To evaluate the effects of systematic rehabilitation on both the neuropsychomotor development, and on the peripheral response from immunological and neuroplastic mediators in children with cerebral palsy.
Methods
This is a prospective cohort study with 90 children with cerebral palsy at 18 months of age. Sixty children received rehabilitation for 6 months, and they were compared to 30 children that were placed in the waiting list. Peripheral biomarkers and neuropsychomotor parameters were compared between the Rehab vs the Nonrehab groups at baseline and at 6 months.
Results
Results showed higher Bayley III scores in the Rehab group, with significant differences in inflammatory and neurotrophic biomarkers between groups. Rehabilitation was associated to decreased levels of IL-12p70, IL-6, IL-1β, CXCL8 IL-8, and CXCL9/MIG and increased levels of BDNF and GDNF. Nonrehab children had stable immune molecule levels but decreased BDNF levels over time.
Conclusion
Rehabilitation improved neurodevelopment parameters and modulated levels of inflammatory (↓) and neurotrophic (↑) biomarkers.
PatelDRNeelakantanMPandherKMerrickJ. Cerebral palsy in children: a clinical overview. Transl Pediatr. 2020; (Suppl 1):S125-S135. doi:https://doi.org/10.21037/tp.2020.01.01
2.
NemanichSTRichTLChenCY, et al.Influence of combined transcranial direct current stimulation and motor training on corticospinal excitability in children with unilateral cerebral palsy. Front Hum Neurosci. 2019;13:137. doi:https://doi.org/10.3389/fnhum.2019.00137
3.
FitzgeraldEBoardmanJPDrakeAJ. Preterm birth and the risk of neurodevelopmental disorders - is there a role for epigenetic dysregulation?Curr Genomics. 2018;19(7):507-521. doi:https://doi.org/10.2174/1389202919666171229144807
4.
AllardMJBrochuMEBergeronJDSeguraMSébireG. Causal role of group B Streptococcus-induced acute chorioamnionitis in intrauterine growth retardation and cerebral palsy-like impairments. J Dev Orig Health Dis. 2019;10(5):595-602. doi:https://doi.org/10.1017/S2040174418001083
EllerySJKelleherMGrigsbyP, et al.Antenatal prevention of cerebral palsy and childhood disability: is the impossible possible?J Physiol. 2018;596(23):5593-5609. doi:https://doi.org/10.1113/JP275595
7.
YanniDKorzeniewskiSJAllredEN, et al.Both antenatal and postnatal inflammation contribute information about the risk of brain damage in extremely preterm newborns. Pediatr Res. 2017;82(4):691-696. doi:https://doi.org/10.1038/pr.2017.128
8.
PatonMCBFinch-EdmondsonMDaleRC, et al.Persistent inflammation in cerebral palsy: pathogenic mediator or comorbidity? A scoping review. J Clin Med.2022;11(24):7368. doi:https://doi.org/10.3390/jcm11247368
9.
SharovaOSmiyanOBorénT. Immunological effects of cerebral palsy and rehabilitation exercises in children. Brain Behav Immun-Health. 2021;18:100365. doi:https://doi.org/10.1016/j.bbih.2021.100365
10.
PingelJBarberLAndersenIT, et al.Systemic inflammatory markers in individuals with cerebral palsy. Eur J Inflamm. 2019;17. doi:https://doi.org/10.1177/2058739218823474
11.
DhillonSKLearCAGalinskyR, et al.The fetus at the tipping point: modifying the outcome of fetal asphyxia. J Physiol. 2018;596(23):5571-5592. doi:https://doi.org/10.1113/JP274949
12.
LibermanACTriasEChagasLS, et al.Neuroimmune and inflammatory signals in complex disorders of the central nervous system. Neuroimmunomodulation. 2018;25(5-6):246-270. doi:https://doi.org/10.1159/000494761
13.
MatuszPJKeyAPGogliottiS, et al.Somatosensory plasticity in pediatric cerebral palsy following constraint-induced movement therapy. Neural Plast. 2018;2018:1891978. doi:https://doi.org/10.1155/2018/1891978
14.
WoodwardKECarlsonHLKuczynskiASaundersJHodgeJKirtonA. Sensory-motor network functional connectivity in children with unilateral cerebral palsy secondary to perinatal stroke. Neuroimage Clin. 2019;2019:101670. doi:https://doi.org/10.1016/j.nicl.2019.101670
15.
JochumsenMShafiqueMHassanANiaziIK. Movement intention detection in adolescents with cerebral palsy from single-trial EEG. J Neural Eng. 2018;15(6):066030. doi:https://doi.org/10.1088/1741-2552/aae4b8
16.
LinkeACWildCZubiaurre-ElorzaL, et al.Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months. Neuroimage Clin. 2018;18:399-406. doi:https://doi.org/10.1016/j.nicl.2018.02.002
17.
GeorgeJMBoydRNColditzPB, et al.PPREMO: a prospective cohort study of preterm infant brain structure and function to predict neurodevelopmental outcome. BMC Pediatr. 2015;15:123. doi:https://doi.org/10.1186/s12887-015-0439-z
MagalhãesRCMoreiraJMVieiraELMRochaNPMirandaDMSimões e SilvaAC. Urinary levels of IL-1β and GDNF in preterm neonates as potential biomarkers of motor development: a prospective study. Mediators Inflamm. 2017;2017:8201423. doi:https://doi.org/10.1155/2017/8201423
20.
BayleyN. Bayley Scales of Infant and Toddler Development - Third Edition, Administration manual. The Psychological Corporation; 2006.
21.
NovakIMorganCFaheyM, et al.State of the evidence traffic lights 2019: systematic review of interventions for preventing and treating children with cerebral palsy. Curr Neurol Neurosci Rep. 2020;20(2):3. doi:https://doi.org/10.1007/s11910-020-1022-z
22.
HoareBDitchfieldMThorleyM, et al.Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study. BMC Neurol. 2018;18(1):63. doi:https://doi.org/10.1186/s12883-018-1070-z
23.
ReidLBBoydRNCunningtonRRoseSE. Interpreting intervention induced neuroplasticity with fMRI: the case for multimodal imaging strategies. Neural Plast. 2016;2016:2643491. doi:https://doi.org/10.1155/2016/2643491
24.
BhattacharjeeSKashyapRAbualaitTAnnabel ChenSHYooWKBashirS. The role of primary motor cortex: more than movement execution. J Mot Behav. 2020;20:1-17. doi:https://doi.org/10.1080/00222895.2020.1738992
25.
KuoHCZewdieECiechanskiPDamjiOKirtonA. Intervention-induced motor cortex plasticity in hemiparetic children with perinatal stroke. Neurorehabil Neural Repair. 2018;32(11):941-952. doi:https://doi.org/10.1177/1545968318801546
26.
PeytonCEinspielerCFjørtoftT, et al.Correlates of normal and abnormal general movements in infancy and long-term neurodevelopment of preterm infants: insights from functional connectivity studies at term equivalence. J Clin Med. 2020;9(3):834. doi:https://doi.org/10.3390/jcm9030834
27.
CarloWAMcDonaldSATysonJE, et al.Cytokines and neurodevelopmental outcomes in extremely low birth weight infants. J Pediatr. 2011;159(6):919-25.e3. doi:https://doi.org/10.1016/j.jpeds.2011.05.042
28.
VasiljevicBMaglajlic-DjukicSGojnicMStankovicSIgnjatovicSLutovacD. New insights into the pathogenesis of perinatal hypoxic-ischemic brain injury. Pediatr Int. 2011;53(4):454-462. doi:https://doi.org/10.1111/j.1442-200X.2010.03290.x
29.
MagalhãesRCPimentaLPBarbosaIG, et al.Inflammatory molecules and neurotrophic factors as biomarkers of neuropsychomotor development in preterm neonates: a systematic review. Int J Dev Neurosci. 2018;65:29-37. doi:https://doi.org/10.1016/j.ijdevneu.2017.10.006
30.
VarnerMWMarshalNERouseDJ, et al.The association of cord serum cytokines with neurodevelopmental outcomes. Am J Perinatol. 2015;30(2):115-122. doi:https://doi.org/10.1055/s-0034-1376185
31.
AllredENDammannOFichorovaRN, et al.Systemic inflammation during the first month and the risk of attention deficit hyperactivity disorder characteristics among 10 years-old children born extremely preterm. J Neuroimmune Pharmacol. 2017;12(3):531-543. doi:https://doi.org/10.1007/s11481-017-9742-9
32.
SchmeerKKTarrenceJ. Racial/ethnic disparities in inflammation: evidence of weathering in childhood?J Health Soc Behav. 2018;59(3):411-428. doi:https://doi.org/10.1177/0022146518784592
33.
DonowitzJRCookHAlamM, et al.Role of maternal health and infant inflammation in nutritional and neurodevelopmental outcomes of two-year-old Bangladeshi children. PLoS Negl Trop Dis. 2018;12(5):e0006363. doi:https://doi.org/10.1371/journal.pntd.0006363
34.
Treble-BarnaAPetersenBAStecZConleyYPFinkELKochanekPM. Brain-derived neurotrophic factor in pediatric acquired brain injury and recovery. Biomolecules. 2024;14(2):191. doi:https://doi.org/10.3390/biom14020191
35.
KarimTMuhitMJahanI, et al.Outcome of community-based early intervention and rehabilitation for children with cerebral palsy in rural Bangladesh: a quasi-experimental study. Brain Sci. 2021;11(9):1189. doi:https://doi.org/10.3390/brainsci11091189
36.
DamianoDLLongoE. Early intervention evidence for infants with or at risk for cerebral palsy: an overview of systematic reviews. Dev Med Child Neurol. 2021;63(7):771-784. doi:https://doi.org/10.1111/dmcn.14855
37.
Sanchez-BezanillaSBeardDJHoodRJ, et al.Growth hormone increases BDNF and mTOR expression in specific brain regions after photothrombotic stroke in mice. Neural Plast. 2022;2022:9983042. doi:https://doi.org/10.1155/2022/9983042
38.
WangJJiangCZhangK, et al.Melatonin receptor activation provides cerebral protection after traumatic brain injury by mitigating oxidative stress and inflammation via the Nrf2 signaling pathway. Free Radic Biol Med. 2019;131:345-355. doi:https://doi.org/10.1016/j.freeradbiomed.2018.12.014.
