ACUTE ISCHEMIC STROKE IN CHILDRENA BRIEF OVERVIEW

Tammy Hennika, M.D.

CHILDHOOD STROKE ACTIVATIONS

What neuroimaging? What labs? What is the treatment? Can we give tPA? If not a stroke, what could it be? If it is a stroke, what is the prognosis? Will it reoccur?

ARTERIAL ISCHEMIC STROKE (AIS)

More common in adults Also occurs in neonates, infants,

children, and young adults Result in significant morbidity and

mortality Incidence 0.6 to 7.9/100,000 children

per year More common in boys than girls

AIS ETIOLOGY AND RISK FACTORS

Older adults: HypertensionSmokingDiabetesHypercholesterolemia

AIS ETIOLOGIES AND RISK FACTORS

Children:Cardiac abnormalitiesVascular lesionsGenetic conditions Hematologic abnormalities (such as

sickle cell disease) Infection

AIS ETIOLOGIES AND RISK FACTORS

Young adults:Vasculopathy (such as arterial

dissection)Recent pregnancy and other

hypercoagulable statesSmoking, drug usePremature atherosclerosisHypertensionPossibly migraine

INTERNATIONAL PEDIATRIC STROKE STUDY (2010)

Multi-center report >600 children (age 29 days to 18

years) with AIS

Most frequent conditions:Arteriopathy (53%)Cardiac disorders (31%) Infection (24%)

AIS RISK FACTORS

Cardiac Abnormalities: Congenital heart disease is a risk

factor for cardioembolic stroke Acquired cardiac lesions such as

endocarditis, cardiomyopathy, and prosthetic valve placement

AIS RISK FACTORS

Hematologic abnormalities Sickle cell disease ~300 times higher than that seen in children without SCD Other inherited or acquired

prothrombotic disorders such as: Anemia (particularly iron deficiency) Antiphospholipid syndrome Factor V Leiden mutation

AIS RISK FACTORS

Vasculopathy Abnormalities of the cerebral

vasculature Inherited or acquired

Pediatric Stroke Study : 525 children (ages 29 days to 19

years) with arterial ischemic stroke Vascular imaging found arteriopathy in

277 (53%)

In the 277 cases with arteriopathy: Focal cerebral arteriopathy of

childhood (25%)Primary or secondary moyamoya

(22%)Dissection (20%)Vasculitis (12%)Sickle cell disease arteriopathy (8%)Postvaricella arteriopathy (7%)Miscellaneous types (4%)Unspecified (3%)

FOCAL CEREBRAL ARTERIOPATHY (FCA) OF CHILDHOOD

Term used by the International Pediatric Stroke Study

Unexplained focal arterial stenosis in a child with arterial ischemic stroke

FOCAL CEREBRAL ARTERIOPATHY (FCA) OF CHILDHOOD

Etiology unknown, probably multifactorial

Possible causes: Inflammation and vasculitis due to

infection (eg antecedent varicella infection) or autoimmune disease

Thromboembolic arterial occlusion or stenosis

Intracranial dissection Arterial spasm Prothrombotic factors

MOYAMOYA SYNDROME

Progressive stenosis of the internal carotid arteries and formation of collateral vessels

Name moyamoya means “puff of smoke” in Japanese and describes the look of the tangle of tiny vessels formed to compensate for the blockage

ARTERIAL DISSECTION

Definite or probable trauma is identified in some cases

Spontaneous dissection also occurs Connective tissue disorders such as

vascular Ehlers- Danlos syndrome and Marfan syndrome can predispose to dissection

VASCULITIS

Inflammatory changes in the cerebral vessels

Primary Kawasaki disease

Secondary Collagen vascular diseases (such

as Lupus) Infections (bacterial meningitis,

viral infections)

OTHER ABNORMITIES OF VESSEL STRUCTURE

Arterial tortuosity syndrome

Vasospasms resulting from subarachnoid hemorrhage

Fibromuscular dysplasia

METABOLIC DISORDERS

Several metabolic conditions associated with arterial ischemic stroke

Generally through effects on the vessel wall

CADASILMELAS

CADASIL

Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Mutation in the Notch3 gene, short arm of chromosome 19

Progressive degeneration of smooth muscle cells in the vessel wall

May present with migraine, TIA, or ischemic stroke in late childhood or early adulthood

MELAS Mitochondrial Encephalopathy with Lactic

Acidosis and Stroke-like episodes

Mutations of mitochondrial DNA Metabolic stroke rather arterial stroke Occurrence of stroke-like episodes:

temporary muscle weakness on one side of the body (hemiparesis)

Other features: focal or generalized seizures, recurrent migraine-like headaches, vomiting, short stature, hearing loss and muscle weakness, dementia

MELAS

Diagnostic criteria: Stroke-like episodes Encephalopathy characterized by

seizures or dementia Blood lactic acidosis or Presence of ragged red fibers in

skeletal muscle biopsy

INGESTION

Cocaine and methamphetamine Can stroke due to hypertension,

vasospasm, or vasculitis

CLINICAL PRESENTATION

Infants with stroke: Seizures, altered mental status, or

focal weakness

Children with stroke: Hemiparesis or other focal neurologic

signs such as aphasia, visual disturbance, or cerebellar signs

Although seizures, headache and lethargy are not uncommon

IF NOT A STROKE, WHAT COULD IT BE?

Broad differential diagnosis Extended in young children because

stroke may present with nonspecific signs such as seizures or lethargy

Vascular abnormalities can present much like AIS:

Intracranial hemorrhage Aneurysms Arteriovenous malformation Cerebral venous thrombosis

NONVASCULAR CONDITIONS THAT MIMIC STROKE IN CHILDREN:

Tumors and other structural brain lesions Prolonged postictal paresis (Todd’s) Complicated migraine Familial alternating hemiplegia Posterior reversible encephalopathy syndrome (PRES) Metabolic stroke Intracranial infection (brain abscess or

meningoencephalitis) Demyelinating conditions (ADEM) Idiopathic intracranial hypertension Drug toxicity Post infectious cerebellitis Psychogenic conditions

WHAT NEUROIMAGING?

Neuroimaging in children with suspected stroke:

Brain MRI Head CT can be substituted of MRI is

not tolerated or will not be available within 48 hours

Also consider - MRA head and neck to evaluate

arteries Axial T1 MRI neck to evaluate for

dissection

WHAT LABS?

EKG, ECHO, O2 saturation Laboratory studies: CBC, BMP, glucose, pt, ptt, Toxicology, blood alcohol, pregnancy

test Hypercoagulable evaluation Vasculitis evaluation (angiography, ESR,

CRP, ANA, varicella titers, HIV, RPR) MELAS suspected, lactate level from

serum and CSF, molecular genetic testing, muscle biopsy

CAN WE GIVE TPA?

Initial treatment of children with acute arterial ischemic stroke :

Recombinant tissue plasminogen activator (tPA) is NOT approved in the United States by the FDA for the use in children <18 years of age with ischemic stroke

The effectiveness, safety and dose of tPA for the treatment of children with arterial ischemic stroke have not been established

Consensus guidelines recommend NOT using thrombolysis or mechanical thrombectomy outside the of specific research protocols or clinical trails

Initial antithrombotic treatment:

No randomized controlled trials examining the effectiveness of antiplatelet or anticoagulation therapy

Limited data suggests that anticoagualtion therapy in children has an acceptable safety profile, although efficacy remains uncertain

WHAT IS THE TREATMENT?

Ischemic stroke of unknown etiology: Aspirin 3 to 5mg/kg per day rather

than anticoagulation as initial therapy

High clinical suspicion for either dissection or cardioembolism:

Short-term anticoagulation with LMWH or unfractionated heparin until vascular imaging and echocardiography are obtained

Anticoagulation should be stopped and aspirin initiated if no indication (eg, a confirmed cardioemboilc source or arterial dissection)

Confirmed cardioemboilc source, arterial dissection, or hypercoagulable state:

Initial anticoagulation treatment (rather than aspirin)

IV unfractionated heparin (goal ptt 60-85) or subcutaneous LMWH (eg, enoxaparin) for 5-7 days

Followed by treatment with LMWH or warfarin

Aspirin (3 to 5mg/kg day) should be given if there is a contraindication to anticoagulation

AIS Resulting from sickle cell disease: Urgent intravenous hydration Urgent exchange transfusion (goal

hemoglobin S fraction <30% of total hemoglobin)

IF IT IS A STROKE, WHAT IS THE PROGNOSIS?

Prognosis: In hospital mortality after ischemic

stroke in children ages 1 to 17 years – 3.4%

Disability: Despite neural plasticity, majority have persistent disability

WILL IT REOCCUR?

Recurrent ischemia, including stroke and TIA:

Common after childhood arterial ischemic stroke

Recurrence ranging from 6.6 to 20% Presence of vasculopathy may be an

important risk factor for recurrent stroke in children with later childhood stroke

Cohort study with cerebrovascualr imaging available for 52 children with later childhood stroke

5-year stroke recurrence rate for children with abnormal vascular imaging was 66%

While children with normal vascular imaging had no recurrences

CONCLUSION

Childhood arterial ischemic stroke differs from adult stroke in risk factors, etiologies, and outcomes

Secondary stroke prevention with antiplatelets or anticoagulation are adapted from adult stroke management

Little is known about the safety and efficacy of acute thrombolytic therapy in various age groups

Further study is greatly needed for a better understanding of the pathogenesis, management, and outcomes in childhood arterial ischemic stroke

REFERENCES Roach ES,Golomb MR, Adams R, et al. Management of stroke in

infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular disease in the Young. Stroke 2008; 39:26644.

Monagle, P, Chan AK, Golenberg NA, et al. Antithrombotic therapy in neonates and children; Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Preactice Guidleline. Chest 2012; 141:e737S.

Pediatric Stroke Working Group. Stroke in childhood: Clinicial guidelines for diagnosis, management and rehabilitation. November 2004. www.rcplondon.ac.uk/pubs/books/chidstroke (accessed on January 14, 2011).

Smith, S, Ischemic stroke in children: Ischemic stroke in children and young adult: Etiology and clinical features. In: UpToDate: 2012.

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