Etiology and Pathogenesis

Estimates of the incidence of stroke in children range from two to 13 per 100,000 children per year. As opposed to adults in which ICH accounts for about 15% of stroke, ICH accounts for about half of pediatric stroke. The incidence of perinatal stroke is approximately one per 4000 live births, with 80% of these secondary to AIS. One-quarter of all strokes in children take place during the perinatal period. The incidence of cerebral venous sinus thrombosis is approximately 0.3 to 0.7 per 100,000 per year, with almost half of these occurring in the perinatal period. Strokes are more common in boys than in girls, with 55% to 60% of all childhood strokes occurring in boys. In the United States, strokes are more common among African American children, even when controlling for the presence of sickle cell disease (SCD).

Unlike adults, in whom hypertension, diabetes, and atherosclerosis predominate as risk factors for ischemic stroke, children presenting with AIS have much more varied etiologies. Approximately 50% of children presenting with stroke have an obvious underlying cause at the time of presentation, with arteriopathy, congenital heart disease, and sickle cell anemia representing some of the most common causes. In an additional 20% to 40%, an underlying cause can be found with further investigation. Somewhere between 10% and 30% are cryptogenic. Factors associated with pediatric AIS include inherited or acquired prothrombotic states, cardiac disease, arteriopathies or vasculopathies, trauma, and infections (Box 79-1). In older teenagers, traditional risk factors for adults, such as hypertension, diabetes, high cholesterol, and smoking, may also play a role. Cocaine or sympathomimetic medications are additional risk factors. Watershed strokes can be seen after cardiac arrest or other causes of shock, near drowning, and cardiac surgery.

ICH in children is also etiologically distinct from ICH in adults. Unlike adults, in whom hypertension and amyloid angiopathy are the most common causes, childhood ICH is most commonly caused by ruptured vascular malformations (e.g., arteriovenous malformations, cavernomas, and aneurysms), hematologic abnormalities, and brain tumors (Box 79-2 and Figure 79-2).

Figure 79-2 Intracerebral hemorrhage: clinical manifestations related to site.

The major risk factors for CSVT include dehydration, head and neck infections, hypercoagulable states, malignancies, congenital heart disease, inflammatory bowel disease, oral contraceptives, and the use of certain chemotherapeutics.

AIS occurs when occlusion of an artery with a thrombus or embolus prevents blood flow to the region supplied by that artery. In watershed infarctions, global or near-global hypoperfusion preferentially damages areas on the border of two different vascular territories. The end result is a complex chain of events in cerebral neurons and support cells in which lack of oxygen and glucose leads to mitochondrial dysfunction, ion pump failure, calcium influx, and glutamate-induced neurotoxicity, eventually producing cell necrosis or apoptosis. The extent of ischemic damage to the region is determined by oxygen demand, collateral blood flow, and time to reperfusion. After an acute ischemic insult, there is a core area of infarction in which cells have sustained irreversible injury. This core is surrounded by an area with reversible ischemia known as the ischemic penumbra. If no further improvement of blood flow takes place or if additional insults occur, the tissue within the penumbra will eventually infarct over a period of hours to days, potentially causing additional neurologic impairment. In TIAs perfusion is restored before infarction can take place, and neuronal dysfunction induced by ischemia is reversed.

In ICH, blood extravasates into the brain parenchyma (intraparenchymal hemorrhage) into the ventricles (intraventricular hemorrhage), or into the subarachnoid space (subarachnoid hemorrhage). Intraparenchymal hemorrhage causes neuronal damage through a combination of mechanical damage and chemical irritation. Secondary ischemic stroke can occur as well because of mechanical deformation of cerebral vasculature by mass effect, vasospasm, and altered pressure dynamics leading to decreased cerebral perfusion pressure. Intraventricular hemorrhage can lead to hydrocephalus.

In CSVT, obstruction of venous blood by clot formation alters blood flow dynamics and overall venous drainage is decreased. Increased cerebral venous pressure causes resistance to cerebral perfusion and can cause venous infarction or hemorrhage. All contribute to increasing intracranial pressure (ICP).

Clinical Presentation

The clinical presentation of a child with stroke depends on the location, type, and size of the stroke and the age and developmental stage of the child. The diagnosis is often missed or delayed in children because of a low index of suspicion on the part of care providers. In addition, children are much more likely than adults to present with headaches, seizures, or altered mental status as the first sign of stroke. Any child with acute onset of a focal neurologic deficit should be investigated for possible stroke, but other situations that should be investigated for possible stroke include seizures in the newborn, seizures in a child of any age occurring after cardiac surgery, and changes in mental status associated with headache.

Approximately 75% percent of AIS in children occurs in the anterior circulation coming from the internal carotid arteries. Older children with ischemic strokes most commonly present with acute hemiparesis, hemisensory loss, or aphasia but may also present with isolated seizures or hemichorea. Children with posterior circulation strokes affecting the vertebrobasilar distributions may present with ataxia, vertigo, visual field cut, or brainstem signs. Children with watershed strokes can present with proximal greater than distal weakness.

Intraparenchymal hemorrhage classically presents with focal neurologic signs or seizures accompanied by severe headache, emesis, and loss of consciousness but may be impossible to distinguish from AIS based on clinical features alone because presentations vary (see Figure 79-2). Children with CSVT may present acutely with headaches, emesis, seizures, altered mental status, or focal neurologic signs but can also present more insidiously with symptoms of increased ICP such as chronic headache, blurry vision, or diplopia secondary to sixth cranial nerve palsies.