PEDIATRICS Vol. 110 No. 5 November 2002, pp. 924-928
Time Lag to Diagnosis of Stroke in Children
From the Department of Neurology, State University of New York at Stony Brook, Stony Brook, New York
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSCASE REPORTSRESULTSDISCUSSIONREFERENCES |
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Objective. Strokes occur rarely in children, and the causes are different from those in adults. Frequently, more than 1 cause is found. The consequences are lifelong significant disability in a majority of cases. Children who are younger than 18 years have not been included in therapeutic trials of thrombolytic or neuroprotective agents. We evaluated whether children who receive a diagnosis of stroke meet a major inclusion criterion for such trials, namely time to diagnosis of <3 to 6 hours.
Methods. Prospective documentation and retrospective chart review was conducted of children who were 0 to 18 years and carried a diagnosis of stroke during the last 2 years in the hospital database, including children who presented with either ischemic or hemorrhagic strokes.
Results. Forty-seven events were encountered in 41 children. Twelve neonates with stroke, diagnosed in the neonatal period, were excluded from the subsequent analysis. In the remaining 29 children, the mean age at presentation was 8.67 years. Accurate time records were available in 24 children. In this group, 28 events were recorded. Time from clinical onset to first medical contact averaged 28.5 hours, and the time to diagnosis of stroke averaged 35.7 hours. We subsequently separated between children with ischemic (21 documented events) and hemorrhagic strokes (7 documented events), because the presentation and the intervention options are different.
Conclusions. Stroke in children is rarely diagnosed in the time frame of 3 to 6 hours. Given the causes and outcome of stroke in children, this age group might benefit from thrombolysis and from neuroprotective therapy, yet the long delay in diagnosis in this age group excludes most cases from being considered for such treatments. This situation should encourage attempts to increase public and professional awareness of stroke in children and of the potential value of early diagnosis and treatment, preferably by broadening current educational efforts to all age groups.
Key Words: children • diagnosis • hemorrhage • stroke
Abbreviations: EMS, Emergency Medical Services • CT, computed tomographic • MRI, magnetic resonance imaging • ED, emergency department
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INTRODUCTION |
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Recent advances in stroke research present several therapeutic options during the acute event, such as thrombolytic and neuroprotective treatments. One major criterion for inclusion in trials of these agents is time frame of <3 to 6 hours from the first occurrence of the symptoms. Patients older than 18 years, in whom the initial imaging study confirms the diagnosis of stroke in the required time frame, are considered for thrombolytic treatment or inclusion in trials of neuroprotective agents.
Stroke in children is a rare occurrence. Studies show that the overall average annual stroke incidence rate for children through 14 years of age is 2.52 to 3.5/100 000 per year.1,2 This incidence is presumed to have risen as a result of increased survival in disorders that might predispose to stroke and were lethal in the past, such as cardiovascular anomalies and malignancies. The causes of cerebrovascular disease in children are multiple, and no 1 risk factor predominates. The probability of identifying the cause depends on the thoroughness of the evaluation. A probable cause of cerebral infarction was identified in 184 (81%) of 228 children in the Canadian Paediatric Ischemic Stroke Registry.3 In approximately 25% of children, the cause is not identified.4 That in many instances the causes are embolus or hypercoagulable state suggests that many children might benefit from thrombolysis. In fact, there are many case reports of children who received tissue plasminogen activator but no controlled trial to prove real benefit.1,5,6
Because of the low incidence, the paucity of information about the best approach to the diagnosis and management of stroke in children and lack of general awareness of cerebrovascular disorders in children all are probably contributors to delay in their diagnosis. In contrast, family members are usually well aware of the significance of an acute neurologic impairment in older individuals and seek medical attention promptly. If delay in diagnosis of stroke in children is long, then this precludes use of thrombolytic agents and other treatments because early diagnosis and initiation of treatment are necessary for efficacy or safety.
In this study, we sought to determine the actual time frame in which children with stroke are medically evaluated and diagnosed. Similar to stroke studies in adults, we measured the time from first symptom to first imaging study. The clinical picture and the first imaging study in adults usually provide enough evidence to consider the above treatments or trials. We found marked delay in diagnosis of stroke in children and postulate explanations for this delay that are supported by our data.
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METHODS |
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The study was conducted at a tertiary hospital, University Medical Center Stony Brook. It is located in Suffolk County, Long Island, and provides care to a population of approximately 1.5 million. The area is covered by Emergency Medical Services (EMS), which uses ambulances and helicopters for transport from distant areas. There are multiple primary care practitioners and clinics and secondary and community hospitals, most of which have a computed tomographic (CT) scanner.
During 1999 to 2000, we documented the occurrence of the first symptom and the path that the child took until the first imaging study was done, for example, whether he or she saw another care provider or whether he or she came with EMS or was transferred from another hospital, as part of the routine history of patients admitted with acute events. At the end of 2000, we retrieved charts of patients with discharge diagnoses of stroke codes in the hospital database. The charts were reviewed retrospectively and were of patients who were younger than 18 years. We recorded anonymously demographic data, initial symptom, time from initial symptom to first medical examination, time to initial imaging, treatment, final diagnosis, and outcome. The data regarding onset of symptoms was retrieved from EMS records and history at admission. The time of imaging was retrieved from CT and magnetic resonance imaging (MRI) reports. The final diagnosis was the entry criteria (by the diagnosis code). Patient outcomes were determined from subsequent inpatient and outpatient medical records. Data were tabulated and analyzed using Excel software (Microsoft, Inc, Redmond, WA).
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CASE REPORTS |
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To illustrate patterns of care that a child with stroke may experience and some of the causes for delays, we present a case with a sizable primary delay and another case with a secondary delay.
Case 1
D.A. was a healthy adolescent, with no known risk factors and negative medical history, who presented with stroke at age 15. He started to feel a severe headache at 10 am and had difficulty with his vision while he was taking an examination in the classroom. He went to the nurse office and complained of double vision and headache. His mother took him home and thought that he was dehydrated. After he drank, he went to sleep until the next morning. The next day, he had the same complaints, so the mother took him to a physician, who did not know him. Delay from initial symptom until first examination was 27 hours. Because of abnormal eye movements confirmed by an ophthalmologist, who saw him in 4 hours, he was referred to the emergency department (ED). He had ataxia, vertical gaze paralysis, and minimal weakness of the right upper extremity. Head CT revealed a small brainstem lesion, and MRI with diffusion-weighted imaging indicated an acute stroke. Delay from initial examination to initial imaging was 7 hours, giving a total delay from symptom onset of 34 hours. Extensive workup for a cause was negative, and he recovered completely.
Case 2
V.F. was an 18-year-old girl, with significantly low height and weight with negative endocrinologic workup, mild cognitive impairment but able to complete regular high school, and seizures since age 12, which were controlled with phenytoin. She had an acute, severe headache and was examined in the primary care clinic. Delay from initial symptom until first examination was 4 hours. She was sent home with a probable diagnosis of viral infection. She started to vomit and became increasingly lethargic. The next day, her parents brought her to the ED, and on examination she seemed dehydrated and in stupor, without localizing signs. CT scan showed a nonvascular distribution of bilateral temporal-parietal infarcts. Delay from initial examination to initial imaging was 32 hours, so total delay time was 36 hours. Elevated serum lactate level and positive A3243G mutation proved the diagnosis of metabolic encephalopathy, lactic acidosis, and stroke-like episodes. She did not have any neurologic deficits from the strokes, but she continued to have progressive myopathy. On MRI and magnetic resonance spectroscopy 1 year later, the infarcts were not seen; however, there was atrophy and elevated brain lactate.
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RESULTS |
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In 2 years, we encountered 47 episodes of stroke in 41 children: 24 boys and 17 girls. Final diagnoses in the 12 neonates with focal infarct or parenchymal hemorrhage (intraventricular hemorrhage and hypoxic-ischemic encephalopathy excluded) were idiopathic in 9 infants (75%), placental embolus in 2 infants, and global hypoxemia in 1 infant. These cases are not considered further in this report.
The other 29 children averaged 8 years and 9 months. Seventy-eight percent had focal infarct, and 22% had parenchymal hemorrhage. The final diagnoses were idiopathic in 18 children (46%) and embolic in 4 children (1 from atrial myxoma and 3 after surgery); a vascular malformation was identified in 3 children, arterial dissection occurred in 2 children, an inherited coagulopathy was found in 3 children, and syndromes were present in 4 children: moyamoya, Cockayne, mitochondrial encephalopathy, and human immunodeficiency virus vasculitis. An underlying known disorder was present in 38%, and in an additional 15%, a predisposing disorder was revealed during the workup for stroke. The initial symptom was headache in 32% of the events, motor symptoms in 60%, sensory symptoms in 7%, aphasia in 14%, seizures or syncope in 10.5%, cranial nerve involvement in 3.5%, cerebellar symptoms in 3.5%, and mental status changes in 21% (Fig 1).
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Accurate time records were available in 24 children. In this group, 28 events were recorded: 1 child with a vascular malformation had recurrent bleed, and 1 child with moyamoya had recurrent stroke. The results of the elapsed time in each of the events are presented in (Fig 1). Mean elapsed time from initial symptom until initial imaging was a total of 35.7 hours (median: 12 hours; range: 0.1–300 hours); however, it was <6 hours in one third of the cases. This time frame included a mean lag of 28.5 hours (median: 5.5 hours; range: 0–240 hours) until initial encounter with a health provider (EMS, physician, or hospital) and an additional mean of 7.2 hours (median: 6.6 hours; range: 0–60 hours) until initial imaging study was done. This second lag includes the time to arrival at a hospital (possible transfer from a different facility) and all other procedures in the hospital until imaging (usually CT scan) was completed.
The information regarding the referral source (pediatrician vs general practitioner) was not available in most cases. Some of the parents contacted a physician or the ED by telephone. However, such telephone encounters were not considered as an initial examination for calculation of the primary delay.
The total time delay was longer for ischemic stroke than for hemorrhage: 42.8 hours (median: 20 hours; range: 0.1–300 hours) for ischemic stroke and 14.3 hours (median: 5 hours; range: 0.1–60 hours) for hemorrhage. The initial encounter with a medical person was a mean of 34.5 hours after symptom onset for ischemic stroke (median: 9 hours; range: 0–240 hours) and 10.8 hours for hemorrhage (median: 2.5 hours; range: 0–48 hours; Fig 2).
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We compared the total delay time in the 14 events that occurred in children who were younger than 8 years with the 14 events that occurred to children who were older than 8 years. In the younger group, the mean total delay was 57.5 hours (50.9 hours from initial symptom to initial examination); in the older group, the total delay was 13. 8 hours (6.1 hour until first examination; P = .05). The difference for the total delay time was not significant, but the P value was .05 for the time from initial symptom to initial examination. This difference is mainly related to the fact that most of the events of hemorrhage occurred in the older group and prompted faster presentation. If we eliminate the hemorrhages, then there is a longer delay in the younger group, which is not statistically significant.
The outcome was severe impairment in 25% of the events, including 1 death. Forty percent of the events left a mild neurologic deficit, and 36% resolved without any measurable impairment.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSCASE REPORTSRESULTSDISCUSSIONREFERENCES |
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Stroke in children is rarely diagnosed in the time frame of 3 to 6 hours, unless hemorrhage occurs. With a massive hemorrhage, the symptoms are overt and dramatic, which prompts immediate medical attention. From our study, it seems that the main delay was in seeking medical attention. In addition, most of the children arrived at the ED with additional delay and without the sense of emergency that a stroke in adults conveys. Results of a large-scale study in adults7 showed that in 1207 adult subjects, the symptom onset to ED arrival was 2.6 hours (range: 1.2- 6.3), time to initial imaging was 1.1 hour (range: 0.7–1.8), and the total delay time (symptom onset until CT completion) was 4 hours (range: 2.3–8.3).
There are difficulties for the caregiver, either parents or school professionals, in recognizing the urgency of various symptoms. The initial symptom can be a common complaint, such as headache or fatigue, and the child might not complain. Neurologic signs might be difficult to recognize in children, for example, aphasia in a child who had not yet mastered language or new deficits in a child with developmental delay or previous neurologic impairment. An additional barrier to early diagnosis is children's difficulty in describing a symptom and in conveying the severity and the acuteness to the caregiver or to the physician. Even an older child with appropriate verbal skills will have difficulty describing sensory or cerebellar symptoms, and without an appropriate description, a physician will be less likely to elicit various abnormalities on examination and to appreciate the full significance of the event.
We checked these issues by dividing our patients by age. Comparing younger children with older children, we found a nonsignificant tendency to a longer delay in the young group, which is consistent with interference with diagnosis as a result of their poorer ability to recognize symptoms, such as aphasia, and to explain them to an adult. Developmental delay, preexisting in 3 children, would have increased this problem.
The 2 case reports presented demonstrate the complexity of stroke in children and the frequent initial complaint of headache, unlike adults. The workup for the final diagnosis was long and expensive, but the initial diagnosis of stroke was reached after inexpensive tests: history, examination, and head CT.8
Considering the causes and the sequelae of their strokes, children might benefit from thrombolytic and neuroprotective treatments. For both thrombotic and hemorrhagic events, control of oxygenation, blood pressure (either very high or very low), dehydration, hyperthermia, hyperglycemia, and aspiration are general measures for preservation of brain tissue in the "penumbra" area of potentially reversible ischemia and prevention of additional damage.9 Cerebral ischemia and reperfusion trigger a cascade of events that involve presynaptic release of glutamate (excitatory neurotransmitter), activation of proteases as a result of increased intracellular calcium, generation of free radicals, and subsequent inflammatory response. For arresting those processes, several neuroprotective agents, such as N-methyl-d-aspartate receptor antagonists, glycine antagonists, calcium blockers, free radicals scavengers, and antiinflammatory agents, are under investigation.9 However, all of those agents also have a time-limiting factor because they are directed toward prevention of early steps of the cascade. For extensive hemorrhages, surgical evacuation might be warranted. For thrombotic events, accumulating experience with antithrombotic and anticoagulant treatment in children suggests that these agents can be used safely in children, although their efficacy and proper dose still need to be clarified. Thrombolytic agents should be as effective in children as in adults and might be safer in children. Retrospective analysis of causes shows that 7 patients in our study had embolic phenomena or a hypercoagulable state, and it is plausible that in these cases, as well as in idiopathic cases, thrombolysis might have reduced the damage. Other risks and benefits of these treatments are certainly not defined in children, and we definitely do not advocate their use. At the present time, however, if diagnosis can be made in the phase when a penumbra is still present, then such interventions can be considered.
A few childhood disorders predispose to the occurrence of stroke, such as sickle cell disease, collagen-vascular disorders, and hypercoagulable states. Such predisposing disorders were present in more than one third of the children in our study, but the lag to diagnosis in this group was not shorter. Cardiac disease remains the most common cause of ischemic cerebral infarction in children. Most of these children have congenital heart lesions that are identified well before an infarction occurs. Ischemic infarction may occur frequently enough to warrant controlled trials of prophylactic or neuroprotective agents, when the risk of stroke is higher. Families of children who are at risk could be taught to recognize subtle acute neurologic deficits and the possible value of early intervention.
Increased awareness to predisposing conditions and recognition of neurologic deficits by the public and by medical personnel will potentially improve access of pediatric stroke patients to newer forms therapy. This should encourage educational efforts to all age groups about the potential value of early diagnosis and treatment of stroke in children.
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FOOTNOTES |
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Received for publication Dec 26, 2001; Accepted Jun 7, 2002.
Reprint requests to (L.V.G.) Division of Developmental Disabilities, South Campus, Putnam Hall, State University of New York, Stony Brook, NY 11794-8790. E-mail: lgabis{at}notes.cc.sunysb.edu
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PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
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