Transcript CEREBRAL VASCULAR ACCIDENTS Pediatric Critical Care Medicine Emory University Children’s Healthcare of Atlanta Objectives • • • • Epidemiology Risk factors Catergories Treatments.

CEREBRAL VASCULAR
ACCIDENTS
Pediatric Critical Care Medicine
Emory University
Children’s Healthcare of Atlanta
Objectives
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Epidemiology
Risk factors
Catergories
Treatments
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
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Cardiac Disease
Coagulation Disorders
Dehydration
Vasculitis
Infection
Dissection
Neoplasm
Metabolic Disorder
Moyamoya
Sickle Cell Anemia
Perinatal Complication
Other
19%
14%
11%
7%
6%
5%
4%
3%
2%
2%
2%
2%
Multiple risk factors are often present
& predict worse outcome
Lamthier et al. (2000)
Neurology
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
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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
Pediatric Arterial Ischemic Strokes (AIS)
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Primary Hemiparesis: new focal deficits
Ataxic gait
Chorea
Vertigo
Speech and visual disturbance
Headaches with neurological deficits
Pediatric Arterial Ischemic Strokes (AIS)
• 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
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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 Strokes (AIS)
• Ischemic
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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
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Pediatric Arterial Ischemic Strokes (AIS)
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Pediatric Arterial Ischemic Strokes (AIS)
• 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
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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
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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
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Capillary telaangioma
Venous angioma
ngiectasia
Cavernous Sturge-Weber syndrome:
venous angioma of the
leptomeninges, coroidal angioma
and a facial capillary hemangioma
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 <5%
– ¾ presented with ICH
» 10-15%: Post-traumatic
» 10-15%: mycotic
» Others: polycystic kidney dz,
SCD, TS, Marfan, EhlersDanlos 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
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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
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Severe HA associated with vomiting, sleepiness, double vision
Visual disturbances
Severe dizziness or unsteadiness
Sz activity
CSVT
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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
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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
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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
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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 Reye’s syndrome
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Stroke Treatments
• Aspirin therapy
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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
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Stroke Treatments
• Thrombolytic agents: urokinase & streptokinase
– No evidence to support efficacy- 203 (pooled literature) for noncerebral 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 <30% or HgB 10=12.5)
• Top off transfusion if exchange transfusion is delayed or
severe anemia
• Chronic exchange transfusion
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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
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Intracranial Hemorrhage
• Risk factors
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AV malformation
25%
Hematologic anomalies
10-13%
Brain tumors
Cavernous Hemangiomas
Vasculopathy
Vasculitis
Infection
Illicit drug uses
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
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– Decrease morbidity and mortality
– Potential for systemic effect causing severe hypotension