What causes cerebral palsy?

Causes of Cerebral Palsy

Cerebral palsy is caused by a complex interplay of genetic factors, prenatal events, perinatal complications, and postnatal injuries that lead to nonprogressive disturbances in the developing fetal or infant brain. 1 The etiology is multifactorial with approximately 80% of cases having no single identifiable complete causal pathway.

Primary Etiological Categories

Genetic Factors

• Recent evidence shows that genetic causes play a much larger role than previously recognized:
  • Approximately 31% of cerebral palsy cases have identifiable genetic causes through exome sequencing 1
  • The diagnostic yield is higher in pediatric populations (34.8%) compared to adults (26.9%) 1
  • Genetic abnormalities include copy number variants (CNVs) and single-nucleotide variants (SNVs) 1

Prenatal Risk Factors

• Preconception risks:

  • History of stillbirths or miscarriages
  • Low socioeconomic status
  • Assisted reproduction
  • Abnormal genetic copy number variations 1

• Pregnancy-related risks:

  • Maternal thyroid disease or preeclampsia
  • Intrauterine infections
  • Intrauterine growth restriction
  • Multiple gestations (twins, triplets)
  • Birth defects
  • Substance abuse during pregnancy 1

Perinatal Factors

• Prematurity (major risk factor)
• Low birth weight
• Birth complications
• Birth asphyxia (accounts for less than 10% of cases, contrary to previous beliefs) 1
• Neonatal encephalopathy

Postnatal Causes

• Infections (meningitis, encephalitis)
• Traumatic brain injuries
• Stroke
• Severe hyperbilirubinemia

Neuroimaging Findings

Neuroimaging reveals three main patterns of brain injury associated with cerebral palsy 1:

1. White matter injury (56% of cases)

   • Cystic periventricular leukomalacia
   • Periventricular hemorrhagic infarctions

2. Cortical and deep gray matter lesions (18% of cases)

   • Basal ganglia or thalamus lesions
   • Watershed injury (parasagittal injury)
   • Multicystic encephalomalacia
   • Stroke

3. Brain maldevelopments (9% of cases)

   • Lissencephaly
   • Pachygyria
   • Cortical dysplasia
   • Polymicrogyria
   • Schizencephaly

Clinical Pathways to Cerebral Palsy

Two distinct pathways to diagnosis have been identified 1:

1. Newborn-detectable risks pathway (50% of cases)

   • High-risk indicators identifiable in the newborn period
   • Includes prematurity, atypical intrauterine growth, encephalopathy, genetic abnormalities, and seizures
   • Typically diagnosed before 5 months' corrected age

2. Infant-detectable risks pathway (50% of cases)

   • Pregnancy and labor may appear uneventful
   • Parents or healthcare providers notice delayed motor milestones or asymmetries
   • Often diagnosed after 5 months' corrected age
   • Particularly common in unilateral cerebral palsy

Common Misconceptions

• Birth asphyxia is not the primary cause of cerebral palsy as once believed; it accounts for less than 10% of cases 1
• The complete causal pathway remains unclear in approximately 80% of cases 1
• Cerebral palsy is not a progressive condition; the brain injury is static, though clinical manifestations may change over time

Clinical Implications

• Early diagnosis is now possible before 6 months of age using tools like MRI, the Prechtl Qualitative Assessment of General Movements, and the Hammersmith Infant Neurological Examination 1
• Genetic testing, particularly exome sequencing, should be considered in the diagnostic evaluation of individuals with cerebral palsy, similar to recommendations for other neurodevelopmental disorders 1
• Understanding the etiology can guide appropriate interventions and family counseling, particularly regarding recurrence risk

The heterogeneous nature of cerebral palsy requires a comprehensive approach to diagnosis that considers the full spectrum of potential causes rather than focusing on a single etiology.