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

Ultrasound of the head combined with color and pulsed Doppler imaging remains a useful technique to evaluate the circle of Willis, in particular the regions of signal loss on MRA. If an intraluminal clot is identified or confirmed, bedside Doppler imaging can be used to monitor for recanalization and decreases in resistive indices that may occur as a result of secondary hyperperfusion.

In two thirds of patients, neurologic deficits with hemiplegia develop if the posterior limb of the internal capsule, motor strip, or basal ganglia is involved on the initial studies.

On long-term follow-up, regions of AIS can evolve into regions of volume loss, glial scarring, or cystic encephalomalacia, depending on the severity of the injury.

AIS also can develop as a result of bacterial meningitis as inflammatory cells infiltrate the vessel wall, leading to foci of necrosis that incite thrombosis of the arteries or veins coursing through the infected space (Fig. 37-3).

Venous Stroke

Venous strokes are associated with vasogenic edema, hemorrhage, and ischemic necrosis in a venous distribution. A venous stroke can occur as a result of transient mechanical or thrombotic occlusion of a vein or venous sinus. Newborns present with nonspecific symptoms related to increased intracranial pressure, lethargy, or seizures. A significant proportion of neonatal sinovenous thrombosis (SVT) is classified as idiopathic, but risk factors include dehydration, sepsis, asphyxia, maternal diabetes, and thrombophilia.⁸ Isolated SVT has a good prognosis, except in rare cases when the deep venous system becomes involved.

CT may show a hyperdense clot in the involved vein or venous sinus and can identify intraventricular hemorrhage seen with involvement of the deep venous system. MRI is the preferred modality for confirming the diagnosis and determining the presence and extent of the associated brain injury. T2* gradient-echo or susceptibility-weighted images are particularly useful in demonstrating the thrombus as a region of “blooming” in the venous system and detecting intraparenchymal hemorrhage (Fig. 37-4 and Boxes 37-2 and 37-3). On follow-up examinations, brain parenchyma affected by a venous stroke can show atrophy or can almost completely resolve, depending on the severity and duration of the injury.

Ultrasound can be used to visualize the echogenic clot at the bedside and to monitor its evolution. It also can be used to screen for additional complications, such as hydrocephalus as a result of intraventricular hemorrhage.

Arterial Ischemic Stroke

In more than half of childhood cases of AIS, the precise etiology is never determined. In the remaining cases, a variety of pathologies are found, including thromboembolism (from intracranial or extracranial vessels, cardiac disorders such as congenital or acquired heart disease, intracardiac shunts, and procedures), arteriopathy (arterial dissection, moyamoya disease, vasculitis, sickle cell disease [SCD] arteriopathy, postvaricella angiopathy, and idiopathic focal cerebral arteriopathy), and hypercoagulable states (protein C or S deficiency, antithrombin III, and factor V Leiden mutation).10,11

SCD, a common risk factor for stroke in children, increases the risk of having a stroke approximately 200 to 400 times. The rigid, sickle-shaped red blood cells lead to vascular occlusion. Additionally, adherence to the vessel wall damages the intima and media, resulting in fibrosed and stenotic vessels. Proximal MCA or distal internal carotid artery branches are the most commonly involved vessels. In approximately 5% to 8% of patients with SCD, symptomatic cerebrovascular disease develops, and in about 20% of cases, a clinically silent stroke also may develop.

On imaging, acute infarction is usually superimposed on a diseased brain with atrophy and chronic changes. MRA commonly shows irregular stenotic arteries involving the anterior circulation with leptomeningeal collaterals, often longstanding. CT angiography (CTA) use is limited because iodinated contrast predisposes to sickling crises. Low osmolar agents should be used when iodinated contrast is deemed necessary, along with transfusion and hydration to reduce the risk of complications. Biannual screening with transcranial Doppler imaging is routinely performed, and abnormally elevated time-averaged mean velocities (>200 cm/sec) from stenotic arteries necessitates blood transfusion to prevent stroke.¹² Brain MRI is usually performed to evaluate children with sickle cell anemia presenting with seizures or motor or sensory deficit.

Moyamoya disease accounts for approximately 6% of AIS incidence in Western countries. Moyamoya disease is a progressive vasculopathy causing stenosis of intracranial arteries with a predilection for terminal portions of the internal carotid arteries (Fig. 37-5). It can be associated with neurofibromatosis type 1, radiation vasculitis, Down syndrome, and SCD; if the cause remains undetermined, it is referred to as moyamoya disease. Collateral formation from the lenticulostriate vessels and thalamoperforators lead to a classic “puff-of-smoke” appearance on angiography. MRI can demonstrate loss of the normal flow void in the distal carotid branches on T2-weighted images, as well as development of abnormally large and irregular collateral vessels. Fluid attenuated inversion recovery images often show increased signal in distal vessels with decreased flow. Carotid stenosis also can be observed on MRA, but its severity can be overestimated because of slow and turbulent flow.¹³ Postcontrast MRA and, in particular, CTA can improve accuracy. DWI demonstrates acute areas of ischemic necrosis, whereas perfusion imaging and arterial spin labeling can demonstrate peripheral areas of delayed cerebral flow.

Arterial dissection may occur spontaneously or after trauma. Arterial dissection leads to formation of an intramural thrombus, which can propagate and embolize distally, or it can lead to vascular occlusion. The common locations are at the junction between relatively fixed and mobile segments of arteries and among the intracranial arteries; the supraclinoid internal carotid artery often is affected. T1-weighted fat-saturated sequences performed from the aortic arch to the cavernous sinus can demonstrate concentric hyperintense signal because of methemoglobin in the vessel wall in the subacute phase. If the dissection is recent, close inspection of the images is necessary to rule out isointense concentric wall thickening. If MRA is degraded by flow artifacts, CTA can be performed (Fig. 37-6). The angiographic findings are abrupt segmental narrowing with an intimal flap, a beaded appearance, or pseudoaneurysm formation.¹⁴

Mitochondrial disorders usually involve multiple systems, but the strokelike events that appear as focal neurologic deficits of abrupt onset can mimic and be clinically indistinguishable from AIS. Mitochondrial injuries do not follow the vascular boundaries, and on MRI, the ADC values are typically normal to elevated, as opposed to the classically low values seen with AIS⁶ (see Chapter 33).

The presence of transient neurologic symptoms in patients with migraine also can simulate stroke. Migraine with aura has been associated with increased risk for stroke in the adult population, and the literature includes some case reports of migrainous infarct in adolescents. The association between these two entities is thought to be related to a dysfunction of cerebral arteries during migraine bouts (Fig. 37-7).¹⁵

Venous Stroke

In children, SVT is the primary cause of venous stroke. Dehydration, complicated otitis media, and sinusitis are the major risk factors in older children. Less commonly, a prothrombotic disorder, trauma, or medication is the identified cause. If the superficial cortical veins are involved, SVT leads to regional cerebral edema, which has a good prognosis. SVT is demonstrated as hyperdensity on CT and variable signal intensity on conventional MRI sequences. MRI with susceptibility-weighted images, DWI, MR venography, and postcontrast volumetric T1 imaging are the sequences of choice. DWI is helpful for determining whether vasogenic edema or ischemic necrosis is present. Postcontrast volumetric T1 images provide direct visualization of filling defects in the venous system and allow secondary evaluation of regions of signal dropout on MR venography.¹⁶ Identification of the clot on susceptibility sequences is the best confirmation of SVT. If MRI is equivocal, CT venography can give a better delineation of the venous system, at the expense of radiation exposure (Fig. 37-8).

Jackson, BF, Porcher, FK, Zapton, DT, et al. Cerebral sinovenous thrombosis in children: diagnosis and treatment. Pediatr Emerg Care. 2011;27(9):874–880.

Mackay, MT, Wiznitzer, M, Benedict, SL, et al. Arterial ischemic stroke risk factors: the International Pediatric Stroke Study, International Pediatric Stroke Study Group. Ann Neurol. 2011;69(1):130–140.

Rodrigues, K, Grant, PE. Diffusion-weighted imaging in neonates. Neuroimaging Clin N Am. 2011;21(1):127–151.

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15. Ming, X, Yacoub, H, Khanna, A, et al. Two young patients with stroke in conjunction with migraineus headache. Open Neurol J. 2010;15(4):111–116.

16. Jackson, BF, Porcher, FK, Zapton, DT, et al. Cerebral sinovenous thrombosis in children: diagnosis and treatment. Pediatr Emerg Care. 2011;27(9):874–880.