Acute management of childhood stroke

Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13]. For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13].For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13].For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26]. AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13].For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes. Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13].For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28]. Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13]. For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13].For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13].For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26]. AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13].For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes. Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13].For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28]. Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13]. For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].Purpose of reviewThe purpose of this paper is to review recent updates in the acute management of childhood arterial ischemic stroke, including reperfusion therapies and neuroprotective measures.With the emergence of pediatric stroke centers in recent years, processes facilitating rapid diagnosis and treatment have resulted in improved implementation of early targeted neuroprotective measures as well as the increased use of reperfusion therapies in childhood arterial ischemic stroke. Retrospective data has demonstrated that alteplase is safe in carefully selected children with arterial ischemic stroke in the first 4.5 h from symptom onset, though data regarding its efficacy in children are still lacking. There is also increasing data that suggests that thrombectomy in children with large vessel occlusion improves functional outcomes. Recent adult studies, including the use of Tenecteplase as an alteplase alternative and expansion of late thrombectomy to include patients with large ischemic cores, also are reviewed along with limitations to application of the adult data to pediatric care.There have been significant advances in the hyperacute care of children with ischemic stroke and early diagnosis and targeted management are of the upmost importance in improving long-term outcomes.Papers of particular interest, published within the annual period of review, have been highlighted as:Arterial ischemic stroke (AIS) occurs is approximately 1 to 2 per 100 000 children and is a cause of significant morbidity and mortality [1-3]. More than 1300 children per year in the United States are hospitalized with acute AIS with AIS, with an average length of stay of 7 days [4]. Over the last decade, the early management of pediatric stroke has evolved with increasing use of hyperacute therapies. We review the current recommendations for acute management with a focus upon childhood arterial ischemic stroke (CAIS); neonatal AIS is not specifically addressed since neonatal stroke differs significantly from CAIS in regards to presentation, etiology and risk of recurrence with resulting differences in management. no caption availableEarly and accurate diagnoses are essential for optimal early management of CAIS. In part due to low prevalence of CAIS and frequent stroke mimics, stroke is less likely to be diagnosed in a timely fashion in children than in adults [5]. In 2009, a retrospective study reported that the average time from stroke presentation to diagnosis was 12.7 h [6]. The average time from symptom onset to presentation was under 2 h, suggesting the opportunity for early intervention existed but better mechanisms to identify these children were needed. A driving force in this systemic change was The Thrombolysis in Pediatric Stroke (TIPS) trial despite the fact that the study ended early due to low enrollment [7]. The TIPS protocol and the experience that the TIPS sites gained in preparing for administration of tPA spurred development of pediatric specific stroke pathways and dedicated 24/7 pediatric stroke teams [7,8]. In order to treat CAIS promptly and effectively, the American Heart Association pediatric stroke guidelines for recommends that institutions establish institutional pediatric hyperacute stroke pathways [9]. A recent survey of pediatric stroke specialists found that at least 41 pediatric centers in the United States and Canada now have acute stroke pathways [10]. A unique aspect of pediatric stroke pathways is the utilization of rapid magnetic brain resonance imaging (MRI) to confirm the presence of acute stroke [11,12,13].For children with suspected or confirmed AIS, implementation of neuroprotective measures is recommended to protect at-risk brain tissue, minimize stroke extension, and avoid secondary complications. Most children with acute AIS warrant Initial observation in an intensive care setting to optimize supportive measures and monitor for deterioration [9]. Recommendations for management are largely extrapolated from adult guidelines and general principals of neuroprotection given limited evidence about the impact of specific interventions upon long-term outcomes in CAIS [9,14].Patients with inability to protect their airway due to altered mental status or bulbar dysfunction may require airway support. Early airway control also should be considered if there is concern for significant cerebral edema and high risk for worsening with hypercarbia, particularly with large posterior circulation or complete middle cerebral artery territory strokes. In patients with flow limiting stenosis, such as moyamoya disease (MMD), hypocarbia (and associated risk of cerebral hypoperfusion) must be carefully avoided [15]. Adequate oxygenation should be maintained. Adult guidelines recommend supplemental oxygen be provided to maintain oxygen saturation of at least 94% [14]. However, oxygenation goals should be individualized in children with cyanotic heart disease with a more complex relationship between systemic and pulmonary blood flow ratio (Qp/Qs). For acute ischemia due to MMD, some experts recommend a trial of supplementation oxygen even in the absence of overt hypoxemia due to elevated brain oxygen extraction fraction in these children [16].Exact blood pressure goals are not well established for CAIS but there is likely a U-shaped relationship between blood pressure and outcomes, similar to what is seen in adults. Hypotension generally should be avoided especially since autoregulation may be impaired post stroke. In a retrospective study of 98 children with acute AIS, hypotension in the first 5 days postadmission was associated with poor neurological outcome [17]. Avoidance of hypotension is particularly important in children with preexisting flow-limiting vasculopathy, such as MMD [18]. Children with preexisting flow-limiting vasculopathy, such as MMD, are especially at risk for decreased cerebral blood flow with changes in blood pressure and may have baseline compensatory hypertension that is necessary to maintain adequate blood flow [19]. Fluid loading, pressors, and placement of the head of the bed flat may help maintain adequate blood pressure/cerebral blood flow in MMD [16,19-21]. Hypertension, on the other hand, has an unclear causative effect on stroke outcomes. While some studies have shown an increased risk of death when hypertension is present in the initial days after stroke, others have failed to redemonstrate this association [17,22,23]. Larger prospective studies in children are needed to better understand the relationship between blood pressure and outcome in CAIS. Currently, the AHA pediatric stroke guidelines do not provide specific blood pressure goals after acute stroke but many pediatric stroke experts recommend a minimum blood pressure goal of at least 50th to 95th percentile for age, though upper limits are variable and individualized particularly for children with arteriopathy. Noninvasive multimodal monitoring such as near infrared spectroscopy (NIRS) to calculate cerebral oximetry index, can also be used as adjuncts to determine personalized blood pressure goals [20,24]. Personalized hemodynamic goals also should be discussed with the multidisciplinary care team for children with complex congenital heart disease given the complicated interplay between Qp/Qs.In adults, hyperglycemia and fever are associated with worse outcome after stroke [25]. In a retrospective pediatric study of 98 cases of CAIS, glucose >= 200 mg/dL in the first 5 days post stroke was associated with poor outcome at 3 months after AIS; there was no relationship between fever and outcome [17]. Given the paucity of pediatric data, euglycemia and avoidance of fever, particularly in patients with cerebral edema are recommended based upon the adult studies [26].AHA guidelines for management of pediatric stroke did not recommend a specific hemoglobin goal after CAIS except for in patients in sickle cell disease (SCD). The consensus statement on red blood cell transfusion in critical ill children recommended a hemoglobin goal of 7-10 g/dl in the setting of acute brain injury, including stroke [27]. Further studies are needed to determine best practice but patients with elevated oxygen extraction fraction, such as those with moyamoya disease or sickle cell anemia, may benefit from transfusion goals at the higher end of this range [5,28].