Enlarged Perivascular Spaces in Lacunar Stroke

Enlarged Perivascular Spaces
in Lacunar Stroke
The Secondary Prevention of Small Subcortical
Stroke (SPS3) study
H Ohba, LA Pearce, GM Potter, OR Benavente
NIH/NINDS #U01 NS38529-04A1
University of British Columbia,
Vancouver, Canada
www.clinicaltrials.gov NCT00059306

Presenter Disclosure
Information
Hideki Ohba MD, PhD
Enlarged Perivascular Spaces in Lacunar Stroke Patients.
The Secondary Prevention of Small Subcortical Stroked
(SPS3) trial.
FINANCIAL DISCLOSURE:
None
UNLABELED/UNAPPROVED USES DISCLOSURE:
None
2

SPS3
Enlarged Perivascular Spaces (EPVS)
• EPVS are commonly found on MRIs.
• Reported associations with aging, hypertension,
lacunar stroke, cognitive impairment, CADASIL and
white matter disease, etc.
• The pathophysiology and significance are still
unclear.
• However, EPVS may be a marker for cerebral small
vessel disease

SPS3
Secondary Prevention of Small
Subcortical Stroke (SPS3) Study
Randomized multicenter trial,
Recent lacunar strokes verified by MRI
No cortical stroke, cardioembolic source / carotid stenosis
Recruitment completed in April 2011 with 3020 participants
Randomized to 2 interventions in a factorial design:
1) Antiplatelet therapy:
-aspirin 325 mg + placebo
-aspirin 325 mg + clopidogrel 75 mg
2) Target levels of blood pressure:
-”usual” 130-149 mmHg systolic
-”intensive”

SPS3
Aims
To evaluate the association between stroke risk
factors, cognitive function and MRI findings with
EPVS in the SPS3 cohort

SPS3
EPVS Definition and Rating
• EPVS rated on T2-WI; basal ganglia and centrum
semiovale were rated separately for left and right
Small, sharply delineated structures, 40
MacLullich AM,. J Neurol Neurosurg Psychiatry. 2004;75:1519–1523

SPS3
Score 1 = 1-10 EPVS
EPVS Rating
T2-WI in Basal ganglia (BG)
Score 3 = 21-40 EPVS
Score 2 = 11-20 EPVS
Score 4 >40 EPVS

SPS3
Score 1
=1-10 EPVS
EPVS Rating
T2-WI in Centrum semiovale
Score 2
=11-20 EPVS
Score 3
=21-40 EPVS
Score 4
>40 EPVS

SPS3
1632
English speaking participants from USA
and Canadian sites
Exclude: 203
T2-WI not available.
Cohort
N:1172
Included in the
analysis
Exclude: 251
motion artifacts in one or
more places

SPS3
Results: Baseline Characteristics I
N= 1172
Age in years, mean (sd) 62 (11)
Male, % 57
Diabetes mellitus, % 31
Hypertension, % 79
Ischemic heart disease, % 14
Hyperlipidemia, % 57
Prior Stroke, % 10
CASI, median 91
Cognitive assessment screening instrument (CASI)

SPS3
Results: Baseline Characteristics II
eGFR per CKD-EPI equation, ml/min/1.73m 2 , mean(sd)
Age Related White Matter Changes (ARWMC)
Multiple lacunar infarcts (5-15mm) on MRI
N= 1172

%
SPS3
70
60
50
40
30
20
10
0
EPVS
N= EPVS:
of EPB
Results: Baseline EPVS Scores
1
2
58
31
BG CS
28
Score = 0 Score = 1 Score = 2 Score = 3 Score = 4
40
p40)
10
22
3
7

SPS3
Results: Basal Ganglia
EPVS Number
< 10 11-20 21+ p-value
Age, mean 59 63 70 < 0.001
Male, % 58 58 57 1.0
Diabetes mellitus, % 34 31 22 0.01
Hyperlipidemia, % 56 59 55 0.6
Hypertension, % 75 84 86 < 0.001
IHD, % 11 14 18 0.05
Prior Stroke, % 8 12 13 0.05
eGFR, mean 83 80 74 < 0.001

SPS3
Results: Centrum Semiovale
EPVS Number
< 10 11-20 21+ p-value
Age, mean 59 62 64 < 0.001
Male, % 56 57 60 0.6
Diabetes mellitus, % 35 30 30 0.2
Hyperlipidemia, % 59 56 56 0.6
Hypertension, % 76 78 83 0.05
IHD, % 12 14 13 0.5
Prior Stroke, % 11 9 11 0.7
eGFR, mean 83 80 79 0.01

SPS3
Results: Associations Between
Number of EPVS and MRI Findings
Max Basal Ganglia EPVS Number
ARWMC total, median 3 6 8 < 0.001
Fazekas total, median 4 6 8 < 0.001
Multiple infarcts, % 11 19 29 < 0.001
Max Centrum Semiovale EPVS Number
< 10 11-20 21+ p-value
ARWMC total, median 3 4 5 < 0.001
Fazekas total, median 4 5 6 < 0.001
Multiple infarcts, % 12 14 21 0.003
ARWMC: Age Related White Matter Changes
Fazekas: Rating scale periventricular and white matter abnormality

SPS3
High Number of EPVS (>11)
Multivariate Analysis
Odds Ratio 95% CI
Basal Ganglia
• Age per 10 year ↑ 1.9 1.7-2.1
• Hypertension 1.7 1.2-2.3
• Multiple infarcts 2.4 1.7-3.4
Centrum Semiovale
• Age per 10 year ↑ 1.5 1.3-1.6

SPS3
Results: Cognitive Impairment
Max BG EPVS Number Max CS EPVS Number
< 10 11-20 21+ p < 10 11-20 21+ p
N 680 333 159 367 471 334
• z-score CASI,
median
• Mild cognitive
impairment
NCI
MCI-a
MCI-na
MCI-md
-0.25 -0.45 -0.34 0.2 -0.34 -0.34 -0.35 0.5
54
16
13
18
55
16
11
18
54
16
18
12
CASI = Cognitive Abilities Screening Instrument
MCI = mild cognitive impairment
NCI: not cognitively impaired
MCI-a: amnestic (memory impairment only)
MCI-na: non amnestic (non-memory impairment only; may be perceptual-verbal processing speed and/or executive functioning)
MCI-md: multi-domain (both memory and non-memory impairment)
0.3
52
14
14
20
55
16
13
16
56
17
13
15
0.5

SPS3
Conclusions
In this well-defined large cohort of lacunar stroke
patients, EPVS in BG were independently associated
with age, hypertension and multiple infarcts.
EPVS were not associated with cognitive impairment
EPVS share similar risk factors with lacunar stroke
and may be a marker for small vessel disease.

SPS3
Thank You!
Our sincere thanks to our SPS3 colleagues,
patients and NINDS/NIH for contributing to
this study
Study Progress
Antiplatelet Trial Results: February 3 rd 2012
Blood Pressure Trial completion: April 2012
Results Anticipated: Late 2012