Ischemic Stroke in Children: Overview of Diagnosis, Treatment and Outcomes from the Pediatric Stroke Program

Neil Goldenberg, MD, PhD, Co-Director, Pediatric Thrombosis and Stroke Programs
Assistant Professor, Pediatrics and Internal Medicine, Division of Hematology/Oncology/Bone Marrow Transplant,
University of Colorado School of Medicine

Timothy Bernard, MD, Co-Director, Pediatric Stroke Program, Children's Hospital Colorado
Assistant Professor of Pediatrics, Division of Neurology, University of Colorado School of Medicine

Jennifer Armstrong-Wells, MD, MPH, Pediatric Stroke Program, Children's Hospital Colorado
Director, Perinatal and Hemorrhagic Stroke Programs,
Assistant Professor of Pediatrics, Division of Neurology, University of Colorado School of Medicine

What is ischemic stroke?

There are two major types of stroke: hemorrhagic (stroke due to bleeding) and ischemic. Ischemic stroke is an event or process leading to brain tissue injury, caused by too little blood flow and/or supply of oxygen and other nutrients to the brain. Often, this occurs in an arterial distribution (i.e., arterial ischemic stroke). This article focuses on ischemic stroke in neonates and older children.

Why is ischemic stroke important in children?

Ischemic stroke in children occurs less commonly than in elderly adults, but its consequences can be equally devastating. The incidence of pediatric stroke is approximately 1 in 4,000 during the neonatal period and 1 in 100,000 in older childhood. The risk of recurrent stroke is 3 percent or less for neonatal stroke but is approximately 20 percent when the initial event has occurred beyond the neonatal period (i.e., what is called "childhood-onset stroke"). Issues of evaluation for causes and risk factors, short-term stroke treatments, rehabilitation, and long-term prevention of future strokes all play a very prominent role in stroke care for children. Recent data from a large international series indicate that acute neurological deficits are seen in approximately 70 percent of children,¹ and other published data from single institutions suggest a similar rate of long-term impairment.

Because stroke is a rare disorder in children, optimal stroke care in young people requires expertise from a variety of medical specialties, including coagulation hematology, neurology, radiology, rehabilitation, neuropsychology, and in some cases cardiology, neurosurgery and rheumatology. Although some guidelines have been proposed for the evaluation and treatment of stroke in U.S. children,^2,3 the particular circumstances of each patient must also be considered. This highlights the importance of expertise in stroke care for young people.

What causes ischemic stroke in children?

Causes for stroke in children are more heterogeneous than among elderly adults. Stroke in elderly adults is typically due to high blood pressure, atherosclerosis or arrhythmia. In children and young adults, stroke can be caused by abnormalities in blood vessels in the brain or neck (e.g., cervical arterial dissection, cerebral arteritis), cardioembolism (e.g., cardiac catheterization in a child with congenital cardiac disease), hypercoagulable states (also called “thrombophilia”), sickle cell disease, and certain heart or metabolic conditions. Often, however, the cause of stroke in young people remains unclear. This is especially true for stroke occurring in the perinatal period, where gestational factors causing maternal-placental-fetal insufficiency are being actively researched.

How is ischemic stroke diagnosed in children?

Ischemic stroke in young people may occur with a variety of signs and symptoms, depending mainly on the area of the brain that is affected. These signs and symptoms can include: new-onset seizure; one-sided weakness or numbness; facial droop; slurred speech; sudden change in vision; difficulties with walking, balance, or coordination; or unexplained change in level of consciousness. In neonates, seizure is the most common presentation; in older children, focal neurologic deficits predominate, although seizure is a frequently associated sequela.

Radiologic imaging tests

Suspected stroke is confirmed by radiologic scans, typically magnetic resonance imaging (MRI) of the brain. Computed tomography (CT) of the brain is often also performed initially, and is effective in first establishing whether the patient’s signs/symptoms are explained by intracerebral hemorrhage. When brain MRI is performed to confirm ischemic stroke, magnetic resonance angiography (MRA) is used to evaluate for associated abnormalities of the cerebral and cervical arterial circulation. Diffusion weighted imaging as part of a stroke imaging protocol in children helps to establish the timing of onset of the ischemia; particularly in cardioembolic subtypes of stroke in children, both old and new areas of infarct may be found. Fat-saturation imaging of the neck during MRA also assists in the identification of arterial dissection.

Laboratory tests and other exams

Key components of the diagnostic evaluation include echocardiograpy with agitated saline injection to evaluate for anatomic defects serving as a source or route for embolism (e.g., right-to-left shunting lesion), and laboratory testing for thrombophilia. Thrombophilia testing for stroke risk factors can vary across treatment centers. However, because thrombophilia is common in young stroke patients and has the potential to affect treatments and secondary prevention, comprehensive thrombophilia testing is routinely performed at many specialty centers.

When underlying rheumatologic conditions and/or infections are suspected, the evaluation also includes blood and often cerebrospinal fluid (CSF) testing for these etiologies. In some cases, laboratory evaluation for specific genetic and metabolic disorders may be warranted based upon the clinical history, associated findings, and/or infarct pattern.

How is ischemic stroke treated in children?

The initial treatment of ischemic stroke in young people is complex and varies with condition and etiologic subtype.⁴ Recent international experience in over 600 cases of childhood-onset ischemic stroke reflects this variability.¹ To date, other than in sickle cell disease patients, no clinical trials have been completed to guide the initial treatment of ischemic stroke in children.

Acute management includes the safe medical control of blood pressure, oxygenation, fluid and electrolyties, glycemia and seizure. Additional important treatment decisions involve consideration of the identified causes and risk factors for stroke, the amount and area of the brain affected, and the medical status of the patient. Acute anticoagulation (i.e., unfractionated or low-molecular weight heparins) is often employed in dissection and cardioembolic subtypes of stroke, whereas acute antiplatelet therapy (i.e., aspirin) is typically used for other stroke etiologies. With very large strokes (e.g., 2/3 or more of a cerebral hemisphere), these antithrombotic therapies may be withheld initially due to a high risk for hemorrhagic conversion, and then carefully instituted when the peak of brain edema has passed. Also, given the low risk of recurrence in most cases of non-cardiogenic ischemic stroke in neonates, antithrombotic therapy is generally not administered in this setting. Unlike ischemic stroke in adults, the role of acute thrombolytic interventions (e.g., intravenous or catheter-directed tissue plasminogen activator infusion) have not been studied in children; their use is consequently recommended only at a highly experienced pediatric stroke center and ideally in the context of a closely monitored clinical trial.³

Rehabilitation therapies are also a key component of stroke care in children. Physical, occupational and speech therapies are often needed. In addition, neuropsychological assessment may identify academic, mood and behavioral concerns requiring intervention. A multidisciplinary approach to pediatric stroke management is therefore necessary in order to optimize outcomes for these children.

Children's Hospital Colorado Pediatric Stroke Program

Formally established in 2006, Children's Hospital Colorado's Pediatric Stroke Program cares for pediatric stroke patients and their families in a multidisciplinary setting. Goals of the Program include: establishing and providing coordinated state-of-the-art care for pediatric stroke in the Mountain States region of the U.S. from the time of the occurrence through long-term follow-up; educating affected patients, their families and the community about pediatric stroke; advancing the fields of clinical, translational and outcomes research in pediatric stroke.

Children's Pediatric Stroke Program runs three multidisciplinary clinics, each occurring on a monthly or twice-monthly basis: Arterial Ischemic Stroke (AIS) Clinic; Hemorrhagic Stroke Clinic; and Cerebral Sinovenous Thrombosis (CSVT) Clinic. The first clinic was established in 2003 to evaluate and care for neonates and older children who suffered arterial ischemic stroke. The stroke clinics take a multidisciplinary approach to pediatric care from the time of first follow-up after acute hospitalization through long-term follow-up. The team includes experts from the departments of neurology, hematology, rehabilitation, neuropsychology, radiology and clinical pharmacy, with the additional involvement of neurosurgery, rheumatology and cardiology as needed. These disciplines offer devoted expertise in: defining stroke risk factors; instituting and monitoring safe and effective approaches to both acute treatment and long-term secondary stroke prevention; and providing ongoing education to stroke patients, their families and their primary care providers. Patient needs are reassessed on an ongoing basis in follow-up, as these needs frequently vary with the degree of response to prior treatment and the continued development of the child. The multidisciplinary team of pediatric stroke experts at Children's is firmly committed to the belief that, in a rare disease where the risks of second events and long-term sequelae are often high, experienced and devoted specialists must work together throughout long-term follow-up in order to optimize the outcomes for children with stroke.

Stroke Program Services

Conditions treated

• Neonatal arterial ischemic stroke
• Childhood arterial ischemic stroke
• Recurrent transient ischemic attack
• Moyamoya syndrome/disease
• Neonatal hemorrhagic stroke
• Childhood hemorrhagic stroke
• Neonatal cerebral sinovenous thrombosis
• Childhood cerebral sinovenous thrombosis
  

Services offered

• Neurological evaluation
• Hematological evaluation
• Antithrombotic treatment and monitoring
• Rehabilitation Medicine evaluation and care
• Neuropsychological evaluation and care
• Neuro/neurovascular imaging
• Preventive medicine
• Clinical and translational research

Referrals, Transfers and Consultations

For outpatient clinic referrals, please contact Elizabeth Pounder, PA, clinic coordinator, at (720) 777-6578.

For consultations or acute stroke patient transfers to Children's, please contact the Neurologist on-call via the One Call physician's line at (720) 777-3999 or (800) 525-4871 who will assemble the Stroke Team and activate the Stroke Alert system, as appropriate.