Issues in the classification and epidemiology of cerebral palsy

Blair, Eve; Stanley, Fiona

doi:10.1002/(sici)1098-2779(1997)3:2<184::aid-mrdd10>3.0.co;2-r

Cited by 39 publications

(23 citation statements)

References 77 publications

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“…Congenital infections appear to contribute up to 5% of cerebral palsy cases 1,2 and may sensitize the brain to perinatal hypoxic ischemic (HI) insult. [3][4][5] This synergistic effect was also reproduced in mammalian and avian animal models, combining HI insult and the lipopolysaccharide break-down product of bacteria in HI animal models.6-10 However, the molecular mediators of this endotoxin effect in vivo are currently still unknown.Both in vitro and in vivo studies show that endotoxin will upregulate numerous cytokines and chemokines, 11 upregulate signaling enzymes, such as inducible nitrogen oxide synthase (iNOS), and cyclo-oxygenase-2 (COX2) and enhance the expression of adhesion molecules on parenchymal microglia and the brain vascular endothelium. …”

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confidence: 71%

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TNF gene cluster deletion abolishes lipopolysaccharide-mediated sensitization of the neonatal brain to hypoxic ischemic insult

Kendall

Hirstova

Horn

et al. 2011

Laboratory Investigation

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In the current study, we explored the role of TNF cluster cytokines on the lipopolysaccharide (LPS)-mediated, synergistic increase in brain injury after hypoxic ischemic insult in postnatal day 7 mice. Pretreatment with moderate doses of LPS (0.3 mg/g) resulted in particularly pronounced synergistic injury within 12 h. Systemic application of LPS alone resulted in a strong upregulation of inflammation-associated cytokines TNFa, LTb, interleukin (IL) 1b, IL6, chemokines, such as CXCL1, and adhesion molecules E-Selectin, P-Selectin and intercellular adhesion molecule-1 (ICAM1), as well as a trend toward increased LTa levels in day 7 mouse forebrain. In addition, it was also associated with strong activation of brain blood vessel endothelia and local microglial cells. Here, deletion of the entire TNF gene cluster, removing TNFa, LTb and LTa completely abolished endotoxin-mediated increase in the volume of cerebral infarct. Interestingly, the same deletion also prevented endothelial and microglial activation following application of LPS alone, suggesting the involvement of these cell types in bringing about the LPS-mediated sensitization to neonatal brain injury. KEYWORDS: encephalopathy; hypoxia; inflammation; ischemia; neonate; TNF Although bacteria and viruses can directly infect and injure developing brain, infections occurring outside the brain frequently will also have a damaging effect. Congenital infections appear to contribute up to 5% of cerebral palsy cases 1,2 and may sensitize the brain to perinatal hypoxic ischemic (HI) insult. [3][4][5] This synergistic effect was also reproduced in mammalian and avian animal models, combining HI insult and the lipopolysaccharide break-down product of bacteria in HI animal models.6-10 However, the molecular mediators of this endotoxin effect in vivo are currently still unknown.Both in vitro and in vivo studies show that endotoxin will upregulate numerous cytokines and chemokines, 11 upregulate signaling enzymes, such as inducible nitrogen oxide synthase (iNOS), and cyclo-oxygenase-2 (COX2) and enhance the expression of adhesion molecules on parenchymal microglia and the brain vascular endothelium. 12-15Follow on molecular studies reveal that these effects are transmitted through the classical endotoxin receptors, primarily the toll-like receptor 4 (TLR4), on blood vessel endothelia and microglia, 16,17 and involve MyD88 and NF-kappa-B components of the innate immunity cascade. 17In particular, endotoxin-induced pro-inflammatory cytokines, including TNFa and interleukin 1b (IL1b) are known to have a number of deleterious effects, including a direct toxic effect on neurones and vulnerable oligodendrocyte precursors, 18,19 astrogliosis with release of nitric oxide, and mitochondrial dysfunction, 20 as well as microglial activation with release of nitric oxide, superoxide and a panel of other inflammation-associated molecules.

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confidence: 71%

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confidence: 99%

TNF gene cluster deletion abolishes lipopolysaccharide-mediated sensitization of the neonatal brain to hypoxic ischemic insult

Kendall

Hirstova

Horn

et al. 2011

Laboratory Investigation

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“…The rate of cerebral palsy for the most recent quinquennium was 2.45 per thousand compared with rates of between 2.0 and 3.0 in the international literature 12-2315-17have continued to rise; in Italy23 the rate peaked in 1985 before declining; rates are steady in Avon (UK),24declining in Norway,18 and fluctuating in Australia 21. Birth weight specific rates for newborns in our study are still rising both for babies < 1500 g and those 1500–2499 g. For normal birth weight babies, there is no sign of a fall.…”

Section: Discussionmentioning

confidence: 87%

“…The only comparable studies in terms of duration and continuity are from the United Kingdom (Mersey),1Sweden,17 and Australia,20 21 which, like ours, benefit from consistent application of inclusion and exclusion criteria for motor impairments associated with syndromes and diseases 25. The Swedish study, however, identifies currently resident cases every five years rather than reporting cases from a cohort resident at birth, as we do, and excludes children who die before 2 years of age.…”

Section: Discussionmentioning

confidence: 99%

Increasing rates of cerebral palsy across the severity spectrum in north-east England 1964-1993

Colver

Gibson²,

Hey³

et al. 2000

Archives of Disease in Childhood - Fetal and Neonatal Edition

151

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Objectives-To report epidemiological trends in cerebral palsy including analyses by severity. Design-Descriptive longitudinal study in north-east England. Every child with suspected cerebral palsy was examined by a developmental paediatrician to confirm the diagnosis. Severity of impact of disability was derived from a parent completed questionnaire already developed and validated for this purpose. Subjects-All children with cerebral palsy, not associated with any known postneonatal insult, born 1964-1993 to mothers resident at the time of birth in the study area. Main outcome measures-Cerebral palsy rates by year, birth weight, and severity. Severity of 30% and above defines the more reliably ascertained cases; children who died before assessment at around 6 years of age are included in the most severe group (70% and above). Results-584 cases of cerebral palsy were ascertained, yielding a rate that rose from 1.68 per 1000 neonatal survivors during 1964-1968 to 2.45 during 1989-1993 (rise = 0.77; 95% confidence interval 0.2-1.3). For the more reliably ascertained cases there was a twofold increase in rate from 0.98 to 1.96 (rise = 0.98; 95% confidence interval 0.5-1.4). By birth weight, increases in rates were from 29.8 to 74.2 per 1000 neonatal survivors < 1500 g and from 3.9 to 11.5 for those 1500-2499 g. Newborns < 2500 g now contribute one half of all cases of cerebral palsy and just over half of the most severe cases, whereas in the first decade of this study they contributed one third of all cases and only one sixth of the most severe ( 2 and 2 for trend p < 0.001). Conclusions-The rate of cerebral palsy has risen in spite of falling perinatal and neonatal mortality rates, a rise that is even more pronounced when the mildest and least reliably ascertained are excluded. The eVect of modern care seems to be that many babies < 2500 g who would have died in the perinatal period now survive with severe cerebral palsy. A global measure of severity should be included in registers of cerebral palsy to determine a minimum threshold for international comparisons of rates, and to monitor changes in the distribution of severity. (Arch Dis Child Fetal Neonatal Ed 2000;83:F7-F12)

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“…13 It should be remembered that the majority of CP diagnosed in term infants in developed countries is caused by prenatal influences and is not associated with significant neonatal encephalopathy. 21 Such an asymptomatic infant would therefore not be selected for neuroimaging as a neonate. However, as the infant developed and abnormal neuromotor signs and symptoms became apparent, neuroimaging would be a key part of the diagnostic assessment of the pathogenesis and severity of the associated brain injury.…”

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confidence: 99%