Pathophysiology of cerebral palsy

Abstract

Cerebral palsy (CP), defined as a group of nonprogressive disorders of movement and posture, is the most common cause of severe neurodisability in children. Understanding its physiopathology is crucial to developing some protective strategies. Interruption of oxygen supply to the fetus or brain asphyxia was classically considered to be the main causal factor explaining later CP. However several ante-, peri-, and postnatal factors could be involved in the origins of CP syndromes. Congenital malformations are rarely identified. CP is most often the result of environmental factors, which might interact with genetic vulnerabilities, and could be severe enough to cause the destructive injuries visible with standard imaging (i.e., ultrasonographic study or MRI), predominantly in the white matter in preterm infants and in the gray matter and the brainstem nuclei in full-term newborns. Moreover they act on an immature brain and could alter the remarkable series of developmental events. Biochemical key factors originating in cell death or cell process loss, observed in hypoxic-ischemic as well as inflammatory conditions, are excessive production of proinflammatory cytokines, oxidative stress, maternal growth factor deprivation, extracellular matrix modifications, and excessive release of glutamate, triggering the excitotoxic cascade. Only two strategies have succeeded in decreasing CP in 2-year-old children: hypothermia in full-term newborns with moderate neonatal encephalopathy and administration of magnesium sulfate to mothers in preterm labor.