Developmental Profiles of Preschool Children With Spastic Diplegic and Quadriplegic Cerebral Palsy

Cerebral palsy (CP) is a disorder of movement and posture control with multiple impairments. The clinical manifestations of CP vary among children. The aim of this study was to compare the developmental profiles of preschool children with either of two types of CP: spastic diplegic (SD) CP and spastic quadriplegic (SQ) CP. Relationships between the children's various developmental functions were also investigated. We recruited 137 children with spastic CP, aged 1-5 years (mean age = 3.7 ± 2.1 years), and we classified them into two groups: SD (n = 59) and SQ (n = 78). The comparison group comprised 18 children with typical development. Developmental functions were assessed in all the children, using the Chinese Child Development Inventory with the updated norms. This scale addressed eight functional domains: gross motor ability, fine motor ability, expressive language ability, concept comprehension ability, situation comprehension ability, self-help ability, personal-social skills, and general development. A development quotient (DQ) was determined for each domain as a percentage of the developmental age divided by the chronological age. The developmental profiles of the CP subtypes were found to differ. Children with SQ were found to have lower DQs than those with SD (p < 0.01). There was also a difference in the distribution of DQs between the SD and SQ groups, although the lowest DQ in both groups was for the gross motor domain. An uneven delay in the development of gross motor function was found in both groups of children with CP. Motor functions, including gross motor and fine motor functions, were significantly related to self-help ability. Complex and significant correlations among developmental functions were also identified in children with CP. The findings in the present study may allow clinicians to anticipate the developmental profile of children with CP on the basis of whether they have the SD or SQ subtype. This, in turn, is likely to facilitate individual assessment, goal setting, and the planning of interventions in children with CP

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Effects of Respiratory Muscle Training on Baroreflex Sensitivity, Respiratory Function, and Serum Oxidative Stress in Acute Cervical Spinal Cord Injury

Background: respiratory complications are a leading cause of morbidity and mortality in individuals with spinal cord injury (SCI). We examined the effects of respiratory muscle training (RMT) in patients with acute cervical SCI. Methods: this prospective trial enrolled 44 adults with acute cervical SCI, of which twenty received RMT and twenty-four did not receive RMT. Respiratory function, cardiovascular autonomic function, and reactive oxidative species (ROS) were compared. The experimental group received 40-min high-intensity home-based RMT 7 days per week for 10 weeks. The control group received a sham intervention for a similar period. The primary outcomes were the effects of RMT on pulmonary and cardiovascular autonomic function, and ROS production in individuals with acute cervical SCI. Results: significant differences between the two groups in cardiovascular autonomic function and the heart rate response to deep breathing (p = 0.017) were found at the 6-month follow-up. After RMT, the maximal inspiratory pressure (p = 0.042) and thiobarbituric acid-reactive substances (TBARS) (p = 0.006) improved significantly, while there was no significant difference in the maximal expiratory pressure. Significant differences between the two groups in tidal volume (p = 0.005) and the rapid shallow breathing index (p = 0.031) were found at 6 months. Notably, the SF-36 (both the physical (PCS) and mental (MCS) component summaries) in the RMT group had decreased significantly at the 6-month follow-up, whereas the clinical scores did not differ significantly (p = 0.333) after RMT therapy. Conclusions: High-intensity home-based RMT can improve pulmonary function and endurance and reduce breathing difficulties in patients with respiratory muscle weakness after injury. It is recommended for rehabilitation after spinal cord injury