Ischemic Stroke 101. David Y. Huang, MD, PhD

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1 Ischemic Stroke 101 David Y. Huang, MD, PhD Director, UNC Hospitals Stroke Center Associate Professor, Department of Neurology UNC School of Medicine

2 Outline What is a stroke? Acute Stroke: EMS Management t-pa» Use of intravenous (IV) t-pa from 0-3 hours» IV rt-pa hours» Treatment delays negatively impact overall benefit Interventional Treatments at UNC» Intra-arterial (IA) rt-pa» MERCI Clot Retriever» Penumbra System 8/28/2012 2

3 What is a STROKE? Definition: A stroke is an illness of sudden onset causing injury to the brain that results from occlusion or rupture of a blood vessel that supplies a specific region of the brain STROKE IS AN EMERGENCY

4 Circulation of the Brain 4

5 5

6 Functional Map of the Brain 6

7 STROKE CLASSIFICATIONS Ischemic Strokes» blood vessel occlusion Hemorrhagic Strokes» blood vessel rupture

8 STROKE SUBTYPES Albers GW et al. Chest. 1998;114:683S-698S. Rosamond WD et al. Stroke. 1999;30:

9 STROKE is a BRAIN ATTACK Time = Brain Early Recognition = Brain Saved STROKE IS AN EMERGENCY

10 Stroke Care: AHA 7 D s Adams et al. Stroke (2007) 38:

11 Acute Stroke: Barriers to Treatment A large proportion of stroke patients do not know the signs or symptoms of stroke Only 5-20% of stroke patients seek medical attention within 3 hours of symptom onset

12 What are some barriers to calling 911? When raised in rural townships you don t go to the doctor immediately. You lie down and rest first. Older African American men were highly suspicious of the medical community and perceived they received less treatment than whites. Men admitted to being less likely to go to a doctor or hospital for care thinking they would just get better. Denial about the possibility of having a major illness. High cost or lack of insurance prohibited seeking care. Did not want the embarrassment of overreacting to symptoms.

13 Stroke: EMS Management Time Is Brain and Lost Time Is Lost Brain

14 EMS Evaluation ABCs/CABs History» Onset of symptoms» Recent events Stroke, Myocardial infarction, Trauma, Surgery, Bleeding» Comorbid diseases Hypertension Diabetes mellitus Vascular disease» Stroke» CAD» PVD» Medications Anticoagulants Insulin Antihypertensives» Allergies Stroke Screening Tools» Cincinnati Prehospital Stroke Scale (CPSS)» Los Angeles Prehospital Stroke Screen (LAPSS)» Sensitivity for identifying patients with stroke Standard training 61% to 66% Training with stroke assessment tool 86% to 97% Adams et al. Stroke (2007) 38:

15 Screening for Stroke Cincinnati Prehospital Stroke Scale Normal: Abnormal: Normal: Abnormal: Normal: Abnormal: Facial Droop Both sides of the face move equally One side of the face does not move at all Arm Drift Both arms move equally or not at all One arm drifts compared with the other Speech Patient uses correct words with no slurring Slurred or inappropriate words or mute Source: University of Cincinnati College of Medicine.

16 Screening for Stroke Los Angeles Prehospital Stroke Screen (LAPSS) 1. Age >45 years 2. History of seizures or epilepsy absent 3. Symptom duration <24 hours 4. At baseline, patient is not wheelchair bound or bedridden 5. Blood glucose between 60 and 400 mg/dl 6. Obvious asymmetry (right vs left) in any of the following 3 exam categories (must be unilateral):» Facial smile/grimace» Grip» Arm strength AHA Adult Stroke Guidelines. Circulation. 2005;112(suppl 24):IV-1-IV-203.

17 EMS Management Adams et al. Stroke (2007) 38:

18 Objectives for EMS Stabilization of the patient Rapid identification of stroke as the cause of the patient s findings Elimination of co-morbid conditions that could mimic stroke Rapid transportation of the patient to the closest appropriate ED Notification of the receiving institution about impending arrival of a patient with suspected stroke Adams et al. Stroke (2007) 38:

19 EMS Management While EMS has the ability to predict stroke, only imaging (CT or MRI) can determine whether a person is suffering from an ischemic stroke or a hemorrhagic stroke. Early Ischemic Intracerebral Hemorrhage Epidural Hemorrhage Late Ischemic Subarachnoid Hemorrhage Subdural Hemorrhage 19

20 N.C. Stroke Care Collaborative Registry 13,894 records evaluated Arrival by EMS (versus private transport) was associated with faster evaluations Brain imaging completed within 25 minutes» EMS with prenotification: risk ratio, 3.0; 95% CI, 2.1 to 4.1» EMS without prenotification: risk ratio, 1.9; 95% CI, 1.6 to 2.3) and Brain imaging interpreted within 45 minutes» EMS with prenotification: ratio, 2.7; 95% CI, 2.3 to 3.3» EMS without prenotification: ratio, 1.7; 95% CI, 1.4 to 2.1 Stroke. 2011;42: Published online June 9, 2011

21 UNC Hospitals ED Stroke Pre-Hospital Notification» Radio» Secondary process ED Charge Nurse ED Attending (main ED number) 8/28/

22 Acute Ischemic Stroke Treatments Rapid triage model after trauma and MI For IV tpa eligible patients: Golden Hour» 60 minute door-to-needle time Protocols and training to insure MDs and nurses are comfortable assessing and administering treatment 22

23 NINDS t-pa Trial Endpoint rt-pa Placebo Odds Ratio (95% CI) P Favorable Outcome (mrs 0-1) at 90 Days (%) ( ) As compared with patients given placebo, patients treated with t-pa were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales. Endpoints rt-pa Placebo P Symptomatic ICH, NINDS definition (%) < Mortality at 3 months (%) NINDS Part 2, NEJM1995:

24 t-pa: the sooner, the better The odds ratio for favorable outcome at 3 months in patients treated with t-pa decreases as a function of the interval between stroke onset and onset of the treatment (OTT) Source: Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-pa stroke trials. Lancet. 2004; 363(9411):

25 ECASS-3 A randomized, placebo-controlled, phase 3 trial conducted at 130 sites in 19 European countries to examine safety and efficacy of rt-pa in the 3 to 4.5 hour treatment window; 821 patients aged 18 to 80 years were enrolled 10% of patients were treated between 3 and 3.5 hours, 46.8% between 3.5 and 4 hours, and 39.2% between 4 and 4.5 hours Mean time to treatment was 3 hours and 59 minutes Endpoint rt-pa Placebo Odds Ratio (95% CI) P Favorable Outcome (mrs 0-1) at 90 Days (%) ( ).04 Endpoints rt-pa Placebo P Symptomatic ICH, NINDS definition (%) Mortality (%) NEJM :

26 ECASS-3 Differences compared to NINDS» Patients older than 80 years were not studied» Patients with a combination of previous stroke and diabetes mellitus were excluded» Patients taking oral anticoagulant treatment were excluded» Patients with severe stroke as assessed clinically (e.g., NIHSS score >25) or by appropriate imaging techniques were excluded As a result of this study, many centers started offering rt- PA in the hour window» Considered off-label usage 26

27 Intra-Arterial Treatments 3-6 hours» Intra-arterial tpa: within 6 hours of symptom onset 3-8 hours» MERCI Clot Retrieval» Penumbra System

28 MERCI: Basilar Case Study 31 year old male NIHSS Score 10 (dysarthria and right-sided weakness) Progressed to unresponsive with vertical nystagmus Symptom Onset to Treatment 4h 30min Source: Yu et al. Neurology (2003) 61:

29 MERCI: Basilar Case Study NIHSSS 24 hours 0 30 days 0 mrs 90 days 0 Source: Yu et al. Neurology (2003) 61:

30 PENUMBRA System Clot Retrieved Pre-PENUMBRA Post-PENUMBRA

31 Intra-Arterial Therapies Intra-Arterial Therapies are not tpa substitutes!» Pros Expand the treatment window» Cons Not widely available currently limited to comprehensive stroke centers with interventional capabilities Narrow eligibility criteria Anatomical limitations IA therapies are not as well-studied Benefits are controversial» IA rt-pa is off-label» Although the FDA-approved devices have demonstrated that they can remove a clot, no study has shown that the intervention benefits a patient s long-term outcome 31

32 Related Trial Comparisons* Revascularization Stroke 2005;36: AJNR 2006;27: JAMA1999;282: N. Eng J M 2004;351:2170 * Population observation rates, and 95% Exact Binomial Confidence Intervals

33 Related Trial Comparisons* mrs 2 at 90 Days PROACT II Control (n=59) 4 1. Stroke 2005;36: AJNR 2006;27: JAMA1999;282: N. Eng J M 2004;351:2170 * Population observation rates, and 95% Exact Binomial Confidence Intervals

34 Related Trial Comparisons* Symptomatic ICH PROACT II Control (n=59) 4 1. Stroke 2005;36: AJNR 2006;27: JAMA1999;282: N. Eng J M 2004;351:2170 * Population observation rates, and 95% Exact Binomial Confidence Intervals

35 The standard for acute stroke care is still IV rt-pa Intra-arterial treatments are not equivalent to the IV rt-pa Systems for acute stroke care should be designed to optimize delivery of standard stroke care (IV rt-pa) Other stroke interventions should be considered rescue for patients who are not eligible for IV tpa 35

36 UNC Comprehensive Stroke Center Ground & Air transportation Emergency Services: ED & VIR Neurosciences ICU ISCU: Step-Down 6NSH Neurology Acute Care Rehab Unit Stroke Clinic UNC Transfer Center UNC Neurology (Stroke) clinic offices NP

37 UNC Stroke NP Program Susan Wilson, FNP » Provides post-discharge support for patients and caregivers» Provides follow-up to referring MDs and PCPs» Provides follow-up to EMS providers who bring patients directly to UNC EMS information portal 37

38 Summary Time is Brain!» Assess and transport patients quickly rt-pa» IV rt-pa is the indicated treatment for eligible patients presenting in the 3-hour window» Treatment delays have significant impact on overall benefit» IV rt-pa from hours is a reasonable treatment and is recommended for most acute stroke patients Interventional Treatments» Limited availability» Only a small fraction of stroke patients qualify clinically» Benefits not proven in large-scale studies On the Horizon» Work continues to find new (more effective and safer) ways to treat stroke

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