Aetiology and epidemiology of cerebral palsy

Yep, it's another post about the development of cerebral palsy (see here for more). Since we don't know the "true cause" of cerebral palsy, this post will mainly discuss different risk factors.

Brain damage in cerebral palsy

The cause of brain damage in cerebral palsy is thought to be a combination of cytokine-induced periventricular leukomalacia (PVL) (which I have explained here) and ischaemic damage (possibly caused by asphyxia), complicated by later intraventricular haemorrhage and hydrocephalus (fluid in the brain).

PVL usually affects the brain between 20-32 weeks, and while often associated with diplegic cerebral palsy, it is not exclusively associated with diplegia. PVL may also occur in infants with sepsis, or in young children treated with alpha-interferon for giant haemangioma (tangle of blood vessels).

Acute intrapartum asphyxia is thought to only be involved in 2-10% of cases of cerebral palsy. Some fetuses may already be damaged before entering labour, but a difficult labour may increase the amount of damage. Cooling the baby to reduce metabolic need may reduce early neurodisability.

Birth weight

Birth weight is a risk factor for cerebral palsy. Babies that are small for gestation age are more likely to be damaged by hypoxic-ischaemic events, while babies that are large for gestational age are at a higher risk related to maternal diabetes and obstructed labour. Symmetrical growth retardation (underweight, short, small head circumference) also increases the risk of developmental delay, even when asphyxia does not occur.

It has also been suggested that intrauterine growth restriction, which may result in babies being small for gestational age, might be a result of the brain damage that causes cerebral palsy, rather than being a cause of the brain damage. After an insult to the brain, intrauterine growth restriction of the brain may help to preserve or divert energy to critical areas.

Socioeconomic factors

Cerebral palsy is more prevalent among those of a lower socioeconomic class. It is unsure as to why this may be the case, but hypotheses include possible nutritional deficiencies and/or infections.

Multiple births

Multiple births (twins, triplets, etc.) increases the risk of cerebral palsy. This may be due to a variety of factors, such as twin-to-twin transfusions or in-utero death of a twin, and the increased risk of vascular anomalies of the placenta, prematurity, small size for gestational age (see above), premature rupture of membranes, and/or hypoxia.

Genetic factors

There is some evidence suggesting at least a partial genetic basis for cerebral palsy. There is an increased risk in twins, particularly in monozygotic twins. There is also an increased risk of a sibling has cerebral palsy. Cerebral palsy often appears in familial "clusters" where several members have similar types of cerebral palsy, and there is a greater risk in cosanguineous ("inter-breeding") families. In fact, some families with multiple affected children have been found to have some kind of autosomal recessive disorder, but this only accounts for a very small number of childrren with cerebral palsy.

It is thought that the genetic factors underlying cerebral palsy might impact the intrauterine environment, rather than the fetus itself. Some of the genes that have been investigated are associated with polymorphism in IL-6 and mutations in the prothrombin gene.

Malformations

Up to 12% of children with cerebral palsy have some kind of brain malformation, such as hydrocephalis (fluid in the brain) and microcephaly (small brain). Some of these malformations may be acquired, others genetic. People with cerebral palsy also have a higher likelihood of malformations in the heart, palate, eyes and limbs as compared to typically developing children. (Interestingly, these malformations are more common in people with cerebral palsy who were born at full term, as opposed to preterm.) Some of the brain malformations in cerebral palsy may be due to genetic factors which produce disorders of cortical migration, such as lissencephaly ("smooth brain," i.e. a brain without the usual bumps and folds).

Cerebrovascular events

Cerebrovascular events may also contribute to the development of cerebral palsy. In the 1st and 2nd trimester, the most common type of cerebrovascular event is cortical migration disorder (which is also seen in congenital cytomegalovirus infection- hmm, maybe that's why the Cerebral Palsy Alliance keeps posting about CMV on Facebook...). In the 3rd trimester, the most common type of event is a discrete infarct. Maternal and fetal thrombotic or haemorrhagic disorders may also contribute to these types of events, and ultimately to cerebral palsy.

Placental pathology

There is no single placental pathology associated with cerebral palsy. Furthermore, the extent of damage is important as the placenta has around 30% spare capacity before fetal growth is affected.

Chronic inflammatory placental lesions are one type of pathology that is associated with cerebral palsy. These lesions are associated with PVL and diplegic cerebral palsy and are likely linked with IL-1, IL-6, and TNF-alpha, which damage developing oligodendrocytes. (Such cytokine-induced white matter damage may also be seen occasionally after neonatal meningitis.)

Maternal genitourinary tract infections (e.g. Chlamydia, Trichomonas, UTIs, etc.) during pregnancy may also increase the risk of cerebral palsy, particularly if these infections occur during the first or second trimesters. Gestational age and birth weight are protective factors against such harm. Paradoxically, treating these infections might even increase the risk of cerebral palsy in some cases, perhaps by enhancing cytokine responses, but this is still uncertain.

A note on similar disorders

There are many disorders that present similarly to cerebral palsy, but are actually something different. Some of these disorders, unlike cerebral palsy, have known causes and are treatable. For instance, some disorders of dopamine metabolism may present similarly to cerebral palsy, but can be treated.

References

Eunson, P 2012, 'Aetiology and epidemiology of cerebral palsy', Paediatrics and Child Health, vol. 22, no. 9, pp. 361-366.