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In-Hospital Pediatric Stroke Alert Activation
Pediatric Neurology 88 (2018) 31 35
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
In-Hospital Pediatric Stroke Alert Activation Megan Barry, DO a,b, Truc M. Le, MD c, Melissa C. Gindville, MS a, Lori C. Jordan, MD, PhD a* a
Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, Tennessee Department of Pediatrics, Division of Pediatric Neurology, University of Colorado Medical Center, Aurora, Colorado c Department of Pediatrics, Division of Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee b
ARTICLE INFO
ABSTRACT
Article history: Received 9 May 2018 Received in revised form 31 July 2018 Accepted 4 August 2018
BACKGROUND: Pediatric stroke alerts or “code strokes” allow for rapid evaluation, imaging,
Keywords: Stroke Children Ischemic Hemorrhagic
and treatment of children presenting with stroke-like symptoms. In a previous study of emergency department-initiated pediatric stroke alerts, 24% of children had confirmed strokes. The purpose of this study was to characterize in-hospital pediatric stroke alerts. METHODS: Demographic and clinical information was obtained from a quality improvement database and medical records for children (zero to 20 years) at a single institution for whom a stroke alert was activated after hospital admission between April 2011 and December 2016. Stroke alert activation criteria included a new focal neurological defect occurring within 48 hours. A neurologist evaluated the patient within 15 minutes and rapid magnetic resonance imaging was available. RESULTS: Medical personnel activated in-hospital stroke alerts for 56 children (median age 6.5 years, interquartile range 1 to 13, 52% male). Stroke was the final diagnosis of 25 (45%), 72% ischemic, and 28% hemorrhagic strokes. Other diagnoses included neurological urgencies: seizure (21%), posterior reversible encephalopathy syndrome (7%), transient ischemic attack (5%), and acute disseminated encephalomyelitis (4%). Of the stroke diagnoses, 68% were stroke alerts called in the pediatric intensive care unit or pediatric cardiac intensive care unit. Rapid neuroimaging was completed in 91%; magnetic resonance imaging brain was the first image in 55%. CONCLUSIONS: Of in-hospital pediatric stroke alerts, 45% were stroke while 38% were other neurological conditions requiring urgent evaluation. In-hospital stroke alerts were commonly activated for children with complicated medical histories. Rapid neurological evaluation facilitated care. No child underwent thrombolysis or thrombectomy. © 2018 Elsevier Inc. All rights reserved.
Introduction
In the last decade, preparedness for pediatric acute stroke care at children's hospitals has increased. In Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declarations of Interest: None
* Communications should be addressed to: Lori C. Jordan MD, PhD, Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN 37232-9559. E-mail address: [email protected] https://doi.org/10.1016/j.pediatrneurol.2018.08.003 0887-8994/© 2018 Elsevier Inc. All rights reserved.
conjunction with the first pediatric acute stroke treatment study, the Thrombolysis in Pediatric Stroke trial,1 pediatric stroke centers developed new methods for identifying and treating children with stroke that included the development of stroke teams, creation of institutional pathways, and availability of 24/7 magnetic resonance imaging (MRI). As a result, these centers reported a significant increase in self-assessed preparedness for pediatric stroke cases.2 Despite advances in stroke alert systems, the ability of in-hospital stroke alerts to rapidly and effectively identify children with stroke has never been reported. Known
32
M. Barry et al. / Pediatric Neurology 88 (2018) 31 35
pediatric stroke risk factors including congenital heart disease, sickle cell disease, infections, and other prothrombotic conditions are common reasons children are admitted to the hospital.3 Early recognition and evaluation of acute stroke symptoms has the potential to identify children as candidates for intravenous tissue plasminogen activator (tPA) and thrombectomy, especially with adult stroke treatment windows rapidly expanding.4 We aimed to evaluate the characteristics, final diagnosis, and outcomes of children whose admission involved an in-hospital stroke alert. Methods Our freestanding children's hospital serves a referral area of approximately 2,000,000 people, has about 15,000 annual inpatient visits with a 24-bed medical/surgical pediatric intensive care unit, and has an 18-bed pediatric cardiovascular intensive care unit. Pediatric stroke alerts are paged through a central paging system and logged prospectively in a quality improvement database. Urgent stroke protocol MRIs and head computed tomography (CT) as well as brain MRIs with indication for examination noted as concern for stroke are logged in an imaging quality improvement database. Clinical and demographic information was obtained from medical records for patients, aged 29 days to 20 years, with a pediatric acute stroke alert activated after hospital admission from April, 2011 to December, 2016. A stroke alert is activated if a child develops a focal neurological deficit concerning for transient ischemic attack (TIA) or acute stroke with symptom duration less than 48 hours. A stroke alert is not activated for neonatal/perinatal strokes. A neurology resident sees all stroke alert patients within 15 minutes; MRI is acutely made available. Neurologists work with the primary team to evaluate the child and select the best imaging option with the goal of offering an acute stroke treatment if indicated and appropriate supportive care. The institutional review board approved this study; consent was waived. Descriptive statistics were utilized for data analysis.
TABLE 1. Study Population Characteristics of Children With a Final Diagnosis of Stroke (n = 25) and No Stroke (n = 31) Stroke Age, y, median (IQR) Sex Male Race White, Non-Hispanic/Latino White, Hispanic/Latino Black Other Comorbid condition* Cardiac Congenital heart disease Other/Acquired Hematologic/Oncologic Sickle cell disease Cancer Other Immunologic/Rheumatologic Infectious Chronic/Systemic disease Genetic Trisomy 21 Neurological Seizure Prior stroke/TIA Other Vascular Reason for admission Worsening of previously known medical condition Postoperative Medical treatment for known medical condition Infection Trauma Other
3 (1-10) n (%)
No Stroke 9 (5-14) n (%)
13 (52)
16 (52)
17 3 5 0 21 16 13 3 8 1 3 4 0 0 5 4 3 6 1 5 1 1
15 2 13 1 27 7 5 2 16 6 8 2 1 2 10 2 1 13 5 4 5 2
(68) (12) (20) (0) (84) (64) (52) (12) (32) (4) (12) (16) (0) (0) (20) (16) (12) (24) (4) (20) (4) (4)
(48) (6) (42) (3) (87) (23) (16) (6) (52) (19) (26) (6) (3) (6) (32) (6) (1) (42) (16) (13) (16) (6)
6 (24)
7 (22)
7 (28) 2 (8)
4 (13) 5 (16)
5 (20) 2 (8) 6 (24)
13 (42) 0 (0) 4 (13)
IQR, interquartile range; TIA, transient ischemic attack; y, years. *Some children had more than one area of past medical history; percentages do not add up to 100%.
Results
A total of 56 pediatric stroke alerts were activated with a median age 6.5 years (interquartile range [IQR] 113), 52% male. The majority of children (85.7%) had at least one comorbid condition; over 50% had multiple categories, Table 1. Stroke, either ischemic or hemorrhagic, was the final diagnosis for 25 (45%) of the in-hospital stroke alerts (Fig 1). Ischemic stroke etiologies for 18 children included: seven that were cardioembolic, six that were periprocedural between zero and 12 days after a cardiac surgery, one that was idiopathic and four ischemic strokes from other causes including vessel compression from brain tumor, moyamoya, and secondary to systemic illness. Hemorrhagic strokes occurred in seven children: three due to anticoagulation, three due to vascular malformation, and one secondary to severe thrombocytopenia. Among children with stroke, the reason for admission was most commonly postoperative from cardiac procedures whereas children without stroke (n = 31) were most commonly admitted for infection. Of the 56 in-hospital stroke alerts, seven (13%) were activated by a pediatric neurology resident after a neurology consult was placed and four (7%) were activated after the inpatient care team had obtained a head CT concerning for stroke.
The final nonstroke diagnoses for the in-hospital stroke alerts included seizure (21%), posterior reversible encephalopathy syndrome (7%), TIA (5%) and acute disseminated encephalomyelitis (4%), Fig 1. Iatrogenic causes of “stroke like symptoms” included medication side effects and sedation following cardiac surgery. Other final diagnoses included metabolic derangement and acute psychosis. Patient location at initiation of a stroke alert can be found in Fig 2. MRI brain was the most frequent initial imaging modality (n = 31) followed by CT head (n = 20). Five children had no neuroimaging; stroke alerts were cancelled after neurology evaluation, as stroke was no longer suspected. Reasons MRI was not the first image included: need for sedation, temporary contraindications for MRI, and patient too ill for immediate MRI. Thirteen patients had CT head completed but never had MRI, most commonly due to presence of a MRI incompatible medical device (61%). Most children (63%) did not require sedation for neuroimaging or were already sedated secondary to other medical conditions (18%). No child with in-hospital ischemic stroke received thrombolysis or thrombectomy. In 18 children with ischemic stroke, median time from symptom onset to
M. Barry et al. / Pediatric Neurology 88 (2018) 31 35
33
FIGURE 1. Final diagnosis for 56 children evaluated urgently for stroke-like symptoms while hospitalized. Eight children had more than one diagnosis.
stroke alert activation was 69 minutes (IQR 21-172 minutes) for 15 of 18 children with clear times documented and median time from stroke alert activation to neuroimaging was 65 minutes (IQR 39 to 149 minutes) (Table 2). Eight children had activation more than 4.5 hours from symptom onset. The other 10 children had stroke alerts less than 4.5 hours from symptom onset;
two were postoperative from major cardiac surgery, six were anticoagulated, and two were on chemotherapy. All of the children with ischemic stroke had at least one contraindication for intravenous tPA; two had a large vessel occlusion but were not candidates for thrombectomy. Of seven children with hemorrhagic stroke, three had emergency procedures to relieve increased intracranial
FIGURE 2. Stroke and nonstroke diagnoses by hospital location.
34
M. Barry et al. / Pediatric Neurology 88 (2018) 31 35
TABLE 2. Minutes From Symptom Onset to Stroke Alert Activation and From Stroke Alert to Neuroimaging (Median and IQR)
Symptom onset to stroke alert Stroke alert to neuroimaging
All Stroke Alerts (n = 47)
Confirmed Strokes (n = 15)
30 (12-180) 78 (56-126)
69 (21-172) 65 (39-149)
IQR, interquartile range.
pressure. Of all 56 stroke alerts, 47 had reliable times recorded in the chart. Time to stroke alert and imaging for all stroke alerts can be found in Table 2. Of 56 pediatric stroke alerts, 12 children died during the same hospitalization. Nine children with stroke died; four secondary to the stroke and five transitioned to comfort care related to both stroke and other underlying medical problems. Three children without stroke died; two secondary to cerebral edema from encephalitis and one was transitioned to comfort care due to other medical problems.
Discussion
Following activation of an in-hospital pediatric stroke alert, 45% had a final diagnosis of stroke. This is a higher proportion of children with a stroke diagnosis than seen in a pediatric emergency department in our previous study (24%).5 Of the 55% with a final nonstroke diagnosis, 38% had a stroke mimic requiring urgent neurological evaluation including seizure, posterior reversible encephalopathy syndrome, TIA, and acute disseminated encephalomyelitis. The frequency of stroke after a pediatric stroke alert of 45% seems high in this sample, however in the adult literature, after an in-hospital stroke alert, 42.5% of adults were found to have a stroke with another 6.9% diagnosed with TIA. Thus the percentages found in children were similar.6 Stroke alerts included in this study straddled the time before and after the American Heart Association 2015 update on acute endovascular therapy,7 and occurred before the new 2018 guidelines.4 In 2015, American Heart Association guidelines were updated to reflect multiple successful endovascular trials that showed treatment with endovascular therapy for adults with large vessel occlusion less than six hours from last known normal was superior to medical management, signifying a new standard of care for adults with an internal carotid or middle cerebral artery occlusion.7 In 2018, endovascular guidelines were updated again to reflect successful trials with an extended window for endovascular treatment, up to 24 hours in some cases.4 Our prior review of pediatric stroke alerts in the emergency department reported off-label stroke interventions in three of 30 children with ischemic stroke, two children underwent mechanical thrombectomy and one received intra-arterial tPA.5 None of the children in this series was a candidate for either intravenous tPA or mechanical thrombectomy, although two had large vessel occlusions. Published reports suggest that children with cardioembolic strokes and arteriopathies are more commonly treated with thrombectomy and thrombolysis.8,9 Within this group, children with complex congenital heart disease are at high-risk for cardioembolic
stroke and may be in the hospital at the time of their stroke. That none of our patients underwent these treatments presumably reflects a small sample size with 18 children with ischemic stroke. In the recent Swiss review of 216 children with AIS, 16 (7%) received thrombolysis or thrombectomy.8 While this study demonstrates that stroke alerts allow rapid response to children with stroke and/or dangerous stroke mimics, it remains unclear if children will benefit from the expanded stroke intervention time windows, as endovascular treatment in children remains unstudied and controversial. As such, future research should focus on safety and efficacy of endovascular treatment for children with stroke. In the current study, the median time from stroke alert to imaging completion was 78 minutes (IQR 56 to 126 minutes). This is slightly faster than times reported in our emergency room, where in 2013 to 2014, time from presentation to imaging was a median of 94 minutes, (IQR 53-136 minutes).5 A pediatric stroke alert is activated at our center in response to an acute onset of stroke-like symptoms within 48 hours of last seen normal because we believe that rapid diagnosis allows for supportive care and prevention of recurrent strokes. One important limitation of our work is that systematic data collection did not occur for incidental strokes found on imaging without symptoms or for missed strokes when acute stroke alert was not activated in a timely fashion. As part of a monthly quality improvement meeting for pediatric stroke alerts, the Department of Radiology generates a list of urgent stroke protocol brain MRIs and any head CTs and brain MRIs with concern for stroke listed as an indication for neuroimaging. These lists were reviewed, and brain imaging that was completed and should have been a stroke alert (missed stroke alerts) was not identified. However, of the 56 in-hospital stroke alerts, four (7%) were activated by the inpatient care team after a head CT had been obtained and seven (13%) were activated by a pediatric neurology resident after a neurology consult was placed, suggesting both decreased recognition of stroke and some lack of awareness of the stroke alert process. Conclusions
Activation of an in-hospital pediatric stroke alert was most often a stroke or other neurological urgency. Stroke alert activation allowed rapid evaluation by a neurologist and prioritization of neuroimaging. While no child in this series received acute stroke intervention, all received supportive care and stroke prevention therapy when possible. More acute stroke treatments may be available for children in the future, and children's hospitals should strive to be prepared to rapidly evaluate and treat these patients. This study utilized REDCap, which was funded by NCAT/NIHUL1 TR000445.
References 1. Amlie-Lefond C, Chan AK, Kirton A, et al. Thrombolysis in acute childhood stroke: design and challenges of the thrombolysis in pediatric stroke clinical trial. Neuroepidemiology. 2009;32:279–286.
M. Barry et al. / Pediatric Neurology 88 (2018) 31 35 2. Bernard TJ, Rivkin MJ, Scholz K, et al. Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke (TIPS) trial. Stroke. 2014;45:2018–2023. 3. Lyle CA, Bernard TJ, Goldenberg NA. Childhood arterial ischemic stroke: a review of etiologies, antithrombotic treatments, prognostic factors, and priorities for future research. Semin Thromb Hemostasis. 2011;37:786–793. 4. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46–110. 5. Ladner TR, Mahdi J, Gindville MC, et al. Pediatric acute stroke protocol activation in a children's hospital emergency department. Stroke. 2015;46:2328–2331.
35
6. Cumbler E, Simpson J. Code stroke: multicenter experience with in-hospital stroke alerts. J Hosp Med. 2015;10:179–183. 7. Powers WJ, Derdeyn CP, Biller J, et al. 2015 AHA/ASA focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46: 3020–3035. 8. Bigi S, Dulcey A, Gralla J, et al. Feasibility, safety and outcome of recanalisation treatment in childhood stroke. Ann Neurol. 2018. https://doi.org/10.1002/ana.25242. Apr 20. Epub ahead of print. 9. Buompadre MC, Andres K, Slater LA, et al. Thrombectomy for acute stroke in childhood: a case report, literature review, and recommendations. Pediatr Neurol. 2017;66:21–27.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
In-Hospital Pediatric Stroke Alert Activation Megan Barry, DO a,b, Truc M. Le, MD c, Melissa C. Gindville, MS a, Lori C. Jordan, MD, PhD a* a
Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, Tennessee Department of Pediatrics, Division of Pediatric Neurology, University of Colorado Medical Center, Aurora, Colorado c Department of Pediatrics, Division of Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee b
ARTICLE INFO
ABSTRACT
Article history: Received 9 May 2018 Received in revised form 31 July 2018 Accepted 4 August 2018
BACKGROUND: Pediatric stroke alerts or “code strokes” allow for rapid evaluation, imaging,
Keywords: Stroke Children Ischemic Hemorrhagic
and treatment of children presenting with stroke-like symptoms. In a previous study of emergency department-initiated pediatric stroke alerts, 24% of children had confirmed strokes. The purpose of this study was to characterize in-hospital pediatric stroke alerts. METHODS: Demographic and clinical information was obtained from a quality improvement database and medical records for children (zero to 20 years) at a single institution for whom a stroke alert was activated after hospital admission between April 2011 and December 2016. Stroke alert activation criteria included a new focal neurological defect occurring within 48 hours. A neurologist evaluated the patient within 15 minutes and rapid magnetic resonance imaging was available. RESULTS: Medical personnel activated in-hospital stroke alerts for 56 children (median age 6.5 years, interquartile range 1 to 13, 52% male). Stroke was the final diagnosis of 25 (45%), 72% ischemic, and 28% hemorrhagic strokes. Other diagnoses included neurological urgencies: seizure (21%), posterior reversible encephalopathy syndrome (7%), transient ischemic attack (5%), and acute disseminated encephalomyelitis (4%). Of the stroke diagnoses, 68% were stroke alerts called in the pediatric intensive care unit or pediatric cardiac intensive care unit. Rapid neuroimaging was completed in 91%; magnetic resonance imaging brain was the first image in 55%. CONCLUSIONS: Of in-hospital pediatric stroke alerts, 45% were stroke while 38% were other neurological conditions requiring urgent evaluation. In-hospital stroke alerts were commonly activated for children with complicated medical histories. Rapid neurological evaluation facilitated care. No child underwent thrombolysis or thrombectomy. © 2018 Elsevier Inc. All rights reserved.
Introduction
In the last decade, preparedness for pediatric acute stroke care at children's hospitals has increased. In Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declarations of Interest: None
* Communications should be addressed to: Lori C. Jordan MD, PhD, Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN 37232-9559. E-mail address: [email protected] https://doi.org/10.1016/j.pediatrneurol.2018.08.003 0887-8994/© 2018 Elsevier Inc. All rights reserved.
conjunction with the first pediatric acute stroke treatment study, the Thrombolysis in Pediatric Stroke trial,1 pediatric stroke centers developed new methods for identifying and treating children with stroke that included the development of stroke teams, creation of institutional pathways, and availability of 24/7 magnetic resonance imaging (MRI). As a result, these centers reported a significant increase in self-assessed preparedness for pediatric stroke cases.2 Despite advances in stroke alert systems, the ability of in-hospital stroke alerts to rapidly and effectively identify children with stroke has never been reported. Known
32
M. Barry et al. / Pediatric Neurology 88 (2018) 31 35
pediatric stroke risk factors including congenital heart disease, sickle cell disease, infections, and other prothrombotic conditions are common reasons children are admitted to the hospital.3 Early recognition and evaluation of acute stroke symptoms has the potential to identify children as candidates for intravenous tissue plasminogen activator (tPA) and thrombectomy, especially with adult stroke treatment windows rapidly expanding.4 We aimed to evaluate the characteristics, final diagnosis, and outcomes of children whose admission involved an in-hospital stroke alert. Methods Our freestanding children's hospital serves a referral area of approximately 2,000,000 people, has about 15,000 annual inpatient visits with a 24-bed medical/surgical pediatric intensive care unit, and has an 18-bed pediatric cardiovascular intensive care unit. Pediatric stroke alerts are paged through a central paging system and logged prospectively in a quality improvement database. Urgent stroke protocol MRIs and head computed tomography (CT) as well as brain MRIs with indication for examination noted as concern for stroke are logged in an imaging quality improvement database. Clinical and demographic information was obtained from medical records for patients, aged 29 days to 20 years, with a pediatric acute stroke alert activated after hospital admission from April, 2011 to December, 2016. A stroke alert is activated if a child develops a focal neurological deficit concerning for transient ischemic attack (TIA) or acute stroke with symptom duration less than 48 hours. A stroke alert is not activated for neonatal/perinatal strokes. A neurology resident sees all stroke alert patients within 15 minutes; MRI is acutely made available. Neurologists work with the primary team to evaluate the child and select the best imaging option with the goal of offering an acute stroke treatment if indicated and appropriate supportive care. The institutional review board approved this study; consent was waived. Descriptive statistics were utilized for data analysis.
TABLE 1. Study Population Characteristics of Children With a Final Diagnosis of Stroke (n = 25) and No Stroke (n = 31) Stroke Age, y, median (IQR) Sex Male Race White, Non-Hispanic/Latino White, Hispanic/Latino Black Other Comorbid condition* Cardiac Congenital heart disease Other/Acquired Hematologic/Oncologic Sickle cell disease Cancer Other Immunologic/Rheumatologic Infectious Chronic/Systemic disease Genetic Trisomy 21 Neurological Seizure Prior stroke/TIA Other Vascular Reason for admission Worsening of previously known medical condition Postoperative Medical treatment for known medical condition Infection Trauma Other
3 (1-10) n (%)
No Stroke 9 (5-14) n (%)
13 (52)
16 (52)
17 3 5 0 21 16 13 3 8 1 3 4 0 0 5 4 3 6 1 5 1 1
15 2 13 1 27 7 5 2 16 6 8 2 1 2 10 2 1 13 5 4 5 2
(68) (12) (20) (0) (84) (64) (52) (12) (32) (4) (12) (16) (0) (0) (20) (16) (12) (24) (4) (20) (4) (4)
(48) (6) (42) (3) (87) (23) (16) (6) (52) (19) (26) (6) (3) (6) (32) (6) (1) (42) (16) (13) (16) (6)
6 (24)
7 (22)
7 (28) 2 (8)
4 (13) 5 (16)
5 (20) 2 (8) 6 (24)
13 (42) 0 (0) 4 (13)
IQR, interquartile range; TIA, transient ischemic attack; y, years. *Some children had more than one area of past medical history; percentages do not add up to 100%.
Results
A total of 56 pediatric stroke alerts were activated with a median age 6.5 years (interquartile range [IQR] 113), 52% male. The majority of children (85.7%) had at least one comorbid condition; over 50% had multiple categories, Table 1. Stroke, either ischemic or hemorrhagic, was the final diagnosis for 25 (45%) of the in-hospital stroke alerts (Fig 1). Ischemic stroke etiologies for 18 children included: seven that were cardioembolic, six that were periprocedural between zero and 12 days after a cardiac surgery, one that was idiopathic and four ischemic strokes from other causes including vessel compression from brain tumor, moyamoya, and secondary to systemic illness. Hemorrhagic strokes occurred in seven children: three due to anticoagulation, three due to vascular malformation, and one secondary to severe thrombocytopenia. Among children with stroke, the reason for admission was most commonly postoperative from cardiac procedures whereas children without stroke (n = 31) were most commonly admitted for infection. Of the 56 in-hospital stroke alerts, seven (13%) were activated by a pediatric neurology resident after a neurology consult was placed and four (7%) were activated after the inpatient care team had obtained a head CT concerning for stroke.
The final nonstroke diagnoses for the in-hospital stroke alerts included seizure (21%), posterior reversible encephalopathy syndrome (7%), TIA (5%) and acute disseminated encephalomyelitis (4%), Fig 1. Iatrogenic causes of “stroke like symptoms” included medication side effects and sedation following cardiac surgery. Other final diagnoses included metabolic derangement and acute psychosis. Patient location at initiation of a stroke alert can be found in Fig 2. MRI brain was the most frequent initial imaging modality (n = 31) followed by CT head (n = 20). Five children had no neuroimaging; stroke alerts were cancelled after neurology evaluation, as stroke was no longer suspected. Reasons MRI was not the first image included: need for sedation, temporary contraindications for MRI, and patient too ill for immediate MRI. Thirteen patients had CT head completed but never had MRI, most commonly due to presence of a MRI incompatible medical device (61%). Most children (63%) did not require sedation for neuroimaging or were already sedated secondary to other medical conditions (18%). No child with in-hospital ischemic stroke received thrombolysis or thrombectomy. In 18 children with ischemic stroke, median time from symptom onset to
M. Barry et al. / Pediatric Neurology 88 (2018) 31 35
33
FIGURE 1. Final diagnosis for 56 children evaluated urgently for stroke-like symptoms while hospitalized. Eight children had more than one diagnosis.
stroke alert activation was 69 minutes (IQR 21-172 minutes) for 15 of 18 children with clear times documented and median time from stroke alert activation to neuroimaging was 65 minutes (IQR 39 to 149 minutes) (Table 2). Eight children had activation more than 4.5 hours from symptom onset. The other 10 children had stroke alerts less than 4.5 hours from symptom onset;
two were postoperative from major cardiac surgery, six were anticoagulated, and two were on chemotherapy. All of the children with ischemic stroke had at least one contraindication for intravenous tPA; two had a large vessel occlusion but were not candidates for thrombectomy. Of seven children with hemorrhagic stroke, three had emergency procedures to relieve increased intracranial
FIGURE 2. Stroke and nonstroke diagnoses by hospital location.
34
M. Barry et al. / Pediatric Neurology 88 (2018) 31 35
TABLE 2. Minutes From Symptom Onset to Stroke Alert Activation and From Stroke Alert to Neuroimaging (Median and IQR)
Symptom onset to stroke alert Stroke alert to neuroimaging
All Stroke Alerts (n = 47)
Confirmed Strokes (n = 15)
30 (12-180) 78 (56-126)
69 (21-172) 65 (39-149)
IQR, interquartile range.
pressure. Of all 56 stroke alerts, 47 had reliable times recorded in the chart. Time to stroke alert and imaging for all stroke alerts can be found in Table 2. Of 56 pediatric stroke alerts, 12 children died during the same hospitalization. Nine children with stroke died; four secondary to the stroke and five transitioned to comfort care related to both stroke and other underlying medical problems. Three children without stroke died; two secondary to cerebral edema from encephalitis and one was transitioned to comfort care due to other medical problems.
Discussion
Following activation of an in-hospital pediatric stroke alert, 45% had a final diagnosis of stroke. This is a higher proportion of children with a stroke diagnosis than seen in a pediatric emergency department in our previous study (24%).5 Of the 55% with a final nonstroke diagnosis, 38% had a stroke mimic requiring urgent neurological evaluation including seizure, posterior reversible encephalopathy syndrome, TIA, and acute disseminated encephalomyelitis. The frequency of stroke after a pediatric stroke alert of 45% seems high in this sample, however in the adult literature, after an in-hospital stroke alert, 42.5% of adults were found to have a stroke with another 6.9% diagnosed with TIA. Thus the percentages found in children were similar.6 Stroke alerts included in this study straddled the time before and after the American Heart Association 2015 update on acute endovascular therapy,7 and occurred before the new 2018 guidelines.4 In 2015, American Heart Association guidelines were updated to reflect multiple successful endovascular trials that showed treatment with endovascular therapy for adults with large vessel occlusion less than six hours from last known normal was superior to medical management, signifying a new standard of care for adults with an internal carotid or middle cerebral artery occlusion.7 In 2018, endovascular guidelines were updated again to reflect successful trials with an extended window for endovascular treatment, up to 24 hours in some cases.4 Our prior review of pediatric stroke alerts in the emergency department reported off-label stroke interventions in three of 30 children with ischemic stroke, two children underwent mechanical thrombectomy and one received intra-arterial tPA.5 None of the children in this series was a candidate for either intravenous tPA or mechanical thrombectomy, although two had large vessel occlusions. Published reports suggest that children with cardioembolic strokes and arteriopathies are more commonly treated with thrombectomy and thrombolysis.8,9 Within this group, children with complex congenital heart disease are at high-risk for cardioembolic
stroke and may be in the hospital at the time of their stroke. That none of our patients underwent these treatments presumably reflects a small sample size with 18 children with ischemic stroke. In the recent Swiss review of 216 children with AIS, 16 (7%) received thrombolysis or thrombectomy.8 While this study demonstrates that stroke alerts allow rapid response to children with stroke and/or dangerous stroke mimics, it remains unclear if children will benefit from the expanded stroke intervention time windows, as endovascular treatment in children remains unstudied and controversial. As such, future research should focus on safety and efficacy of endovascular treatment for children with stroke. In the current study, the median time from stroke alert to imaging completion was 78 minutes (IQR 56 to 126 minutes). This is slightly faster than times reported in our emergency room, where in 2013 to 2014, time from presentation to imaging was a median of 94 minutes, (IQR 53-136 minutes).5 A pediatric stroke alert is activated at our center in response to an acute onset of stroke-like symptoms within 48 hours of last seen normal because we believe that rapid diagnosis allows for supportive care and prevention of recurrent strokes. One important limitation of our work is that systematic data collection did not occur for incidental strokes found on imaging without symptoms or for missed strokes when acute stroke alert was not activated in a timely fashion. As part of a monthly quality improvement meeting for pediatric stroke alerts, the Department of Radiology generates a list of urgent stroke protocol brain MRIs and any head CTs and brain MRIs with concern for stroke listed as an indication for neuroimaging. These lists were reviewed, and brain imaging that was completed and should have been a stroke alert (missed stroke alerts) was not identified. However, of the 56 in-hospital stroke alerts, four (7%) were activated by the inpatient care team after a head CT had been obtained and seven (13%) were activated by a pediatric neurology resident after a neurology consult was placed, suggesting both decreased recognition of stroke and some lack of awareness of the stroke alert process. Conclusions
Activation of an in-hospital pediatric stroke alert was most often a stroke or other neurological urgency. Stroke alert activation allowed rapid evaluation by a neurologist and prioritization of neuroimaging. While no child in this series received acute stroke intervention, all received supportive care and stroke prevention therapy when possible. More acute stroke treatments may be available for children in the future, and children's hospitals should strive to be prepared to rapidly evaluate and treat these patients. This study utilized REDCap, which was funded by NCAT/NIHUL1 TR000445.
References 1. Amlie-Lefond C, Chan AK, Kirton A, et al. Thrombolysis in acute childhood stroke: design and challenges of the thrombolysis in pediatric stroke clinical trial. Neuroepidemiology. 2009;32:279–286.
M. Barry et al. / Pediatric Neurology 88 (2018) 31 35 2. Bernard TJ, Rivkin MJ, Scholz K, et al. Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke (TIPS) trial. Stroke. 2014;45:2018–2023. 3. Lyle CA, Bernard TJ, Goldenberg NA. Childhood arterial ischemic stroke: a review of etiologies, antithrombotic treatments, prognostic factors, and priorities for future research. Semin Thromb Hemostasis. 2011;37:786–793. 4. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46–110. 5. Ladner TR, Mahdi J, Gindville MC, et al. Pediatric acute stroke protocol activation in a children's hospital emergency department. Stroke. 2015;46:2328–2331.
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