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:3 Questions: –Sensitivity of CTA and MRA in detecting aneurysms? –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?

III Nerve Palsy – MRA? Jacobson and Trobe (1999):Jacobson and Trobe (1999): –Risk of MRA missing P Comm aneurysm: 1.5% 1.5%

Posterior Communicating Artery (P-Comm) Aneurysms Causing Third Nerve Palsy Jacobson and Trobe (1999):Jacobson and Trobe (1999): Aneurysm AneurysmDiameter Proportion causing palsy (%) Not detected by MRA (%) Proportion causing palsy & not detected by 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):Jacobson and Trobe (1999): Aneurysm Diameter Aneurysm Diameter Proportion causing palsy & not detected by MRA (%) 8-Year Rupture Rate (%) 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)International Study of Unruptured Intracranial Aneurysms (ISUIA) (2003) 5-year risk of rupture: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):Juvela et al (1993 & 2000):

Symptomatic Unruptured Aneurysms Yanaka et al (2003):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):Jacobson and Trobe (modified): Aneurysm AneurysmDiameter 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):White et al (2000): –  3 mm: 94% Kupersmith et al (2005):Kupersmith et al (2005): –Prospective study of MRA

MRA Sensitivity for Detecting Aneurysms Kupersmith et al (2005):Kupersmith et al (2005):

MRA Sensitivity for Detecting Aneurysms White et al (2000):White et al (2000): –  3 mm: 94% Kupersmith et al (2005):Kupersmith et al (2005): – Prospective study of MRA –  3 mm: 100% (n = 42) – Confidence interval: 93% - 100%

P Comm Aneurysms Causing Third Nerve Palsy Jacobson and Trobe (modified again):Jacobson and Trobe (modified again): Aneurysm Diameter Proportion causing palsy (%) Not detected by MRA (%) Proportion not detected by MRA and liable to rupture (%)  3 mm

CTA Sensitivity for Detecting Aneurysms

Hoh et al (2004):Hoh et al (2004): –225 aneurysms 109 ruptured109 ruptured 114 unruptured114 unruptured 28 P Comm aneurysms28 P Comm aneurysms Sensitivity: 100%Sensitivity: 100% CI 95 overall: 98.7% - 100%CI 95 overall: 98.7% - 100% CI 95 unruptured aneurysms: 97.4%– 100%CI 95 unruptured aneurysms: 97.4%– 100%

CTA Sensitivity for Detecting Aneurysms Kangasniemi et al (2004):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: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 CI 95 CTA senstivity: 96% %

CTA Sensitivity for Detecting Aneurysms Multislice helical CT:Multislice helical CT: Aneurysm AneurysmDiameter Proportion causing palsy (%) Not detected by CTA (%) Proportion not detected by CTA and liable to rupture (%)  3 mm

Third Nerve Palsy Can CTA replace DSA? 3 Questions:3 Questions: –Sensitivity of CTA in detecting aneurysms? –Prevalence (pre-CTA probability) of aneurysm in TNP? With pupil-sparing incomplete palsyWith pupil-sparing incomplete palsy –Risk of complications from DSA?

Pupil-sparing incomplete palsy Pre-CTA probability of aneurysm  Maximum Pre-CTA probability = 12% (2.3/20.3) Cause Cause Proportion of all 3rd nerve palsies (%) Proportion pupil-sparing incomplete (%) (%) Proportion of all 3 rd n palsies pupil-sparing incomplete (%) Aneurysm Aneurysm ≤18 x 13 (n=64) = ≤ 2.3 Ischemia ≥40 x 46 (n=141) = ≥ 18

Pupil-sparing incomplete palsy Probability of aneurysm after normal CTA Maximum Pre-CTA Probability (%) Minimum CTA Sensitivity (%) Maximum Post-CTA Probability (%)  0.4

Third Nerve Palsy Can CTA replace DSA? 3 Questions:3 Questions: –Sensitivity of CTA in detecting aneurysms? –Prevalence (pre-CTA probability) of aneurysm in TNP? With relative pupil-sparing palsyWith relative pupil-sparing palsy –Risk of complications from DSA?

Relative pupil-sparing palsy Pre-CTA probability of aneurysm  Maximum Pre-CTA probability = 28% (2.2/7.8) Cause Cause Proportion of all 3rd nerve palsies (%) Relative pupil- sparing (%) Proportion of all 3 rd n palsies relative pupil- sparing (%) Aneurysm ≤18 x 12 = 2.2 Ischemia ≥40 x 14 = 5.6

Relative pupil-sparing palsy Probability of aneurysm after normal CTA Maximum Pre-CTA Probability (%) Minimum CTA Sensitivity (%) Maximum Post-CTA Probability (%)  1.2

Third Nerve Palsy Can CTA replace DSA? 3 Questions: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:Permanent neurological complications: –Cloft et al (1999) meta-analysis: 3,517 studies: 0.3% (upper CI %)3,517 studies: 0.3% (upper CI %) –Willinsky et al (2003) prospective: 2,899 studies: 0.5% (upper CI %)2,899 studies: 0.5% (upper CI %)

Factors modifying CTA sensitivity CTA technology, quality, interpretationCTA technology, quality, interpretation

Factors modifying aneurysm prevalence Age < 50-years oldAge < 50-years old –Chou et al (2004): 29 III nerve palsy patients ≥ 50-years old29 III nerve palsy patients ≥ 50-years old 86% ischemia, 7% aneurysm86% ischemia, 7% aneurysm

Factors modifying aneurysm prevalence GenderGender –M:F ratio - 1:3 for PComm aneurysms –Capo et al (1992) & Renowden et al (1993): 75 patients with III palsy:womenmen75 patients with III palsy:womenmen % aneurysm 24 7 % ischemia –Max. post-CTA risk: % % Pupil-sparing incomplete Relative pupil-sparing

Pupil-Sparing Incomplete Palsy Caveats Pupils should be re-examined within a week of onsetPupils should be re-examined within a week of onset Isolated superior division palsy: greater risk ?Isolated superior division palsy: greater risk ?

Relative Pupil-Sparing Palsies Caveats Pupils should be re-examined within a week of onsetPupils should be re-examined within a week of onset Anisocoria ≥ 2.0 mmAnisocoria ≥ 2.0 mm

DSA after negative CTA? Internal Dysfunction External Dysfunction External Dysfunction NonePartialComplete Partial No DSA, unless: Age< 50Age< 50OR Sup div’n palsySup div’n palsy DSA, unless: Male ≥ 50-years oldMale ≥ 50-years oldAND Anisocoria < 2 mmAnisocoria < 2 mmAND External dysfunct’nExternal dysfunct’nDSA Complete No DSA DSA, unless: Male ≥ 50-years oldMale ≥ 50-years oldDSA