RESUMO
Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients' quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of "metabolic memory" in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.
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Neuropatias Diabéticas/genética , Epigênese Genética , Epigenômica , Animais , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/terapia , Predisposição Genética para Doença , Humanos , Inflamação/patologia , Sistema Nervoso Periférico/patologia , Sistema Nervoso Periférico/fisiopatologiaRESUMO
Background and Aim: Adverse effects are common in children treated with antiepileptic medications and may affect parental beliefs about treatment. The aim of the study was to investigate the relationship between adverse effects and parental beliefs about antiepileptic drugs used for the treatment of their children. Methods: The study was performed at the University Children's Hospital, Belgrade, Serbia from 2013â»2015. Parents of children treated with valproic acid, carbamazepine or lamotrigine, were eligible. They were asked to fill in the Beliefs about Medications Questionnaire (BMQ) and The Liverpool Adverse Events Profile (LAEP). Results: Parents of 127 children (average age 9.88 ± 4.16 years) of whom 111 had epilepsy (67 generalized, 44 focal) and 16 with febrile seizures participated in the study. Nervousness and/or agitation, weight gain, restlessness, headache, difficulty in concentrating, feeling of aggression and upset stomach were most frequent adverse effects, reported in 37% of the population. BMQ-specific necessity scores significantly correlated with parental education; parents with elementary school showed lower scores than those with higher education. The presence of difficulty in concentrating of their child was associated with higher BMQ concern scores (20.73 ± 4.25 vs. 18.99 ± 3.60, p = 0.043) as well as necessity scores (18.42 ± 3.31 vs. 16.40 ± 2.73, p = 0.017). Higher scores of BMQ-general overuse were reported in the presence of a headache (8.79 ± 2.81 vs. 7.64 ± 2.72, p = 0.027). Conclusions: The main finding of our study is that parental beliefs about antiepileptic drugs were associated with the presence of adverse effects. Understanding this relationship could allow physicians and pharmacists to structure better educational programs for parents of children treated with antiepileptic drugs. Education should be more focused towards understanding the adverse effects of antiepileptics which could alleviate parental concerns and strengthen their beliefs about the necessity of medication use in their children.
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Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Pais/psicologia , Inquéritos e Questionários , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Epilepsia/psicologia , Feminino , Humanos , Lactente , Masculino , SérviaRESUMO
Long-term studies indicated changes in aspects of cognition, psychopathology, and quality of life (QOL) in children and adolescents followed up after the diagnosis of epilepsy. However, evidence is limited regarding what happens during the first few months after epilepsy is diagnosed because at this phase is possible to adjust and/or change an AED regimen or add other treatment interventions, if needed. This is a naturalistic, six months follow-up study that evaluated changes in overall cognitive profiles, levels of psychopathological symptoms, and quality of life (QOL) in newly diagnosed, uncomplicated pediatric epilepsy. In total, 61 (35 [57.4%] males) children and adolescents aged 7-18 years were assessed at the time of diagnosis and the initiation of antiepileptic drug (AED) treatment and six months afterward. The Revised Wechsler Intelligence Scale for Children, the Revised Child Anxiety and Depression Scale (RCADS), Nisonger Child Behavior Rating Form for typically developing children and adolescents (NCBRF), KIDSCREEN-10 Quality of Life Measure, and Adverse Event Profile (AEP) were used. The RCADS and NCBRF scores significantly increased over time, while the KIDSCREEN-10 scores significantly decreased. The most significant increases were observed in scores measuring social phobia and depressive symptoms and inattentiveness. Verbal cognitive abilities and full-scale intelligence scores changed slightly, while more changes were found in aspects of non-verbal cognitive abilities. This study showed that six months after epilepsy diagnosis and AED initiation, there were marked increases in anxiety levels, depressive symptoms, and behavioral problems, with deteriorations in QOL, while cognitive changes were relatively minimal. Therefore, monitoring levels of psychopathological symptoms and QOL in newly diagnosed epilepsy is highly recommended.
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Magnesium is frequently used for pediatric migraine prophylaxis. The aim of this study was to evaluate to which extent the disability levels, quality of life (QOL), and anxiety and depressive symptoms change after 6-month magnesium prophylaxis in pediatric migraine. This is a follow-up study of 34 children aged 7-17 years with migraine treated with oral magnesium. Disability due to migraine was assessed by the Pediatric Migraine Disability Assessment tool (PedMIDAS), QOL was assessed by the KIDSCREEN-27, and anxiety and depressive symptoms were assessed by the Revised Child Anxiety and Depression Scale (RCADS). PedMIDAS scores significantly decreased from baseline to end-point (F(df, dferror) = 11.10 (1.63, 50.49), p<0.001), as well as anxiety (F(df, dferror) = 8.95 (1.64, 50.67), p = 0.001) and depressive symptoms (F(df, dferror) = 8.91 (1.59, 49.29), p = 0.001). Considering the KIDSCREEN-27, scores for physical and psychological well-being and social support domain significantly increased from baseline to end-point (p≤0.01). After 6 months of magnesium prophylaxis, disability due to migraine significantly decreased, whereas physical and psychosocial well-being improved. Children also reported fewer anxiety and depressive symptoms. More follow-up and randomized controlled clinical trials are needed to propose clinical recommendations for magnesium prophylaxis in pediatric migraine.
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Ansiedade/complicações , Ansiedade/tratamento farmacológico , Depressão/complicações , Depressão/tratamento farmacológico , Magnésio/uso terapêutico , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/tratamento farmacológico , Qualidade de Vida , Criança , Seguimentos , HumanosRESUMO
To identify potential risk factors for the development of subclinical hypothyroidism following long-term valproic acid monotherapy in children with epilepsy. Serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyreoglobulin antibodies, and thyroid peroxidase antibodies were determined in 41 patients and in 41 sex- and age-matched healthy children. Mean valproic acid treatment duration was 2.80±1.96 years. The valproic acid group had higher serum thyroid-stimulating hormone (p<0.001) and free triiodothyronine (p<0.05) levels compared to the control group. Serum thyroid-stimulating hormone and free triiodothyronine were above the upper limit for healthy controls in 34% and 32% of patients, respectively, and no clinical features of thyroid dysfunction were observed. Duration of valproic acid monotherapy for less than four years was a risk factor for elevated thyroid-stimulating hormone levels. One third of children with normal range serum valproic acid levels may have elevated serum thyroid-stimulating hormone and free triiodothyronine levels, especially in the first four years of treatment.
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Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Ácido Valproico/efeitos adversos , Adolescente , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Estudos Transversais , Epilepsia/sangue , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Masculino , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tireotropina/sangue , Fatores de Tempo , Resultado do Tratamento , Tri-Iodotironina/sangue , Ácido Valproico/uso terapêutico , Adulto JovemRESUMO
INTRODUCTION: Parenteral nutrition-associated cholestasis is well recognized phenomenon in the term and preterm infant receiving long-term parenteral nutrition. OBJECTIVES: The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) use on cholestasis in newborns on prolonged TPN. METHODS: A total of 56 infants were enrolled in this retrospective study: control group consisted of lower (1500 g) birth weight infants (n = 30), as well as the group of pediatric (n = 11) and surgical patients (n = 15) treated with UDCA. Blood chemistries were obtained two times weekly. RESULTS: All of 56 newborns developed cholestasis but duration of parenteral nutrition (PN) before onset of cholestasis was significantly longer in UDCA treated patients. Average duration of PN before the onset of cholestasis in control group of patients was 25 days in distinction from treated pediatric and surgical patients (39 and 34 days, respectively).The peak serum conjugated bilirubin (CB), AST, ALT and alkaline phosphatase (AP) levels were significantly lower in the treated groups.There was no significant difference among treated pediatric and surgical patients and between lower and higher birth weight infants considering the CB, ALT, AST and AP peak. Duration of cholestasis was significantly decreased in all treated groups.There was a significant difference in time needed to achieve complete enteral intake between pediatric and surgical patient group. CONCLUSION: Cholestasis developed significantly later in treated groups than in the controls. UDCA appears to be very successful in reducing the symptoms of cholestasis. The difference in efficacy of UDCA treatment between lower and higher birth weight infants could not be proven.
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Colestase/etiologia , Colestase/prevenção & controle , Nutrição Parenteral/efeitos adversos , Ácido Ursodesoxicólico/uso terapêutico , Peso ao Nascer/efeitos dos fármacos , Estudos de Casos e Controles , Colestase/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Retrospectivos , Nascimento a TermoRESUMO
INTRODUCTION: The prevalence of microalbuminuria (MA), the most important early marker of incipient nephropathy in patients with type 1 diabetes mellitus (T1DM), increases during puberty, the period of exaggerated physiological insulin resistance. OBJECTIVE: To assess the prevalence of MA and the relationship between MA and metabolic risk factors and pubertal hormones in adolescents with T1DM. METHODS: In a cross-section study involving a group of 100 adolescents of both sexes of mean age 14.90+/-2.18 years and with mean duration ofT1DM 5.99+/-73.64 years, we assessed the presence of MA. In all patients, we determined albumin-to-creatinine ratio (ACR) in two or three morning first-void urine samples in the period up to 6 months. Persistent MA was confirmed in the patients with the finding of ACR rating 2.5-25 mg/mmol in males and 3.5-25 mg/mmol in females in two out of three first morning urine samples. RESULTS: MA developed in 16 (16.0%) patients. Predictors of MA determined by using multiple logistic regression were high HbA1c (OR 4.6; 95% CI 2.1-10.0), higher night-time SBP (OR 1.9; 95% CI 0.8-1.3) and higher insulin dose (OR 62.6; 95% CI 2.3-1678.5). Markers of insulin resistance such as higher body mass index (BMI) which was statistically significantly related to MA (p= 0.241, p<0.05) and higher dehydroepiandrosterone sulfate (DHEA-S) which was significantly higher in patients with MA (7.82 micromol/L vs. 5.02 micromol/L, p<0.01), were also identified as predictors but did not remain significant by multivariate analysis, possibly because of a small sample of subjects with persistent MA. CONCLUSION: In addition to poor glycemic control and higher night-time systolic blood pressure, markers of insulin resistance (higher insulin dose, higher BMI and higher DHEA-S) contribute to the increased risk of MA.
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Albuminúria , Sulfato de Desidroepiandrosterona/sangue , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Insulina/administração & dosagem , Adolescente , Albuminúria/epidemiologia , Albuminúria/etiologia , Albuminúria/metabolismo , Biomarcadores/sangue , Determinação da Pressão Arterial/métodos , Índice de Massa Corporal , Creatinina/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/metabolismo , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Prevalência , Puberdade/metabolismo , Fatores de RiscoRESUMO
Neuromyelitis optica is a rare autoimmune demyelinating disease of the central nervous system in childhood. Its relapsing form is usually reported in adults. We report a 3-year-old girl with relapsing, IgG seropositive neuromyelitis optica. Initially she presented with optic neuritis, followed by three relapses with deterioration of optic neuritis and developing transverse myelitis. With each relapse, the treatment was less effective. Four years after the onset of the disease, the patient was blind, had paraplegia associated with urinary and bowel incontinence and short stature.
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Neuromielite Óptica/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Neuromielite Óptica/patologia , Recidiva , Medula Espinal/patologiaRESUMO
INTRODUCTION: West Syndrome (WS) is age-related epileptic encephalopathy characterised by a triad of symptoms: specific seizure type, pathognomonic electroencephalographic (EEG) pattern--hypsarrhythmia and delay and/or regression in psychomotor development (PMD). Aetiologically, it occurs in three forms: symptomatic, cryptogenic and idiopathic. OBJECTIVE: Estimation of PMD in children with WS according to aetiology. METHODS: The observed group consisted of 65 children. Age range was between 6 and 30 months. The patients were divided into three groups according to aetiology. All patients underwent psychological examination with Brunet-Lesine test, as well as PMD evaluation based on achieved developmental milestones for the corresponding age. RESULTS: Statistically significant better values in the Human Developmental Index (HDI) had patients with idiopathic compared to otherforms of WS, at testing after 12 months (93.0 +/- 8.1 vs. 46.8 +/- 6.1 vs. 45.6 +/- 3.8), as well as after 24 months (93.9 +/- 7.7 vs. 51.9 +/- 5.5 vs. 50.9 +/- 4.4). The best values of HDI after 24 months had patients with improvement in PMD with the average of 66.2 +/- 4.4, which was statistically significant compared to those with unchanged PMD (41.5 +/- 5.3) and with further regression in PMD (28.3 +/- 4.4). Significant correlation was obtained between PMD after 12 and 24 months (r = 0.477), as well as a considerable improvement in HDI from the 12th to 24th month (49.4 +/- 4.0 vs. 53.7 +/- 3.9). CONCLUSION: The patients with idiopathic WS accomplished the best PMD. Improvement in PMD after 12 and 24 months of treatment was associated with improved HDI. Improvement in PMD was observed in all patients after 2 years of follow-up.
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Deficiências do Desenvolvimento/diagnóstico , Espasmos Infantis/complicações , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Humanos , LactenteRESUMO
Children with inherited neuromuscular diseases often require anaesthesia for diagnostic or therapy procedures. These patients have an increased risk of perioperative complications due to the nature of the disease and medications administered during anaesthesia. Many anaesthetics and muscle relaxants can aggravate the underlying disease and trigger life-threatening reactions (cardiorespiratory complications, malignant hyperthermia). Besides, the neuromuscular disorders are associated with atypical and undesirable responses to drugs used during anaesthesia and the perioperative period. The paper presents pathophysiological basis of inherited/genetic neuromuscular diseases and specific anaesthesiological problems. The recommendations are suggested with the aim to make the perioperative course in children optimally safe.
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Anestesia/métodos , Doenças Neuromusculares/genética , Criança , HumanosRESUMO
Refractory convulsive status epilepticus (RCSE) is life-threatening condition, with seizures lasting over one hour and not responding to first and second-line anticonvulsant drug therapy. Any mistreatment or delayed proper treatment significantly increase mortality and neurologic sequelae. First line drugs for convulsion ceasing are benzodiazepines, phenobarbital and phenytoin. In case of refractory status, infusion of midazolam and general anesthesia should be administered. The most important measures of the intensive care are control of vital functions, homeostasis, prevention and therapy for possible brain and systemic complications. Discovery of etiology of status epilepticus is highly important because symptomatic therapy should be administered. Overall mortality rate during RCSE is 13.5%, and is much higher in acute symptomatic group--28.6%. Early sequelae rate is 40.6%, 27.3% and 70% in idiopathic and acute symptomatic groups, respectively.
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Estado Epiléptico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/etiologiaRESUMO
Physical treatment plays very important role in treatment of children with neuromuscular disorders. It is usually symptomatic and preventive, not being usual, except in children with cerebral palsy. Physical treatment of children with neuromuscular disorders is specific because good clinical knowledge as well as additional education for application of procedures is required during treatment with final evaluation of the achieved results. In fact, whole scientific philosophy is needed since natural development of child with neuromuscular disorders is in close correlation with the degree of retardation that may vary from one disease to another in relation to child's age as well as to clinical presentation of the disease. Upon neurological diagnose and medicamentous treatment, different physical procedures are applied in order to achieve the best possible results in motor development and in psychic and social reeducation as well.