Post on 24-Feb-2016
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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