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					FERNE / MEMC IV Brain Illness and Injury Course:
Acute Ischemic Stroke
E. Bradshaw Bunney, MD, FACEP




               Acute
          Ischemic Stroke                             FERNE Brain Illness
                                                       and Injury Course
              Update
                          E. Bradshaw Bunney, MD                        E. Bradshaw Bunney, MD




           4th Mediterranean
                                                         E. Bradshaw Bunney
          Emergency Medicine                             Associate Professor
               Congress
             Sorrento, Italy                         Department of Emergency Medicine
                                                   University of Illinois College of Medicine
          September 17, 2007                                       Chicago, IL

                          E. Bradshaw Bunney, MD                        E. Bradshaw Bunney, MD




           Attending Physician                               Board Member
           Emergency Medicine
           University of Illinois Hospital
                                                                 FERNE
       Our Lady of the Resurrection Hospital
                                                                 Chicago, IL
                   Chicago, IL
                          E. Bradshaw Bunney, MD                        E. Bradshaw Bunney, MD




                                                                                                 1
FERNE / MEMC IV Brain Illness and Injury Course:
Acute Ischemic Stroke
E. Bradshaw Bunney, MD, FACEP



                        Disclosures
          •   Genentech, AstraZeneca advisory group
          •   ACEP Scientific Review Committee
          •   Executive Board, FERNE
          •   FERNE support by Abbott, Eisai, Pfizer,
              UCB



                                                                               www.ferne.org
                                    E. Bradshaw Bunney, MD                              E. Bradshaw Bunney, MD




                    Key Clinical Questions                             Key Clinical Questions
      •       What is primary stroke center                  •   What therapies exist in 2007 for the
              designation?                                       treatment of ischemic stroke after 3
      •       What stroke surveillance systems                   hours?
              currently exist?                               •   What new therapies are on the
      •       How are patients not at stroke centers             horizon and how will they impact the
              treated?                                           EM management of stroke?
      •       How are telemedicine systems utilized          •   What is new in the 2007 ASA
              in these stroke systems?                           Guidelines?
                                    E. Bradshaw Bunney, MD                              E. Bradshaw Bunney, MD




                               Case                                               Case
                •   19 yo female collapsed a work on               •   In ED – Friend confirms onset time
                    Super Bowl Sunday 2006                         •   Friend states no PMHx, no drug or
                •   EMS found her not moving her right                 alcohol use
                    side, aphasic, eyes deviated to the
                    left                                           •   PE - R arm 0/5 strength, R leg 3/5,
                •   Onset time 20 minutes prior to EMS                 aphasic, eyes deviated to L
                    arrival                                        •   No family available
                •   BP 120/62, HR 84, RR 14

                                    E. Bradshaw Bunney, MD                              E. Bradshaw Bunney, MD




                                                                                                                 2
FERNE / MEMC IV Brain Illness and Injury Course:
Acute Ischemic Stroke
E. Bradshaw Bunney, MD, FACEP



                                                     Case
       •   Glucose = 97
       •
       •
           Not pregnant
           CBC, electrolytes, coagulation all normal
                                                                                                   Stroke in Perspective
       •   CT head = normal
       •   Differential Diagnosis:
           • Stroke

           • Multiple Sclerosis

           • Hysteria

           • Conversion Reaction

           • Intoxicant          E. Bradshaw Bunney, MD                                                                                           E. Bradshaw Bunney, MD




                    Patient Aversion to
                 Various Stroke Outcomes                                                                 Primary Stroke Centers
                                                                                                     •   Patient care areas                       •   Support services
                                                                                                          • Acute stroke teams                         • Stroke center
                10
                 9
                                                                                                          • Written care                                 director
                 8
                                                                                       Aversion:
                                                                                                            protocols                                  • Neuroimaging
                 7                                                                                        • Emergency medical                            services
                 6                                                                      Mild
                 5                                                                      Moderate            services                                   • Laboratory services
                 4                                                                                        • Emergency                                  • Outcome and
                 3
                                                                                        Severe
                 2                                                                                          department                                   quality
                 1                                                                                        • Stroke unit                                  improvement
                 0
                                                                                                          • Neurosurgical                                activities
                       Language                 Cognitive       Motor          Death                        services                                   • Continuing medical
                        deficits                 deficits      deficits
                                                                                                                                                         education

                Solomon NA et al Stroke 1994 25(9):1721-5.   E. Bradshaw Bunney, MD                Alberts MJ, et al. JAMA. 2000;283:3102-3109.   E. Bradshaw Bunney, MD




               Primary Stroke Centers                                                                               Stroke Registries
           •   Approximately 5,000 hospitals in the US                                                   •   Senator Paul Coverdell from
           •   As of June 2007 there are 352 certified                                                       Georgia
               Stroke Centers                                                                            •   Died July 2000
           •   94 more in the pipeline                                                                   •   CDC awarding grants to states to
           •   40 states                                                                                     establish registries
           •   State certification in several states                                                     •   National link



                                                             E. Bradshaw Bunney, MD                                                               E. Bradshaw Bunney, MD




                                                                                                                                                                               3
FERNE / MEMC IV Brain Illness and Injury Course:
Acute Ischemic Stroke
E. Bradshaw Bunney, MD, FACEP



            Coverdell Stroke Registry                                         Stroke Networks
        •       6867 stroke admissions at 98 hospitals
        •       4 states (MI, GA, OH, MA)                              •   Consultation agreements
        •       Less that 2/3 had documented onset times.
        •       Less than 50% had:                                     •   Rotating call between institutions
                   dysphagia screening (45%)
                 •

                 • lipid testing (34%)
                                                                       •   Consolidating resources among a
                 • smoking cessation counseling (21%)                      network of hospitals
        •       3% received tPA in MI, GA, OH, while 8% received
                tPA in MA.                                             •   Uniform protocol usage
        •       Conclusion: only a minority of acute stroke patients   •   Maximize therapy usage
                are treated according to established guidelines.
        •       Protocols will be redesigned to improve compliance
                with the established guidelines which may reveal
                outcomes benefit.

                                           E. Bradshaw Bunney, MD                           E. Bradshaw Bunney, MD




                           Rural Nevada                                    Telemedicine Systems
        •       One designated stroke center                           •   Two-
                                                                           Two-way videoconferencing to
        •       25 rural EDs                                               connect a treating physician
        •       One protocol agreed to by all hospitals                    with a remote consultant
        •       Central stroke team                                    •   Management option for the
        •       Site visits to confirm protocol                            treatment of acute stroke
                adherence and promote team approach                        patients in hospitals without the
        •       Help to raise the treatment of stroke                      resources to provide acute
                patients to a common norm                                  stroke care.
                                           E. Bradshaw Bunney, MD                           E. Bradshaw Bunney, MD




                  Telemedicine Systems
            •   Telemedicine consultation on 24 acute stroke
                patients
            •   6 (25%) received tPA
                 •                            (+/-
                   door to needle time of 106 (+/- 22) minutes
                                                                            Ischemic Stroke
            •
                 •                              (+/-
                   consult to needle time of 36 (+/- 15) minutes.
                No protocol violations                                         Treatment
            •   May increase the number of stroke patients
                receiving therapy
            •   May assist in delineating a group of patients that
                can receive optimal treatment at the originating
                hospital thus improving the utilization of scarce
                resources.

                                           E. Bradshaw Bunney, MD                           E. Bradshaw Bunney, MD




                                                                                                                     4
FERNE / MEMC IV Brain Illness and Injury Course:
Acute Ischemic Stroke
E. Bradshaw Bunney, MD, FACEP



          Treatment: Thrombolysis                           Treatment: Thrombolysis
                                                       •   14% absolute increase for the best clinical
          •   NINDS 1995, 3 hour window
                                                           outcomes as measured by an NIHSS of 0-1.   0-
          •   30 day: absolute benefit toward          •                                           t-
                                                           Benefit = Need to treat 8 patients with t-PA in
              favorable outcome 14% (relative              order to have 1 additional patient with this
              30%) (OR 1.7)                                best outcome.
                                                       •   6% absolute increase in the number of
          •   Symptomatic ICH 6.4% vs 0.6%                 symptomatic ICH.
          •   Mortality the same                       •   Harm = Will have one symptomatic ICH for
                                                                                          t-
                                                           every 16 patients treated with t-PA.
                                                       •   2 patients will have a minimal or no deficit for
                                                           everyone patient with a symptomatic ICH
                              E. Bradshaw Bunney, MD                                    E. Bradshaw Bunney, MD




                                                                               CT Head

                   CT Imaging




                              E. Bradshaw Bunney, MD                                    E. Bradshaw Bunney, MD




               CT Angio & Perfusion                                      CTA and CTP
                                                               •   Essential questions
                                                                   •   Is there hemorrhage?
                                                                   •   Is there large vessel
                                                                       occlusion?
                                                                   •             irreversibly”
                                                                       Is there “irreversibly”
                                                                       infarcted core?
                                                                   •                risk”
                                                                       Is there “at risk” penumbra?
                                                               •   One contrast bolus yields
                                                                   two datasets
                                                                   •   Vessel patency
                                                                   •   Infarct versus salvageable
                                                                       penumbra


                              E. Bradshaw Bunney, MD                                    E. Bradshaw Bunney, MD




                                                                                                                 5
FERNE / MEMC IV Brain Illness and Injury Course:
Acute Ischemic Stroke
E. Bradshaw Bunney, MD, FACEP



                                                                  DWI/PWI Mismatch
                                                          •   Subtract DWI hyperintense signal
                                                              area from the PWI hypoperfused
                  MR Imaging                                  area = DWI/PWI mismatch
                                                              • Hypoperfused
                                                              area that is still
                                                              viable
                                                              (penumbra)
                                                              • Target area for

                             E. Bradshaw Bunney, MD           reperfusion          E. Bradshaw Bunney, MD




            New Therapies                                 Intra-Arterial Thrombolysis
                                                      •   Two randomized trials – PROACT 1 & 2
                                                      •   Tested prourokinase vs. heparin <6 hours
                                                      •   MCA occlusions only
                                                      •   Recanalization improved with IA
                                                      •   Mortality identical
                                                      •   Relative risk reduction for outcome – 60%
                                                      •   Risk of invasive procedure


                             E. Bradshaw Bunney, MD                                E. Bradshaw Bunney, MD




              IA in Clinical Practice                            Pre-             t-
                                                                 Pre- and Post IA t-PA
       •   Numerous clinical series published
       •   Basilar artery thrombosis series
           suggest benefit
       •   Benefit with basilar may be late
              (12-
             (12-24 hrs)
       •   MRI diffusion/perfusion may aid
           selection

                             E. Bradshaw Bunney, MD                                E. Bradshaw Bunney, MD




                                                                                                            6
FERNE / MEMC IV Brain Illness and Injury Course:
Acute Ischemic Stroke
E. Bradshaw Bunney, MD, FACEP



               Mechanical Clot Removal                               Multi MERCI Trial
       •   Invasive                                     •   N = 164
           neuroradiologist/neurosurgeon                •   Baseline NIHSS = 19.3
       •   Window extended to 8 to 12 hours             •   Revascularization = 68%
       •   Intra-
           Intra-arterial thrombolysis may be           •                    (90-
                                                            Good Outcome (90-day mRS < 2) = 36%
           given after clot removal                     •   SICH = 9.8%
                                                        •   Mortality at 90 days = 33%

                               E. Bradshaw Bunney, MD                             E. Bradshaw Bunney, MD




                   Multi MERCI Trial                              MERCI Clot Retriever
           •   Subgroup of 29% (48/164) that
                         t-
               failed IV t-PA
           •   Revascularization = 73%
           •   mRS < 2 at 90 days = 38%
           •   SICH 10.4%



                               E. Bradshaw Bunney, MD                             E. Bradshaw Bunney, MD




                 MERCI Clot Retriever                                  Desmoteplase
                                                            •   DIAS, DEDAS studies
                                                            •   More fibrin specific, longer half life
                                                            •   MRI diffusion / perfusion mismatch
                                                                >20%
                                                            •          4-
                                                                NIHSS 4-20
                                                            •   3-9 hours after onset


                               E. Bradshaw Bunney, MD                             E. Bradshaw Bunney, MD




                                                                                                           7
FERNE / MEMC IV Brain Illness and Injury Course:
Acute Ischemic Stroke
E. Bradshaw Bunney, MD, FACEP



                         Desmoteplase                                           ASA Guidelines 2007
          •   N = 37                                                       •   New EMS Section
                                                                               • Educate the public
          •   No symptomatic ICH                                               • EMS use of scales

          •   Reperfusion:                                                     • “Closest institution that can provide

                                                                                                    care”
                                                                                 emergency stroke care”
              • Placebo 37%
                                                                           •   New Stroke Center Section
              • 125 ug/kg 53%                                                  • Creation of Primary Stroke Center

                                                                                 strongly recommended
          •   Good clinical outcome (composite):                               • Develop Comprehensive Stroke

              • Placebo 25%                                                      Centers
                                                                               • Bypass hospitals that do not have the
              • 125 ug/kg 60%          E. Bradshaw Bunney, MD                    resources to treat stroke Bunney, MD
                                                                                                     E. Bradshaw




                     ASA Guidelines 2007                                        ASA Guidelines 2007
      •       ED Evaluation Section (Not Changed)                  •   Management Section
                                                                        • Management of HTN is controversial
               • Develop strict protocol
                                                                        • No good data to guide selection of BP meds,
               • Use stroke scale
                                                                          NTG paste??
      •       Imaging Section
                                                                        • If treat must maintain BP at 180/105 for 24 h
               • CT provides the information needed to treat
                                                                        • Glucose >140 mg/dl: poor outcome seen
               • Dense artery sign assoc. with poor outcome
                                                                   •   TPA Section
               • CTA and MR provide additional information
                                                                        • Caution should be exercised in treating pts
               • Insufficient data to say that other signs on CT
                                                                          with major deficits, NIHSS > 20
                 should stop therapy
                                                                        • Aware of side effect of angioedema
               • Do not delay treatment for other images
                                                                        • Seizure is not a contraindication

                                       E. Bradshaw Bunney, MD                                      E. Bradshaw Bunney, MD




                         Case Outcome                                                 Case Outcome
                 •   Small hospital, no neurologist                    •                                 t- PA”
                                                                           Stroke neurologist = “Give IV t-PA”
                     interested in seeing the patient                  •   t-PA given at 2 hours 15 minutes
                 •   Called 2 Universities before                          from onset
                     finding one to accept the patient                 •   R arm movement and aphasia
                 •   Family arrived, patient not                           improving prior to transfer
                     improving


                                       E. Bradshaw Bunney, MD                                      E. Bradshaw Bunney, MD




                                                                                                                            8
FERNE / MEMC IV Brain Illness and Injury Course:
Acute Ischemic Stroke
E. Bradshaw Bunney, MD, FACEP



                                Case Outcome                                                        Conclusions
           •   MRI at University = small infarct                                        •   Stroke center certification provides
                                                                                            a method of measuring quality
           •   ECHO cardiogram = Patent foramen                                             improvement in stroke patient care
               ovale, likely embolic stroke                                             •   Stroke networks allow a region to
           •   Outcome = normal except small                                                achieve a particular quality standard
               vision loss.                                                             •   Outcomes measurement needs to
                                                                                            be continued to establish the role of
                                                                                            stroke systems as well as therapies

                                                               E. Bradshaw Bunney, MD                         E. Bradshaw Bunney, MD




                                   Conclusions                                                      Conclusions
       •       IA thrombolysis and mechanical clot                                      •   Accurate measurement of the
               removal provide an alternative at                                            penumbra may surpass the strict
               institutions able to use it                                                  time nature of treatment
       •       CTA and CT perfusion may become                                          •   New therapies based on the percent
               routine                                                                      of penumbra remaining may allow
       •                 brain”
               “Time is brain” may be replaced by                                           for time to be relatively unimportant
                                brain”
               “Physiology is brain”

                                                               E. Bradshaw Bunney, MD                         E. Bradshaw Bunney, MD




                                 Questions?
                  www.FERNE.org

                  bbunney@uic.edu
                  312 413 7484

       ferne_memc_2007_braincourse_bunney_ais_091707_finalcd
       9/27/2007 10:59 AM
                                                               E. Bradshaw Bunney, MD




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