Stroke in Children: Stroke Subtype How often does that happen? - - PowerPoint PPT Presentation

9/6/2014 1

Advances in Pediatric Stroke

Heather J. Fullerton, MD, MAS Professor of Neurology & Pediatrics Director, Pediatric Stroke & Cerebrovascular Disease Center

What’s New in Pediatric Stroke?

• Epidemiology: more common than we thought
• Risk Factors: the role of infection

(&vaccination)

• Hyperacute Treatment
• (A few) Pediatric Stroke Syndromes

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Stroke in Children: How often does that happen?

• Incidence:

– 4.6 per 100,000 children/year in US – About 5,000 US kids/year

– 1 per 3,500 neonates

Agrawal, Stroke, 2009

Stroke Subtype

Hemorrhagic Ischemic

Children

Adults Ischemic Hemorrhagic Broderick, J Child Neuro, 1993

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Etiologies of Childhood Stroke: The Typical Laundry List

• Cardiac

– Congenital ht dz – Bacterial endocarditis – Rheumatic ht dz – Arrythmias

• Vascular disease

– Transient Cerebral Arteriopathy – Moyamoya – Arterial dissection – FMD

• Hematologic

– Sickle cell dz – Leukemia – Polycythemia

• Hypercoaguable state

– Aquired: sepsis, nephrotic syndrome, liver failure, SLE, anti-phospholipid syndrome, cancer – Inherited: protein c/s deficiency, AT III deficiency, Factor V Leiden, MTHFR, prothrombin 20210

• Infection

– Meningitis/encephalitis – Chicken pox

• Drugs

– Cocaine – OCP’s – Chemotx (L-asp)

• Metabolic/Genetic

– Homocystinuria – Fabry’s – Organic acidemias – Majewski’s Osteopdysplastic Primordial Dwarfism, type II – Collagen vascular (e.g., Ehlers-Danlos)

• Neurocutaneous d/o’s: NF1, TS

Etiologies of Childhood Stroke: The Typical Laundry List

• Cardiac

– Congenital ht dz – Bacterial endocarditis – Rheumatic ht dz – Arrythmias

• Vascular disease

– Transient Cerebral Arteriopathy – Moyamoya – Arterial dissection – FMD

• Hematologic

– Sickle cell dz – Leukemia – Polycythemia

• Hypercoaguable state

– Aquired: sepsis, nephrotic syndrome, liver failure, SLE, anti-phospholipid syndrome, cancer – Inherited: protein c/s deficiency, AT III deficiency, Factor V Leiden, MTHFR, prothrombin 20210

• Infection

– Meningitis/encephalitis – Chicken pox

• Drugs

– Cocaine – OCP’s – Chemotx (L-asp)

• Metabolic/Genetic

– Homocystinuria – Fabry’s – Organic acidemias – Majewski’s Osteopdysplastic Primordial Dwarfism, type II – Collagen vascular (e.g., Ehlers-Danlos)

• Neurocutaneous d/o’s: NF1, TS

What triggers stroke in a chronic disease?

Infection & Stroke in Adults

Hedley A. Emsley, J CBF&Metabolism, 2011

Results: Infection

Infection ≤ 1 week prior to stroke/interview date conferred a 6.5-fold risk of AIS (p<0.0001).

20 40 60 80 100

Prior week Prior month Prior six months

Percent of children Controls Cases * statistically significant

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Prior: 1 week* 1 month* 6 months

Odds Ratios with 95% confidence intervals

Hills, et al. International Stroke Conference, 2014

9/6/2014 3 Results:

• Published

seroprevalence (IgG)

– 20% by age 5 years – plateaus during later childhood – 40-60% in young adulthood (20-40 years)

• After adjusting for age:

– OR 9 (95% CI 3.1, 39; p=0.0004)

41%

9% p=0.0001, Fishers exact

Fullerton, et al. International Stroke Conference, 2014

Results: Vaccination

Children reported to have had some/few/no routine vaccinations had 7 times the risk of stroke compared to those receiving all or most of their routine vaccinations. OR= 6.6

(95% CI2.3, 19.2), p=0.001

20 40 60 80 100

All/Most Some/Few/None Percent reported

Controls Cases

Hills, et al. International Stroke Conference, 2014

Odds Ratios for Stroke by Vaccination Type

0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 Odds Ratio

MMR* Polio DPT Pneumococcus* Varicella* Hep B Hep A Meningococcus

Hills, et al. International Stroke Conference, 2014

Hyperacute therapy in pediatric stroke: when to consider?

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9/6/2014 4 IV tPA: Cost/Benefit Ratio

• Adults:

Cost: 10x risk of ICH Benefit: Improved neuro

• utcome

IV tPA: Cost/Benefit Ratio

• Kids?:

? Cost: Risk of ICH

? Benefit

TIPS Trial: Thrombolysis in Pediatric Stroke

• safety & dosing study only
• closed due to lack of enrollment

Special Considerations in Children

• Very limited data (case reports)
• Acute hemiparesis more likely to be non-

stroke (migraine, seizure)

• Delayed stroke diagnosis
• Predominantly large vessel stroke
• Immature coagulation system--? tPA dosing

When We Consider Hyperacute Tx

• Not very often—not standard of care

– Older teenagers – Basilar artery thrombosis – Dominant MCA strokes

• But only with full disclosure to family of limited data in

children, potential risks

9/6/2014 5 (A few) Pediatric Stroke

Syndromes

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Childhood arteriopathies are important to recognize and diagnose because…

Arteriopathies predict recurrent ischemic stroke in children

0.00 0.20 0.40 0.60 0.80 1.00 Proportion recurrence free 1 2 3 4 Time (years) from index stroke

Kaplan-Meier survival estimates, by abvascim_x_occl

Normal vascular imaging, n=30 Abnormal vascular imaging, n=22 P<0.0001 by log-rank 66%

(95% CI 43-87%)

Fullerton, Pediatrics, 2007

7 y.o. girl, previously healthy, R HP & aphasia

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“Transient” Cerebral Arteriopathy (TCA)

• Natural history:

– Monophasic disease – Initial progression (2-6 months) – Nonprogression after 6 months – Improvement or stabilization; rarely normalization

– Chabrier & Sebire, J Child Neurol 1998; Danchaivijitr, Ann Neurol 2006

• Tx: aspirin

Courtesy of G. DeVeber

Acute 2 months 12 months

9/6/2014 6 3 y.o. girl with “blown pupils” & left HP

• PMHx:
• Congenital

mydriasis

• Patent ductus

arteriosis

• “Large bladder,”

recurrent UTIs Angiogram 1/31/2013 ACTA 2 Mutations

• De novo (parents not affected)
• Arg179His (most common), Arg179Leu, Arg179Cys, Arg39Cys
• Affect smooth muscle function

– Vascular disease: “moyamoya,” aortic aneurysms, aortic dissections, PDA, pulmonary hypertension – Congenital fixed dilated pupils (mydriasis) – Hypotonic bladder – Gut malrotation, delayed gastric emptying, constipation

• Tx: cautious revascularization (high surgical

morbidity)

Normal ACTA2 Moyamoya Munot, Ganesan, Brain 2012

9/6/2014 7 6 y.o. boy with recurrent posterior circulation ischemic strokes R vertebral, Neutral Head turned 45 degrees, left

Right Vertebral

Head turned 60 degrees, left

Right Vertebral

“Vertebral Artery CRIMP” Syndrome

• Cervical
• Rotational
• Injury
• eMbolism
• Posterior circulation
• Stout C, et al, under review
• Chronic mechanical

injury to the vertebral artery at C1/C2

• Progressive occlusion

with head turning at the level of injury

• Tx: surgical

decompression or endovascular vertebral

• cclusion

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9/6/2014 8 Take Home Points

• Children have strokes (≈5,000 US kids per year)
• Infection can act as an acute trigger

– Vaccinations are probably protective

• No answers on safety or efficacy of tPA in children

– Not standard of care, but reasonable to consider in older teens with full disclosure to family on lack of data

• Arteriopathies in children are

– Common – Strongest predictor of recurrence – Heterogeneous, with variable treatment approaches

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Acknowledgements

• UCSF Pediatric Stroke &

Cerebrovascular Disease Center

– Pedi Vascular Neurologists: Fox, Fullerton, Shapiro – Neurosurgery: Auguste, Gupta, Lawton, Raffel – NIR: Cooke, Dowd, Halbach, Hetts, Higashida – Neuropsych: Lundy – Hematology: Huang – RN: Sara Rzasa

• Part of the

Pediatric Brain Center

– (855)PBC-UCSF

– [(855)722-8273]

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