© 2010, american heart association. all rights reserved. this slide set was adapted from the...

© 2010, American Heart Association. All rights reserved.

• This slide set was adapted from the This slide set was adapted from the Management of Stroke in Infants and Management of Stroke in Infants and Children paperChildren paper

• This guideline reflects a consensus of This guideline reflects a consensus of expert opinion following thorough expert opinion following thorough literature review that consisted of a look literature review that consisted of a look at clinical trials and other evidence at clinical trials and other evidence related to the management of children.related to the management of children.


Management of Stroke in Management of Stroke in Infants and ChildrenInfants and Children

A Scientific Statement for Healthcare Professionals A Scientific Statement for Healthcare Professionals from a Special Writing Group of the Stroke Council, from a Special Writing Group of the Stroke Council, American Heart AssociationAmerican Heart Association

Cosponsored by the Council on Cardiovascular Cosponsored by the Council on Cardiovascular Disease in the YoungDisease in the YoungE. Steve Roach, MD, Chair; Meredith R. Golomb, MD, MSc; Robert Adams, E. Steve Roach, MD, Chair; Meredith R. Golomb, MD, MSc; Robert Adams, MS, MD; Jose Biller, MD; Stephen Daniels, MD, PhD; Gabrielle deVeber, MD; MS, MD; Jose Biller, MD; Stephen Daniels, MD, PhD; Gabrielle deVeber, MD; Donna Ferriero, MD; Blaise V. Jones, MD; Fenella J. Kirkham, MB, MD; R. Donna Ferriero, MD; Blaise V. Jones, MD; Fenella J. Kirkham, MB, MD; R. Michael Scott, MD; Edward R. Smith, MDMichael Scott, MD; Edward R. Smith, MD


Applying classification of Applying classification of recommendations and levels recommendations and levels of evidence.of evidence.


Introduction• Stroke in children has become increasingly

more recognized in recent years.• Children and adolescents have a remarkable

different presentation compared with older adults. An example of this are children with TIA, who commonly have a brain infarction by brain imaging despite the transient nature of presenting symptoms.

• Stroke subtype also varies with age.• In children about 55% are ischemic and about

45% are hemorrhagic.


Etiologies of Stroke in Children• About ½ of children presenting with an acute focal neurological About ½ of children presenting with an acute focal neurological

deficit have a previously know risk factor, and one or more RFs deficit have a previously know risk factor, and one or more RFs are uncovered in the remaining patients.are uncovered in the remaining patients.

• For ischemic stroke the most common underlying RF is sickle For ischemic stroke the most common underlying RF is sickle cell disease (SCD).cell disease (SCD).

• Heart Disease and chronic anemia (SCD and B-thalassemia) are Heart Disease and chronic anemia (SCD and B-thalassemia) are also RFs for CVST.also RFs for CVST.

• Head trauma can trigger ischemic stroke in children, and Head trauma can trigger ischemic stroke in children, and dehydration in venous stroke. dehydration in venous stroke.

• Infections, including Varicella, meningitis, tonsilitis, and otitis Infections, including Varicella, meningitis, tonsilitis, and otitis media, and anemia, leukocytosis and prothrombotic disorders media, and anemia, leukocytosis and prothrombotic disorders are thought to RFs for both.are thought to RFs for both.


Epidemiology of Childhood StrokeEpidemiology of Childhood Stroke

• Several studies have shown varying rates of stroke in children.

• The true frequency for ischemic stroke may be greater than previously suggested.

• Neonatal stroke estimates have shown 1/4000 live births. This study was done prior to the widespread use of brain CT, cranial ultrasound, and MRI.

• In the National Hospital Discharge Survey indicate that the rate of hemorrhagic stroke in term infants was 6.7/100,000 per year.


Definitions of Neonatal and Perinatal Stroke

• Neonatal stroke describes ischemic & Neonatal stroke describes ischemic & hemorrhagic events resulting from disruption hemorrhagic events resulting from disruption of arteries or veins from early gestation of arteries or veins from early gestation through the first month of life.through the first month of life.

• Perinatal stroke describes cerebrovascular Perinatal stroke describes cerebrovascular lesions occurring from 28 days gestation lesions occurring from 28 days gestation through the first 7 days of life. Some liberalize through the first 7 days of life. Some liberalize this definition from 20 weeks gestation to 28 this definition from 20 weeks gestation to 28 days after birth; lesions occurring before 28 days after birth; lesions occurring before 28 weeks have been documented.weeks have been documented.


Recommendations for Perinatal Stroke

Class I Recommendations

1. Markedly low platelet counts should be corrected in individuals with intracranial hemorrhage. (Class I, Level of Evidence B)

2. Neonates with ICH due to coagulation factor deficiency require replacement of the deficient coagulation factors. (Class I, Level of Evidence B)

3. Vitamin K should be administered to individuals with vitamin K–dependent coagulation disorders. (Class I, Level of Evidence B) Higher doses of vitamin K may be required in neonates with factor deficiencies resulting from maternal medications.

4. Patients who develop hydrocephalus following an intracranial hemorrhage should undergo ventricular drainage and later shunting if significant hydrocephalus persists. (Class I, Level of Evidence B)


Recommendations for Perinatal Stroke - Con’t

Class II RecommendationsClass II Recommendations

1. It is reasonable to treat dehydration and anemia in neonates with stroke. 1. It is reasonable to treat dehydration and anemia in neonates with stroke.

(Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C)

2. It is reasonable to use rehabilitation and ongoing physical therapy in an 2. It is reasonable to use rehabilitation and ongoing physical therapy in an effort to reduce neurological dysfunction in individuals with perinatal effort to reduce neurological dysfunction in individuals with perinatal stroke. stroke.

(Class IIa, Level of Evidence B)(Class IIa, Level of Evidence B)

3. It is reasonable to give folate and B vitamins to individuals with a MTHFR 3. It is reasonable to give folate and B vitamins to individuals with a MTHFR mutation in an effort to normalize homocysteine levels. mutation in an effort to normalize homocysteine levels. (Class IIa, Level (Class IIa, Level of Evidence C) of Evidence C)


Recommendations for Perinatal StrokeClass II (continued)Class II (continued)

4. It is reasonable to evacuate an intraparenchymal brain hematoma in order to 4. It is reasonable to evacuate an intraparenchymal brain hematoma in order to reduce very high intracranial pressure, although it is not clear whether this reduce very high intracranial pressure, although it is not clear whether this approach always improves the outcome. approach always improves the outcome. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C)

5. Anticoagulation with LMWH or UFH may be considered in selected neonates with 5. Anticoagulation with LMWH or UFH may be considered in selected neonates with severe thrombophilic disorders, multiple cerebral or systemic emboli, or clinical severe thrombophilic disorders, multiple cerebral or systemic emboli, or clinical or radiological evidence of propagating CVST despite supportive therapy. or radiological evidence of propagating CVST despite supportive therapy. (Class (Class IIb, Level of Evidence C)IIb, Level of Evidence C) Until the availability of additional information on its Until the availability of additional information on its safety and efficacy, a recommendation on the use of anticoagulation in other safety and efficacy, a recommendation on the use of anticoagulation in other neonates with CVST is not possible.neonates with CVST is not possible.

Class III RecommendationClass III Recommendation

Thrombolytic agents are not recommended in neonates until more information Thrombolytic agents are not recommended in neonates until more information about the safety and effectiveness of these agents is known. about the safety and effectiveness of these agents is known. (Class III, Level of (Class III, Level of Evidence C) Evidence C)


Recommendations for Children with Sickle Cell Disease

Class I RecommendationsClass I Recommendations

Acute management of ischemic stroke due to SCD should include optimal Acute management of ischemic stroke due to SCD should include optimal hydration, correction of hypoxemia, and correction of systemic hypotension. hydration, correction of hypoxemia, and correction of systemic hypotension. (Class I, Level of Evidence C)(Class I, Level of Evidence C)

2. Periodic transfusions to reduce the percentage of sickle hemoglobin are 2. Periodic transfusions to reduce the percentage of sickle hemoglobin are effective for reducing the risk of stroke in children 2 to 16 years of age with effective for reducing the risk of stroke in children 2 to 16 years of age with abnormal TCD results due to SCD and are recommended. abnormal TCD results due to SCD and are recommended. (Class I, Level (Class I, Level of Evidence A)of Evidence A)

3. Children with SCD and a confirmed cerebral infarction should be placed on a 3. Children with SCD and a confirmed cerebral infarction should be placed on a regular program of red cell transfusion in conjunction with measures to regular program of red cell transfusion in conjunction with measures to prevent iron overload. prevent iron overload. (Class I, Level of Evidence B)(Class I, Level of Evidence B)

4. Reducing the percentage of sickle hemoglobin with transfusions prior to 4. Reducing the percentage of sickle hemoglobin with transfusions prior to performing CA is indicated in an individual with SCD. performing CA is indicated in an individual with SCD. (Class I, Level of (Class I, Level of Evidence C)Evidence C)


Sickle Cell Disease and StrokeSickle Cell Disease and Stroke• Stroke a major complication of sickle cell Stroke a major complication of sickle cell

disease.disease.• Rates of stroke in SCD are much higher than Rates of stroke in SCD are much higher than

stroke in children in general. stroke in children in general. • Stroke rates overall in the Baltimore-Stroke rates overall in the Baltimore-

Washington area were calculated at Washington area were calculated at 1.29/100,000/yr, but for those with SCD the 1.29/100,000/yr, but for those with SCD the incidence rate was 285/100,000/yr (.28%/yr).incidence rate was 285/100,000/yr (.28%/yr).

• Rates of both ischemic and hemorrhagic stroke Rates of both ischemic and hemorrhagic stroke are higher in children with SCD.are higher in children with SCD.


Recommendations for Children Recommendations for Children with Sickle Cell Diseasewith Sickle Cell Disease

Class II Recommendations

1. For acute cerebral infarction, exchange transfusion designed to reduce Hb S to <30% total hemoglobin is reasonable. (Class IIa, Level of Evidence C)

2. In children with SCD and an intracranial hemorrhage, it is reasonable to evaluate for a structural vascular lesion. (Class IIa, Level of Evidence B)

3. In children with SCD, it is reasonable to repeat a normal TCD annually and to repeat an abnormal study in 1 month. (Class IIa, Level of Evidence B) Borderline and mildly abnormal TCD studies may be repeated in 3 to 6 months.

4. Hydroxyurea may be considered in children and young adults with SCD and stroke who cannot continue on long-term transfusion. (Class IIb, Level of Evidence B)

5. Bone marrow transplantation may be considered for children with SCD. (Class IIb, Level of Evidence C)

6. Surgical revascularization procedures may be considered as a last resort in children with SCD who continue to have cerebrovascular dysfunction despite optimal medical management. (Class IIb, Level of Evidence C)


Moyamoya Disease and Moyamoya Disease and Childhood StrokeChildhood Stroke

• Moyamoya syndrome is characterized by chronic progressive stenosis of the distal intracranial ICA, and less often, stenosis of the proximal ACA and MCA, the basilar artery, and the PCAs.

• Moyamoya is a Japanese word meaning “hazy, like a cloud of smoke drifting through the air”, referring to the often hazy angiographic appearance of the distal collateral network on angiography. Moyamoya syndrome.

• Those persons with no known risk factors are said to have Moyamoya disease.


Moyamoya Disease and Moyamoya Disease and Childhood StrokeChildhood Stroke

• Moyamoya is a relatively rare disease, Moyamoya is a relatively rare disease, 0.086/100,000 children in the United States).0.086/100,000 children in the United States).

• There are limited studies on it’s diagnosis, There are limited studies on it’s diagnosis, treatment, and outcome in the US.treatment, and outcome in the US.

• There are no randomized clinical trials to guide There are no randomized clinical trials to guide therapy.therapy.


Clinical Features and Clinical Features and DiagnosisDiagnosis• Stenosis involving the region of the Stenosis involving the region of the

distal ICA bifurcation (CI) and proximal distal ICA bifurcation (CI) and proximal portions of the ACA (A1) and MCA (M1).portions of the ACA (A1) and MCA (M1).

• Appearance of dilated basal collateral Appearance of dilated basal collateral arteriesarteries

• Bilateral abnormalities.Bilateral abnormalities.


Clinical Features and Clinical Features and DiagnosisDiagnosis• Accounts for approximately 6% of Accounts for approximately 6% of

childhood strokes in Western countries.childhood strokes in Western countries.• Half of the patients present before the Half of the patients present before the

age of 10 years.age of 10 years.• Some patients have intermittent Some patients have intermittent

ischemic events or even extended ischemic events or even extended periods of clinical stabilityperiods of clinical stability

• Others have a more fulminant rapid Others have a more fulminant rapid neurological decline.neurological decline.

• Children with moyamoya typically Children with moyamoya typically present with ischemic stroke or TIAs.present with ischemic stroke or TIAs.


Associated ConditionsAssociated Conditions• Genetic factors are involved.Genetic factors are involved.• Familial incidence affect 1st degree relatives in Familial incidence affect 1st degree relatives in

Japan (7%-12%); 6% was found at the Japan (7%-12%); 6% was found at the Children’s Hospital, Boston series.Children’s Hospital, Boston series.

• Linked to several genetic loci.Linked to several genetic loci.• Linked to specific human leukocyte antigen Linked to specific human leukocyte antigen

(HLA) haplotypes (HLA-B40 antigen (pts. (HLA) haplotypes (HLA-B40 antigen (pts. younger than 10 years) and HPA B52 antigen in younger than 10 years) and HPA B52 antigen in those older than 10 years.those older than 10 years.

• Association with AW24, BW46, B51-DR4, and Association with AW24, BW46, B51-DR4, and BW54 antigens.BW54 antigens.

• Elevated FGF may play a role.Elevated FGF may play a role.


Associated ConditionsAssociated Conditions

• Clinical conditions associated with Clinical conditions associated with MoyamoyaMoyamoya– Cranial radiotherapyCranial radiotherapy– Down syndromeDown syndrome– Neurobifromatosis type 1Neurobifromatosis type 1– Sickle cell disease (also see table 6 in Sickle cell disease (also see table 6 in

the manuscript)the manuscript)


Recommendations for Treatment Recommendations for Treatment of Moyamoya in Childrenof Moyamoya in Children


1. Different revascularization techniques are useful to effectively reduce the 1. Different revascularization techniques are useful to effectively reduce the risk of stroke due to moyamoya disease. risk of stroke due to moyamoya disease. (Class I, Level of Evidence B)(Class I, Level of Evidence B) However, despite a vast literature on moyamoya, there are no However, despite a vast literature on moyamoya, there are no controlled clinical trials to guide the selection of therapy. controlled clinical trials to guide the selection of therapy.

2. Indirect revascularization techniques are generally preferable and should 2. Indirect revascularization techniques are generally preferable and should be used in younger children whose small caliber vessels make direct be used in younger children whose small caliber vessels make direct anastomosis difficult; whereas direct bypass techniques are preferable anastomosis difficult; whereas direct bypass techniques are preferable in older individuals. in older individuals. (Class I, Level of Evidence C)(Class I, Level of Evidence C)

3. Revascularization surgery is useful for moyamoya. 3. Revascularization surgery is useful for moyamoya. (Class I, Level of (Class I, Level of Evidence B)Evidence B) Indications for revascularization surgery include Indications for revascularization surgery include progressive ischemic symptoms or evidence of inadequate blood flow progressive ischemic symptoms or evidence of inadequate blood flow or cerebral perfusion reserve in an individual without a contraindication or cerebral perfusion reserve in an individual without a contraindication to surgery to surgery (Class I, Level of Evidence B)(Class I, Level of Evidence B). .


Recommendations for Treatment Recommendations for Treatment of Moyamoya in Children - Con’tof Moyamoya in Children - Con’t


1. TCD may be useful in the evaluation and follow-up of individuals with 1. TCD may be useful in the evaluation and follow-up of individuals with moyamoya. moyamoya. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)

2. Techniques to minimize anxiety and pain during hospitalizations may 2. Techniques to minimize anxiety and pain during hospitalizations may reduce the likelihood of stroke caused by hyperventilation-induced reduce the likelihood of stroke caused by hyperventilation-induced vasoconstriction in individuals with moyamoya. vasoconstriction in individuals with moyamoya. (Class IIb, Level (Class IIb, Level of Evidence C)of Evidence C)

3. Management of systemic hypotension, hypovolemia, hyperthermia, and 3. Management of systemic hypotension, hypovolemia, hyperthermia, and hypocarbia during the intraoperative and perioperative periods may hypocarbia during the intraoperative and perioperative periods may reduce the risk of perioperative stroke in individuals with moyamoya reduce the risk of perioperative stroke in individuals with moyamoya disease. disease. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)



Class II (continued)Class II (continued)

4. Aspirin may be considered in individuals with moyamoya following 4. Aspirin may be considered in individuals with moyamoya following revascularization surgery or in asymptomatic individuals for whom revascularization surgery or in asymptomatic individuals for whom surgery is not anticipated. surgery is not anticipated. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)

5. Techniques to measure cerebral perfusion and blood flow reserve may 5. Techniques to measure cerebral perfusion and blood flow reserve may assist in the evaluation and follow-up of individuals with moyamoya assist in the evaluation and follow-up of individuals with moyamoya disease. disease. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)



Class III RecommendationsClass III Recommendations

1.1. Except in selected individuals with frequent TIAs or multiple Except in selected individuals with frequent TIAs or multiple infarctions despite antiplatelet therapy and surgery, anticoagulants infarctions despite antiplatelet therapy and surgery, anticoagulants are not recommended for most individuals with moyamoya because are not recommended for most individuals with moyamoya because of the risk of hemorrhage as well as the difficulty of maintaining of the risk of hemorrhage as well as the difficulty of maintaining therapeutic levels in children. therapeutic levels in children. (Class III, Level of Evidence C)(Class III, Level of Evidence C)

2. 2. In the absence of a strong family history of moyamoya disease or In the absence of a strong family history of moyamoya disease or medical conditions that predispose to moyamoya syndrome, there is medical conditions that predispose to moyamoya syndrome, there is insufficient evidence to justify screening studies for moyamoya insufficient evidence to justify screening studies for moyamoya disease in asymptomatic individuals or in relatives of patients with disease in asymptomatic individuals or in relatives of patients with moyamoya syndrome. moyamoya syndrome. (Class III, Level of Evidence C)(Class III, Level of Evidence C)


Dissections in Children as a Dissections in Children as a cause of Stroke (CCAD)cause of Stroke (CCAD)• CCAD accounts for 16 in 213 children (7.5%) CCAD accounts for 16 in 213 children (7.5%)

with ischemic stroke in one series.with ischemic stroke in one series.• In children the site of dissection of often In children the site of dissection of often

intracranial.intracranial.• Recurrence rate of CCADs is about 1%/yr.Recurrence rate of CCADs is about 1%/yr.• Greater among younger with inherited Greater among younger with inherited

arteriopathies such as Ehlers-Danlos syndrome arteriopathies such as Ehlers-Danlos syndrome type IVtype IV


Clinical associations of CCADClinical associations of CCAD• Marfan syndromeMarfan syndrome• Coartation of the aortaCoartation of the aorta• Cystic medical necrosisCystic medical necrosis• Autosomal dominant polycystic kidney diseaseAutosomal dominant polycystic kidney disease• Osteogenesis imperfectaOsteogenesis imperfecta• AtherosclerosisAtherosclerosis• Extreme arterial tortuosityExtreme arterial tortuosity• Moyamoya syndromeMoyamoya syndrome• Pharyngeal infectionsPharyngeal infections


Cervico-cephalic Arterial Cervico-cephalic Arterial Dissections (CCAD) in ChildrenDissections (CCAD) in ChildrenClass II RecommendationsClass II Recommendations

1. In children with extracranial CCAD, it is reasonable to begin either UFH or LMWH as a bridge to 1. In children with extracranial CCAD, it is reasonable to begin either UFH or LMWH as a bridge to oral anticoagulation. oral anticoagulation. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C)

2. It is reasonable to treat a child with an extracranial CCAD with either subcutaneous LMWH or 2. It is reasonable to treat a child with an extracranial CCAD with either subcutaneous LMWH or warfarin for 3 to 6 months.warfarin for 3 to 6 months. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C) Alternatively, an antiplatelet agent Alternatively, an antiplatelet agent may be substituted for LMWH or warfarin. Extending anticoagulant therapy beyond 6 months is may be substituted for LMWH or warfarin. Extending anticoagulant therapy beyond 6 months is a reasonable option for individuals who develop recurrent symptoms. a reasonable option for individuals who develop recurrent symptoms. (Class (Class IIa, Level of Evidence C)IIa, Level of Evidence C) It is reasonable to continue antiplatelet agents beyond 6 months, It is reasonable to continue antiplatelet agents beyond 6 months, especially when there is radiographic evidence of a residual abnormality of the dissected especially when there is radiographic evidence of a residual abnormality of the dissected artery. artery. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C)

3. In patients who continue to have symptoms from a CCAD despite optimal medical therapy, 3. In patients who continue to have symptoms from a CCAD despite optimal medical therapy, surgical procedures may be considered. surgical procedures may be considered. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)


Anticoagulation is not recommended for children with an intracranial dissection or those with SAH Anticoagulation is not recommended for children with an intracranial dissection or those with SAH due to CCAD. due to CCAD. (Class III, Level of Evidence C)(Class III, Level of Evidence C)


Migraine and Stroke in ChildrenMigraine and Stroke in Children• The exact contribution of migraine to the risk of stroke on The exact contribution of migraine to the risk of stroke on

children is unknown.children is unknown.• Migraine with aura seems to increase the risk of stroke in the Migraine with aura seems to increase the risk of stroke in the

young, and especially in those of childbearing potential and young, and especially in those of childbearing potential and those taking oral contraceptives.those taking oral contraceptives.

• Common migraine alone is unlikely to cause ischemic stroke, Common migraine alone is unlikely to cause ischemic stroke, but coupled with other RFs (smoking, pregnancy, oral but coupled with other RFs (smoking, pregnancy, oral contraceptives) may raise concern.contraceptives) may raise concern.

• It is prudent to evaluate a young patient with infarction for: It is prudent to evaluate a young patient with infarction for: history of migraine (and migraine like headache, such as in history of migraine (and migraine like headache, such as in CCAD. CCAD.

• Cerebral autosomal dominant arteriopathy with subcortical Cerebral autosomal dominant arteriopathy with subcortical infarcts an leukoencephalopathy (CADASIL), moyamoya and infarcts an leukoencephalopathy (CADASIL), moyamoya and mitochondrial encephalomyopathy, lactic acidosis, and stroke-mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events (MELAS).like events (MELAS).


Migraine and Stroke in ChildrenMigraine and Stroke in Children• Three genes promote familial hemiplegia migraine Three genes promote familial hemiplegia migraine

(affecting a subunit of a different ion channel).(affecting a subunit of a different ion channel).• Since oral contraception alters coagulation, it might be Since oral contraception alters coagulation, it might be

advisable for individuals with migraine and AIS on oral advisable for individuals with migraine and AIS on oral contraception to switch to another form of birth control.contraception to switch to another form of birth control.

• Options for prophylactic amitriptyline, sodium valproate, Options for prophylactic amitriptyline, sodium valproate, cyproheptadine or a combination of short acting cyproheptadine or a combination of short acting verapamil hydrochloride or other calcium blocker and verapamil hydrochloride or other calcium blocker and aspirin if not contraindicated.aspirin if not contraindicated.

• Currently there is no treatment for patients with Currently there is no treatment for patients with CADASIL, antiplatelets may be tried. CADASIL, antiplatelets may be tried.


Migraine as a Pediatric Stroke Migraine as a Pediatric Stroke Risk FactorRisk FactorClass II RecommendationsClass II Recommendations

1. Individuals with AIS and symptoms of migraine may be evaluated for other 1. Individuals with AIS and symptoms of migraine may be evaluated for other stroke risk factors. stroke risk factors. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)

2. It is reasonable to advise individuals with migraine and AIS who are taking oral 2. It is reasonable to advise individuals with migraine and AIS who are taking oral contraceptives to switch to another form of birth control. contraceptives to switch to another form of birth control. (Class IIa, Level of (Class IIa, Level of Evidence C)Evidence C)

3. It is reasonable to avoid triptan agents in children with hemiplegic migraine, 3. It is reasonable to avoid triptan agents in children with hemiplegic migraine, basilar migraine, known vascular risk factors, or prior cardiac or cerebral basilar migraine, known vascular risk factors, or prior cardiac or cerebral ischemia, at least pending the availability of more information. ischemia, at least pending the availability of more information. (Class IIa, (Class IIa, Level of Evidence C)Level of Evidence C)


Heart Disease and StrokeHeart Disease and Strokein Childrenin Children

• About ¼ of ischemic strokes in children are caused by cardiac About ¼ of ischemic strokes in children are caused by cardiac disease and most are known to have a cardiac lesion at the disease and most are known to have a cardiac lesion at the time of their stroke.time of their stroke.

• Complex cardiac disease, right-to-left shunting and cyanosis Complex cardiac disease, right-to-left shunting and cyanosis are high risk for stroke.are high risk for stroke.

• Emboli can arise at the atrial level (atrial septal defect with Emboli can arise at the atrial level (atrial septal defect with pulmonary hypertension) or at the arterial level (pulmonary pulmonary hypertension) or at the arterial level (pulmonary arterivenous fistula).arterivenous fistula).

• Occasionally children develop stroke due to acquired Occasionally children develop stroke due to acquired disorders: rheumatic, prosthetic, myxomatous, inflammatory, disorders: rheumatic, prosthetic, myxomatous, inflammatory, infective, marantic, traumatic, degenerative or congenital infective, marantic, traumatic, degenerative or congenital disorders.disorders.

• Rheumatic heart disease is less common (antibiotic therapy).Rheumatic heart disease is less common (antibiotic therapy).• The lifetime risk of systemic thromboembolism from untreated The lifetime risk of systemic thromboembolism from untreated

mitrail stenosis is 20%.mitrail stenosis is 20%.


Heart Disease and StrokeHeart Disease and Strokein Childrenin Children• Patients with prosthetic heart valves are at risk for endocarditis Patients with prosthetic heart valves are at risk for endocarditis

as well as stroke.as well as stroke.• Thromboembolic stroke can complicate cardiac cath and Thromboembolic stroke can complicate cardiac cath and

cardiac surgery.cardiac surgery.• Surgical repair of congenital cardiac defects reduces the Surgical repair of congenital cardiac defects reduces the

chance of stroke but does not eliminate the long-term risk of chance of stroke but does not eliminate the long-term risk of thromboembolism.thromboembolism.

• Neurological injury during cardiac surgery can also be caused Neurological injury during cardiac surgery can also be caused by global ischemia and reperfusion.by global ischemia and reperfusion.

• Children with heart disease who have low hemoglobin Children with heart disease who have low hemoglobin concentrations due to iron deficiency seem to have a higher concentrations due to iron deficiency seem to have a higher risk of arterial stroke (precise mechanism is not known).risk of arterial stroke (precise mechanism is not known).


Heart Disease and Stroke in Heart Disease and Stroke in ChildrenChildren• The foramen ovale usually closes at birth, but stays open in The foramen ovale usually closes at birth, but stays open in

about 35% of people between the ages of 1-29 years of age.about 35% of people between the ages of 1-29 years of age.• Patency provides the opportunity for right-to-left shunting.Patency provides the opportunity for right-to-left shunting.• Optimal treatment of parodoxical embolism associated with Optimal treatment of parodoxical embolism associated with

PFO is not known; ongoing studies in adults of transcatheter PFO is not known; ongoing studies in adults of transcatheter PFO closure may provide additional evidence that might apply PFO closure may provide additional evidence that might apply to children.to children.

• Neurological complication occur in 20-40% of individuals with Neurological complication occur in 20-40% of individuals with infective endocarditis involving the left side of the heart.infective endocarditis involving the left side of the heart.

• Stroke accounts for about ½ of the neurological events, and Stroke accounts for about ½ of the neurological events, and most often in the MCA territory or its branches.most often in the MCA territory or its branches.


Heart Disease and StrokeHeart Disease and Strokein Childrenin Children• ICH, TIAs and seizures also occur.ICH, TIAs and seizures also occur.• Pathophysiological mechanisms include septic embolism, Pathophysiological mechanisms include septic embolism,

infective aneurysm formation and vasculitis.infective aneurysm formation and vasculitis.• Cardiac arrhythmias are not common in children, but various Cardiac arrhythmias are not common in children, but various

types have been described.types have been described.• Atrial fibrillation occurs more frequently in children with Atrial fibrillation occurs more frequently in children with

hyperthyroidism or rheumatic heart disease as well as after hyperthyroidism or rheumatic heart disease as well as after surgery for congenital heart disease.surgery for congenital heart disease.

• Heart failure with reduced ejection fraction increases the risk of Heart failure with reduced ejection fraction increases the risk of embolism.embolism.

• Cardiomyopathy or MI from various causes can lead to cardiac Cardiomyopathy or MI from various causes can lead to cardiac arrhythmia or to cerebral embolism.arrhythmia or to cerebral embolism.


Children with Stroke and Children with Stroke and Heart DiseaseHeart DiseaseClass I RecommendationsClass I Recommendations

1. Therapy for congestive heart failure is indicated and may reduce the 1. Therapy for congestive heart failure is indicated and may reduce the likelihood of cardiogenic embolism. likelihood of cardiogenic embolism. (Class A, Level of Evidence C)(Class A, Level of Evidence C)

2. When feasible, congenital heart lesions, especially complex heart lesions 2. When feasible, congenital heart lesions, especially complex heart lesions with a high stroke risk, should be repaired, both to improve cardiac with a high stroke risk, should be repaired, both to improve cardiac function and to reduce the subsequent risk of stroke. function and to reduce the subsequent risk of stroke. (Class I, Level of (Class I, Level of Evidence C)Evidence C) This recommendation does not yet apply to PFOs. This recommendation does not yet apply to PFOs.

3. Resection of an atrial myxoma is indicated given its ongoing risk of 3. Resection of an atrial myxoma is indicated given its ongoing risk of cerebrovascular complications. cerebrovascular complications. (Class I, Level of Evidence C)(Class I, Level of Evidence C)


Children with Stroke and Children with Stroke and Heart Disease – Con’tHeart Disease – Con’t

1. For children with a cardiac embolism 1. For children with a cardiac embolism Class II RecommendationsClass II Recommendations

related to a PFO who are judged to have a high risk of recurrent related to a PFO who are judged to have a high risk of recurrent embolism, it is reasonable to initially introduce UFH or LMWH while embolism, it is reasonable to initially introduce UFH or LMWH while warfarin therapy is initiated and adjusted. warfarin therapy is initiated and adjusted. (Class IIa, Level of Evidence (Class IIa, Level of Evidence B)B) Alternatively, it is reasonable to use LMWH initially in this situation Alternatively, it is reasonable to use LMWH initially in this situation and to continue it instead of warfarin. and to continue it instead of warfarin. (Class IIa, Level of Evidence C(Class IIa, Level of Evidence C

2. In children with a risk of cardiac embolism, it is reasonable to continue 2. In children with a risk of cardiac embolism, it is reasonable to continue either LMWH or warfarin for at least 1 year or until the lesion either LMWH or warfarin for at least 1 year or until the lesion responsible for the risk has been corrected. responsible for the risk has been corrected. (Class IIa, Level of (Class IIa, Level of Evidence C)Evidence C) If the risk of If the risk of recurrent embolism is judged to be high, it is reasonable to continue recurrent embolism is judged to be high, it is reasonable to continue anticoagulation indefinitely as long as it is well tolerated. anticoagulation indefinitely as long as it is well tolerated. (Class IIa, (Class IIa, Level of Evidence C)Level of Evidence C)


Children with Stroke and Children with Stroke and Heart DiseaseHeart Disease

Class II (continued)Class II (continued)

3. For children with a suspected cardiac embolism unrelated to a PFO with a 3. For children with a suspected cardiac embolism unrelated to a PFO with a lower or unknown risk of stroke, it is reasonable to begin aspirin and continue lower or unknown risk of stroke, it is reasonable to begin aspirin and continue it for at least 1 year. it for at least 1 year. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C)

4. Surgical repair or transcatheter closure is reasonable in individuals with a 4. Surgical repair or transcatheter closure is reasonable in individuals with a major atrial septal defect both to reduce the stroke risk and to prevent long-major atrial septal defect both to reduce the stroke risk and to prevent long-term cardiac complications. term cardiac complications. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C) This recommendation does not apply to individuals with a PFO This recommendation does not apply to individuals with a PFO pending additional data.pending additional data.

5. There are few data to govern our management of patients with prosthetic valve 5. There are few data to govern our management of patients with prosthetic valve endocarditis, but it may be reasonable to continue maintenance endocarditis, but it may be reasonable to continue maintenance anticoagulation in individuals who are already taking it. anticoagulation in individuals who are already taking it. (Class IIb, Level of (Class IIb, Level of Evidence C)Evidence C)


Children with Stroke and Children with Stroke and Heart DiseaseHeart DiseaseClass III RecommendationsClass III Recommendations

1. Anticoagulant therapy is not recommended for individuals with native 1. Anticoagulant therapy is not recommended for individuals with native valve endocarditis. valve endocarditis. (Class III, Level of Evidence C)(Class III, Level of Evidence C)

2. Surgical removal of a cardiac rhabdomyoma is not necessary in 2. Surgical removal of a cardiac rhabdomyoma is not necessary in asymptomatic individuals with no stroke history. asymptomatic individuals with no stroke history.

(Class III, Level of Evidence C)(Class III, Level of Evidence C)


Hypercoagulable Disorders in Hypercoagulable Disorders in ChildrenChildren

• Various hypercoagulable disorders have been reported in Various hypercoagulable disorders have been reported in children.children.

• 20-50% of children presenting with AIS have a prothrombotic 20-50% of children presenting with AIS have a prothrombotic state.state.

• 33-99% of children with CVST have a hypercoagulable 33-99% of children with CVST have a hypercoagulable disorder.disorder.

• A prothrombotic state may be suspected in individuals with A prothrombotic state may be suspected in individuals with recurrent episodes of DVT, recurrent PE, a family hx of recurrent episodes of DVT, recurrent PE, a family hx of thrombotic events, or if the thrombotic event occurs during thrombotic events, or if the thrombotic event occurs during childhood, adolescence or early adulthood.childhood, adolescence or early adulthood.

• Stroke in children with prothrombotic states is relatively low, Stroke in children with prothrombotic states is relatively low, but increases in children with other risk factors.but increases in children with other risk factors.

• It is reasonable to evaluate for at least the more common It is reasonable to evaluate for at least the more common prothrombotic states even when another stroke risk factor prothrombotic states even when another stroke risk factor has been identified.has been identified.



• Coagulation abnormalities identified in stroke in Coagulation abnormalities identified in stroke in children:children:– Antithrombin Antithrombin – Protein C or protein S deficienciesProtein C or protein S deficiencies– Activated protein C resistanceActivated protein C resistance– Factor V Leiden mutationFactor V Leiden mutation– Prothrombin gene mutation (G20210A)Prothrombin gene mutation (G20210A)– Antiphospholipid antibody syndrome (APAS)Antiphospholipid antibody syndrome (APAS)



• Pregnancy as a stroke RF in teenaged girlsPregnancy as a stroke RF in teenaged girls– Brain infarction and ICH is increased during the first 6 Brain infarction and ICH is increased during the first 6

weeks after delivery but not during pregnancy.weeks after delivery but not during pregnancy.– AIS and ICH account for 4-8.5% of maternal mortality AIS and ICH account for 4-8.5% of maternal mortality

in the US.in the US.– SAH is responsible for 5-12% of maternal deaths SAH is responsible for 5-12% of maternal deaths

during pregnancy.during pregnancy.– Alterations of multiple coagulation factors occur Alterations of multiple coagulation factors occur

during pregnancy (increased platelet adhesion, during pregnancy (increased platelet adhesion, increased fibrinogen, increased factors VII, VIII, IX, X increased fibrinogen, increased factors VII, VIII, IX, X & XII; decreased fibrinolysis, reduced levels of & XII; decreased fibrinolysis, reduced levels of available circulating plasminogen activator).available circulating plasminogen activator).

– Levels of Protein C and S fall.Levels of Protein C and S fall.


Hypercoagulable Disorders in Hypercoagulable Disorders in ChildrenChildren• Pregnancy as a stroke RF in teenaged girlsPregnancy as a stroke RF in teenaged girls

– Arterial strokes are more common during pregnancy, Arterial strokes are more common during pregnancy, whereas venous occlusion is more common during whereas venous occlusion is more common during the puerperium.the puerperium.

– Eclampsia is a leading cause of both ICH and non-Eclampsia is a leading cause of both ICH and non-hemorrhagic stroke.hemorrhagic stroke.


Hypercoagulable States in Hypercoagulable States in ChildrenChildrenClass II RecommendationsClass II Recommendations

1. Although the risk of stroke from most prothrombotic states is relatively low, the risk 1. Although the risk of stroke from most prothrombotic states is relatively low, the risk tends to increase when a prothrombotic disorder occurs in children with other risk tends to increase when a prothrombotic disorder occurs in children with other risk factors. Thus, it is reasonable to evaluate for the more common prothrombotic factors. Thus, it is reasonable to evaluate for the more common prothrombotic states even when another stroke risk factor has been identified. states even when another stroke risk factor has been identified. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C)

2. It is reasonable to discontinue oral contraceptives in adolescents with AIS or CVST. 2. It is reasonable to discontinue oral contraceptives in adolescents with AIS or CVST. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C)

3. It is reasonable to measure the serum homocysteine level of children with CVST or 3. It is reasonable to measure the serum homocysteine level of children with CVST or AIS. AIS. (Class IIa, Level of Evidence B)(Class IIa, Level of Evidence B) and to institute measures to lower the and to institute measures to lower the homocysteine level when it is higher than normal. homocysteine level when it is higher than normal. (Class IIa, Level of Evidence B)(Class IIa, Level of Evidence B) Measures to lower the homocysteine level might include diet or supplementation of Measures to lower the homocysteine level might include diet or supplementation of folate, vitamin B6, or vitamin B12.folate, vitamin B6, or vitamin B12.


Risk Modification in ChildrenRisk Modification in Children• Fabry’s disease (Anderson Fabry disease or Fabry’s disease (Anderson Fabry disease or

angiokeratoma corporis diffusum) is a X-linked angiokeratoma corporis diffusum) is a X-linked deficiency of alpha-galactosidase characterized by deficiency of alpha-galactosidase characterized by curaneous andiogeratomas, corneal and lenticular curaneous andiogeratomas, corneal and lenticular opacities, and painful paresthesias.opacities, and painful paresthesias.

• Vascular complications are common in those with Fabry Vascular complications are common in those with Fabry disease (renal failure, arterial hypertension, MI and disease (renal failure, arterial hypertension, MI and cerebral ischemia – in young and middle-aged men).cerebral ischemia – in young and middle-aged men).

• Brain infarction in Fabry disease is most common in the Brain infarction in Fabry disease is most common in the posterior circulation.posterior circulation.

• Enzyme replacement therapy with genetically engineered Enzyme replacement therapy with genetically engineered galactosidase A (agalsidase alpha) reduces symptoms galactosidase A (agalsidase alpha) reduces symptoms and vascular complications.and vascular complications.


Risk Modification in ChildrenRisk Modification in Children• Ischemic and hemorrhagic strokes have been reported in Ischemic and hemorrhagic strokes have been reported in

individuals who use cocaine.individuals who use cocaine.• Stroke has been associated in individuals using Stroke has been associated in individuals using

amphetamines, ecstasy and with drugs such as amphetamines, ecstasy and with drugs such as phentermine (used as an appetite suppressant – phentermine (used as an appetite suppressant – although reported in adults rather than in children).although reported in adults rather than in children).

• Phencyclidine (PCP or angel dust) may increase the risk Phencyclidine (PCP or angel dust) may increase the risk if ICH.if ICH.

• Anabolic steroids could potentially lead to systemic Anabolic steroids could potentially lead to systemic hypertension and thrombogenesis.hypertension and thrombogenesis.


Modifying Stroke Risk FactorsModifying Stroke Risk Factorsin Childrenin ChildrenClass I RecommendationsClass I Recommendations

1. Individuals with Fabry disease should receive alpha galactosidase 1. Individuals with Fabry disease should receive alpha galactosidase replacement therapy. replacement therapy. (Class I, Level of Evidence B)(Class I, Level of Evidence B)

2. If a treatable stroke risk factor is discovered in a child who has had a 2. If a treatable stroke risk factor is discovered in a child who has had a stroke, the underlying condition should be treated. stroke, the underlying condition should be treated. (Class I, Level of (Class I, Level of Evidence C)Evidence C)


Modifying Stroke Risk FactorsModifying Stroke Risk Factorsin Childrenin Children


1. It is reasonable to seek and to treat iron deficiency because it may increase the risk of AIS 1. It is reasonable to seek and to treat iron deficiency because it may increase the risk of AIS in conjunction with other risk factors. in conjunction with other risk factors. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C) Drinking cow’s Drinking cow’s milk has been known to promote iron deficiency, so limiting its consumption may be milk has been known to promote iron deficiency, so limiting its consumption may be considered. considered. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)

2. It is reasonable to counsel children with stroke and their families regarding dietary 2. It is reasonable to counsel children with stroke and their families regarding dietary improvement, the benefits of exercise, and the avoidance of tobacco products. improvement, the benefits of exercise, and the avoidance of tobacco products. (Class IIa, (Class IIa, Level of Evidence C)Level of Evidence C)

3. It is reasonable to suggest an alternative to oral contraceptives following a stroke, 3. It is reasonable to suggest an alternative to oral contraceptives following a stroke, particularly if there is evidence of a prothrombotic state. particularly if there is evidence of a prothrombotic state. (Class IIa, Level of (Class IIa, Level of Evidence C)Evidence C)


Outcome and Rehabilitation Outcome and Rehabilitation after Stroke in Childrenafter Stroke in Children• 20-40% of children die after a stroke.20-40% of children die after a stroke.• Mortality is higher for ICH (about 1/3) than for ischemic Mortality is higher for ICH (about 1/3) than for ischemic

stroke (up to 20% with ½ related to underlying systemic stroke (up to 20% with ½ related to underlying systemic illness rather than the stroke itself).illness rather than the stroke itself).

• Death during the acute phase is predicted by the level of Death during the acute phase is predicted by the level of consciousness on admission.consciousness on admission.

• Recurrent stroke: 6-15% and mortality is highest in this Recurrent stroke: 6-15% and mortality is highest in this group.group.

• Intractable hypertension is a major predictor or poor Intractable hypertension is a major predictor or poor outcome in patients with a large ICH or intracerebellar outcome in patients with a large ICH or intracerebellar hemorrhage and massive hemispheric or cerebellar hemorrhage and massive hemispheric or cerebellar infarction.infarction.


Outcome and Rehabilitation Outcome and Rehabilitation after Stroke in Childrenafter Stroke in Children• 50-80% of surviving children have neurological 50-80% of surviving children have neurological

impairment, most commonly hemiparesis.impairment, most commonly hemiparesis.• Neurological outcome is worse in those with ICH, CVST Neurological outcome is worse in those with ICH, CVST

and posterior circulation stroke.and posterior circulation stroke.• Other problems include: neuropsychological deficits, Other problems include: neuropsychological deficits,

poor attention, behavioral problems, and poor quality of poor attention, behavioral problems, and poor quality of life.life.

• Predictors of poor neurological, cognitive and behavioral Predictors of poor neurological, cognitive and behavioral outcome include: systemic disease, multiple risk factors, outcome include: systemic disease, multiple risk factors, infarct size, cortical involvement, thromboembolism and infarct size, cortical involvement, thromboembolism and moyamoya.moyamoya.


Outcome and Rehabilitation Outcome and Rehabilitation after Stroke in Childrenafter Stroke in Children• Early evaluation of physical and cognitive disability is Early evaluation of physical and cognitive disability is

key to preventing avoidable complications and in key to preventing avoidable complications and in planning rehabilitation, which should involve the planning rehabilitation, which should involve the multidisciplinary team.multidisciplinary team.

• Constrain therapy may be adapted for children and Constrain therapy may be adapted for children and appears to be associated with improved function of the appears to be associated with improved function of the hemiparetic hand.hemiparetic hand.


Rehabilitation after Rehabilitation after Childhood StrokeChildhood StrokeClass I RecommendationsClass I Recommendations1. Age-appropriate rehabilitation and therapy programs are indicated for 1. Age-appropriate rehabilitation and therapy programs are indicated for

children following a stroke. children following a stroke. (Class I, Level of Evidence C)(Class I, Level of Evidence C)

2. Psychological assessment to document cognitive and language deficits 2. Psychological assessment to document cognitive and language deficits is useful for planning therapy and educational programs after a child’s is useful for planning therapy and educational programs after a child’s stroke. stroke. (Class I, Level of Evidence C)(Class I, Level of Evidence C)

* See also earlier recommendation for SCD, CCAD, hypercoagulable state, and moyamoya disease.


Cerebral HemorrhageCerebral Hemorrhagein Childrenin Children• Intracranial hemorrhage in older children.Intracranial hemorrhage in older children.

– Specific hemorrhage risk factors include: arteriovenous Specific hemorrhage risk factors include: arteriovenous malformations (AVMs), intracranial aneurysms, or malformations (AVMs), intracranial aneurysms, or hemophilia.hemophilia.

• Brain hemorrhage in children presents much like adults:Brain hemorrhage in children presents much like adults:– Acute headache, vomiting and rapid deterioration of Acute headache, vomiting and rapid deterioration of

neurological function.neurological function.– In children the presentation may be subtler unless the In children the presentation may be subtler unless the

hemorrhage involves the motor pathways or the brainstem.hemorrhage involves the motor pathways or the brainstem.

• Hemorrhage in Infants and Term Neonates.Hemorrhage in Infants and Term Neonates.– Symptoms may be more subtler and less specific in infants Symptoms may be more subtler and less specific in infants

and neonates than in older children, especially smaller and neonates than in older children, especially smaller hemorrhages.hemorrhages.


Evaluation and Treatment of Evaluation and Treatment of Hemorrhage in ChildrenHemorrhage in Children


1. Children with non-traumatic brain hemorrhage should undergo a thorough risk 1. Children with non-traumatic brain hemorrhage should undergo a thorough risk factor evaluation, including standard cerebral angiography when noninvasive tests factor evaluation, including standard cerebral angiography when noninvasive tests have failed to establish an etiology, in an effort to identify treatable risk factors have failed to establish an etiology, in an effort to identify treatable risk factors before another hemorrhage occurs. before another hemorrhage occurs. (Class I, Level of Evidence C)(Class I, Level of Evidence C)

2. Children with a severe coagulation factor deficiency should receive appropriate 2. Children with a severe coagulation factor deficiency should receive appropriate factor replacement therapy, and children with less severe factor deficiency should factor replacement therapy, and children with less severe factor deficiency should receive factor replacement following trauma. receive factor replacement following trauma. (Class I, Level of Evidence A)(Class I, Level of Evidence A)

3. Given the risk of repeat hemorrhage from congenital vascular anomalies, these 3. Given the risk of repeat hemorrhage from congenital vascular anomalies, these lesions should be identified and corrected whenever it is clinically feasible. lesions should be identified and corrected whenever it is clinically feasible. Similarly, other treatable hemorrhage risk factors should be corrected. Similarly, other treatable hemorrhage risk factors should be corrected. (Class I, Level of Evidence C)(Class I, Level of Evidence C)

4. Stabilizing measures in patients with brain hemorrhage should include optimizing 4. Stabilizing measures in patients with brain hemorrhage should include optimizing the respiratory effort, controlling systemic hypertension, controlling epileptic the respiratory effort, controlling systemic hypertension, controlling epileptic seizures, and managing increased intracranial pressure. seizures, and managing increased intracranial pressure. (Class I, Level of Evidence C)(Class I, Level of Evidence C)


Evaluation and Treatment of Evaluation and Treatment of Hemorrhage in ChildrenHemorrhage in ChildrenClass II RecommendationsClass II Recommendations

1. It is reasonable to follow asymptomatic individuals who have a condition that 1. It is reasonable to follow asymptomatic individuals who have a condition that predisposes them to intracranial aneurysms with a cranial MRA every 1 to 5 predisposes them to intracranial aneurysms with a cranial MRA every 1 to 5 years depending on the perceived level of risk posed by an underlying condition. years depending on the perceived level of risk posed by an underlying condition. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C) Should the individual develop symptoms that Should the individual develop symptoms that could be explained by an aneurysm, CT angiography or catheter angiography could be explained by an aneurysm, CT angiography or catheter angiography may be considered even if the patient’s MRA fails to show evidence of an may be considered even if the patient’s MRA fails to show evidence of an aneurysm. aneurysm. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C) Given the possible need for repeated Given the possible need for repeated studies over a period of years, CT angiography may be preferable to catheter studies over a period of years, CT angiography may be preferable to catheter angiography for screening individuals at risk for aneurysm. angiography for screening individuals at risk for aneurysm. (Class IIb, Level of (Class IIb, Level of Evidence C)Evidence C)

2. Individuals with SAH may benefit from measures to control cerebral vasospasm. 2. Individuals with SAH may benefit from measures to control cerebral vasospasm. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)


Evaluation and Treatment of Evaluation and Treatment of Hemorrhage in ChildrenHemorrhage in Children


1. Surgical evacuation of a supratentorial intracerebral hematoma is not 1. Surgical evacuation of a supratentorial intracerebral hematoma is not recommended for most patients. recommended for most patients. (Class III, Level of Evidence C)(Class III, Level of Evidence C) However, information from small numbers of patients suggests that However, information from small numbers of patients suggests that surgery may help selected individuals with developing brain surgery may help selected individuals with developing brain herniation or extremely elevated intracranial pressure.herniation or extremely elevated intracranial pressure.

2. Although there is strong evidence to support the use of periodic blood 2. Although there is strong evidence to support the use of periodic blood transfusions in individuals with SCD who are at high risk for ischemic transfusions in individuals with SCD who are at high risk for ischemic infarction (see section II.B.3.a), there are no data to indicate that infarction (see section II.B.3.a), there are no data to indicate that periodic transfusions reduce the risk of intracranial hemorrhage due periodic transfusions reduce the risk of intracranial hemorrhage due to SCD. to SCD. (Class III, Level of Evidence B)(Class III, Level of Evidence B)


Cerebral Venous Sinus Cerebral Venous Sinus Thrombosis (CVST) in ChildrenThrombosis (CVST) in Children

• Clinical manifestations of CVST in children Clinical manifestations of CVST in children are sometimes non-specific and subtle.are sometimes non-specific and subtle.

• Presenting symptoms include: seizures, Presenting symptoms include: seizures, increased intracranial pressure, and increased intracranial pressure, and headache. headache.

• Some children develop hydrocephalus, Some children develop hydrocephalus, subdural hematoma, SAH or ICH or subdural hematoma, SAH or ICH or infarction.infarction.



• Underlying conditions associated with CVSTUnderlying conditions associated with CVST• Ilnesses such as otitis media, meningitis and Ilnesses such as otitis media, meningitis and

diabetic ketoacidosis may be complicated by diabetic ketoacidosis may be complicated by CVST.CVST.

• L-aspariginase therapy, used primarily in L-aspariginase therapy, used primarily in children with leukemia may result in CVST.children with leukemia may result in CVST.

• Some chronic illnesses such as inflammatory Some chronic illnesses such as inflammatory bowel disease, SLE, thyrotosicosis, nephrotic bowel disease, SLE, thyrotosicosis, nephrotic syndrome, and gastroenteritis may increase the syndrome, and gastroenteritis may increase the likelihood of CVST especially in the setting of likelihood of CVST especially in the setting of dehydration. dehydration.



• CVST can occur in the context of chronic hemolytic anemia, B-thalassemia major and SCD.

• Prothrombotic disorders and CVST in Children.– Prothrombotic disorders are found in 1/3 to 2/3 of children

with CVST.– Hereditary defects account for most prothrombotic states in

children; some have acquired deficiencies of protein C, protein S, or antithrombin.

– Occasionally, infants with homozygous protein C deficiency develop severe dysfunction from widespread thrombosis.

– Elevated factor VIII levels also have been reported.– Patients with homocystinuria and homozygotes for

thermolabile variant of the MTHFR gene may have some increased risk of CVST.



• Neuroimaging in CVSTNeuroimaging in CVST– Neuroimaging findings are similar in children and Neuroimaging findings are similar in children and

adults.adults.– It is important to study the patient early because It is important to study the patient early because

occluded venous sinuses commonly recanalize.occluded venous sinuses commonly recanalize.– Unenhance CT scans may detect deep vein Unenhance CT scans may detect deep vein

thrombosis as linear densities in the deep and thrombosis as linear densities in the deep and cortical veins.cortical veins.

– As the thrombus becomes less dense, contrast-As the thrombus becomes less dense, contrast-enhanced CT may demonstrate the “empty delta” enhanced CT may demonstrate the “empty delta” sign, a filling defect, in the posterior part of the sign, a filling defect, in the posterior part of the saggital sinus.saggital sinus.



• Neuroimaging in CVSTNeuroimaging in CVST– Diffusion and perfusion MRI detect venous Diffusion and perfusion MRI detect venous

congestion in CVST and help differential congestion in CVST and help differential cytotoxic and vasogenic edema.cytotoxic and vasogenic edema.

– CT venography and MRI with MRV are now CT venography and MRI with MRV are now the preferred methods for investigation of the preferred methods for investigation of CVST.CVST.



• Treatment includes supportive and Treatment includes supportive and symptomatic measures such as symptomatic measures such as hydration appropriate hydration appropriate antimicrobials, control of seizures antimicrobials, control of seizures with anticonvulsants and contral of with anticonvulsants and contral of intracranial pressure.intracranial pressure.


Treatment of Cerebral Venous Treatment of Cerebral Venous Sinus ThrombosisSinus Thrombosis


1. Supportive measures for children with CVST should include appropriate hydration, 1. Supportive measures for children with CVST should include appropriate hydration, control of epileptic seizures, and treatment of elevated intracranial pressure. control of epileptic seizures, and treatment of elevated intracranial pressure. (Class (Class I, Level of Evidence C) I, Level of Evidence C)

2. Children with CVST should have a complete blood count. 2. Children with CVST should have a complete blood count. (Class I, Level of Evidence (Class I, Level of Evidence C)C)

3. Children with a CVST and a suspected bacterial infection should receive appropriate 3. Children with a CVST and a suspected bacterial infection should receive appropriate antibiotics. antibiotics. (Class I, Level of Evidence C) (Class I, Level of Evidence C)

4. Given the potential for visual loss due to severe or long-standing increased 4. Given the potential for visual loss due to severe or long-standing increased intracranial pressure in children with CVST, periodic assessments of the visual intracranial pressure in children with CVST, periodic assessments of the visual fields and the visual acuity should be done, and appropriate measures to control fields and the visual acuity should be done, and appropriate measures to control elevated intracranial pressure and its complications should be instituted. elevated intracranial pressure and its complications should be instituted. (Class I, (Class I, Level of Evidence C)Level of Evidence C)




1. Children with CVST may benefit from a thorough thrombophilic screen to identify 1. Children with CVST may benefit from a thorough thrombophilic screen to identify underlying coagulation defects, some of which could affect the risk of subsequent underlying coagulation defects, some of which could affect the risk of subsequent re-thromboses and influence therapeutic decisions. re-thromboses and influence therapeutic decisions. (Class IIb, Level of Evidence (Class IIb, Level of Evidence B)B)

2. Children with CVST may benefit from investigation for underlying infections with 2. Children with CVST may benefit from investigation for underlying infections with blood cultures and sinus radiographs. blood cultures and sinus radiographs. (Class IIb, Level of Evidence B)(Class IIb, Level of Evidence B)

3. Monitoring the intracranial pressure may be considered during the acute phase of 3. Monitoring the intracranial pressure may be considered during the acute phase of CVST. CVST. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)

4. It is reasonable to repeat the neuroimaging studies in children with CVST to confirm 4. It is reasonable to repeat the neuroimaging studies in children with CVST to confirm vessel recanalization or recurrence of the thrombus. vessel recanalization or recurrence of the thrombus. (Class IIa, Level of Evidence (Class IIa, Level of Evidence C)C)


Treatment of Cerebral Venous Treatment of Cerebral Venous Sinus Thrombosis – Con’tSinus Thrombosis – Con’t

5. Given the frequency of epileptic seizures in children with an acute CVST, continuous EEG monitoring may be considered for individuals who are unconscious and/or mechanically ventilated. (Class IIb, Level of Evidence C)

6. It is reasonable to institute either intravenous UFH or subcutaneous LMWH in children with CVST, whether or not there is secondary hemorrhage, followed by warfarin therapy for 3 to 6 months. (Class IIa, Level of Evidence C)

7. In selected children with CVST, the administration of a thrombolytic agent may be considered. (Class IIb, Level of Evidence C)



Class III RecommendationClass III RecommendationUntil there is more evidence of safety and effectiveness, anticoagulation is not Until there is more evidence of safety and effectiveness, anticoagulation is not appropriate for most neonates with CVST. appropriate for most neonates with CVST. (Class III, Level of Evidence C)(Class III, Level of Evidence C) An An exception may be considered in individuals with severe prothrombotic exception may be considered in individuals with severe prothrombotic disorders, multiple cerebral or systemic emboli, or radiological evidence of disorders, multiple cerebral or systemic emboli, or radiological evidence of propagating CVST despite supportive therapy.propagating CVST despite supportive therapy.


Supportive Therapy afterSupportive Therapy afterStroke in ChildrenStroke in ChildrenClass I RecommendationsClass I Recommendations

1. Supportive measures for AIS should include control of fever, maintenance of 1. Supportive measures for AIS should include control of fever, maintenance of normal oxygenation, control of systemic hypertension, and normalization of normal oxygenation, control of systemic hypertension, and normalization of serum glucose levels. serum glucose levels. (Class I, Level of Evidence C)(Class I, Level of Evidence C)

Class II RecommendationClass II Recommendation

It is reasonable to treat dehydration and anemia in children with stroke. It is reasonable to treat dehydration and anemia in children with stroke. (Class (Class IIa, Level of Evidence C)IIa, Level of Evidence C)


Supportive Therapy after Supportive Therapy after Stroke in ChildrenStroke in Children


1. There is no evidence that the use of supplemental oxygen is beneficial in children 1. There is no evidence that the use of supplemental oxygen is beneficial in children with stroke in the absence of hypoxemia. with stroke in the absence of hypoxemia. (Class III, Level of Evidence C)(Class III, Level of Evidence C)

2. In the absence of clinical or electrographic seizures, prophylactic administration 2. In the absence of clinical or electrographic seizures, prophylactic administration of antiepileptic medications in children with ischemic stroke is not necessary. of antiepileptic medications in children with ischemic stroke is not necessary. (Class III, Level of Evidence C)(Class III, Level of Evidence C)

3. In the absence of additional data confirming its safety and efficacy, hypothermia 3. In the absence of additional data confirming its safety and efficacy, hypothermia should not be used in children with stroke except in the context of a clinical trial. should not be used in children with stroke except in the context of a clinical trial. (Class III, Level of Evidence C)(Class III, Level of Evidence C)


Recommendations for LMWH Recommendations for LMWH in Children with Strokein Children with StrokeClass I Recommendation

Anticoagulation with LMWH is useful for long-term anticoagulation of children with a substantial risk of recurrent cardiac embolism, CVST, and selected hypercoagulable states. (Class I, Level of Evidence C)

Class II Recommendations

1. The protocol outlined in Table 10 is a reasonable approach to the initiation and adjustment of LMWH in children with stroke who require its use. (Class IIa, Level of Evidence C)

2. The administration of LMWH or UFH may be considered in children for up to 1 week after an ischemic stroke pending further evaluation to determine the stroke’s etiology. (Class IIb, Level of Evidence C)


Warfarin in ChildrenWarfarin in Childrenwith Strokewith StrokeClass II RecommendationsClass II Recommendations

1. Anticoagulation with warfarin is reasonable for the long-term 1. Anticoagulation with warfarin is reasonable for the long-term anticoagulation of children with a substantial risk of recurrent cardiac anticoagulation of children with a substantial risk of recurrent cardiac embolism, CCAD, CVST, or selected hypercoagulable states. embolism, CCAD, CVST, or selected hypercoagulable states. (Class IIa, (Class IIa, Level of Evidence C)Level of Evidence C)

2. The protocol outlined in Table 11 is a reasonable approach to the 2. The protocol outlined in Table 11 is a reasonable approach to the initiation and maintenance of warfarin in children with stroke who initiation and maintenance of warfarin in children with stroke who require its use. require its use. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C)


Aspirin Use in ChildrenAspirin Use in Childrenwith Strokewith Stroke


1. Aspirin is a reasonable option for the secondary prevention of AIS in children 1. Aspirin is a reasonable option for the secondary prevention of AIS in children whose infarction is not due to SCD and in children who are not known to have a whose infarction is not due to SCD and in children who are not known to have a high risk of recurrent embolism or a severe hypercoagulable disorder. high risk of recurrent embolism or a severe hypercoagulable disorder. (Class IIa, (Class IIa, Level of Evidence C) Level of Evidence C)

2. A dose of 3 to 5 mg/kg per day is a reasonable initial aspirin dose for stroke 2. A dose of 3 to 5 mg/kg per day is a reasonable initial aspirin dose for stroke prevention in children (Class IIa, Level of Evidence C). If dose-related side effects prevention in children (Class IIa, Level of Evidence C). If dose-related side effects occur with this aspirin dose, a dose reduction to 1 to 3 mg/kg may be considered. occur with this aspirin dose, a dose reduction to 1 to 3 mg/kg may be considered. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)

3. In children taking aspirin for stroke prevention, it is reasonable to vaccinate for 3. In children taking aspirin for stroke prevention, it is reasonable to vaccinate for varicella and to administer an annual influenza vaccine in an effort to reduce the varicella and to administer an annual influenza vaccine in an effort to reduce the risk of Reye’s syndrome. risk of Reye’s syndrome. (Class IIa, Level of Evidence C)(Class IIa, Level of Evidence C) It is reasonable to It is reasonable to withhold aspirin during influenza and varicella infections. withhold aspirin during influenza and varicella infections. (Class IIa, Level of (Class IIa, Level of Evidence C)Evidence C)

* Most authorities would recommend discontinuation of aspirin (of any dose) during symptomatic * Most authorities would recommend discontinuation of aspirin (of any dose) during symptomatic varicella (chicken pox) or influenza.varicella (chicken pox) or influenza.


Thrombolytic Therapy for Thrombolytic Therapy for Childhood StrokeChildhood StrokeClass II RecommendationClass II Recommendation

Thrombolytic therapy with tPA may be considered in selected children with Thrombolytic therapy with tPA may be considered in selected children with CVST. CVST. (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)


Until there are additional published safety and efficacy data, tPA is not Until there are additional published safety and efficacy data, tPA is not recommended for AIS outside of a clinical trial. recommended for AIS outside of a clinical trial. (Class III, Level of Evidence C)(Class III, Level of Evidence C)


Screening Family Members Screening Family Members for Stroke Risk Factorsfor Stroke Risk Factors


1. Thrombophilia screening may be offered to family members of children with 1. Thrombophilia screening may be offered to family members of children with ischemic stroke or CVST and known thrombophilic defects. It is reasonable to ischemic stroke or CVST and known thrombophilic defects. It is reasonable to counsel family members about the risks and benefits of this screening. counsel family members about the risks and benefits of this screening. (Class IIa, (Class IIa, Level of Evidence C)Level of Evidence C)

2. Thrombophilia screening may be offered to the mothers of children with ischemic 2. Thrombophilia screening may be offered to the mothers of children with ischemic stroke that occurred before, during, or immediately after birth even if stroke that occurred before, during, or immediately after birth even if thrombophilia screening in the neonate is negative. It is reasonable to counsel thrombophilia screening in the neonate is negative. It is reasonable to counsel the individual about the risks and benefits of this screening. the individual about the risks and benefits of this screening. (Class IIa, Level of (Class IIa, Level of Evidence C)Evidence C)


Protocol for Heparin AdministrationProtocol for Heparin Administrationand Adjustment in Childrenand Adjustment in Children

Stage Description aPTT Bolus (units/Kg) Hold (min) Change rate (%)

Repeat aPTT

I. Loading dose 75 IV over 10 minutes

__ __ __

II. Begin maintenance Age < 1 year Age > 1 year

28 units/ Kg hour20 units/Kg/ hour

__ __ __

III. A PTT adjustment* < 50 50-59 60-85 86-95 96-120 > 120

50 units/Kg-----

0000

3040

+10%+10%

0-10%-10%-15%

4 hours4 hours

Next day4 hours4 hours4 hours

IV. Obtain aPTT 4 hours after heparin load and 4 hours after any infusion rate change

V. When aPTT values are in therapeutic range, measure daily CBC and aPTT

*Heparin adjusted to maintain aPTT at 60 to 85 seconds, assuming that this reflects an anti–factor Xa level of 0.35 to 0.70. *Heparin adjusted to maintain aPTT at 60 to 85 seconds, assuming that this reflects an anti–factor Xa level of 0.35 to 0.70. aPTT = activated prothrombin time. This table adapted from Michelson et al. and the experience of the writing group.aPTT = activated prothrombin time. This table adapted from Michelson et al. and the experience of the writing group.


Protocol for Using Low-Molecular-Protocol for Using Low-Molecular-Weight Heparin in ChildrenWeight Heparin in Children

Initial Initial Initial Initial

TreatmentTreatment ProphylacticProphylactic

PreparationPreparation DoseDose DoseDose

Reviparin

Body weight–dependent dose (Units/kg per12 hours)

<5 kg 150 50

>5 kg 100 30

Enoxaparin

Age-dependent dose (mg/kg per 12 hours)

<2 mo 1.5 0.75

>2 mo 1.0 0.5

Dalteparin

All-age pediatric dose (Units/kg per 24 hours) 129 ± 43 92 ± 52

Tinzaparin

Age-dependent dose (Units/kg)

0-2 mo 275

2-12 mo 250

1-5 years 240

5-10 years 200

10-16 years 275

Adapted from Monagle et al. and the experience of the writing group.


Warfarin Anticoagulation Protocol Warfarin Anticoagulation Protocol for Childrenfor Children

StageStage INR INR ActionAction

Day 1 1.0-1.3 0.2 mg/kg orally

Days 2-4 1.1 –1.3 Repeat day 1 loading dose

1.4 –1.9 50% of day 1 loading dose



>3.5 Hold dosing until INR is <3.5

then restart according to stage

III guidelines

Maintenance

1.1 –1.4 Increase by 20% of dose

1.5 –1.9 Increase by 10% of dose

1.0–3.0 No change

3.1 –3.5 Decrease by 10% of dose

>3.5 Hold dosing until INR is <3.5 then restart at 20% less than last dose

INR indicates international normalized ratio.INR indicates international normalized ratio.

*The protocol is designed to maintain an INR between 2 and 3 with warfarin.*The protocol is designed to maintain an INR between 2 and 3 with warfarin.Adapted from Michelson et al and the experience of the writing groupAdapted from Michelson et al and the experience of the writing group..

© 2010, american heart association. all rights reserved. this slide set was adapted from the...

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