Etiology Of Cerebral Palsy Research Articles

Antenatal Antecedents and the Impact of Obstetric Care in the Etiology of Cerebral Palsy

Cerebral palsy (CP) affects 2/1000 live-born children. Multiple antenatal factors, including preterm delivery, low birth weight, infection/inflammation, multiple gestation, and other pregnancy complications, are mostly associated with CP in both the preterm and term infant, with birth asphyxia playing a minor role. Owing to the increasing survival of the very preterm and very low birth weight infant secondary to improvements in neonatal and obstetric care, the incidence of CP may be increasing. The focus of this paper is to explore antenatal antecedents as etiologies of CP and the impact of obstetric care on the prevention of CP.

Family patterns of gestational age at delivery and growth in utero in moderate and severe cerebral palsy.

The relation of familial factors to the aetiology of cerebral palsy was assessed in a case-control study of all moderate and severe cases born in Western Australia between 1980 and 1986. The data did not suggest recurrence of cerebral palsy, congenital malformations or reproductive loss in cerebral palsy families. Preterm and small-for-gestational-age birth recurred within both case and control families. Cases and controls did not differ significantly from their siblings in measures of intra-uterine growth, but (with the exception of controls unmatched for both birthweight and gestational age) were born significantly earlier than their siblings. A family history of preterm or small-for-gestational-age birth was found to affect the risk of cerebral palsy by influencing the risk of preterm birth or growth retardation in the index pregnancy.

The Clinical Spectrum Of Paediatric Neurological Disorders In Aminu Kano Teaching Hospital, Kano

Background: Neurological disorders have been noted to account for more than 20% of global disease burden and that poor countries are disproportionately affected. The aim of this review was to highlight the clinical spectrum of neurologic disease seen in Kano as there had been no previous report from the center. Materials and methods: The medical records of all children who attended the paediatric neurologic clinic over 8-year period were examined and all relevant data were extracted and analysed. Results: Three hundred and fifty six patients were reviewed. There were 222 males and 134 females with ratio of 1.7:1. Age range was 2 months – 12years. Some patients had multiple morbidities. The predominant neurologic morbidities included: cerebral palsy (42.4%), epilepsy (27.8%), febrile seizure (6.5%), mental retardation(6.2%), microcephaly (5.6%), behavioral problems (5.6%), poliomyelitis (4.5%), hydrocephalus (4.2%), visual impairment (2.8%), down syndrome (1.7%), and attention deficit hyperactivity disorder (1.4%). A few others occurred infrequently. Birth asphyxia featured prominently in aetiology of cerebral palsy and epilepsy. Conclusion: It is suggested that preventive measures through health education and improved perinatal health services will greatly help in reduction of neurologic morbidities in Kano Keywords: Review, Neurological, DisordersSahel Medical Journal Vol. 11 (1) 2008: pp. 12-14

High dose botulinum toxin A for the treatment of lower extremity hypertonicity in children with cerebral palsy

The aim of this study was to determine the safety profile of high dose (15-25 units/kg) of botulinum toxin A (BTX-A) in children with cerebral palsy (CP) and increased lower extremity muscle tone. We performed a retrospective review of 929 patient encounters at the Movement Disorders Center at Washington University. A total of 261 patients (105 females; 156 males) were treated during these visits, ages 6 months to 21 years (mean 8 y 4 mo [SD 4 y 8 mo]). Ambulatory ability at the time of BTX-A injection was independent ambulation (36.4%, n=95), ambulation with a walker (27.6%, n=72), and non-ambulatory (31.8%, n=83). A few patients (4.2%, n=11) were able to ambulate with a cane or crutch at the time of injection. Participants were characterized according to BTX-A dose, CP etiology, motor involvement pattern, muscles injected, ambulatory ability, and use of oral tone medications. Follow-up records were searched for reported adverse events (AEs), with a mean time to AE assessment of 6.5 weeks (SD 3.38). The AE occurrence was determined for doses of 0 to 4.9 units/kg, 5 to 9.9 units/kg, 10 to 14.9 units/kg, 15 to 19.9 units/kg, and 20 to 25 units/kg. The overall AE occurrence was 4.2%. Standard doses of BTX-A had side-effect occurrences of 3.9% for 5 to 10 units/kg and 7.6% for 10 to 15 units/kg. Among higher doses (15-20 units/kg and 20-25 units/kg) the AE occurrence was 3.5% and 8.6% respectively. No patient developed botulism. AEs were randomly distributed across dosing groups, CP etiologies, clinical phenotypes, ambulatory status, and treatment duration. All doses were associated with a significant increase in passive range of motion using the Tardieu scale. We conclude that higher dose BTX-A is safe in children with a spectrum of CP phenotypes and are well tolerated over time.

Aetiology of cerebral palsy in children presenting at Tygerberg Hospital

Two hundred and forty-two records of children with cerebral palsy were reviewed with regard to the aetiology of their condition. The origin of the insult was prenatal in 70 (28.9%), perinatal/neonatal in 92 (38%), acquired in 51 (21%) and unclassifiable in 29 (11.98%). Cerebral malformations (15.7%) and stroke (5.7%) were the most frequent antenatal causes, while birth asphyxia (17.3%), encephalopathy of prematurity (17.7%) and to a lesser degree kernicterus (2%) constituted the most frequent perinatal causes. Acquired cerebral palsy, particularly secondary to nervous system infections (82%), constituted a significant proportion of cases. Spastic quadriplegia (40%) was the most common type of cerebral palsy. The predominance of cases of perinatal and acquired aetiology is in contrast to the antenatal preponderance reported in developed countries.

Infections and other inflammatory conditions

The etiology of cerebral palsy and other related perinatal brain injuries is poorly understood. Infections of the central nervous system are rare but important causes of neurodisability. Recent evidence suggests that infections and other inflammatory conditions apparently limited to the placenta are also associated with an increased risk of neurologic impairment. A major hypothesis to explain this connection is that cytokines, activated inflammatory cells, and other mediators of the innate immune response are released into the fetal circulation where they can directly or indirectly affect the development or integrity of the central nervous system. This review surveys the organisms, mediators, and placental lesions that have been associated with perinatal brain injury.

Cyclooxygenase-2 mediates the sensitizing effects of systemic IL-1-beta on excitotoxic brain lesions in newborn mice

Epidemiological and experimental data implicate maternal-fetal infection and an associated increase in circulating cytokines in the etiology of cerebral palsy. We have previously shown that pretreatment of newborn mice with systemic interleukin-1-beta exacerbates ibotenate-induced excitotoxic brain lesions. Such lesions are consistent with those observed in cerebral palsy. The present study builds on this murine model to assess the role of cyclooxygenase in interleukin-1-beta-induced brain toxicity. Pups pretreated with interleukin-1-beta developed greater ibotenate-induced brain damage than controls, an effect blocked by the co-administration of nimesulide (cyclooxygenase-2 inhibitor) or indomethacin (cyclooxygenase-1 and -2 inhibitor). Cyclooxygenase inhibitor administration prevented the interleukin-1-beta-induced increase in the production of brain prostaglandin E(2) (a cyclooxygenase metabolite) and changes in the expression of brain interleukin-6, interleukin-18, tumor necrosis factor-alpha, and brain-derived neurotrophic factor. It also stimulated the expression of brain interleukin-10. Our data suggest that the sensitizing effects of circulating inflammatory cytokines on the brain are mediated by the inducible isoform cyclooxygenase-2, which generates excess prostaglandin E(2). Some of these deleterious effects could involve an autocrine/paracrine loop leading to a disruption of the balance between pro- and anti-inflammatory cytokines in the brain.

Development of hand–arm bimanual intensive training (HABIT) for improving bimanual coordination in children with hemiplegic cerebral palsy

Constraint-induced (CI) movement therapy is a physical intervention that has been receiving increasing attention in pediatric rehabilitation. So far, the evidence suggests that practice associated with CI therapy may improve impaired unimanual hand function in some children with hemiplegic cerebral palsy (CP). However, CI therapy has several important limitations. Most importantly, children with hemiplegia have impairments in bimanual coordination beyond their unilateral impairments. Thus, an intervention approach to increase functional independence during activities of daily living by using both hands in cooperation is needed. Here we briefly review the etiology of hemiplegic CP, describe studies of pediatric CI therapy efficacy in relation to the etiology, discuss the conceptual and practical limitations of CI therapy for this population, and describe bimanual coordination impairments in children with hemiplegia. Finally, we introduce a new intervention for children with hemiplegia, hand-arm bimanual intensive training (HABIT), to address the limitations of CI therapy and to improve bimanual coordination. HABIT retains the two major elements of pediatric CI therapy (intensive structured practice and child-friendliness). The proposed methodology demonstrates that extensive targeted practice can be provided in a child-friendly manner without using a physical restraint, although the efficacy of such an approach remains to be determined.

The role of perinatal and intrapartum risk factors in the etiologyof cerebral palsy in term deliveries in a Turkish population

Objective. To investigate the relationship between cerebral palsy (CP) and perinatal and intrapartum risk factors and markers of birth asphyxia.Methods. This was a retrospective case–control study of 101 children with CP and 308 controls who were born at the Zeynep Kamil Hospital between 1990 and 2000. The roles of possible perinatal and intrapartum risk factors were investigated in CP development. Chi-square tests, Fisher's exact tests, Student t-tests, and regression analysis were used for statistical analysis (p < 0.05).Results. The only significant perinatal risk factor was neonatal weight of <2500 grams. The CP rate in the presence of solely intrapartum risk factors was estimated as 24.7% (n = 25). In 39.6% of cases, no risk factor could be identified. When regression analysis was performed, the following factors were significant: decreased beat-to-beat variability on electronic fetal monitoring (EFM) (p = 0.02), an Apgar score of <7 at 1 and 5 minutes (p = 0.02), and the necessity for neonatal intensive care unit admission (p < 0.0001).Conclusion. Intrapartum risk factors were significantly more frequent in the CP group (p < 0.01). An increased cesarean section rate could not prevent CP, suggesting that the hypoxic insult that causes CP might be of chronic onset. The development of diagnostic tests to detect non-reassuring fetal status in its intrauterine life and interventions at appropriate times may decrease the CP rate.

Control de la epilepsia en niños y adolescentes con parálisis cerebral con respecto a la etiología y la lesión cerebral de base

Epilepsy in children with cerebral palsy is a very important problem of public health, with a prevalence 750/1,000. AIM. To describe the relationship between cerebral palsy-etiologies and the cerebral injuries in the epilepsy control. Retrospective study included 398 subjects, both genders, subjects under 18 years old with evidence of epilepsy related to infantile cerebral palsy (ICP). For comparison analysis purposes the entire population was studied on two principally aspects: ICP based on its etiology, and ICP based on cerebral injury background by means of computer tomography (CT). The etiology was subdivided into: hypoxic-ischemic encephalopathy (HIE), cerebral malformation (CM), and others causes (O). Cerebral lesions were classified into: diffuse cerebral injury (DCI), focal location injury (FLI), basal ganglia injury (BGI), cerebral dysgenesia (CD), hydrocephaly (H) and non-CT evidence (N). The impact of the epileptic seizures was determined according to the cerebral injury background and its etiology. The findings after clinical surveillance and statistical analysis were able to affirm that seizures control with respect to etiology was: HIE: 77.9%, CM: 72%, O: 86% without statistical significance (p < 0.28). We found in the cerebral lesion: DCI: 70.7 %, FLI: 82.4%, BGI: 87.5%, CD: 79.3%, H: 77.8%, N: 83.3%, statistical significance was found in these subgroups (p < 0.04). Cerebral injury in children suffering from cerebral has a prognostic reliance value in the control of epilepsy, regardless its etiology.

Comparison of risk factors for cerebral palsy in twins and singletons

The aim of this study was to investigate the difference in rates of cerebral palsy (CP) between singletons and twins by considering factors that may be predictive of CP. Data were taken from the Scottish Register of Children with a Motor Deficit of Central Origin and the Scottish Morbidity Record series. All children born in Scotland between 1984 and 1990 inclusive comprised the cohort. There were 646 children with CP (370 males, 276 females) of whom 57 were from twin pregnancies. Prevalence of CP was higher in twins than in singletons. Also, for singleton and twin births, the prevalence of CP was higher for infants who had low birth weight for gestational age (GA), were preterm, and who were male. Prevalence of CP by GA followed a different pattern for twins than for singletons, being lower for twins in the middle range of GAs than for singletons. After allowing for GA and birth weight, twins appeared to be at increased risk for CP compared with singletons. The type of CP in singletons and twins also differed with 64.9% of twins having spastic bilateral CP compared with 48.5% for singletons. The aetiology of CP in twins and singletons may differ.

Comparison of risk factors for cerebral palsy in twins and singletons

The aim of this study was to investigate the difference in rates of cerebral palsy (CP) between singletons and twins by considering factors that may be predictive of CP. Data were taken from the Scottish Register of Children with a Motor Deficit of Central Origin and the Scottish Morbidity Record series. All children born in Scotland between 1984 and 1990 inclusive comprised the cohort. There were 646 children with CP (370 males, 276 females) of whom 57 were from twin pregnancies. Prevalence of CP was higher in twins than in singletons. Also, for singleton and twin births, the prevalence of CP was higher for infants who had low birthweight for gestational age (GA), were preterm, and who were male. Prevalence of CP by GA followed a different pattern for twins than for singletons, being lower for twins in the middle range of GAs than for singletons. After allowing for GA and birthweight, twins appeared to be at increased risk for CP compared with singletons. The type of CP in singletons and twins also differed with 64.9% of twins having spastic bilateral CP compared with 48.5% for singletons. The aetiology of CP in twins and singletons may differ.

Ante- and Perinatal Factors for Cerebral Palsy: Case-Control Study in Estonia

Establishing consistency between cerebral palsy registries in reporting of new cases enables more effective collaboration in terms of researching predisposing factors. To identify antenatal and intrapartum risk factors for cerebral palsy in the Estonian population, we undertook a matched case-control study of 153 children with cerebral palsy, ascertained from a population-based survey. One hundred two maternal, antenatal, and intrapartum variables were initially retrieved from medical records. Main outcome measures were the odds ratio estimates of relative risk of cerebral palsy. As a result of the study, and considering the whole spectrum of severity, the relevant risk factors during pregnancy were bleeding after 20 weeks, anemia in the second half of pregnancy, pregnancy-induced hypertension in the second half of pregnancy, and preeclampsia. The most important intrapartum factors were premature birth, placental abruption, an acute hypoxic event during delivery, and any fetal presentation other than vertex. Predisposing factors related to neonatal condition were an Apgar score < or = 7 at the first and fifth minutes of life, hypoxic-ischemic encephalopathy, and assisted ventilation. Our findings suggest that intrapartum factors, including those hypothetically realized through hypoxic-ischemic pathways, are not of low importance in the etiology of cerebral palsy.

Antioxidant enzymes and lipid peroxides in children with cerebral palsy

Impaired antioxidant mechanisms are unable to inactivate free radicals that may induce a number of pathophysiological processes and result in cell injury. Thus, any abnormality in antioxidant defense systems could affect neurodevelopmental processes and could have an important role in the etiology of cerebral palsy (CP). The plasma levels of lipid peroxidation as plasma levels of malondialdehyde (MDA), activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) in plasma and erythrocytes were investigated in 34 CP children and compared with 61 normal controls. SOD, GPx and GR activities were spectrophotometrically assayed. Activities of SOD, GPx and GR in plasma did not differ significantly between CP children and the control group. Activities of erythrocyte GR in the CP patients were significantly lower compared with controls. MDA concentration did not differ statistically between the CP children and healthy subjects. In conclusion our results suggest that increased activities of erythrocyte GPx and decreased erythrocyte GR activities might be due to lesser physical activity of children with CP.

Why is there a modifying effect of gestational age on risk factors for cerebral palsy?

Objective: To investigate risk factors for cerebral palsy in relation to gestational age. Design: Three case-control studies within a geographically defined cohort. Setting: The former Oxfordshire Health Authority. Participants: A...

Congenital abnormalities among children with cerebral palsy: More evidence for prenatal antecedents

Objectives: To investigate the association between cerebral palsy (CP) and congenital abnormalities among children with very low, low, and normal birth weight. Study design: A population-based, case-control study among the cohort of 155,636 live births delivered between 1983 and 1985 in 4 California counties. Children with moderate or severe congenital CP (n = 192) diagnosed by age 3 were identified from 2 California State service agencies, and 551 control children were randomly sampled from birth certificate files. Information on congenital abnormalities diagnosed by the age of 1 year was obtained from the California Birth Defects Monitoring Program registry. Odds ratios (OR) and 95% CIs were calculated to estimate risk for CP associated with congenital abnormalities. Results: Among singletons, congenital abnormalities were present in 33 (19.2%) children with CP and 21 (4.3%) control children (OR = 5.2, 95% CI 2.8-9.7). For each birth weight group, the percent of children with congenital abnormalities among children with CP exceeded that among control children. Structural abnormalities of the central nervous system were more common among children with CP (OR = 16.2, 95% CI 5.8-49.3) than control children. In contrast, the percent of children with non–central nervous system abnormalities only was similar between case patients and control subjects. Conclusion: These findings provide further evidence that factors operating in the prenatal period contribute significantly to the etiology of CP. (J Pediatr 2001;138:804-10)

Correlation between ICIDH handicap code and Gross Motor Function Classification System in children with cerebral palsy.

The aim of this study was to apply the International Classification of Impairments, Disabilities and Handicap (ICIDH; WHO 1980) parallel to the Gross Motor Function Classification System (GMFCS; Palisano et al. 1997) in a population-based series of children with cerebral palsy (CP). Of the 116 children studied, birth characteristics, data on gross motor function, and level of handicap at 5 to 6 years of age, were retrospectively collected from medical records and documentation made by rehabilitation team members. Low handicap scores and mild levels of gross motor disability were present in children with hemiplegic CP, moderate scores in children with diplegic CP, simple ataxia, and athetotic CP, and high scores in children with dystonic CP and tetraplegic CP. A significant correlation was found between high handicap scores as well as high levels on the GMFCS and the presence of learning disability, epilepsy, and obvious aetiology of CP. A strong correlation was found between the handicap code and the GMFCS, the strongest concerning the dimension of mobility (r = 0.95,p<0.0001). A striking similarity in the grading of disability was present between the ICIDH handicap code and the GMFCS. The GMFCS is considerably less time-consuming and can be evaluated retrospectively. The handicap code requires more detailed information and is more useful for a comprehensive profile of the child.

Correlation between ICIDH handicap code and Gross Motor Function Classification System in children with cerebral palsy

The aim of this study was to apply the International Classification of Impairments, Disabilities and Handicap (ICIDH; WHO 1980) parallel to the Gross Motor Function Classification System (GMFCS; Palisano et al. 1997) in a population‐based series of children with cerebral palsy (CP). Of the 116 children studied, birth characteristics, data on gross motor function, and level of handicap at 5 to 6 years of age, were retrospectively collected from medical records and documentation made by rehabilitation team members. Low handicap scores and mild levels of gross motor disability were present in children with hemiplegic CP, moderate scores in children with diplegic CP, simple ataxia, and athetotic CP, and high scores in children with dystonic CP and tetraplegic CP. A significant correlation was found between high handicap scores as well as high levels on the GMFCS and the presence of learning disability, epilepsy, and obvious aetiology of CP. A strong correlation was found between the handicap code and the GMFCS, the strongest concerning the dimension of mobility (r=0.95, p&lt;0.0001). A striking similarity in the grading of disability was present between the ICIDH handicap code and the GMFCS. The GMFCS is considerably less time‐consuming and can be evaluated retrospectively. The handicap code requires more detailed information and is more useful for a comprehensive profile of the child.

A gene for ataxic cerebral palsy maps to chromosome 9p12-q12.

Cerebral palsy (CP) has an incidence of approximately 1 in 750 births, although this varies between ethnic groups. Genetic forms of the disease account for about 2% of cases in most countries, but contribute a larger proportion in certain sub-types of the condition and in populations with a large proportion of consanguineous marriages. Ataxic cerebral palsy accounts for 5-10% of all forms of CP and it is estimated that approximately 50% of ataxic cerebral palsy is inherited as an autosomal recessive trait. We have identified a complex consanguineous Asian pedigree with four children in two sibships affected with ataxic cerebral palsy and have used homozygosity mapping to map the disorder in this family. A genome-wide search was performed using 343 fluorescently labelled polymorphic markers and linkage to chromosome 9p12-q12 was demonstrated. A maximum Lod score of 3.4 was observed between the markers D9S50 and D9S167 using multipoint analysis, a region of approximately 23cM. We have identified a family that segregates both ataxic CP and ataxic diplegia and have mapped the genetic locus responsible in this family to chromosome 9p12-q12. The identification of gene(s) involved in the aetiology of CP will offer the possibility of prenatal/premarital testing to some families with children affected with the disorder and will greatly increase our understanding of the development of the control of motor function.

Utility of brainstem auditory evoked potentials in children with spastic cerebral palsy

In a retrospective study of 75 children with spastic cerebral palsy (CP), brainstem auditory evoked potentials (BAEP) were recorded and subsequently correlated with birthweight, gestational age, aetiology and type of CP, neuroradiological findings, additional impairments and disabilities (including the inability to walk independently). Seventeen patients (22.7%) had abnormal BAEP recordings. Thirteen of these 17 patients (76.5%) had spastic tetraplegia, 16 patients (94.1%) were full-term infants, 12 patients (70.6%) had myoskeletal problems, 9 (52.9%) had epilepsy, 16 (94.1%) had visual impairment, 13 patients (76.5%) were unable to walk independently, while all 17 patients (100%) had speech impairment and mental retardation. The aetiology of CP was prenatal in 2 of these 17 patients (11.8%) and perinatal in 15 patients (88.2%). Thirteen patients (76.5%) had cortical atrophy determined by either computed tomography or magnetic resonance imaging, two patients (11.8%) had an infarct picture and two patients (11.8%) had maldevelopment of the central nervous system. There was a definite statistically significant association between abnormal BAEP recordings and full-term delivery, perinatal aetiology of CP, spastic tetraplegia, speech, visual and myoskeletal impairments, epilepsy, mental retardation, inability to walk independently and cortical atrophy on neuroimaging (p < 0.001). We conclude that abnormal BAEP recordings in children with spastic CP are indicative of poor prognosis and associated with a "multihandicap state". BAEP testing should be incorporated into the diagnostic plan of all children with spastic CP newly referred to neurodevelopmental centres.