Sandbox cerebral palsy

Causes

Birth asphyxia is believed to be the principal etiology for cerebral palsy. However, recent studies demonstrated that 70% to 80% of cases of cerebral palsy are due to antenatal factors, while only 10% to 28% of cases are due to birth asphyxia in term and near-term infants. Causes of cerebral palsy are often multifactorial. For example, an intrauterine infection may result in growth restriction, maternal fever, and prematurity, all of which have been associated with cerebral palsy.

Prenatal causes

• Placental insufficiency
• Intrauterine infection
• Chromosomal abnormalities
• Maternal illness
  • Chorioamnionitis
  • Thyroid disease
  • Thrombotic disorders including factor V Leiden mutations
  • TORCH infections (toxoplasmosis, syphilis, rubella, cytomegalovirus, varicella zoster, HIV, herpes viruses)
• Multiple births
• Teratogen exposure
• Metabolic disorders
• Fetal brain malformation

Placental pathology

• Thrombotic lesions
• Placental ischemia has been associated with spastic diplegia
• Chronic villitis
• Pre-eclampsia

Perinatal causes

• Hypoxia-ischemia
• Neonatal encephalopathy
• Periventricular leukomalacia (PVL)
  • PVL increases the risk of cerebral palsy, independent of gestational age.
  • Approximately 75% of infants with cystic PVL develop cerebral palsy.
• Fetal/neonatal stroke
• Hyperbilirubinemia
• Hemolytic disease
• Kernicterus

Postnatal causes

• Stroke
• Trauma
• Infection

Cerebral palsy

Antenatal

Perinatal

Postnatal

Prematurity and low birth weight Intrauterine infections Multiple gestations Pregnancy complications

Birth Asphyxia complicated labour and delivery

Head trauma Meningitis Cardio-pulmonary arrest

In 2004 the International Executive Committee for the Definition of Cerebral Palsy revised the definition of cerebral palsy and described Cerebral palsy (CP) as a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy often are accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems.

Pathophysiology

Cerebral palsy is a heterogeneous disorder of movement and posture that has a wide variety of presentations, ranging from mild motor disturbance to severe total body involvement. Because of this variability in clinical presentation and the absence of a definitive diagnostic test, defining exactly what cerebral palsy is has been difficult and controversial. It is generally agreed that there are three distinctive features common to all patients with cerebral palsy:

• Some degree of motor impairment, which distinguishes it from other conditions, such as global developmental delay or autism
• An insult to the developing brain, making it different from conditions that affect the mature brain in older children and adults
• A neurologic deficit that is nonprogressive, which distinguishes it from other motor diseases of childhood, such as the muscular dystrophies.

Initial Insult

• The premature neonatal brain is susceptible to two main pathologies intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL).
• Although both pathologies increase the risk of cerebral palsy, periventricular leukomalacia is more closely related to cerebral palsy and is the leading cause in preterm infants.
• Both IVH and PVL cause cerebral palsy because of the corticospinal tracts, composed of descending motor axons, course through the periventricular region.
• The insult to the brain is believed to occur between the time of conception and age 2 years, at which time a significant amount of motor development has occurred.
• A similar injury to the brain after age 2 years can have a similar effect, however, and often is results in classic picture of cerebral palsy.
• By 8 years of age, most of the development of the immature brain is complete, as is gait development, and an insult to the brain results in a more adult-type clinical picture and outcome.

Prematurity

Intraventricluar hemorrhage

Periventricular watershed zones

Immature autoregulatory mechanisms

Ischemia/Hypoxia

Cytokines

Reactive oygen species

Exitotoxicity by glutamate

Periventricular leukomalacia

Cerebral Palsy

Disease progression

• Although the neurologic deficit is permanent and nonprogressive, the effect it can have on the patient is dynamic, and the orthopaedic aspects of cerebral palsy can change dramatically with growth and development.
• Growth, along with altered muscle forces across joints, can lead to progressive loss of motion, contracture, and eventually joint subluxation or dislocation, resulting in degeneration that may require orthopaedic intervention.*Injury to the developing brain can occur at any time from gestation to early childhood and typically is categorized as prenatal, perinatal, or postnatal.

Intraventricular hemorrhage

• Intraventricular hemorrhage is defined as a condition in which bleeding from the subependymal matrix occurs into the ventricles of the brain.
• Preterm infants are at increased risk of intraventricular hemorrhage because of underdeveloped blood vessels.
• The risk of cerebral palsy increases with the severity of intraventricular hemorrhage.

Periventricular leukomalacia

Ischemia and infection are two important factors that play a vital role in the pathogenesis of periventricular leukomalacia.

Ischemia/hypoxia

• The periventricular white matter of the neonatal brain is supplied by the distal segments of adjacent cerebral arteries.
• Although collateral blood flow from two arterial sources protects the area when one artery is blocked (e.g., thromboembolic stroke), this watershed zone is susceptible to damage from cerebral hypoperfusion (i.e., decreased cerebral blood flow in the brain overall).
• Since preterm and even term neonates have low cerebral blood flow, the periventricular white matter is susceptible to ischemic damage.
• Autoregulation of cerebral blood flow usually protects the fetal brain from hypoperfusion, however, it is limited in preterm infants due to immature vasoregulatory mechanisms and underdevelopment of arteriolar smooth muscles.

Infection and inflammation

• This process involves microglial (brain macrophage) cell activation and cytokine release, which causes damage to a specific cell type in the developing brain called the oligodendrocyte.
• The oligodendrocytes are a type of supportive brain cell that wraps around neurons to form the myelin sheath, which is essential for white matter development.
• Intrauterine infections activate the fetal immune system, which produces cytokines (e.g., interferon γ and TNF-α) that are toxic to premyelinating oligodendrocytes.
• Infections also activate microglial cells, which release free radicals. Premyelinating oligodendrocytes have immature defences against reactive oxygen species (e.g., low production of glutathione, an important antioxidant).
• IVH is hypothesized to cause PVL because iron-rich blood causes iron-mediated conversion of hydrogen peroxide to hydroxyl radical, contributing to oxidative damage.

Excitotoxicity

• Excitotoxicity is a process where increased extracellular glutamate levels stimulate oligodendrocytes to increase calcium influx, which stimulates reactive oxidative species release.
• Glutamate is increased because hypoxia causes white matter cells to reduce reuptake of glutamate due to lack of energy to operate glutamate pumps.
• Glutamate is also released from microglial cells during the inflammatory response.

Classification

The Manual Ability Classification System (MACS) describes how children with cerebral palsy (CP) use their hands to handle objects in daily activities. MACS describes five levels. The levels are based on the children’s self-initiated ability to handle objects and their need for assistance or adaptation to perform manual activities in everyday life.

Does the child handle most kind of daily activities independently ( during play and leisure, eating and dressing)

Yes

No

Does the child handle even more difficult tasks with fair speed and accuracy and does not need alternative ways to perform

Does the child perform number of mannual tasks which commonly need to prepared or adapted and help is needed occasionally

Yes

No

Yes

No

Level 1 Handles objects easily and successfully

Level 2 Handles most objects with reduced quality and speed of acheivement

Level 3 Handles objects with difficulty but needs preparation

Can the child perform easy activites with frequent support

Yes

No

Level 4 Handles easy activites with limitations and support

Level 5 Cannot handle daily activites has severely limited abilities to perform even simple actions

Prognosis

• Prognosis for motor functions in patients with cerebral palsy depends on the type and severity of motor impairment.
• Individuals with cerebral palsy on average have a life expectancy that is 44% of normal.
• Mortality risk increases with increasing number of impairments.
• The strongest predictors of early mortality are immobility and impaired feeding ability.