Hyperacute Therapy for Pediatric Stroke€¦ · Pediatric Stroke Jenny Wilson, MD Pediatric Neurology Oregon Health & Science University September, 2019 [email protected] •I have

Pediatric Stroke

Jenny Wilson, MDPediatric Neurology

Oregon Health & Science UniversitySeptember, 2019

[email protected]

• I have no disclosures

• Off-label treatments will be discussed

• Neonatal stroke: 2.5-4/1000 live births

• Pediatric arterial ischemic stroke: 1-8/100,000 per year

• Hemorrhage: 3/100,000 per year

• Cerebral venous sinus thrombosis: 1/100,000 per year

Epidemiology

Impact

• Stroke is among the top 10 causes of death in children

• About 60% of children with stroke develop disability

• Neonatal stroke is the most common cause of hemiplegic cerebral palsy

Case 1

• Baby boy born after an unremarkable pregnancy at term

• At 24 hours of life starts having left arm jerking that is not suppressible

MRI

Evaluation and Treatment

• Vascular imaging normal

• Echocardiogram unremarkable

• No treatment given

• Referred for early intervention services

Outcome

• At 4-6 months noted to not be using his left arm as well as his right

• Receives the diagnosis of hemiplegic CP

Perinatal Stroke: overview

The 2 periods of life in which the risk of having a stroke is highest are in the elderly and in the perinatal period.

Ischemic stroke between 20 weeksgestation and 28 days postnatal age.

Stroke. 2007; 38: 742-745

Perinatal Stroke: etiology

Govaert et al. Acta Paediatr. 2009;98(11):1720.

Perinatal Stroke: risk factors

Govaert et al. Acta Paediatr. 2009;98(11):1720.

Raju et al.

Clinical presentation

Kirton et al. Pediatrics 2011;128;e1402 (IPSS)

•72% present with seizures in first few days•63% present with encephalopathy or other nonspecific symptoms• 30% present with hemiparesis

• 40% go unrecognized in the newborn period, typically presenting with seizure or hemiparesis in infancy (“presumed perinatal ischemic stroke”)

Perinatal Stroke: evaluation

• MR angiogram (consider MR venogram)

• Echocardiogram

• Hypercoagulable work-up:– Recurrence risk is so low, not predicted by

thrombophilia testing, and rates of thrombophiliasnot clearly different than the general population

Perinatal Stroke: management

• No acute therapies• Treat seizures, but then get them off seizure

medications • No clear evidence for anti-coagulation or anti-

platelet therapy (recurrence risk 1-3%).– Exceptions – congenital heart disease, venous sinus

thrombosis, major hypercoagulable state

• Education• Alleviate guilt – “it’s not your fault”• Rehabilitation

Perinatal Stroke Outcome

• Normal developmental outcome –up to 1/3

• Cerebral palsy: 25-30%– Hemiplegic, most walk

independently

• Epilepsy: 15-55%• Cognitive deficits: 25%• Language disorders in 20-25%

– Side of stroke does not predict language deficits

• Impaired vision: 25%• Attention, learning problems

J Child Neurol. 2007 Nov;22(11):1274-80

Case 2

• A 9 yo previously well girl develops acute onset right sided weakness and difficulty speaking. She has a headache.

• She arrives at the ER 3 hours after onset of symptoms.

• NIHSS 13

• Head CT – no hemorrhage

How should this child be treated?

a. IV tPA

b. Get vascular imaging, thrombectomy if ICA or M1 occlusion

c. Get vascular imaging and perfusion imaging, thrombectomy if ICA or M1 occlusion and mismatch ratio>1.8

d. Give aspirin, lay flat, run normal saline, get an MRI/MRA, echocardiogram and hematology consult

e. a. and b.

f. aaahhh!!! I have no idea!!!

9 years3 hoursNIHSS 13

Neuroprotection: first 24 hours--Start immediately

• HOB flat - Exceptions: if intubated, or increased ICP, then HOB 30 degrees.

• Isotonic fluids

• Normothermia

• Normoglycemia

• Normotension

• Avoid hypoxia

• Treat seizures

IV tPA: children• IV tPA is not FDA approved nor well studied in children

• About 2% of children are treated with IV tPA

• Retrospective data suggests hemorrhage rate is not higher in children than adults: 4.9% in study of 99 children given IV tPA, with no deaths

• Unclear if it is beneficial for children

• AHA Guidelines state: “IV tPA should only be given in the setting of a clinical trial, though no consensus on use in adolescents.”

• Some centers consider IV tPA down to age 2, based on the TIPS trial protocol (closed due to lack of enrollment)

(Nasr et al Pediatric Neurology 51 (2014) 624e631)Roach et al. Stroke. 2008;39:2644-2691Rivkin et al Pediatric Neurology 56 (2016) 8e17

Thrombolysis in Pediatric Stroke (TIPS) Study

• Dose-adaptive, phase I cohort study (0.75, 0.9, 1 mg/kg)

• 17 sites, ages 2-17 years, within 4.5 hours onset

• MRI/MRA or CT/CTA prior to treatment

• Closed in December 2013 by the sponsor for lack of recruitment: 1 of 93 screened children was enrolled into the study

Rivkin et al. Stroke. 2015;46:00-00.

IV tPA at for children OHSU

• Consider for adolescents ≥ 12 years

• Within 3 hours of onset of symptoms

• Significant deficits (NIHSS ≥ 4), not rapidly resolving

• No contraindications

• Imaging: establish no blood and demonstrate clot in the vessel supplying the territory of the deficit – either CT/CTA or MRI/MRA

• Risk/benefit discussion with the family

• Note that given the 3 hr window, this therapy will rarely be an option

Endovascular Therapy: children

• Data limited to case series, reviews

• 2019 review – 113 cases, 91% with good outcomes

• Children as young as 9 months have been treated.

• 2015 AHA guidelines: “Endovascular therapy with stent retrievers may be reasonable for some patients <18 years of age with acute ischemic stroke who have demonstrated large vessel occlusion in whom treatment can be initiated within 6 hours of symptom onset.”

• No specific statement about pediatrics in the 2018 AHA guidelines which extended the time window in adults

Powers et al. Stroke. 2015 Oct;46(10):3020-35

2019 Pediatric Stroke AHA guidelines

Survey of 31 Pediatric Stroke Physicians

Endovascular Therapy: at OHSU

• Consider for children with anterior circulation stroke:

≥ 8 years

Within 24 hours

NIHSS ≥ 8

– For basilar thrombosis - may consider treatment up to 24 hours

Thrombectomy experience at OHSU

Patient Year Age Location Cause Vessel NIHSS Time to treatment

Outcome

1 (SS) 2015 12 trauma Trauma Basilar 34X 40+ deceased

2 (KB) 2016 9 OSH, portland

Myocarditis M1 14 6.5 Visual field deficit

3 (JL) 2017 15 Medford Cardiac myxoma

M1 24X 7ASPECTS 3MM 1.9

Expressive aphasia, mild hemiparesis

4 (AB) 2018 15 Roseburg Cryptogenic ICA terminus

15 9ASPECTS 9

Mild hemiparesis, anxiety/executive function

Risk Factors

Pediatric arterial ischemic stroke - Risk factors

Adults

Hypertension

Diabetes

Hypercholesterolemia

Smoking

Children

Heart disease

Sickle cell disease

Infection

Vasculopathy

Risk factors

Lancet Neurology 2014; 13: 35-43.

The Infection Connection

• Infectious risk factors in 28%

• Certain infections associated with stroke: TB, varicella

• Children with stroke more likely to have recent minor infection (URI, gastro): 33% cases vs. 13% controls

• Acute herpesvirus infections increase risk of childhood AIS - present in almost half of strokes, mostly as subclinical and primary infections

• Vaccinations may be protective against pediatric stroke

Hills et al. Neurology. 2014 Sep 2;83(10):890-7 Lancet Neurology 2014; 13: 35-43.Fullerton et al. Neurology® Infection, vaccination, and childhood arterial ischemic stroke2015;85:1–8

The Infection Connection

Transient Cerebral Arteriopathy(TCA)

– Etiology of 7-20% of childhood stroke

– Involves distal ICA or proximal MCA

– Monophasic: resolves by 6 months

– Associated with recent URI (OR 2.3) or varicella

– Steroids could be useful

Hills et al. Neurology. 2014 Sep 2;83(10):890-7Lancet Neurology 2014; 13: 35-43.

Stroke. 2014;45:3597-3605

Clinical presentation

Clinical presentation: pediatric stroke

• Acute onset focal deficit – 85% of patients

• Diffuse features:

– Headache in more than half

– Altered mental status in 35-60%

– Seizure

• 3% of adults with stroke present with seizure

• 30% of children with stroke present with seizure

• 75% of infants with stroke present with seizure

Lancet Neurology 2014; 13: 35-43.

Delay in Diagnosis

• Time to pediatric stroke diagnosis: 24 hours.

– Most (2/3) present to care within 3 hours.

Rafay et al. Stroke. 2009;40:58-64.

Reasons for Delay in DiagnosisPrior to arrival:

– “it looked like a stroke but children don’t have strokes….”

– May not articulate symptoms

After arrival: Physicians suspected stroke in 26-38%

• Stroke mimics are common

• False reassurance from normal head CT

• Delays in obtaining MRI

Rafay et al. Stroke. 2009;40:58-64.

Stroke mimics

• One study found that 54% of children suspected of having stroke by a pediatric neurologist had a stroke mimic

Rivkin et al. Stroke. 2015;46:00-00. Shellhaas et al. PEDIATRICS Volume 118, Number 2, August 2006

Pediatric Stroke Evaluation

• Echo with bubble

• MRI/MRA head and neck (ultrasound not sufficient)

• Hypercoagulable work-up/heme consult

Recurrence

• VIPS study (vascular effects of inflammation in pediatric stroke)

• N=355 AIS, prospective, 2009-2014

• 11% recurrence at median follow-up 2 years, Only arteriopathy predicted recurrence, increased recurrence risk x 5

Stroke. 2016 Jan;47(1):53-9. doi: 10.1161/STROKEAHA.115.011173. Epub 2015 Nov 10.Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study.Fullerton HJ1

Recurrence

Stroke. 2016 Jan;47(1):53-9. doi: 10.1161/STROKEAHA.115.011173. Epub 2015 Nov 10.Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study.Fullerton HJ1

Recurrence risk at 1 yr:Idiopathic: 4.5%Cardioembolic 8.1%Possible arteriopathy 12%Definite arteriopathy 21%

Secondary Prevention:

AHA guidelines:

• Aspirin if recurrence risk is not high, for 2-5 years

• Anticoagulation if high risk of recurrent cardioembolism, CSVT, certain hypercoagulable disorders, may use for cervical arterial dissection.

• May use anticoagulation short-term pending evaluation for etiology of stroke

• Discontinue oral contraceptives

• Avoid triptans

• Treat iron deficiency, which may increase the risk of arterial ischemic stroke in conjunction with other risk factors

• Counsel children and their families regarding dietary improvement, the benefits of exercise, and avoidance of tobacco products

Outcomes in Pediatric Stroke

Outcomes in Pediatric Stroke

• 5% of children with stroke die

• 70% have long-term neurological deficits.

• 15% have severe long-term deficits

• IQ, in most studies, in the average or low average range

• 20% develop epilepsy

Amlie-Lefond. Lancet Neurol 2009; 8: 530–36Elbers et al. J Child Neurol. 2013 Apr 15;29(6):782-788

Children’s Hemiplegiaand Stroke Association (CHASA)

Outcomes in pediatric stroke: silent disabilities

• Behavioral problems 44%

• ADHD in up to 46%

• Depression in 20-30%

• Anxiety 30%

• Frequently, abnormal scores on subtests of cognitive evaluations

Amlie-Lefond. Lancet Neurol 2009; 8: 530–36Elbers et al. J Child Neurol. 2013 Apr 15;29(6):782-788

Studer et al. Neurology® 2014;82:784–792

Recovery

• 7 year follow-up data comparing children to young adults with stroke. ~55% in both groups had a favorable outcome. Similar mortality rates.

Goeggel. Neurology. 2015; 84:1941-1947.

Summary

• Children have strokes!

• Present with focal deficits, may also have seizures/HAs

• Pediatric stroke a different disease than adult stroke.

• Acute care is primarily supportive.

• Acute therapies infrequently an option.

• Aspirin for secondary prevention, in most cases.

• Cryptogenic stroke rarely recurs.

• Most kids are left with deficits.

Pediatric Stroke Program at OHSU

• Clinic: referral to OHSU Child Development and Rehabilitation Center (CDRC), stroke clinic

• Can also call consult line/transfer line

Jenny Wilson, MDPediatric neurology

Trisha Wong, MDPediatric hematology

Mina Nguyen-Driver, PsyDPediatric Psychology

Kimberly Solondz, OTOccupational therapy

Cynthia Green, SLPSpeech-language therapy

Will Foran, PT, PCSPhysical therapy

Erin Stang, LCSWSocial work