What is the epidemiology, risk factors, pathophysiology, clinical presentation, diagnosis, management, and outcomes of perinatal ischemic stroke?

Perinatal Ischemic Stroke: Epidemiology, Risk Factors, Pathophysiology, Clinical Presentation, Diagnosis, Management, and Outcomes

Perinatal ischemic stroke occurs in approximately 1 per 4000 live births, representing a significantly higher rate than stroke in older children, with approximately 80% of cases being ischemic in nature. 1 This condition represents one of the most focused lifetime risks for stroke, occurring primarily during the first week after birth.

Epidemiology

• Incidence: 1 per 4000 live births 1
• Timing: Occurs between 20 weeks gestation and 28 days of postnatal life 2
• Distribution: 80% ischemic, 20% due to cerebral sinovenous thrombosis (CVST) or hemorrhage 1
• Demographics: Higher incidence in boys and in children of black ethnicity 1
• Peak age: First year of life accounts for approximately one-third of all pediatric stroke cases 1

Risk Factors

Multiple risk factors have been identified for perinatal ischemic stroke:

• Maternal factors:

  • History of infertility
  • Chorioamnionitis
  • Premature rupture of membranes
  • Preeclampsia 1

• Infant factors:

  • Cardiac disorders
  • Coagulation disorders/thrombophilia
  • Infection
  • Trauma
  • Perinatal asphyxia 1
  • Dehydration 1

The risk of perinatal arterial ischemic stroke increases dramatically with the number of risk factors present, suggesting a multifactorial etiology in many cases 1.

Pathophysiology

Perinatal ischemic stroke results from focal disruption of cerebral blood flow, typically involving:

• Arterial occlusion: Most commonly affecting the middle cerebral artery territory through thromboembolism from intracranial/extracranial vessels, heart, or placenta 3
• Venous thrombosis: Involving cerebral sinovenous vessels 1

The developing brain has unique vulnerabilities that differ between term and preterm infants:

• Term neonates: Injury typically affects cortex, basal ganglia, and internal capsule 4
• Preterm neonates: Injury more commonly affects periventricular white matter 4

Clinical Presentation

Perinatal stroke often presents with:

1. Acute neonatal presentation:

   • Seizures (most common) - typically focal motor seizures involving one extremity 1
   • Stroke accounts for approximately 10% of seizures in term neonates 1

2. Delayed presentation:

   • Early handedness (before expected developmental milestone)
   • Developmental delay
   • Motor asymmetry in the first year of life 1, 2

Many children with perinatal stroke appear normal in the neonatal period and only present later with signs of hemiparesis or developmental concerns 1.

Diagnosis

The diagnostic approach depends on clinical presentation and patient stability:

1. Imaging modalities:

   • Cranial ultrasound: Safe and readily available but may miss superficial and ischemic lesions 1
   • CT scan: Quick and accurate for hemorrhagic lesions but may miss early arterial ischemic stroke and venous thrombosis 1
   • MRI with diffusion-weighted imaging: Gold standard that can confirm infarction earlier than other modalities 1, 4
   • MR angiography (MRA) and venography (MRV): Accurately define arterial or venous occlusion sites 1
   • CT angiography (CTA): Useful for identifying vascular abnormalities with unexplained hemorrhagic lesions 1

2. Diagnostic workup:

   • Evaluation for cardiac disorders
   • Coagulation studies for thrombophilia
   • Infection screening
   • Metabolic testing as indicated 1

Management

Management of perinatal ischemic stroke focuses on supportive care and prevention of complications:

Acute Management

1. Supportive care:

   • Treatment of dehydration and anemia (Class IIa, Level of Evidence C) 1
   • Management of seizures 1

2. Specific interventions:

   • Anticoagulation: May be considered in selected neonates with severe thrombophilic disorders, multiple cerebral or systemic emboli, or evidence of propagating CVST (Class IIb, Level of Evidence C) 1
   • Surgical intervention: Evacuation of intraparenchymal hematoma may be reasonable to reduce very high intracranial pressure (Class IIa, Level of Evidence C) 1
   • Nutritional supplementation: Folate and B vitamins for individuals with MTHFR mutation to normalize homocysteine levels (Class IIa, Level of Evidence C) 1

Long-term Management

• Rehabilitation: Early intervention with physical therapy to reduce neurological dysfunction 1
• Seizure management: Anticonvulsant therapy as needed 1
• Developmental support: Speech therapy, occupational therapy, and educational interventions based on specific deficits 1

Outcomes

Outcomes after perinatal ischemic stroke vary widely:

Motor Outcomes

• Hemiparetic cerebral palsy is the most common long-term motor outcome 2
• Lesions involving the cortex, basal ganglia, and internal capsule on MRI are more likely to cause hemiplegia than strokes involving only one of these regions 1
• Large stroke size and injury to Broca's area, internal capsule, Wernicke's area, or basal ganglia are associated with cerebral palsy 1
• Bilateral infarctions decrease the likelihood of walking 1

Cognitive Outcomes

• Cognitive impairment after perinatal arterial ischemic stroke ranges from 0% to 55% 1
• Language delay occurs in approximately 25% of children with perinatal stroke 1
• Developmental delay after neonatal CVST ranges from 28% to 58% 1

Seizure Outcomes

• Most neonates with stroke do not develop epilepsy, but those who present with seizures in the neonatal period may be at higher risk for abnormal neurodevelopmental outcomes 1
• Abnormal EEG background predicts childhood hemiplegia 1

Recurrence Risk

• Recurrent symptomatic thromboembolism occurs in approximately 3% of children with neonatal arterial ischemic stroke 1
• Factors associated with increased recurrence include thrombophilic states and comorbidities such as complex congenital heart disease or dehydration 1
• Recurrence after neonatal CVST occurs in approximately 8% of cases 1

Prognostic Factors

Several factors influence prognosis:

• Favorable prognostic factors:

  • Absence of major cerebral lesions on MRI 4
  • CVST without infarction 1

• Unfavorable prognostic factors:

  • Seizures in the neonatal period 1
  • Abnormal EEG background 1
  • Large stroke size 1
  • Involvement of specific brain regions (Broca's area, internal capsule, Wernicke's area, basal ganglia) 1
  • Bilateral infarctions 1
  • Presence of thrombophilic disorders 1

Early identification and intervention are crucial to optimize outcomes for children with perinatal ischemic stroke, with rehabilitation efforts focused on minimizing long-term disability and maximizing quality of life.