Neuroregenerative evidences demonstrated by diverse MRI analysis in cerebral palsy children who showed significant clinical improvement following repeated G-CSF injection

Background & Aim We tried to confirm the structural changes of magnetic resonance imaging (MRI) and their relation with clinical improvement in cerebral palsy (CP) children who treated with repeated granulocyte colony-stimulating factor (G-CSF) injection. Methods, Results & Conclusion We performed a phase II, randomized placebo controlled clinical trials to reveal clinical improvement after repeated G-CSF injection. Forty-four children with CP were enrolled, and their ages were 2-10 years old. G-CSF (5μg/kg) was administered for 5 days subcutaneously every 3 months during 18 months. We evaluated motor and cognitive functions along with MRI study. To compare the structural changes of MRI between treated and placebo groups, we analyzed the white matter integrity in region of interest as well as in functional networks. We also analyzed the subcortical volume and cortical thickness in MRI. The treated group showed significantly greater increases in cognitive function scores noted in picture memory subtest and expressive vocabulary test as well as increasing tendency in visual motor integrity test. Diverse neuroimaging analysis revealed decrease of mean diffusivity (MD) of region of superior longitudinal fasciculus and cingulum, and also decrease of MD of sensori-motor network and language network. Increase of cortical thickness of left inferior frontal gyrus was also noted. These changes suggested structural improvement in circuit of sensori-motor information and motor language area, and were compatible with the improvement of picture memory and expressive language in cognitive function tests. By the same method of analysis, the structural improvement in the area of cerebral cortex and basal ganglia were noted, which suggest the improvement of visual motor integration in cognitive function tests. The increase of subcortical volume of nucleus accumbens was also noted, suggesting improvement of socialization. In conclusion, we demonstrated the neuroregenerative evidences by diverse MRI analysis as well as the improvement of cognitive functions after repeated G-CSF injection in children with CP.