What Are the Classifications of Perinatal Stroke?

Patient Presentation
A 3-year-old female came to clinic for her initial health maintenance visit after moving to the area. She had a history of neonatal stroke for which she had received physical and occupational therapy. She still had some minor difficulty with her left hand and needed a referral to a new occupational therapist for continued therapy. Otherwise she was described as a normally developing child. The past medical history showed she was a 38 week infant who had neonatal seizures that were easily controlled. She was weaned off antiepileptics after not having additional seizures several months later. The mother and medical records confirmed that a cause had not been determined but the child had a neonatal arterial ischemic stroke. The mother had been evaluated for hypercoagulability which was negative.

The pertinent physical exam showed a smiling preschooler with growth parameters in the 50-75%. She had some mild decreased strength on the left compared to the right, but it was very mild.

The diagnosis of a healthy female with previous neonatal stroke and continued mild left arm impairment was made. The child was referred to an occupational therapist.

Case Image
Figure 133 – Axial CT without contrast of the brain (above left) suggests a triangular shaped area of decreased density in the anterior right middle cerebral artery distribution. Axial T2 MRI of the brain (above right) shows edema in this area with loss of gray matter – white matter differentiation. Axial diffusion weighted MRI (below left) shows bright signal in this area and corresponding dark signal in this area on the ADC map (below right), thus showing restricted diffusion in this area, implying it is an area of acute ischemia.

Perinatal stroke occurs in about 1:1000 live births and is a “focal vascular injury from the fetal period to 28 days postnatal age.” Perinatal stroke is the most common cause of hemiparetic cerebral palsy and causes other significant morbidity including cognitive deficits, learning disabilities, motor problems, sensory problems including visual and hearing disorders, epilepsy, and behavioral and psychological problems. Family members are also affected because of the potential anxiety and guilt feelings that having a child with a stroke presents, along with the care that may be needed over the child’s lifetime. Risk factors are inconsistent among studies and probably are due to complex interactions between the maternal-fetal intrauterine environment, the mother, the newborn, along with genetic and anatomic factors. For example, the placenta can be a source of emboli to the fetal brain and could be a factor in neonatal arterial ischemic stroke. Hypercoagulable states, central nervous system infection, brain vulnerability at different time periods, and congenital malformations are all considerations for increased risk of perinatal stroke.

As noted below, acute neonatal seizures along with other symptoms such as mental status changes (irritability, lethargy), poor feeding or frank signs of increased intracranial pressure can be associated with perinatal stroke but can also be associated with other problems such as meningitis, hypoxic-ischemic encephalopathy, and many other problems. In older infants and children, delayed motor skills are common including early hand preference as presentations. Trauma including non-accidental trauma needs to be considered as a possible alternative cause for presumed perinatal stroke too.

Cranial magnetic resonance imaging is the standard for perinatal stroke diagnosis and classification. Other imaging (often ultrasound) may be used depending on patient clinical status, imaging availability and timing. Other evaluations are completed to include or exclude alternative and concurrent diagnoses (e.g. perinatal stroke and bacterial meningitis) and to evaluate potential causes. These may include echocardiogram, lumbar puncture, and hematological studies for bleeding. Treatment may include anti-epileptics, antibiotics, therapeutic hypothermia, and other interventions.

Learning Point
The classification of perinatal stroke includes six entities based on vascular involvement, ischemic/hemorrhagic cause and timing.
These include:



        Neonatal Arterial Ischemic Stroke (NAIS) – most common, 80-90% of perinatal stroke

          Cause: Ischemic stroke
          Location: Occurs in arterial regions with middle cerebral artery being the most common
          Presentation: Focal seizures in first few days of life
          Imaging: Acute ischemia with restricted diffusion

        Arterial Presumed Perinatal Ischemic Stroke (APPIS) – 1:3600 live births

          Cause: Ischemic stroke
          Location: Occurs in arterial regions with middle cerebral artery being the most common
          Presentation: Asymmetric motor movement usually in first year of life or later childhood. Seizures can occur at any time
          Imaging: Infarction that appears chronic such as cystic encephalomalacia


        Neonatal Hemorrhagic Stroke (NHS) – 1:6300 births

          Cause: Accumulation of blood in brain parenchyma, primarily hemorrhagic but can include ischemia, can be caused by bleeding problems or arterial venous malformation
          Location: Any
          Presentation: seizures in first few days, change of consciousness, increased intracranial pressure signs
          Imaging: Hemorrhage is seen

        Presumed Perinatal Hemorrhagic Stroke (PPHS) – rare

          Cause: Similar to APPIS, initially hemorrhagic though


      Perientricular Venous Infarction (PVI)

        Cause: Hemorrhage into the germinal matrix causes medullary vein compression. Occurs in utero usually mid gestation, common in premature infants
        Location: Any but mainly motor
        Presentation: Hand preference too early or gait changes in infancy or early childhood
        Imaging: Circumscribed lesions of the white matter, with sparing of grey matter and deep cortical structures

      Central Venous Sinus Thrombosis (CSVT) – 1-12:100,000 births

        Cause/Location: Thrombosis in cerebral venous sinuses or veins. Not technically a stroke itself but can cause edema leading to venous infarction in about 50% of patients
        Presentation: Seizures that are more delayed but can be acute. Often subtle neurological findings
        Imaging: Thrombosis and/or venous infarction is seen

Questions for Further Discussion
1. How is pediatric stroke different than perinatal stroke? A review and differential diagnosis can be found here
2. How is hypoxic-ischemic encephalopathy different than perinatal stroke? A review can be found here
3. What is the role of longitudinal neurodevelopmental evaluation for preterm infants?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Seizures and Stroke.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Lee S, Mirsky DM, Beslow LA, et al. Pathways for Neuroimaging of Neonatal Stroke. Pediatr Neurol. 2017;69:37-48. doi:10.1016/j.pediatrneurol.2016.12.008

Dunbar M, Kirton A. Perinatal Stroke. Semin Pediatr Neurol. 2019;32:100767. doi:10.1016/j.spen.2019.08.003

Steggerda SJ, de Vries LS. Neonatal stroke in premature neonates. Semin Perinatol. 2021;45(7):151471. doi:10.1016/j.semperi.2021.151471

Srivastava R, Kirton A. Perinatal Stroke: A Practical Approach to Diagnosis and Management. NeoReviews. 2021;22(3):e163-e176. doi:10.1542/neo.22-3-e163

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa