Pediatric Stroke Part 1: Disease/Disorder and Essentials of Assessment

Disease/Disorder

Definition

Stroke described a cerebrovascular event that causes a disturbance in blood flow to a brain region. This includes various conditions such as arterial ischemic stroke, cerebral venous thromboembolism, infarction, and non-traumatic brain hemorrhage.⁴

Etiology

Hemorrhagic stroke occurs when intracranial vessels rupture and bleed into tissues due to arteriovenous malformation (AVM), aneurysm, traumatic injury, hematological disorders, brain tumors, and rare entities like moyamoya disease or septicemia. The most common location of hemorrhage is cerebral, followed by intraventricular and subarachnoid.⁶

Ischemic strokes result from an interruption in blood flow due to inadequate systolic cardiac function, inappropriate vasoconstriction, or thromboembolic occlusion of a vessel. Arteriopathies are the most important risk factor for arterial ischemic stroke (AIS).

The Childhood AIS Standardized Classification and Diagnostic Evaluation (CASCADE) criteria describe strokes according to their distribution and progression during the acute and chronic phases. It includes small vessel arteriopathy, focal cerebral arteriopathy (FCA), bilateral cerebral arteriopathy, aortic/cervical arteriopathy, cardioembolic, and multifactorial. FCA includes transient cerebral arteriopathy and other forms of arteriopathy that present as a transient worsening over the first 3-6 months, followed by improvement or resolution.²⁴

The perinatal AIS is often multifactorial due to the hypercoagulable nature of pregnancy and the complex interaction between maternal and fetal circulations. There is a consistent association of infection, congenital heart disease, and hypercoagulable disorders with perinatal AIS.⁴

Epidemiology including risk factors and primary prevention

The estimated incidence of stroke in children ranges from 2 to 13 per 100,000 children per year.¹ Incidence of pediatric stroke can be categorized by age at onset, etiology, and ethnicity.

Pediatric Stroke based on age is subgrouped into

• Perinatal stroke: This type of stroke occurs before 29 days of life.⁴ The incidence of perinatal stroke is 1 in 2300 to 5000 births.²
• Childhood stroke: This type of stroke occurs between 29 days and 20 years of age.⁴ Childhood stroke has an incidence of 2-13 per 100,000.²

Pediatric Stroke by etiology

• Hemorrhagic Stroke impact 2.3 million individuals under 20 years old. The average annual incidence rate is 1.4 per 100,000 children.³ Ischemic stroke are more common among younger children and males. The annual incidence rates range from 0.6 to 7.9 per 100,000 children per year. Ischemic strokes constitute around 55% of pediatric strokes, with basilar artery strokes having a lower incidence rate.⁴
• Moyamoya and arteriovenous malformations represent, significant sources of ischemic and hemorrhagic stroke in children after the first year of life.²² Moyamoya disease is an arteriopathy of unknown origin affecting the branches of the internal carotid artery. The arteriopathy can present as an isolated condition affecting both sides of the brain (“moyamoya disease”) or as a unilateral condition found in association with systemic disorders (“moyamoya syndrome”).The ischemia resulting from the narrowing predisposes children to transient ischemic attacks and stroke.²⁰ Moyamoya is implicated in 6% of pediatric ischemic strokes. The incidence rates in the US are approximately 0.086 per 100,000 patients.²¹ AVMs are abnormal connections between arteries and veins bypassing capillaries, featuring coiled and tortuous vascular networks. AVMs are the most frequent intracranial circulatory abnormality and a leading cause of spontaneous intraparenchymal hemorrhage in pediatric cases. Their prevalence is estimated between 0.06% and 0.11% based on autopsy studies.²³

Pediatric Stroke by ethnicity

• Asians and African American have higher risk of AIS.⁸
• Moyamoya disease is the most common pediatric cerebrovascular disease in East Asian populations with an incidence rate of 0.94/100,000 in Japan, and 2.3/100,000 in South Korea.^25,26
• African Americans are affected more commonly than Caucasian or Hispanics even when corrected for sickle cell disease. Sickle cell disease (SCD) is a very common cause of pediatric stroke. 11% of patients with SCD will have a clinically apparent stroke by age 20. Strokes may occur as early as 18 months of age, but most children present after five years of age.¹¹

Morbidity and Mortality

Pediatric stroke leads to significant morbidity and mortality. Roughly 10–25% of children with a stroke will succumb to death. Up to 25% of children may have recurrence, mostly due to an underlying etiology, and up to 66% will have persistent neurological deficits or develop subsequent seizure disorders, learning, or developmental problems.²⁷

Risk factors

Primary risk factors for pediatric stroke encompass vasculopathies such as arteriovenous malformation (AVM) and Moyamoya disease (MMD), infections, cardiac issues, and coagulopathies. Additional factors comprise hematological and renal diseases, autoimmune disorders, and head trauma.⁴ However, it’s important to note that no single risk factor leads to reduced neurological damage.

Primary prevention in select populations

• Sickle cell disease: Periodic blood transfusion is recommended to reduce risk of first stroke if two transcranial Doppler studies demonstrate high velocity flow in the middle cerebral artery or distal internal carotid artery.¹¹ Use of hydroxyurea is indicated to prevent sickling.
• Routine vaccines have been shown to protect against pediatric stroke. This is likely due to the direct protective effects of vaccination against infections. The study was unable to show if any one vaccine was more protective, rather it is thought that overall vaccinations are protective.¹²

Patho-anatomy/physiology

The middle cerebral artery is the most commonly affected distribution in ischemic strokes. Hemorrhagic strokes are typically supratentorial. Cerebral venous sinus thrombosis occurs more often in the superficial venous system than within the deep veins.¹

Ischemic alterations at the cellular level initiate a cascade of processes leading to tissue necrosis. Cellular damage prompts the activation of enzymes responsible for breaking down proteins, genetic material, and lipids. Additionally, the affected cells initiate additional harm by activating N-methyl-D-aspartate receptors and generating reactive oxygen species. Following the initial injury, inflammatory cells swiftly migrate to the affected site. Subsequent hours to days witness further alterations surrounding the ischemic area.¹

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

New onset/acute^1,4

• Abrupt onset of focal neurologic signs or rapid decline in neurologic function. Altered mental status or seizure may be the only presenting symptom. In Intracranial hemorrhage: nausea, vomiting, and headache.
• Seizures are present in 94% of neonatal AIS and in 17% of childhood AIS.¹³
• Signs and symptoms may be subtle, especially in infants. Nonspecific symptoms seen in pediatric stroke, include decreased level of consciousness, headache, and vomiting.⁶   However, hemiparesis and facial weakness, similar to adult presentation, are often seen. Despite this, the diagnosis of Pediatric Stroke is commonly delayed. ⁶This is in part due to poor awareness among professionals about pediatric strokes because of low prevalence, keeping pediatric stroke lower on the differential, and the risk factors for children are very different than that of adults.⁶ The median time from symptom onset to diagnosis of AIS was around 23 hours.¹⁴
• FAST (Face, Arms, Speech Time) criteria is a method to screen for stroke (Royal College of Pediatrics and Child Health Full Recommendations for Childhood Stroke).¹⁵

Subacute

Patients who have had previously unrecognized or misdiagnosed strokes may present in the subacute period with a history of stepwise or progressive decline in function over time.

Chronic/stable

Most studies estimate that over 50% of pediatric stroke patients will have long-lasting or permanent neurologic sequelae.¹¹ Most pediatric stroke patients achieved independence with activities of daily living (ADL). However, children were more likely to regain function in a previously learned domain than accomplish a new skill. Thus, younger age is a risk factor that may limit progress in ADL independence.⁷

In the chronic phase, regression in function is rare. Recurrent stroke should be suspected if a child develops new deficits.⁷

Specific secondary or associated conditions and complications

• Neurologic deficits (moderate to severe impairment)
• Hemiparesis²⁰
• Cerebral Palsy
• Seizure disorder
  • Epilepsy-Can be as high as 50%¹³  
  • Infantile Spasm-around 25%¹³
• Hemiplegia/quadriplegia
• Spasticity
• Visual deficits
• Speech and language impairment
• Dysphagia-around 40% in neonates and children¹⁸
• Oral motor-around 25% in children and neonates¹⁸
• Motor speech-around 25% in children and neonates¹⁸
• Cognitive impairment
• Head Growth Deceleration-associated with poor outcomes
• Obstructive Sleep Apnea

Essentials of Assessment

History

A thorough history in a child with suspected stroke should include

• Time of symptom onset
• Specific sensory or motor deficits, vision changes, dysphagia
• Seizure activity
• Headache
• Trauma
• Screening for potential risk factors, including recent infections
• Birth and developmental history
• Family history of clots, miscarriages, drug exposure

Physical examination

Initial examination

• Closely monitor vital signs acutely.
• Document seizure activity.
• Look for signs of increased intracranial pressure, such as papilledema.
• A full neurologic exam should be completed, including mental status, cranial nerves, motor function, sensory testing, reflexes, and coordination. Later stages: assess ADL skills, transfer skills, other functional mobility.

Functional assessment

The Pediatric NIH Stroke Scale (PedNIHSS) can be used to quantitate stroke severity in the short-term and is adapted for the pediatric population. A guide to using the scale is available online.²¹

The Pediatric Stroke Outcome Measure (PSOM) is a validated tool used specifically for the pediatric stroke population. PSOM is used to predict future long-term functional outcomes in children after a stroke and when used in conjunction with disability measures that measure impact of stroke in activities and participation, it serves as standard of care for comprehensive evaluation in this population .²²

Laboratory studies

Laboratory studies that may facilitate the evaluation of a patient with suspected stroke include:

• A complete blood count (anemia, platelet disorders). If abnormal, peripheral blood smear to further characterize.
• A metabolic panel (electrolyte abnormalities, dehydration).
• Coagulation panel (APTT, PT, lupus anticoagulant, anti-cardiolipin antibodies, ANA, anti-B2GP1 antibodies, platelet aggregation, factor VIII activity, d-dimers, thrombin time, factor V Leiden, Protein C antigen, Protein S antigen, Plasminogen activator inhibitor, homocysteine, coagulation factor assays)
• Inflammatory markers including sedimentation rate and C-reactive protein (inflammatory or infectious conditions).
• Maternal labs for syphilis testing (VDRL, toxicology screen)

Imaging

MRI, when available, is preferred for first line imaging study for a child with stroke like symptoms. The optimal imaging study is somewhat dependent on the child’s clinical stability. If MRI is not available, then CT brain can be used.²³ CT/MRI differentiates hemorrhagic verses ischemic lesions which also guide in formulating plan for using thrombolytics which are contra-indicated in hemorrhagic strokes.

CT brain quickly and accurately depicts superficial or hemorrhagic lesions and confirms the lesion location. However, venous thrombosis and early acute ischemic stroke (AIS) are easily missed with CT. Reports have shown CT can miss up to 47% of acute ischemic strokes.²³

MRI, magnetic resonance angiography (MRA), and magnetic venography (MRV) may more accurately define the site of an arterial or venous occlusion without exposure to ionizing radiation. Additionally, MR studies often demonstrate associated parenchymal abnormalities more clearly, including non-ischemic lesions that clinically mimic arterial or venous stroke such as soft tissue lesions or quantitative hemometabolic markers.²³

Diffusion-weighted imaging (DWI) can confirm the presence and location of an infarction earlier than other MRA sequences or CT. This DWI study can be performed in around 30 seconds.²⁶

Other advancing MRI techniques include pH-weighted arterial spin labeling (AST), amide proton transfer (APT), vessel wall imaging, blood oxygen level-dependent (BOLD), T2-relaxation-under-spin lagging, asymmetric spin echo and edited spectroscopy.²³

CT angiography (CTA) is an accurate means of identifying primary vascular abnormalities when there is an unexplained hemorrhagic lesion. CTA can fail to differentiate between a stroke and a stroke mimic, like hemiplegic migraine and seizure with postictal paralysis. CTA requires a correctly time contrast injection through a small intravenous line while exposing a child to increased radiation making it not recommended as the first line approach. Catheter angiography (CA) is technically more difficult in babies and tends to be done only when endovascular surgical intervention is anticipated.²³

Vascular imaging by MRI or CTA is done either at the same time or after the initial imaging study due to the high likelihood of an arteriopathy, which is a poor prognostic factor and has a higher chance of stroke recurrence. Follow-up imaging 6 to 12 weeks after the initial stroke is recommended to monitor arteriopathy changes or to find previously missed arteriopathy and/or new infarcts.²

Supplemental assessment tools

ECG and echocardiogram should be obtained after acute ischemic stroke (arrhythmia, thrombus, or congenital cardiac defects). Generalized activity suppression or subtle presentation of focal seizure activity can be seen on EEG.²⁴

Neuropsychology testing plays an important role in assessing cognitive and memory deficits.²³

Environmental

Prior to discharge, consider the physical accessibility of the child’s discharge destination. A thorough discussion with caregivers may help to identify additional equipment or home adaptation needs.²⁵

Social role and social support system

After assessing the child’s mobility, independence with activities of daily living, speech, and cognitive changes, caregivers may find that the child will need more frequent assistance or more intensive care than they previously required. Functional parenting styles, positive discipline practices, and autonomy-supportive strategies for task engagement should be encouraged when intervening with these children. Parents should be supported to engage in these practices in all aspects of daily activities.²⁶

Mentoring support groups such as hemi-kids and CHASA are available in the community.

Mental health illnesses are a concern in both the child and the family members. In the child post stroke, depression, anxiety, and post-traumatic stress disorder (PTSD) are common. PTSD, depression and anxiety are common in the mothers, while PTSD and depression are seen in fathers of children after a stroke.²⁶

Rehabilitation Management and Treatments

See Pediatric Stroke Part 2

Cutting Edge/Emerging and Unique Concepts and Practice

See Pediatric Stroke Part 2

Gaps in the Evidence-Based Knowledge

See Pediatric Stroke Part 2

References

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6. Meyer-Heim AD, Boltshauser E. Spontaneous intracranial hemorrhage in children: aetiology, presentation and outcome. Brain Dev. 2003 Sep;25(6):416-21. doi: 10.1016/s0387-7604(03)00029-9. PMID: 12907276.
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8. Fullerton HJ, Hills NK, Elkind MS, Dowling MM, Wintermark M, Glaser CA, Tan M, Rivkin MJ, Titomanlio L, Barkovich AJ, deVeber GA; VIPS Investigators. Infection, vaccination, and childhood arterial ischemic stroke: Results of the VIPS study. Neurology. 2015 Oct 27;85(17):1459-66. doi: 10.1212/WNL.0000000000002065. Epub 2015 Sep 30. PMID: 26423434; PMCID: PMC4631070.
9. Billinghurst LL, Beslow LA, Abend NS, Uohara M, Jastrzab L, Licht DJ, Ichord RN. Incidence and predictors of epilepsy after pediatric arterial ischemic stroke. Neurology. 2017 Feb 14;88(7):630-637. doi: 10.1212/WNL.0000000000003603. Epub 2017 Jan 13. PMID: 28087825; PMCID: PMC5317388.
10. Rafay MF, Pontigon AM, Chiang J, Adams M, Jarvis DA, Silver F, Macgregor D, Deveber GA. Delay to diagnosis in acute pediatric arterial ischemic stroke. Stroke. 2009 Jan;40(1):58-64. doi: 10.1161/STROKEAHA.108.519066. Epub 2008 Sep 18. PMID: 18802206.
11. Royal College of Pediatrics and Child Health. Full recommendations for childhood stroke. 2017. https://www.rcpch.ac.uk/sites/default/files/2019-04/20160314%20Full%20Recommendations%2008.04.19.pdf
12. Sherman V, Martino R, Bhathal I, DeVeber MG, Dlamini N, MacGregor D, Pulcine E, Beal DS, Thorpe KE, Moharir M. Swallowing, Oral Motor, Motor Speech, and Language Impairments Following Acute Pediatric Ischemic Stroke. Stroke. 2021 Mar 1:STROKEAHA120031893. doi: 10.1161/STROKEAHA.120.031893. Epub ahead of print. PMID: 33641384.
13. Ullman, N., & Licht, D. J. (2023). Grand challenges in pediatric stroke. Frontiers in Stroke. https://doi.org/10.3389/fstro.2023.1204718
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15. Slim, M, Fox, CK, Friefeld, S, Nomazulu, D, Westmacott, R, Moharir, M, MacGregor D, deVeber, G. Validation of the pediatric stroke outcomes measures for classifying overall neurological deficit. Pediatric Research. 2020, 88, 234-242, doi: 101038/s41390-020-0842-5
16. Donahue MJ, Dlamini N, Bhatia A, Jordan LC. Neuroimaging Advances in Pediatric Stroke. Stroke. 2019 Feb;50(2):240-248. doi: 10.1161/STROKEAHA.118.020478. PMID: 30661496; PMCID: PMC6450544.
17. Hollist M, Au K, Morgan L, Shetty PA, Rane R, Hollist A, Amaniampong A, Kirmani BF. Pediatric Stroke: Overview and Recent Updates. Aging Dis. 2021 Jul 1;12(4):1043-1055. doi: 10.14336/AD.2021.0219. PMID: 34221548; PMCID: PMC8219494.
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21. Ibrahimi, D.M., Tamargo, R.J. & Ahn, E.S. Moyamoya disease in children. Childs Nerv Syst 26, 1297–1308 (2010). https://doi.org/10.1007/s00381-010-1209-8
22. Smith, Edward R.. Structural causes of ischemic and hemorrhagic stroke in children: moyamoya and arteriovenous malformations. Current Opinion in Pediatrics 27(6):p 706-711, December 2015. | DOI: 10.1097/MOP.0000000000000280
23. Mohammad El-Ghanem, Tareq Kass-Hout, Omar Kass-Hout, Yazan J. Alderazi, Krishna Amuluru, Fawaz Al-Mufti, Charles J. Prestigiacomo, Chirag D. Gandhi; Arteriovenous Malformations in the Pediatric Population: Review of the Existing Literature. Interventional Neurology 16 September 2016; 5 (3-4): 218–225.
24. Bernard, Timothy J et al. “Towards a Consensus-Based Classification of Childhood Arterial Ischemic Stroke.” Stroke (1970) 43.2 (2012): 371–377. Web.
25. Baba T, Houkin K, Kuroda S. Novel epidemiological features of moyamoya disease. J Neurol Neurosurg Psychiatry. 2008;79:900–904. doi: 10.1136/jnnp.2007.130666.
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Original Version of the Topic

Edward Hurvitz, MD and Alecia Daunter, MD. Pediatric Stroke. 9/20/2013

Previous Revision(s) of the Topic

Rajashree Srinivasan, MD and Saylee Dhamdhere MD, UTSW. Pediatric Stroke. 8/8/2017

Sathya Vadivelu, DO, Joshua Kaseff, MS. Pediatric Stroke. 4/20/2021

Author Disclosures

Michael Nguyen, MD, MPH
Nothing to Disclose

Mara Martinez Santori, MD, MS
Nothing to Disclose

Catherine Velasquez Ignacio, MD
Nothing to Disclose

Sonia Mejia, MD
Nothing to Disclose

Alyssa Miller, BS
Nothing to Disclose

Elizabeth Chan, MD
Nothing to Disclose