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A CUTE I SCHEMIC S TROKE IN C HILDREN A B RIEF O VERVIEW Tammy Hennika, M.D.

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Presentation on theme: "A CUTE I SCHEMIC S TROKE IN C HILDREN A B RIEF O VERVIEW Tammy Hennika, M.D."— Presentation transcript:

1 A CUTE I SCHEMIC S TROKE IN C HILDREN A B RIEF O VERVIEW Tammy Hennika, M.D.

2 C HILDHOOD 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?

3 A RTERIAL 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

4 AIS E TIOLOGY AND R ISK FACTORS Older adults:  Hypertension  Smoking  Diabetes  Hypercholesterolemia

5 AIS E TIOLOGIES AND R ISK FACTORS Children:  Cardiac abnormalities  Vascular lesions  Genetic conditions  Hematologic abnormalities (such as sickle cell disease)  Infection

6 AIS E TIOLOGIES AND R ISK FACTORS Young adults:  Vasculopathy (such as arterial dissection)  Recent pregnancy and other hypercoagulable states  Smoking, drug use  Premature atherosclerosis  Hypertension  Possibly migraine

7 I NTERNATIONAL P EDIATRIC S TROKE S TUDY (2010) Multi-center report >600 children (age 29 days to 18 years) with AIS Most frequent conditions:  Arteriopathy (53%)  Cardiac disorders (31%)  Infection (24%)

8 AIS R ISK F ACTORS  Cardiac Abnormalities: Congenital heart disease is a risk factor for cardioembolic stroke Acquired cardiac lesions such as endocarditis, cardiomyopathy, and prosthetic valve placement

9 AIS R ISK F ACTORS  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

10 AIS R ISK F ACTORS  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%)

11 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%)

12 F OCAL CEREBRAL ARTERIOPATHY (FCA) OF CHILDHOOD Term used by the International Pediatric Stroke Study Unexplained focal arterial stenosis in a child with arterial ischemic stroke

13 F OCAL 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

14 M OYAMOYA 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

15 A RTERIAL D ISSECTION 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

16 V ASCULITIS Inflammatory changes in the cerebral vessels  Primary Kawasaki disease  Secondary Collagen vascular diseases (such as Lupus) Infections (bacterial meningitis, viral infections)

17 O THER ABNORMITIES OF VESSEL STRUCTURE  Arterial tortuosity syndrome  Vasospasms resulting from subarachnoid hemorrhage  Fibromuscular dysplasia

18 M ETABOLIC DISORDERS Several metabolic conditions associated with arterial ischemic stroke Generally through effects on the vessel wall  CADASIL  MELAS

19 CADASIL C erebral A utosomal- D ominant A rteriopathy with S ubcortical Infarcts and L eukoencephalopathy 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

20 MELAS M itochondrial E ncephalopathy with L actic A cidosis and S troke-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

21 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

22 I NGESTION Cocaine and methamphetamine Can stroke due to hypertension, vasospasm, or vasculitis

23 C LINICAL 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

24 I F 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

25 Vascular abnormalities can present much like AIS: Intracranial hemorrhage Aneurysms Arteriovenous malformation Cerebral venous thrombosis

26 N ONVASCULAR 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

27 W HAT 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

28 W HAT 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

29 C AN WE GIVE T PA? 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

30 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

31 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

32 W HAT IS THE TREATMENT ? Ischemic stroke of unknown etiology: Aspirin 3 to 5mg/kg per day rather than anticoagulation as initial therapy

33 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)

34 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

35 AIS Resulting from sickle cell disease: Urgent intravenous hydration Urgent exchange transfusion (goal hemoglobin S fraction <30% of total hemoglobin)

36 I F 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

37 W ILL 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

38 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

39 C ONCLUSION  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

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

41 R EFERENCES 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: Monagle, P, Chan AK, Golenberg NA, et al. Antithrombotic therapy in neonates and children; Antithrombotic Therapy and Prevention of Thrombosis, 9 th 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 (accessed on January 14, 2011). Smith, S, Ischemic stroke in children: Ischemic stroke in children and young adult: Etiology and clinical features. In: UpToDate: Smith, S, Ischemic stroke in children: Evaluation, initial management, and prognosis. In: UpToDate: 2012.


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