Development Of Cerebral Palsy Research Articles

Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurological Impairment in Neonates With Stroke.

Research investigating neonatal arterial ischemic stroke (NAIS) outcomes have shown that combined cortical and basal ganglia infarction or involvement of the corticospinal tract predict cerebral palsy (CP). The research question was whether voxel-based lesion-symptom mapping (VLSM) on acute MRI can identify brain regions associated with CP and neurodevelopmental impairments in neonatal arterial ischemic stroke (NAIS). Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language and cognitive-behavioral impairments were assessed using the Pediatric Stroke Outcome Measure, dichotomized to good (0-0.5) or poor (≥ 1), at ≥18 months of age. Infarcts were manually segmented using diffusion-weighted imaging, registered to a neonatal-specific brain template. VLSM was conducted using MATLAB SPM12 toolbox. A general linear model was used to correlate lesion masks with motor, language and cognitive-behavioral outcomes. Voxel-wise t-test statistics were calculated, correcting for multiple comparisons using family-wise error rate (FWE). Eighty-five newborns met inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%) and bilateral (30%). At median age 2.1 years (IQR 1.9-2.6), 33% developed CP and 42% had neurological impairments. 54 grey and white matter regions correlated with CP (t>4.33; FWE <0.05), including primary motor pathway regions, such as the precentral gyrus, and cerebral peduncle, and regions functionally connected to the primary motor pathway, such as the pallidum, and corpus callosum motor segment. No significant correlations were found for language or cognitive-behavioral outcomes. CP following NAIS correlates with infarct regions directly involved in motor control and, or in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear.

The association between congenital cytomegalovirus infection and cerebral palsy: A systematic review and meta-analysis.

Cytomegalovirus (CMV) is the most common cause of congenital infection, affecting 1% of all live births. Intrauterine infection such as CMV infection is a risk factor for developing cerebral palsy. This study aims to investigate the association between congenital CMV infection and the development of cerebral palsy. A systematic literature search was conducted in PubMed, Web of Science and Ovid SP to identify relevant studies. The quality of studies was assessed using the Newcastle-Ottawa Scale. The random-effect model was used to calculate the pooled prevalence. The generic inverse variance method was used for statistical analysis. A total of 12 studies were included in this systematic review and meta-analysis. The overall pooled prevalence of cerebral palsy among patients diagnosed with congenital CMV infection was 26% (95% confidence interval (CI), 13-40%). The overall pooled prevalence of congenital CMV infection among patients with cerebral palsy was 10.9% (95% CI, 5-16%). Congenital CMV infection was significantly associated with the development of cerebral palsy in children. Routine follow-ups should be offered to screen for cerebral palsy.

Fate of hips complicated by avascular necrosis of the femoral head following reconstructive surgery in nonambulatory patients with cerebral palsy

The purpose of this study was to evaluate the influence of avascular necrosis of the femoral head (AVN) following hip reconstructions on the future hip development of cerebral palsy (CP) patients. A retrospective study of 394 hips in 205 nonambulatory patients with spastic CP who underwent reconstructive hip surgery was performed. The mean age at surgery was 7.3 ± 2.4 years. The mean follow-up duration was 5.6 ± 2.7 years, and the mean age at the latest follow-up was 12.8 ± 3.4 years. AVN was classified in terms of its severity and location. Femoral head remodelling was assessed by the spherical index and the Mose circle. An unsatisfactory radiological outcome was defined as having a migration percentage of more than 30% at the final follow-up. AVN was observed in 169 (42.9%) hips. Older age at the time of surgery, higher preoperative migration percentage, and open reduction procedures were predictors for the development of AVN. Hips with AVN confined to the lateral epiphysis, and AVN involving the entire epiphysis with preserved height experienced successful remodelling. 27 (65.9%) of the 41 hips with unsatisfactory outcomes experienced AVN. Younger age, higher postoperative migration percentage, and occurrence of AVN were related to unsatisfactory outcomes. The highest incidence of failed remodelling and unsatisfactory outcomes were observed in hips with entire epiphyseal involvement and more than 50% loss of its height. AVN following hip reconstructions is not necessarily associated with poor hip development, however, depending on the severity and location, it is a prognostic factor for unsatisfactory radiological outcomes.

Оценка уровня эндотелиального фактора роста сосудов и моноцитарного хемоаттрактанта при детском церебральном параличе

Objective. The aim of this article is to assess the role of vascular endothelial growth factor and monocytic chemoattractant in the development of cerebral palsy in children. Materials and methods. Examination of 77 children with different clinical forms of infantile cerebral palsy in the age group from 1 to 16 years was carried out. The content of monocyte chemoattractant (MCP) and vascular growth factor (VEGF) was determined in different forms of cerebral palsy. The obtained data were processed statistically. Results. The analysis of the obtained data revealed a significant increase in the indicators of monocytic chemoattractant and vascular growth factor in children with infantile cerebral palsy compared with healthy children. There were no significant differences between the indicators of MCP and VEGF in children with cerebral palsy and comorbid pathology and children with cerebral palsy without concomitant pathology. Conclusion. The authors of the presented analysis conclude that the determination of monocytic chemoattractant and vascular growth factor has a high diagnostic value for identifying a predisposition to the development of cerebral palsy. Timely detection of an increase in the level of these factors provides a broader prospective for early diagnosis of the disease and for the early implementation of rehabilitation measures accordingly.

Early detection relationship of cerebral palsy markers using brain structure and general movements in infants born

AimTo detect early brain structural and clinical functional markers of brain injury and development based on a magnetic resonance imaging (MRI) scoring system and a general movement assessment (GMA) for preterm infants later diagnosed with cerebral palsy (CP). Study designRetrospective cohort study. General movements (GMs) were scored according to a semiquantitative scoring system: the GMs optimality score (GMOS) at preterm and term ages and the Motor Optimality Score (MOS) at the corrected age of 3 months after birth. Brain magnetic resonance imaging (MRI) at term-equivalent age was scored using an MRI scoring system. We analyzed the relationship between the early degree of cerebral white matter (WM) abnormality and the GMOS and the MOS for infants born <32 weeks gestational age later diagnosed with CP in a comparison group of neurotypical controls. SubjectsSixteen preterm infants were included in this study who underwent MRI and GMs assessment. 8 out of the 16 preterm infants were later diagnosed with CP, while the other 8 infants with normal motor development (N) were placed into the control group. Their median gestational age was 30w6d and 27w6d for each group respectively. ResultsThe cerebral WM MRI scores were significantly higher in the CP group than in the control group (p < 0.01). The GMOS and MOS were significantly higher in the control group than in the CP group (p < 0.05). The MOS showed a strong correlation to the cerebral WM MRI score (r = -0.88) and the subscale of cerebral WM items (the cystic degeneration and the focal signal abnormalities) of the MRI score (r = -0.94) in the CP group. The MOS also showed a correlation with corrected biparietal diameter (cBPD) in the preterm infant group with CP (r = 0.75). Results of linear regression analyses between term MRI and GMs measures in preterm infants with CP are presented. Cerebral WM scores were associated with the MOS (β = −0.63; 95%CI = −0.97, −0.29; p < 0.01). Cerebral WM injury, including the subscale of cystic degeneration and focal signal abnormalities was closely associated with the MOS (β = −0.83; 95%CI = −1.13, −0.54; p < 0.001). ConclusionCerebral WM scores show a strong association with a decreased motor performance on the MOS in preterm infants later diagnosed with CP. Severe white matter injury and significantly decreased MOS scores may provide useful early markers and strong evidence to early predict the risk of later development of cerebral palsy in preterm infants.

Early micro- and macrostructure of sensorimotor tracts and development of cerebral palsy in high risk infants.

Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro‐ and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term‐equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3–4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole‐brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel‐based (FB) analysis to compute fiber density (FD), fiber‐bundle cross‐section (FC), and combined fiber density and cross‐section (FDC) for each tract. Of 223 VPT infants with high‐quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort's mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants.

Correlation of Postural Asymmetries with Gross Motor Functional Classification among Cerebral Palsy Children

Background: Motor control and posture disorders are responsible in the development of cerebral palsy (CP). Spastic CP, the most common type of CP is associated with postural asymmetries resulting in functional limitation among children and compromising their quality of life. Therefore, the study aimed to describe the severity of postural asymmetries among special school going children with spastic cerebral palsy in correlation with Gross Motor Function Classification System levels (GMFCS). Methods: Thirty-four subjects from Lahore who were special school going children diagnosed with spastic CP for more than 6 months and less than 1 year were recruited. Children with uncontrolled seizures, hearing and visual impairment, surgery scheduled and other types of cerebral palsy were excluded. The scale used for the assessment of postural asymmetries was Posture and Postural Ability Scale with the reliability of 0.99. ANOVA test was applied with p&lt;0.05 considered as statistically significant. Results: Severe asymmetries were found in standing position with 5.9% (n=2) in frontal and 20.6% (n=7) in sagittal plane. There were mild asymmetries in supine position, 55.9% (n=19) in frontal and 50% (n=17) in sagittal plane. In prone position, reported asymmetries were 55.9% (n=19) in frontal and 44.1% (n=15) in sagittal plane. In sitting position 76.5% (n=26) accounted for both frontal and sagittal plane asymmetries. p&lt;0.05 showed significant distribution of postural asymmetries. Conclusion: Severe postural asymmetries were found in standing position (p&lt;0.05). However, high frequency of pain, scoliosis and hip dislocation were observed at level III of GMFCS among special school going children diagnosed with spastic cerebral palsy. Keywords: Cerebral Palsy; Children; Spastic; Muscle Spasticity.

The influence of neonatal infections on the development of cerebral palsy

One of the most significant biological factors predisposing to cerebral palsy (CP) are infections. The paper aims to analyze neonatal infections’ influence in the risk of CP development with consideration of all significant risk factors including single, twin, full-term and pre-term pregnancies. 278 children with CP attending the chosen school-educational centers in Poland were included in the questionnaire. The control group included data obtained from the medical documentation of 435 children born in Limanowa County Hospital, Poland. Socio-economic factors, factors connected with pregnancy, and the coexisting disorders and diseases in children were taken into consideration. Constructed models of logistic regression were applied in the statistical analysis. Neonatal infections increase the risk of CP development in all children (odds ratio (OR) 5.1, 95% confidence interval (CI) 2.6–9.8), children from single pregnancies (OR 5.8, 95% CI: 3.0–11.29), full-term (OR 6.2, 95% CI: 3.2–12.3), and single full-term pregnancies (OR 6.0, 95% CI: 3.0–12.0). The influence of neonatal infections in the risk of CP development in children from pre-term and single premature pregnancies was not indicated. Neonatal infections are an independent risk factor for CP development in newborns from full-term pregnancy (&gt;37 weeks of pregnancy). The patho-mechanism of CP is different in children from full-term and premature pregnancy and results from interrelating factors are discussed in this paper.

Maternal Δ-aminolevulinic acid dehydratase 1-2 genotype enhances fetal lead exposure and increases the susceptibility to the development of cerebral palsy.

Limited epidemiologic studies questioned the association between pre- and postnatal lead exposure and the development of cerebral palsy (CP). Moreover, the genotypes of δ-aminolevulinic acid dehydratase (δ-ALAD) in CP patients and their mothers and their association to the blood lead levels (BLLs) were not previously studied. This study aimed to evaluate the association between δ-ALAD gene polymorphism and BLL in cases of CP and their mothers. A case control study was carried out on 23 CP cases and equal number of healthy matched controls. The mothers of the included children were asked to answer a questionnaire involving the baseline clinical and demographic characteristics. Also, questionnaires were done to detect the sources of environmental lead exposure and screen lead exposure during the pregnancy period. BLL, δ-ALAD enzyme activity, and genetic analysis for ALAD G177C were done for each child and his mother. There was significant (p < 0.001) elevation of BLL in CP cases and their mothers that was positively correlated (r = 0.436, p < 0.05). There were progressive decreases in δ-ALAD activity with increasing BLL in both children and mothers (p < 0.05). There were non-significant (p > 0.05) differences between CP and the control group regarding frequency of ALAD G177C genotypes, while there was a significant (p = 0.04) increase in the frequency of ALAD 1-2 (GC) genotype in the mothers of the CP group associated with high BLL and significant decrease in δ-ALAD activity (p < 0.001). The study can indicate the significance of δ-ALAD gene polymorphism in the prenatal exposure to lead and the affection of the developing brain, pointing to the importance of controlling lead in pregnant women especially those with ALAD 1-2 genotype.

The effect of increased bilirubin level on the risk of cerebral palsy

Increased bilirubin level in blood is mentioned among the potential factors with causal effect on cerebral palsy. The objective of the study was the analysis of its effect on the risk of cerebral palsy, considering all the significant risk factors as well as division into singleton, twin, term and preterm births. The research included a group of 278 children with cerebral palsy from selected educational-therapeutic institutions in Poland. The control group consisted of data from medical records of 435 neonates born in God’s Mercy Hospital in Limanowa, Poland. The analysis considered socio-economic factors, factors associated with pregnancy and parturition as well as accompanying disturbances and diseases of the children. Constructed models of logistic regression were used in statistcal analysis. The results were presented as the odds ratio (OR) with 95% confidence interval (CI). Testing the effect of increased bilirubin level in blood showed that the increased level of bilirubin is a significant predictor of CP in the categories of all children (OR 2.52, 95% CI: 1.47–4.33), children from singleton births (OR 2.66, 95% CI: 1.55–4.57), term births (OR 2.18, 95% CI: 1.24–3.84), term singleton births (OR 2.35, 95% CI: 1.31–4.21), preterm births (4.87, 95% CI: 1.56–15.21) and preterm singleton births (OR 3.62, 95% CI: 1.24–10.58). Increased bilirubin level is an independent risk factor in the development of cerebral palsy.

Abstract 54: Investigating Correlations Between Infarct Topography and Long-Term Outcomes Following Neonatal Arterial Ischemic Stroke Using Voxel-Based Lesion-Symptom Mapping

Objectives: To investigate correlations between infarct topography on acute diffusion weighted MRI, using voxel-based lesion-symptom mapping (VLSM), and later development of cerebral palsy (CP) and neurological impairments, in neonatal arterial ischaemic stroke (AIS). Methods: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language or cognitive-behavioural impairments were assessed using the Pediatric Stroke Outcome Measure dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using axial DWI images, and coregistered to the Melbourne Children’s Regional Infant Brain 2.0 atlas. All lesions were projected to the left hemisphere to obtain binary union masks. VLSM was conducted using MATLAB SPM12 toolbox. A generalised linear model was used to correlate the lesion mask with outcomes. Voxel-wise t test statistics were calculated, and corrected for multiple comparisons using family-wise error rate (FWE). Results: 85 newborns (55 male) met inclusion criteria. Infarct lateralization was left hemisphere in 62%, right in 8% and bilateral in 29%. At median age 2.1 years (IQR1.9-2.6), 34% developed CP and 42% had neurological impairments. 54 ROIs were correlated with CP (t&gt;4.33; FWE &lt;0.05); the 12 highest correlated ROIs were the superior corona radiata, putamen, anterior corona radiata, insula, thalamus, external capsule, pars triangularis, caudate, lateral orbitofrontal cortex, superior temporal cortex, pars opercularis and precentral cortex. (Figure) No significant correlations were found for poor language or cognitive-behavioural outcomes. Conclusions: Cerebral palsy following neonatal AIS correlates predominantly with regions of acute infarction directly involved in motor control, or in functionally connected regions. Brain regions associated with language or cognitive-behavioural impairment are less clear.

Cognitive Outcomes of Children with Very Low Birth Weight at 3 to 5 Years of Age.

BackgroundThe cognitive consequences and risk factors based long-term outcome of very-low-birth-weight (VLBW; < 1,500 g) infants in Korea has not been studied. The aim of this study was to determine the influence of perinatal and neonatal risk factors on the cognitive performance of VLBW children at 3 to 5 years of age.MethodsWe enrolled 88 VLBW infants without cystic periventricular leukomalacia for the assessment of their demographic data, cognitive performance, and development of cerebral palsy (CP) at 3 to 5 years of age. Cognitive performance was assessed using the Korean version of the Wechsler Preschool and Primary Scale of Intelligence IV. Growth data were assessed with measurements of weight, height, and head circumference (HC) at the corrected ages of 6, 12, and 18 months, and 3 to 5 years of age.ResultsIn the VLBW group, the full-scale intelligence quotient (FSIQ) was 96.1 ± 15.2 at the mean age of 4.5 years. The incidence rate of CP was 3.4%. Overall, 17% (15/88) of the VLBW children had a below-average FSIQ (< 85). We divided the VLBW children into the abnormal FSIQ group (< 85, n = 15) and the normal FSIQ group (≥ 85, n = 73). VLBW children with intrauterine growth retardation (IUGR) was associated with a below-average FSIQ at the mean age of 4.5 years (< 85, 8/15, 53.3% vs. ≥ 85, 5/73, 6.8%; P < 0.001). After controlling for associated clinical factors, IUGR in the VLBW children was found to be associated with an abnormal FSIQ at the mean age of 4.5 years (P = 0.025). The weight, height, and HC obtained for both groups showed that normal growth was maintained at the mean age of 4.5 years with no significant difference between abnormal and normal FSIQ groups.ConclusionFifteen of 88 (17%) of the VLBW children had a below-average FSIQ (< 85). VLBW with IUGR is associated with poor cognitive outcomes at the mean age of 4.5 years.

Genetic Aspects of Pathogenesis of Congenital Spastic Cerebral Paralysis

Congenital spastic cerebral palsy (СР) is a large group of non-progressive disorders of the nervous system. The basis of the pathogenesis of these conditions is considered the impact of many factors. The clinical diversity of the disease and the syndromic principle of classification determine the existing uncertainties in the diagnosis of these diseases. The multifactorial nature of the underlying brain lesions is obvious and beyond doubt. The volume of information accumulated to date does not allow one to exclude the role and significance of the direct effect of acute asphyxiation in childbirth on a fetus normally formed during pregnancy, the role of infectious brain lesions, and disorders of neuronal migration. It is impossible to ignore the dependence of the clinical picture of the disease on what stage of ontogenesis the impact of the damaging agent occurs. As one of the pathogenetic factors, the genetic determinism of the phenotype of the clinical picture of a disease is fairly considered. This review focuses on the genetic aspects of the pathogenesis of this pathology. The information on monogenic mechanisms of inheritance is analyzed in detail. Such genetically determined mechanisms of pathogenesis as the inheritance of prerequisites for brain trauma in the perinatal period are considered separately. The new clinically significant variants of chromosomal mutations found in patients with CР are reviewed in detail, the evidence of the influence of genetic factors on the development of cerebral palsy in the absence of a pronounced monogenic cause of the disease, obtained through twin studies, is reviewed. Lit search of polymorphisms markers of predisposition to the development of cerebral palsy genes of the folate cycle, genes of glutamate receptors, the gene of apolipoprotein and of the gene for the transcription factor of oligodendrocytes (OLIG2) in Detail the role of epigenetic effects on the activity of genes coding for mitochondrial proteins.

Early Detection of Cerebral Palsy Using Sensorimotor Tract Biomarkers in Very Preterm Infants

BackgroundOur objectives were to evaluate the brain's sensorimotor network microstructure using diffusion magnetic resonance imaging (MRI) at term-corrected age and test the ability of sensorimotor microstructural parameters to accurately predict cerebral palsy in extremely-low-birth-weight infants. MethodsWe enrolled a prospective pilot cohort of extremely-low-birth-weight preterm infants (birth weight ≤ 1000 g) before neonatal intensive care unit discharge and studied them with structural and diffusion MRI at term-corrected age. Six sensorimotor tracts were segmented, and microstructural parameters from these tracts were evaluated for their ability to predict later development of cerebral palsy, diagnosed at 18 to 22 months corrected age. ResultsWe found significant differences in multiple diffusion MRI parameters from five of the six sensorimotor tracts in infants who developed cerebral palsy (n = 5) versus those who did not (n = 36). When compared with structural MRI or individual diffusion MRI biomarkers, the combination of two individual biomarkers—fractional anisotropy of superior thalamic radiations (sensory component) and radial diffusivity of the corticospinal tract—exhibited the highest sensitivity (80%), specificity (97%), and positive likelihood ratio (28.0) for prediction of cerebral palsy. This combination of diffusion MRI biomarkers accurately classified 95% of the study infants. ConclusionsDevelopment of cerebral palsy in very preterm infants is preceded by early brain injury or immaturity to one or more sensorimotor tracts. A larger study is warranted to evaluate if a combination of sensorimotor microstructural biomarkers could accurately facilitate early diagnosis of cerebral palsy.

Maternal concentrations of human chorionic gonadotropin (hCG) and risk for cerebral palsy (CP) in the child. A case control study

BackgroundIntrauterine conditions may be important in the development of cerebral palsy in the child. The hormone, human chorionic gonadotropin (hCG), is synthesized in the placenta, and hCG plays an important role in placental angiogenesis and development. Thus, maternal hCG concentrations may be an indicator of placental function and thereby the intrauterine environment for the offspring. We studied the associations of maternal concentrations of hCG during pregnancy with cerebral palsy in the child. MethodsWe performed a case-control study nested within a cohort of 29,948 pregnancies in Norway during 1992–1994. Cases were all women within the cohort who gave birth to a singleton child with cerebral palsy diagnosed before five years of age (n = 63). Controls were a random sample of women with a singleton child without cerebral palsy (n = 182). ResultsThe adjusted odds ratio (OR) for cerebral palsyin the child was 0.78 (95% CI: 0.55–1.10) per log-transformed unit of maternal hCG in the 1 st trimester, and the OR was 1.42 (95% CI: 0.94–2.16) in the 2nd trimester. Thus, women who did not have high hCG concentrations in the 1 st trimester and low hCG concentrations in the 2nd trimester, had increased risk for giving birth to a child with cerebral palsy. Adjustments were made for pregnancy week of serum sampling, maternal age and parity. ConclusionsThe abnormal hCG concentrations in pregnancies with cerebral palsy in the offspring, could suggest placental factors as causes of cerebral palsy.

Combined Analysis of Interleukin-10 Gene Polymorphisms and Protein Expression in Children With Cerebral Palsy.

Interleukin-10 (IL-10) is an important anti-inflammatory and immunosuppressive cytokine, and it has indispensable functions in both the onset and development of inflammatory disorders. The association between persistent inflammation and the development of cerebral palsy (CP) has attracted much attention. The purpose of this study was to investigate whether IL-10 gene polymorphisms and plasma protein expression are associated with CP and to analyze the role of IL-10 in CP. A total of 282 CP patients and 197 healthy controls were genotyped for IL-10 polymorphisms (rs1554286, rs1518111, rs3024490, rs1800871, and rs1800896). Among them, 95 CP patients and 93 healthy controls were selected for plasma IL-10 measurement. The differences in the rs3024490 (p = 0.033) and rs1800871 (p = 0.033) allele frequencies of IL-10 were determined between CP patients and controls. The frequencies of allele and genotype between CP patients with spastic tetraplegia and normal controls of IL-10 polymorphisms showed significant differences for rs1554286, rs151811, rs3024490, rs1800871, and rs1800896 (pallele = 0.015, 0.009, 0.006, 0.003, and 0.006, pgenotype = 0.039, 0.018, 0.027, 0.012, and 0.03, respectively). The plasma IL-10 protein level in CP patients was higher than normal controls (9.13 ± 0.77 vs. 6.73 ± 0.63 pg/ml, p = 0.017). IL-10 polymorphisms and protein association analysis showed that the TT genotype had higher plasma IL-10 protein levels compared to the GG + GT genotype at rs3024490 (11.14 ± 7.27 vs. 7.44 ± 6.95 pg/ml, p = 0.045, respectively) in CP cases. These findings provide an important contribution toward explaining the pleiotropic role of IL-10 in the complex etiology of CP.

Apolipoprotein E allelic variants and cerebral palsy.

Gümüş E, Aras BD, Çilingir O, Yarar C, Çarman KB, Laçiner-Gürlevik S, Koçak O, Artan S. Apolipoprotein E allelic variants and cerebral palsy. Turk J Pediatr 2018; 60: 361-371. Cerebral palsy (CP) is the most frequent cause of mobility restriction and posture disturbance in childhood. Against the complexity in disease etiology, genetic factors, including Apolipoprotein E allelic distribution in this patient population, are worthy targets for investigation. ApoE is a lipoprotein of central nervous system encoded by ApoE gene with its 3 main co-dominant alleles, 2, 3 and 4. We aimed to evaluate the allelic frequencies of ApoE gene and its association with coexisting clinical entities such as vision and hearing impairment, cognitive problems, seizures and MRI findings in a pediatric patient population native to middle Anatolian region. Seventy-eight children with CP and 60 healthy controls were genotyped. Genotypic variations along with coexisting clinical conditions and CP-related medical findings were compared between the patient and control groups. The Denver Developmental Screening Test for all, the Wechsler Intelligence Scale for Children-IV (short form WISC-IV; Turkish version) for the patients > 6y and the Stanford-Binet Intelligence Scale (SB-5) for those who aged 2-6 years old were employed to evaluate cognitive and mental abilities of the patients. ApoE 2 and 4 alleles were more frequent in the patient group (p < 0.05), whereas ApoE 3 allele was more frequent in the healthy controls. ApoE 2/4 genotype has been determined 29% in the case group, but none in healthy control group. In the patient group with apolipoprotein 4 or 2 alleles, the rate of emergency cesarean section was found being significantly higher than the group with 3 allele. Brain MRI findings were not significantly different among ApoE allelic variants within the patient group. Our data show that the ApoE alleles may be effective in the development of cerebral palsy and may be associated with some clinical manifestations in those patients.

The role of intrauterine infections in the development of cerebral palsy in children

The role of intrauterine infections in the development of cerebral palsy in children

Analysis of risk factors in the development of cerebral palsy in children

Analysis of risk factors in the development of cerebral palsy in children

Reactive astrocyte COX2-PGE2 production inhibits oligodendrocyte maturation in neonatal white matter injury.

Inflammation is a major risk factor for neonatal white matter injury (NWMI), which is associated with later development of cerebral palsy. Although recent studies have demonstrated maturation arrest of oligodendrocyte progenitor cells (OPCs) in NWMI, the identity of inflammatory mediators with direct effects on OPCs has been unclear. Here, we investigated downstream effects of pro-inflammatory IL-1β to induce cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) production in white matter. First, we assessed COX2 expression in human fetal brain and term neonatal brain affected by hypoxic-ischemic encephalopathy (HIE). In the developing human brain, COX2 was expressed in radial glia, microglia, and endothelial cells. In human term neonatal HIE cases with subcortical WMI, COX2 was strongly induced in reactive astrocytes with "A2" reactivity. Next, we show that OPCs express the EP1 receptor for PGE2, and PGE2 acts directly on OPCs to block maturation in vitro. Pharmacologic blockade with EP1-specific inhibitors (ONO-8711, SC-51089), or genetic deficiency of EP1 attenuated effects of PGE2. In an IL-1β-induced model of NWMI, astrocytes also exhibit "A2" reactivity and induce COX2. Furthermore, in vivo inhibition of COX2 with Nimesulide rescues hypomyelination and behavioral impairment. These findings suggest that neonatal white matter astrocytes can develop "A2" reactivity that contributes to OPC maturation arrest in NWMI through induction of COX2-PGE2 signaling, a pathway that can be targeted for neonatal neuroprotection.