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

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

When Not to Intervene Undesirable Outcomes No recanalization 9 10 11 12 7 8 6 5 1 2 3 4 Control Undesirable Outcomes No recanalization No improvement Massive cerebral edema Hemorrhage

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

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

Symptomatic Hemorrhage After IV tPA Community Hospital Experience Tanne et al. Neurology 1999:53;424-427

Timing of Sx Hem after IV tPA 8 6 4 2 NINDS tPA Stroke Study Group Stroke 1997;28:2109

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

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

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

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

Malignant Pattern Outcomes Modified Rankin Scale at Day 30 0-1 4-6 Malignant Pattern n=6 33 33 83 33 17 0-1 2-3 4-6 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

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

CT Perfusion Irreversible Infarction MTT CBV CBF CT

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