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

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

3.  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.  Diagnosis/Intervention  Save The Brain  Hospital Admission and Work-up  Secondary Prevention  Rehabilitation  Recovery

5. Time Is Brain!

6. 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.

7.  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.  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.  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.  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.  Currently no approved treatments  IA Therapy  Unproven  MRI based selection for IV Therapy: No tPA IV tPA

12.  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 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.  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.  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.  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.  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.  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.  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.  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.  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.  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.  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.  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.  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.  Acute Treatement:  Individualized care  More IV therapies  Secondary Prevention  Early aggressive treatment with taper  Recovery  SSRIs