In children, arterial alterations occur with increased intima-media thickness as well as vascular diameter enlargement. Both conditions correlate with higher cardiovascular risk in adults, and both the array and proportion of these alterations are important hemodynamic parameters. In terms of functional adaptation processes, they influence several arterial wall properties as for example the shear and tensile stress of the vessel. There are no reference values for the vascular diameter and intima-media thickness/diameter ratio of the carotid artery in children. Therefore, this study aimed to assess vascular diameter, intima-media thickness/diameter ratio and related tensile stress values in children and to further investigate the influence of sex, age, body mass index, and blood pressure. The parameters were measured with high-resolution semi-automated ultrasound. Sex- and age-dependent values were calculated with the LMS method for a cross-sectional sample of 642 healthy, non-obese children aged 8–17 years. The mean vascular diameter was 5.45 ± 0.46 mm; the median intima-media thickness/diameter ratio was 0.085 (0.079–0.092); the median tensile stress was 105.4 (95.2–116.4) kPa. The vascular diameter and the tensile stress were higher, and the intima-media thickness/diameter ratio was lower in boys than in girls. In comparison to the normal weight study population the excludedobese children had a significantly higher diameter, a lower intima-media thickness/diameter ratio, and a higher tensile stress. In multiple regression analyses of diameter, intima-media thickness/diameter ratio, and tensile stress, all parameters were influenced by sex and body mass index. Furthermore, systolic and diastolic blood pressure significantly influenced the vascular diameter, and systolic blood pressure significantly influenced the intima-media thickness/diameter ratio. Conclusion: This study is the first to report values for the diameter, the intima-media thickness/diameter ratio of the carotid artery, and the related tensile stress allowing a more differentiated view of cardiovascular adaptations as it combines structural and functional vascular parameters. What is known:• Intima-media thickness and vascular diameter are related to a higher cardiovascular risk in adults• The intima-media thickness/diameter ratio gives information about hemodynamic and functional vessel adaptationWhat is new:• Values for vascular diameter, intima-media thickness/diameter ratio, and tensile stress of the carotid artery in children are presented in this study• Intima-media thickness as a surrogate marker for arterial health in children should be complemented by intima-media thickness/diameter ratio measurement
Background: COQ4 codes for a mitochondrial protein required for coenzyme Q 10 (CoQ 10 ) biosynthesis. Autosomal recessive COQ4associated CoQ 10 deficiency leads to an early-onset mitochondrial multi-organ disorder. Methods: In-house exome and genome datasets (n = 14,303) were screened for patients with bi-allelic variants in COQ4. Work-up included clinical characterization and functional studies in patient-derived cell lines.Results: Six different COQ4 variants, three of them novel, were identified in six adult patients from four different families. Three patients had a phenotype of hereditary spastic paraparesis, two sisters showed a predominant cerebellar ataxia, and one patient had mild signs of both. Studies in patient-derived fibroblast lines revealed significantly reduced amounts of COQ4 protein, decreased CoQ 10 concentrations, and elevated levels of the metabolic intermediate 6-demethoxyubiquinone. Conclusion:We report bi-allelic variants in COQ4 causing an adult-onset ataxia-spasticity spectrum phenotype and a disease course much milder than previously reported.
Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.
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