register by International Classification of Diseases 10 codes assigned to acute demyelinating episodes, and we reviewed all medical records to validate ADEM. RESULTS: We found 52 children up to the age of 18 years with a verified clinical diagnosis of ADEM (incidence rate 0.54/100 000 person-years; all had abnormal brain magnetic resonance imaging). Only 18 (35%) fulfilled the IPMSSG criteria regarding encephalopathy and polyfocal neurological deficits. Among all 52 children with ADEM, 33 per cent had clinical sequelae after a median follow-up of 4 years 6 months (range: 10mo-8y 3mo). Surprisingly, none progressed to multiphasic ADEM or multiple sclerosis, but median age at end of follow-up was only 10 years 9 months (range: 2y-24y 3mo). INTERPRETATION: Among 52 children with ADEM, none converted to multiphasic ADEM or multiple sclerosis (median follow-up: 4y 6mo; range: 10mo-8y 3mo). Applying the IPMSSG criteria to all children with a diagnosis of ADEM leaves 65 per cent of the cases without a diagnosis and lowers the incidence rate of paediatric ADEM. WHAT THIS PAPER ADDS: The incidence of paediatric acute disseminated encephalomyelitis (ADEM) was 0.54 per 100 000 person-years in children younger than 18 years. Only 35 per cent of children with ADEM fulfilled the International Paediatric Study Group consensus criteria. ADEM in clinical practice was primarily based on magnetic resonance imaging findings. Paediatric neurologists diagnosed ADEM in the absence of encephalopathy. None of the children with ADEM progressed to multiple sclerosis/multiphasic ADEM during follow-up.


Assuntos
Encefalomielite Aguda Disseminada/diagnóstico , Encefalomielite Aguda Disseminada/epidemiologia , Adolescente , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Consenso , Dinamarca , Feminino , Seguimentos , Humanos , Incidência , Lactente , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla , Sistema de Registros , Adulto Jovem
16.
BMC Pediatr ; 18(1): 181, 2018 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-29855286

RESUMO

BACKGROUND: Cerebral palsy is the most frequent motor disability in childhood, but little is known about its etiology. It has been suggested that cerebral palsy risk may be increased by prenatal thyroid hormone disturbances. The objective of this study was to investigate whether maternal thyroid disorder is associated with increased risk of cerebral palsy. METHODS: A population-based cohort study using two study populations. 1) 1,270,079 children born in Denmark 1979-2007 identified in nationwide registers, and 2) 192,918 children born 1996-2009 recruited into the Danish National Birth Cohort and The Norwegian Mother and Child Cohort study, combined in the MOthers and BAbies in Norway and Denmark (MOBAND) collaboration cohort. Register-based and self-reported information on maternal thyroid disorder was studied in relation to risk of cerebral palsy and its unilateral and bilateral spastic subtypes using multiple logistic regression. Children were followed from the age of 1 year to the age of 6 years, and cerebral palsy was identified in nationwide registers with verified diagnoses. RESULTS: In register data, hypothyroidism was recognized in 12,929 (1.0%), hyperthyroidism in 9943 (0.8%), and unclassifiable thyroid disorder in 753 (< 0.1%) of the mothers. The odds ratio for an association between maternal thyroid disorder and bilateral spastic cerebral palsy was 1.0 (95% CI: 0.7-1.5). Maternal thyroid disorder identified during pregnancy was associated with elevated risk of unilateral spastic cerebral palsy (odds ratio 3.1 (95% CI: 1.2-8.4)). In MOBAND, 3042 (1.6%) of the mothers reported a thyroid disorder in pregnancy, which was not associated with cerebral palsy overall (odds ratio 1.2 (95% CI: 0.6-2.4)). CONCLUSIONS: Maternal thyroid disorder overall was not related to bilateral spastic cerebral palsy, but maternal thyroid disorder identified in pregnancy was associated with increased risk of unilateral spastic cerebral palsy. These findings should be replicated in studies making use of maternal blood samples.


Assuntos
Paralisia Cerebral/epidemiologia , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Doenças da Glândula Tireoide/complicações , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Noruega/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Sistema de Registros , Fatores de Risco , Doenças da Glândula Tireoide/epidemiologia , Adulto Jovem
18.
Dev Psychobiol ; 59(8): 1010-1020, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28888057

RESUMO

Heightened levels of glucocorticoids in children and adolescents have previously been linked to prolonged changes in the diurnal regulation of the stress-hormone cortisol, a glucocorticoid regulated by the hypothalamic-pituitary-adrenal-axis (HPA-axis). To address this question, we examined the salivary cortisol awakening response (CAR) and daily cortisol output in 36 children and adolescents (25 girls/11 boys) aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder and 36 healthy controls. Patients and controls did not significantly differ in the CAR or diurnal cortisol output; however, sex-dependent group differences were observed. Specifically, female patients had a higher CAR relative to female controls, while male patients had higher daily cortisol levels compared to male controls. Notably, CAR in female patients and daily cortisol levels in male patients showed a positive linear relationship with the mean daily glucocorticoid doses administered during treatment. The observed dose-response associations suggest that glucocorticoid therapy during childhood and adolescence might trigger long-term changes in HPA-axis regulation, which may differ for males and females.


Assuntos
Ritmo Circadiano/fisiologia , Glucocorticoides/farmacologia , Hidrocortisona/metabolismo , Adolescente , Criança , Ritmo Circadiano/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Síndrome Nefrótica/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Fatores Sexuais
19.
Epilepsia ; 56(12): e203-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26537434

RESUMO

The first mutations identified in SLC2A1, encoding the glucose transporter type 1 (GLUT1) protein of the blood-brain barrier, were associated with severe epileptic encephalopathy. Recently, dominant SLC2A1 mutations were found in rare autosomal dominant families with various forms of epilepsy including early onset absence epilepsy (EOAE), myoclonic astatic epilepsy (MAE), and genetic generalized epilepsy (GGE). Our study aimed to investigate the possible role of SLC2A1 in various forms of epilepsy including MAE and absence epilepsy with early onset. We also aimed to estimate the frequency of GLUT1 deficiency syndrome in the Danish population. One hundred twenty patients with MAE, 50 patients with absence epilepsy, and 37 patients with unselected epilepsies, intellectual disability (ID), and/or various movement disorders were screened for mutations in SLC2A1. Mutations in SLC2A1 were detected in 5 (10%) of 50 patients with absence epilepsy, and in one (2.7%) of 37 patient with unselected epilepsies, ID, and/or various movement disorders. None of the 120 MAE patients harbored SLC2A1 mutations. We estimated the frequency of SLC2A1 mutations in the Danish population to be approximately 1:83,000. Our study confirmed the role of SLC2A1 mutations in absence epilepsy with early onset. However, our study failed to support the notion that SLC2A1 aberrations are a cause of MAE without associated features such as movement disorders.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/epidemiologia , Epilepsias Mioclônicas/genética , Epilepsia Tipo Ausência/genética , Transportador de Glucose Tipo 1/genética , Proteínas de Transporte de Monossacarídeos/deficiência , Erros Inatos do Metabolismo dos Carboidratos/genética , Pré-Escolar , Dinamarca/epidemiologia , Epilepsia Generalizada/genética , Transportador de Glucose Tipo 1/deficiência , Transportador de Glucose Tipo 1/fisiologia , Humanos , Lactente , Proteínas de Transporte de Monossacarídeos/genética , Mutação , Síndrome
20.
Dev Med Child Neurol ; 57(8): 768-75, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26154654

RESUMO

AIM: To analyse the social situation of parents who have a child with cerebral palsy (CP). METHOD: This was a population-based longitudinal study with linkage to public registries. Parents of children with CP (n=3671) identified in the Danish CP Registry were compared with 17,983 parents of children without CP. Employment, income, cohabitation status, and presence of additional children were factors analysed during a follow-up period of 28 years. We followed parents from before their child was born and up to the age of 43 years of the child. RESULTS: Mothers of children with CP under the age of 10 were less often employed: odds ratio [OR] of employment at age 5y 0.45 (95% confidence interval [CI] 0.36-0.57), but only 11% left the labour market. Mothers of children without CP had higher incomes: ratio full-time working 1.11 (95% CI 1.07-1.15). The risk of not living together was not increased among parents of children with CP: at age 5 years OR 1.04 (95% CI 0.84-1.28). Parents of children with CP as the first born postponed or more seldom had subsequent children: hazard ratio [HR] 0.75 (95% CI 0.68-0.83). INTERPRETATION: The Danish welfare system seems to have succeeded in keeping parents in the labour market and living together with their child. Special attention needs to be paid to the financial situation of families with children with CP under 10 years of age.


Assuntos
Paralisia Cerebral , Emprego/estatística & dados numéricos , Características da Família , Renda/estatística & dados numéricos , Mães/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Dinamarca , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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