1. UBC-Case 1 Samuel Yip PhD, MD, FRCPC Western Stroke Day 2012

2. History 30 year old RH female Recently from UK While pushing herself off a table, sudden onset of left hemiplegia and decrease LOC 6 months ago she had1 spell of sudden onset of dizziness No neck pain and no neck trauma No SOB and no leg pain

3. History No other stroke risk factors Non-smoker No Family history of stroke OCP (12 yrs) for Endometriosis

4. Examination Initial Examination: –AVSS –Mild decrease in left nasolabial fold –Left deltoid weakness of 4+; no drift –NIHSS = 1

9. Too Good to Treat StudyYearMedian NIHSS NPoor Outcome Barber et al., 20011996-19993-mild; 6-RI9832.7% (NHD) Nedeltchev et al., 20072000-20062 (1 to 14)16223.5% (mRS 2 to 5) Smith et al., 200520024132.7% (NHD) Smith et al., 20112003-20092 (1 to 5)2920028.3% (NHD) van den Berg et al., 200920052711.1% (mRS 2 to 3) Willey et al, 20112004-20081(0 to 19)12710.2%(NHD) NHD = No Home Discharge

10. TREATMENT OPTIONS Iv-tPA Heparin ASA +/- Plavix ASA +/- Plavix + Heparin Enroll into a RCT – TEMPO-1

13. Fluids, ASA, Heparin sc BASELINE CTA 24 hr CTA

15. Case Cont: Investigations TTE and TEE showed –Large PFO –Spontaneous Right to Left shunt Hypercoagulable workup was negative Pelvic and Leg U/S showed no DVTs

16. Giant Hepatic Hemangiomas

17. Diagnosis ? Paradoxical Embolism –Hepatic Hemangioma – Large venous lakes with potential stasis 2 case reports suggesting hemangioma causing pulmonary embolism –Recent travel –Valsalva maneuver –Large spontaneous right  left shunt

18. Secondary Prevention Stop OCP ASA 81 mg once a day Coumadin Coumadin then PFO Closure

19. PFO and Stroke: Atrial septum – overlapping of the septum primum and septum secundum. When the fusion of these 2 structures fails, then a patent foramen is formed. This act as conduit for R to L shunt in adult life.

20. PFO and Cryptogenic Stroke 25% of general population have a PFO ~ 40% of young cryptogenic stroke patients have a PFO Overall et al., 2000

21. PFO and Stroke: Pathophysiology Paradoxical Embolism

22. LA RA AO IAS T Srivastava etl., NEJM 1997

23. PFO and Stroke: Pathophysiology Paradoxical Embolism Atrial Vulnerability – Paroxysmal Atrial Fibrillation Endothelial dysfunction

24. PFO and cryptogenic stroke: Natural History Risk of recurrent stroke is low – ~ 0.5 to 1% per year. (From recent cohort study and placebo randomized control trials ).

25. PFO in Cryptogenic Stroke Study (PICSS) Substudy of WARSS (Multicenter, randomized, DB study, ASA (325 mg) vs Warfarin (mean INR 2.1); n = 2206) –Excluded symptomatic carotid and cardioembolic stroke 630 patients underwent TEE –42% had a cryptogenic stroke –39% of the cryptogenic stroke had a PFO Primary end point: recurrent ischemic stroke or death in 2 years Homma et al., Circulation, 2002

26. PICSS Results Homma et al., Circulation, 2002

27. PFO Closure Devices for Cryptogenic Stroke StudyDevice MedicalRisk Ratio (95% CI) CLOSURE 1STARFlex Septal Closure System 12/44713/4620.90 (0.41,1.98) RESPECTAmplatzer PFO Occluder 9/49916/4810.49 (0.21,1.11) PCAmplatzer PFO Occluder 1/2045/2100.20 (0.02,1.72) CLOSURE – Fulran et al., NEJM 2012 RESPECT – Carroll et al., TCT 2012 PC - Meier, et al., TCT 2012

28. PFO Closure in Cryptogenic Stroke: Conclusion There is no evidence for routine PFO closure in patients with cryptogenic stroke. We should continue to enroll patients in RCT trials to evaluate the effectiveness of endovascular PFO closure as a secondary stroke prevention strategy.

29. PFO CLOSURE