Can CTA or MRA replace Can CTA or MRA replace intra-arterial digital intra-arterial digital

subtraction angiography subtraction angiography (DSA) in the investigation (DSA) in the investigation

of isolated third nerve of isolated third nerve palsy?palsy?

William A. Fletcher, M.D., William A. Fletcher, M.D., FRCPCFRCPC

University of CalgaryUniversity of Calgary

DSA?DSA?Or is MRA or CTA Or is MRA or CTA sufficient? sufficient?

Kissel et al (1983)Kissel et al (1983)25 aneurysmal palsies: 25 aneurysmal palsies: 12% pupil-sparing incomplete12% pupil-sparing incomplete

Third Nerve Palsy – Can CTA Third Nerve Palsy – Can CTA or MRA Replace DSA?or MRA Replace DSA?

• 3 Questions:3 Questions:– Sensitivity of CTA and MRA in Sensitivity of CTA and MRA in

detecting aneurysms? detecting aneurysms?

– Prevalence of aneurysm in III palsy?Prevalence of aneurysm in III palsy?• With pupil-sparing incomplete palsyWith pupil-sparing incomplete palsy

• With relative pupil-sparing palsyWith relative pupil-sparing palsy

– Risk of complications from DSA?Risk of complications from DSA?

III Nerve Palsy – MRA?III Nerve Palsy – MRA?

• Jacobson and Trobe (1999):Jacobson and Trobe (1999):– Risk of MRA missing P Comm Risk of MRA missing P Comm

aneurysm:aneurysm:

1.5%1.5%

Posterior Communicating Posterior Communicating Artery (P-Comm) Aneurysms Artery (P-Comm) Aneurysms Causing Third Nerve Palsy Causing Third Nerve Palsy

• Jacobson and Trobe (1999):Jacobson and Trobe (1999):

AneurysmAneurysm

DiameterDiameter

Proportion Proportion causing causing palsy palsy

(%)(%)

Not Not detected detected by MRA by MRA

(%)(%)

Proportion Proportion causing palsy causing palsy

& not & not detected by detected by

MRA (%)MRA (%)

5 mm5 mm 91.391.3 x 3 x 3 = 2.7= 2.7

5 mm5 mm 8.7 8.7 x 46x 46 = 4.0= 4.0

P-Comm Aneurysms Causing P-Comm Aneurysms Causing Third Nerve Palsy Third Nerve Palsy

• Jacobson and Trobe (1999):Jacobson and Trobe (1999):

AneurysAneurysmDiametmDiamet

erer

Proportion Proportion causing palsy causing palsy

& not & not detected by detected by

MRA (%)MRA (%)

8-Year 8-Year RupturRupture Rate e Rate

(%) (%)

Proportion not Proportion not detected by detected by

MRA and liable MRA and liable to rupture (%)to rupture (%)

5 mm5 mm 2.72.7 x 31 x 31

= 0.85= 0.85

5 mm5 mm 4.0 4.0 x 16x 16 = 0.65= 0.65

Total 1.5Total 1.5

P-Comm AneurysmsP-Comm Aneurysms

• International Study of Unruptured International Study of Unruptured Intracranial Aneurysms (ISUIA) Intracranial Aneurysms (ISUIA) (2003)(2003)

• 5-year risk of rupture:5-year risk of rupture:– 7 mm: 2.5%7 mm: 2.5%– 7 – 12 mm: 14.5%7 – 12 mm: 14.5%

Symptomatic Unruptured Symptomatic Unruptured Aneurysms: Risk of RuptureAneurysms: Risk of Rupture

• Juvela et al (1993 & 2000):Juvela et al (1993 & 2000):

Symptomatic Unruptured Symptomatic Unruptured AneurysmsAneurysms

• Yanaka et al (2003):Yanaka et al (2003):– 16 patients with acute third nerve 16 patients with acute third nerve

palsiespalsies– all aneurysms all aneurysms 10 mm 10 mm– 1 aneurysm (6mm) ruptured on day 31 aneurysm (6mm) ruptured on day 3

risk of rupture unknownrisk of rupture unknown

P-Comm Aneurysms Causing P-Comm Aneurysms Causing III Nerve Palsy III Nerve Palsy

• Jacobson and Trobe (modified):Jacobson and Trobe (modified):

AneurysmAneurysm

DiameterDiameter

Proportion Proportion causing causing palsy palsy

(%)(%)

Not Not detected detected by MRA by MRA

(%)(%)

Proportion not Proportion not detected by detected by

MRA and liable MRA and liable to rupture (%)to rupture (%)

5 mm5 mm 91.391.3 x 3 x 3 = 2.7= 2.7

5 mm5 mm 8.7 8.7 x 46x 46 = 4.0= 4.0

Total 6.7Total 6.7

MRA Sensitivity for Detecting MRA Sensitivity for Detecting AneurysmsAneurysms

• White et al (2000):White et al (2000):– 3 mm: 94%3 mm: 94%

• Kupersmith et al (2005):Kupersmith et al (2005):– Prospective study of MRAProspective study of MRA

MRA Sensitivity for Detecting MRA Sensitivity for Detecting AneurysmsAneurysms

• Kupersmith et al (2005):Kupersmith et al (2005):

MRA Sensitivity for Detecting MRA Sensitivity for Detecting AneurysmsAneurysms

• White et al (2000):White et al (2000):– 3 mm: 94%3 mm: 94%

• Kupersmith et al (2005):Kupersmith et al (2005):– Prospective study of MRAProspective study of MRA– 3 mm: 100% (n = 42)3 mm: 100% (n = 42)– Confidence interval: 93% - 100%Confidence interval: 93% - 100%

CTA Sensitivity for Detecting CTA Sensitivity for Detecting AneurysmsAneurysms

CTA Sensitivity for Detecting CTA Sensitivity for Detecting AneurysmsAneurysms

• Hoh et al (2004):Hoh et al (2004):– 225 aneurysms225 aneurysms

• 109 ruptured109 ruptured• 114 unruptured114 unruptured• 28 P Comm aneurysms28 P Comm aneurysms• Sensitivity: 100%Sensitivity: 100%

• CICI9595 overall: 98.7% - 100% overall: 98.7% - 100%

• CICI9595 unruptured aneurysms: 97.4%– 100% unruptured aneurysms: 97.4%– 100%

CTA Sensitivity for Detecting CTA Sensitivity for Detecting AneurysmsAneurysms

• Kangasniemi et al (2004):Kangasniemi et al (2004):– 168 aneurysms 168 aneurysms 2 mm 2 mm– Sensitivity: 99.4% (CI: 97% – 100%)Sensitivity: 99.4% (CI: 97% – 100%)

CTA Sensitivity for Detecting CTA Sensitivity for Detecting AneurysmsAneurysms

• 8 studies of multi-slice CTA and 8 studies of multi-slice CTA and aneurysms:aneurysms:

– 712 aneurysms 712 aneurysms ≥ 3mm on DSA≥ 3mm on DSA– 1.1% not visible on CTA (= 98.9% sensitivity)1.1% not visible on CTA (= 98.9% sensitivity)– 1.4% observer error (= 97.5% sensitivity)1.4% observer error (= 97.5% sensitivity)

Lower CILower CI95 95 CTA senstivity: 96% - 97.8%CTA senstivity: 96% - 97.8%

Third Nerve Palsy Third Nerve Palsy Can CTA replace DSA?Can CTA replace DSA?

• 3 Questions:3 Questions:

– Sensitivity of CTA in detecting Sensitivity of CTA in detecting

aneurysms? aneurysms?

– Prevalence (pre-CTA probability) of Prevalence (pre-CTA probability) of

aneurysm in TNP?aneurysm in TNP?

•With pupil-sparing incomplete palsyWith pupil-sparing incomplete palsy

– Risk of complications from DSA?Risk of complications from DSA?

Pupil-sparing incomplete palsyPupil-sparing incomplete palsy Pre-CTA probability of aneurysmPre-CTA probability of aneurysm

Maximum Pre-CTA probability = 12% Maximum Pre-CTA probability = 12% (2.3/20.3)(2.3/20.3)

CauseCause

ProportioProportion of all n of all

3rd nerve 3rd nerve palsies palsies

(%)(%)

Proportion Proportion pupil-pupil-sparing sparing incompleteincomplete

(%)(%)

Proportion of Proportion of all 3all 3rdrd n n

palsies pupil-palsies pupil-sparing sparing

incomplete incomplete

(%)(%)

AneurysAneurys

mm≤≤18 18 x 13 x 13

(n=64) (n=64) = = ≤≤ 2.3 2.3

IschemiaIschemia ≥≥40 40 x 46 x 46 (n=141) (n=141)

= = ≥≥ 18 18

Pupil-sparing incomplete palsyPupil-sparing incomplete palsy

Probability of aneurysm after normal Probability of aneurysm after normal CTACTA

MaximumMaximum

Pre-CTA Pre-CTA Probability Probability

(%)(%)

Minimum Minimum CTA CTA

SensitivitSensitivity (%)y (%)

Maximum Maximum Post-CTA Post-CTA

Probability Probability (%) (%)

12 12 97 97 0.40.4

Third Nerve Palsy Third Nerve Palsy Can CTA replace DSA?Can CTA replace DSA?

• 3 Questions:3 Questions:

– Sensitivity of CTA in detecting Sensitivity of CTA in detecting

aneurysms? aneurysms?

– Prevalence (pre-CTA probability) of Prevalence (pre-CTA probability) of

aneurysm in TNP?aneurysm in TNP?

•With relative pupil-sparing palsyWith relative pupil-sparing palsy

– Risk of complications from DSA?Risk of complications from DSA?

Relative pupil-sparing palsy Relative pupil-sparing palsy Pre-CTA probability of aneurysmPre-CTA probability of aneurysm

Maximum Pre-CTA probability = 28% (2.2/7.8)Maximum Pre-CTA probability = 28% (2.2/7.8)

CauseCause

Proportion Proportion of all 3rd of all 3rd

nerve nerve palsies palsies

(%)(%)

Relative Relative pupil-pupil-

sparing sparing (%)(%)

Proportion of Proportion of all 3all 3rdrd n n palsies palsies

relative pupil-relative pupil-sparing (%)sparing (%)

AneurysAneurysmm

≤≤1818 x 12 x 12 = 2.2= 2.2

IschemiaIschemia ≥≥40 40 x 14x 14 = 5.6= 5.6

Relative pupil-sparing palsyRelative pupil-sparing palsy

Probability of aneurysm after normal Probability of aneurysm after normal CTACTA

MaximuMaximumPre-mPre-CTA CTA

ProbabilitProbability(%)y(%)

Minimum Minimum CTA CTA

SensitivitSensitivity(%)y(%)

Maximum Maximum Post-CTA Post-CTA

Probability Probability (%) (%)

28 28 97 97 1.21.2

Third Nerve Palsy Third Nerve Palsy Can CTA replace DSA?Can CTA replace DSA?

• 3 Questions:3 Questions:

– Sensitivity of CTA in detecting Sensitivity of CTA in detecting

aneurysms? aneurysms?

– Prevalence (pre-CTA probability) of Prevalence (pre-CTA probability) of

aneurysm in TNP?aneurysm in TNP?

– Risk of complications from DSA?Risk of complications from DSA?

Risk of complications from Risk of complications from DSA?DSA?

• Permanent neurological complications:Permanent neurological complications:– Cloft et al (1999) meta-analysis: Cloft et al (1999) meta-analysis:

• 3,517 studies: 0.3% (upper CI3,517 studies: 0.3% (upper CI9595 - 0.5%) - 0.5%)

– Willinsky et al (2003) prospective:Willinsky et al (2003) prospective:

• 2,899 studies: 0.5% (upper CI2,899 studies: 0.5% (upper CI9595 - 0.7%) - 0.7%)

Factors modifying CTA Factors modifying CTA sensitivitysensitivity

• CTA technology, quality, CTA technology, quality,

interpretationinterpretation

Factors modifying Factors modifying aneurysm prevalenceaneurysm prevalence

• Age Age < 50-years old< 50-years old– Chou et al (2004): Chou et al (2004):

• 29 III nerve palsy patients ≥ 50-years 29 III nerve palsy patients ≥ 50-years oldold

• 86% ischemia, 7% aneurysm86% ischemia, 7% aneurysm

Factors modifying aneurysm Factors modifying aneurysm prevalenceprevalence

• GenderGender– M:F ratio - 1:3 for PComm aneurysmsM:F ratio - 1:3 for PComm aneurysms

– Capo et al (1992) & Renowden et al (1993):Capo et al (1992) & Renowden et al (1993):• 75 patients with III palsy:75 patients with III palsy: womenwomen menmen

% aneurysm% aneurysm 24 24 7 7

% ischemia% ischemia 50 50 59 59

– Max. post-CTA risk:Max. post-CTA risk: %% %%

Pupil-sparing incompletePupil-sparing incomplete 0.4 0.4 0.1 0.1

Relative pupil-sparingRelative pupil-sparing 1.2 1.2 0.3 0.3

Pupil-Sparing Incomplete Pupil-Sparing Incomplete PalsyPalsy

CaveatsCaveats• Pupils should be re-examined Pupils should be re-examined

within a week of onsetwithin a week of onset• Isolated superior division palsy: Isolated superior division palsy:

greater risk ?greater risk ?

Relative Pupil-Sparing Relative Pupil-Sparing PalsiesPalsiesCaveatsCaveats

• Pupils should be re-examined Pupils should be re-examined within a week of onsetwithin a week of onset

• Anisocoria Anisocoria ≥≥ 2.0 mm 2.0 mm

DSA after negative CTA?DSA after negative CTA?Internal DysfunctionInternal Dysfunction

E

xternal Dysfunction

External D

ysfunction

NoneNone PartialPartial CompleteComplete

Partial

Partial

No DSA, unless:No DSA, unless:•Age< 50Age< 50

OROR•Sup div’n palsySup div’n palsy

DSA, unless:DSA, unless:•Male Male ≥ 50-years old≥ 50-years old

ANDAND•Anisocoria < 2 mmAnisocoria < 2 mm

ANDAND•External dysfunct’nExternal dysfunct’n

DSADSA

Com

pleteC

omplete

No DSANo DSADSA, unless:DSA, unless:

•Male Male ≥ 50-years old≥ 50-years old DSADSA