1. What is the prognosis of mild and severe stroke? Eivind Berge Oslo University Hospital ESC, Lisbon, May 23 rd 2012

2. «What is the prognosis of mild and severe stroke?» What is the natural course of mild and severe strokes? What is the effect of rt-PA on the course of mild and severe strokes?

3. Mild strokes: Should they be treated with rt-PA? No:Mild strokes have of «low chance of benefit» and have not been studied in clinical trials Yes: «Mild» strokes are not always mild strokes Yes:Observational studies have indicated similar- sized effects of rt-PA in mild stroke 1,2 1 Mishra NK. Stroke 2010;41:2612 2 Saposnik G. Stroke 2012;43:1315

4. Severe strokes: Should they be treated with rt-PA? No:Severe strokes have «high risk of harm» and have not been studied in clinical trials No:Observational studies have indicated lower effects of rt-PA in severe stroke 1 1 Saposnik G. Stroke 2012;43:1315 RR Stroke severity (iScore)

5. Severe strokes: Should they be treated with rt-PA? No:Severe strokes have «high risk of harm» and have been excluded from clinical trials Yes:Other studies have indicated similar-sized effects in severe strokes 1,2 1 Mishra NK. Stroke 2010;41:2612 NIHSS score 2 Ingall TJ. Stroke 2004;35:2418

6. Markers of «mild» and «severe» stroke in IST-3 NIHSS score (neurological deficits) OCSP class (stroke syndrome) Predicted probability of poor outcome at 6 months 1 1 König IR, et al. Stroke 2008;39:1821

7. Measure of prognosis in IST-3 Proportion of patients «alive and independent» at 6 months (OHS/mRS 0-2)

8. Proportion «alive and independent» at 6 months in control group

11. Effect of rt-PA on the proportion «alive and independent» at 6 months

15. Summary: Prognosis of mild and severe strokes «Mild» strokes are not always mild, and «severe» strokes are almost always severe There was no clear evidence of a differential effect of rt-PA in mild or severe strokes There was a trend towards a better effect in severe stroke, even after adjustment for key prognostic variables

16. Implications for practice and research There is no reason to routinely withhold rt-PA from mild or severe strokes –«Mild» strokes are not always mild, and are likely to benefit from treatment –«Severe» strokes have a very poor prognosis if left untreated, and are very likely to benefit The PRISMS trial is being planned in the US to determine the effect of rt-PA in mild strokes (NIHSS score ≤ 5)