A CUTE I SCHEMIC S TROKE IN C HILDREN A B RIEF O VERVIEW Tammy Hennika, M.D.
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Transcript of A CUTE I SCHEMIC S TROKE IN C HILDREN A B RIEF O VERVIEW Tammy Hennika, M.D.
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.
Smith, S, Ischemic stroke in children: Evaluation, initial management, and prognosis. In: UpToDate: 2012.