Pathways for Neuroimaging of Childhood Stroke

doi:10.1016/j.pediatrneurol.2016.12.004

Pediatric Neurology

Volume 69, April 2017, Pages 11-23

https://doi.org/10.1016/j.pediatrneurol.2016.12.004 Get rights and content

Abstract

Background

The purpose of this article is to aid practitioners in choosing appropriate neuroimaging for children who present with symptoms that could be caused by stroke.

Methods

The Writing Group members participated in one or more pediatric stroke neuroimaging symposiums hosted by the Stroke Imaging Laboratory for Children housed at the Hospital for Sick Children in Toronto, Ontario, Canada. Through collaboration, literature review, and discussion among child neurologists with expertise diagnosing and treating childhood stroke and pediatric neuroradiologists and neuroradiologists with expertise in pediatric neurovascular disease, suggested imaging protocols are presented for children with suspected stroke syndromes including arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke.

Results

This article presents information about the epidemiology and classification of childhood stroke with definitions based on the National Institutes of Health Common Data Elements. The role of imaging for the diagnosis of childhood stroke is examined in depth, with separate sections for arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke. Abbreviated neuroimaging protocols for rapid diagnosis are discussed. The Writing Group provides suggestions for optimal neuroimaging investigation of various stroke types in the acute setting and suggestions for follow-up neuroimaging. Advanced sequences such as diffusion tensor imaging, perfusion imaging, and vessel wall imaging are also discussed.

Conclusions

This article provides protocols for the imaging of children who present with suspected stroke.

Section snippets

Introduction and epidemiology

Stroke is a major cause of morbidity and mortality in children worldwide. The reported annual incidence of childhood stroke ranges from 2.3 to 13 per 100,000 children per year in developed countries.1, 2, 3 Despite increasing awareness, this condition is often overlooked by medical providers and families. In adults, presentation with sudden onset hemiparesis with or without facial weakness and language problems constitutes hallmark presenting features of stroke which raise concern for the

Pediatric stroke classification

Childhood stroke is defined as occurring in children aged 29 days after birth to 18 years. Perinatal stroke, defined as stroke occurring from birth to 28 days of life (and in some cases in utero beginning at 20 weeks' gestation), will be discussed in a separate article. Stroke is traditionally subdivided into two types: ischemic and hemorrhagic. As opposed to adults who have ischemic stroke 85% of the time, stroke in children is almost evenly divided between ischemic and hemorrhagic events.³

Childhood AIS

After childhood AIS, more than 75% of children will suffer long-term neurological deficits and 10% of children will die.5, 6, 7, 8, 9 Recurrence risk after childhood AIS has been estimated at 12% at one year¹⁰ and 19% at five years.⁹

Approximately 30% of children with AIS encountered in academic centers have an associated cardiac disorder that presumably leads to cardioembolism (Fig 1), whereas cerebral arteriopathy is found in up to half of all children with childhood AIS.11, 12 The presence of

Role of imaging in childhood AIS

Timely diagnosis of acute stroke remains challenging because of the following factors: (1) the wider differential diagnosis in children relative to adults, (2) the relative rarity of stroke in children compared with adults (including a lack of knowledge that children have strokes and that treatment is time-dependent in some circumstances), and (3) challenges to acquisition of urgent diagnostic neuroimaging in children.³⁰ Twenty percent to more than half of children presenting urgently with

Transient ischemic attack

TIAs occur in children, although the true incidence remains unclear as TIAs often cannot be distinguished from stroke mimics. The significance of TIA in children has not been as thoroughly evaluated as it has in adults. In adults, stroke occurs within 3 months of a TIA in 10% to 15% of patients with TIAs.40, 41 In a recent retrospective cohort of pediatric patients with childhood AIS, 13% had a stroke after TIA with a mean follow-up period of 4.5 years. Female sex, autoimmune disorders, and

CSVT and cortical vein thrombosis

Childhood CSVT is uncommon, with an incidence of 0.4 to 0.7 per 100,000 children per year.⁴⁶ However, CSVT is increasingly diagnosed with heightened awareness and increased use of modern neuroimaging. As in adults, etiology of CSVT in children is often multifactorial⁴⁷; associated risk factors include acute conditions such as infection and trauma, and chronic conditions such as anemia, polycythemia, and prothrombotic disorders. Increased intracranial pressure from obstructed venous outflow can

Hemorrhagic stroke

Hemorrhagic stroke refers to nontraumatic intracerebral hemorrhage (with or without intraventricular extension), IVH, and subarachnoid hemorrhage (https://commondataelements.ninds.nih.gov/stroke.aspx#tab=Data_Standards). Childhood hemorrhagic stroke is typically defined as occurring after 28 days of life to age 18 years, and perinatal hemorrhagic stroke (discussed in a separate article) is defined as those occurring in neonates greater than 36 weeks' gestation at birth to 28 days of life to

Stroke mimics

In adults, presentation with sudden onset hemiparesis with or without facial weakness and speech problems are hallmark presenting features, which clinch the diagnosis of stroke without unnecessary delay in most cases. In children, the stroke diagnosis is not as straightforward. Despite a growth in awareness about childhood stroke, when children present with acute neurological deficits, stroke is often not the first diagnosis considered by health personnel. The diagnosis is even more challenging

Future areas of investigation

Pediatric stroke is a growing field with many avenues to explore. An initial focus should be directed toward aid to centers for streamlining childhood stroke imaging protocols that minimize delays and diagnose stroke syndromes rapidly while at the same time evaluating the vasculature for stroke risk factors. In addition, given that there are many other neurological diseases that can present similarly to stroke, sequences that diagnose stroke mimics should also be included when possible.

Future

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To determine factors associated with magnetic resonance imaging (MRI) and noninvasive diagnostic angiography among children presenting to the emergency department (ED) with acute ischemic stroke.
We performed a cross-sectional study using data from >50 US children’s hospitals. We included children 29 days through 17 years old hospitalized from the ED with an International Classification of Diseases, Tenth Revision, Clinical Modification, diagnosis code for acute ischemic stroke between October 1, 2015, and November 30, 2022. We excluded children with a principal diagnosis code of trauma/external injury, without neuroimaging on day of presentation, and into-ED transfers. Our outcomes were defined as acquisition of MRI (vs computed tomography only) and angiography (vs no angiography) on day of presentation. We performed generalized linear mixed modeling with hospital as a random effect to determine the association of demographics, known comorbidities, and treatment factors with each outcome.
We included 1601 children. In multivariable analysis, younger age, mechanical ventilation, and Black race were associated with lower odds of MRI acquisition, whereas history of moyamoya disease and sickle cell disease were associated with greater odds. Younger age, mechanical ventilation, Hispanic ethnicity, Black race, other races, history of metabolic disease, and history of seizures were associated with lower odds of angiography.
Younger and non-White children experienced lower odds of MRI and angiography, which may be driven by health system limitations or provider implicit biases or both. Our results expose risk factors for underdiagnosis of ischemic stroke and provide opportunities to tailor institutional pathways reflective of underlying pathophysiology.
The development of the pediatric stroke neuroimaging platform (PEDSNIP)
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Childhood stroke occurs from birth to 18 years of age, ranks among the top ten childhood causes of death, and leaves lifelong neurological impairments. Arterial ischemic stroke in infancy and childhood occurs due to arterial occlusion in the brain, resulting in a focal lesion. Our understanding of mechanisms of injury and repair associated with focal injury in the developing brain remains rudimentary. Neuroimaging can reveal important insights into these mechanisms. In adult stroke population, multi-center neuroimaging studies are common and have accelerated the translation process leading to improvements in treatment and outcome. These studies are centered on the growing evidence that neuroimaging measures and other biomarkers (e.g., from blood and cerebrospinal fluid) can enhance our understanding of mechanisms of risk and injury and be used as complementary outcome markers. These factors have yet to be studied in pediatric stroke because most neuroimaging studies in this population have been conducted in single-centred, small cohorts. By pooling neuroimaging data across multiple sites, larger cohorts of patients can significantly boost study feasibility and power in elucidating mechanisms of brain injury, repair and outcomes. These aims are particularly relevant in pediatric stroke because of the decreased incidence rates and the lack of mechanism-targeted trials.
Toward these aims, we developed the Pediatric Stroke Neuroimaging Platform (PEDSNIP) in 2015, funded by The Brain Canada Platform Support Grant, to focus on three identified neuroimaging priorities. These were: developing and harmonizing multisite clinical protocols, creating the infrastructure and methods to import, store and organize the large clinical neuroimaging dataset from multiple sites through the International Pediatric Stroke Study (IPSS), and enabling central searchability. To do this, developed a two-pronged approach that included building 1) A Clinical-MRI Data Repository (standard of care imaging) linked to clinical data and longitudinal outcomes and 2) A Research-MRI neuroimaging data set acquired through our extensive collaborative, multi-center, multidisciplinary network. This dataset was collected prospectively in eight North American centers to test the feasibility and implementation of harmonized advanced Research-MRI, with the addition of clinical information, genetic and proteomic studies, in a cohort of children presenting with acute ischemic stroke.
Here we describe the process that enabled the development of PEDSNIP built to provide the infrastructure to support neuroimaging research priorities in pediatric stroke. Having built this Platform, we are now able to utilize the largest neuroimaging and clinical data pool on pediatric stroke data worldwide to conduct hypothesis-driven research. We are actively working on a bioinformatics approach to develop predictive models of risk, injury and repair and accelerate breakthrough discoveries leading to mechanism-targeted treatments that improve outcomes and minimize the burden following childhood stroke. This unique transformational resource for scientists and researchers has the potential to result in a paradigm shift in the management, outcomes and quality of life in children with stroke and their families, with far-reaching benefits for other brain conditions of people across the lifespan.
Management of Pediatric Stroke - Challenges and Perspectives from Resource-limited Settings
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Childhood stroke is not as common as adult stroke, but it is underrecognized the world over. Diagnosis is often delayed due to lack of awareness not only by the lay public but also by emergency and front-line health care workers. Despite the relative rarity of childhood stroke, the impact on morbidity, mortality and the economic burden for families and society is high, especially in poorly resourced settings. The risk factors for stroke in children differ from the adult population where lifestyle factors play a more important role. The developmental aspects of the pediatric cerebral vasculature and hematological maturational biology affects the clinical presentation, investigation, management and outcomes of childhood stroke in a different way compared to adults. The management of childhood stroke is currently based on expert guidelines and evidence extrapolated from adult studies. Hyperacute therapies that have revolutionized the treatment of stroke in adults cannot be easily applied to children at this stage due to the diagnostic delays, diverse risk factors and developmental considerations mentioned above. Much has been achieved in the understanding of genetic, acquired, preventable and recurrent stroke risk factors in the past decade through international collaborative efforts like the International Pediatric Stroke Study. Evidence for the prevention and treatment of childhood stroke remains elusive. Even more elusive are relevant and achievable management guidelines for pediatric stroke in resource-limited settings. This narrative review focusses on the current management practices globally, emphasizing the challenges, and gaps in knowledge of pediatric stroke in low- and middle-income countries and other areas with limited resources. Priorities and some potential solutions at national and local level are suggested for these settings.
Diagnosis of Pediatric Stroke in Resource Limited Settings
2022, Seminars in Pediatric Neurology
Global awareness of stroke as a significant cause of neurologic sequelae and death in children has increased over the years as more data in this field becomes available. However, most published literature on pediatric stroke have limited geographic representation. Data on childhood stroke from developing countries remains limited. Thus, this paper reviewed geographic/ethnic differences in pediatric stroke risk factors highlighting those reported in low- and middle-income countries, and proposes a childhood arterial ischemic stroke diagnostic algorithm for resource limited settings. Stroke risk factors include cardiac disorders, infectious diseases, cerebral arteriopathies, hematologic disorders, inflammatory diseases, thrombophilia and genetic conditions. Infection of the central nervous system particularly tuberculous meningitis, is a leading cause of pediatric arterial ischemic stroke in developing countries. Stroke should be considered in children with acute focal neurologic deficit especially in the presence of aforementioned risk factors. Cranial magnetic resonance imaging with angiography is the neuroimaging modality of choice but if unavailable, cranial computed tomography with angiography may be performed as an alternative. If both are not available, transcranial doppler together with neurologic exam may be used to screen children for arterial ischemic stroke. Etiological diagnosis follows with the aid of appropriate laboratory tests that are available in each level of care. International collaborative research on stroke risk factors that are prevalent in low and middle income countries will provide information for drafting of stroke care guidelines that are universal yet inclusive taking into consideration regional differences in available resources with the goal of reducing global stroke burden.
Closing the Gap in Pediatric Hemorrhagic Stroke: A Systematic Review
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Pediatric hemorrhagic stroke (HS) accounts for a large proportion of childhood strokes, 1 of the top 10 causes of pediatric deaths. Morbidity and mortality lead to significant socio-economic and psychosocial burdens. To understand published data on recognizing and managing children with HS, we conducted a systematic review of the literature presented here. We searched PubMed, Embase, CINAHL and the Cochrane Library databases limited to English language and included 174 studies, most conducted in the USA (52%). Terminology used interchangeably for HS included intraparenchymal/intracranial hemorrhage, spontaneous ICH, and cerebrovascular accident (CVA).
Key assessments informing prognosis and management included clinical scoring (Glasgow coma scale), and neuroimaging. HS etiologies reported were systemic coagulopathy (genetic, acquired pathologic, or iatrogenic), or focal cerebrovascular lesions (brain arteriovenous malformations, cavernous malformations, aneurysms, or tumor vascularity). Several scales were used to measure outcome: Glasgow outcome score (GOS), Kings outcome score for head injury (KOSCHI), modified Rankin scale (mRS) and pediatric stroke outcome measure (PSOM).
Most studies described treatments of at-risk lesions. Few studies described neurocritical care management including raised ICP, seizures, vasospasm, or blood pressure.
Predictors of poor outcome included ethnicity, comorbidity, location of bleed, and hematoma >2% of total brain volume. Motor and cognitive outcomes followed independent patterns. Few studies reported on cognitive outcomes, rehabilitation, and transition of care models. Interdisciplinary approach to managing HS is urgently needed, informed by larger cohort studies targeting key clinical question (eg development of a field-guide for the clinician managing patients with HS that is reproducible internationally).
Neuroimaging in Pediatric Stroke
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Citation Excerpt :
Despite advances such as rapid pediatric stroke protocols, neuroimaging capability still differs from center to center15,20 and between health care settings. In places where MRI is not accessible in the emergency setting, for instance outside business hours, non-contrast enhanced CT(NCCT) remains the first choice for initial triage based on guidelines.12,13,21 NCCT may be normal in the first 6-12 hours after onset in the case of an ischemic stroke but is sensitive for detection of acute hemorrhage.
Pediatric stroke is unfortunately not a rare condition. It is associated with severe disability and mortality because of the complexity of potential clinical manifestations, and the resulting delay in seeking care and in diagnosis. Neuroimaging plays an important role in the multidisciplinary response for pediatric stroke patients. The rapid development of adult endovascular thrombectomy has created a new momentum in health professionals caring for pediatric stroke patients. Neuroimaging is critical to make decisions of identifying appropriate candidates for thrombectomy. This review article will review current neuroimaging techniques, imaging work-up strategies and special considerations in pediatric stroke. For resources limited areas, recommendation of substitute imaging approaches will be provided. Finally, promising new techniques and hypothesis-driven research protocols will be discussed.

View all citing articles on Scopus

¹: Co-first authors, the authors contributed equally to this work.

²: Co-senior authors.

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Topical ReviewPathways for Neuroimaging of Childhood Stroke

Abstract

Background

Methods

Results

Conclusions

Section snippets

Introduction and epidemiology

Pediatric stroke classification

Childhood AIS

Role of imaging in childhood AIS

Transient ischemic attack

CSVT and cortical vein thrombosis

Hemorrhagic stroke

Stroke mimics

Future areas of investigation

J Clin Epidemiol

Semin Pediatr Neurol

Blood

Blood

Blood

Blood

J Neurol Sci

Neurosurg Clin N Am

Brain Dev

Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke

Pediatrics

Risk of stroke in children: ethnic and gender disparities

Neurology

Isolated cortical vein thrombosis: case series

J Neurosurg

Prognosis of ischemic stroke in childhood: a long-term follow-up study

Dev Med Child Neurol

Outcome after ischaemic stroke in childhood

Dev Med Child Neurol

Deaths from stroke in US children, 1979 to 1998

Neurology

Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging

Pediatrics

Risk of recurrent arterial ischemic stroke in childhood: a Prospective International Study

Stroke

Arterial ischemic stroke risk factors: the International Pediatric Stroke Study

Ann Neurol

Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the vascular effects of infection in pediatric stroke study

Stroke

Predictors of stroke after transient ischemic attack in children

Stroke

Craniocervical arterial dissection in children: clinical and radiographic presentation and outcome

J Child Neurol

Stroke in childhood: outcome and recurrence risk by mechanism in 59 patients

J Child Neurol

Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Pediatric Stroke Study

Circulation

Arterial dissection and stroke in children

Neurology

Diagnosis of vertebral artery dissection in childhood posterior circulation arterial ischaemic stroke

Dev Med Child Neurol

Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with stroke

J Child Neurol

Stroke in children and sickle-cell disease: Baltimore-Washington Cooperative Young Stroke Study

Neurology

Pial synangiosis for moyamoya syndrome in children with sickle cell anemia: a comprehensive review of reported cases

Neurosurg Focus

Reduction in overt and silent stroke recurrence rate following cerebral revascularization surgery in children with sickle cell disease and severe cerebral vasculopathy

Pediatr Blood Cancer

MR imaging and angiography of primary CNS vasculitis of childhood

AJNR Am J Neuroradiol

The spectrum of CNS vasculitis in children and adults

Nat Rev Rheumatol

Fibromuscular dysplasia and childhood stroke

Brain

Topical Review
Pathways for Neuroimaging of Childhood Stroke