Acute Stroke: New Treatment Concepts

1. Richard Leigh, M.D. Johns Hopkins University School of Medicine Acute Stroke: New Treatment Concepts

2. Stroke Neurology • Training • Medical Internship • Neurology Residency • Vascular Neurology Fellowship • Inpatient Stroke Service • Stroke Unit • Telemetry • Specialized nursing • Acute Stroke Treatment

3. 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

4. Ischemic Stroke Management • Diagnosis/Intervention • Save The Brain • Hospital Admission and Work-up • Secondary Prevention • Rehabilitation • Recovery

5. Acute Treatment Time Is Brain!

6. Time = Disability Good clinical outcome after ischemic stroke with successful revascularization is time-dependent. KhatriP, 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.

7. 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

8. 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

9. 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

10. 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

11. Treatment Beyond 4.5 Hours • Currently no approved treatments • IA Therapy • Unproven • MRI based selection for IV Therapy: No tPA IV tPA

12. 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

13. DWI ADC PWI FLAIR • Volumetrics : • DWI volume of 13cc • 6 sec PWI deficit of 67cc • 10sec PWI deficit of 40cc • Mismatch Ratio 5.15

14. 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)

15. 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

16. 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!

17. 2 4 6 8 TTP thresholds in seconds Before induced hypertension

18. 2 4 6 8 TTP thresholds in seconds After induced hypertension

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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?

27. 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

28. 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

29. The Future of Stroke • Acute Treatement: • Individualized care • More IV therapies • Secondary Prevention • Early aggressive treatment with taper • Recovery • SSRIs