beyond the basics of stroke evaluation rebbeca grysiewicz, do director, comprehensive stroke center...

Beyond the Basics of Stroke Evaluation

Rebbeca Grysiewicz, DO

Director, Comprehensive Stroke Center

Beaumont Health System- Royal Oak

Disclosures

None

Objectives

Discuss brief overview of stroke epidemiology

Review endovascular reperfusion therapy updates

Analyze the role of stroke mobile units

During a stroke 32,000 neurons die per second…

The brain ages 3.6 years each hour without treatment during an ischemic stroke.

Epidemiology

Annually, 15 million people worldwide suffer a stroke

One-third of these individuals die and another one- third are left permanently disabled

The World Health Organization (WHO) estimates that a stroke occurs every 5 seconds

Epidemiology

In the United States, approximately 795,000 people have a new or recurrent stroke each year

About 600,000 are new strokes and 195,000 are recurrent strokes

A stroke occurs approximately every 40 seconds, which is 2160 strokes per day

Epidemiology

In the U.S., stroke is the primary cause of long term disability with an estimated 6.5 million survivors among adults age 20 and older (2.6 million males and 3.9 million females)

The estimated 2015 direct and indirect cost of stroke is $95 billion

Epidemiology

Stroke mortality extends beyond 150,000 people annually

Stroke is now the fifth leading cause of death in the U.S., and the second leading cause of death globally

Stroke accounts for nearly 1 out of every 16 deaths in the U.S. and approximately 10% of all deaths worldwide

Epidemiology

Stroke can either be ischemic (an occlusion of a blood vessel) or hemorrhagic (a rupture of a blood vessel)

Hemorrhagic strokes include intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH)

Epidemiology

Epidemiology

Of all strokes in the U.S., 87 percent are ischemic, 10 percent are ICH and 3 percent are SAH

Ischemic strokes are further classified into subtypes according to the mechanism of injury

Pathophysiology

The degree of damage is dependent on duration of ischemia and degree of collateral flow

Normal cerebral blood flow is greater than 50mL/100mg/min, but if blood flow is decreased to less than 10mL/100mg/min, irreversible neuronal death occurs quickly

Pathophysiology

Blood flow between 11 and 20 mL/100mg/min is thought to represent the ischemic penumbra

This is an area of neurons that are ischemic, but still viable if blood flow is restored

The ischemic penumbra is the target of most acute stroke interventions in which recanalization of a vessel should theoretically restore perfusion to the penumbra

Pathophysiology

Acute management: thrombolysis

IV thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the only FDA approved drug treatment for acute ischemic stroke

Endogenous tissue-plaminogen activators convert plasminogen to plasmin, an enzyme that catalyzes fibrin breakdown

Fibrinolysis is strongly enhanced by rt-PA


Double blinded placebo-controlled trial with 624 patients randomized to IV rt-PA or placebo

Patients who received rt-PA within 3 hours had more favorable outcomes and were 30% more likely to have minimal or no disability at 3 months (odds ratio 1.7, 95% CI 1.2 to 2.6)

Modified Rankin Scale (mRS)

The scale runs from 0-6, running from perfect health without symptoms to death. 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.

http://en.wikipedia.org/wiki/Death


Only a select group of patients are eligible to received rt-PA

The major adverse affect of rt-PA is hemorrhage

The symptomatic intracranial hemorrhage rate in the NINDS trial was 6.4%

Symptomatic ICH was seen primarily from hemorrhagic transformation of the ischemic infarct


An additional landmark study was the European Cooperative Acute Stroke Study (ECASS) III published in the New England Journal of Medicine in September 2008

It is a double-blinded placebo-controlled study with 821 patients randomized to IV rt-PA or placebo


Patients who received intravenous rt-PA administered between 3 and 4.5 hours after the onset of symptoms had statistically significant improved clinical outcomes compared with placebo (52.4% vs. 45.2%; P=0.04)

The incidence of symptomatic ICH was higher with rt-PA than placebo (2.4% vs. 0.2%; P=0.008), but mortality did not significantly differ between the two groups


In May 2009, the American Heart Association/ American Stroke Association released a Science Advisory recommending the expansion of the time window for treatment of acute ischemic stroke with rt-PA from 3 hours to 4.5 hours after onset of symptoms


However, the FDA has declined to extend the approved time window for IV-tPA administration beyond 3 hours

Acute management: endovascular thrombolysis

Endovascular therapy for acute ischemic stroke includes intra-arterial fibrinolysis, mechanical clot retrieval or a combination of the two

There has been a 6 fold increase in endovascular treatment from 2004 to 2009 (0.1% vs 0.6%; P<0.001)

Mortality decreased (OR=0.7; P=0.007), but moderate to severe disability increased from 2008-2009 (OR=1.4; P=0.0002)


4 mechanical devices with FDA clearance: Merci Retrieval System (2004), the Penumbra System (2007), the Solitaire Flow Restoration Device (2012), and the Trevo Retriever (2012)

Devices are cleared as mechanical means for recanalization of acutely occluded arteries based on studies without noninterventional control groups

Acute Management: endovascular thrombolysis

3 endovascular thrombectomy trials were highlighted at the 2013 International Stroke Conference

IMS III MR RESCUE SYNTHESIS Expansion


All 3 trials failed to show a statistically significant difference between the endovascular therapy group and the best medical management group (which could include IV-tPA) as measured by an mRS of 2 or less

MR CLEAN: A Randomized Trial of Intra-arterial Treatment for Acute Ischemic Stroke

Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands

Published January 1, 2015

500 patients with large vessel occlusion(LVO) confirmed by CTA were randomized to intra-arterial treatment (n=233) or medical management (n=267) within 6 hours of symptom onset

32.6% of patients who received endovascular treatment achieved a good functional outcome (mRS 0-2) compared to 19.1% of patients who received medical management

Berkhemer OA et al. N Engl J Med 2015;372:11-20.

MR CLEAN: A Randomized Trial of Intra-arterial Treatment for Acute Ischemic Stroke

Berkhemer OA et al. N Engl J Med 2015;372:11-20.


3 endovascular thrombectomy trials were highlighted at the February 2015 International Stroke Conference in Nashville, TN

ESCAPE EXTEND-IA SWIFT PRIME


All 3 trials showed a statistically significant difference between the endovascular therapy group and the best medical management group (which could include IV-tPA) as measured by an mRS of 2 or less

Goyal M et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1414905

ESCAPE: Randomized Assessment of Rapid Endovascular Treatment Ischemic Stroke

Published February 11, 2015

Trial was stopped early because of efficacy

316 patients with proximal large vessel occlusion (LVO) and good collateral circulation confirmed by CTA were randomized to endovascular intervention (n=165) or medical management (n=150) within 12 hours of symptoms onset

Rates of functional independence (mRS 0-2) at 90 days was statistically significant for the endovascular intervention group compared to the control group (53.0% vs. 29.3%; p< 0.001)

Endovascular intervention was associated with reduced mortality (10.4% vs 19.0%; p=0.04)

ESCAPE: Randomized Assessment of Rapid Endovascular Treatment Ischemic Stroke

Goyal M et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1414905

Campbell BC et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1414792

EXTEND-IA: Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection

Published February 11, 2015

Trial was stopped early due to efficacy

70 patients with internal carotid or middle cerebral artery occlusion, salvageable brain tissue, and ischemic core < 70 ml confirmed by CTP were randomized to endovascular thrombectomy with the Solitaire FR stent retriever (m=35) or alteplase alone (n=35) within 4.5 hours of symptom onset

The endovascular reperfusion group achieved greater reperfusion at 24 hours (median, 100% vs. 37%; p,0.001) and increased early neurologic improvement at 3 days (80% vs. 37%, p=0.002) as measured by the NIHSS

No significant difference in mortality or symptomatic ICH

Campbell BC et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1414792

EXTEND-IA: Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection

Saver J. International Stroke Conference 2015 Invited Presentation. Presented February 11, 2015.

SWIFT PRIME

Results presented at ISC on February 11, 2015

Trial was stopped early due to efficacy

196 patients with large vessel occlusion (LVO) confirmed by CTA or MRA were randomized to endovascular treatment with the Solitaire FR stent retriever (n=98) or alteplase alone (n=98) within 6 hours of symptom onset

The OR for mRS shift at 90 days in the endovascular treatment group compared to the alteplase alone group was statistically significant (p=0.0002), and good functional outcome (mRS 0-2) was achieved in 60.2% of the patients in the endovascular treatment group compared to 35.5% of the patients in the control group (p=0.0008)

Saver J. International Stroke Conference 2015 Invited Presentation. Presented February 11, 2015

SWIFT PRIME: Secondary Endpoints

Endpoints Endovascular Treatment Control P Value

mRS score of 0 - 2 at 90 d (%) 60.2 35.5 .0008

Mortality (%) 9.2 12.4 .50Mean improvement in NIHSS score at 27 h (points)

8.5 3.9 <.0001

Impact on acute stroke treatment

All 4 trials showed statistically significant evidence of endovascular treatment in select acute ischemic stroke patients

Selection of patients should be confirmed by vascular imaging

IV rt-PA should always be the first line treatment for eligible acute ischemic stroke patients

On average approximately 5% of stroke patients receive acute stroke treatment

We need to continue to improve community and physician awareness

Mobile Stroke Units

Mobile Stroke Units debuted in Cleveland and Houston during the past year

Units resemble a typical ambulance, but are equipped with a portal CT scanner, lab testing capabilities and the ability to administer IV-tPA

Mobile Stroke Units cost about $1 million and are staffed with a critical care nurse, a paramedic and CT technology expert

Physicians are able to remotely evaluate a patient with two-way video conferencing

Hussain MS. International Stroke Conference 2015.

Mobile Stroke Units

In Cleveland, the stroke unit operates from 8 am to 8 pm daily

Researchers found that on average patients received a CT scan 20 minutes faster than through the EC

There was also a significant reduction in average treatment time for the mobile stroke unit (64 minutes) compared to the emergency room (104 minutes)

More research is needed to determine if Mobile stroke units lead to overall better stroke outcomes and if they are cost effective in different locations.

Conclusion

Every minute 1.9 million neurons die during a stroke

Just because we have 4.5 hours to administer IV rt-PA, does not mean that we should wait 4.5 hours to give IV rt-PA

Endovascular reperfusion therapy is beneficial for appropriately selected stroke patients

Time is brain!

Questions?

Thank you!

beyond the basics of stroke evaluation rebbeca grysiewicz, do director, comprehensive stroke center...

Documents

epidemiology slide

thrombolysis slide

pathophysiology slide

penumbra slide

seconds slide

second slide

day slide

epidemiology stroke