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

9/6/2014 What’s New in Pediatric Stroke? • Epidemiology: more common than we thought Advances in • Risk Factors: the role of infection Pediatric Stroke (&vaccination) • Hyperacute Treatment Heather J. Fullerton, MD, MAS • (A few) Pediatric Stroke Syndromes Professor of Neurology & Pediatrics Director, Pediatric Stroke & Cerebrovascular Disease Center 2 Stroke in Children: Stroke Subtype How often does that happen? • Incidence: – 1 per 3,500 neonates – 4.6 per 100,000 children/year in US Ischemic Hemorrhagic Hemorrhagic – About 5,000 US kids/year Adults Children Ischemic Broderick, J Child Neuro, 1993 Agrawal, Stroke, 2009 1

9/6/2014 What triggers Etiologies of Childhood Stroke: Etiologies of Childhood Stroke: stroke in a chronic The Typical Laundry List The Typical Laundry List disease? Infection Infection • • – Meningitis/encephalitis – Meningitis/encephalitis Cardiac Cardiac • • – Chicken pox – Chicken pox – Congenital ht dz – Congenital ht dz Drugs Drugs – Bacterial endocarditis • – Bacterial endocarditis • – Rheumatic ht dz – Cocaine – Rheumatic ht dz – Cocaine – Arrythmias – OCP’s – Arrythmias – OCP’s Vascular disease Vascular disease – Chemotx (L-asp) – Chemotx (L-asp) • • – Transient Cerebral Arteriopathy – Transient Cerebral Arteriopathy Metabolic/Genetic Metabolic/Genetic • • – Moyamoya – Moyamoya – Homocystinuria – Homocystinuria – Arterial dissection – Arterial dissection – Fabry’s – Fabry’s – FMD – FMD – Organic acidemias – Organic acidemias Hematologic Hematologic • • – Majewski’s Osteopdysplastic Primordial – Majewski’s Osteopdysplastic Primordial – Sickle cell dz – Sickle cell dz Dwarfism, type II Dwarfism, type II – Leukemia – Leukemia – Collagen vascular (e.g., Ehlers-Danlos) – Collagen vascular (e.g., Ehlers-Danlos) – Polycythemia – Polycythemia Neurocutaneous d/o’s: NF1, TS Neurocutaneous d/o’s: NF1, TS Hypercoaguable state • Hypercoaguable state • • • – Aquired: sepsis, nephrotic syndrome, – Aquired: sepsis, nephrotic syndrome, liver failure, SLE, anti-phospholipid liver failure, SLE, anti-phospholipid syndrome, cancer syndrome, cancer – Inherited: protein c/s deficiency, AT – Inherited: protein c/s deficiency, AT III deficiency, Factor V Leiden, III deficiency, Factor V Leiden, MTHFR, prothrombin 20210 MTHFR, prothrombin 20210 Infection & Stroke in Adults Results: Infection Infection ≤ 1 week prior to stroke/interview date conferred a 6.5-fold risk of AIS (p<0.0001). 14 13 12 11 100 10 Odds Ratios Controls Cases 9 Percent of children with 95% 80 8 confidence 7 60 intervals 6 40 5 4 20 3 2 0 1 Prior week Prior month Prior six months 0 Prior: 1 week* 1 month* 6 months * statistically significant Hills, et al. International Stroke Conference, 2014 Hedley A. Emsley, J CBF&Metabolism, 2011 2

9/6/2014 Results: Vaccination • Published Results: seroprevalence (IgG) – 20% by age 5 years Children reported to have had some/few/no routine – plateaus during later childhood vaccinations had 7 times the risk of stroke compared – 40-60% in young adulthood (20-40 to those receiving all or most of their routine years) vaccinations. OR= 6.6 (95% CI2.3, 19.2), p=0.001 • After adjusting for age: 100 OR 9 – Percent reported 80 41% (95% CI 3.1, 39; p=0.0004) p=0.0001, 60 Fishers exact Hills, et al. International Stroke 40 Conference, 2014 9% 20 0 All/Most Some/Few/None Controls Cases Fullerton, et al. International Stroke Conference, 2014 Odds Ratios for Stroke by Vaccination Type Hyperacute therapy in pediatric stroke: when to consider? 1.80 1.60 DPT 1.40 Hep A 1.20 Odds Ratio Varicella* 1.00 0.80 MMR* Hep B 0.60 0.40 Meningococcus 0.20 Pneumococcus* Polio 0.00 Hills, et al. International Stroke Conference, 2014 12 3

9/6/2014 IV tPA: Cost/Benefit Ratio IV tPA: Cost/Benefit Ratio • Adults: • Kids?: ? Benefit Cost: 10x risk of ICH ? Cost: Benefit: Risk of ICH Improved neuro outcome TIPS Trial: Thrombolysis in Pediatric Stroke -safety & dosing study only -closed due to lack of enrollment Special Considerations in When We Consider Hyperacute Tx Children • Not very often—not standard of care • Very limited data (case reports) – Older teenagers • Acute hemiparesis more likely to be non- – Basilar artery thrombosis stroke (migraine, seizure) – Dominant MCA strokes • Delayed stroke diagnosis • But only with full disclosure to family of limited data in children, potential risks • Predominantly large vessel stroke • Immature coagulation system--? tPA dosing 4

9/6/2014 Arteriopathies predict recurrent ischemic stroke in children Kaplan-Meier survival estimates, by abvascim_x_occl (A few) Pediatric Stroke Normal vascular imaging, n=30 1.00 Syndromes 0.80 Proportion recurrence free P<0.0001 by log-rank 0.60 0.40 Abnormal vascular imaging, n=22 Childhood arteriopathies 0.20 are important to 66% recognize and diagnose 0.00 (95% CI 43-87%) because… 0 1 2 3 4 Time (years) from index stroke Fullerton, Pediatrics , 2007 17 “Transient” Cerebral Arteriopathy (TCA) 7 y.o. girl, previously healthy, • Natural history: R HP & aphasia – Monophasic disease – Initial progression (2-6 months) – Nonprogression after 6 months – Improvement or stabilization; rarely normalization Acute – Chabrier & Sebire, J Child 2 months 12 months Neurol 1998; Danchaivijitr, Ann Neurol 2006 • Tx: aspirin Courtesy of G. DeVeber 19 5

9/6/2014 3 y.o. girl with “blown pupils” & left HP Angiogram 1/31/2013 • PMHx: • Congenital mydriasis • Patent ductus arteriosis • “Large bladder,” recurrent UTIs 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 Normal ACTA2 – Congenital fixed dilated pupils (mydriasis) Moyamoya – Hypotonic bladder – Gut malrotation, delayed gastric emptying, Munot, constipation Ganesan, Brain 2012 • Tx: cautious revascularization (high surgical morbidity) 6

9/6/2014 6 y.o. boy with recurrent posterior Right Vertebral circulation ischemic strokes R vertebral, Head turned 45 Neutral degrees, left Right Vertebral “Vertebral Artery CRIMP” Syndrome • Cervical • Chronic mechanical injury to the vertebral • Rotational Head turned artery at C1/C2 • Injury 60 degrees, • Progressive occlusion • eMbolism with head turning at the left level of injury • Posterior circulation • Tx: surgical decompression or • Stout C, et al, under review endovascular vertebral occlusion 28 7

9/6/2014 Acknowledgements Take Home Points • UCSF Pediatric Stroke & • Part of the • Children have strokes ( ≈ 5,000 US kids per year) Cerebrovascular Disease Pediatric Brain Center Center • Infection can act as an acute trigger – (855)PBC-UCSF – Vaccinations are probably protective – Pedi Vascular Neurologists: – [(855)722-8273] Fox, Fullerton, Shapiro • No answers on safety or efficacy of tPA in children – Neurosurgery: Auguste, – Not standard of care, but reasonable to consider in older teens Gupta, Lawton, Raffel with full disclosure to family on lack of data – NIR: Cooke, Dowd, Halbach, • Arteriopathies in children are Hetts, Higashida – Common – Neuropsych: Lundy – Strongest predictor of recurrence – Hematology: Huang – Heterogeneous, with variable treatment approaches – RN: Sara Rzasa 29 30 8