CEREBRAL VASCULAR ACCIDENTS Pediatric Critical Care Medicine Emory University Children’s Healthcare of Atlanta

CEREBRAL VASCULAR ACCIDENTS

Pediatric Critical Care MedicineEmory University

Children’s Healthcare of Atlanta

2

Objectives• Epidemiology• Risk factors• Catergories• Treatments

3

Epidemiology• 2.52/100,000/yr – children thru 14 yrs

– 1.89/100,000/yr – hemorrhagic– 0.65/100,000/yr - ischemic

• As common as brain tumors• Neonatal strokes 28/100,000 live births

4

Epidemiology• Increased awareness & reporting• Improved imagings• Better survival of underlying diseases

5

Epidemiology• Impacts of strokes

– Mortality 6-40% (hemorrhagic 2x ischemic)– Morbidity

» Neurological disability – 60%» Seizures – 15%» Headaches

Risk Factors• Cardiac Disease 19%• Coagulation Disorders 14%• Dehydration 11%• Vasculitis 7%• Infection 6%• Dissection 5%• Neoplasm 4%• Metabolic Disorder 3%• Moyamoya 2%• Sickle Cell Anemia 2%• Perinatal Complication 2%• Other 2%

Multiple risk factors are often present& predict worse outcome

Lamthier et al. (2000)Neurology

7

Risk factors• Congenital Heart Disease

– Asymptomatic aortic valvular disease » Associated with dissection » Undiagnosed cardiac disease (PFO)- rare

– Inherited connective tissue diseases» Marfan» Erlos-Danlos

8

Risk factors• Coagulation disorders

– Factor V Leiden » common in Caucasian» most common cause of activated Protein C resistance

– Prothrombin 20210 mutation» Neonatal & childhood CSVT

• Infection, Inflammation, Immune Deficiency– 1/3 cases associated with infection (esp vacicella

within the previous year)– High WBC (in association with SCD) increase recurrence– Inflammation: harmful effects on the endothelium

9

Risk factors• Sickle Cell Disease

– 25 % with stroke by the age 45– Ischemic stroke predominantly in childhood

» Hemorrhagic with steroid and Hypertension» Sinovenous thrombosis, posterior

leukoencephalopathy, watershed ischemia» Silent infarcts

– Hemorrhagic (ICH or SAH) in adult secondary to aneurysm

– High WBC associated with infection can precipitate CVD – indicate chronic infection

10

Risk factors• Anemias

– Hemolytic anemias: thalassemia, hereditary spherocytosis & paroxysmal nocturnal hemoglobinuria

• Metabolic disorders– Homocysteinemia: predispose to vessel abn.– Lipid abnormality:

» Elevation in Cholesterol (9%), TG (31%), Lipoprotein (22%)

» Apolipoprotein abnormality

11

Risk factors• Vascular abnormality

– Vascular adhesion» Adhesion of WBC, RBC, platelets causing endothelial

damage

• Hypertension– Highest risk in young adult & elderly– Largely ignored in pediatric population– ½ strokes with SBP>90th percentile– Abnormality of angiotensinogen gene: 4X increase

in risk of strokes in SCD

12

Pediatric Arterial Ischemic Strokes (AIS)

• Primary Hemiparesis: new focal deficits• Ataxic gait• Chorea• Vertigo • Speech and visual disturbance• Headaches with neurological deficits

13


• Median presentation of 5.6 hrs after AIS symptoms onset– ½ presented within the first 6 hrs– ½ presented >24 hrs

• Main factor in delayed presentation: was the failure of parents to recognize that a child was having neurologic symptoms


14


15

Pediatric Arterial Ischemic Stroke s (AIS)

• Ischemic- Mortality 6-20%- 30% recurrence risks- 5 yr survival

- 1.2% after perinatal- 19% after child hood

- Median time 2.7 months- 60% recurrence if

associated with vasc. abn

• Hemorrhagic- Mortality 8-40%- 10-20% recurrence

rate but associated with higher mortality

- Recurrence is higher with struct. abn.- Girls>boys (16% vs 3%)

excluding trauma- Lower neurological

morbidity

16

17

18

19


20


• Dissection:– ICA>vertebral – Intracranial: anterior

circulation 60% (ICA, MCA & anterior cerebral

– Extracranial: 80% of posterior circulation with ½ located within the vertebral artery at C1=C2

– Trauma is common cause

21


• Moyamoya– Bil. severe stenosis of end ICA

with collaterals

22

23


• Transient Cerebral arteriopathy– Inflammatory response to infection (varicell, Borrelia or

tonsilitis– Multi-focal lesions– Most cases stabilize but some progress to recurrent

strokes

24


• Sickle Cell Disease– Narrowing of distal ICA & proximal MCA, anterior

cerebral arteries– Gradual progression to occlusion– Endothelial proliferation– Silent infarcts occur in MCA territory or in border zones– High recurrence rate– 25% with CVD by age 45

» Ischemic in children» Hemorrhagic in adults


• Vascular Malformation– 10-500/100,000– Hi flow AV shunts without capillary

bed– In children: hemorrhagic

presentation, deep areas– Types

» Capillary telaangioma» Venous angioma» ngiectasia» Cavernous Sturge-Weber

syndrome: venous angioma of the leptomeninges, coroidal angioma and a facial capillary hemangioma

25


• Vein of Galen Malformation– Male predominance– Embryonic choroidal AVM– Presentation: high output heart

failure, hydrocephalus, sz

26

PEDIATRIC AIS

• Aneurysm– Acquired, rare in children

<5%– ¾ presented with ICH

» 10-15%: Post-traumatic» 10-15%: mycotic» Others: polycystic kidney

dz, SCD, TS, Marfan, Ehlers-Danlos etc.

Cerebral sinovenous thrombosis (CSVT)

• Superficial & Deep– Superficial: cortical veins superior sagittal sinus

right lateral sinus– Deep: inferior sagittal sinus & paired internal cerebral

veins, join to form v. of Galen & straight sinus

• Flow is highly responsive to changes in MAP which can cause reversal of flow

• Relative low thrombomodulin prothrombotic

28


29


30

CSVT• Pathophysiology

– Mechanical: birth trauma– Trauma, sepsis, underlying disease (malignancy,

systemic inflamation)– Septic foci: inner ear, mastoid or air sinuses– Dehydration, anemia, coagulation disorders

• Venous Infarction: venous HTN by outflow obstruction

• Intracranial Hypertension: disruption of CSF absorption

31

CSVT• Signs/symptoms

– Severe HA associated with vomiting, sleepiness, double vision

– Visual disturbances– Severe dizziness or unsteadiness– Sz activity

32

CSVT

33

Other Strokes Mimics• Posterior Circulation Arterial Strokes

– Posterior infarction of cerebellum, brain stem– Boys>girls– Trauma, subluxation of cervical spines causing arterial

dissection

• Reversible Posterior Leukoencephalopathy– Sx: sz, AMS, disorder of consciousness, visual abn., HA– Predominant post. White matter abn.– Clinical condition: HTN encephalopathy, eclampsia, AC in SCD,

immunosuppression– Acute hypotension (poor cardiac fxn/anemia)– Rapid resolution: vasogenic cerebral edema prob secondary to

autoregulation & endothelial injury

• Acute Disseminated Encephalomyelitis

34

Other Strokes Mimics• Metabolic Strokes: Diabetes, inborn errors of

metabolism– Vascular injury

» Homocysteine: direct endothelial injury» Fabry: lysosomal storage with accumulation and deposition

of glycosphingolipid in blood vessels endothelial cells» Menkes: deficiency in copper; obliteration of intracranial

vasculature

– Non-vascular injury: diabetes, organic acidemias, Urea cycle defects etc.

» MILAS (mitochondrial dz with LA and stroke like sx): lacking of energy supply with generation of oxygen free radicals

» Others: accumulation of toxic substances

35

Diagnosis – w/o SCD• First 24 hours

– Angiogram– MRA– Blood cultures if febrile– Toxicology screen

• 24-72 hours– Echo with bubble study– Limited initial pro-thrombotic evaluation– Lupus anticoagulants, antiphospholipid abs, lipid profile,

lipoprotein A, Homocysteine, gene mutation– Systemic inflammatory disease evaluation: ANA, ESR, CRP, UA

Rollins N, Dowling M, Booth T, Purdy P, AJNR, 2000substances

36

Diagnosis – w/o SCD• After acute setting

– Further prothrombotic evaluation» Protein C & S» Antithrombin» Factor VIII» Confirmation of early abnormal tests

Rollins N, Dowling M, Booth T, Purdy P, AJNR, 2000substances

37

Ischemic Stroke Treatments• General management

– Normo-thermia– Normal oxygen saturation– Cerebral protection with the presence of increase ICP

• Specific management– Early neurosurgery consult as indicated

38

Stroke Treatments• Anticoagulation

– Commonly use in: » AIS: Heparin or LMWH for 5-7 days until cardioembolic stroke

and dissection are excluded» CSVT: 3-6 months of therapy reduced risk of recurrent

systemic or cerebral thrombosis» High risk of embolism with underlying disease» Dissection: 3-6 months with extracranial dissection.» Known prothrombotic abnormalities

– With cardiac embolism: controversial– Balance of risk with precipitate hemorrhage vs recurrence

embolic event (lower risk in children for progression to hemorrhage)

39

Stroke Treatments• Anticoagulation: • 115 w/ first AIS treated by standardized guidelines

– Warfarin: 44 pts 2 (4.5%) major bleed (non-fatal)» Keep INR 2-3

– LMWH: 51 pts for 7-14 days no major bleed– ASA: 103 pts (3-5mg/kg/day) no major bleed, no Reye’s syndrome

40

Stroke Treatments• Aspirin therapy

– Efficacy and dose are unknown– Usual dose 5mg/lg/day– Long term prophylaxis dose may be lower– No report case of Rye’s syndrome

» One case in adult when the pt increased ASA dosage with flu like sx

41

Stroke Treatments• Thrombolytic agents: urokinase & streptokinase

– No evidence to support efficacy- 203 (pooled literature) for non-cerebral thrombotic complication

» 80% thrombus cleared» 54% minor bleeding (no transfusion needed)» 1 pt with intra-cranial hemorrhage

– Toronto: 29 pts treated with tPA (0.5mg/kg)» 79% - clot was dissolved» ¼ of the pts had bleeding required transfusion

– No good data regarding outcomes, therefore treatment is controversial

42

Stroke Treatments - SCD• ½ will have another stroke• Urgent exchange transfusion (HbS <30% or HgB

10=12.5)• Top off transfusion if exchange transfusion is delayed

or severe anemia• Chronic exchange transfusion

– Keep HgS <50%– Relapse if stop even with period of symptoms free– Risk: iron overload treated with chelation– Use of hydroxyurea to prevent stroke

» Induction of HbF» Generation of Nitric Oxide

43

Intracranial Hemorrhage• Risk factors

– AV malformation 25%– Hematologic anomalies 10-13%– Brain tumors– Cavernous Hemangiomas– Vasculopathy– Vasculitis– Infection– Illicit drug uses

44

Intracranial Hemorrhage• Non traumatic SAH mostly caused by aneurysms• 10% are secondary to CSVT

– Controversial in anti-coag of CSVT with hemorrhage

• 25% mortality with 42% significant disability• No standard management and treatm

45

Treatments: ICH• Treat ICP, cerebral protection• Reverse coagulopathy

– Recombinant activated Factor VII within the first 4 hrs: limited growth of hematoma, reduced mortality, improved functional outcomes

• Treat space occupying lesion• Treat associated vasospasm (SAH) with Triple H

therapy• Supportive treatment

46

Treatments: SAH• Vasospasm associated with 20-30% of aneurysmal SAH• Related to spasmogenic substances generated during

lysis of subarachnoid blood clots• Present no earlier than day 3, peak day 7-8• Triple-H therapy

– Moderate hemodilution– Hypertension– Hypervolumia

• Nimodipine: selective cerebral vessel Ca channel blocker, start within 4 days– Decrease morbidity and mortality– Potential for systemic effect causing severe hypotension

47

Documents

CEREBRAL VASCULAR ACCIDENTS Pediatric Critical Care Medicine Emory University Children’s Healthcare of Atlanta