Cerebrovascular Disease
Daniel 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
Medical conditions
• Hypertension
• Heart disease
• Atrial fibrillation
• Hypercholesterolemia
• Diabetes mellitus
• Carotid stenosis
• Prior stroke or TIA
• PFO
• Elevated homocysteine,
Lp(a)
• Prothrombotic
conditions
• Migraine
• Sleep Apnea
Behaviors
• Smoking
• Sedentary lifestyle
• Obesity
• Alcohol abuse
Major Modifiable Stroke Risk Factors
Risk factor
Relative Risk
Prevalence
Hypertension
3.0-5.0
25-40%
Smoking
1.5-2.5
20-40%
Diabetes
1.0-3.0
4-20%
Hyperlipidemia
1.0-2.0
6-40%
Physical Inactivity
2.7
20-40%
Heavy alcohol use
1.0-3.0
5-30%
Hyperhomocyst(e)inemia
2.0-3.0
10-15%
Atrial Fibrillation
4.0-18.0
1-2%
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
Cerebrovascular Disease:
Stroke Types
Ischemic Stroke (80%)
Atherothrombotic
Cerebrovascular
Disease (20%)
Cryptogenic (30%)
Hemorrhagic Stroke (20%)
Intracerebral
Hemorrhage (70%)
?
Lacunar (25%)
(small vessel disease)
Cardioembolic (20%)
Albers GW et al. Chest. 1998;119:683S-698S.
Rosamond WD et al. Stroke. 1999;30:736-743.
Subarachnoid Hemorrhage (30%)
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
Normal SI:
CSF < GM < WM
Interpretation:
• Anatomic delineation
• Only a few things are bright:
– Fat
– Protein (colloid cysts,
melanin,
methemoglobin)
– Gadolinium
T2-weighted Images
Normal SI:
WM < GM < CSF
Interpretation:
• Signal intensity generally
follows water content.
• Vasogenic edema looks
bright.
• Many pathologic processes
result in increased water
content.
FLAIR Images
“Fluid Attenuated Inversion Recovery”
Normal SI:
CSF < WM < GM
Interpretation:
• 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
“Susceptibility” images
Gradient Echo images
Normal SI:
WM < GM < CSF
Interpretation:
• 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).
Diffusion-Weighted Images
(DWI)
Normal SI:
CSF < WM < GM
Interpretation:
Normal SI:
• T2-weighted image, in which
substances look brighter if
water diffusion is restricted.
• In acute stroke, water
diffusion is restricted, so
tissue looks bright.
Vessel imaging
•
•
•
•
Ultrasound
CT angiography
MR angiography
Conventional catheter angiography
Magnetic Resonance Angiography
(MRA)
Interpretation:
• 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.
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
NINDS 12%
Lancet 2004; 363: 768–74
ECASS3 7%
Comparison of Efficacy
Trials
Pts Rx
CEA (NASCET) 6
Pro-UK
7
tPA NINDS
8
tPA ECASS3
14
Stroke Unit^
18
CEA (ACAS)
15-20
OAT AFIB
20
tPA AMI*
26
To Prevent
1 major stroke
1 major stroke
1 major stroke
1 major stroke
1 major stroke/death
1 stroke
1 stroke /yr
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
From Schievink WI, NEJM 2001
• 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 ages
Intimal tear  sub intimal
or sub adventitial
hematoma (arterial
occlusion, ‘pseudo’
aneurysm)
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 Prevention
of Ischemic Stroke
– Carotid endarterectomy: >50% stenosis
– Anticoagulation therapy: Cardioembolic
stroke
– Antiplatelet therapy: Most common
therapy
Antiplatelet Agents
for Stroke Prevention
– Aspirin
– Ticlopidine
– Clopidogrel
– Dipyridamole
Efficacy of Antiplatelet Agents
for Prevention of Stroke, MI,
or Vascular Death
Risk Reductions
Patient
Population
Relative Risk
Odds
Reduction (%) Reduction (%)
Therapy
All Vascular
Diseases
All antiplatelet
regimens
22
27
Stroke/TIA
All antiplatelet
regimens
17
22
Stroke/TIA
Aspirin
13
16
Source: Antiplatelet Trialists’ Collaboration, 1994: Algra and Van Gijn 1996.
Efficacy of Antiplatelet Agents vs
Placebo for Prevention of Stroke, MI, or
Vascular Death in Stroke/TIA Patients
Antiplatelet Agent
Aspirin (all doses)
No. of Studies
Relative Risk
Reduction (%)
10
13
Ticlopidine
1
23
Dipyridamole + ASA
4
30
18
17
All Antiplatelet Agents
Source: Algra and Van Gijn 1996; Gent et al.
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
Lacunar
Other
144 (13.1)
612 (55.5)
66 (6.0)
115 (10.4)
625 (56.7)
68 (6.2)
Carotid Endarterectomy Trials
• NASCET I (70-99%)
• Medical
• Surgical
26%
9% (5.8% risk of stroke or death within 30 days)
• NASCET II (50-69%)
• Medical
• Surgical
22.2%
15.7% ( 6.7% risk of stroke or death within 30 days)
• ACAS (>60%)
• Medical
• Sugical
11%
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, placebocontrolled, 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.
Potential Stroke Risk Reduction for Individuals -- AHA
Guidelines
Factor
Hypertension
Potential Benefit with Treatment
30% - 40%
Smoking
50% within 1 year, baseline after 5
years
Diabetes
44% reduction in hypertensive
diabetics with tight blood pressure
control
Hyperlipidemia
Atrial fibrillation
20-30% with statins in patients
with known coronary heart
disease
68% (warfarin)
21% (aspirin)
Adapted from Goldstein, et al. Circulation 2001;103:163-182.
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