Childhood StrokeChildhood Stroke

Gita V. Massey, MDGita V. Massey, MD

Coagulation Update 2006Coagulation Update 2006

September 30, 2006September 30, 2006

The challenge……………..The challenge……………..

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

What the experts say…….What the experts say…….

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

EpidemiologyEpidemiology

Incidence 8/100,000/year (1.3-13)Incidence 8/100,000/year (1.3-13)

Incidence in neonates 1/4,000/yearIncidence in neonates 1/4,000/year

Incidence increasingIncidence increasing– More sensitive imagingMore sensitive imaging– Effective Rx for predisposing condition (CHD, Effective Rx for predisposing condition (CHD,

prematurity, tumors)prematurity, tumors)

Death in 6% (top 10 causes of death in children)Death in 6% (top 10 causes of death in children)

Neurologic deficits in 2/3Neurologic deficits in 2/3

20-30% recurrence risk20-30% recurrence risk

Children are not little adults……Children are not little adults……

Incidence is rareIncidence is rare

Subtle neurologic Subtle neurologic presentationpresentation

Underdiagnosis and Underdiagnosis and delay in diagnosisdelay in diagnosis

Multiple types of Multiple types of strokestroke

Multiple risk factorsMultiple risk factors

Type of StrokeType of Stroke

STROKE

Acute Ischemic Stroke(AIS)

Hemorrhagic Stroke(HS)

Cerebral Venous Thrombosis (CVT)

Infection

Dehydration

Prothrombotic states

Vascular malformations

ITP/Hemophilia

Brain tumors

Acute Ischemic StrokeAcute Ischemic Stroke

Incidence is 3/100,000, yearIncidence is 3/100,000, year

Neonates account for 25% of AIS – Neonates account for 25% of AIS – median age 5 yrsmedian age 5 yrs

Male predominance (60%)Male predominance (60%)

Predominance in African-American Predominance in African-American populationpopulation

Clinical Features of AISClinical Features of AIS

Canadian RegistryCanadian Registry– 51% hemiparesis51% hemiparesis– 48% seizures48% seizures– 17% speech disorder17% speech disorder– 50% headache, lethargy, confusion50% headache, lethargy, confusion

NeonatesNeonates– <25% hemiparesis<25% hemiparesis– Lethargy and seizures predominateLethargy and seizures predominate– No symptoms (early hand dominance)No symptoms (early hand dominance)

Risk Factors for AISRisk Factors for AIS

Embolic Intra-vascular

Vascular

AIS

Vascular Risk FactorsVascular Risk Factors

Vascular

Arteriopathies Vasospastic VasculitisSystemic vascular

disease

Transient

Progressive

Infectious

Connective tissue disease

Drugs

Embolic Risk FactorsEmbolic Risk Factors

Embolic

Congenital Heart Disease

Acquired HeartDisease

Trauma

Cyanotic Heart Disease

PFO

Cardiomyopathy

Arrhythmia

Intravascular Risk FactorsIntravascular Risk Factors(The Hematologist’s Domain)(The Hematologist’s Domain)

Intravascular

Hematologic Disorders

Prothrombotic States

Metabolic

Sickle cell

Iron deficiency

Leukemia

Acquired

Congenital

Hyperhomocysteinemia

Hyperlipidemia

The Acquired Prothrombotic StatesThe Acquired Prothrombotic States

LupusAnticoagulants

Pregnancy

Meds

Acquired

The Congenital Prothrombotic The Congenital Prothrombotic StatesStates

Lipoproteina

MTHFR

PT20210

Plasminogen

Protein S

APC resistance

Protein C

ATIII

Congenital

The Confusing Realm of The Confusing Realm of Prothrombotic StatesProthrombotic States

How much do they How much do they contribute?contribute?

Rare disordersRare disorders

Age related Age related differencesdifferences

Acute differencesAcute differences

Dietary variationsDietary variations

Vascular

IntravascularEmbolic

Inter-relationsInter-relations

The Diagnostic Work-UpThe Diagnostic Work-Up

HistoryHistory– Trauma, infection, palpitations, mental status Trauma, infection, palpitations, mental status

chages, underlying diseasechages, underlying disease– Previous DVT’s, family historyPrevious DVT’s, family history

Physical ExamPhysical Exam– Marfanoid body habitusMarfanoid body habitus– Cutaneous lesionsCutaneous lesions

Café au lait spotsCafé au lait spots

xanthomaxanthoma

The Diagnostic Work-UpThe Diagnostic Work-Up

Laboratory StudiesLaboratory Studies– CBC, comprehensive metabolic panel, ESRCBC, comprehensive metabolic panel, ESR– Toxicology and infectious studiesToxicology and infectious studies– The hypercoagulation studiesThe hypercoagulation studies

Imaging StudiesImaging Studies– CTCT– MRI/MRA/MRVMRI/MRA/MRV– EchoEcho

The hypercoagulation profileThe hypercoagulation profile

Implicated in 38%-75% of childhood stroke Implicated in 38%-75% of childhood stroke patientspatients

ExpensiveExpensive

Rare disordersRare disorders

Transient disordersTransient disorders

What can you do about it?What can you do about it?– B12, folate, B6 in hyperhomocystenemiaB12, folate, B6 in hyperhomocystenemia– Niacin in lipoprotein aNiacin in lipoprotein a

TherapyTherapy

Absence of RCTAbsence of RCT

Adapted from adultsAdapted from adults

Treat underlying risk factorTreat underlying risk factor

Prevent recurrencePrevent recurrence

Consensus on……Consensus on……

Sickle cell diseaseSickle cell disease

Acute therapyAcute therapy– Exchange transfusionExchange transfusion

Preventive therapyPreventive therapy– Blood transfusion every 3-6 weeks to maintain Blood transfusion every 3-6 weeks to maintain

HbS<30%HbS<30%– ?HU, stem cell transplant?HU, stem cell transplant– Transcranial dopplersTranscranial dopplers

Current recommendations……Current recommendations……

Neonatal AIS – no therapyNeonatal AIS – no therapyDissecting vasculopathy – anticoagulation Dissecting vasculopathy – anticoagulation 3-6 months3-6 monthsCardiogenic embolism – anticoagulation Cardiogenic embolism – anticoagulation but no consensus on length of timebut no consensus on length of timeVasculopathy – ASA (no consensus on Vasculopathy – ASA (no consensus on dose 1-5mg/kg/day)dose 1-5mg/kg/day)Recurrent stroke – consider Recurrent stroke – consider anticoagulationanticoagulation

Current practice…..Current practice…..

Most (>50%) will use LMWH/UH 5-7 days Most (>50%) will use LMWH/UH 5-7 days in non neonatal period followed by ASAin non neonatal period followed by ASA

Thrombolytic agents are rarely used in Thrombolytic agents are rarely used in pediatrics and their use is recommended pediatrics and their use is recommended only in conjuction with clinical trials.only in conjuction with clinical trials.

Outcomes of Childhood AISOutcomes of Childhood AIS

1991 – 85% long-term sequelae1991 – 85% long-term sequelae

2001 – 60% long-term sequelae2001 – 60% long-term sequelae

Hemiparesis, speech, learning and behaviorHemiparesis, speech, learning and behavior

WORSE IF…..WORSE IF…..– Multiple risk factorsMultiple risk factors– CHD/progressive vasculopathyCHD/progressive vasculopathy– Larger infarctLarger infarct– Stroke after neonatal periodStroke after neonatal period– Seizures with strokeSeizures with stroke

What do we need for the future?What do we need for the future?

Prospective cohort Prospective cohort studiesstudies– Standard evaluation of Standard evaluation of

risk and outcomerisk and outcome– Develop therapy and Develop therapy and

prevention strategiesprevention strategies

Incidence studiesIncidence studies

Case control studies Case control studies of risk factorsof risk factors

Outcome studiesOutcome studies