Neonatal Stroke

Neonatal stroke is a focal cerebrovascular event between 28 weeks of gestation and 28 days of life. It includes arterial ischaemic stroke, cerebral sinovenous thrombosis and haemorrhagic stroke, and is a leading cause of hemiplegic cerebral palsy.

Arterial ischaemic stroke occurs in about 1 in 2500 to 1 in 5000 live births. It presents either acutely, usually with focal seizures in the first 3 days of life, or later as a presumed perinatal stroke when hand preference before 12 months or hemiparesis is noticed.

Risk factors are mostly multiple. Maternal factors include infertility, pre-eclampsia, chorioamnionitis, prolonged rupture of membranes and diabetes. Neonatal factors include congenital heart disease, polycythaemia, sepsis and meningitis, dehydration, hypoglycaemia, thrombophilia, extracorporeal support and placental disease (infarction or thrombosis). In many infants no cause is found.

Pathophysiology.

Arterial occlusion, usually in the middle cerebral artery territory on the left, results from placental or cardiac emboli, vasculopathy or thrombophilia. The neonatal brain is vulnerable because of high coagulability and a patent foramen ovale.

Venous infarction in sinovenous thrombosis is caused by raised venous pressure and haemorrhage. Ischaemia triggers excitotoxicity and inflammation, which produce seizures and injury over days.

• Focal clonic seizures, often only one limb, in an otherwise well appearing term infant in the first days of life.
• Encephalopathy, apnoea, poor feeding and hypotonia in some infants.
• Many infants are asymptomatic and present at 4 to 12 months with early hand preference, delayed motor milestones or hemiparesis.

Red flags.

• Seizures in the first 72 hours in a term infant without a hypoxic event.
• Fever or signs of sepsis, congenital heart disease, or polycythaemia.
• Sinovenous thrombosis with intracranial haemorrhage or raised intracranial pressure.

• MRI brain with diffusion weighted imaging (best at 2 to 5 days of life), with MR angiography and venography. Cranial ultrasound can miss stroke and is not sufficient.
• EEG for seizures and background, glucose, calcium, magnesium and electrolytes, blood gas, lactate and ammonia.
• Full blood count and haematocrit, coagulation screen, CRP and cultures when infection is suspected.
• Echocardiography for cardiac sources of embolus. Placental histology.
• Thrombophilia assessment (factor V Leiden, prothrombin gene variant, protein C, protein S, antithrombin, lipoprotein(a), homocysteine, antiphospholipid antibodies), interpreting protein levels with care in the newborn. Test the mother where indicated.

Differential diagnosis. Hypoxic ischaemic encephalopathy, intracranial haemorrhage, sepsis and meningitis, metabolic disease, hypoglycaemia, neonatal epilepsy syndromes and brain malformations.

Supportive care.

• Treat seizures with phenobarbital 20 mg/kg IV over 20 minutes, repeated at 10 mg/kg up to a total of 40 mg/kg, with levetiracetam 40 to 60 mg/kg IV as a second line agent.
• Maintain normal glucose, temperature, oxygenation, blood pressure and hydration. Correct polycythaemia or anaemia, coagulopathy and infection.
• Avoid routine anticoagulation for arterial stroke. Consider it only for cardiac embolic stroke or proven recurrent events.

Sinovenous thrombosis.

• Consider anticoagulation for propagating clot or venous infarction without large haemorrhage, with enoxaparin 1.5 mg/kg SC every 12 hours in term infants (2 mg/kg every 12 hours in preterm infants) to a target anti-Xa of 0.5 to 1.0 units/mL measured 4 hours after the dose. Treat for 6 weeks to 3 months. Repeat imaging at 1 to 2 weeks to monitor clot extension.
• Specialist haematology and neurology direction is needed because of the risk of haemorrhage.

Rehabilitation. Early physiotherapy and occupational therapy, assessment of hand function from 3 months, constraint based therapy for hemiparesis, and spasticity management.

Prognosis. About a third to a half develop cerebral palsy (usually hemiplegia), around 1 in 4 develop epilepsy, and cognitive and language problems occur. Recurrence of arterial stroke is under 2%.

Monitoring. Neurodevelopment, motor function, vision and epilepsy to at least school age.

Referral and escalation. Refer to a paediatric stroke or neurology service, a haematologist when thrombosis is present, and a cardiologist when a heart defect is found.