Can CTA or MRA replace
intra-arterial digital subtraction
angiography (DSA) in the
investigation of isolated third
nerve palsy?
William A. Fletcher, M.D., FRCPC
University of Calgary
DSA?
Or is MRA or CTA
sufficient?
Kissel et al (1983)
25 aneurysmal palsies:
12% pupil-sparing incomplete
Third Nerve Palsy – Can CTA or
MRA Replace DSA?
• 3 Questions:
– Sensitivity of CTA and MRA in detecting
aneurysms?
– Prevalence of aneurysm in III palsy?
• With pupil-sparing incomplete palsy
• With relative pupil-sparing palsy
– Risk of complications from DSA?
III Nerve Palsy – MRA?
• Jacobson and Trobe (1999):
– Risk of MRA missing P Comm aneurysm:
1.5%
Posterior Communicating Artery
(P-Comm) Aneurysms Causing
Third Nerve Palsy
• Jacobson and Trobe (1999):
Proportion
Not
Proportion
causing
detected causing palsy &
Aneurysm
palsy
(%)
by
MRA
not
detected
by
Diameter
(%)
MRA (%)
 5 mm
91.3
x
3
=
2.7
 5 mm
8.7
x
46
=
4.0
P-Comm Aneurysms Causing
Third Nerve Palsy
• Jacobson and Trobe (1999):
Proportion
8-Year
causing palsy & Rupture
Rate
Aneurysm not detected by
MRA (%)
(%)
Diameter
Proportion not
detected by
MRA and liable
to rupture (%)
 5 mm
2.7
x
31
=
0.85
 5 mm
4.0
x
16
=
0.65
Total 1.5
P-Comm Aneurysms
• International Study of Unruptured
Intracranial Aneurysms (ISUIA) (2003)
• 5-year risk of rupture:
–  7 mm: 2.5%
– 7 – 12 mm: 14.5%
Symptomatic Unruptured
Aneurysms: Risk of Rupture
• Juvela et al (1993 & 2000):
Symptomatic Unruptured
Aneurysms
• Yanaka et al (2003):
– 16 patients with acute third nerve palsies
– all aneurysms  10 mm
– 1 aneurysm (6mm) ruptured on day 3
risk of rupture unknown
P-Comm Aneurysms Causing III
Nerve Palsy
• Jacobson and Trobe (modified):
Aneurysm
Diameter
Proportion
causing
palsy (%)
Not
detected
by MRA
(%)
Proportion not
detected by MRA
and liable to
rupture (%)
 5 mm
91.3
x
3
=
2.7
 5 mm
8.7
x
46
=
4.0
Total
6.7
MRA Sensitivity for Detecting
Aneurysms
• White et al (2000):
–  3 mm: 94%
• Kupersmith et al (2005):
– Prospective study of MRA
MRA Sensitivity for Detecting
Aneurysms
• Kupersmith et al (2005):
MRA Sensitivity for Detecting
Aneurysms
• White et al (2000):
–  3 mm: 94%
• Kupersmith et al (2005):
– Prospective study of MRA
–  3 mm: 100% (n = 42)
– Confidence interval: 93% - 100%
CTA Sensitivity for Detecting
Aneurysms
CTA Sensitivity for Detecting
Aneurysms
• Hoh et al (2004):
– 225 aneurysms
• 109 ruptured
• 114 unruptured
• 28 P Comm aneurysms
• Sensitivity: 100%
• CI95 overall: 98.7% - 100%
• CI95 unruptured aneurysms: 97.4%– 100%
CTA Sensitivity for Detecting
Aneurysms
• Kangasniemi et al (2004):
– 168 aneurysms  2 mm
– Sensitivity: 99.4% (CI: 97% – 100%)
CTA Sensitivity for Detecting
Aneurysms
• 8 studies of multi-slice CTA and aneurysms:
– 712 aneurysms ≥ 3mm on DSA
– 1.1% not visible on CTA (= 98.9% sensitivity)
– 1.4% observer error (= 97.5% sensitivity)
 Lower CI95 CTA senstivity: 96% - 97.8%
Third Nerve Palsy
Can CTA replace DSA?
• 3 Questions:
– Sensitivity of CTA in detecting aneurysms?
– Prevalence (pre-CTA probability) of
aneurysm in TNP?
• With pupil-sparing incomplete palsy
– Risk of complications from DSA?
Pupil-sparing incomplete palsy
Pre-CTA probability of aneurysm
Cause
Proportion Proportion
Proportion of
of all 3rd pupil-sparing all 3rd n palsies
nerve
incomplete
pupil-sparing
palsies
incomplete
(%)
(%)
(%)
Aneurysm
≤18
x 13 (n=64)
=
≤ 2.3
Ischemia
≥40
x 46 (n=141) =
≥ 18
 Maximum Pre-CTA probability = 12% (2.3/20.3)
Pupil-sparing incomplete palsy
Probability of aneurysm after normal CTA
Maximum
Pre-CTA
Probability
(%)
12
Minimum
CTA
Sensitivity
(%)
97
Maximum
Post-CTA
Probability
(%)

0.4
Third Nerve Palsy
Can CTA replace DSA?
• 3 Questions:
– Sensitivity of CTA in detecting aneurysms?
– Prevalence (pre-CTA probability) of
aneurysm in TNP?
• With relative pupil-sparing palsy
– Risk of complications from DSA?
Relative pupil-sparing palsy
Pre-CTA probability of aneurysm
Cause
Proportion of
all 3rd nerve
palsies
(%)
Relative
pupilsparing
(%)
Proportion of all
3rd n palsies
relative pupilsparing (%)
Aneurysm
≤18
x
12
=
2.2
Ischemia
≥40
x
14
=
5.6
 Maximum Pre-CTA probability = 28% (2.2/7.8)
Relative pupil-sparing palsy
Probability of aneurysm after normal CTA
Maximum Minimum
Pre-CTA
CTA
Probability Sensitivity
(%)
(%)
28
97
Maximum
Post-CTA
Probability
(%)

1.2
Third Nerve Palsy
Can CTA replace DSA?
• 3 Questions:
– Sensitivity of CTA in detecting aneurysms?
– Prevalence (pre-CTA probability) of
aneurysm in TNP?
– Risk of complications from DSA?
Risk of complications from
DSA?
• Permanent neurological complications:
– Cloft et al (1999) meta-analysis:
• 3,517 studies: 0.3% (upper CI95 - 0.5%)
– Willinsky et al (2003) prospective:
• 2,899 studies: 0.5% (upper CI95 - 0.7%)
Factors modifying CTA sensitivity
• CTA technology, quality, interpretation
Factors modifying aneurysm
prevalence
• Age < 50-years old
– Chou et al (2004):
• 29 III nerve palsy patients ≥ 50-years old
• 86% ischemia, 7% aneurysm
Factors modifying aneurysm
prevalence
• Gender
– M:F ratio - 1:3 for PComm aneurysms
– Capo et al (1992) & Renowden et al (1993):
• 75 patients with III palsy:
women
men
% aneurysm
24
7
% ischemia
50
59
%
%
Pupil-sparing incomplete
0.4
0.1
Relative pupil-sparing
1.2
0.3
– Max. post-CTA risk:
Pupil-Sparing Incomplete Palsy
Caveats
• Pupils should be re-examined within a
week of onset
• Isolated superior division palsy: greater
risk ?
Relative Pupil-Sparing Palsies
Caveats
• Pupils should be re-examined within a
week of onset
• Anisocoria ≥ 2.0 mm
DSA after negative CTA?
Internal Dysfunction
None
Partial
Partial
Complete
External Dysfunction
DSA, unless:
No DSA, unless: •Male ≥ 50-years old
•Age< 50
AND
OR
•Anisocoria < 2 mm
•Sup div’n palsy
AND
•External dysfunct’n
No DSA
DSA, unless:
•Male ≥ 50-years old
Complete
DSA
DSA