Cerebral Palsy

Key points

·         Cerebral palsy (CP) refers to a nonprogressive disease of the brain originating during the prenatal, neonatal, or early postnatal period

·         Spasticity of motor movement is by far the most common presentation of CP

·         More subtle manifestations of CP include difficulties with speech, perceptive impairment, urinary incontinence, sensory loss, and difficulties with balance

·         Treatment may require multiple specialty consultation and a combined approach to therapy across several providers including oral medications, injections, and even orthopedic surgery

Background

Description

·         Cerebral palsy (CP) is a nonprogressive (static) disorder of motor function and movement that usually manifests early in life as a result of central nervous system damage to the developing brain

·         CP remains a clinical diagnosis. Evidence of motor dysfunction must be present, and clinical findings and symptoms may evolve over time. Most patients exhibit symptoms as infants or toddlers; diagnosis is often made before 2 years of age

·         Delayed motor milestones are one of the most common complaints

·         Patients with dystonia or movement disorders present later in childhood (aged older than 2 years)

·         Often associated with abnormalities of speech, vision, intellect, and (frequently) seizures

·         CP encompasses a wide spectrum of clinical presentations ranging from normal intelligence with mild motor deficits to severe retardation and inability to walk. Although there is delay in developmental motor milestones, mental retardation is seen in only 30% to 50% of patients with cerebral palsy

·         Therapy, whether for movement, speech, or activities of daily living, is the cornerstone of cerebral palsy management

·         Patients with cerebral palsy and comorbid seizure disorders should receive anti-epileptic agents suitable for the type of seizures that they experience

·         Cardinal features:

o    Hypotonia with spasticities

o    Delay in developmental milestones

o    Extrapyramidal symptoms

o    Diplegia

o    Hemiplegia

o    Seizures (30%)

o    Mental retardation (30%)

Epidemiology

Incidence and prevalence

·         1.5 to 2.5 per 1,000 live births

·         Time trends in CP are due to advances in perinatal care in the last 40 years: there was a sharp increase in prevalence of CP in very low birth weight (VLBW) infants during the 1980s, which has been attributed to the increased survival in VLBW infants due to advances in newborn intensive care. This recent increase seems to have leveled off and may be on the decline

·         Patients with mild forms of CP that do not result in severe functional impairment may remain undiagnosed, leading to underestimation of the true prevalence of CP

Demographics

Age:

·         CP is more common in children who are born very prematurely or at term

·         Swedish data indicate that 36% of patients were born at less than 28 weeks' gestation, 25% between 28 and 32 weeks' gestation, 2.5% between 32 and 38 weeks' gestation, and 37% at full term

·         Most patients are identified by 2 years of age due to delayed motor milestones

Gender:

·         There is a slightly higher prevalence in the male population, with a male:female ratio of 1.5:1.

Race:

·         There is a higher prevalence among black non-Hispanic children compared with white non-Hispanic children

Socioeconomic status:

·         Poor prenatal care may increase the incidence of cerebral palsy

·         Living in substandard housing with lead paint may increase the incidence of cerebral palsy

Causes and risk factors

·         Birth asphyxia used to be considered the principal etiology for CP. However, it is now believed that 70% to 80% of cases of CP are due to antenatal factors, while only 10% to 28% of cases are due to birth asphyxia in term and near-term infants

·         More than 1 etiologic factor is often identified. For example, intrauterine infection may result in growth restriction, maternal fever, and prematurity, all of which have been associated with CP

Prenatal causes:

·         Abnormal intrauterine growth may be the result of multiple factors such as placental insufficiency, intrauterine infection, and chromosomal abnormalities, among others

·         Maternal infections and fever: evidence of maternal fever around the time of delivery and chorioamnionitis have been associated with low Apgar scores, neonatal encephalopathy, seizures, and increased risk of CP

o    TORCH infections (toxoplasmosis, syphilis, rubella, cytomegalovirus, varicella zoster, HIV, herpes viruses) are thought to be responsible for 5% of CP cases

·         Multiple births: twins carry a higher risk of CP when compared to single births; risk of having a child with CP is 0.2% for single births, 1.3% for twins, and 7.6% for triplets

o    Weight discordance greater than 30% is associated with a 5-fold increased risk of CP

o    Death of a co-twin or co-triplet is associated with a 10% and 29% risk of CP for the surviving twin or triplets, respectively

·         Placental pathology:

o    Thrombotic lesions and placental ischemia have been associated with spastic diplegia

o    Chronic villitis (focal areas of inflammation) has been associated with growth restriction, preterm birth and pre-eclampsia

·         Genetic factors

·         Maternal metabolic disturbances (diabetes mellitus type 1 or type 2 or thyroid abnormalities)

·         Intrauterine exposure to toxins

·         Malformations of cortical development

Perinatal causes:

·         Hypoxia-ischemia: 6% of children with CP have an identifiable birth complication that could result in hypoxia. Neonatal encephalopathy is usually present

·         Periventricular leukomalacia (PVL) increases the risk of CP, independent of gestational age. Approximately 75% of infants with cystic PVL develop CP

·         Fetal/neonatal stroke: most often resulting in hemiplegic CP

·         Hyperbilirubinemia

o    Hemolytic disease in the newborn, especially due to Rh incompatibility, was previously a common cause of kernicterus and CP prior to the use of Rho(D) immune globulin. It is still being reported in North America, Western Europe and the developing world

o    Kernicterus is the preferred term to describe the chronic permanent sequelae of bilirubin toxicity. Affected children often develop severe athetoid CP

Postnatal causes:

·         Stroke

·         Trauma

·         Infection

Associated disorders

·         Seizures

·         Scoliosis

·         Deafness

·         Mental retardation

·         Visual impairments: strabismus, nystagmus, optic atrophy

·         Speech deficits

·         Feeding difficulties

·         Urinary incontinence

·         Attention deficit hyperactivity disorder

·         Learning disabilities

·         Depression

·         Autism

Screening

Not applicable.

Primary prevention

Summary approach

·         Since the cause of cerebral palsy is not always known, it is difficult to prevent; however, some prenatal causes can be prevented with appropriate prenatal care

o    The risks associated with preterm delivery may be minimized with early and regular prenatal physician visits

o    The use of antenatal corticosteroids (ie, betamethasone) in patients at risk for pre-term delivery seems to reduce the risk of CP by protecting against neonatal intraventricular hemorrhage (IVH)

o    Prophylactic magnesium sulfate was administered to women for whom preterm delivery was imminent in the Beneficial Effect of Antenatal Magnesium (BEAM) trial to assess reduction in the risk of death or moderate to severe cerebral palsy in their children. The results suggested that although the risk of death or moderate to severe CP did not seem to decrease, the overall rate of CP was reduced among child survivors

·         Head injuries can be prevented by proper positioning in car seats

·         Routine vaccinations in infants can prevent many cases of meningitis that leads to brain injury

Preventive measures

·         Administering prophylactic magnesium sulfate to women for whom preterm delivery is imminent may reduce the incidence of CP

·         Pregnant women should be advised not to smoke because it increases the risk of prematurity. Smoking also damages the placenta and can contribute to neonatal hypoxia and brain damage, which increases the risk of cerebral palsy

·         Pregnant women should be advised not to drink alcohol or take unprescribed drugs because of risk of neural tube damage to the baby. Early brain damage during development in utero can lead to cerebral palsy

·         Pregnant women should avoid eating raw shellfish and soft cheeses

·         Pregnant women should avoid all unnecessary X-ray radiation because it may damage developing neural tissue, which can increase the risk of developing cerebral palsy

·         Exposure to toxins should be avoided, such as ingestion or inhalation of lead paint

·         Ensure that any high-risk delivery occurs in a center where any complications can be managed (eg, cesarean section for prolonged labor, fetal distress, or dystocia)

·         If a preterm delivery is imminent, ensure that the adequate staff and facilities are available to manage the neonate and prevent hypoxia and acidosis after delivery. Low birth weight infants are at increased risk of developing cerebral palsy from intracerebral hemorrhage and periventricular leukomalacia. Prematurity is the most common natal cause of cerebral palsy

·         Infants should receive Haemophilus influenzae type b and pneumococcal vaccines to protect against meningitis

·         Rh-negative women should receive Rho(D) immune globulin to prevent destruction of fetal blood cells

·         Pregnant women should be assessed for immunity to rubella. Rubella infections during pregnancy can damage the developing brain

·         Ensure that any diabetic woman has good glycemic control when pregnant to decrease the risk of developmental problems in the fetus

·         Minimize intrauterine exposure to maternal infection

Evidence

·         A systematic review assessed the effects of magnesium sulfate as a neuroprotective agent when given to women considered at risk of preterm birth in 5 RCTs inclusive of 6,145 neonates. Women presenting from 24.0 to 31.6 weeks' gestation with advanced preterm labor or premature rupture of the membranes and no recent exposure to magnesium sulfate were randomized to receive either intravenous magnesium sulfate or masked study drug placebo. If after 12 hours delivery had not occurred and was not anticipated, the infusion was stopped. Patients were assessed for signs of intolerance to the study medications and maternal data were collected up to hospital discharge. Up to 3 follow-up visits were scheduled over 2 years where certified examiners, masked to study group assignment, collected physical and neurological data, including a modified Gross Motor Function Classification Scale. The Bayley Scale of Infant Development was also administered. Antenatal magnesium sulfate reduced the risk of cerebral palsy. There was also a significant reduction in the rate of substantial gross motor dysfunction. Overall there were no significant effects of antenatal magnesium therapy on combined rates of mortality with cerebral palsy. There were higher rates of minor maternal side effects in the magnesium groups, but no significant effects on major maternal complications.[1]Level of evidence: 1