1. Time is still Brain Victoria Parada MD Clinical Director Neuroscience and Stroke Program Valley Baptist Medical Center Harlingen Management of Acute Ischemic Stroke and Transitory Ischemic Attack

2. Address opportunities for optimal care in the acute phase of ischemic stroke through: A review of latest scientific guidelines from the American Stroke Association published in March 2013 for the treatment of acute ischemic stroke (US Food and Drug Administration approved and evidence-based care, including IV thrombolysis with recombinant tissue- type plasminogen activator) A review of the new recommendations and safety of ivTPA administration to patients where the treatment was previously contraindicated A review of the role of Primary and Comprehensive Stroke Centers in the Community and the role of Regional Stroke Systems of Care Objectives

3. IN THE USA ON AVERAGE SOMEONE SUFFERS A STROKE EVERY 45 SECONDS 795,000 AMERICANS HAVE STROKES ANNUALLY, 200,000 - 500,000 PRESENT WITH TIA 185,000 PATIENTS SUFFER A RECURRENT STROKE STROKE DECLINES FROM 3RD TO 4TH LEADING CAUSE OF DEATH IN THE USA BY 2008 STROKE MORTALITY RATE WAS 75% LESS THAN 1931- 1960 RATE 3 STROKE AN EQUAL OPPORTUNITY DISEASE

4. ✤ TRADE OFF MORTALITY REDUCTION THROUGH BETTER ACUTE STROKE CARE IS AN INCREASE IN SURVIVORS WITH POST-STROKE CONSEQUENCES ✤ ESTIMATED $73.7 BILLION IN ECONOMIC COSTS (2010) ✤ INCALCULABLE HUMAN AND SOCIAL COST TO PATIENTS AND FAMILIES 4 STROKE REMAINS THE LEADING CAUSE OF DISABILITY IN THE USA

5. TIA is a brief episode of neurological dysfunction caused by a focal disturbance of brain or retinal ischemia, which clinical symptoms typically lasting less than 60 minutes and without evidence of infarction STROKE any neurological dysfunction caused by a focal disturbance of brain or retinal ischemia lasting longer than 60 minutes with radiological evidence of infarction TIA AND ACUTE ISCHEMIC STROKE

6. 6 87 % Ischemic 87 % Ischemic 10 % Hemorrhagic 10 % Hemorrhagic 3 % SAH 3 % SAH

10. The first goal of evaluation is to confirm that patient’s symptoms are due to ischemic stroke Second the urgent evaluation helps determine advisability for acute treatment with thrombolytic agents Third, diagnostic studies are carried out to screen for acute medical or neurological complications of stroke Fourth, the evaluation provides historical data useful to establish the vascular distribution of the stroke and provide clues about its etiology Fifth, these data are essential to make decisions about optimal secondary stroke prevention How do we translate these information into daily clinical practice?

11. ER STAFF REHAB SERVICES EMS STROKECODETEAM STROKE UNIT/ NICU COMUNITY

12. Detectionearly recognition AIS and TIA symptoms Detectionearly recognition AIS and TIA symptoms DispatchIMMEDIATE ACTIVATION 911 and priority EMS DispatchIMMEDIATE ACTIVATION 911 and priority EMS DeliveryPrompt transport TO MOST APPROPRIATE STROKE HOSPITAL and prehospital notification DeliveryPrompt transport TO MOST APPROPRIATE STROKE HOSPITAL and prehospital notification DoorImmediate ER triage to HIGH ACUITY AREA DoorImmediate ER triage to HIGH ACUITY AREA Data ER evaluation, STROKE TEAM ACTIVATION, laboratory, and brain imaging Data ER evaluation, STROKE TEAM ACTIVATION, laboratory, and brain imaging DecisionDiagnosis and determination of most appropriate therapy, DISCUSSION WITH PATIENT /FAMILY DecisionDiagnosis and determination of most appropriate therapy, DISCUSSION WITH PATIENT /FAMILY Drug Administration of appropriate drugs or other interventions Drug Administration of appropriate drugs or other interventions Disposition TIMELY admission to STROKE UNIT OR NICU Disposition TIMELY admission to STROKE UNIT OR NICU STROKE CHAIN OF SURVIVAL

13. PREHOSPITAL EVALUATION Asses and manage ABC’s Initiate cardiac monitoring Provide supplemental Oxigen to mantain O2 saturation >94% Establish IV access per local protocol Determine blood glucose and treat accordingly Determine time of symptom onset or last known normal, family contact TRIAGE AND RAPIDLY TRANSPORT TO THE CLOSEST AVAILABLE CERTIFIED PRIMARY OR COMPREHENSIVE STROKE CENTER

14. Primary Comprehensive Acute Stroke Ready Highly specialized treatments for ALL types of strokes Research Wide range of hospitals ivTPA, Stroke Units Standard Stroke Care Telemedicine Drip and Ship Protocol

15. BENEFITS PSC increased the use of IV tPA from 1.5 % to 10.2% CSC increased the use of lytic agents and improved overall care and outcomes for ISCHEMIC STROKE, INTRACRANIAL BLEEDS AND SUBARACHNOID HEMORRHAGE In hospital deaths are reduced by almost 50 % in hospitals with vascular neurologists and multidisciplinary neuroscience critical team In hospital deaths are reduced by 24 % in hospitals with a stroke team, stroke units and neuro critical care units.

16. Timely evaluation and diagnosis are paramount Timely evaluation and diagnosis are paramount ER most have an efficient pathway to identify and evaluate potential stroke patients ER most have an efficient pathway to identify and evaluate potential stroke patients Patients with suspected acute stroke should be triaged with same priority than serious trauma or MI, regardless of severity of deficits Patients with suspected acute stroke should be triaged with same priority than serious trauma or MI, regardless of severity of deficits PROCESS OF CARE FROM SYMPTOM ONSET GOAL 60 MINUTES FROM DOOR TO NEEDLE ED ARRIVAL MD EVAL STROKE TEAM CT CT READ tPA bolus Door to STROKE UNIT OR NICU ADM 0 min <10 min <15 min <25 min < 45 min <60 minuts < 3 HOURS EMERGENCY EVALUATION AND DIAGNOSIS OF ACUTE ISCHEMIC STROKE

18. Accurate time of symptom onset Focused bedside assessment Rapid interpretation of ancillary tests Acute stroke therapy

19. The examination should focus on identifying signs of lateralized hemispheric or brainstem dysfunction consistent with focal cerebral ischemia (NIHSS) Neurologic Examination

22. blood glucose electrolytes complete blood count prothrombin time activated partial thromboplastin time, international normalized ratio renal function cardiac enzymes and a 12-lead EKG Ancillary Testing

23. Early signs of ischemic stroke: Hyper-dense vessel sign Loss of insular ribbon Obscuration of lenticular nucleus Loss of gray-white matter distinction Sulcal effacement Areas of hypo-attenuation CT of brain w/o contrast

25. Non invasive vascular study is strongly recommended during initial evaluation if mechanical thrombectomy is contemplated CT perfusion for measurements of infarct core and penumbra is recommended for selection of acute reperfusion therapy beyond 3 hours

26. Non invasive imaging of cervical vessels CTA or MRA of intracranial vasculature to exclude the presence of proximal intracranial stenosis or oclussio. Confirmation with catheter angiography is recommended. PATIENTS WITH TIA SHOULD UNDERGO NEUROIMAGING EVALUATION WITHIN 24 HOURS FROM SYMPTOMS ONSET RECOMMENDATIONS FOR PATIENTS WITH SYMPTOMS OF AIS THAT HAVE RESOLVED

27. IV thrombolytic therapy remains the cornerstone of evidence-based acute ischemic stroke therapy (Class I; level A) IV rt-PA is efficacious and cost-effective for patients with acute ischemic stroke treated within 3 hours of symptom onset 6.6% complication of symptomatic intracranial hemorrhage (sICH) Intravenous rTPA

28. 4.5 for 0 -90 minutes 9.0 for 91-180 minutes 14.1 for 181-270 minutes 21.4 for 271-360 minutes iv TPA NNT

29. The above figure demonstrates that the likelihood of a favorable clinical outcome diminishes as time to the initiation of IV rt-PA initiation increases. This model was derived from a pooled analysis of major IV rt-PA strokes trials-the ATLANTIS Parts A and B, ECASS I and II, and National Institute of Neurological Disorders and Stroke Parts I and II trials-after adjustment for age, baseline glucose concentration, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline diastolic blood pressure, history of hypertension, and interaction between age and baseline NIHSS measurement. DOOR TO NEEDLE TIME <60 MINS (Class I; level A)

30. Compared with the NINDS rt-PA trial the design of ECASS III had three notable differences in exclusion criteria: (1) Exclusion criteria included age greater than 80 years (2) Severe stroke (NIHSS score greater than 25) (3) History of diabetes with prior stroke 3 to 4.5 hours window (Class I; Level B)

31. I nclusion and Exclusion characteristics of Patients AIS who could be treated with IV tpa within 3 hours from symptom onset Inclusion criteria Diagnosis of AIS causing measurable neurological deficit Onset of symptoms < 3hours before beginning treatment Age >18 or older

32. Exclusion Criteria Significant head trauma or prior stroke in the last 3 months Symptoms suggest SAH Arterial puncture in non compressible site <7 days History of previous ICH Intracranial neoplasm, AVM or aneurysm Recent intracranial or intraspinal surgery Elevated BP (SBP >185 or DBP> 110 mm Hg) Active internal bleeding Platelet count <100,000 Heparin received <48 hours resulting in elevated PTT Current use of anticoagulant with INR >1.7 or PT >15 secs Current use of Direct Thrombin inhibitors or factor Xa inhibitors Blood glucose concentration <50 mg/dl CT with multilobar infarction (> 1/3 of cerebral hemisphere)

33. RELATIVE EXCLUSION CRITERIA Class IIB; level C CONSIDER RISK TO BENEFIT OF IVrTPA ADMINSTRATION CAREFULLY IF ANY OF THESE RELATIVE CONTRAINDICATIONS EXISTS: MINOR OR RAPIDLY IMPROVING SYMPTOMS SEIZURE AT ONSET WITH POST ICTAL IMPAIRMENTS MAJOR SURGERY OR SERIOUS TRAUMA <14 DAYS RECENT GI OR URINARY TRACT HEMORRHAGE <21 DAYS RECENT ACUTE MI <3 MONTHS

34. “1/3 of patients who are not treated with IVrTPA due to mild or rapid improvement of symptoms will have a poor final stroke outcome” 10 BMJ 2004;328;326

35. Neurology.2009 Jun2;72(22):1941-7 11

36. Acute ischemic stroke is typically a clinical diagnosis. A noncontrast CT scan is necessary to exclude intracranial hemorrhage. When the diagnosis is unclear, additional neuroimaging studies, such as MRI or CT angiography, may be helpful Minor or isolated symptoms typically are not treated However, treating isolated disabling symptoms, such as aphasia, is reasonable. If the exact time of symptom onset cannot be determined, then the time the patient was last seen to be normal should be substituted for the time of symptom onset LESSONS LEARNED...

37. The finger-stick blood glucose level should be reviewed during the eligibility evaluation It is reasonable to proceed with IV rt-PA administration prior to obtaining coagulation results if there is no clinical suspicion of a potential abnormality and awaiting theses results would delay treatment Ask about use of new anticoagulants, use in last 48h may limit use of iv TPA administration Treatment in the setting of myocardial infarction is often a consideration in consultation with cardiology Stroke patients with recent surgery may be considered for thrombolysis or Endovascular thrombectomy if available at experienced center Notes on specific eligibility criteria

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40. Patients elegible for IVrTPA should receive it even if endovascular treatments are being considered (Class I; Level A) As with IVrTPA reduced TIME from symptom onset to reperfusion therapy is highly correlated with better outcomes (Class I; level B) Stent retrievers such as Solitaire FR and Trevo are preferred for coil retrievers over the Merci device when mechanical thrombectomy is used (Class I; Level A) Intra-arterial therapy or mechanical thrombectomy is reasonable in patients who have contraindications for IVrTPA (Class IIa, level C) Rescue intra-arterial therapy or mechanical thrombectomy may be reasonable approaches to recanalization to patients with large artery occlusion and no response to IVrTPA (Class IIb; level B) Catheter guided endovascular interventions

41. IV r TPA administration protocols Class I; Level B Infuse at 0.9mg/kg max dose 90 mg over 60 min, 10% dose bolus Admit to NICU or Stroke Unit for monitoring If severe headache, acute peak hypertension, nausea or vomiting, or worsening of neurological exam, discontinue infusion and obtain STAT CT Measure blood pressure and perform assessments every 15 min during infusion and after two hours, every 30 min for 6 hours, then hourly until 24 hours completed Increase frequency of BP monitoring if SBP>180 or DBP>105, administer IV blood pressure medicines as per protocol to maintain below that range Delay placement of NG tubes, indwelling catheters Follow up CT or MRI of brain w/o at 24 h post IVrTPA Have protocols for STAT assessment and treatment of symptomatic ICH or angiodema

42. Action Points!!! TIME = BRAIN DOOR TO NEEDLE TIME <60 MIN REGIONAL STROKE NETWORKS EXPANDED ELIGIBILITY FOR IVrTPA ENDOVASCULAR TREATMENTS MAY BENEFIT SELECTED PATIENTS MULTIDISCIPLINARY TEAM APPROACH FAVORS PATIENTS OUTCOMES

43. Valley Baptist Neuroscience Team