Cerebrovascular Disease Daniel Costello CUH. Cerebral Vasculature Arterial system Venous system.
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Transcript of Cerebrovascular Disease Daniel Costello CUH. Cerebral Vasculature Arterial system Venous system.
Cerebrovascular DiseaseDaniel Costello
CUH
Cerebral Vasculature
Arterial system
Venous system
Mechanisms of Vascular Disease
Arterial (high flow)
Embolic occlusion
In situ occlusion
Rupture
Dissection
Inflammation
Spasm
Venous (low flow)
Embolic occlusion
In situ occlusion
Rupture
Dissection
Inflammation
Spasm
Risk Factors - Modifiable
• Hypertension• Heart disease• Atrial fibrillation• Hypercholesterolemia• Diabetes mellitus• Carotid stenosis• Prior stroke or TIA• PFO• Elevated homocysteine,
Lp(a)• Prothrombotic
conditions• Migraine• Sleep Apnea
• Smoking• Sedentary lifestyle• Obesity• Alcohol abuse
Medical conditions Behaviors
Major Modifiable Stroke Risk Factors
10-15%2.0-3.0Hyperhomocyst(e)inemia
1-2%4.0-18.0Atrial Fibrillation
5-30%1.0-3.0Heavy alcohol use
20-40%2.7Physical Inactivity
6-40%1.0-2.0Hyperlipidemia
4-20%1.0-3.0Diabetes
20-40%1.5-2.5Smoking
25-40%3.0-5.0Hypertension
PrevalenceRelative RiskRisk factor
Stroke Epidemiology in Ireland
• Approximately 10,000 Stroke per annum in Ireland
• Stroke:TIA ratio 4:1
• 3rd commonest cause of death in Western World
• Short & long term consequences
Stroke Epidemiology in Ireland
Acute Ischaemic Stroke
Albers GW et al. Chest. 1998;119:683S-698S.Rosamond WD et al. Stroke. 1999;30:736-743.
Cardioembolic (20%)Lacunar (25%)(small vessel disease)
Ischemic Stroke (80%) Hemorrhagic Stroke (20%)
Subarachnoid Hemorrhage (30%)
Cryptogenic (30%)
Atherothrombotic CerebrovascularDisease (20%)
IntracerebralHemorrhage (70%)
Cerebrovascular Disease: Stroke Types
?
TIA: old vs new definitions
“Penumbra”=Tissue at risk
Making a diagnosis
• Sudden onset neurological deficits• Loss of consciousness uncommon• Involuntary movements uncommon• Headache common
• Investigations determine:- effect of stroke i.e. ‘brain damage’- cause of this stroke - risk of future strokes
Vascular territories (Anterior)
Vascular territories (Posterior)
Vascular territories- MCA
Vascular territories- MCA
Vascular territories- MCA
Vascular territories- ACA & PCA
Vascular territories- Posterior
Vascular territories- vertebrobasilar
Investigations
Brain imaging• CT Brain• MRI Brain ‘Stroke
protocol’ with diffusion sequences
Vessel imaging• CTA• MRA• Ultrasound carotids
•Cardiac- telemetry, Echocardiography
•Clotting
•Aorta- trans-oesophageal echocardiography
Head CT
Brain Stroke ‘window’
T1-weighted Images
Interpretation:
• Anatomic delineation
• Only a few things are bright:
– Fat
– Protein (colloid cysts, melanin, methemoglobin)
– Gadolinium
Normal SI: CSF < GM < WM
Normal SI: WM < GM < CSF
• Signal intensity generally follows water content.
• Vasogenic edema looks bright.
• Many pathologic processes result in increased water content.
Interpretation:
T2-weighted Images
“Fluid Attenuated Inversion Recovery”
• T2-weighted image in which signal from CSF has been suppressed.
• Distinguishes CSF spaces from T2-bright lesions.• Increased conspicuity of T2-bright lesions next to
CSF.• CSF signal will not suppress if:
– SAH– Protein (as in infection/inflammation)– Hyperoxygenation– Propofol– Prior gadolinium
FLAIR Images
Normal SI: CSF < WM < GM
Interpretation:
Gradient Echo images
“Susceptibility” images
Normal SI: WM < GM < CSF
• T2 weighted image.
• Substances that exhibit susceptibility effect will look dark and “bloom:”– Deoxyhemoglobin– Intracellular methemoglobin– Hemosiderin– Calcium (sometimes)– Air– Metal (aneurysm clips,
earrings, braces, etc).
Interpretation:
Normal SI:
Diffusion-Weighted Images (DWI)
Normal SI: CSF < WM < GM
• T2-weighted image, in which substances look brighter if water diffusion is restricted.
• In acute stroke, water diffusion is restricted, so tissue looks bright.
Interpretation:
Vessel imaging
• Ultrasound
• CT angiography
• MR angiography
• Conventional catheter angiography
Magnetic Resonance Angiography (MRA)
• Moving blood looks bright.• All other substances dark.• No contrast necessary (but
we use gadolinium for better neck MRA images).
• Less spatial resolution than CTA, more motion-sensitive.
Interpretation:
Treatment of Acute Ischaemic Stroke
• Rapid assessment- NIHSS• Consider tPA (IV or IA)• Anti-coagulation• Anti-platelet agent• Blood pressure, glucose monitoring, fever control• Surgery• Early evaluation- fasting glucose & lipids, brain &
vessel imaging, screen for Atrial Fibrillation, TTE +- TOE
• Rehabilitation- SALT, PT, OT
ECASS III: tPA 3-4.5 hrs
ECASS III Outcomes
• 821- 418 to alteplase group and 403 to placebo.• Median NIHSS lower in tPA group (9 vs 10, p=.03)
and fewer patients with prior stroke (7.7% vs. 14.1%; p= 0.03)
• The median OTT time was 3 hours 59 minutes. • More patients had a favorable outcome with
alteplase (52.4% vs. 45.2%; odds ratio, 1.34; 95% CI 1.02 to 1.76; P = 0.04).
• In the global endpoint, the outcome was also improved with alteplase (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05).
• An adjusted analysis accounting for predictors of poor outcome showed a more favorable (odds ratio, 1.42; 95% CI, 1.02 to 1.98; P = 0.04)
ECASS III Safety
• The incidence of intracranial hemorrhage was higher with alteplase than with placebo for any ICH, (27.0% vs. 17.6%; P = 0.001) or for symptomatic ICH (2.4% vs. 0.2%; P = 0.008). Mortality did not differ (7.7% and 8.4%; P = 0.68).
• There was no significant difference in the rate of other serious adverse events.
Meta-Analysis of the major IV tPA trials shows clear benefit up to 3 hrs and beyond
Lancet 2004; 363: 768–74
NINDS 12% ECASS3 7%
Comparison of EfficacyTrials Pts Rx To Prevent CEA (NASCET) 6 1 major stroke
Pro-UK 7 1 major stroke
tPA NINDS 8 1 major stroke
tPA ECASS314 1 major stroke
Stroke Unit^ 18 1 major stroke/death
CEA (ACAS) 15-20 1 stroke
OAT AFIB 20 1 stroke /yr
tPA AMI* 26 1 death from MI
NASCET (n=659), NINDS (n=624) ^ BMJ 1997; 314:1151-9. *Lancet 1994;343:311-22
Courtesy Dr. Huang-Hellinger
Carotid and Vertebral Artery Dissection
• 2% of all ischemic strokes• 25% of stroke in young• Incidence 2.6 per 100,000
(carotid) and 1.0 per 100,000 (vertebral)
• Peaks in the 5th decade• Intracranial dissections are
rare, occur at younger agesIntimal tear sub intimal or sub adventitial hematoma (arterial occlusion, ‘pseudo’ aneurysm)From Schievink WI, NEJM 2001
Dissection: management
Management is controversial, no RCT
• Medical– Short term anticoagulation with heparin / warfarin
followed by long term anti-platelet agents– CTA, MRA, Carotid duplex useful for follow-up
• Endovascular– Balloon occlusion or stenting considered if
recurrent symptoms occur despite medical treatment
– Coiling of a ‘pseudo’aneurysm
• Surgical– Bypass, Surgery for pseudoaneurysm
Secondary Preventionof Ischemic Stroke
– Carotid endarterectomy: >50% stenosis
– Anticoagulation therapy: Cardioembolic stroke
– Antiplatelet therapy: Most common therapy
Antiplatelet Agentsfor Stroke Prevention
– Aspirin
– Ticlopidine
– Clopidogrel
– Dipyridamole
PatientPatient Relative RiskRelative Risk OddsOddsPopulationPopulation TherapyTherapy Reduction (%)Reduction (%) Reduction Reduction (%)(%)
Efficacy of Antiplatelet Agentsfor Prevention of Stroke, MI,
or Vascular Death
All VascularAll Vascular All antiplateletAll antiplatelet 2222 2727DiseasesDiseases regimensregimens
Stroke/TIAStroke/TIA All antiplateletAll antiplatelet 1717 2222regimensregimens
Stroke/TIAStroke/TIA AspirinAspirin 1313 1616
Source: Antiplatelet Trialists’ Collaboration, 1994: Algra and Van Gijn 1996.Source: Antiplatelet Trialists’ Collaboration, 1994: Algra and Van Gijn 1996.
Risk ReductionsRisk Reductions
Efficacy of Antiplatelet Agents vs Placebo for Prevention of Stroke, MI, or Vascular Death in Stroke/TIA Patients
Aspirin (all doses)Aspirin (all doses) 1010 1313
TiclopidineTiclopidine 11 2323
Dipyridamole + ASADipyridamole + ASA 44 3030
All Antiplatelet AgentsAll Antiplatelet Agents 1818 1717
Relative RiskRelative Risk Antiplatelet Agent Antiplatelet Agent No. of Studies No. of Studies Reduction (%)Reduction (%)
Source: Algra and Van Gijn 1996; Gent et al.Source: Algra and Van Gijn 1996; Gent et al.1989; Tijssen, 1998; Antiplatelet Trialists’ Collaboration, 1994.1989; Tijssen, 1998; Antiplatelet Trialists’ Collaboration, 1994.
• Double-blind, randomized, multicenter trial
• Warfarin (INR 1.4-2.8) vs Aspirin (325 mg/day)
• Primary Endpoint: Recurrent Ischemic Stroke or Death
• Eligible: Ischemic Stroke (Non-cardioembolic,
Non-operable Atherosclerotic) within prior 30 days
• Sample size: 30% risk reduction (n=2206)
• Secondary Endpoints: TIA, MI
• Adverse Experience: Hemorrhage
Stroke Subtypes in WARSS
Aspirin Warfarin N (%) N(%)
Cryptogenic embolic 281(25.5) 295 (26.7)
Large Artery 144 (13.1) 115 (10.4)
Lacunar 612 (55.5) 625 (56.7)
Other 66 (6.0) 68 (6.2)
Carotid Endarterectomy Trials
• NASCET I (70-99%)• Medical 26%• Surgical 9% (5.8% risk of stroke or death within 30 days)
• NASCET II (50-69%)• Medical 22.2%• Surgical 15.7% ( 6.7% risk of stroke or death within 30 days)
• ACAS (>60%)• Medical 11%• Sugical 5.1% (2.3% risk of stroke or death within 30 days)
WASID Wafarin v.s. Aspirin for Symptomatic Intracranial Arterial
Stenosis
• Randomized, double-blind, placebo-controlled, multicenter trial
• 569 patients with TIA or stroke attributable to 50-99% stenosis of MCA, ICA or V-B system
• Randomized to – Warfarin with target INR 2.0-3.0– ASA 650 mg bid
• Primary endpoint: IS, ICH, death from vascular cause
Chimowitz et al. N Engl J Med. 2005;352:1305-16.
Adapted from Goldstein, et al. Circulation 2001;103:163-182.
68% (warfarin)21% (aspirin)
Atrial fibrillation
20-30% with statins in patients with known coronary heart disease
Hyperlipidemia
44% reduction in hypertensive diabetics with tight blood pressure control
Diabetes
50% within 1 year, baseline after 5 years
Smoking
30% - 40%Hypertension
Potential Benefit with Treatment Factor
Potential Stroke Risk Reduction for Individuals -- AHA
Guidelines
CVST
CVST
Topics not covered
• Vascular Malformations• Extraparenchymal haemorrhage
- Subarachnoid Haemorrhage- Subdural haemorrhage- Extradural haemorrhage
• Inflammation (vasculitis)• Arterial spasm• Strokes in young patients• Rehabilitation after acute stroke