Cerebrovascular disorders

Cerebrovascular Disorders James S. Hutchison, Rebecca Ichord, Anne-Marie Guerguerian, and Gabrielle deVeber Arterial ischemic stroke is being recognized more commonly in the pediatric population. The etiologies differ greatly from those seen in adults. The most common etiologies are congenital heart disease and sickle cell disease. Children may present with or without hemiparesis and may have fever, headache, and depressed level of consciousness. A high index of suspicion is needed to diagnose stroke. Although clinical studies are scarce in children, besides early diagnosis, early specialized care with careful attention to detail ensuring adequate oxygenation and ventilation, prevention of hyperthermia and seizures, and maintenance of blood pressure and metabolic balance are important and likely improve outcome in these children. Selective children may also benefit from anticoagulant therapy, and, as the interval to diagnosis decreases, thrombolytic therapy may become an option although safety data are required. Children with acute stroke should be rapidly transported to and cared for in a pediatric center with a specialized stroke team or access to acute stroke protocols. © 2004 Elsevier Inc. All rights reserved.

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URRENTLY, MANY adult patients with arterial ischemic stroke are managed rapidly at stroke centers with protocols for diagnostic imaging, neurocritical care, and thrombolysis therapy. These protocols reflect evidence-based therapy and are highly focused on the concept of a limited therapeutic time window beyond which there is a decreasing likelihood of rescuing an injured brain. Evidence for the benefit of acute interventions is lacking in the pediatric stroke literature. Design and evaluation of acute interventions is further complicated by the fact that arterial ischemic stroke is less common and of differing etiologies in children than in adults. There are important developmental differences in the coagulation, cerebrovascular, and neurologic systems of infants and children compared with adults that limit the applicability of research performed in adult stroke patients to pediatric patients with stroke. Efforts to build a multicenter clinical research network focused on pediatric stroke began in 2000 supported by the Child Neurology Foundation. Collaboration among the investigators in this network have helped drive the formation of multidisciplinary institutional stroke teams and research protocols in individual centers, while establishing the basis for a pilot, international multi-institutional cohort stroke study. In this article we describe our current understanding of the epidemiology and pathophysiology of pediatric arterial ischemic stroke, as well as our approach to the diagnosis and management of arterial ischemic stroke in children stemming from our experience, research data, and our institutional clinical stroke protocols. We focus our review on the management of arterial ischemic stroke in children, be-

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cause this is the most frequently encountered form of pediatric stroke. EPIDEMIOLOGY OF CHILDHOOD STROKE

Stroke is underdiagnosed in children due in part to the fact that many pediatric patients have transient, nonspecific, or occult symptoms. The use of neuroimaging has revolutionized our ability to diagnose stroke. Estimates of the incidence of childhood stroke vary depending on whether neonatal stroke, hemorrhagic stroke, and venous thrombosis are included. Data published from a populationbased cohort from the Canadian Pediatric Stroke Registry from the 1990s1 showed that the incidence of ischemic stroke was 3.3/100,000 per year from birth through age 18 years. A total of 820 children with ischemic stroke were identified in the first 6 years; arterial ischemic strokes constituted 80% of cases.1,2 This incidence was nearly double the estimates from previous decades and is com-

From the Departments of Critical Care and Pediatrics, Hospital for Sick Children, and Interdepartmental Division of Critical Care, Faculty of Medicine, University of Toronto, Toronto, Canada; Departments of Neurology and Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA; Department of Anesthesiology and Critical Care Medicine, Division of Pediatric Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD; and Division of Pediatric Neurology, Department of Pediatrics, Hospital for Sick Children, Faculty of Medicine, University of Toronto, Toronto, Canada. Address reprint requests to Gabrielle deVeber, MD, Division of Pediatric Neurology, Department of Pediatrics, Hospital for Sick Children, 555 University Ave., Toronto ON M5G 1X8, Canada. © 2004 Elsevier Inc. All rights reserved. 1071-9091/04/1102-0000$30.00/0 doi:10.1016/j.spen.2004.04.004 139

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parable to the incidence of childhood brain tumors. The incidence is highly age-dependent, with estimates of stroke in neonates approaching a rate nearly 10-fold higher than older infants and children.3 Specific high-risk populations experience a much higher risk of stroke, most notably children with congenital heart disease and sickle cell anemia. Patients with sickle cell anemia have a 12% to 20% risk of experiencing a stroke some time during childhood in the absence of primary preventative treatment measures. ETIOLOGY, RISK FACTORS, AND PATHOPHYSIOLOGY OF STROKE

Risk factors for stroke in children are very different than those in adults, in whom atherosclerosis, systemic hypertension, and diabetes mellitus predominate. Standard etiologic classification systems for arterial ischemic stroke in adults fail to account for the vast majority of children with stroke. For an in-depth review of the risk factors for arterial ischemic stroke in children, see the studies and reviews by deVeber4 and Ganesan et al.5 We summarize the risk factors here. In up to 25% of children with ischemic stroke, no specific etiology can be found. The most common identifiable cause of childhood ischemic stroke is complex congenital heart disease. Emboli formed on prosthetic heart valves can reach the cerebral circulation directly. In the presence of an atrial or ventricular septal defect with continuous or intermittent right-to-left intracardiac shunt, systemic venous clots can also reach the cerebral circulation. Nearly 50% of strokes occur within 72 hours of cardiac surgery or catheterization in this patient population. Arterial ischemic stroke occurs in 2.6% to 8.8% of patients after the Fontan procedure. Cyanotic lesions increase the risk of thromboembolism due to polycythemia and anemia. Arterial or venous stroke has been identified in 5% to 12% of children with meningitis. Pediatric stroke has been reported in the following specific infectious disorders: mycoplasma, cat scratch fever, Rocky Mountain spotted fever, coxsackie B4 and A9, influenza A, varicella, human immunodeficiency virus, parvovirus B19 and X, and chlamydia. Postvaricella angiopathy occurring weeks or months after uncomplicated varicella is probably underdiagnosed. Radiographic features of postvaricella angiopathy are distinctive and consist of a combination of basal ganglia infarction and steno-

sis of the distal internal carotid or proximal anterior, middle, or posterior cerebral arteries. A putative mechanism is that the virus is activated in the trigeminal ganglion and spreads along the trigeminal nerve fibers innervating the internal carotid artery and proximal cerebral arteries. Inherited or acquired coagulation disorders can act as predisposing risk factors for arterial ischemic stroke. Prothrombotic abnormalities identified with stroke in children include deficiencies of protein C, protein S, antithrombin, and plasminogen and the presence of abnormal activated protein C resistance (associated with factor V Leiden mutation), anticardiolipin antibody, lupus anticoagulant, nonspecific inhibitor, elevated homocysteine and lipoprotein-a levels, and mutations involving the prothrombin gene and methyltetrahydrofolate reductase. New prothrombotic disorders are being identified at a rapid rate. Comprehensive prospective testing for prothrombotic disorders has identified single or multiple abnormalities in 30% to 50% of children who have sustained arterial ischemic stroke. Most of these disorders are acquired, including anticardiolipin antibodies. Congenital prothrombotic states are less common. The role of prothrombotic factors in childhood stroke likely varies greatly with the demography and case mix. In children with prothrombotic disorders, thromboembolic events usually occur in the setting of additional triggering events or risk factors. Coagulation testing should therefore be performed in any child who has sustained arterial ischemic stroke even when other children with other risk factors are identified. If possible, the coagulation testing should be done after the discontinuation of anticoagulant therapy. Hematologic disorders can also predispose pediatric patients to arterial ischemic stroke. Sickle cell disease is the most common hemoglobinopathy associated with cerebrovascular disease. About 25% of patients with sickle cell disease develop cerebrovascular complications. Platelet disorders, including thrombocytosis, can be associated with arterial ischemic stroke. Iron-deficiency anemia is associated with stroke in older infants. The mechanism behind this is not known, and a cause-andeffect relationship has not yet been fully established. Arterial dissection of the carotid or vertebral arteries can be caused by direct intraoral trauma and rotational or hyperextension injuries to the

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neck, or can occur spontaneously. Postradiation vasculopathy is a progressive large-vessel stenosis that presents with transient ischemic attacks (TIAs) or strokes beginning several years after focusedbeam irradiation of tumors located within the optic chiasm, sella, or suprasellar region. Vasculitis involving the cerebral arteries is increasingly identified in childhood stroke. Polyarteritis nodosa, Takayasu’s arteritis, mixed connective tissue disease, and juvenile temporal arteritis are rare forms of vasculitis associated with childhood arterial ischemic stroke. Most frequently, idiopathic vasculitis is diagnosed. The latter has been referred to as “isolated” or “primary angiitis of the central nervous system,” in which case bilateral progressive lesions are identified, or as “transient cerebral arteriopathy of childhood,” in which case a selfresolving, possibly inflammatory attack on unilateral distal internal carotid, anterior cerebral, or middle cerebral arteries is documented. The latter vasculopathy resembles postvaricella angiopathy, but there is an absence of varicella infection in the preceding year. Other rare causes of childhood stroke include Moyamoya’s disease and syndrome, metabolic diseases such as homozygous homocystinuria, Fabry’s disease, mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome, and hyperlipidemia and migraine. A recent 22-year consecutive cohort study from the UK identified risk factors for 212 children who had sustained arterial ischemic stroke.5 It was found that 54% of the patients had no known risk factors for stroke on presentation, but after full investigation, risk factors or possible contributing factors were identified in all but four cases (⬍2% of the cohort). The patients in this study underwent extensive diagnostic workup, including neuroradiologic imaging of the brain, cerebral vasculature, and neck vessels; echocardiography; and hematologic and prothrombotic tests. Multiple risk factors were identified in a large percentage of cases, for example, the coexistence of known heart defects with cerebral or cervical vascular lesions or prothrombotic risk factors. Altogether, 80% of the subjects were found to have cerebral or cervical vascular abnormalities when they were fully evaluated. The study identified a number of common childhood events that frequently preceded or accompanied the stroke, including head or neck trauma in as many as 10%, prodromal infection in

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30%, concurrent fever with symptom onset in nearly 50%, and varicella zoster infection within the preceding year in 25%. The pathophysiology of arterial ischemic stroke varies with the etiology of the stroke. In situ thrombosis of the cerebral arteries can result from primary disorders of the cerebral arteries or from acquired or congenital prothrombotic states. Under physiological circumstances, the endothelial lining of arteries provides an anticoagulant surface. When the arterial wall is damaged, it becomes prothrombotic and promotes formation of a thrombus through several mechanisms. Cerebral artery stenosis slows blood flow and potentiates nonlaminar blood flow, which provides another mechanism for thrombosis. Embolic sources for arterial ischemic stroke in childhood include congenital heart disease and structural disorders of the cerebral arteries. These abnormalities result in cardiogenic embolism or artery-to-artery embolism. A further mechanism is the presence of an intermittent rightto-left intracardiac shunt, which occurs with atrial septal defects, patent foramen ovale, tetralogy of Fallot, and postoperative residual right-to-left shunt after the Fontan procedure. These shunts lead to paradoxical embolism, effectively allowing systemic venous thrombi to reach the cerebral circulation. The severity of cerebral tissue damage and the resultant neurologic impairments are a function of a multitude of factors. These include the location of the perfusion defect (large-vessel vs small-vessel disease; anterior vs posterior vascular territories), the duration and extent of ischemia (partial vs complete), the preservation or lack thereof of cerebral circulatory regulation; the maturational status of the brain, the capacity of collaterals, and the timing and adequacy of restoring perfusion. Ischemia of sufficient severity and duration, even if temporary, will produce an ischemic core where cells are destined to die. The ischemic core is surrounded by an ischemic penumbra (Fig 1), in which cells are selectively vulnerable to secondary insults, leading to further cell death and enlargement of the stroke. Cell death in the core or the penumbra occurs through a dynamic mix of acute necrosis and apoptosis depending on region-specific vulnerabilities, the maturational state of the brain, and the nature of the ischemic insult. In the penumbra, clinical factors that impair the balance between cerebral metabolic rate and oxygen and

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understand the effect of stroke on the developing brain. CLINICAL PRESENTATION AND THE ABC’S: PROTECTING THE PENUMBRA

Fig 1. Diagram of arterial ischemic stroke. The ischemic core is a zone where the cells are destined to die. The penumbra is a zone of potentially viable brain tissue where hyperglycemia, hypotension and hyperthermia may lead to further cell death. Secondary insults following stroke can lead to expansion of the ischemic core into the penumbra.

glucose delivery will result in further tissue injury and cell death. It is the potential to salvage the penumbra that drives the need for aggressive and early specialized care of the child during the first 48 hours after initiation of the ischemic infarct. The optimization of perfusion, oxygenation, and metabolic conditions requires careful attention to clinical parameters including blood pressure, presence of seizures, fever, and altered blood glucose levels. The loss of autoregulation in damaged tissue within an evolving infarct further increases the vulnerability of the peri-infarct area to decreased cerebral blood flow and results in additional secondary cerebral ischemia in the presence of decreased blood pressure. Much basic science work has been done that helps us understand the pathophysiology, mechanisms, and molecular biology of stroke, including ischemia-reperfusion injury in adult animal models.6 There are exciting new recombinant agents that block the excitotoxicity of NMDA receptors, reduce stroke size, and improve neurologic outcome after middle cerebral arterial occlusion in rodents.7 Work done using the Vanucci model with unilateral carotid occlusion followed by hypoxic insult in immature rats has been important in improving our understanding of ischemic injury in the immature and developing brain, focused particularly on the neonatal rodent brain.8 However, there are few studies in animal models that reproduce the combined features of cerebral vasculopathies, disordered coagulation, and triggering factors that are the hallmarks of childhood stroke outside the neonatal age range. Further work is needed in more mature pediatric models to help us

The clinical features of arterial ischemic stroke are age-related. Any child with an unexplained acute-onset focal neurologic deficit of any duration, or with unexplained altered consciousness, particularly with headache, should be considered to possibly have a cerebrovascular disorder. Other clinical scenarios in which stroke syndromes should be considered include unexplained seizures in a term or near-term newborn and postoperative seizures in infants undergoing cardiac surgery or catheterization. Seizures accompany stroke in approximately 50% of children. Recent data indicate that up to 33% of children who experience arterial ischemic stroke experienced a preceding TIA, although these attacks often go undiagnosed.9 Children with suspected acute stroke should be resuscitated rapidly, especially if they have a depressed level of consciousness. These children should be stabilized promptly and transferred for further management to an institution that can offer comprehensive pediatric neurovascular care and provide a team approach, which should include neurologists, neuroradiologists, neurosurgeons, hematologists, anesthetists, and critical care specialists. Ensure Airway and Oxygenation Apply 100% oxygen via a face mask and initiate cardiorespiratory monitoring including a transcutaneous arterial oxygen saturation monitor. Use bag-mask ventilation and prepare for intubation if needed. Indications for intubation are as follows: 1. Upper airway obstruction from actual or potential loss of pharyngeal muscle tone or loss of protective airway reflexes (cough and gag) 2. Coma or decreasing level of consciousness with a GCS score ⱕ8 or deteriorating GCS score 3. Respiratory arrest, failure, or depression leading to hypoxia despite supplemental oxygen or respiratory acidosis 4. Seizures or status epilepticus 5. Associated decompensated shock. Intubate the trachea using rapid sequence induction of anesthesia. Cervical spine immobilization precautions should be used in cases where the suspected stroke may be associated with trauma.

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Ensure Adequate Ventilation

Optimize Hemoglobin

Monitor quantitative CO2 using end-tidal CO2 or blood PaCO2.

Hemoglobin level should be maintained at ⬎100 g/L.

Maintain Circulation

Provide Specialized Treatment for Sickle Cell Patients

Ensure adequate cardiac output, cerebral blood flow, and oxygen delivery by establishing intravenous access if not already done. Provide maintenance intravenous fluid with non– dextrose-containing isotonic fluids; aiming for normovolemia and blood pressures ⱖ50th percentile for the child’s age- or height-related norms. Monitor cardiopulmonary status continuously, with intermittent frequent checks of blood pressure. Invasive arterial pressure monitoring through an arterial catheter may be necessary. There is evidence in adults with stroke that both hypotension and hypertension are associated with poor outcome.10 Estimate dehydration and plan deficit correction over the next 24 or 48 hours, considering the type of dehydration and sodium balance. Monitor Serum Glucose Level and Maintain Normoglycemia Hypoglycemia and hyperglycemia are associated with worse outcome in adults with stroke and in different models of brain injury, and should be avoided.11-14 Prevent and Treat Hyperthermia Aggressive correction of fever is critical. Aim for maintenance of core temperatures of approximately 36 to 37°C. Treat Seizures Aggressively Initiate treatment with anticonvulsants after any seizure, taking care to avoid transient blood pressure depression from rapid dosing. Protect Against Aspiration Hold oral intake pending hemodynamic and respiratory stability. Nasogastric or small bowel feeds should be instituted in intubated patients or in extubated patients when risk of regurgitation and aspiration is judged to be low. Oral feeds may be resumed when the patient is extubated and awake. Evaluation of adequate swallowing function by a speech therapist may be necessary if coordination of swallowing and airway protective reflexes are an issue.

Sickle cell patients with stroke should receive an exchange transfusion, with extreme care taken to maintain cerebral perfusion pressure throughout the procedure. DIAGNOSTIC TESTS

Laboratory Testing Admitting laboratory and diagnostic studies should include blood gas, chemistry, and hematologic profiles; prothrombin time (PT); partial thromboplastin time (PTT); international ratio; urinalysis; and electrocardiography. More specific testing may be indicated by patient history and physical examination findings, for example, in fever in a patient with sickle cell anemia or a patient with suspected metabolic disease. A full evaluation for thrombophilia should be considered in all children with ischemic stroke, because children often have multiple risk factors for stroke, including thrombophilia. The incidence of recurrent stroke increases in those children with multiple risk factors. Children and their families with identified disorders require prognostic counseling and longterm preventative treatment strategies.1,15 Institutional stroke protocols for specific testing procedures should be developed in individual institutions in consultation with pediatric thrombosis and neurology experts, because these tests and their results are subject to change as research progresses in this area. A sample list of studies to evaluate for thrombophilia is given in Table 1. A thrombophilia workup of other family members may be appropriate in these hereditary disorders. Additional laboratory studies often include rheumatologic investigations, particularly in the presence of vascular stenosis. These include erythrocyte sedimentation rate, complement studies, antinuclear antibodies, and C-reactive protein values. Cardiology consultation is advised in children with arterial ischemic stroke, and a minimal diagnostic evaluation should include a transthoracic echocardiogram. Transesophageal or agitated bubble echocardiogram (for right-to-left shunt) may be considered for patients in whom no other major vascular

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Table 1.

Laboratory Evaluation for Thrombophilia

Lab Test

CBC, PT/PTT Protein C: Functional Protein C: Immunologic if ⬍6 months Protein S: Functional and free Antithrombin III Factor V Leiden mutation Prothrombin mutation Lupus inhibitor screen

Comments

Send before giving heparin. Not helpful if the patient is on coumadin. Normal levels in neonates are based on immunologic test. Not helpful if the patient is on coumadin. Send before giving heparin. This is not a factor V level. Includes anticardiolipin antibodies, anti-beta-2-glycoprotein-1 antibody, and dilute Russell viper venom time.

Methylenetetrahydrofolate reductase gene mutation Plasma homocysteine level Lipoprotein(a)

cause is identified and transthoracic echocardiogram findings are normal or equivocal.

litis is suspected, which is not well visualized on MR angiography.

Neuroimaging

LIMITING/LYSING THE THROMBUS

The key to specific diagnosis lies in neuroimaging. An urgent head computed tomography (CT) scan should be obtained in all children with clinically suspected stroke syndrome. A helical CT angiogram may also be helpful, and may detect vessel abnormalities as well as a magnetic resonance (MR) angiogram.16 MR imaging (MRI) should then be obtained in the acute stages, if feasible, because it is far superior to CT in confirming and characterizing the acute stroke syndrome. The use of diffusion-weighted imaging in MRI enables the detection of very early infarcts that frequently are not visible on CT scans. Because the differential diagnosis for acute hemiplegia in children is much wider than that in adults, treatment for stroke is at best presumptive until the diagnosis is confirmed. During the acute stages of presumed stroke, CT and MRI images should be reviewed by a senior neuroradiologist who is part of the stroke team, to help quickly narrow down the differential diagnosis to a limited number of possibilities that have immediate treatment options. Generally speaking, an MRI protocol for acute stroke will include T2- and T1-weighted axials, fluid-attenuated inversion recovery, and diffusion-weighted imaging at a minimum. Vascular imaging should be included with the initial MRI, and in all cases, MR angiography or venography should be obtained. Conventional cerebral angiography may also be indicated in some cases when MR angiography is negative or equivocal, or when small- and medium-vessel involvement by vascu-

There is no evidence that systemic intravenous tissue plasminogen activator (tPA) therapy is of benefit in treating children with stroke. Current recommendations in adults who meet strict inclusion criteria specifies administering intravenous tPA within 3 hours of stroke onset, because this therapy improves neurologic outcome. This therapy is associated with a risk of intracranial hemorrhage.17,18 To date, intravenous tPA has been associated with worsened outcome and a higher risk of intracranial hemorrhage19 when administered between 3 and 5 hours poststroke in adults and should not be considered during this time window in children. The use of thrombolysis therapy for systemic clots carries a higher risk of hemorrhagic complications in children than in adults.20 Intra-arterial tPA therapy in adults has extended the therapeutic window of thrombolytic therapy for stroke in adults to 3 to 5 hours,21 but further research is needed. There are case reports of use of intra-arterial tPA in children with stroke.22-24 We are currently developing research protocols for consecutive cohort safety and feasibility studies for the use of intra-arterial tPA in older children with nonhemorrhagic arterial ischemic stroke seen within 5 hours, applying the same strict inclusion criteria as adults and with documented arterial occlusion by admission MR or CT angiography at our institutions. Based on concerns about the relatively increased role played by the coagulation system in pediatric

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ischemic stroke compared with adult stroke, as well as the apparent safety in our early experience in children compared with adults, some centers currently use standard heparin or low molecular

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weight heparin in children with acute arterial ischemic stroke during the first 5 to 7 days. Arterial ischemic stroke is first confirmed, and then cerebral hemorrhage is ruled out using diagnostic neuroimaging before an anticoagulant protocol is instituted. For standard heparin, we recommend no loading dose and a maintenance dose of 28 U/kg/hr for patients age 2 years and younger and 20 U/kg/hr for patients over age 2 years (adjust heparin to maintain PTT at 60 to 85 seconds). For low molecular weight heparin, we use enoxaparin 1.5 mg/kg administered subcutaneously every 12 hours for patients age 2 years and younger of age and 1 mg/kg subcutaneously every 12 hours for patients over age 2 years. The heparin is replaced with aspirin when cardiogenic emboli, dissection, prothrombotic disorders, and vasculitis have been excluded and when oral intake is resumed. Aspirin is continued until the risk of recurrence is assessed to be negligible (usually indefinitely). We use a dose of 3 to 5 mg/kg/day administered either daily or three times a week. When arterial ischemic stroke is due to cardiogenic emboli, large-vessel dissection, a prothrombotic disorder, or vasculitis, heparin is replaced by warfarin rather than aspirin. TREATING CEREBRAL EDEMA AND INTRACRANIAL HYPERTENSION

If cerebral edema develops, intravenous mannitol and hypertonic saline can be administered. Hypothermia therapy may be of benefit (Fig 2). No beneficial effects of steroids have been demonstrated in stroke. The use of intracranial pressure monitoring in patients with large arterial ischemic strokes who have significant cerebral edema is controversial.25 In patients with large strokes, decreasing level of consciousness, midline shift, and impending herniation on CT scan, decompressive craniectomy

4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™

Fig 2. (A) Head CT 6 hours after onset of right hemiplegia, gaze preference, and global aphasia in a 2-year-old, previously healthy girl. There is subtle effacement of sulci and loss of gray-white differentiation in the left middle cerebral arterial territory. (B) Repeat head CT obtained 36 hours later, after the appearance of anisocoria and decerebrate posturing. Extensive edema and hypodensity are seen in the territory of the left middle and anterior cerebral arteries, with left-to-right shift and uncal herniation. The child was intubated and ventilated, underwent decompressive craniectomy later that day, and was cooled to 34°C. She recovered consciousness within 72 hours, and 4 months later she demonstrated complete language recovery and ambulation with residual moderate hemiparesis.

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can be a life-saving procedure that may lead to improved functional outcome (Fig 2).26 SUPPORTIVE CARE

Patients should have good nutritional support, with enteral feeding started early. Attention should be paid to preventing infections, deep venous thrombosis, and skin ulcers. Rehabilitation services should be consulted early to involve them in mobilizing the patient, and psychosocial support should be given to the family. CONCLUSION

We stand at an exciting and rapidly advancing point in our understanding of pediatric ischemic

stroke. Current approaches are based on the known mechanisms of stroke, with selective extrapolation of evidence from adult and animal models of stroke, and are not evidence-based therapies, given the absence of pediatric stroke trials. Until such trials are completed, the individual management of the child with stroke requires a team approach incorporating aggressive initial neuroprotective strategies and preventing the early complications of acute stroke that increase mortality in adults. The strategies described in this article are best managed with critical care colleagues in close attendance and a team with expertise in managing pediatric stroke, to optimize the management and outcome of these children.

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relevance to secondary brain injury after head trauma in infants. Exp Toxicol Pathol 51:151-162, 1999 14. Lindsberg PJ, Roine RO: Hyperglycemia in acute stroke. Stroke 35:363-364, 2004 15. Chan AK, deVeber G: Prothrombotic disorders and ischemic stroke in children. Semin Pediatr Neurol 7:301-308, 2000 16. Alberico RA, Barnes P, Robertson RL, et al: Helical CT angiography: Dynamic cerebrovascular imaging in children. Am J Neuroradiol 20:328-334, 1999 17. Hacke W, Donnan G, Fieschi C, et al: Association of outcome with early stroke treatment: Pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 363:768-774, 2004 18. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333:1581-1587, 1995 19. Clark WM, Wissman S, Albers GW, et al: Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: A randomized controlled trial. JAMA 282:2019-2026, 1999 20. Gupta AA, Leaker M, Andrew M, et al: Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children. J Pediatr 139:682-688, 2001 21. Xavier AR, Siddiqui AM, Kirmani JF, et al: Clinical potential of intra-arterial thrombolytic therapy in patients with acute ischemic stroke. Drugs 17:213-224, 2003 22. Carlson MD, Leber S, Deveikis J, et al: Successful use of rt-PA in pediatric stroke. Neurology 57:157-158, 2001 23. Gruber A, Nasel C, Lang W, et al: Intra-arterial thrombolysis for the treatment of perioperative childhood cardioembolic stroke. Neurology 54:1684-1686, 2000 24. Kirton A, Wong JH, Mah J, et al: Successful endovascular therapy for acute basilar thrombosis in an adolescent. Pediatrics 112:e248-e251, 2003 25. Steiner T, Pilz J, Schellinger P, et al: Multimodal online monitoring in middle cerebral artery territory stroke. Stroke 32:2500-2506, 2001 26. Koh MS, Goh KY, Tung MY, et al: Is decompressive craniectomy for acute cerebral infarction of any benefit? Surg Neurol 53:225-230, 2000