Cerebral Palsy-Trends in Epidemiology and Recent Development in Prenatal Mechanisms of Disease, Treatment, and Prevention

Abstract

Cerebral palsy (CP) is the most common motor disability in childhood. This syndrome is the manifestation of intrauterine pathologies, intrapartum complications, and the postnatal sequel, especially among preterm neonates. A double hit model theory is proposed suggesting that an intrauterine condition along with intrapartum or postnatal insult lead to the development of CP. Recent reports demonstrated that treatment during the process of preterm birth such as magnesium sulfate and postnatal modalities such as cooling may prevent or reduce the prevalence of this syndrome. Moreover, animal models demonstrated that postnatal treatment with anti-inflammatory drugs coupled with nanoparticles may affect the course of the disease in pups with neuroinflammation. This review will describe the changes in the epidemiology of this disease, the underlying prenatal mechanisms, and possible treatments that may reduce the prevalence of CP and alter the course of the disease.

Keywords: N-acetyl cysteine; birth asphyxia; cerebral palsy; intrauterine infection; magnesium sulfate; nanoparticles; neuroinflammation; progesterone.

Figure 1

Underlying mechanisms leading to cerebral palsy (CP). The mechanisms leading to cerebral palsy can be attributed to the following exposures: (1) intrauterine exposure including infection elicit a fetal inflammatory response syndrome and white matter damage in the fetus, fetal growth restriction, placental vascular disorders that are associated with vascular injuries in the fetal brain and congenital anomalies. (2) Intrapartum events that affect the fetus during the process of labor and delivery such as chorioamnionitis, birth asphyxia, and placental abruption are all acute events that are associated with further implication on the fetal/neonatal brain. (3) Post-partum exposure to infection of prematurity complications that affect the neonate and subsequently lead to CP. These events can be isolated but also combined, and the two-hit theory proposed that a neonate who suffered from hostile intrauterine environment such as infection may be further affected by acute intrapartum event such as abruption or post-partum complication and develop CP.

Figure 2

Strategies for the reduction of cerebral palsy (CP). The strategies to reduce the rate of CP are as follows: (1) prevention of adverse events during pregnancy mainly of preterm birth (spontaneous or indicated); (2) the administrations of supportive medical treatment during an acute event such as magnesium sulfate of betamethasone during preterm labor; and (3) postexposure treatment to reduce the neurologic injury.