Dataset Information

Epigenetic Marks at the Ribosomal DNA Promoter in Skeletal Muscle Are Negatively Associated With Degree of Impairment in Cerebral Palsy.

ABSTRACT: Introduction: Cerebral palsy (CP) is the most common motor impairment in children. Skeletal muscles in individuals with CP are typically weak, thin, and stiff. Whether epigenetic changes at the ribosomal DNA (rDNA) promoter are involved in this dysregulation remains unknown. Methods: Skeletal muscle samples were collected from 19 children with CP and 10 typically developed (TD) control children. Methylation of the rDNA promoter was analyzed using the Agena Epityper Mass array and gene expression by qRT-PCR. Results: Biceps brachii muscle ribosome biogenesis was suppressed in CP as compared to TD. Average methylation of the rDNA promoter was not different between CP and TD but negatively correlated to elbow flexor contracture in the CP group. Discussions: We observed a negative correlation between rDNA promoter methylation and degree of muscle contracture in the CP group. Children with CP with more severe motor impairment had less methylation of the rDNA promoter compared to less affected children. This finding suggests the importance of neural input and voluntary muscle movements for promoter methylation to occur in the biceps muscle.

SUBMITTER: von Walden F

PROVIDER: S-EPMC7283884 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Epigenetic Marks at the Ribosomal DNA Promoter in Skeletal Muscle Are Negatively Associated With Degree of Impairment in Cerebral Palsy.

von Walden Ferdinand F Fernandez-Gonzalo Rodrigo R Pingel Jessica J McCarthy John J Stål Per P Pontén Eva E

Frontiers in pediatrics 20200603

<b>Introduction:</b> Cerebral palsy (CP) is the most common motor impairment in children. Skeletal muscles in individuals with CP are typically weak, thin, and stiff. Whether epigenetic changes at the ribosomal DNA (rDNA) promoter are involved in this dysregulation remains unknown. <b>Methods:</b> Skeletal muscle samples were collected from 19 children with CP and 10 typically developed (TD) control children. Methylation of the rDNA promoter was analyzed using the Agena Epityper Mass array and g ...[more]

PMID: 32582584

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Project description:BackgroundCerebral Visual Impairment (CVI) is a very common finding in children affected by Cerebral Palsy (CP). In this paper we studied the characteristics of CVI of a large group of children with CP and CVI, describing their neurovisual profiles according to three different age subgroups (subgroup 1: infants 6 months-2 years; subgroup 2: pre-school age 3-5 years; subgroup 3: school age ≥ 6 years).MethodsWe enrolled 180 subjects (104 males, mean age 66 ± 42.6 months; range 6-192 months) with CP and CVI for the study. We carried out a demographic and clinical data collection, neurological examination, developmental or cognitive assessment, and a video-recorded visual function assessment including an evaluation of ophthalmological characteristics, oculomotor functions, and basic visual functions. In school-aged children, we also performed an evaluation of their cognitive-visual profiles.ResultsThere were signs of CVI in all the three subgroups. Subgroup 1 (62 children) and subgroup 2 (50 children) were different for fixation (p = 0.02), visual acuity (p = 0.03) and contrast sensitivity (p < 0.01), being more frequently impaired in younger children. Comparing subgroup 2 with subgroup 3 (68 children), the older children presented more frequently myopia (p = 0.02) while the younger ones esotropia (p = 0.02) and alteration in smooth pursuit (p = 0.03) and saccades (p < 0.01). Furthermore, fixation, smooth pursuit, visual acuity, contrast sensitivity and visual filed (p < 0.01) were more frequently impaired in younger children (subgroup 1) compared to the older ones. Multiple correspondence analysis (MCA) confirmed the different neurovisual profiles according to age: younger children with CP showed more signs of CVI compared to the older ones. 34 out of 68 children belonging to subgroup 3 underwent the cognitive visual evaluation; an impairment of cognitive visual skills was detected in 21 subjects.ConclusionYounger children with CP showed more signs of CVI compared to the older ones, likely for the physiological maturation of visual system and mechanisms of neuroplasticity. In this direction, we suggest an early neurovisual evaluation to detect any weak visual functions.

Project description:AIM:To assess the responsiveness, concurrent validity, and feasibility of the Dyskinesia Impairment Scale (DIS) in non-ambulatory patients with dyskinetic cerebral palsy (CP). METHOD:The study is a secondary analysis of data collected in the IDYS trial, a randomized controlled trial on the effects of intrathecal baclofen (ITB). The DIS and Barry-Albright Dystonia Scale (BADS) were conducted at baseline and after 3 months of ITB or placebo treatment. Responsiveness was assessed by comparing the effect sizes and correlation of change after treatment between the DIS and BADS. Concurrent validity was evaluated by assessing the correlations between scales. Feasibility was evaluated for each DIS item by the number of participants who successfully accomplished the item. RESULTS:Thirty-three non-ambulatory patients (9 females, 24 males) with dyskinetic CP (ITB-treated: n=17, mean [SD] age: 14y 1mo [4y 1mo]; placebo-treated: n=16, mean [SD] age: 14y 7mo [4y]) were included in the study. The effect sizes for BADS and DIS were similar in The ITB-treated group (-0.29 and -0.22 respectively). Changes after treatment on the DIS dystonia subscale correlated with changes on the BADS (r=0.64; p<0.001). The DIS dystonia subscale and BADS correlated at baseline and follow-up (r=0.78; p<0.001 and r=0.79; p<0.001). Not all DIS activity items could be performed in this sample of patients. INTERPRETATION:For non-ambulatory patients with dyskinetic CP, the responsiveness of the DIS equalled the responsiveness of BADS. Concurrent validity was adequate. Feasibility for activity items was restricted in patients with severe dyskinetic CP. WHAT THIS PAPER ADDS:The Dyskinesia Impairment Scale (DIS) and Barry-Albright Dystonia Scale showed similar responsiveness in non-ambulatory patients with dyskinetic cerebral palsy (CP). No floor or ceiling effect was observed for DIS in non-ambulatory participants. The concurrent validity of DIS was adequate in non-ambulatory participants. Patients with dyskinetic CP in Gross Motor Function Classification System levels IV and V could not perform all DIS activity items.

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Dataset Information

Epigenetic Marks at the Ribosomal DNA Promoter in Skeletal Muscle Are Negatively Associated With Degree of Impairment in Cerebral Palsy.

Publications

Epigenetic Marks at the Ribosomal DNA Promoter in Skeletal Muscle Are Negatively Associated With Degree of Impairment in Cerebral Palsy.

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