Stroke Systems of Care

V.T. Doss, D.O.Stroke Medical Director, BMH-MemphisAssistant Professor, Neurology & Neurosurgery, UTHSC

Intro

Neurological emergency Ischemic vs. Hemorrhagic TOAST classification(1) thrombosis /embolism due to atherosclerosis of a large

artery(2) cardioembolic origin(3) occlusion of a small blood vessel(4) other determined cause (CSVT, vasculitis, trauma)(5) undetermined cause (two possible causes, no cause

identified, or incomplete investigation)

Memphis- the capitol of atherosclerosis?

Stroke death rates, 2000–2006: adults ≥35 years of age, by county.

Writing Group Members et al. Circulation 2012;125:e2-e220

Copyright © American Heart Association

US Stats  95% of strokes at age

>45, and 2/3 of strokes occur in those >65

leading cause death/disability

10% deaths worldwide 795,000 strokes/yr,

610,000 of these are first strokes. About 185,000 people who survive a stroke go on to have another

In 2010, stroke cost the US $53.9 billion

According to the WHO, 15 million people suffer stroke worldwide each year.Of these, 5 million die and another 5 million are permanently disabled.

Stroke is the second single most common cause of death in Europe: accounting for almost 1.1 million deaths each year.

Over one in seven women (15%) and one in ten men (10%) die from the disease.

Why is Time Important? The area peripheral to a core infarct where

metabolism is active but blood flow is diminished is called the ischemic penumbra

This is salvageable tissue that is at risk for infarction.

The penumbra lies in a 'no-man's land' between a zone of low blood flow that is < 25 ml/100 mg brain tissue/min and a zone where brain tissue is undergoing necrosis/death, flow of < 8-10 ml/100 mg/min1

Without restoration of blood flow/oxygen, the ischemic penumbra will convert to ischemic core or tissue death

1- http://medical-dictionary.thefreedictionary.com/ischemic+penumbra

BrainIschemic Penumbr

a

Core Infarct

Time is Brain !!

Neurology. 2000 Dec 12;55(11):1649-55.

RPCT – TPA v. Placebo < 3 hours (Dose .9mg/kg IV)Inclusion Criteria: Stroke with clear time of onset, CT without ICH, & measurable deficit on NIHSSExclusion Criteria: Recent GI or GU Bleed w/in 21 days, Ischemic stroke within 3 months,hx of ICH, recent arterial puncture at a noncompressible site w/in 7 days, SBP > 185 or DBP > 110 that can’t be controlled, INR > 1.5, platelets < 100K, glucose > 400 or < 50 Seizure at onset

Phase I (N=291): TPA clinical activity @ 24 hours NIHSS improvement of >/= 447% TPA vs. 39% placebo, p= 0.21

Phase II (N=333): Primary Outcomes (MRS < 2) at 90 days, ARR 12%, NNT = 8 SICH 6.4 % vs. 0.6 % (P < 0.001)

IV TPA APPROVED by FDA in 1996NOW THE ACCEPTED STANDARD OF CARE

THROUGHOUT US, EUROPE AND ASIA

Expanded time window for milder strokes, NIHHS < 25 with less than 1/3 of MCA territory on CTN=821Primary endpoint: MRS < 2 @ 90 days. 52.4% vs. 45.2, P = 0.04

Number Needed to Treat = 14

Modified Rankin Scale

0 - No symptoms. 1 - No significant disability. Able to carry out all usual

activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs

without assistance, but unable to carry out all previous activities.

3 - Moderate disability. Requires some help, but able to walk unassisted.

4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.

5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.

6 - Dead.

NINDS NINDS randomized 624 subjects within 3 hours of stroke onset to

receive 0.9 mg/kg of intravenous tPA or placebo found that patients treated with tPA within 3 hours of onset had a

substantially better chance of functional independence with minimal or no disability 3 months after treatment

The proportion of patients with minimal or no disability increased from 38% with placebo to 50% with tPA, a 12% absolute improvement

The NNT for 1 more patient to have a normal or near normal outcome was 8

NNT for 1 more patient to have an improved outcome was 3.1 Brain hemorrhages related to tPA caused severe worsened final

outcome in 1% of patients Overall, for every 100 patients treated within the first 3 hours, 32

had a better outcome as a result and 3 had a worse outcome.

ECASS III

821 pts, 3-4.5 hr no difference in mortality between the two groups

(approximately 8%)  sICH higher in tpa group (2.4%) odds for a favorable outcome (MRS 0-1) after stroke

were 28% higher with alteplase than with placebo Time is tissue

 NINDS and ACLS Recommended Benchmarks for Potential Thrombolysis Candidate

Interval Target

Door to doctor 10 min

Access to neuro expertise 15 min

Door to CT completion 25 min

Door to CT interpretation 45 min

Door to IV-rTPA 60 min

Admission to stroke unit or ICU 3 hours

Casting a wider net

Expanding time window Stroke centers- primary,

comprehensive Tele-stroke Multi-modal imaging New agents/devices Less is more? Neuroprotection

Direction/Innovations

EMS Advances Telemedicine Spoke and

Hub Models

Tele-Stroke 24hr access to

neuro specialist Avoids stroke

mimickers Allows smaller

hospitals to keep these patients

CSCPhysicians Vascular Neurology Vascular Neurosurgery Vascular Surgery Diagnostic radiology and neuroradiology Interventional/endovascular physicians Critical care medicine Physiatrists

Surgical and interventional therapies CEA Intracranial aneurysm clipping Surgical removal or draining of blood

from the brain Placement of EVD and intracranial

pressure monitors Endovascular treatment

of aneurysms and arteriovenous malformations

Intra-arterial reperfusion therapy Endovascular treatment of vasospasm

Infrastructure• Stroke Unit• Intensive Care Unit• Operating room staffed 24/7• Interventional staff available 24/7• Stroke registry

Diagnostic techniques• MRI with diffusion• MRA and MRV• Computed Tomography Angiogram (CTA)• Digital cerebral angiography• Transcranial dopplers• Carotid duplex ultrasound• TTE and TEE

Rehabilitation (PT/OT/ST)Advanced Practice Nursing /Staff stroke nursesRespiratory Therapists

Educational/research programs• Clinical research• Community education/prevention• Professional education

Mobile Stroke Unit

Point-of-Care-based laboratory compact CT scan results, reviewed

remotely by hospital physicians results in early pre-hospital IV-

thrombolysis and subsequent bridging therapy later with IA recanalization in the hospital

Options for Patients Experiencing an Ischemic Stroke

Endovascular Clot Removal

Mechanical disruption or removal of the clot using standard endovascular

approaches

IV tPAGold-standard in ischemic

stroke care. Drug is designed to break apart

the clot.

Medical Management

Monitor vitals and provide secondary stroke

prevention. Patient is send to rehab or a

nursing facility when stable.

Bridging Therapy

Endovascular Therapy

Anterior 12 hours Posterior <24h NIHSS >7 Evidence of Large vessel occlusion,

hemodynamically unstable Large penumbra or clinical mismatch

Recanalization rate IV TPA: M1: 22%, M2:44%‡

Mortality:

25% vs 42.9%##

Recanalization rate with IV TPA: <10%

Mortality: 73%(persistent occlusion)^^

MCA Occlusion

Internal Carotid Occlusion

Basilar OcclusionRecanalization rate with IV TPA: <10%

Mortality: 90%(persistent occlusion)**

‡Alexandrov et al. Stroke ## Proact II: Jama 1999

**Meta analysis Furlan et al

^^ Flint et al. MERCI Registry Stroke 2008

The Importance of Recanalization

Recanalization is strongly associated with improved

function outcomes and reduced mortality.

Meta-analysis shows a strong correlation between opening the blood vessel and patient good outcomes

Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke. 2007 Mar;38(3):967-73.

58.1%

14.4% 13.7%

24.8%

41.6%

12.5%

0%

10%

20%

30%

40%

50%

60%

70%

Good Outcome(mRS 0-2)

90-Day Mortality SICH

% of

Pati

ents

Revascularized Non-revascularized

Clinical Trials

Most recent published EVT (endovascular therapy) trial results

Lessons learned Current trial design

New EVT Stroke Trials

IMS IIIMR RESCUESYNTHESIS - EXPANSION

NEJM February 7, 2013

IMS III

IMS III: Interventional Management of Stroke 3

Patients who had received intravenous rt-PA within 3 hours after symptom onset were randomized 2:1 to: IV tPA + IA therapy IV t-PA alone

Primary outcome measure: 90-day mRS ≤ 2

Broderick JP. NEJM 2013;368:893-903

Primary outcome: IMS III

mRS < 2 95% CI: -6.1% to +9.1% 40.8% with endovascular + IV rt-

PA38.7% with IV rt-PA alone

Broderick JP. NEJM 368: 893-903, 2013

MR RESCUE

MR RESCUE: Methods

≤ 8 hours of onset Anterior circulation LVO Randomized to either EVT or

Medical Mgmt “penumbral” pattern by CT or MRI

Penumbra : “Small core” (<90 cc), large penumbra

Non-Penumbral: Large core and small/absent penumbra

Kidwell CS. NEJM 2013 Mar 7;368(10):914-23

MR RESCUE: 90-day mRS

NO DIFFERENCE IN OUTCOMES Endovascular vs. medical therapy Penumbra vs. no penumbra

p=0.23

p=0.32

Kidwell CS. NEJM 368: 914-23, 2013

Synthesis Expansion

Synthesis Expansion: Outcomes

Primary Outcome (mRS < 1) 30.4% EVT 34.8% IV tPA

Death Rates EVT: 14 (8%) IV tPA: 11 (6%)

“EVT is not superior to standard treatment with IV tPA”

Italian Medicines Agency (AIFA)

Ciccone A. NEJM 368: 904-13, 2013

IMS III Protocol Versus Contemporary Practice

The majority of patients included in the study Were not imaged using modern approaches Were not triaged using modern approaches Were not treated using modern approaches

Basic Head CT only in most patientsMore than 40% of IMS III patients had baseline CT

with ASPECTS < 7

Imaging Assessment

ASPECTS (Alberta Stroke Program Early CT Score)

ASPECTS Score - 4

Patient Selection Matters: Penumbra Pivotal Trial

Small Infarct

15/30 pts

Large Infarct

8/53 pts Goyal M. Stroke 2010

Independent Blinded Retrospective AnalysisBaseline NCCT Data Using ASPECTS

mRS ≤ 2

IMS III - Imaging Assessment

Patients with “large clear regions of hypodensity” (darker than white matter and brighter than CSF) on CT, greater than 1/3rd of MCA territory were excluded Sulcal effacement and loss of grey-white matter

differentiation were not contraindications Many patients would have likely been excluded with more

conservative CT reading (ASPECTS), CTA-SI (source image) ASPECTS, MR Diffusion ASPECTS, CT Perfusion or MR Perfusion

Imaging Based Selection:Perfusion Imaging

89 patients with ”no treatable or treated thrombus” 33 no thrombus seen 34 thrombus not treatable by EVT 12 with treatable thrombus but not treated

No reason (1)Couldn’t safely cross occlusion (3)Recanalization during angio (2)Occlusion not responsible for clinical

presentation (2)No reason (2)

Would ALL have been screened out with CTA

IMS III – EVT Arm

43% of large vessel occlusions have greater than 8 mm clot lengths1

Clot characteristics (length)

No Clot > 8mm recanalized with IV tPA

IMS III: Baseline CTA Occlusion Present – 90 day mRS

van Elteren test p-value 0.0114

IMS III: Baseline CTA Occlusion Present - NIHSS > 20

van Elteren test p-value 0.0330

TICI Score Grade 0 No perfusion Grade 1 Perfusion past the initial obstruction, but limited

distal branch filling with little or slow distal perfusion Grade 2a Perfusion of less than ½ of the vascular

distribution of the occluded artery (e.g., filling and perfusion through 1 M2 division)

Grade 2b Perfusion of ½ or greater of the vascular distribution of the occluded artery (e.g., filling and perfusion through 2 or more M2 divisions)

Grade 3 Full perfusion with filling of all distal branches

Percentage of Patients Who Achieved a Functional Outcome in IMS III Based on Reperfusion Result (p=0.001)

In IMS III, independent functional outcome (mRS 0-2) was strongly associated with TICI 2b-3 revascularization.

Total endovascular treatments = 334/434 IA tPA 138 EKOS + tPA 22 Merci 38 Merci + tPA 57 Penumbra 16 Penumbra + tPA 38 Solitaire 2 Solitaire + tPA 3

‘modern’ devices = 13% of endovascular cohort

IMS III

IMS III

IMS-III endovascular reperfusion rates:≥ TICI 2a ≥ TICI 2b

ICA 65% 38%M1 81% 44%M2 77% 44%Overall 70% 40%

TREVO2* 92% 68%SWIFT* 94% 76%

*Both are high quality independent core lab adjudicated, published in Lancet

Systems and Process Issues in the Era of Comprehensive Stroke Center Designation

Relative to IMS I and II, the IMS III trial suffered from a dramatic delay between the initiation of iv tPA and endovascular therapy

At over two hours, this lag impedes the ability of reperfusion to realize clinical benefit.

IMS III patients further suffered a significant lag between groin access and initiation of IAT at the lesion Fourty-four minutes is far beyond reported standards with modern guide and distal access catheter technology

Time to Treatment

IMS III Onset to arrival: 57 min Arrival to IV tPA: 66 min IV to groin puncture: 86 mins Groin puncture to IA: 44 mins

MR RESCUE Mean time from imaging to groin puncture:

2h 4 min SYNTHESIS

Time from onset to start of treatment EVT 3.75 hrs IV 2.75 hrs

130 mins between IV tPA and start of IA therapy By comparison STAR

registry:Groin Puncture to guide cath placement: 12 minsGuide cath to TICI 2B/3 flow: 20 mins

Critical as IA group did NOT receive IV tpa

Lessons LearnedEndovascular Therapy is safe – as safe as IV rt-PA

Lessons Learned from Recent Ischemic Stroke Trials

It is not IV vs EVT IV tPA is proven Class 1 – it should not be denied from patients Future trials should compare best medical management versus best

medical management + EVT Only enroll patients with LVO (large vessel occlusion) Excellent recanalization is needed

TICI 2B or 3 Time is Brain Better determination of salvageable brain tissue

ASPECTS CT Perfusion MRI Diffusion/Perfusion

Merci Retriever “Cork Screw”

Newer Technologies = Better Recanalization

Solitaire FR

Trevo

Separator 3-D

Penumbra Max System

Distal aspiration with retrievable stent assisted thrombectomy for the treatment of acute ischemic strokeWilliam Humphries1, Daniel Hoit1, Vinodh T Doss1, Lucas Elijovich1, Adam S Arthur1

Abstract

Objective Flexible large lumen aspiration catheters and stent retrievers have recently become available in the USA for the revascularization of large vessel occlusions presenting within the context of acute ischemic stroke (AIS). We describe a multicenter experience using a combined aspiration and stent retrieval technique for thrombectomy.Design A retrospective analysis to identify patients receiving combined manual aspiration and stent retrieval for treatment of AIS between August 2012 and April 2013 at six high volume stroke centers was conducted. Outcome variables, including recanalization rate, post-treatment National Institutes of Health Stroke Scale (NIHSS) score, symptomatic intracranial hemorrhage, discharge 90 day modified Rankin Scale (mRS) score, and mortality were evaluated.

Results 105 patients were found that met the inclusion criteria for this retrospective study. Successful recanalization (Thrombolysis in Cerebral Infarction score 2B) was achieved in 92 (88%) of these patients. 44% of patients had favorable (mRS score 0–2) outcomes at 90 days. There were five (4.8%) symptomatic intracerebral hemorrhages and three procedure related deaths (2.9%).

Conclusions Mechanical thrombectomy utilizing combined manual aspiration with a stent retriever is an effective and safe strategy for endovascular recanalization of large vessel occlusions presenting within the context of AIS.

J NeuroIntervent Surg doi:10.1136/neurintsurg-2013-010986

Case 1

53yo male presented with L MCA syndrome

NIHSS 21 Onset 1 hour Received iv-tpa within 60 min from

door

Pre-treatment

Post-treatment

Case 1

Dysfluency and hemiparesis d/c to rehab with mRS of 2 1 mo f/u mRS of 1

Case 2

75yo male consulted for acute stroke Pseudobulbar palsy Post. circulation strokes 3 months

prior, d/c mRS 0, was on ASA/plavix

April 2013

Case 3

35yo AA male presents with 2 hours of inability to produce speech and right sided weakness.

PMH: bipolar d/o

Exam: awake, not following commands, globally aphasicRight hemiplaegia

NIHSS: 22

IMG_0512.MOV

At Discharge: mRS- 0, NIHSS 1

Conclusions Stroke systems and patient selection critical to

outcomes EMS critical to triage, stabilizing and

transporting to stroke center Imperative to recognize signs and symptoms of

stroke especially large vessel occlusion IV-TPA standard of care Endovascular treatment can be performed

quickly and safely Time is Brain!

Questions?

Email:vdoss@semmes-murphey.com