•Six-months of physical exercise improved quality of life in children with epilepsy.•Seizure frequency did not increase with the exercise program.•A Six-month of exercise program improved motor and ...Cardiorespiratory Fitness.•Monitoring by the researchers stimulated the performance of physical exercise.
to investigate the effects of a physical exercise (PE) program, supported by wearable technology (WT), in children with drug-resistant epilepsy (DRE).
29 children with DRE were randomized to experimental (EG) and control (CG) groups. To encourage PE, the EG performed one hour of aerobic activity three days a week for six months, outside the school setting. Compliance was monitored using activity wristbands, with data reported weekly by parents. Health-related quality of life (HRQoL), seizure frequency, physical activity (PA), physical fitness (musculoskeletal, motor, and Cardiorespiratory Fitness), and body composition, were assessed at baseline, at three and six months.
Seizure frequency in the last six months evolved from 10.5 seizures/week at baseline, to 4.5 at the end of the study in the EG, and from 5.2 seizures/week to one in the CG. Significant differences were found in weekly hours-PE (η2= 0.49); motor fitness (η2= 0.08); Cardiorespiratory Fitness (η2= 0.19); weight (η2= 0.003); Triceps skinfold thickness (η2= 0.05); lower limb muscular strength (η2= 0.03); HRQoL (η2= 0.02); and PA (η2= 0.22). Post-hoc ANOVA revealed that EG improved significantly (p < 0.05) between baseline and six months. Negative correlations were observed between PA and seizure frequency.
Supported by WT, children with DRE increased the weekly hours of PE at three and six months, with no increase in seizure frequency. Our study provides evidence of the effectiveness of PE for improving HRQoL.
•Both original QOLCE-16 and Spanish version showed similar psychometric properties.•This study should enable to conduct an in-depth study of quality of life in CWE.•This study provides evidence for ...the use of QOLCE-16 among Spanish speakers.•This work provides an instrument to validly and reliably assess quality of life in CWE.
The aim of this study was the translation and cultural adaptation (TCA) of the Spanish version of the16-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-16) and an initial assessment of its psychometric properties.
The English version of the QOLCE-16 was cross-culturally adapted into Spanish using a back TCA procedure. Subsequently, for the process of validation of the Spanish version of QOLCE-16, the parents of 75 children with epilepsy (CWE) completed the QOLCE-16 questionnaire, the Pediatric Quality-of-Life Inventory (PedsQL™ 4.0), and the Pediatric Sleep Questionnaire (PSQ) twice in an interval of 7–10 days. The psychometric properties of the four domains of functioning (cognitive, emotional, social, and physical functioning subscales) were analyzed, together with the total QOLCE-16 score using Classical Test Theory.
The scores of the Spanish version of the QOLCE-16 were obtained (alpha coefficient: 0.882, intraclass coefficient: 0.945). The standard error of measurement for the total score was 4.58, and the minimal detectable change was 13.44. Construct validity was tested using Confirmatory Factor Analysis. The estimates of the loadings for the four factors were higher than 0.35 and significant (α = 0.05). The four-factor model for QOLCE-16 Chi- squared (p = 0.0540), comparative fit index = 0.985, Tucker–Lewis index = 0.982, root mean square error of approximation = 0.056 (0.000–0.0987), weighted root mean square residual = 0.707 showed good fit to these data.
Convergent validity with PedsQL™ 4.0. was 0.791 and the discriminant validity of the QOLCE-16 with PSQ was −0.280.
The Spanish version of the QOLCE-16 displays good psychometric properties of validity and reliability. All goodness-of-fit indices represent a good model fit, maintaining the multidimensional Health-related quality-of-life (HRQoL) model of the original English version. The Spanish version of this test can be used reliably to assess HRQoL in CWE in a Spanish-speaking population.
•Assessing quality of life in children with epilepsy is a highly complex process.•Our results support the reliability and validity of the Spanish version of the QOLCE-55.•This study introduces a ...version of the QOLCE-55 to evaluate Spanish-speaking children with epilepsy.•The QOLCE-55 is a valid instrument for measuring quality of life across cultures.
The aims of the present study were to translate and validate the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) into Spanish.
A backtranslation procedure was used to translate the English version of QOLCE-55 to Spanish, and subsequently, parents of 88 children (aged four to 12 years), completed the Spanish version of three self-reported questionnaires: the QOLCE-55, the Pediatric Quality-of-Life Inventory (PedsQLTM 4.0), and the Pediatric Sleep Questionnaire (PSQ). Seven to 10 days later, parents completed the questionnaires again under the same conditions.
Internal consistency was between 0.669 and 0.968 for the four subscales: cognitive (CF), emotional (EF), social (SF) and physical functioning (PF); and 0.954 for the total score. The test–retest reliability assessed with the intraclass correlation coefficient obtained values from 0.683 for SF to 0.962 for CF. The standard error of measurement for the total score was 5.776, and the minimal detectable change was 16.01. Spearman correlations between the total score of the Spanish version of the QOLCE-55 with the subscales was 0.760 for the CF, 0.776 for the EF, 0.799 for the SF, and 0.682 for the PF (p < 0.001). Convergent validity of QOLCE-55 with the PedsQLTM 4.0 scale was −0.962 (p < 0.001), and the discriminant validity of the QOLCE-55 with PSQ was 0.154 (p = 0.272). This version presented a correlation with maximum lifetime consumption of anti-epileptic drugs (0.500; p < 0.001), and current consumption (0.448; p < 0.001).
The Spanish version of the QOLCE-55 has demonstrated adequate psychometric properties, indicating that it can be confidently used to measure the health-related quality-of-life (HRQoL) in children with epilepsy in a Spanish-speaking population. These results corroborate the instrument's cross-cultural validity.
Pathogenic variants in KANSL1 and 17q21.31 microdeletions are causative of Koolen-de Vries syndrome (KdVS), a neurodevelopmental syndrome with characteristic facial dysmorphia. Our previous work has ...shown that syndromic conditions caused by pathogenic variants in epigenetic regulatory genes have identifiable patterns of DNA methylation (DNAm) change: DNAm signatures or episignatures. Given the role of KANSL1 in histone acetylation, we tested whether variants underlying KdVS are associated with a DNAm signature. We profiled whole-blood DNAm for 13 individuals with KANSL1 variants, four individuals with 17q21.31 microdeletions, and 21 typically developing individuals, using Illumina's Infinium EPIC array. In this study, we identified a robust DNAm signature of 456 significant CpG sites in 8 individuals with KdVS, a pattern independently validated in an additional 7 individuals with KdVS. We also demonstrate the diagnostic utility of the signature and classify two KANSL1 VUS as well as four variants in individuals with atypical clinical presentation. Lastly, we investigated tissue-specific DNAm changes in fibroblast cells from individuals with KdVS. Collectively, our findings contribute to the understanding of the epigenetic landscape related to KdVS and aid in the diagnosis and classification of variants in this structurally complex genomic region.
Purpose
Inborn errors of neurotransmitters are rare monogenic diseases. In general, conventional neuroimaging is not useful for diagnosis. Nevertheless, advanced neuroimaging techniques could provide ...novel diagnosis and prognosis biomarkers. We aim to describe cerebral volumetric findings in a group of Spanish patients with neurotransmitter disorders.
Methods
Fifteen 3D T1-weighted brain images from the International Working Group on Neurotransmitter related Disorders Spanish cohort were assessed (eight with monoamine and seven with amino acid disorders). Volumes of cortical and subcortical brain structures were obtained for each patient and then compared with those of two healthy individuals matched by sex and age.
Results
Regardless of the underlying disease, patients showed a smaller total cerebral tissue volume, which was apparently associated with clinical severity. A characteristic volumetric deficit pattern, including the right Heschl gyrus and the bilateral occipital gyrus, was identified. In severe cases, a distinctive pattern comprised the middle and posterior portions of the right cingulate, the left superior motor area and the cerebellum. In succinate semialdehyde dehydrogenase deficiency, volumetric affection seems to worsen over life.
Conclusion
Despite the heterogeneity and limited size of our cohort, we found novel and relevant data. Total volume deficit appears to be a marker of severity, regardless of the specific neurotransmitter disease and irrespective of the information obtained from conventional neuroimaging. Volumetric assessment of individual brain structures could provide a deeper knowledge about pathophysiology, disease severity and specific clinical traits.
In order to characterize the genetic architecture of epilepsy in a paediatric population from the Iberian Peninsula (including the Canary Islands), we conducted targeted exome sequencing of 246 ...patients with infantile-onset seizures with or without neurodevelopmental delay. We detected 107 variants in 48 different genes, which were implicated in neuronal excitability, neurodevelopment, synaptic transmission, and metabolic pathways. In 104 cases (42%) we detected variant(s) that we classified as pathogenic or likely pathogenic. Of the 48 mutated genes, 32 were dominant, 8 recessive and 8 X-linked. Of the patients for whom family studies could be performed and in whom pathogenic variants were identified in dominant or X-linked genes, 82% carried de novo mutations. The involvement of small copy number variations (CNVs) is 9%. The use of progressively updated custom panels with high mean vertical coverage enabled establishment of a definitive diagnosis in a large proportion of cases (42%) and detection of CNVs (even duplications) with high fidelity. In 10.5% of patients we detected associations that are pending confirmation via functional and/or familial studies. Our findings had important consequences for the clinical management of the probands, since a large proportion of the cohort had been clinically misdiagnosed, and their families were subsequently able to avail of genetic counselling. In some cases, a more appropriate treatment was selected for the patient in question, or an inappropriate treatment discontinued. Our findings suggest the existence of modifier genes that may explain the incomplete penetrance of some epilepsy-related genes. We discuss possible reasons for nondiagnosis and future research directions. Further studies will be required to uncover the roles of structural variants, epimutations, and oligogenic inheritance in epilepsy, thereby providing a more complete molecular picture of this disease. In summary, given the broad phenotypic spectrum of most epilepsy-related genes, efficient genomic tools like the targeted exome sequencing panel described here are essential for early diagnosis and treatment, and should be implemented as first-tier diagnostic tools for children with epilepsy without a clear etiologic basis.
Glucose transporter 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder caused by haploinsufficiency of the GLUT1 glucose transporter (encoded by SLC2A1) leading to defective glucose ...transport across the blood–brain barrier. This work describes the genetic analysis of 56 patients with clinical or biochemical GLUT1DS hallmarks. 55.4% of these patients had a pathogenic variant of SLC2A1, and 23.2% had a variant in one of 13 different genes. No pathogenic variant was identified for the remaining patients. Expression analysis of SLC2A1 indicated a reduction in SLC2A1 mRNA in patients with pathogenic variants of this gene, as well as in one patient with a pathogenic variant in SLC9A6, and in three for whom no candidate variant was identified. Thus, the clinical and biochemical hallmarks generally associated with GLUT1DS may be caused by defects in genes other than SLC2A1.
Training in autistic spectrum disorders is crucial in order to achieve an early diagnosis. However, the number of papers describing this training is limited. This study describes this level of ...knowledge among paediatricians from tertiary care hospitals in different regions of Spain and detects areas that need improvement.
A total of one hundred and fifty-seven (157) paediatricians working in tertiary healthcare hospitals located in three different regions in Spain consented to complete an online questionnaire divided in three sections (socio-demographic, knowledge about childhood autism, and opinion). Data were analysed using SPSS version 15.
The total mean score of participating paediatricians in the questionnaire was 20.34 (± 2.43 SD) out of a total possible score of 23. Approximately two-thirds (65%) of paediatricians scored more or equal to the mean score. The knowledge gap was found to be higher with symptoms of repetitive behaviour patterns, concept of autism, and comorbidity, with no statistical significance. There were no differences in paediatrician scores within different socio-demographic groups. Just under two-thirds (64%) of paediatricians subscribed to the opinion that their own knowledge about autism is limited, and there is a significant lack of knowledge about facilities in every region.
There is a sufficient level of knowledge about autism among paediatricians in tertiary healthcare, although a lack of awareness about the management of these patients, with poor coordination between the different specialists that are involved in their treatment. Efforts should focus on achieving a better coordination between these specialists, and update the knowledge gaps identified.
Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes ...causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine lactate, ketoglutarate, and 2-oxoacid levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. A Western blot analysis revealed a reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation, and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and α-lipoic acid, which is capable of rescuing LIPT1 pathophysiology, increasing the LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations.
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