1. Childhood Stroke Gita V. Massey, MD Coagulation Update 2006 September 30, 2006

2. The challenge…………….. How to cover this enormous topic in 30 minutes and give some insightful advice to the practicing hematologist………… …

3. What the experts say……. Jordon, LC; Stroke in Childhood. The Neurologist; 12, 94-102; 2006 deVeber, G; In pursuit of evidence-based treatments for paediatric stroke. The Lancet Neurology; 4, 432-436; 2005 Lynch, JK and Han CJ; Pediatric Stroke: What do we know and what do we need to know? Sem in Neurology; 25,410-423; 2005 deVeber, G; Arterial ischemic strokes in infants and children: and overview of current approaches; Sem in Thromb and Hemost; 29, 567-573; 2003.

4. Epidemiology Incidence 8/100,000/year (1.3-13) Incidence in neonates 1/4,000/year Incidence increasing –More sensitive imaging –Effective Rx for predisposing condition (CHD, prematurity, tumors) Death in 6% (top 10 causes of death in children) Neurologic deficits in 2/3 20-30% recurrence risk

5. Children are not little adults…… Incidence is rare Subtle neurologic presentation Underdiagnosis and delay in diagnosis Multiple types of stroke Multiple risk factors

6. Type of Stroke STROKE Acute Ischemic Stroke (AIS) Hemorrhagic Stroke (HS) Vascular malformations ITP/Hemophilia Brain tumors Cerebral Venous Thrombosis (CVT) Infection Dehydration Prothrombotic states

7. Acute Ischemic Stroke Incidence is 3/100,000, year Neonates account for 25% of AIS – median age 5 yrs Male predominance (60%) Predominance in African-American population

8. Clinical Features of AIS Canadian Registry –51% hemiparesis –48% seizures –17% speech disorder –50% headache, lethargy, confusion Neonates –<25% hemiparesis –Lethargy and seizures predominate –No symptoms (early hand dominance)

9. Risk Factors for AIS AIS Vascular Intra- vascular Embolic

10. Vascular Risk Factors Vascular Arteriopathies Transient Progressive VasospasticVasculitis Infectious Connective tissue disease Drugs Systemic vascular disease

11. Embolic Risk Factors Embolic Congenital Heart Disease Cyanotic Heart Disease PFO Acquired Heart Disease Cardiomyopathy Arrhythmia Trauma

12. Intravascular Risk Factors (The Hematologist’s Domain) Intravascular Hematologic Disorders Sickle cell Iron deficiency Leukemia Prothrombotic States Acquired Congenital Metabolic Hyper homocysteinemia Hyperlipidemia

13. The Acquired Prothrombotic States Acquired MedsPregnancy Lupus Anticoagulants

14. The Congenital Prothrombotic States Congenital ATIIIProtein C APC resistance Protein SPlasminogenPT20210MTHFR Lipoprotein a

15. The Confusing Realm of Prothrombotic States How much do they contribute? Rare disorders Age related differences Acute differences Dietary variations

16. Vascular IntravascularEmbolic Inter-relations

17. The Diagnostic Work-Up History –Trauma, infection, palpitations, mental status chages, underlying disease –Previous DVT’s, family history Physical Exam –Marfanoid body habitus –Cutaneous lesions Café au lait spots xanthoma

18. The Diagnostic Work-Up Laboratory Studies –CBC, comprehensive metabolic panel, ESR –Toxicology and infectious studies –The hypercoagulation studies Imaging Studies –CT –MRI/MRA/MRV –Echo

19. The hypercoagulation profile Implicated in 38%-75% of childhood stroke patients Expensive Rare disorders Transient disorders What can you do about it? –B12, folate, B6 in hyperhomocystenemia –Niacin in lipoprotein a

20. Therapy Absence of RCT Adapted from adults Treat underlying risk factor Prevent recurrence

21. Consensus on…… Sickle cell disease Acute therapy –Exchange transfusion Preventive therapy –Blood transfusion every 3-6 weeks to maintain HbS<30% –?HU, stem cell transplant –Transcranial dopplers

22. Current recommendations…… Neonatal AIS – no therapy Dissecting vasculopathy – anticoagulation 3-6 months Cardiogenic embolism – anticoagulation but no consensus on length of time Vasculopathy – ASA (no consensus on dose 1-5mg/kg/day) Recurrent stroke – consider anticoagulation

23. Current practice….. Most (>50%) will use LMWH/UH 5-7 days in non neonatal period followed by ASA Thrombolytic agents are rarely used in pediatrics and their use is recommended only in conjuction with clinical trials.

24. Outcomes of Childhood AIS 1991 – 85% long-term sequelae 2001 – 60% long-term sequelae Hemiparesis, speech, learning and behavior WORSE IF….. –Multiple risk factors –CHD/progressive vasculopathy –Larger infarct –Stroke after neonatal period –Seizures with stroke

25. What do we need for the future? Prospective cohort studies –Standard evaluation of risk and outcome –Develop therapy and prevention strategies Incidence studies Case control studies of risk factors Outcome studies