Two important factors, the blood supply and the metabolic needs of the brain region supplied, govern the extent of damage to nervous tissue produced by cerebrovascular disease. Blood is supplied to the brain by two essentially separate circulations, the carotid (anterior) and vertebrobasilar (posterior) systems, and to a lesser extent by small perforating blood vessels from the meninges. Anastomoses between the carotid and vertebrobasilar systems exist at the circle of Willis and in the meninges. These anastomoses are important because they may prevent hypoperfusion when circulation is reduced in the territory of a single vessel. The efficiency of these anastomoses in preventing ischemia and infarction is dependent on how quickly flow is interrupted. With slower occlusion, the region of brain supplied by the vessel more likely will remain adequately perfused by collateral vessels, and the area of ischemia and subsequent infarction will be minimized. When end arteries, which are smaller vessels that have few or ineffective anastomoses, become occluded, the likelihood of infarction is relatively higher. Brain parenchyma situated between the most distal portions of the two circulations or major arteries within a circulation (e.g., those from the anterior and middle cerebral arteries in the anterior circulation) is termed a watershed zone or area. These “zones” have some blood supply from both circulations and, consequently, have some protection from occlusion of one or other circulation. However, watershed areas are especially vulnerable to damage from a general decrease in the cerebral perfusion pressure that can occur with severe systemic hypotension or with very high intracranial pressure (ICP) that produces decreased cerebral perfusion.

Two fundamental mechanisms protect the brain in the setting of decreased perfusion and oxygenation: autoregulation and elevation of the oxygen extraction fraction. Autoregulation is an important physiologic mechanism that supports maintained normal cerebral perfusion (the difference between mean arterial pressure and ICP or central venous pressure) in the setting of decreased and increased systemic pressures by altering the resistance of blood vessels in the brain. To what extent the developing cerebral vasculature can autoregulate or modulate oxygen extraction and at what age the capacity for these mechanisms reaches maturity remain unclear.

Recent research has improved the understanding of the pathophysiologic processes involved in stroke and has suggested some therapeutic strategies. Experimental data suggest that ischemic brain injury is an evolving process, with the amount of injury related to the degree of diminution of local cerebral blood flow (CBF). The ischemic penumbra in stroke refers to a region of tissue that is electrically silent as a result of absent or decreased perfusion. Ultimately, the central core of this ischemic penumbra will be damaged irreversibly, and a surrounding ischemic zone will, with return of perfusion, survive with normal or near-normal function. If blood flow falls further in these surrounding regions, more extensive infarction will occurs, and “progression” of the stroke will be seen. When flow to these ischemic regions is restored, then clinical improvement occurs. In adults, CBF is roughly 50 mL/100g/minute. Clinical manifestations of cerebral ischemia manifest when CBF falls to less than 20 mL/100g/minute. When CBF is less than 15 mg/mL/minute, recipient tissue becomes electrically silent. CBF of less than 8 to 10 mg/mL/minute leads to the failure of ion conductance. The corresponding parameters are not well understood in the developing brain. The concept of a penumbra has suggested strategies for decreasing the ultimate size of infarcted tissue by effectively restoring blood flow to ischemic regions. Therapeutic strategies include reperfusion of ischemic areas by thrombolytic drugs or angioplasty, neuroprotection using drugs that may ameliorate the neurotoxicity of released chemicals, and anticoagulation to prevent further embolic phenomena. Prompt diagnosis and treatment may decrease the extent of infarction and may thereby reduce the ultimate morbidity in stroke.

A stroke also can be caused by obstructing the outflow of blood from the brain, which can be seen if cerebral veins or the venous sinuses are occluded. The pathophysiology of this entity is related to “backpressure,” which results in stasis and subsequent ischemia, as well as raising ICP and decreasing the perfusion of the brain. This type of backpressure also may result in the rupture of smaller vessels that feed the venous sinuses.

A transient ischemic attack (TIA) is defined as loss of neurologic function lasting less than 24 hours with subsequent complete return of normal function. By definition, TIA is caused by ischemia, but not infarction, of brain tissue.

Classically, the clinical presentation of cerebrovascular disease is thought to depend on the specific brain regions and/or white matter pathways damaged and the functions subserved by these regions. Indeed, a great deal of what is known about the localization of function in the human brain stems from the consequence of cerebrovascular disease and stroke. Strokes in the anterior (internal carotid) system usually present with hemiplegia, hemisensory loss, aphasia, or hemianopsia, whereas events in the posterior (vertebrobasilar) circulation typically present with brainstem dysfunction such as bilateral motor, sensory, and visual disturbances, vertigo, abnormal eye
movements, and problems with balance and coordination. Specific stroke syndromes have been well characterized but are beyond the scope of this chapter. The reader is referred to standard neurology textbooks for detailed accounts.

Stroke is a relatively rare occurrence in children. In population-based studies from Minnesota and California, the annual incidence rate was roughly 2.5 cases per 100,000 population, or approximately one-half the incidence for primary intracranial neoplasm. Of these, 0.6 to1.2 per 100,000 were ischemic strokes and 1.1 to 1.9 per 100,000 were hemorrhages, depending on whether patients with sickle cell anemia were included in the analysis (absent for Minnesota, present for California). Adult series report between 90 and 110 cerebrovascular accidents per 100,000 adults/year. Of these, most are thrombotic strokes related to occlusive vascular disease. African American children are more likely to develop ischemic strokes and hemorrhagic strokes, even when those with sickle cell disease are excluded. Their risk of death also is greater. Male patients, in general, are more likely to die of stroke in childhood.

Many strokes in children are without a known origin or are a complication of a disease originating outside the central nervous system (CNS). Congenital heart disease, sickle cell disease, vasculitis, infection, hypercoagulable states, vascular dissection, and trauma are the usual causes of childhood stroke. Although these diseases usually are evident before the stroke occurs, sometimes stroke is the presenting problem. Atherosclerosis and hypertension, the major systemic disorders associated with occlusive vascular disease in adults, are rare causes of stroke in the pediatric population.

Cerebrovascular disorders usually present as an acute alteration in neurologic function, but changes occasionally occur in a gradual or stepwise fashion. Other disorders may present with similar symptoms and need to be considered in the differential diagnosis of acute neurologic dysfunction. Brain tumors may mimic cerebrovascular disorder because of the rapid onset of surrounding edema or hemorrhage into the tumor. Unwitnessed focal seizures may present as hemiparesis, but, in contrast to hemiparesis caused by a vascular event, the signs usually begin to resolve at around 6 hours and are resolved completely within 24 to 48 hours (e.g., Todd paresis). In embolic stroke or stroke associated with an arteriovenous malformation (AVM), a focal seizure may herald the event. In these cases, the hemiparesis usually will persist for more than 24 hours. Intracranial infections, such as meningitis, may be associated with cerebrovascular events because they can involve vessel walls leading to spasm or local thrombotic occlusion. Tuberculous meningitis, a chronic form of meningitis, may present with gradual neurologic dysfunction and/or may be associated with stroke. Cerebral abscess may mimic a cerebrovascular event, but other symptoms such as fever or a source of infected emboli should help to differentiate an abscess from a vascular occlusion.

Mechanisms for thrombotic and embolic occlusive cerebrovascular disease in children are listed in Box 400.1.