Stroke in the pediatric population is being identified more frequently, and its effects, once thought to be limited, are now being recognized as more serious. Estimates of incidence range between 2 and 8 per 100,000, with neonates being disproportionately affected. A recent population-based study found that perinatal arterial ischemic stroke (PAS) was recognized in 1 in 2300 term infants.1 The rise in diagnosis of stroke is in part attributable to improved diagnostic techniques and to greater survival of susceptible children.2,3 Definitions and epidemiology of specific types of stroke in children are detailed below in the discussion of differential diagnosis.

In the past, it was felt that children generally recover from stroke with minimal long-term deficit (due to plasticity of the young brain). Recent studies reveal, however, that only 31% of children with ischemic stroke recovered to a normal neurological examination. Approximately 17% had persistent cognitive deficits. Disability can include physical, cognitive, behavioral, and psychiatric sequelae. Despite significant advances in management, stroke continues to be one of the leading causes of death among children.

The relative lack of controlled clinical trials significantly limits the current treatment guidelines, and the evidence-based interventions established for adults cannot be directly extrapolated to pediatric patients. Differences in the hemodynamic and coagulation pathways as well as in the significant risk factors that contribute to cerebrovascular events distinguish the two. For instance, atherosclerosis is one of the most common sources of adult stroke but rarely contributes to stroke risk in the pediatric population.3

Ischemic strokes occur secondary to insufficient cerebral oxygen delivery. This may occur because of occlusion of a vessel secondary to plaque formation (more common in adults), fibromyscular dysplasia, or vascular dissection. Cardioembolic sources of stroke are more common in children. Hematologic sources of stroke include hyperviscosity syndromes, sickle cell disease, and leukemia. Each of these disorders is discussed in much greater detail in the following sections.

Intracranial hemorrhage also occurs in several distinct subtypes. Subarachnoid hemorrhage may arise secondary to aneurysm rupture or trauma. Subdural and epidural hematomas often occur secondary to traumatic injury. Parenchymal hemorrhages may be related to a number of etiologies including trauma, abuse, collagen vascular diseases, and ischemic stroke.

In order to know appropriately manage stroke patients (see “Management” later in the chapter), the acutely presenting pediatric stroke patient must be recognized in a timely fashion. Unfortunately, the average delay between symptom onset and first diagnostic study is 28.5 hours, largely prohibiting the institution of hyperacute interventions.4 This delay stems from the often nonspecific symptoms with which pediatric stroke patients present. Neonates with underlying stroke frequently present with seizures as well as lethargy and apnea, whereas older children may present with more focal neurological deficits such as speech abnormalities, visual or sensory changes, or hemiparesis.5

The differential diagnosis can be vast, including infections and metabolic imbalances. A few key stroke masqueraders should also be considered. Familial hemiplegic migraine is characterized by family history and EEG pattern of unilateral slow background rhythm.5 Postictal or “Todd” paralysis is a consideration when focal weakness occurs after a seizure, and can closely mimic stroke. Patients should be treated with the urgency of an acute cerebral infarction until proven otherwise.

Physicians must be aware of predisposing conditions and risk factors to have the index of suspicion required to diagnose stroke. This involves awareness of three main categories of cerebrovascular events: arterial ischemic, hemorrhagic, and sinovenous thrombosis. Risk factors overlap for stroke subtypes, but treatment may differ.

Perinatal Stroke

Definitions and Epidemiology

A number of ischemic and hemorrhagic insults may affect the developing fetal or neonatal brain. It is therefore important for the clinician to be aware of the different types of events that can cause perinatal stroke, as the evaluation, management, and expected outcome may be related to the type of lesion. Perinatal arterial ischemic stroke refers to a cerobrovascular event occurring during fetal or neonatal life, before 28 days after birth, with pathologic or radiologic evidence of focal arterial infarction of brain.6 Sinovenous thrombosis describes thrombosis in one or more of the cerebral venous sinuses and may be associated with secondary hemorrhage.7 Primary hemorrhagic stroke and other types of intracranial hemorrhages that tend to affect near-term and term infants tend to be associated with specific risk factors responsible for the hemorrhage. Periventricular hermorrhagic infarction, a lesion that mainly affects preterm infants, is a serious complication of germinal matrix-intraventricular hemorrhage.

Clinical Presentation

Although these lesions tend to have significant overlap in terms of being hemorrhagic or ischemic, the effects of these types of events on the neonate may result in immediate or eventual death, with other long-term complications including cerebral palsy, epilepsy, blindness, behavioral disburbances, and congnitive dysfunction. Despite the type of lesion, symptoms may be subtle and are often nonspecific. The acute and chronic manifestations of perinatal stroke are reviewed in Table 18-1.

Perinatal Arterial Ischemic Stroke

Definitions and Epidemiology

Perinatal arterial ischemic stroke, occurring more frequently in the near-term and term infant, has a prevalence ranging from 17 to 93 per 100,000 live births.7-10 Most lesions occur in the left hemisphere within the distribution of the middle cerebral artery. Rarely, multifocal lesions occur but tend to be embolic in origin.7

Pathogenesis

A wide range of risk factors have been implicated in the etiology of perinatal arterial ischemic stroke, and these are listed in Table 18-2.7,9,11-13 However, some studies report no finding of an obvious precipitating event in as many as 25% to 77% of cases.14-16 The difficulty with identifying a specific risk factor for the development of the lesion is that neonates often have multiple risk factors present, making it likely that a combination of environmental risk factors interacting with genetic vulnerabilities is often responsible for the ischemic event.6 The exact role of genetic thrombophilias in the pathogenesis of perinatal arterial ischemic stroke is yet to be defined,17 but disorders such as factor V Leiden mutation, the prothrombin 20210 promoter mutation, hyperhomocystinemia, elevated lipoprotein (a) levels, antiphospholipid antibodies, and relative protein C deficiency have been described with increased frequency in infants who have perinatal arterial ischemic stroke when compared with healthy control subjects.18-24 Other genetic thrombophilias have also been implicated and are provided in Table 18-3. Further studies are required to better define the potential role of infantile thrombophilia in the pathogenesis and outcome of perinatal arterial ischemic stroke, but experts in the field do recommend a comprehensive thrombophilia assessment for all infants presenting with perinatal arterial ischemic stroke, regardless of other risk factors present.17,25

Clinical Presentation

The difficulty with identifying perinatal arterial ischemic stroke in the neonate is that symptoms tend to be nonspecific and often are difficult to identify. In many cases, the symptoms may not become evident until quite some time after the stroke. The acute and chronic manifestations of perinatal arterial ischemic stroke are reviewed in Table 18-1. Figure 18-1 reveals a multifocal infarction on diffusion-weighted MRI involving the pons and temporal lobe.

Sinovenous Thrombosis

Clinical Presentation

Most cases of sinovenous thrombosis occur in term infants and present with nonspecific clinical features as listed in Table 18-1. The superficial and lateral sinuses are most frequently involved, and venous infarction has been reported in up to 30% of cases.26 An example of magnetic resonance venography (MRV) in a normal patient is shown in Figure 18-2.

Pathogenesis

Risk factors for the development of sinovenous thrombosis are similar to those for perinatal arterial ischemic stroke and are listed in Table 18-3, although a significant number of cases are reported as idiopathic.16

Hemorrhage

Definitions and Epidemiology

Primary hemorrhagic stroke and other types of intracranial hemorrhage include subdural, primary subarachnoid, intracerebellar, intraventricular hemorrhage, and other miscellaneous types such as focal hemorrhages into the thalamus, basal ganglia, brainstem, or spinal cord.4

Periventricular hemorrhage (PVHI) is a venous hemorrhagic infarct in the drainage area of the periventricular terminal vein.27,28 A complication mainly associated with prematurity, a recent study found that 1% of infants less than 2500 g met the diagnostic criteria for PVHI, with the highest percentage (9.9%) being those less than 750 g.28

Pathogenesis

The majority of these types of hemorrhages tend to be antepartum or during the stresses of delivery and associated with specific risk factors as outlined in Table 18-3. Intrapartum risk factors associated with the development of PVHI include emergent cesarean section, low Apgar scores, and need for respiratory resuscitation; while postnatal factors include pneumothorax, pulmonary hemorrhage, patent ductus arteriosus, acidosis, hypotension requiring pressure support, and significant hypercarbia.28 Although an exact cause/effect relationship of these risk factors and correct knowledge of when these events occur has been difficult to prove, it is felt that disturbances in systemic and cerebral hemodynamics occurring around the intrapartum and early neonatal period are important in the development of PVHI.28

Clinical Presentation

Figure 18-3 shows a hemorrhage in the thalamic region on CT. In general, primary subarachnoid hemorrhages are more frequently seen in the premature infant but tend to be clinically benign; in contrast to intracerebellar hemorrhages which, although also more frequently observed in premature infants, tend to be serious.27 Subdural and other miscellaneous types of hemorrhages tend to affect full-term infants, and their outcome is variable. Although intraventricular hemorrhages tend to predominately occur in premature infants (discussed later), they have been reported to occur in term infants as well.

PVHI usually accompanies a large germinal matrix-intraventricular hemorrhage.28 See Figures 18-4 and 18-5 for examples of PVHI.

Arterial Ischemic Stroke

Definitions and Epidemiology

Arterial ischemic stroke can be related to a number of vascular, hematologic, cardiac, and metabolic risk factors. Potential causes of ischemic stroke in children are presented in Table 18-4.