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Guidelines for Urgent Management of Stroke in Children

  • Michael J. Rivkin
    Correspondence
    Communications should be addressed to: Dr. Rivkin; Department of Neurology; Boston Children's Hospital; Fegan 11; 300 Longwood Avenue; Boston, MA 02115.
    Affiliations
    Department of Neurology, Boston Children's Hospital, Boston, Massachusetts

    Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts

    Department of Radiology, Boston Children's Hospital, Boston, Massachusetts

    Department of Neurology, Harvard Medical School, Boston, Massachusetts
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  • Timothy J. Bernard
    Affiliations
    Department of Pediatrics, Hemophilia and Thrombosis Center, Aurora, Colorado

    Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado
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  • Michael M. Dowling
    Affiliations
    Division of Pediatric Neurology, University of Texas Southwestern Medical Center Dallas, Dallas, Texas

    Department of Pediatrics, University of Texas Southwestern Medical Center Dallas, Dallas, Texas

    Department of Neurology, University of Texas Southwestern Medical Center Dallas, Dallas, Texas
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  • Catherine Amlie-Lefond
    Affiliations
    Department of Neurology, Seattle Children's Hospital, Seattle, Washington

    Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington
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      Abstract

      Stroke in children carries lasting morbidity. Once recognized, it is important to evaluate and treat children with acute stroke efficiently and accurately. All children should receive neuroprotective measures. It is reasonable to consider treatment with advanced thrombolytic and endovascular agents. Delivery of such care requires purposeful institutional planning and organization in pediatric acute care centers. Primary stroke centers established for adults provide an example of the multidisciplinary approach that can be applied to the evaluation and treatment of children who present with acute stroke. The organizational infrastructure of these centers can be employed and adapted for treatment of children with acute stroke. It is likely that care for children with acute stroke can best be delivered by regional pediatric primary stroke centers dedicated to the care of children with pediatric stroke.

      Keywords

      Although both children and adults can experience strokes that affect very similar vascular territories in brain and share similar features on neuroimaging, the course of clinical management of the patient in each age group can vary considerably. An adult who suddenly develops typical symptoms of a stroke such as hemiparesis, aphasia, ataxia, or hemianopsia comes to medical attention quickly, often is assessed in the field and in hospital by teams with special training in the evaluation and care of adults with stroke, and is treated in a medical center designated as a primary stroke center. Children with stroke, in contradistinction to adults, encounter delay in their delivery to medical attention. Once in a medical setting, the acute neurological deficit often is not recognized, and stroke as etiology of presenting signs and symptoms is often not considered. Consequently, children who have stroke encounter considerable delay before acquisition of diagnostic imaging. Examination of the diagnostic process for children in the emergency department and on the inpatient service who have had stroke revealed considerable diagnostic delay due to failure to include stroke in the differential diagnosis.
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      Delay to diagnosis in acute pediatric arterial ischemic stroke.
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      Time lag to diagnosis of stroke in children.
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      • Phan T.G.
      • et al.
      Delayed recognition of initial stroke in children: need for increased awareness.
      We will examine the development of adult primary acute stroke centers. Next, features that compel the development of multidisciplinary acute stroke programs for children will be presented. Subsequently, a method for construction of a pediatric stroke center and components of care for children with acute arterial stroke will be considered. Finally, these features will be illustrated through presentation of an actual patient with acute arterial stroke who was treated successfully with tissue plasminogen activator (tPA).
      The first decade of the twenty-first century brought transformation in acute stroke care for adults, and more than half of all adults access to care at a primary stroke center.
      • Song S.
      • Saver J.
      Growth of regional acute stroke systems of care in the United States in the first decade of the 21st century.
      Indeed, an adult with acute stroke may be evaluated and treated in the field by an emergency medical team especially trained in the care of patients with acute stroke. Communication between the field team and the hospital-based primary stroke center medical team will facilitate the arrangement of emergency room, neuroradiological, pharmacologic, or interventional services even before the patient arrives to the hospital (analogous to primary coronary intervention in acute myocardial infarction).
      Children with acute stroke should be diagnosed within 4.5 hours following symptom onset so that thrombolytic treatment
      • Demaerschalk B.M.
      • Silver B.
      • Wong E.
      • Merino J.G.
      • Tamayo A.
      • Hachinski V.
      ASPECT scoring to estimate >1/3 middle cerebral artery territory infarction.
      Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group.
      or thrombectomy might be administered.
      • Rivkin M.J.
      • deVeber G.
      • Ichord R.N.
      • et al.
      Thrombolysis in pediatric stroke study.
      Administration of tPA facilitates degradation of fibrin in thrombus and can lead to early recanalization of an artery occluded by thrombus. Although the use of tPA treatment for adults with acute stroke is established, experience with its use in children remains limited. Questions remain regarding its use in patients younger than two years, at times greater than 4.5 hours from stroke onset, and in those at either extreme of clinical severity.
      Studies in adults have revealed that despite an increased risk of fatal intracranial hemorrhage during the first few days after treatment, tPA significantly improves the likelihood of a favorable outcome when administered within 4.5 hours of stroke onset in appropriately selected patients. Moreover, it appears that earlier treatment correlates with better outcome.
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      • et al.
      Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.
      Potential adverse effects of tPA include idiosyncratic nausea, vomiting, bradycardia, fever, allergic response, cardiac arrhythmia, and hypotension (in up to 10%).
      • Saver J.L.
      • Goyal M.
      • Bonafe A.
      • et al.
      Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.
      Life-threatening nonidiosyncratic side effects consist of hemorrhage in gastrointestinal (5% of patients), genitourinary (4%), or central nervous system (6.4%). Symptomatic intracranial hemorrhage, in particular, remains a concern following administration of tPA in patients. The Alberta Stroke Program Early CT Scoring (ASPECTS) scheme has proved accurate and useful in identifying stroke size in the middle cerebral artery (MCA) territory on head computed tomography (CT) and in the estimation of the likelihood of occurrence of symptomatic intracranial hemorrhage following treatment with tPA.
      • Demaerschalk B.M.
      • Silver B.
      • Wong E.
      • Merino J.G.
      • Tamayo A.
      • Hachinski V.
      ASPECT scoring to estimate >1/3 middle cerebral artery territory infarction.
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      • Coutts S.B.
      • et al.
      Extent of early ischemic changes on computed tomography (CT) before thrombolysis: prognostic value of the Alberta Stroke Program Early CT Score in ECASS II.
      Magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) specifically are even more sensitive than CT in the detection of acute stroke.
      • Lansberg M.G.
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      • Beaulieu C.
      • Marks M.P.
      Comparison of diffusion-weighted MRI and CT in acute stroke.
      However, as found with head CT, the size of DWI abnormality was found to correlate directly with the likelihood of symptomatic intracranial hemorrhage following tPA therapy.
      • Lansberg M.G.
      • Thijs V.N.
      • Bammer R.
      • et al.
      Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke.
      Recent developments in endovascular therapy of adults with stroke have reverberated across the field of pediatric stroke. The Multicenter Randomized CLinical trial of Endovascular treatment for Acute stroke in the Netherlands (MR CLEAN) multicenter study of endovascular therapy administered to adults with proximal large cerebral artery occlusion many of whom had already been treated with intravenous tPA demonstrated not only more rapid arterial recanalization but also superior outcome compared with standard medical therapy.
      • Berkhemer O.A.
      • Fransen P.S.
      • Beumer D.
      • et al.
      A randomized trial of intraarterial treatment for acute ischemic stroke.
      These results were confirmed in both Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) as well as Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) studies.
      • Saver J.L.
      • Goyal M.
      • Bonafe A.
      • et al.
      Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.
      • Goyal M.
      • Demchuk A.M.
      • Menon B.K.
      • et al.
      Randomized assessment of rapid endovascular treatment of ischemic stroke.
      The exciting results from these studies have revealed endovascular therapy and thrombectomy to be first-line treatments for acute stroke in adults with large cerebral vessel occlusion. Although exciting for adults with stroke, the role of this therapeutic procedure in children with acute stroke is not yet clear.
      In adults, the benefit of treatment by a medical team organized and trained in the care of patients with acute stroke extends beyond the use of intravenous tPA or endovascular therapy. Patients treated in primary stroke centers follow an improved clinical course compared with those treated by clinicians not organized into stroke teams. Lower mortality rate, readmission rate, and complication rate and shorter length of in-patient stays have been observed in patients treated at adult primary stroke centers.
      • Lichtman J.H.
      • Allen N.B.
      • Wang Y.
      • Watanabe E.
      • Jones S.B.
      • Goldstein L.B.
      Stroke patient outcomes in US hospitals before the start of the Joint Commission Primary Stroke Center certification program.
      • Ayis S.A.
      • Coker B.
      • Bhalia A.
      • et al.
      Variations in acute stroke care and the impact of organised care on survival from a European perspective: the European Registers of Stroke (EROS) investigators.
      • Langhonre P.
      Organized inpatient (stroke unit) care for stroke.
      These features argue strongly for a similar approach to care of children with acute stroke.

      Reason to emulate the adult experience of acute stroke care in children

      Stroke, although regarded by many to be rare in children, is not. Both prevention of mortality and attenuation of morbidity constitute potent reasons to optimize the ability to recognize and to treat rapidly children with stroke. Cerebrovascular disease represents one of the ten most common causes of mortality in patients ranging in age from five through 24 years.
      • Heron M.
      Deaths: leading causes for 2010.
      Although stroke occurs with a frequency 175 to 200/100,000 among adults, stroke occurs in children older than one month as frequently as 13/100,000 per year.
      • Giroud M.
      • Lemesle M.
      • Madinier G.
      • Manceau E.
      • Osseby G.V.
      • Dumas R.
      Stroke in children under 16 years of age. Clinical and etiological difference with adults.
      The stroke incidence is higher in neonates (25 to 40/100,000 births) and is highest among premature infants (up to 100/100,000 births).
      The morbidity in children following arterial stroke is considerable. As many as 50% of neonates and 65% of children older than 1 month sustain lasting motor deficits as a consequence of stroke. Furthermore, up to 60% of children who have had neonatal stroke demonstrate cognitive deficits, especially those of executive function and language. Similarly, half of children who have stroke at greater than age one month have been found to have cognitive deficits.
      • Ganesan V.
      • Hogan A.
      • Shack N.
      • Gordon A.
      • Isaacs E.
      • Kirkham F.J.
      Outcome after ischaemic stroke in childhood.
      • deVeber G.A.
      • MacGregor D.
      • Curtis R.
      • Mayank S.
      Neurologic outcome in survivors of childhood arterial ischemic stroke and sinovenous thrombosis.
      • Kolk A.
      • Ennok M.
      • Laugesaar R.
      • Kaldoja M.L.
      • Talvik T.
      Long-term cognitive outcomes after pediatric stroke.
      • Westmacott R.
      • Askalan R.
      • MacGregor D.
      • Anderson P.
      • deVeber G.
      Late emergence of cognitive deficits after unilateral neonatal stroke.
      • Ricci D.
      • Mercuri E.
      • Barnett A.
      • et al.
      Cognitive outcome at early school age in term-born children with perinatally acquired middle cerebral artery territory infarction.
      The mortality rate for children with stroke is one third that found in adults with either ischemic or hemorrhagic stroke. Consequently, a much higher proportion of children than adults carry the consequences of their cerebral injury for decades.
      • Grysiewicz R.A.
      • Thomas K.
      • Pandey D.K.
      Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors.
      • Statler K.D.
      • Dong L.
      • Nielsen D.M.
      • Bratton S.L.
      Pediatric stroke: clinical characteristics, acute care utilization patterns, and mortality.
      • Gardner M.A.
      • Hills N.K.
      • Sidney S.
      • Johnston S.C.
      • Fullerton H.J.
      The 5-year direct medical cost of neonatal and childhood stroke in a population-based cohort.
      • Lo W.
      • Zamel K.
      • Ponnappa K.
      • et al.
      The cost of pediatric stroke care and rehabilitation.
      The cost for care of children who have had a stroke at either in the neonatal or at an older age appears to be both high and sustained.
      • Gardner M.A.
      • Hills N.K.
      • Sidney S.
      • Johnston S.C.
      • Fullerton H.J.
      The 5-year direct medical cost of neonatal and childhood stroke in a population-based cohort.
      Consequently, the aggregate cost for care of a patient with stroke is likely greater for a child than for an adult.
      • Perkins E.
      • Stephens J.
      • Xiang H.
      • Lo W.
      The cost of pediatric stroke acute care in the United States.

      Organization for a primary pediatric stroke center: Just little adult centers?

      The morbidity and mortality associated with cerebrovascular disease argues convincingly for mobilization of resources to evaluate and treat children with stroke as early as possible. The establishment of primary stroke centers across the United States has resulted in multidisciplinary teams and facilities trained in and adept at providing hyperacute care for adults with stroke that includes intravenous thrombolytic and endovascular thrombectomy for patients with acute stroke.
      • Saver J.L.
      • Goyal M.
      • Bonafe A.
      • et al.
      Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.
      • Alberts M.J.
      • Latchaw R.E.
      • Jagoda A.
      • et al.
      Revised and updated recommendations for the establishment of primary stroke centers: a summary statement from the brain attack coalition.
      Recently, pediatric centers participating in the landmark Thrombolysis in Pediatric Stroke (TIPS) study organized systematically to gain competence in the response to and assessment of children presenting with acute stroke for treatment with tPA.
      • Rivkin M.J.
      • deVeber G.
      • Ichord R.N.
      • et al.
      Thrombolysis in pediatric stroke study.
      • Amlie-Lefond C.
      • Chan A.K.
      • Kirton A.
      • et al.
      Thrombolysis in Acute Childhood Stroke: Design and Challenges of the Thrombolysis in Pediatric Stroke Clinical Trial.
      • Bernard T.J.
      • Rivkin M.J.
      • Scholz K.
      • et al.
      Emergence of the primary pediatric stroke center: impact of the Thrombolysis in Pediatric Stroke trial.
      As a group and in the course of preparation for study participation the 23 centers developed pediatric stroke teams able to respond immediately to patients around the clock, built pediatric stroke emergency department and intensive care unit (ICU) ordersets, and arranged for both acute pediatric stroke MRI evaluation as well as anesthesiologist support for imaging at any time of day or night.
      • Bernard T.J.
      • Rivkin M.J.
      • Scholz K.
      • et al.
      Emergence of the primary pediatric stroke center: impact of the Thrombolysis in Pediatric Stroke trial.
      Remarkably, in the process of preparation for urgent evaluation and treatment of children with acute arterial ischemic stroke, these centers fulfilled most criteria that adult centers meet to attain designation as a primary stroke center for treatment of adults with stroke.
      • Bernard T.J.
      • Rivkin M.J.
      • Scholz K.
      • et al.
      Emergence of the primary pediatric stroke center: impact of the Thrombolysis in Pediatric Stroke trial.
      In so doing, these pediatric centers have moved the field forward to define the safety guidelines for use of tPA as therapy for children who present with acute arterial stroke.
      • Rivkin M.J.
      • deVeber G.
      • Ichord R.N.
      • et al.
      Thrombolysis in pediatric stroke study.
      Currently, the total dose of tPA considered appropriate for administration to children who present within 4.5 hours of stroke onset and who qualify for treatment is the same as the dose used in adults, 0.9 mg/kg, with the first 10% given as a bolus. The developmental trajectory of the fibrinolytic system during childhood is well documented and raises the possibility that the most effective dose of tPA for children may be higher than 0.9 mg/kg.
      • Parmar N.
      • Albisetti M.
      • Berry L.R.
      • Chan A.K.
      The fibrinolytic system in newborns and children.
      Stroke team organization and patient screening constitute important initial steps in an algorithm for assessment of children with acute stroke. By definition, the pediatric acute stroke team is a multidisciplinary group that can respond quickly and work well together. Close cooperation with the ICU team is important because patients who receive thrombolytic or endovascular treatment will be transferred to the ICU immediately following therapy. Consequently, planning, preparation, and practice using mock code routines are all essential for successful deployment of the team when a patient actually presents. The acute stroke team at Boston Children's Hospital comprises the cerebrovascular disorders and stroke neurology attending physician, cerebrovascular disorders and stroke fellow, neurology on-call resident, neuroradiologist, medical-surgical ICU fellow, central pharmacist, and on-call anesthesiologist (Fig 1). The team is activated by pager through a hospital central communication center and is available around the clock. Team members converge to assess the patient rapidly at the point of care. Most patients are located in the emergency department at the time of presentation. However, children with symptoms of acute stroke can present in the pediatric ICU, surgical recovery room, or in-patient hospital ward. Children two years or older who present with sudden symptom onset of unilateral weakness or sensory deficit, acute vision loss or diplopia, sudden onset aphasia, or difficulty walking and who have been symptomatic for less than five hours are considered ideal candidates for screening by the team for thrombolytic treatment. In addition, because seizure constitutes a very common presenting sign of acute stroke in children, any child with first-time seizure and focal findings on neurological examination is also urgently evaluated for acute stroke.
      • Abend N.S.
      • Beslow L.A.
      • Smith S.E.
      • et al.
      Seizures as a presenting symptom of acute arterial ischemic stroke in childhood.
      Each patient is examined quickly for assignment of a pediatric National Institutes of Health Stroke Scale (NIHSS) score and conveyed to the MRI suite for evaluation by a hyperacute stroke evaluation, which consists of axial DWI, fluid-attenuated inversion recovery, susceptibility-weighted imaging, and time-of-flight magnetic resonance angiography of head and neck acquisitions. Imaging is read immediately and shared with the clinical team responsible for the patient. If MRI is not immediately available, cranial computed tomography with CT angiography can be substituted. In either instance, the absence of intracranial hemorrhage and other excluding features, evidence of early ischemic brain injury, and presence of arterial obstruction in a vessel subserving the region of parenchymal ischemia have been prerequisites for use of tPA (Fig 2).
      • Rivkin M.J.
      • deVeber G.
      • Ichord R.N.
      • et al.
      Thrombolysis in pediatric stroke study.
      Figure thumbnail gr1
      Figure 1First steps of algorithm for assessment and care of children who present to Boston Children's Hospital (BCH) with signs and symptoms of acute arterial ischemic stroke. AED, antiepileptic drug; BP, blood pressure; CBC, complete blood count; ED, emergency department; HTN, hypertension; ICU, intensive care unit; INR, international normalized ratio; IV, intravenous; MRI, magnetic resonance imaging; MSICU, medical-surgical ICU; NIHSS, National Institutes of Health Stroke Scale; NPO, nothing by mouth; PLT, platelet; PTT, partial thromboplastin time; tPA, tissue plasminogen activator. (The color version of this figure is available in the online edition.)
      Figure thumbnail gr2
      Figure 2Boston Children's Hospital algorithm for evaluation and care of children who present with signs and symptoms of acute arterial ischemic stroke: magnetic resonance imaging (MRI) acquisition and steps for determination of eligibility for treatment with tissue plasminogen activator (tPA). ASPECTS, Alberta Stroke Program Early CT Scoring; AVM, arteriovenous malformation; COW, Circle of Willis; CHAMPS, Children's Hospital Applications Maximizing Patient Safety; CT, computed tomography; DWI, diffusion-weighted imaging; ED, emergency department; FLAIR, fluid-attenuated inversion recovery; GI, gastrointestinal; GU, genitourinary; IA, intra-arterial; ICU, intensive care unit; INR, international normalized ratio; IV, intravenous; MCA, middle cerebral artery; MI, myocardial infarction; MRA, magnetic resonance angiography; MSICU, medical-surgical ICU; PedNIHSS, pediatric National Institutes of Health Stroke Scale; PT, prothrombin time; PTT, partial thromboplastin time; SAH, subarachnoid hemorrhage; SBE, subacute bacterial endocarditis; SWI, susceptibility-weighted imaging; TOF, time-of-flight. (The color version of this figure is available in the online edition.)
      As discussed earlier, several trials of endovascular treatment and thrombectomy have established efficacy of this therapy in adults presenting with acute stroke due to occlusion of large cerebral arteries. These developments have generated considerable interest in the field of pediatric stroke regarding use of this treatment in children. The role of this therapeutic procedure in children with acute stroke is not yet clear. However, given the establishment of pediatric acute stroke centers through TIPS, it is anticipated that this question will be addressed soon.
      Several neuroprotective measures can be taken irrespective of whether a pediatric patient qualifies for thrombolytic treatment with tPA. Maintenance of normoglycemia has been identified as a therapeutic objective in the care of patients with acute stroke. Study of both animal models and humans has demonstrated that hyperglycemia is detrimental following brain ischemia affecting vasoregulatory, thrombotic, and inflammatory pathways.
      • Martini S.R.
      • Kent T.A.
      Hyperglycemia in acute ischemic stroke: a vascular perspective.
      Hyperthermia following stroke correlates with the presence of an elevated white blood cell count, antibiotic use, and high NIHSS score and has been associated with worsened outcome in patients with stroke.
      • Saini M.
      • Saqqur M.
      • Kamrussaman A.
      • Lees K.R.
      • Shuaib A.
      Effect of hyperthermia on prognosis after acute ischemic stroke.
      Blood pressure targets during treatment for acute arterial ischemic stroke have received considerable attention in adults. Initially, studies suggested that elevations of systolic, diastolic, and mean arterial pressure in acute stroke correlated with either mortality or increased morbidity.
      • Leonardi-Bee J.
      • Bath P.M.
      • Phillips S.J.
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      Blood pressure and clinical outcomes in the International Stroke Trial.
      • Willmot M.
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      • Bath P.M.
      High blood pressure in acute stroke and subsequent outcome: a systematic review.
      Subsequent, placebo-controlled study demonstrated no difference in outcome between patients treated with placebo or antihypertensive medicine after acute stroke. Moreover, high blood pressure often normalized within 24 hours in most cases.
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      • Zhang Y.
      • Xu T.
      • et al.
      Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial.
      • Potter J.F.
      • Robihson T.G.
      • Ford G.A.
      • et al.
      Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial.
      • Robinson T.G.
      • Potter J.F.
      • Ford G.A.
      • et al.
      Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial.
      • Jauch E.C.
      • Saver J.L.
      • Adams Jr., H.P.
      • et al.
      Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.
      Blood pressure management during treatment for acute stroke has received scant attention in children. Brush
      • Brush L.N.
      • Monagle P.T.
      • Mackay M.T.
      • Gordon A.L.
      Hypertension at time of diagnosis and long-term outcome after childhood ischemic stroke.
      conducted a retrospective review of blood pressure after acute stroke in children and found that hypertension occurred on at least one occasion in over 60%. Although 12-month and in-hospital mortality were higher among children who had hypertension following acute stroke, there was no relationship found between hypertension and vascular territory, etiology, or neurological disability.
      • Brush L.N.
      • Monagle P.T.
      • Mackay M.T.
      • Gordon A.L.
      Hypertension at time of diagnosis and long-term outcome after childhood ischemic stroke.
      Adil and colleagues
      • Adil M.M.
      • Beslow L.A.
      • Qureshi A.I.
      • Malik A.A.
      • Jordan L.C.
      Hypertension is associated with increased mortality in children hospitalized with arterial ischemic stroke.
      demonstrated that systemic hypertension in children with ischemic stroke was associated with increased length of hospitalization and increased mortality. Currently, the best approach to blood pressure management in children with acute stroke has yet to be defined. At our center, blood pressure is treated when it exceeds 15% above the 95th percentile for sex, age, and height for greater than an hour or anytime the blood pressure exceeds 20% above the 95th percentile (Fig 3, example from Boston Children's Hospital).
      Figure thumbnail gr3
      Figure 3Boston Children's Hospital algorithm for evaluation and care of children who present with signs and symptoms of acute arterial ischemic stroke: intravenous (IV) tissue plasminogen activator (tPA) treatment and blood pressure (BP) management. CT, computed tomography; CTA, CT angiography; ED, emergency department; MR, magnetic resonance; MSICU, medical-surgical intensive care unit. (The color version of this figure is available in the online edition.)
      As mentioned earlier, seizure can be a presenting sign of acute stroke in a child and is associated with increased risk of subsequent epilepsy.
      • Abend N.S.
      • Beslow L.A.
      • Smith S.E.
      • et al.
      Seizures as a presenting symptom of acute arterial ischemic stroke in childhood.
      • Fox C.K.
      • Glass H.C.
      • Sidney S.
      • Lowenstein D.H.
      • Fullerton H.J.
      Acute seizures predict epilepsy after childhood stroke.
      Seizure should be treated with anticonvulsant therapy. Repeated seizure and status epilepticus should be aggressively treated and effectively suppressed. Continuous electroencephalography monitoring should be considered to evaluate for subclinical seizure.
      • Abend N.S.
      • Beslow L.A.
      • Smith S.E.
      • et al.
      Seizures as a presenting symptom of acute arterial ischemic stroke in childhood.
      Finally, decompressive hemicraniectomy (DCH) can be performed to afford relief from increased intracranial pressure in patients with acute stroke accompanied by an extreme amount of cerebral edema. This surgical procedure can mitigate fatal herniation syndromes and diminish additional pressure-related ischemic injury found in malignant MCA syndromes. The malignant MCA syndrome as defined in adults with acute stroke is defined as involvement of >50% of the MCA territory by cranial CT or >145 mL of MCA volume on DWI by acute infarction accompanied clinically by a depressed level of consciousness. In this circumstance a DCH can be both life-saving and associated with a good outcome. Notably, among adults DCH has been associated with better outcomes especially when performed in younger patients and earlier in the course of acute stroke.
      • Vahedi K.
      • Hofmeijer J.
      • Juettler E.
      • et al.
      Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials.
      • Vahedi K.
      • Viacut E.
      • Mateo J.
      • et al.
      Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial).
      • Hofmeijer J.
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      • Algra A.
      • et al.
      Hemicraniectomy After Middle Cerebral Artery Infarction with Life-Threatening Edema Trial (HAMLET). Protocol for a randomised controlled trial of decompressive surgery in space-occupying hemispheric infarction.
      • Schwab S.
      • Steiner T.
      • Aschoff A.
      • et al.
      Early hemicraniectomy in patients with complete middle cerebral artery infarction.
      Among children with acute stroke, 26 patients treated with DCH as part of their treatment for stroke have been reported in the literature. Strokes involved right or left MCA territories. The time to DCH from presentation with symptoms ranged widely, from two to 291 hours. Although quantitative measures of neurological outcome were not provided, neurological deficits were generally described as mild to moderate.
      • Shah S.
      • Murthy S.B.
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      • Jea A.
      • Nassif L.M.
      Decompressive hemicraniectomy in pediatric patients with malignant middle cerebral artery infarction: case series and review of the literature.
      • Omay S.B.
      • Carrion-Grant G.M.
      • Kuzmik G.A.
      • et al.
      Decompressive hemicraniectomy for ischemic stroke in the pediatric population.
      At our centers, DCH has been employed effectively in children who present with large MCA territory stroke and who demonstrate declining mental status as well as cerebral edema early in their clinical course (Fig 4, example of patient treated with DCH at Boston Children's Hospital).
      Figure thumbnail gr4
      Figure 4Example of decompressive hemicraniectomy in pediatric stroke. A 17-year-old male presented with sudden onset of left hemiparesis and hemianopia. Magnetic resonance imaging showed diffusion-weighted signal abnormality to indicate ischemic injury involving much greater than 33% of the middle cerebral artery territory on the right (A, B, arrows). Large size of infarct in the middle cerebral artery territory, declining mental state, and evidence of early cerebral edema led to diagnosis of acute right middle cerebral artery stroke with malignant middle cerebral artery syndrome. Decompressive hemicraniectomy was performed, which accommodated the right hemispheric cerebral edema and expansion. Note extent of decompressive hemicraniectomy (C, D); see arrowheads and its accommodation of increasingly edematous right hemisphere. ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; T2W, T2 weighted. (The color version of this figure is available in the online edition.)

      An illustrative patient for treatment of acute arterial stroke

      A 16-year-old male developed halting speech and right-sided weakness while at home with his family making dinner. He was immediately brought to the Boston Children's Hospital Emergency Department at which he arrived 45 minutes after symptom onset. In the Emergency Department a right hemiparesis and expressive aphasia were documented on examination and a Stroke Stat was called. Assessment by the Stroke Stat Team produced a pediatric NIHSS score of 7. He was taken for MRI that began 1.5 hours after onset of symptoms. The MRI revealed an area of restricted diffusion in the left postcentral gyrus consistent with an acute infarct (see Fig 5). Arterial spin label perfusion-weighted imaging demonstrated hypoperfusion corresponding to the area of restricted diffusion and extending beyond it (Fig 5). The magnetic resonance arteriography revealed abrupt focal change in the caliber of an M2 branch of the left MCA within the Sylvian fissure that corresponded to a small focus of susceptibility on susceptibility-weighted imaging
      • Omay S.B.
      • Carrion-Grant G.M.
      • Kuzmik G.A.
      • et al.
      Decompressive hemicraniectomy for ischemic stroke in the pediatric population.
      (Fig 5). Other intracranial and extracranial arteries demonstrated normal flow signal. The patient met all standard adult inclusion and exclusion criteria for intravenous tPA therapy, including blood pressure parameters, laboratory studies, and lack of intracranial hemorrhage on head imaging. Intravenous tPA was infused 3.5 hours after onset of symptoms using a dose of 0.9 mg/kg, with 10% of the total dose given over 5 minutes and the remaining 90% given over one hour. During the infusion the patient's pediatric NIHSS score improved from 7 to 3. Follow-up MRI imaging obtained 24 hours later revealed no evidence of intracranial hemorrhage and resolution of hypoperfusion signal on arterial spin label perfusion-weighted imaging (Fig 5). The patient continued to improve and was discharged two days later with a pediatric NIHSS score of 1.
      Figure thumbnail gr5
      Figure 5Magnetic resonance imaging of a male who presented with aphasia and right-sided weakness. (A, B) Consecutive fluid-attenuated inversion recovery (FLAIR) (left) and diffusion-weighted imaging (DWI)-trace (right) images showing diffusion restriction (see arrows) with no clear increased signal in FLAIR images in left postcentral gyrus indicative of early stroke. Arterial spin label perfusion-weighted imaging (ASL PWI) (C) shows region of asymmetrically darker signal in the left hemisphere including and extending beyond the postcentral gyrus indicating regional hypoperfusion (arrows). (E) Magnetic resonance arteriography (MRA) shows flow signal loss in arterial branch from M2 portion of the middle cerebral artery on left (arrow). (F) Susceptibility-weighted image (SWI) showing small round area of susceptibility signal in region corresponding to flow signal loss in MRA (E, see arrow) indicating middle cerebral artery M2 branch occlusion by thrombus. (D) ASL PWI following treatment with intravenous tissue plasminogen activator that shows resolution of hypoperfusion seen in ASL PWI (C) before treatment with intravenous tissue plasminogen activator.

      Conclusion

      Stroke in children carries lasting and often life-long morbidity. Although the possibility of acute stroke can be overlooked, if recognized it is reasonable to consider treatment with advanced thrombolytic and endovascular agents. All children should receive neuroprotective measures. Such care requires purposeful institutional planning and organization in pediatric acute care centers. Primary stroke centers established for adults provide an example of the multidisciplinary approach that can be applied to the evaluation and treatment of patients who present with acute stroke. The organizational infrastructure of these centers can be employed and adapted for treatment of children with acute stroke. It is likely that care for children beset by acute stroke can best be delivered by regional pediatric primary stroke centers dedicated to the care of children with pediatric stroke.

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