Stroke

P. Ellen Grant and Katyucia De Macedo Rodrigues

Stroke is an important cause of mortality and long-term neurologic morbidity in children. In the pediatric age group, it is defined as a cerebrovascular event occurring between 14 weeks of gestation and 18 years of life. It ranks among the top 10 causes of death in children,¹ with the highest incidence observed in the perinatal period. It occurs in approximately 25 per 100,000 live births in the neonatal population and in 2 to 3 per 100,000 in children between 30 days and 18 years. Recurrence is estimated to be around 3% to 5% in neonates and ranges from 20% to 40% in older children. Among those who survive, more than 50% progress to the development of permanent neurologic or cognitive sequelae.² The required treatment and rehabilitation programs usually result in a large economic burden to the family and society (Box 37-1).

Box 37-1 Causes of Pediatric Stroke

Arterial Ischemic Stroke

Cardiac

• Congenital heart disease

• Valvular heart disease

• Neoplasm, myxomas

• Cardiac surgery

• Myocarditis, cardiomyopathy

Cerebral Vasculopathy

• Infection (e.g., meningitis)

• Collagen vascular disease (e.g., systemic lupus erythematosus, giant cell arteritis, Takayasu arteritis, Kawasaki arteritis)

• Primary angitis of the central nervous system

• Viral infection (e.g., varicella)

• Trauma, dissection

Disorders of Coagulation

• Protein C or S deficiency

• Antithrombin III deficiency

• Anticardiolipin antibodies

• Lupus anticoagulant

• Dysfibrinogenemia

• Polycythemia and hyperviscosity

Moyamoya Disease

• Idiopathic/familial (Japanese)

• Secondary (e.g., sickle cell disease)

• Neurofibromatosis type 1

• Radiation vasculopathy

Inborn Errors of Metabolism

• Fabry disease

• Hyperhomocysteinemia

• Ehlers-Danlos syndrome (type IV)

Sinovenous Thrombosis

• Infection of the head and neck

• Dehydration

• Hypercoagulable states

• Chemotherapeutic agents

• Iatrogenic

The reported incidence of pediatric stroke has been on the rise, perhaps because of increased awareness among medical professionals, but also because of improved diagnostic imaging techniques. In the past, infectious processes such as meningitis often were found, but today congenital heart disease, sickle cell anemia, extracranial carotid dissection, and thrombophilia constitute most cases. Even though it often is possible to identify more than one risk factor, in approximately 50% of cases, a definite cause remains undetermined. Clinical management of children who have had a stroke remains controversial, despite the fact that treatment algorithms have been established for adults.

Fetal Stroke

Fetal stroke occurs between 14 weeks of gestation until the onset of labor. Because of the lack of maternal or otherwise detectable fetal symptoms, the true incidence of fetal stroke is unknown; usually it is only diagnosed incidentally by antenatal ultrasound performed late in the second trimester or in the third trimester. Sometimes a fetal stroke is detected only during the neonatal period or later in life when developmental delays become perceptible.

Maternal, placental, and fetal risk factors have been reported, but in more than 50% of cases, no obvious cause is found. The common maternal conditions associated with fetal stroke are alloimmune thrombocytopenia, diabetes, anticoagulant or antiepileptic therapy, and trauma. Placental factors include placental hemorrhage, abruption, and thromboemboli.³ It is unclear whether coagulopathy is a risk factor, but a case of fetal protein C deficiency has been reported.

Intraparenchymal hemorrhage, cerebral cavitary lesions, and ventriculomegaly are common findings on antenatal ultrasound. These findings are not specific for the type of stroke; however, the location of the injury and the distribution (arterial or venous) may suggest an underlying mechanism. Acute injury and small ischemic lesions can be difficult to detect with ultrasound.

Once an abnormality is found on a prenatal ultrasound examination, fetal magnetic resonance imaging (MRI) usually is performed; it is the imaging modality of choice for assessing fetal brain injury (Fig. 37-1). Hemorrhagic lesions have been reported in more than 90% of cases, compared with porencephalic cysts, which are reported in 10% of cases. Arterial ischemic stroke (AIS) typically involves the major arterial territories, most commonly the middle cerebral artery (MCA). Arterial ischemic insults occurring in the second trimester can cause cortical disorganization, resulting in polymicrogyria. If fetal hemorrhagic strokes are similar in origin to the vast majority of preterm and term hemorrhages, it is likely that many fetal hemorrhagic strokes are venous strokes. When tissue destruction occurs as a result of a fetal stroke, the type of tissue response identified on postnatal imaging can help determine the time of the intrapartum event. Porencephalic cysts lack a surrounding astroglial response and develop with injuries between 22 and 27 weeks of gestation. Thereafter, cystic encephalomalacia with gliosis is seen on pathology and MRI. Unlike in neonates and adults, diffusion-weighted imaging (DWI) may not be reliable in predicting the approximate date of an event.⁴

Figure 37-1 Fetal stroke.
A 30-year-old woman underwent a magnetic resonance imaging scan after fetal ventriculomegaly was found on a routine prenatal ultrasound at 29 weeks’ gestational age. A, B, and C, T2-weighted images show dilatation of the lateral ventricles associated with T2 prolongation, thinning, and irregularity of the periatrial white matter. D, T1-weighted image. E, Diffusion-weighted image. F, Apparent diffusion coefficient map. Reduced diffusion also is observed within the periventricular white matter, suggesting evolving ischemic necrosis.

Finally, although a fetal stroke is often subclinical, strokes identified by prenatal screening are typically large and result in death or an adverse neurodevelopmental outcome in more than three quarters of cases.

Perinatal or Neonatal Stroke

Perinatal or neonatal stroke is an event that occurs between the late third trimester and the first month of life. The pathophysiology is complex and typically multifactorial. Recently, prothrombotic abnormalities of the coagulation pathway have been of particular interest because of the evolving role and potential use of antithrombotic agents for both treatment and prevention.⁵

It is important to differentiate ischemic stroke from hypoxic-ischemic injury, even though both can coexist, because management and prognosis can be different.

Arterial Ischemic Stroke

Perinatal AIS leads to focal ischemic necrosis in an arterial distribution, most commonly in the MCA territory. The cause is undetermined in more than half of all cases. In the remainder of cases, the source of the thromboemboli may be an intracranial or extracranial vessel, the heart, or the placenta. An increased incidence of dehydration and sepsis also is found, along with cardiac and coagulation disorders.² AIS may be clinically subtle, and newborns often present with seizures without encephalopathy 2 to 3 days after birth. At the time of clinical presentation, ultrasound of the head can be have false-negative results. Computed tomography (CT) can detect hemorrhage and areas of advanced infarction but also may have false-negative results. Furthermore, ionizing radiation exposure is discouraged in neonates. Acute AIS is easily identified on MRI as regions of bright signal on DWI and decreased signal on apparent diffusion coefficient (ADC) maps within a vascular territory. The reduction in ADC values results from the presence of acute ischemic necrosis and the associated physiologic changes, such as cellular swelling, increased tortuosity of the extracellular space, decreased intracellular cytosolic streaming, and increased intracellular viscosity. The reduction in ADC can persist for up to 2 weeks, being more conspicuous during the first 4 days.⁶

On T2-weighted images, subtle loss of gray-white matter differentiation often is identified, although it may be negative within the first hours after clinical presentation. MR angiography (MRA) may be helpful in excluding complete occlusion of a major intracranial artery, but turbulent or fast flow often can result in signal dropout, which generates a concern for partially occlusive thrombus in this clinical context. Cerebral perfusion can be obtained using arterial spin labeling. This technique uses arterial blood water magnetically labeled by a radiofrequency pulse to obtain cerebral blood flow measurements; it does not require intravenous injection of contrast media (see Chapter 28). This technique can be particularly useful in determining the presence of reperfusion in areas of abnormal ADC (Fig. 37-2).⁷