Stroke is a neurological injury caused by the occlusion or rupture of cerebral blood vessels. Strokes are primarily classified as ischemic, hemorrhagic or combination (e.g. thrombotic stroke with hemorrhagic transformation)
Pediatric stroke was reported in the earliest medical literature as ‘cerebral apoplexy’ ‘acute infantile hemiplegia’ ‘acute hemiplegia of childhood’ ‘congenital hemiplegia’ and ‘hemiplegic cerebral palsy’.
First documented case of pediatric stroke in the medical literature was presented by Thomas Willis (1621–1675) in the 17th century.
Giovanni Battista Morgagni’s (1682–1771) proposed that lesions occur in the brain opposite the site of hemiplegia.
Matthew Baillie (1761–1823), first described cerebral hemorrhage as the consequence of disease of the blood vessels of the brain.
Hemorrhagic stroke occurs when intracranial vessels rupture and bleed into cerebral tissues due to malformation, traumatic injury, and/or bleeding diathesis. Cerebral venous sinus thrombosis results in back pressure and leakage of blood into brain tissue, or loss of flow into areas of the brain due to the higher pressure.
Ischemic strokes result from an interruption in blood flow due to inadequate systolic cardiac function, inappropriate vasoconstriction, or thromboembolic occlusion of a vessel.
Epidemiology including risk factors and primary prevention
The estimated incidence of stroke in children ranges 2 to 13 per 100,000 children per year.
A retrospective cohort study of 2.3 million children (age <20 years) followed for more than a decade revealed an average annual incidence rate of 1.4 per 100,000 children for hemorrhagic stroke. Among hemorrhagic stroke subtypes, the estimated annual incidence of intra cerebral hemorrhage in developed countries ranges from 1.1 to 5.2 per 100,000 children, while the estimated annual incidence of subarachnoid hemorrhage is 0.4 per 100,000 children. Annual incidence rates of arterial ischemic stroke (AIS) in infants and children range from 0.6 to 7.9/100,000 children per year. AIS is more common in the younger age group whereas hemorrhagic strokes occur more frequently in older Children’s Medical Center. Pediatric ischemic stroke is more common in boys than in girls
Approximately 55% of pediatric strokes are ischemic, (in adults, greater than 80%).Basilar artery stroke: 0.037 per 100,000 children per year.
Ethnicity: 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 Sickle cell disease will have a clinically apparent stroke by age of 20 years. Strokes may occur as early as 18 months of age, but most children present after five years of age. 25% of patients with Sickle cell disease will have a stroke by age 45.
Risk factors include: 1,5
- Trauma: Children who have experienced head and neck trauma are at risk of developing an ischemic event subsequent to dissection of the carotid or vertebral arteries, hyperextension or rotational injuries
- Illicit drug use.
- Hypercoagulable states: such as sickle cell anemia, protein C or S deficiency, fibrinogen disorders, thalassemia, thrombophilia, oral contraceptives, chemotherapeutic agents, malignancy, pregnancy.
- Other genetic disorders: neurofibromatosis type 1, connective tissue disorders, disorders of metabolism.
- Arteriovenous malformations (AVM) are the most common cause of hemorrhagic stroke after infancy, but can also cause thrombotic stroke
- Vasculitis including Moyamoya, autoimmune, primary angitis of CNS, collagen vascular disease, systemic vasculitides, vasculopathies1
- Migraine with aura, over use of ergot alkaloids (especially in those of childbearing age and those using oral contraceptives).
- Substance abuse with amphetamines, ecstasy, cocaine, phencyclidine (PCP), and glue sniffing. Stimulants and heroin can also cause vasculopathies predisposing to infarction.
- Cardiac: congenital heart disease, cardiomyopathy, arrhythmia, valvular disease, cardiac tumors, carditis, artificial valves, endocarditis, cardiac surgeries1
- Children with cancer are at increased risk for AIS as a result of their disease, subsequent treatment, and susceptibility to infection.
Predisposing factors for Pediatric arterial ischemic stroke (AIS)2. is mineralizing angiopathy and mild trauma immediately or shortly preceding stroke onset.
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.3,5 Use of hydroxyurea is indicated to prevent sickling.
- Administering folic acid, niacin and B12 in an effort to normalize homocysteine levels is beneficial.
- Cardiac: Aspirin and anti-coagulants have been used to reduce the risk of cardiac origin stroke. Surgical repair can reduce risk of embolic stroke.5
- Activity precautions in patients with stroke resulting from bleeding diathesis especially resistive exercises
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
On a cellular level, ischemic changes precipitate a series of events that result in tissue necrosis. Cell injury leads to activation of enzymes that degrade the cell’s proteins, genetic material, and lipids. The injured cells also trigger further cellular injury through activation of N-methyl-D-aspartate receptors and formation of reactive oxygen species. Soon after the initial insult, there is an influx of inflammatory cells to the site of injury. Further changes take place in the area surrounding the ischemic focus over subsequent hours to days.1
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
- 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.
- Signs and symptoms may be subtle, especially in infants.
- 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.
- Most studies estimate that over 50% of pediatric stroke patients will have long-lasting or permanent neurologic sequelae.5
- In one study, the majority of pediatric stroke patients achieved independence with activities of daily living (ADL) Children were more likely to regain function in a previously learned domain than achieve a new skill. Thus, younger age is a risk factor which may limit progress in ADL independence.4
- In the chronic phase, regression in function is rare.4 Recurrent stroke should be suspected if a child develops new deficits
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 will have a recurrence, and up to 66% will have persistent neurological deficits or develop subsequent seizure disorders, learning, or developmental problems. All of the above may impact a child’s mobility and/or independence with activities of daily living, as well as achievement of desired adult outcomes.
Specific secondary or associated conditions and complications
Sequelae of pediatric stroke may include:
- Seizure disorder.
- Muscle contractures.
- Visual deficits.
- Speech and language impairment.
- Cognitive impairment.
All of the above may impact a child’s mobility and/or independence with activities of daily living.
2. ESSENTIALS OF ASSESSMENT
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.
- Screening for potential risk factors, including recent infections.
- Birth and developmental history
- Family history of clots, miscarriages, drug exposure
- 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.
The Pediatric NIH Stroke Scale (PedNIHSS) can be used to quantitate stroke severity and is adapted for the pediatric population. A guide to using the scale is available online.13
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)
The optimal imaging study is somewhat dependent on the child’s clinical stability.
Cranial ultrasound is safe and readily available, but it may miss superficial and ischemic lesions and cannot be done after the fontanelles are closed. It is primarily used to evaluate extra cranial blood vessels.
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.
MRI, magnetic resonance angiography (MRA), and magnetic venography (MRV) may more accurately define the site of an arterial or venous occlusion. Additionally, MR studies often demonstrate associated parenchymal abnormalities more clearly, including non ischemic lesions that clinically mimic arterial or venous stroke.
CT/MRI differentiates hemorrhagic verses ischemic lesions which also guide in formulating plan for using thrombolytics which are contra-indicated in hemorrhagic strokes
Diffusion-weighted imaging can confirm the presence and location of an infarction earlier than other MRA sequences or CT
CT angiography (CTA) is an accurate means of identifying primary vascular abnormalities when there is an unexplained hemorrhagic lesion.
Catheter angiography (CA) is technically more difficult in babies and tends to be done only when endovascular surgical intervention is anticipated.
Supplemental assessment tools
EKG and echocardiogram should be obtained after acute ischemic stroke (arrhythmia, thrombus, or congenital cardiac defects).1
Generalized activity suppression or subtle presentation of focal seizure activity can be seen on EEG
Neuropsychology testing plays an important role in assessing cognitive and memory deficits
Early predictions of outcomes
For ischemic strokes, a low PedNIHSS is the best predictor of having no symptoms or mild symptoms in 3-6 months.6
Hemorrhagic strokes cause higher mortality in the acute phase. Most studies have found an in-hospital mortality rate of 6-9% for pediatric hemorrhagic strokes.6 Larger volume of hemorrhage correlates to worse 30-day outcomes.7
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.
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.
Mentoring support groups such as hemi-kids and CHASA are available in the community.
3. REHABILITATION MANAGEMENT AND TREATMENTS
Available or current treatment guidelines
Class I Recommendations
- Early dysphagia screening is recommended for acute stroke patients to identify dysphagia or aspiration, which can lead to pneumonia, malnutrition, dehydration, and other complications
- Enteral feedings (tube feedings) should be initiated within 7 days after stroke for patients who cannot safely swallow; NG tube should be used short term (2-3 weeks) for nutritional support.
- Nasogastric tube feeding should be used for short term (2–3 weeks) nutritional support for patients who cannot swallow safely
- Enriched environments to increase engagement with cognitive activities are recommended
- Treatment for aphasia should include communication partner training.
- Targeted injection of botulinum toxin into localized upper limb muscles is recommended to reduce spasticity
- Individuals with stroke should be evaluated for balance, balance confidence, and fall risk
- Intensive, repetitive, mobility- task training is recommended for all individuals with gait limitations after stroke.
- An AFO after stroke is recommended in individuals with remediable gait impairments ( foot drop) to compensate for foot drop and to improve mobility
- After completion of formal stroke rehabilitation, participation in a program of exercise or physical activity at home or in the community is recommended.
- Goal-directed upper limb training has been successful in enhancing functional outcomes of children with hemiplegia. Motivation has been identified as the only individual characteristic unrelated to health state, that influences motor change and functional outcomes for children with CP engaged in rehabilitation programs. Children’s persistence with object-oriented tasks as well as manual abilities needs to be considered when undertaking Upper limb Intervention.
Class II Recommendations:
- Nutritional supplements are reasonable to consider for patients who are malnourished or at risk of malnourishment
- Incorporating principles of neuroplasticity into dysphagia rehabilitation strategies/interventions is reasonable
- Compensatory strategies may be considered to improve memory functions, including the use of internalized strategies (e.g., visual imagery, semantic organization, and spaced practice) and external memory assistive technology (e.g., notebooks, paging systems, computers, and other prompting devices).
- Music therapy may be reasonable for improving verbal memory.
- Strategy training or gesture training for apraxia may be considered.
- Group treatment may be useful across the continuum of care, including the use of community-based aphasia groups
- Telerehabilitation may be useful when face-to face treatment is impossible or impractical
- Physical modalities such as NMES or vibration applied to spastic muscles may be reasonable to improve spasticity temporarily as an adjunct to rehabilitation therapy
- Postural training and task-oriented therapy may be considered for rehabilitation of ataxia.
- Incorporating cardiovascular exercise and strengthening interventions is reasonable to consider for recovery of gait capacity and gait related mobility tasks.
- Robot-assisted movement training to improve motor function and mobility after stroke in combination with conventional therapy may be considered.
Class III Recommendations:
- Drug therapy, NMES, pharyngeal electrical stimulation, physical stimulation, tDCS, and transcranial magnetic stimulation are of uncertain benefit and not currently recommended
Anodal tDCS over the left dorsolateral prefrontal cortex to improve language-based complex attention (working memory) remains experimental.
At different disease stages
- Supportive care, including hydration and management of hypoxia or hypotension. Seizure activity should be treated. Monitor for signs of increased intracranial pressure.
- Neurology or a stroke consult service should be involved as early as possible in the acute setting for making timely decisions for thrombolytic therapies for eligible patients. Guidelines have not yet been established for using tissue plasminogen activator in the pediatric population. In 2010, the National Institute of Neurological disorders and stroke (NINDS) funded the first prospective treatment trial in acute pediatric stroke, the Thrombolysis in Pediatric Stroke (TIPS) trial. The former TIPS sites have continued to identify patients who would have been eligible for TIPS and have treated children with TPA using the TIPS protocol. Heparin is not used widely in children with perinatal AIS, although children with severe pro-thrombotic disorders or with cardiac or multiple systemic thrombi may benefit.35
- Surgical evacuation of hemorrhage is not typically indicated, but may be useful in select patients with persistently increased intracranial pressure refractory to medical management.
- Markedly low platelet counts and factor deficiencies should be corrected. Vitamin K deficiency may be an issue in areas of the world where vitamin K is not routinely administered to newborns, in infants with biliary atresia, or in babies whose mothers ingested warfarin, phenytoin, or barbiturates during pregnancy.
- Thorough documentation of deficits will facilitate involvement of appropriate members of the rehabilitation team.
Sub acute, chronic/stable
- Secondary prevention and disease management strategies
- Sickle cell patients with confirmed infarct will require a long-term red blood cell transfusion program for secondary prevention. Those who cannot receive ongoing transfusions may receive hydroxyurea.
- Revascularization is useful in patients with Moyamoya (a congenital syndrome of cerebral arterial malformation).
- Patients with extra cranial arterial dissection or cardio embolism can be started on heparin therapy and transitioned to warfarin. The duration of therapy is 3-6 months for dissection, and one year or longer for cardio embolic causes (depending on whether the causative lesion can be corrected).
- Congenital vascular abnormalities should be treated with surgery, endovascular repair, or radiosurgery when possible.
- Patients may wish to discontinue oral contraceptives, consider other forms of birth control.
- In patients with elevated homocysteine levels, diet changes and/or folate, vitamin B6, and vitamin B12 supplementation may be used in attempt to decrease homocysteine.
- There is little information about the long-term use of prophylactic therapies such as LMWH in neonates. Although recurrent stroke is uncommon in these patients, individuals with prothrombotic conditions plus other risk factors including complex congenital heart disease, dehydration, or prolonged bed rest may have a higher likelihood of recurrent venous and arterial thrombosis, and prophylaxis may be considered in these individuals. It is reasonable to supplement folate and B vitamins for children with a methylene tetra hydro-folate reductase (MTHFR) mutation in an effort to normalize homocysteine levels.
- Planning a child’s individualized therapy and educational programs may involve multiple team members. Plans must include a thorough assessment of deficits
- Provide information about resources available through school, and how to request a 504 plan or an Individual Education Plan (IEP). This plan should specify educational adaptations, educationally related therapy services, and nursing services to be provided by the school.
- Orthotics, adaptive equipment, and medical management of spasticity can all be used to facilitate a child’s recovery.
Coordination of care
Multidisciplinary teams remain the standard of care for pediatric stroke patients.
In acute care setting: Involvement of critical care team, neurology, hematology, trauma service and neurosurgery, care co-ordination, physiatry
In Rehab setting: Involvement of physiatry, pediatrician, physical therapy, occupational therapy, speech therapy, neuropsychology, dietician, child life therapies, recreational therapies, care-coordinators, social worker, nursing staff. Services that had evaluated the patient during acute management to f/up on any pending health concerns
Patient & family education
Most sources do indicate cautious optimism is warranted; a good balance of honesty about probable long term deficits but also overall strong potential for recovery that is possible should be provided
The Children’s Hemiplegia and Stroke Association (http://www.chasa.org/) is an excellent starting point for families to meet others with similar experiences, learn about stroke rehabilitation, and find events and activities for children who have had a stroke.
Several validated measures have been used to document outcomes, but not all are specific to pediatric stroke. The Pediatric Stroke Outcomes Measure, Pediatric Stroke Recurrence and Recovery Questionnaire, and the PedNIHSS were developed specifically for this population.
Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills
Remember to keep stroke in the differential diagnosis for children with neurologic complaints, headache, or vomiting. Misdiagnosis or delayed diagnosis is common.
4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE
Cutting edge concepts and practice
Robotic therapies to improve upper extremity function have been tested in adult stroke patients and in children with cerebral palsy. Expansion to the pediatric stroke population is a logical next step.
Constraint induced therapy (CIT) may help improve function in the affected hand.16Any child who can understand simple directions and does not have significant contracture may be a candidate for this therapy, even with minimal motor function of the affected side. Adjunct interventions, including functional electrical stimulation and botulinum toxin-type A have been combined with CIMT. The addition of primed, low-frequency repetitive transcranial magnetic stimulation (rTMS) to CIMT is a novel method to ramp up the potential for activity-dependent plasticity in older children. This is an exciting preliminary study and despite the potentially invasive nature, no serious adverse events were reported.11
5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE
Gaps in the evidence-based knowledge
Extensive pediatric research in the field of pediatric stroke is lacking due to relative low incidence of stroke in pediatric population.
Further multi-centre studies are needed to establish guidelines for tissue plasminogen activator use in children.
- Advances in pediatrics in Pediatric stroke: past, present and future. Neil Friedman MBChB. DOI 10:1016/j.yapad.2009.08.003.
- Stroke in infancy: a convergence of causes. GABRIELLE DEVEBER doi: 10.1111/dmcn.12296
- Ishihara C, Sawada K, Tateno A. Bilateral basal ganglia infarction after mild head trauma. Pediatr Int 2009; 51: 829–31.
- Hurvitz E, Beale L, Ried S, Nelson V. Functional outcome of paediatric stroke survivors. Pediatr Rehabil. 1999;3(2):43-51.
- Lee MT, Piomelli S, Granger S, et al. Stroke prevention trial in sickle cell anemia (STOP): extended follow up and final results. Blood. 2006; 08(3): 847-852.
- Bigi S, Fischer U, Wehrli E, et al. Acute ischemic stroke in children versus young adults. Ann Neurol. 2011;70(2):245-254.
- Jordan LC, Kleinman JT, Hillis AE. Intracerebral hemorrhage volume predicts poor neurologic outcome in children. Stroke. 2009;40(5):1666-1671.
- Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Paul Monagle , MBBS , MD , FCCP ; Anthony K. C. Chan , MBBS ; Neil A. Goldenberg , MD , PhD ; Rebecca N. Ichord , MD ; Janna M. Journeycake , MD , MSCS ; Ulrike Nowak-Göttl , MD ; and Sara K. Vesely , PhD.
- 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 E. Steve Roach, MD, FAHA, Chair; Meredith R. Golomb, MD, MSc; Robert Adams, MD, MS, FAHA; Jose Biller, MD, FAHA; Stephen Daniels, MD, PhD, FAHA; Gabrielle deVeber, MD; Donna Ferriero, MD; Blaise V. Jones, MD; Fenella J. Kirkham, MB, MD; R. Michael Scott, MD, FAHA; Edward R. Smith, MD.
- Guidelines for Adult Stroke Rehabilitation and Recovery A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association DOI: 10.1161/STR.0000000000000098.
- Gillick BT, Krach LE, Feyma T, et al. Primed Low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: a randomized controlled trial. Dev Med Child Neurol 2014; 56: 44–52.
Original Version of the Topic
Edward Hurvitz, MD and Alecia Daunter, MD. Pediatric stroke. 9/20/2013.
Rajashree Srinivasan, MD
Nothing to Disclose
Saylee Dhamdhere MD, UTSW
Nothing to Disclose