Acute Stroke: New Treatment Concepts

Richard Leigh, M.D.Johns Hopkins University School of Medicine

Stroke Neurology

Training Medical Internship Neurology Residency Vascular Neurology Fellowship

Inpatient Stroke Service Stroke Unit

▪ Telemetry▪ Specialized nursing

Acute Stroke Treatment

Ischemic Stroke

Different than hemorrhagic stroke in cause treatment and prevention.

Broadly divided into: Small vessel

▪ Lacunar Embolic

▪ Cardioembolic▪ Large Artery-to-Artery Embolic

Cryptogenic Hypercoagulable

▪ Cancer▪ Primary Hypercoagulability

Ischemic Stroke Management

Diagnosis/Intervention Save The Brain

Hospital Admission and Work-up Secondary Prevention

Rehabilitation Recovery

Acute Treatment

Time Is Brain!

Time = Disability

Good clinical outcome after ischemic stroke with successful revascularization is time-dependent. Khatri P, Abruzzo T, Yeatts SD, Nichols C, Broderick JP, Tomsick TA; IMS I and II Investigators.Neurology. 2009 Sep 29;73(13):1066-72. doi: 10.1212/WNL.0b013e3181b9c847.

Acute Treatment

IV thrombolytics tPA (Alteplase) – only FDA approved treatment Desmotoplase (Currently in Clinical Trial)

Endovascular Recanalization IA tPA Mechanical Thrombectomy

Induced or Permissive Hypertension Fluids Pressors

Heparin? No, Heparin is secondary prevention for some patients

IV Thrombolysis

3 hrs from symptom onset or last seen normal HCT negative for acute disease

▪ Blood▪ Hypodensity

Labs▪ INR if they take warfarin or have liver disease

▪ INR>1.7 is an exclusion▪ Plts/glucose

Historical Contraindications BP limits

IV Thrombolysis - Myths

NIH stroke scale (NIHSS) cutoff? There is none! What is required:

▪ “Quantifiable Neurologic Deficit”▪ Potentially disabling deficit

ASA/plavix exclusion? No!

Age restriction? No! -> not in the 3hr window

Rapidly improving symptoms? Be careful – fluctuating vs. improving symptoms are tough to

distinguish

IV Thrombolysis

3-4.5 hrs from symptom onset or last seen normal Extra exclusions:

▪ Age>80▪ On coumadin (regardless of INR)▪ History of Diabetes and Stroke

Otherwise identical to 3 hour window

Treatment Beyond 4.5 Hours

Currently no approved treatments IA Therapy

Unproven MRI based selection for IV Therapy:

No tPA

IV tPA

IA Therapy

Controversial Has not been validated in a clinical trial Some would say it has been disproven (MR

Rescue) Routinely done at large medical centers Patient Selection Methods

Penumbra DWI/PWI mismatch Malignant Profile Time based

DWI ADC PWI FLAIR

Volumetrics :DWI volume of 13cc6 sec PWI deficit of 67cc10sec PWI deficit of 40ccMismatch Ratio 5.15

IA Therapies

IA tPA Lower dose delivered directly to the clot Only recommended within 6 hours of onset

Mechanical Thrombectomy Stentriever Suction devices Older devices out of favor (corkscrew, ultrasound)

IV/IA Combo Therapy

IMS 3 – multicenter randomized trial Stopped early due to lack of benefit

Drip-and-Ship Model Start the IV tPA at a community hospital and then

transport the patient for IA therapy at a stroke center

This practice essentially ended with IMS 3

Hypertensive Therapy

Permissive HTN Essentially done in all stroke patients Let them auto-hypertense

Induced HTN Need to document a pressure dependent exam Start with fluids (always NS, never hypotonics) May need ICU for pressors Can be transitioned to midodrine or florinef But don’t hypertense them for ever!

2 4 6 8 TTP thresholds in seconds

Before induced hypertension

2 4 6 8 TTP thresholds in seconds

After induced hypertension

Secondary Prevention

The Default Secondary prevention is: ASA 325mg Anticoagulation must be earned!

Statin High dose, High potency Goal LDL<70

HTN ACE inhibitors first line Diuretics are last line

Diabetes Management Smoking Cessation Diet/Excersize

Dual Therapy – ASA+Plavix

MATCH Trial plavix vs. ASA/plavix 18 months Bleeding out weighed any benefit

SAMMPRIS Trial Stenting vs maximal medical therapy for symptomatic intracranial

stenosis. 3 months of ASA/plavix showed clear benefit over not only stenting

but also ASA alone CHANCE Trial

ASA/Plavix for 1 month after minor stroke or TIA Effective an a Chinese population POINT trial ongoing

Anticoagulation Indications

A-fib 24 hours of in house telemetry Cryptogenic stroke patents (whose stroke is embolic

appearing on MRI) will wear a 30 day event monitor as an outpatient

When to start anticoagulation if in afib?▪ Small strokes, right away▪ Big strokes wait a month

▪ ASA to coumadin bridge▪ Rapid recurrent stroke in afib happens but is not common

▪ Cardiac thrombus on echo changes the equation ASA+Plavix for Afib -> Active-A trial

Anticoagulation Indications

Echocardiogram TTE vs TEE

▪ Level of suspicion for cardiac source Looking for

▪ Cardiac thrombus▪ Left atrial dilitation▪ Ejection fraction

▪ WARCEF –> EF<35% benefits from coumadin at 4 years▪ PFO – bubble study

▪ Controversial role in stroke

Anticoagulation Indications

Dissection ASA or Coumadin are acceptable treatments Data suggests recurrent stroke after dissection is rare. Typical management is 3-6 months of anticoagulation.

Cerebral Sinus Thrombosis Venous stroke due to hypercoagulable state 3-6 months of anticoagulation unless it is a primary

hypercoagulable state

Extracranial Carotid Artery Stenosis

Screening for CAS typically done with ultrasound Velocity measures of >70% stenosis generally considered

treatable if symptomatic Stenosis found on ultrasound should be confirmed

with CTA/MRA/angiogram Stenosis of <70% can be symptomatic

Consider vessel wall imaging Asymptomatic stenosis should be treated medically.

Keep in mind that the NACET trial was done in the pre-statin era

Extracranial Carotid Artery Stenosis

Symptomatic carotid artery stenosis should be treated urgently.

Carotid Endarterectomy (CEA) vs. Carotid Artery Stenting (CAS) Generally felt to be equivalent treatments Operator dependent

If going for CEA, start heparin (if stroke not too big)

If going for CAS, start ASA/plavix

Stroke Recovery

We can prevent stroke We can treat stroke Can we affect recovery?

PT/OT/SLP Why do some patients recover completely

and others not at all?

Stroke Recovery

General Principles in Stroke Recovery Strokes get better Most of the recovery is in the first month but

patients can keep recovering for up to a year Younger healthier brains recovery better Rapid improvement in the hospital is a good

prognostic sign

Stroke Recovery

Newer thinking in stroke recovery: Some patients have a predisposition to recover There appears to be a window of recovery which is

opened by the stroke Early intervention may be the key

How can we open/extend the window? SSRIs seem promising FLAME trial – Prozac and Motor recovery Lexapro in cognitive recovery after stroke

The Future of Stroke

Acute Treatement: Individualized care More IV therapies

Secondary Prevention Early aggressive treatment with taper

Recovery SSRIs