CEREBRAL VASCULAR ACCIDENTS

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CEREBRAL VASCULAR ACCIDENTS
Pediatric Critical Care Medicine Emory
University Childrens Healthcare of Atlanta
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Objectives

• Epidemiology
• Risk factors
• Catergories
• Treatments

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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

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Epidemiology

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

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Epidemiology

• Impacts of strokes
• Mortality 6-40 (hemorrhagic 2x ischemic)
• Morbidity
• Neurological disability 60
• Seizures 15
• Headaches

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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

Lamthier et al. (2000) Neurology
Multiple risk factors are often present
predict worse outcome
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Risk factors

• Congenital Heart Disease
• Asymptomatic aortic valvular disease
• Associated with dissection
• Undiagnosed cardiac disease (PFO)- rare
• Inherited connective tissue diseases
• Marfan
• Erlos-Danlos

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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

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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

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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

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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 SBPgt90th percentile
• Abnormality of angiotensinogen gene 4X increase
  in risk of strokes in SCD

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Pediatric Arterial Ischemic Strokes (AIS)

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

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Pediatric Arterial Ischemic Strokes (AIS)

• Median presentation of 5.6 hrs after AIS symptoms
  onset
• ½ presented within the first 6 hrs
• ½ presented gt24 hrs
• Main factor in delayed presentation was the
  failure of parents to recognize that a child was
  having neurologic symptoms

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Pediatric Arterial Ischemic Strokes (AIS)
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Pediatric Arterial Ischemic Strokes (AIS)
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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.
• Girlsgtboys (16 vs 3) excluding trauma
• Lower neurological morbidity

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Pediatric Arterial Ischemic Strokes (AIS)
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Pediatric Arterial Ischemic Strokes (AIS)

• Dissection
• ICAgtvertebral
• Intracranial anterior circulation 60 (ICA, MCA
  anterior cerebral
• Extracranial 80 of posterior circulation with
  ½ located within the vertebral artery at C1C2
• Trauma is common cause

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Pediatric Arterial Ischemic Strokes (AIS)

• Moyamoya
• Bil. severe stenosis of end ICA with collaterals

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Pediatric Arterial Ischemic Strokes (AIS)

• Transient Cerebral arteriopathy
• Inflammatory response to infection (varicell,
  Borrelia or tonsilitis
• Multi-focal lesions
• Most cases stabilize but some progress to
  recurrent strokes

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Pediatric Arterial Ischemic Strokes (AIS)

• 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

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Pediatric Arterial Ischemic Strokes (AIS)

• 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

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Pediatric Arterial Ischemic Strokes (AIS)

• Vein of Galen Malformation
• Male predominance
• Embryonic choroidal AVM
• Presentation high output heart failure,
  hydrocephalus, sz

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PEDIATRIC AIS

• Aneurysm
• Acquired, rare in children lt5
• ¾ presented with ICH
• 10-15 Post-traumatic
• 10-15 mycotic
• Others polycystic kidney dz, SCD, TS, Marfan,
  Ehlers-Danlos etc.

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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

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Cerebral sinovenous thrombosis (CSVT)
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Cerebral sinovenous thrombosis (CSVT)
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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

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CSVT

• Signs/symptoms
• Severe HA associated with vomiting, sleepiness,
  double vision
• Visual disturbances
• Severe dizziness or unsteadiness
• Sz activity

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CSVT
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Other Strokes Mimics

• Posterior Circulation Arterial Strokes
• Posterior infarction of cerebellum, brain stem
• Boysgtgirls
• 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

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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

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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

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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

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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

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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)

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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 Reyes syndrome

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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 Ryes syndrome
• One case in adult when the pt increased ASA
  dosage with flu like sx

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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

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Stroke Treatments - SCD

• ½ will have another stroke
• Urgent exchange transfusion (HbS lt30 or HgB
  1012.5)
• Top off transfusion if exchange transfusion is
  delayed or severe anemia
• Chronic exchange transfusion
• Keep HgS lt50
• 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

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Intracranial Hemorrhage

• Risk factors
• AV malformation 25
• Hematologic anomalies 10-13
• Brain tumors
• Cavernous Hemangiomas
• Vasculopathy
• Vasculitis
• Infection
• Illicit drug uses

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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

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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

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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