1. When Not to Intervene in Acute Stroke or
Primum non nocere
Lawrence R. Wechsler, M.D.
Professor and Chair,
Department of Neurology
University of Pittsburgh

2. Lawrence R. Wechsler, MD
Ownership Interest (Stocks, Stock Options or Ownership Interest)
Neuro Interventional Therapeutic

3. When Not to Intervene Undesirable Outcomes No recanalization9 10 11 12 7 8 6 5 1 2 3 4
Control
Undesirable Outcomes
No recanalization
No improvement
Massive cerebral edema
Hemorrhage

4. Exclusions for IV tPA Stroke mimics
Mild stroke – non disabling (VF deficit, aphasia)
? Severe stroke NIHSS > 20
Rapidly resolving deficits
BP > 185 systolic > 110 diastolic
INR > 1.7, Platelets < 100K
Seizure at onset
Glucose < 50 or > 400 mg/dl

5. Additional Exclusions for IV tPA 3-4.5 Hrs – ECASS III
Age > 80
Severe stroke – NIHSS > 25
Any anticoagulant use regardless of INR
Prior history of stroke and diabetes
Hacke W et al. N Engl J Med. 2008;359:1317

6. Symptomatic Hemorrhage After IV tPA Community Hospital Experience
Tanne et al. Neurology 1999:53;

7. Timing of Sx Hem after IV tPA8 6 4 2
NINDS tPA Stroke Study Group Stroke 1997;28:2109

8. NINDS rt-PA Stroke Study Risk of Symptomatic ICH
NINDS tPA Stroke Study Group Stroke 1997;28:2109

9. When Not to Intervene – Time to Rx
IV tPA > 3 hrs or > 4.5 Hrs in selected pts
IA thrombolytics > 6 hrs
IA devices > 9 hrs
Basilar thrombosis > 12 hrs
Wake-up strokes
Clock v. physiology

10. DEFUSE: Mismatch associated with good outcomes following reperfusion
Before tPA
NIHSS 16
6 cc
4.5 hrs
After tPA
NIHSS 5
Improved
0 cc
IV tPA
3 cc
65 cc
↓ M2 Flow

11. The Malignant Mismatch Pattern
Before
tPA
>100 cc
M1 open
77 cc
4 hr
after tPA
105 cc
215 cc
M1 Occlusion

12. Malignant Pattern Outcomes Modified Rankin Scale at Day 30
Malignant
Pattern
n=6 33 33 83 33 17
p=0.06
All other
Patterns
n=68 12 12 57 19 31 28 41
All fatal ICHs in malignant pattern patients with early reperfusion; n = 3
No SICH occurred in malignant patient without early reperfusion; 1 patient (45 yrs) had a favorable outcome (Rankin 1)
Albers GW et al. Ann Neurol. 2006;60(5):508

13. Pooled Data: DEFUSE / EPITHET
Optimal definition of malignant pattern: PWI Tmax > 8 Sec at least 85cc
Large PWI lesion better predictor of poor outcome than large DWI lesion
Poor Outcome: Rankin 5-6
Reperfusion
No Reperfusion
p value
Malignant Pattern
88% (7/8)
41% (7/17)
0.04
Non Malignant Pattern
10% (5/56)
33% (7/28)
0.09
De Silva, et al on behalf of the DEFUSE-EPITHET Investigators. ISC 2010

14. CT Perfusion Irreversible Infarction
MTT
CBV
CBF CT

15. Summary Severe deficits only relative contraindication
Hemorrhage after IV tPA associated with protocol deviations
Large established infarction predicts hemorrhage and poor outcome