1. Hemiparesis: The Emerging Role of the Emergency Physician in Stroke Management Edward Sloan, MD, MPH Associate Professor Department of Emergency Medicine University of Illinois College of Medicine-Chicago Chicago, IL

2. Edward Sloan, MD, MPH Objectives Present clinical case history Review Emergency Department H&P Examine tPA clinical data Discuss tPA use in ischemic stroke Review other therapies for ischemic stroke Answer clinically relevant questions

3. Edward Sloan, MD, MPH Clinical History A 62 year old female acutely developed aphasia and right sided weakness while in the grocery store. The store clerk immediately called 911, with the arrival of CFD paramedics within 9 minutes, at 6:43 pm. She arrived at the ED at 7:05 pm, completed her head CT at 7:25 pm, and obtained a neuro consult at 7:35 pm, approximately one hour after the onset of her symptoms. What are the next Rx steps?

4. Edward Sloan, MD, MPH ED Presentation On exam, BP 116/63, P 90, RR 16, T 98, and pulse oximetry showed 99% saturation. The patient appeared alert, and was able to slowly respond to simple commands. The patient had a patent airway, no carotid bruits, clear lungs, and a regular cardiac rate and rhythm. The pupils were pinpoint, and there was neglect of the R visual field. There was facial weakness of the R mouth, and R upper and lower extremity motor paralysis. DTRs were 2/2 on the left and 0/2 on the right. Planter reflex was upgoing on the right and downgoing on the left. The patient’s estimated weight was 50 kg.

5. Edward Sloan, MD, MPH Acute Ischemic Stroke Questions What are the epidemiology & etiology? What are the key elements of the exam? What is the NIH stroke scale? What did the NINDS trial show? How should tPA be used by the EM MD? What about hemorrhagic conversion? What about other therapies?

6. Edward Sloan, MD, MPH Acute Stroke: Epidemiology 700,000 Cases annually 20% mortality within one year $30 billion annual costs Ischemic and hemorrhagic strokes

7. Edward Sloan, MD, MPH Acute Ischemic Stroke: Etiology Thrombotic, embolic, hypoperfusion Majority are vessel thrombosis Clot formation on diseased vessel 20% are embolic, from heart, great vessels Hypoperfusion with cardiogenic shock

8. Edward Sloan, MD, MPH Acute Ischemic Stroke: Syndromes Anterior cerebral Middle cerebral Posterior cerebral Vertebrobasilar Basilar artery occlusion Cerebellar Lacunar Arterial dissection

9. Edward Sloan, MD, MPH Acute Stroke: Historical Elements When did symptoms begin? Onset? Prior history of similar symptoms? When was the patient last seen normal? Risk factors? Medical hx that would preclude tPA use?

10. Edward Sloan, MD, MPH Acute Stroke: Physical Exam Vital signs, pulse ox, accucheck HEENT: Pupils, papilledema, airway Neck: Bruits, nuchal rigidity Chest: Rales (CHF, aspiration) Cardiac: Gallops, murmurs

11. Edward Sloan, MD, MPH Acute Stroke: Physical Exam Abd: Evidence of AAA Ext: Evidence of CHF, DVT Skin: Evidence of infectious etiology Neuro: CN, motor, sensory, reflexes, cerebellar, visual, language, neglect, mental status

12. Edward Sloan, MD, MPH Neurologic Exam: Cranial Nerves CN: Anterior vs. brainstem? – Anterior: Contralateral CN deficits – Brainstem: Ipsilateral CN deficits

13. Edward Sloan, MD, MPH Neurologic Exam: Motor Motor: CN, upper & lower ext – CN: Eye motor (Bell’s) – Upper: Pronator drift – Lower: Leg lift

14. Edward Sloan, MD, MPH Neurologic Exam: Sensory Sensory: Light touch, pinprick Graphesthesia

15. Edward Sloan, MD, MPH Neurologic Exam: Reflexes Normal vs. pathologic – Normal: Corneal, gag, DTRs – Pathologic: Babinski, Chadduck

16. Edward Sloan, MD, MPH Neurologic Exam: Cerebellar Truncal ataxia Ataxic gait Rhomberg

17. Edward Sloan, MD, MPH Neurologic Exam: Visual Visual field deficit Homonomous hemianopsia – Neglect of one side

18. Edward Sloan, MD, MPH Neurologic Exam: Language Dysarthria: Poor speech, motor dysfunction Aphasia: Disturbed language processing – Expressive: can’t speak – Receptive: can’t process the spoken word

19. Edward Sloan, MD, MPH Neurologic Exam: Mental Status Level of consciousness (AVPU) – Alert – Responds to verbal – Responds to painful – Unresponsive

20. Edward Sloan, MD, MPH Neurologic Exam: NIH Stroke Scale 13 item scoring system, 7 minute exam Integrates neurologic exam components CN, motor, sensory, cerebellar, visual, language, LOC Maximum score is 31, signifying severe stroke Minimum score is 0, a normal exam Scores greater than 15-20 are more severe

21. Edward Sloan, MD, MPH Acute Ischemic Stroke: NINDS Clinical Trial of tPA Treatment within 180 minutes 0.9 mg/kg of tPA Two part study Endpoint: favorable outcome at 3 months Also examined mortality, hemorrhage

22. Edward Sloan, MD, MPH NINDS Clinical Trial of tPA: Results Good outcome: 30% more patients Odds of favorable outcome: 1.7 (1.2-2.6) 10x greater hemorrhage risk: (6.4 vs. 0.6%) Comparable 3 month mortality: (17 vs. 21%) Conclusion: tPA worth the hemorrhage risk, since there is clear benefit

23. Edward Sloan, MD, MPH NINDS Clinical Trial of tPA: Clinical Upshot tPA must be considered Patient selection is very difficult Must maximize risk/benefit ratio Must avoid hemorrhage, if possible Need adequate severity, but not too severe Less than 2% of patients will meet criteria

24. Edward Sloan, MD, MPH NINDS Clinical Trial of tPA: Timing Issues Early EMS contact is key Door to CT and CT read time important Is there time for a neurologist to consult? A stroke team helps The 3 hour window is not the only issue

25. Edward Sloan, MD, MPH NINDS Clinical Trial of tPA: Clinically Relevant Issues Histories are unreliable Timing issues hard to press for stroke Patient selection is painfully difficult Every CT has a hypodense area Tendency not to intervene First do no harm What we did vs. what was destined to be

26. Edward Sloan, MD, MPH tPA in Acute Ischemic Stroke: Clinical & Documentation Issues Document that tPA was considered If not used, state explicitly why the pt did not meet criteria or why it was deferred When explaining, tell the four key points: – 30% greater chance of good outcome – 10 fold greater risk of bleeding – Same mortality rate, despite bleeding risk – Explain why mortality is comparable

27. Edward Sloan, MD, MPH tPA in Acute Ischemic Stroke: Other Relevant Studies ECASS: No efficacy, higher mortality IA tPA: Effective, feasible ATLANTIS: 5 hour window not possible Cleveland: Non-supportive tPA data – 2% treated, 50% standard of care deviation – 16% bled, 3x higher in-hospital mortality STARS: Favorable outcome and mortality

28. Edward Sloan, MD, MPH Acute Ischemic Stroke: Goals of Other Therapies Recanalization Stop ischemic cascade Minimize hemorrhage Minimize morbidity and mortality

29. Edward Sloan, MD, MPH Acute Ischemic Stroke: Other Therapies LMW heparin: Possibly effective IST study: ASA reduces death & stroke recurrence by 1% PROACT II: IA prourokinase improves outcome STAT: Ancrod (pit viper venom) improves outcome, but causes hemorrhage Neuroprotectants: May provide benefit

30. Edward Sloan, MD, MPH Acute Ischemic Stroke: Other Issues MR Imaging: Feasible, assists pt selection Admission need: Still must admit TIA/CVA pts – No reason not to admit CVAs – Can’t predict progression, complications – Data less clear for TIAs…home observation? – Need HMO experience to be documented

31. Edward Sloan, MD, MPH Acute Ischemic Stroke: Case Management Get the CT scan ASAP Control the blood pressure Start making calls: PMD, family, neurologist Find out the CT results Decide risk/benefit Discuss with pertinent decision makers

32. Edward Sloan, MD, MPH Acute Ischemic Stroke: Clinical Case: CT Results

33. Edward Sloan, MD, MPH Acute Ischemic Stroke: Clinical Case: CT Results

34. Edward Sloan, MD, MPH Acute Ischemic Stroke: Clinical Case: CT Results

35. Edward Sloan, MD, MPH Acute Ischemic Stroke: Clinical Case: ED Management CT: no low density areas or bleed No clear contra-indications to tPA NIH stroke scale: 20-26 Neurologist said OK to treat No family to defer tPA use tPA administered without comp

36. Edward Sloan, MD, MPH Acute Ischemic Stroke: Clinical Case: tPA & Repeat Exam tPA dosing: –8:21 pm, approx 1’45” after CVA sx onset –Initial bolus: 5 mg slow IVP over 2 minutes –Follow-up infusion: 40 mg infusion over 1 hour Repeat exam at 90 minutes: –Repeat Px Exam: Increased speech & use of R arm, decreased mouth droop & visual neglect –Repeat NIH stroke scale: 14-20

37. Edward Sloan, MD, MPH Acute Ischemic Stroke: Hospital Course & Disposition Hospital Course: No hemorrhage, improved neurologic function Disposition: Rehab hospital Deficit: Near complete use of RUE, speech & vision improved, some residual gait deficit

38. Edward Sloan, MD, MPH Acute Ischemic Stroke: Conclusions Ischemic stroke is a big problem There is significant morbidity & mortality tPA is effective in a narrowly defined group Must aggressively work to get tPA used Other therapies hold promise

39. Edward Sloan, MD, MPH Acute Ischemic Stroke: Recommendations Better public education More timely EMS activation More analysis of tPA use re: optimal patients Rapid MR imaging Dvlp other therapies, esp neuroprotectants

40. Edward Sloan, MD, MPH All are true statement about acute ischemic stroke except: a. There are three major categories: thrombotic, embolic, and hypoperfusion. b. The majority of all strokes are caused by vessel thrombosis. c. The symptoms of ischemic stroke develop over minutes to hours. d. The most common source of emboli are the heart and major vessels. e. Middle cerebral artery infarction is associated with ipsilateral weakness and numbness.

41. Edward Sloan, MD, MPH All are true statement about acute ischemic stroke except: Answer e. MCA infarction is associated with contralateral weakness and numbness

42. Edward Sloan, MD, MPH All are true statements about the findings of the NINDS trial except: a. tPA therapy was provided within 3 hours of symptom onset b. At 24 hours, there was no neurologic benefit to the use of tPA (vs. placebo). c. At 90 days, tPA-treated patients were 30% more likely to have a good neurologic outcome. d. Symptomatic intracerebral hemorrhage at 36 hours was 10x higher in tPA-treated patients.. e. At 90 days, mortality in tPA-treated patients was 2x higher.

43. Edward Sloan, MD, MPH All are true statements about the findings of the NINDS trial except: Answer e. Despite a higher rate of intracerebral hemorrhage, tPA therapy was not associated with a higher mortality rate in the NINDS study.

44. Edward Sloan, MD, MPH In the NINDS trial all of the following patients were eligible for tPA therapy except: a. CT scan negative for intracerebral hemorrhage b. Patients with a rapidly improving deficit or minor symptoms. c. A measurable deficit using the NIH stroke scale. d. No history of stroke or traumatic brain injury within three months. e. SBP lower than 185 mm Hg and DBP lower than 110 mm Hg.

45. Edward Sloan, MD, MPH In the NINDS trial all of the following patients were eligible for tPA therapy except: Answer b. Patients with a rapidly improving or minor symptoms were not included in this trial, and should not be considered for thrombolytic therapy.

46. Edward Sloan, MD, MPH All of the following regarding tPA therapy for acute ischemic stroke is true except: a. Because the NINDS trial was the only positive tPA trial, its utility in stroke is questionable. b. The CT finding of ischemic stroke should call into question the timing of symptom onset. c. Patients and their families should be told of the increased risk of bleeding with tPA therapy. d. Other studies have also confirmed a higher hemorrhage rate for tPA-treated patients. e. Mortality rates do not differ with tPA use because of the effects of untreated ischemic stroke.

47. Edward Sloan, MD, MPH All are true statements regarding the use of EEG in SE except: Answer a. The NINDS study was actually two separate studies with the same three month endpoint. In both of these study components, there was a consistent finding of benefit with tPA use. Such consistency leads to the conclusion that the beneficial effects are real.

48. Edward Sloan, MD, MPH All of the following are true of other therapies for ischemic stroke except: a. Low-molecular-weight heparin was shown in one study to improve outcome. b. Asprin reduces the risk of death and recurrent stroke by 1% at six months. c. Intra-arterial prourokinase has been shown to be effective in treating ischemic stroke. d. IV heparin therapy improves outcome in acute ischemic stroke e. Neuroprotectants may work by preventing cell injury and death in the ischemic cascade.

49. Edward Sloan, MD, MPH All of the following are true of other therapies for ischemic stroke except: Answer d. IV heparin has not been shown to be effective in treating acute ischemic stroke.

50. Edward Sloan, MD, MPH The dose and infusion rate for tPA in ischemic cerebral infarct is: a. 9 mg/kg slow IVP over two minutes b. 0.9 mg/kg slow IVP over two minutes c. 0.9 mg/kg infused over one hour d. 0.9 mg/kg, 10% slow IVP over two minutes, then continue the infusion of the 90% over one hour e. 9 mg/kg, 10% slow IVP over two minutes, then continue the infusion of the 90% over one hour

51. Edward Sloan, MD, MPH All of the following are true of other therapies for ischemic stroke except: Answer d. The appropriate dose is 0.9 mg/kg, 10% slow IVP over two minutes, then continue the infusion of the 90% over one hour. The total maximum dose is 90 mg.

52. Questions ?? Edward Sloan, MD, MPH 312 413 7490 Questions ?? Edward Sloan, MD, MPH edsloan@uic.edu 312 413 7490