Constraint-induced movement therapy (CIMT) combined with repetitive transcranial magnetic stimulation (rTMS) have shown great potential in improving function in schoolchildren with unilateral cerebral palsy attributed to perinatal stroke. However, the prospect of application in preschool children with unilateral cerebral palsy (UCP) attributed to various brain disorders remains unclear. In this prospective, assessor-blinded, randomized controlled study, 40 preschool children with UCP (aged 2.5–6 years) were randomized to receive 10 days of CIMT combined with active or sham rTMS. Assessments were performed at baseline, 2 weeks, and 6 months post-intervention to investigate upper limb extremity, social life ability, and perceived changes by parents and motor-evoked potentials. Overall, 35 participants completed the trial. The CIMT plus active stimulation group had greater gains in the affected hand function (range of motion, accuracy, and fluency) than the CIMT plus sham stimulation group (P < 0.05), but there was no significant difference in muscular tone, social life ability, and perceived changes by parents between the two groups (P > 0.05). In addition, there was no significant difference in hand function between children with and without motor-evoked potential (P > 0.05). No participants reported severe adverse events during the study session. In short, the treatment of CIMT combined with rTMS is safe and feasible for preschool children with UCP attributed to various brain disorders. Randomized controlled studies with large samples and long-term effects are warranted.

Background. Little is known about the induction of functional and brain structural reorganization in hemiplegic cerebral palsy (HCP) by constraint-induced movement therapy (CIMT). Objective. We aimed to explore the specific molecular mechanism of functional and structural plasticity related to CIMT in HCP. Methods. The mice were divided into a control group and HCP groups with different interventions (unconstraint-induced movement therapy [UNCIMT], CIMT or siRNA-Nogo-A [SN] treatment): the HCP, HCP+UNCIMT, HCP+CIMT, HCP+SN, and HCP+SN+CIMT groups. Rotarod and front-limb suspension tests, immunohistochemistry, Golgi-Cox staining, transmission electron microscopy, and Western blot analyses were applied to measure motor function, neurons and neurofilament density, dendrites/axon areas, myelin integrity, and Nogo-A/NgR/RhoA/ROCK expression in the motor cortex. Results. The mice in the HCP+CIMT group had better motor function, greater neurons and neurofilament density, dendrites/axon areas, myelin integrity, and lower Nogo-A/NgR/RhoA/ROCK expression in the motor cortex than the HCP and HCP+UNCIMT groups ( P < .05). Moreover, the expression of Nogo-A/NgR/RhoA/ROCK, the improvement of neural remodeling and motor function of mice in the HCP+SN group were similar to those in the HCP+CIMT group ( P > .05). The neural remodeling and motor function of the HCP+SN+CIMT group were significantly greater than those in the HCP+SN and HCP+CIMT groups ( P < .05). Motor function were positively correlated with the density of neurons ( r = 0.450 and 0.309, respectively; P < .05) and neurofilament ( r = 0.717 and 0.567, respectively; P < .05). Conclusions. CIMT might promote the remodeling of neurons, neurofilament, dendrites/axon areas, and myelin in the motor cortex by partially inhibiting the Nogo-A/NgR/RhoA/ROCK pathway, thereby promoting the improvement of motor function in HCP mice.

Cerebral palsy (CP) is a motor and postural disorder syndrome caused by the nonprogressive dysfunction of the developing brain. Previous studies strongly indicated that the Nogo-A gene might be related to the pathogenesis of CP. The objective of this research was to explore the relationship between Nogo-A polymorphisms (rs1012603, rs12464595 and rs2864052) and CP in Southern China. The Hardy-Weinberg equilibrium (HWE) testing, allele and genotype frequencies analysis, and haplotype association analysis were applied to the genotyping of 592 CP children and 600 controls. The results showed that the allele and genotype frequencies of rs1012603 of CP group were significantly different from the control group. The haplotype “TTGGG” was significantly associated with an increased risk of CP. The allele frequencies of rs1012603 were significant differences between CP with spastic diplegia, female CP cases and controls. Furthermore, significant differences in allele and genotype frequencies were also noticed between GMFCS I of CP and controls for rs1012603, and significant differences in allele and genotype frequencies were observed between the ADL (>9) of CP and controls for rs1012603, and rs12464595. This study showed that the SNPs rs1012603 of Nogo-A were significantly correlated with CP, and the correlations were also found in spastic diplegia, GMFCS I of CP, ADL (>9) of CP and female subgroups, indicating that Nogo-A might mainly affected mild types of CP and there might be sex-related differences.

No abstract