1. Management of Acute ISCHEMIC stroke
Internal Medicine
Mini Lecture
June 2016

2. Objectives Establish the components in diagnosing a stroke
Learn which initial imaging is available in acute stroke
Know the management of acute ischemic strokes

3. Causes Ischemic stroke (85% of all strokes)
Atherosclerotic disease
Cardioembolic
Other (cervical artery dissection, endocarditis, vasculitis, hypercoagulable state, herniation)
Hemorrhagic stroke (15% of all strokes)
Intracerebral hemorrhage (ICH)
Subarachnoid hemorrhage (SAH)

4. CODE STROKE Focused history and physical Neurologic assessment
Including contraindications to thrombolytic therapy
Neurologic assessment
facial paresis, arm drift/weakness, and abnormal speech indicate high positive predictive value for stroke
Vitals, glucose
Noncontrast CT Head STAT
To distinguish intracranial hemorrhage from ischemic stroke

5. National Institutes of Health Stroke Scale (NIHSS)
Provides a structured, quantifiable neurologic examination
NIHSS has 11 parts similar to our neurologic exam
Score between 0 and 42
NIHSS scores ≥20 indicate a severe stroke
NIHSS score on admission has been correlated to stroke outcome
Can also download an app on the phone

6. Time is Brain Time of ischemic stroke symptom onset is critical
If unknown, then time the patient was last awake and free of stroke symptoms

7. Initial Imaging Noncontrast CT CT Angiography CT Perfusion
visualizes great vessels, occlusion, and can reconstruct circle of Willis and extracranial cerebral arteries
CT Perfusion
areas of hypoattenuation correlates with ischemic brain regions
Use of all 3 combined shows improved detection of acute infarction when compared with noncontrast CT alone
CT Noncontrast: within six hours of stroke onset, the prevalence of early CT signs of brain infarction was 61 percent
CTA: For detection of intracranial large vessel stenosis and occlusion, CTA in various studies had sensitivities of 92 to 100 percent and specificities of 82 to 100 percent when compared with conventional angiography. CTA has become the standard of practice in many stroke centers to triage patients between intravenous thrombolysis, mechanical thrombectomy, and intra-arterial thrombolysis
CTP: CTP requires repeatedly scanning the same portion of the brain parenchyma over the time required for the bolus to pass through the vasculature.
multimodal evaluation that includes CTA and CTP may permit assessment of the site of vascular occlusion, infarct core, salvageable brain tissue and degree of collateral circulation

8. Acute treatment
Medically: TPA (intravenous tissue plasminogen activator)
FDA: Within 3 hours
AHA/ASA: Within 4.5 hours
the earlier tPA is administered, the higher the likelihood of a positive neurologic outcome
Endovascular: Intra-arterial mechanical thrombectomy
For proximal large vessel occlusion of anterior circulation (intracranial internal carotid, middle cerebral, anterior cerebral)
Within 6 hours of last-seen normal
Can follow TPA administration
RISKS VS BENEFITS of TPA: Benefits include an absolute increase in the odds of an outcome with neurologic improvements at 90 days of 11 to 13 percentage points.
Risk for intracerebral hemorrhage possibly causing neurologic worsening or death is 6%.

9. Main things to remember for TPA:
Inclusion: within 4.5 hours since onset of symptoms or last known normal
Absolute Exclusion:
Head trauma or stroke in last 3 months
Previous ICH, Intracranial tumor, AVM, or aneurysm
Recent intracranial or intraspinal surgery
Active internal bleeding
Bleeding diatheses (plt<100, heparin in last 48h ie abnormal PTT, current anticoagulant use ie INR>1.7)
More exclusion criteria
Relative exclusion criteria:
-minor stroke symptoms or rapidly resolving symptoms
-major surgery or trauma in last 14 days
-GI or GU bleeding in last 21 days
-MI in last 3 months
-seizure at onset of stroke symptoms
-pregnancy

10. Blood pressure in ischemic stroke
If receiving lytic therapy
Prior to: Recommend SBP ≤185 mmHg and DBP ≤110 mmHg
Afterwards: stabilize and maintain BP <180/105 mmHg for at least 24 hours after thrombolytic treatment.
No thrombolytic therapy
BP should not be treated acutely unless hypertension is extreme SBP>220 mmHg or DBP>120 mmHg or other acute issues exist*
When treatment is indicated, cautious lowering of blood pressure by approximately 15% during the first 24h
Perfusion pressure distal to the obstructed vessel is low, blood flow relies on systemic blood pressure.
*BP should not be treated acutely in non-thrombolytic therapies unless the patient has active ischemic coronary disease, heart failure, aortic dissection, hypertensive encephalopathy, acute renal failure, or pre-eclampsia/eclampsia

11. Additional Medical Management
Antithrombotic treatment
Aspirin 160 to 325 mg within 48 hours
High dose statin
Atorvastatin 80mg
Anticoagulation: only in cardioembolic stroke
IV not recommended during first 48h after acute ischemic stroke
Warfarin can be started for small or moderate-sized infarct after 24 hours
ACC/AHA/ASA recommend early (<48h) initiation of aspirin. Clopidogrel or ticlopidine are alternatives however effectiveness of these in acute stroke is not established
Aspirin initiation in acute stroke has shown benefit for the treatment of acute ischemic stroke or TIA and is supported by a meta-analysis from the Antithrombotic Trialists Collaboration (ATC) published in 2002
For patients with TIA or ischemic stroke of atherosclerotic origin who are able to tolerate statins, high-intensity statin therapy should be started, independent of the baseline low-density lipoprotein cholesterol (LDL-C), to reduce the risk of stroke and cardiovascular events
Timing of oral anticoagulation for secondary prevention in patients with cardiogenic embolism is dependent on size of infarct

12. Neurologic symptoms suggestive of acute stroke
CT Head noncontrast shows hemorrhage
Admit to ICU, reverse coagulopathy, manage BP, call Neurosurgery
CT Head noncontrast no hemorrhage
within 4.5 hours
No h/o ICH, recent stroke, head trauma, intracranial surgery, or bleeding diatheses, and BP<185/110
IV TPA
Within 6 hours
Refer for endovascular intervention
Outside therapeutic window
Optimize secondary prevention

13. BP<185/110 prior to giving
BP in stroke
Ischemic stroke
TPA
BP<185/110 prior to giving
BP<180/105 for 24h afterwards
No TPA
Permissive HTN to 220/120

14. Case Vignette
A 57-year-old man is evaluated in the emergency department 45 minutes after developing acute-onset left arm weakness. He has a 50-pack-year smoking history. He has no history of stroke, trauma, bleeding, cardiac disease, or surgery. His only medications is atorvastatin.
On physical examination, blood pressure is 168/98 mm Hg and pulse rate is 86/min and irregular. Neurologic examination reveals left hemineglect, an inferior left visual field deficit, left facial weakness, mild dysarthria, and left arm and leg drift. He scores 6 on the National Institutes of Health Stroke Scale, indicating a moderate stroke.

15. Case Vignette
What is the next step?

16. Case Vignette
What is the next step? Answer: CT Head without contrast

17. Case Vignette
Laboratory study findings shows complete blood count, a comprehensive metabolic profile, and coagulation studies are normal. A noncontrast CT scan of the head shows no acute hemorrhage.
Which of the following is the most appropriate next step in treatment?
High-dose aspirin
Insulin
Intravenous heparin
Intravenous recombinant tissue plasminogen activator

18. Case Vignette
Laboratory study findings shows complete blood count, a comprehensive metabolic profile, and coagulation studies are normal. A noncontrast CT scan of the head shows no acute hemorrhage.
Which of the following is the most appropriate next step in treatment?
High-dose aspirin
Insulin
Intravenous heparin
Intravenous recombinant tissue plasminogen activator D.
In patients with focal neurologic symptoms suggestive of an acute ischemic stroke, recombinant tissue plasminogen activator should be administered within 3 hours of symptom onset to patients who do not meet any of the exclusion criteria.

19. Case Vignette
An electrocardiogram (ECG) shows atrial fibrillation; an ECG obtained 1 year ago was normal. An echocardiogram shows a left ventricular ejection fraction of 50% without valvular disease or wall motion abnormalities. A chest radiograph and a carotid ultrasound show normal findings.
MRI of the head shows an acute infarction in the right parietal and frontal lobes involving half of the hemisphere.
Which of the following is the most appropriate next step in treatment?
Aspirin
Dabigatran
Intravenous heparin
Warfarin

20. Case Vignette
An electrocardiogram (ECG) shows atrial fibrillation; an ECG obtained 1 year ago was normal. An echocardiogram shows a left ventricular ejection fraction of 50% without valvular disease or wall motion abnormalities. A chest radiograph and a carotid ultrasound show normal findings.
MRI of the head shows an acute infarction in the right parietal and frontal lobes involving half of the hemisphere.
Which of the following is the most appropriate next step in treatment?
Aspirin
Dabigatran
Intravenous heparin
Warfarin
Aspirin
In patients with acute ischemic stroke who are ineligible for recombinant tissue plasminogen activator therapy, aspirin should be administered within 48 hours of the stroke to reduce the risk of recurrent ischemic stroke.
Anticoagulation with warfarin or a newer anticoagulant, such as dabigatran, is required to manage this patient's long-term risk of cardioembolic stroke. Some experts will initiate warfarin within 24 hours of stroke onset in medically stable patients with a small infarction, but withholding anticoagulation for 4 days to 2 weeks is typically recommended for patients with moderate to large infarctions. Until that time, patients are managed with aspirin.

21. Summary
Diagnosis of stroke involves focused history and physical, NIHSS, and CT head noncontrast
CT noncon, CTA and CT perfusion combined improves the detection of an acute stroke
TPA within 4.5 hours, thrombectomy within 6 hours
Aspirin should be given within 48 hours
Permissive hypertension to 220/120 is indicated in non-TPA ischemic strokes only

22. References
Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Jauch et al., on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease, and Council on Clinical Cardiology Stroke. 2013;44:
2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Powers et al. on behalf of the American Heart Association Stroke Council Stroke. 2015
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Antithrombotic Trialists' Collaboration. BMJ January 12; 324(7329): 71–86.
Uptodate:
Initial assessment and management of acute stroke (
Neuroimaging of acute ischemic stroke (
Antithrombotic treatment of acute ischemic stroke and transient ischemic attack (