Small Talk – Pediatric Stroke: Presentation, Evaluation, and Management

Welcome to the inaugural post of Small Talk; a new monthly section from emDOCs.  Every first Wednesday of the month we will release high yield PEM content written by PEM talent from around the country.  We hope you enjoy these reviews. Comments, questions, accolades or concerns: feel free to reach out to Joe Ravera, MD (pemgemspod@gmail.com).


Authors:  Peter Gutierrez, MD FAAPa,b,c; Abby Lewis, MDa,b; Jeffrey Okonye, MDa,b; Deborah Young, MD FAAPa,b,c // Reviewed by: Joe Ravera MD (@pemuvm1, Director of Pediatric Emergency Medicine, Assistant Professor of Surgery, Division of Emergency Medicine, University of Vermont Medical Center); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

a: Children’s Healthcare of Atlanta; b: Emory University School of Medicine Department of Pediatrics; c: Emory University School of Medicine Department of Emergency Medicine

Case

An 11-year-old male presents to the emergency department with intractable vomiting and headache that began this morning. After waking up at his typical type, he had an episode of emesis without blood or bile. He was able to eat a little bit of breakfast, but soon had multiple more episodes of emesis. Due to decreased energy, looking pale, and feeling weak, his mother called EMS for transport to the emergency department.

His mother states that he had a headache with vomiting about 4 weeks prior that spontaneously resolved. Since then, he has had 3 more episodes of a similar type of headache with nausea, all of which also spontaneously resolved. She denies noticing any fever, difficulty breathing, chest/abdominal pain, or change in vision. This morning, he reports some minor congestion, rhinorrhea, and cough.

Upon your arrival to the room, he is actively vomiting and appears pale, but is responsive and following commands. His initial vital signs include a temperature of 36.3C, pulse of 83, blood pressure 126/78 mm Hg, respiratory rate of 21, and pulse oximetry of 100% on room air.

His exam is remarkable for a 2-3 second capillary refill time, but is otherwise normal, including a quick neurologic exam. He is found to be orthostatic, with a significant increase in his heart rate going from sitting to standing.

You initially treat him as a vomiting illness, so you place an IV, obtain basic labs, and give a bolus of isotonic crystalloid fluid and a sublingual dose of ondansetron. His complexion, nausea, and cap refill improve after the interventions. His labs are unremarkable (and yes, COVID test was negative).

Unfortunately, as he gets up to go to the bathroom, he has another episode of vomiting, and you note he has an ataxic gait. With the non-specific history of recurrent headache and vomiting, you order a CT scan, which reveals a new, ill-defined hypodensity in the left cerebellar region concerning for infarction.


Presentation of Stroke in Children

Pediatric acute ischemic stroke is defined as a focal neurologic deficit lasting more than 24 hours attributed to causes of vascular origin in patients aged 30 days to 18 years of age (1). Perinatal and neonatal strokes are more common than pediatric strokes and are often multifactorial in nature with most factors related to pregnancy (2). The annual incidence of pediatric stroke ranges from 2.5-13 per 100,000 children per year. While cerebrovascular disease in children is rare, it can cause significant morbidity and mortality and ranks among the top 10 causes of death in children less than 1 year of age (3). Diagnosis of stroke in children is challenging as these patients often present without the classic focal neurologic signs often seen in adult stroke presentation.

Pediatric strokes are classified as ischemic or hemorrhagic in origin. In contrast with adults where approximately 15 percent of strokes are hemorrhagic, nearly half (45%) of strokes in children are hemorrhagic.  Moreover, approximately half of strokes occur in children with at least one predisposing condition. Furthermore, 25% of strokes occur in children with multiple underlying risk factors, so a thorough history and evaluation is required when even one risk factor is identified (1). Hospitalizations for stroke in the 5- to 14-year-old and 15- to 34-year-old age groups have increased in recent years likely due to an increase in modifiable risk factors (4). However, this number has likely also increased due to improved recognition of signs and symptoms and access to improved imaging modalities (4). Recognition of common childhood risk factors for stroke can help support the inclusion of stroke in the differential and diagnostic evaluation of a child presenting with a new neurologic deficit (4). A study by Yock et al. found that the median time from symptom onset to ED presentation was 21 hours for patients with ischemic stroke and 12 hours for patients with hemorrhagic stroke (5). In order to shorten time to diagnosis, there needs to be increased familiarity with presenting signs and symptoms of stroke in children.

Risk factors for pediatric stroke can be subdivided based on type of stroke. The two most common risk factors for acute ischemic stroke in children are arteriopathies (4) and congenital heart disease (1). Rates of stroke are highest after cardiac catheterization or surgery (4). Examples of arteriopathies include non-traumatic and traumatic dissections, vasculitis, Moya-Moya, post-varicella arteriopathy, transient cerebral arteriopathy, primary vascular disorders, and sickle cell disease. Sepsis is also a risk factor for ischemic stroke, with herpes and tuberculosis being the most common acute pathogens. Varicella infection can cause vasculopathy leading to stroke months after initial infection (4). Another risk factor for acute ischemic stroke is hypercoagulable conditions such as methylenetetrahydrofolate reductase deficiency, Factor V Leiden mutation, protein C deficiency, and homocystinuria. Lastly, ischemic stroke risk is increased in survivors of CNS tumors, Hodgkin’s lymphoma, and ALL who received prior radiation (4).

Risk factors for hemorrhagic stroke include vascular abnormalities, hematologic disorders, bleeding into an intracranial tumor, cavernous venous malformation, and vertebral artery dissection (4). Sickle cell disease is the most common hematologic cause, followed by prothrombotic disorders (1). Vascular arteriovenous malformations are the most common cause of hemorrhagic stroke in infancy (1).

Certain risk factors contribute to both ischemic and hemorrhagic stroke. Drug use is a common underlying stroke risk factor with amphetamines, ecstasy, cocaine, and phencyclidine being the most common culprits (1). Certain syndromic and metabolic disorders also have a predisposition to increased risk for stroke, such as Marfan syndrome, Tuberous Sclerosis, and folic and B12 deficiency (1).

The presentation and symptoms of stroke in children is not as readily recognizable as that of stroke in the adult population. The presenting signs of stroke can typically be classified based on the type of stroke. Focal features are the most common presenting feature in children with ischemic stroke (7). Hemiparesis is the most common focal feature, followed by facial weakness, speech disturbance, and visual disturbance (7). Seizure is also a common presenting symptom in children with ischemic stroke, with focal seizures being twice as likely to occur compared to generalized seizures. Approximately 75% of children under a year of age and 26% of those between 1-5 years of age will present with a seizure (7). Very few patients with acute ischemic stroke present with vomiting or altered mental status (5). A study by Yock-Corrales et al. found that most patients with ischemic stroke presented with a Glasgow Coma Scale score of 14 or greater and with at least one focal neurologic sign (5).

Alternatively, patients with hemorrhagic stroke are more likely to present with diffuse features such as altered mentation, headache, and vomiting (5). In the same study by Yock et al., Glasgow Coma Scale score in hemorrhagic stroke patients was found to be less than 14 for 38% of patients, and less than 8 for 19% of patients (5). The study found that 19% of hemorrhagic stroke patients required intubation in the ED for decreased GCS, while none of acute ischemic stroke patients required intubation (5). Presenting features for all types of stroke have not been shown to be significantly different based on sex (7). However, presenting features do vary based on age, with seizures being most common in children less than one year of age and headache being most common in children greater than six years of age (7). This difference is likely confounded by age-related reporting bias as self-reporting a symptom such as headache requires sufficient communication and development (7).


Stroke Mimickers

The differentiation of stroke in children from common mimickers can greatly expedite access to time-critical treatment, such as neuroimaging to confirm diagnosis, initiation of antithrombotic treatment, and neurosurgical intervention (6). Delays in stroke diagnosis in children are often due to lack of knowledge of presenting signs and symptoms and attributing symptoms to other problems (5). Other medical conditions which mimic stroke account for 11-21% of suspected acute stroke cases (4).

Stroke mimickers can be subdivided into benign and non-benign mimickers (4). Benign mimics of stroke include migraine, conversion disorder, musculoskeletal problems (4), Bell’s palsy, and syncope (6). Migraines account for 28% of abrupt onset focal dysfunction in children and are thought to be the most common stroke mimicker (2). Non-benign mimics of stroke include seizure, postictal (Todd’s) paralysis, tumors, encephalitis (5), posterior reversible leukoencephalopathy syndrome, metabolic stroke, CNS demyelination, subdural empyema, intracranial abscess/CNS infection, and drug toxicity (4). Neurotoxicity from certain chemotherapeutic agents can produce stroke-like symptoms, possibly due to cytotoxic edema instead of ischemia (8).

While it can be difficult to differentiate true stroke from stroke mimics, understanding the specific risk factors for pediatric stroke can help prioritize high-risk patients. Factors that are significantly associated with stroke mimics include the presence of other symptoms and the absence of neurological signs on exam (6). Delays in diagnosis of stroke in children limits access to hyperacute interventions that improve outcomes in adult patients (6).


Evaluation of Possible Stroke

After thorough exam and neurological assessment, if stroke is suspected, emergent neurological imaging is needed. In the pediatric population, MRI is the ideal imaging modality, if available. It can detect acute ischemic strokes (AIS), cerebral sinus venous thrombosis (CSVT) and hemorrhagic stroke (9). Additionally, an MRA head and neck should be obtained to view both intracranial and extracranial large arteries. If MRI is not available, the next best studies are a non-contrast CT head with a CT angiogram of the head and neck. CT is quick, confirms lesion locations, and depicts superficial and hemorrhagic lesions. Unfortunately, it can miss signs of AIS and CSVT if it is early in the disease process (10). Basic labs should be obtained, including CBC with differential, serum electrolytes, coagulation studies, and urine pregnancy (if applicable). Lumbar puncture, urine tox screening, and an echocardiogram are also potentially useful adjuncts. Lastly, if initial imaging is negative, but a strong clinical suspicion for stroke is present, conventional angiography should be pursued (11).


Management of Acute Stroke in Children

As with any emergent condition, the ABC’s need to be prioritized. However, there are a few special considerations with regards to the suspected pediatric stroke patient:

Airway: Patency may be affected if the area of ischemia involves the face or pharynx. While no data exists in children, substantial data in adults has evaluated the head positioning in ischemic stroke.  Based on this data, if there is no concern for increased ICP or aspiration, the patient can be laid flat in an attempt to increase CBF, although the clinical effect of this is unknown.  (12,13)

Breathing: The focus should be on avoiding hypoxia, which could result in secondary injury, using a goal of >94% SO2 (12,13).

Circulation:  It is important to aggressively treat hypotension with isotonic crystalloids, as early hypotension is associated with increased mortality. Children will often present with hypertension, which may be secondary to increased ICP in an attempt to maintain cerebral perfusion pressure. There is questionable utility in acutely lowering blood pressure, except in the setting of posterior reversible encephalopathy syndrome (PRES). In such cases, labetalol at 0.2mg/kg can be used with a goal of reducing blood pressure no more than 25% in the first 24 hours. Dropping blood pressure too precipitously can result in secondary ischemic insult (12,13).

Disability: Special attention should be paid to avoiding hypoglycemia, monitoring for and treating seizures, and observing for signs of increased intracranial pressure (12,13).

Exposure: Temperature control is also important, with a goal of a temperature less than 37.5C, utilizing acetaminophen for fever and/or a cooling blanket (12,13).

 

Subsequent management is dependent on the presence of ischemic stroke versus hemorrhagic stroke. Once hemorrhagic stroke has been ruled out, anticoagulation should be initiated with unfractionated heparin, unless there are any present contraindications to doing so (Moyamoya disease, thrombocytopenia with <50,000 platelets, active major bleeding, recent surgery, or history of heparin-induced thrombocytopenia) (12-14). Aspirin can be utilized in some patients with contraindications to heparin therapy (13).

Determining whether to initiate thrombolytic therapy for pediatric acute ischemic stroke is difficult, as it is not approved by the FDA for children, and it can be difficult to determine the time of onset of the neurologic deficit. However, there are consensus-based guidelines that exist that can be utilized should the child present within the appropriate time window and at a pediatric stroke center (13,14).

Similarly, mechanical thrombectomy is also not FDA approved for use in children, but recent studies have shown that it can be safe and efficacious in large vessel occlusions. One recent retrospective study showed significantly improved clinical and radiographic outcomes in a patient population that ranged from 1.8 to 18 years of age, with an average time to treatment of 13.7 hours and a window extending up to 72 hours (15).

If a hemorrhagic stroke is identified, the therapeutic considerations are less robust. In addition to supportive care, a pediatric neurosurgical service should be consulted to determine the need for evacuation of the bleed and identification of the source of the bleed. Any coagulation defects present should be reversed, such as thrombocytopenia or clotting factor deficiency (11).

Any patient with suspected or confirmed stroke from any etiology should be monitored in a pediatric intensive care unit (PICU) for at least 48 hours to observe for recurrence of stroke or worsening clinical status (14).


Management of Stroke in Sickle Cell Disease

Children with sickle cell disease are at increased risk for both ischemic and hemorrhagic stroke compared to the general population, with an incidence rate of 285 for every 100,000 children in one study (16). Initial evaluation should include neuroimaging, complete blood count, reticulocyte count, basic metabolic panel, coagulation studies, type and screen, and hemoglobin electrophoresis to assess the percentage of hemoglobin S present.  Unfortunately, there is little evidence about the optimal management of these patients. Generally accepted practices for the treatment of acute ischemic stroke in patients with sickle cell disease are to do basic supportive care as previously outlined, simple transfusions (if initial hemoglobin is less than 10 mg/dL to prevent hyperviscosity and further neuronal damage), and eventual exchange transfusion with a goal of getting the percentage of hemoglobin S to <30% (17). Anticoagulants, antiplatelet therapies, and thrombolytics are generally not indicated in this patient population.

The treatment of hemorrhagic stroke in children with sickle cell disease is no different from the general population.


Case Conclusion

You consult the pediatric neurology service, who recommend an emergent MRI/MRA of the head and neck. It identifies an acute infarct of the left superior cerebellar artery without hemorrhage and bilateral vertebral dissections. You begin anticoagulation with unfractionated heparin and admit him to the PICU for close monitoring.


Pearls and Pitfalls

  • There is often a significant delay in the treatment of acute stroke in pediatric patients due to delay in presentation and delay in diagnosis.
  • Remember the risk factors:
    • Ischemic stroke- arteriopathies, congenital heart disease, hypercoagulable conditions, and survivors of certain cancers.
    • Hemorrhagic stroke- hematologic abnormalities (especially sickle cell disease), vascular abnormalities, and vertebral artery dissections.
  • Mimickers for stroke include complicated migraine, conversion disorder, seizure, Todd’s paralysis, tumors, encephalitis, PRES, intracranial infection, or medication toxicity.
  • MRI with MRA of the brain and neck are the imaging modality of choice. If unavailable, non-contrasted CT of the head with CTA of the neck is an acceptable alternative. Conventional angiography can be pursued if initial imaging is negative with a high clinical suspicion for stroke.
  • Early management is largely supportive, with emphasis of keeping the head of the bed flat, avoiding hypoxia and hypotension, allowing for permissive hypertension, avoiding hypoglycemia, and aggressively treating seizures and fevers.
  • For acute ischemic stroke, anticoagulation is the mainstay of therapy, initially with unfractionated heparin, unless a contraindication is present.
  • Thrombolytic therapy should be used on a case-by-case basis in conjunction with a pediatric neurologist at a pediatric stroke center. A similar approach should be used for mechanical thrombectomy, if a large vessel is occluded.
  • For hemorrhagic stroke, treatment is largely supportive with consultation with a pediatric neurosurgeon regarding evacuation of the bleed and identifying its source.
  • In a patient with sickle cell disease, acute ischemic stroke should be treated with supportive care, simple transfusion (if hemoglobin less than 10 g/dl), and exchange transfusion. Hemorrhagic stroke is treated similarly to those without sickle cell disease.
  • All patients with stroke should be dispositioned to a PICU.

References

  1. Panagopoulos D, Karydakis P, Markogiannakis G, et al. Pediatric arterial ischemic stroke: Overview of the literature and of the most cited relevant articles, Interdisciplinary Neurosurgery, Volume 23, 2021, 100924, ISSN 2214-7519
  2. Chulpayev B, Benitez S, Dine S, et al. Pediatric Ischemic Strokes. Advances in Clinical Radiology. Vol 2, 2020; 319-324
  3. Zimmer JA, Garg BP, Williams LS, et al. Age-related variation in presenting signs of childhood arterial ischemic stroke. Pediatr Neurol. 2007 Sep;37(3):171-5. doi: 10.1016/j.pediatrneurol.2007.05.010. PMID: 17765804.
  4. Morgan, L. Evaluation and Management of the Child With Suspected Acute Stroke. Clinical Pediatric Emergency Medicine, Volume 16, Issue 1, 2015, Pages 29-36, ISSN 1522-8401
  5. Yock-Corrales A, Mackay MT, Mosley I, et al. Acute childhood arterial ischemic and hemorrhagic stroke in the emergency department. Ann Emerg Med. 2011 Aug;58(2):156-63. doi: 10.1016/j.annemergmed.2010.10.013. Epub 2011 Feb 18. PMID: 21310508.
  6. Mackay MT, Yock-Corrales A, Churilov L, et al. Differentiating Childhood Stroke From Mimics in the Emergency Department. Stroke. 2016 Oct;47(10):2476-81. doi: 10.1161/STROKEAHA.116.014179. Epub 2016 Sep 6. PMID: 27601378; PMCID: PMC5049943.
  7. Mallick AA, Ganesan V, Kirkham FJ, et al. Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study. Lancet Neurol. 2014 Jan;13(1):35-43. doi: 10.1016/S1474-4422(13)70290-4. Epub 2013 Dec 2. PMID: 24304598.
  8. Willis E, Samanta D, Kanfi A. A Not Uncommon Cause of Stroke Mimicker in Children. Pediatr Neurol. 2018 Mar;80:92-93. doi: 10.1016/j.pediatrneurol.2017.11.001. Epub 2017 Nov 13. PMID: 29229230.
  9. Baldovsky M and Okada P. “Pediatric stroke in the emergency department.” Journal of the American College of Emergency Physicians open vol. 1,6 1578-1586. 6 Oct. 2020, doi:10.1002/emp2.12275
  10. Freundlich, Charise L et al. “Pediatric stroke.” Emergency Medicine Clinics of North America vol. 30,3 (2012): 805-28. doi:10.1016/j.emc.2012.05.005
  11. Roach, E Steve et al. “Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young.” Stroke vol. 39,9 (2008): 2644-91. doi:10.1161/STROKEAHA.108.189696
  12. McKinney S, Magruder J, Abramo T. “Update in Pediatric Stroke Protocols.” Pediatr Emer Care. 2018;34:810-817
  13. Amlie-Lefond C, Wainwright M. “Organizing for acute arterial ischemic stroke in children.” Stroke. 2019;50:3662-3668.
  14. Amlie-Lefond C. “Evaluation and Acute Management of Ischemic Stroke in Infants and Children.” Continuum. 2018;24:150–170.
  15. Huang Cobb M, Laarakker A, Gonzaolez F, et al. “Endovascular Therapies for Children with Ischemic Stroke in Children.” Stroke. 2017;48:2026-2030.
  16. Roach ES, Golomb M, Adams R, et al. “Management of Stroke in Infants and Children.” Stroke. 2008;39:2644-2691.
  17. Earley CJ, Kittner SJ, Feeser BR, et al. Stroke in children and sickle-cell disease: Baltimore-Washington Cooperative Young Stroke Study. Neurology. 1998;51:169–176.
  18. Kassim A, Galdanci N, Pruthi S, et al. “How I Treat and Manage Strokes in Sickle Cell Disease.” 2015;125(22):3401–3410.

 

 

 

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