Optimizing ED Ischemic Stroke Patient Care: Horizons in 2007

Edward P. Sloan, MD, MPH, FACEP

Optimizing ED Ischemic Optimizing ED Ischemic Stroke Patient Care: Stroke Patient Care: Horizons in 2007Horizons in 2007


www.ferne.orgwww.ferne.org

FERNE Satellite Session


IEMEIEMECurrent Concepts in Current Concepts in

Emergency CareEmergency Care

Maui, HIMaui, HIDecember 6, 2006December 6, 2006


Edward P. Sloan, MD, MPH FACEP

Professor

Department of Emergency MedicineUniversity of Illinois College of Medicine

Chicago, IL


Attending PhysicianEmergency Medicine

University of Illinois HospitalOur Lady of the Resurrection Hospital

Chicago, IL

Edward Sloan, MD, MPH, FACEP

DisclosuresDisclosures• Consultant to Baxter, Eisai, King Pharma, Novo Consultant to Baxter, Eisai, King Pharma, Novo

NordiskNordisk• Speaker’s bureau EisaiSpeaker’s bureau Eisai• FERNE President and Board ChairFERNE President and Board Chair• ACEP Clinical Policy CommitteeACEP Clinical Policy Committee• FERNE support from Astra Zeneca, Eisai, Novo FERNE support from Astra Zeneca, Eisai, Novo

Nordisk, UCB PharmaNordisk, UCB Pharma

Edward Sloan, MD, MPH, FACEP

Thank YouThank You• IEMEIEME• Marvin Wayne, MD (and Joan)Marvin Wayne, MD (and Joan)• Andrew Asimos, MDAndrew Asimos, MD• The FERNE staff:The FERNE staff:

• Charri, Carla, Jonathan, LiCharri, Carla, Jonathan, Li• Prior FERNE supportersPrior FERNE supporters• All of youAll of you


Clinical ObjectivesClinical Objectives• Treat patients quickly and effectively

• Minimize risk, complications

• Maximize outcome, resource utilization

• Enjoy our patient interactions and EM clinical practice

• Live long and prosper


Ischemic Stroke Pt CareIschemic Stroke Pt Care• Need to utilize tPA when applicable

• No more complicated therapeutic

• Risk of significant hemorrhage 50% that of imparting benefit

• New technologies exist

• Can these new diagnostics improve our ability to utilize this and other therapies?


Ischemic Stroke Ischemic Stroke PathophysiologyPathophysiology

• Cerebrovascular occlusion

• Core infarct: not salvageable

• Ischemic penumbra: salvageable

• Non-contrast CT cannot distinguish

• MRA and CTA may be able to


Diagnostics in ED CVA PtsDiagnostics in ED CVA Pts• Core dead infarct

• Surrounding ischemic penumbra

• Non-contrast CT cannot distinguish these

• MRA and CTA may be able to distinguish

• Therapies based on whether or not there is something to salvage

• This enhances tPA risk/benefit profile


Key Clinical QuestionsKey Clinical Questions• What do MRI and CTA/perfusion offer us

when determining optimal ischemic stroke patient therapies?

• Which test will become our standard of care in the future? Why?


CNS CT, MRI : The TestsCNS CT, MRI : The Tests

• CT with contrast

• CT angiography (CTA)

• MRI, without or with contrast

• MR angiography (MRA)

• Cerebral angiography


MRI/MRAMRI/MRA


Indications for MRI and CT Indications for MRI and CT in Emergent CNS in Emergent CNS Illness & Injury:Illness & Injury:

Beyond the Non-contrast CTBeyond the Non-contrast CT


Gary Strange, MD, FACEPGary Strange, MD, FACEP

ProfessorProfessor

Department of Emergency MedicineDepartment of Emergency MedicineUniversity of Illinois College of MedicineUniversity of Illinois College of Medicine

Chicago, ILChicago, IL



Large, Severe CVAsLarge, Severe CVAs

• Patients with acute stroke

• Moderate severity

• NIHSS ranges from 10-20?

• Acute hemorrhage must be excluded

• Thrombolytic therapy a consideration

• Can pt selection be optimized?


Non-Contrast Cranial CTNon-Contrast Cranial CT• Primary use is to rule out

acute hemorrhage– Contraindication to the use

of thrombolytic therapy– Identification of potential

surgical candidates

• Limited sensitivity for detecting acute cerebral ischemia (31-75%)

• tPA therapy


Acute Ischemic Stroke CTAcute Ischemic Stroke CT• Dense MCA sign• Decreased gray-white differentiation–Especially in the basal ganglia

• Loss of insular ribbon• Effacement of sulci• Edema and mass effect *• Large area of hypodensity* (>1/3 MCA)

*May signify increased risk of hemorrhage with thrombolytic therapy


Magnetic Resonance Imaging (MRI)Magnetic Resonance Imaging (MRI)

• Multimodal MRI

• Demonstrates hyperacute ischemia

• Considered less reliable in identifying early parenchymal hemorrhage

• What role does MRI play in diagnosis and management of the acute stroke pt?


MRI: Stroke Center ApproachesMRI: Stroke Center Approaches

• CT acutely with follow-up MRI –Late delineation of stroke findings

• Both CT and MRI acutely –More expensive, time-consuming

–Possible enhancements in therapy?

• MRI acutely –Is it a reasonable alternative?


What is Multimodal MRI?What is Multimodal MRI?• T1, T2 Imaging: Conventional weighted

pulse sequences

• DWI: Diffusion-Weighted Imaging

• PWI: Perfusion-Weighted Imaging

• GRE: Gradient Recalled Echo pulse sequence (T2*-sensitive)

• FLAIR: Fluid-Attenuated InversionRecovery images


T1 & T2 Weighted Pulse SequencesT1 & T2 Weighted Pulse Sequences

• Sensitive for subacute and chronic blood

• Less sensitive for hyperacute parenchymal hemorrhage?

• Probably adequately sensitive for acute bleed


Gradient Recalled Echo (GRE) Gradient Recalled Echo (GRE) Pulse SequencePulse Sequence

• May be sensitive for hyperacute parenchymal blood

• Detects paramagnetic effects of deoxyhemoglobin & methemoglobin as well as diamagnetic effects of oxyhgb


Gradient Recalled Echo (GRE) Gradient Recalled Echo (GRE) Pulse SequencePulse Sequence

• Core of heterogeneous signal intensity reflecting recently extravasated blood with significant amounts of oxyhgb

• Hypodense rim reflecting blood that is fully deoxygenated


Diffusion-Weighted ImagingDiffusion-Weighted Imaging• Ischemia decreases the

diffusion of water into neurons• Extracellular water accumulates• On DWI, a hyperintense signal• Present within minutes • Irreversible damage delineated• Non-salvageable tissue?• Infarct core


Perfusion-Weighted ImagingPerfusion-Weighted Imaging

• Tracks a gadolinium bolus into brain parenchyma

• PWI detects areas of hypoperfusion

–Infarct core (DWI area) and

–Ischemic penumbra


DWI/PWI MismatchDWI/PWI Mismatch

• Subtract DWI signal (infarct core) from the PWI signal (infarct core and ischemic penumbra)

• DWI/PWI mismatch is the hypoperfused area that may still be viable (ischemic penumbra)


DWI/PWI MismatchDWI/PWI Mismatch• Important clinical implications

• May identify the ischemic penumbra

• If there is a large mismatch, then reperfusion may be of benefit, even beyond the three hour tPA window

• If there is no mismatch, there may be little benefit to thrombolytic therapy, even within the three hour window


DWI/PWI MismatchDWI/PWI Mismatch

• DWI signal• PWI hypoperfused area


So what is the role of MRI in the ED So what is the role of MRI in the ED evaluation of the stroke patient?evaluation of the stroke patient?

• Secondary?– Initial CT to rule out hemorrhage

–Subsequent MRI to fully delineate ischemia, infarct and to follow treatment

• Primary?– Initial and possibly only imaging modality


MRI in Large, Severe CVAsMRI in Large, Severe CVAs

• Primary MRI not current EM standard

• Logistical, timing issues exist

• MRI likely able to diagnose hemorrhage

• DWI/PWI mismatch a promising exam

• Tailored thrombolytic therapy??

• Improved patient outcome??


CT Angiography & CT Angiography & CT PerfusionCT Perfusion

Andrew Asimos, MD, FACEP

Stroke Care after the 3 Hour Window Stroke Care after the 3 Hour Window for IV tPA Use: for IV tPA Use:

What are the Diagnostic and What are the Diagnostic and Therapeutic Options?Therapeutic Options?


44thth EuSEM Congress EuSEM Congress

Crete, GreeceCrete, GreeceOctober 5-7, 2006October 5-7, 2006



Adjunct Associate Professor

Department of Emergency MedicineUniversity of North Carolina School of

Medicine at Chapel HillChapel Hill, NC


Attending PhysicianEmergency Medicine

Carolinas Medical CenterDepartment of Emergency Medicine

Charlotte, NC


DisclosureDisclosure• Will be discussing off label use of Will be discussing off label use of

approved devicesapproved devices


Therapeutic WindowTherapeutic Window• Time from ictus used for practical Time from ictus used for practical

reasons in the EDreasons in the ED• Increasingly will rely on imaging studies Increasingly will rely on imaging studies

to determine ability to salvage at risk to determine ability to salvage at risk CNS tissueCNS tissue


Advanced CT Imaging for Acute Stroke:Advanced CT Imaging for Acute Stroke:CTP versus MRICTP versus MRI

Parameters Definition of Penumbra

Advantages Limitations

CT Perfusion

CBF, CBV, MTT, TTP

Relative CBF <66%; CBV >2.5 mL/200g

•Combined with plain CT•Available•Fast

•Limited brain coverage•Poorly sensitive to posterior circulation•Indirect core visualization•Iodonated contrast

DWI-PWI MRI

CBF, CBV, MTT, TTP, ADC

Relative TTP (or MTT) delay >45s and normal DWI

•Sensitive•No radiation•Directly visualizes core

•Limited availability•CBF and CBV values not accurate•Patient cooperation required•Frequent contraindications

Muir KW et al. Lancet Neurology 2006; 5:755-768


CT Angiography and CT PerfusionCT Angiography and CT Perfusion• Essential questionsEssential questions

• Is there hemorrhage?Is there hemorrhage?• Is there large vessel occlusion?Is there large vessel occlusion?• Is there “irreversibly” infarcted Is there “irreversibly” infarcted

core?core?• Is there “at risk” penumbra?Is there “at risk” penumbra?

• One contrast bolus yields two One contrast bolus yields two datasetsdatasets• Vessel patencyVessel patency• Infarct versus salvageable Infarct versus salvageable

penumbrapenumbra


CT Angio & PerfusionCT Angio & Perfusion


CT Perfusion TerminologyCT Perfusion Terminology

Blood FlowBlood Flow Blood VolumeBlood Volume Mean Transit TimeMean Transit Timeoror

Time to PeakTime to Peak


DefinitionsDefinitions

PerfusionPerfusion The steady-state delivery of blood to The steady-state delivery of blood to cerebral tissue through the capillariescerebral tissue through the capillaries

Cerebral Blood Flow (CBF)Cerebral Blood Flow (CBF) Volume flow rate of blood through the Volume flow rate of blood through the cerebral vasculature per unit timecerebral vasculature per unit time

Cerebral Blood Volume (CBV)Cerebral Blood Volume (CBV) Amount of blood in a given amount of Amount of blood in a given amount of tissue at any timetissue at any time

Mean Transit Time (MTT)Mean Transit Time (MTT) Average time it takes for blood to Average time it takes for blood to traverse from the arterial to the traverse from the arterial to the venous side of the cerebral venous side of the cerebral vasculaturevasculature


Ischemic Stroke Ischemic Stroke Cerebrovascular PathophysiologyCerebrovascular Pathophysiology

CBFCBF CBVCBV MTTMTT

Salvageable Salvageable PenumbraPenumbra

↓↓ ↑↑ ↑↑Nonviable Nonviable Core InfarctCore Infarct

↓↓ ↓↓ ↑ ↑ ↑↑


Relationship between CBV, CBF, Relationship between CBV, CBF, and MTTand MTT

MTT= Blood Flow / Blood VolumeMTT= Blood Flow / Blood Volume

Blood FlowBlood Flow Blood VolumeBlood Volume Mean Transit TimeMean Transit Timeoror

Time to PeakTime to Peak


Value of Perfusion ScanningValue of Perfusion Scanning


Case:Case:Value of CTA/CTP within 3 hour windowValue of CTA/CTP within 3 hour window

• 50 yo male50 yo male• CT within hour of symptom CT within hour of symptom

onsetonset• Awake, alert, dysarthricAwake, alert, dysarthric• Fixed right sided gazeFixed right sided gaze• Left sided weaknessLeft sided weakness

Initial





BF BV TTPInitial



BF BV TTP 3 day fuInitial


Case:Case:“Wake up” Stroke“Wake up” Stroke

0735 at outside hospital


Case:Case: “Wake up” Stroke “Wake up” Stroke



1030 at stroke center



24 hours later at stroke center


Illustrative CTA/CTP Case #1Illustrative CTA/CTP Case #1• 50 yo male, remote CVA, in AF, not on 50 yo male, remote CVA, in AF, not on

coumadincoumadin• Presents 3 hours after symptom onsetPresents 3 hours after symptom onset• Awake, slurred speech, no aphasiaAwake, slurred speech, no aphasia• No field cut, right sided gaze, but able to No field cut, right sided gaze, but able to

pass midlinepass midline• Left facial droop, Left arm & leg 1/5 strengthLeft facial droop, Left arm & leg 1/5 strength• Right arm & leg 5/5 strengthRight arm & leg 5/5 strength• Left sided neglect with double Left sided neglect with double

simultaneous stimulationsimultaneous stimulation• NIHSSS 14NIHSSS 14


Illustrative CTA/CTP Case #1Illustrative CTA/CTP Case #1




CBVCBF MTT





ConclusionsConclusions• Diagnostics may guide future therapies, esp

when onset time and penumbra size uncertain• May be able to maximize benefit and minimize

risk through greater understanding of infarct core and salvageable ischemic penumbra

• Future CTA use like non-contrast CT use today• Software for rapid reconstruction exists• MRI/MRA still has too many technical hurdles• EM physicians need to consider next steps


RecommendationsRecommendations• Determine what capabilities exist in your

institutions and access them• Consider these new diagnostics and your

interventional radiology capacities• Learn how to interpret these new tests

with your radiologists and neurologists• Move into the 21st century with greater

ability to maximize patient outcome

Thank you.Thank you.

[email protected]@ferne.org

[email protected]@uic.edu312 413 7490312 413 7490

ferne_ieme_2006_sloan_strokehorizons_120606_edited_finalcd 04/21/23 01:35 Edward P. Sloan, MD, MPH, FACEP

http://www.ferne.org/

mailto:[email protected]

mailto:[email protected]


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Optimizing ED Ischemic Stroke Patient Care: Horizons in 2007