Acute Ischemic Stroke

W. David Freeman, MD

Professor of Neurology and Neurosurgery

Mayo Clinic

No conflicts of interest or disclosures

Mayo Clinic Flagler Education Day May 3rd 2019

Acute Ischemic Stroke

Yes

Neurocrit Care. 2015 Dec;23 Suppl 2:S94-102. doi: 10.1007/s12028-015-0159-0.

TISSUE-BASED SELECTION (PENUMBRAL CTP IMAGING DAWN Protocol 6-24hr window)

TIME-BASED SELECTION

Acute Ischemic Stroke

Objectives

• Recognize the signs and symptoms of acute stroke with emphasis on the time of onset to guide therapy

• Know the steps in pre-hospitaland 1st hour evaluation of acute stroke symptoms

• Obtain brain imaging in determining the cause of stroke

• Recognize Time and Tissue-based selection criteria

Stroke

Clinical diagnosis

Sudden onset of neurological deficit that can be explained by vascular cause

Unable to distinguish between a hemorrhagic and ischemic stroke until imaging obtained

Prehospital Evaluation

• Initial prehospital evaluation by EMS:

• History & Physical

• Determine LKW (Last Known Well) or LSN (Last Seen Normal)

• ABC’s

• Glucose check

• Stroke Screen Exam

• Obtain IV access (preferably 16-18g antecubital)

• Call and transport to nearest Stroke Center

ED Evaluation

Checklist

☐ Activate stroke code system (if available)

☐ Vital signs

☐ Maintain oxygen saturation >94%

☐ Determine time of onset / LKW

☐ Determine NIHSS score

☐ CT or other brain imaging study

☐ Medication list

☐ IV access – 18g

☐ Labs: capillary glucose, CBC with platelets, PT/INR, PTT, and beta-HCG

☐ EKG

Acute Ischemic Stroke

Yes

Transient Ischemic

Attack

ABCD2 Score

ABCD2 Criteria Points

Age ≥ 60 years 1

BP ≥ 140/90 mmHg at initial evaluation 1

Clinical Features of the TIA: • Speech Disturbance without

Weakness, or • Unilateral weakness

1 2

Duration of Symptoms: • 10-59 minutes, or • ≥ 60 minutes

1 2

Diabetes Mellitus in Patient's History 1

Transient Ischemic Attack

• Start antithrombotic agent – ASA, clopidogrel, ASA/dipyridamole • Start high-intensity statin (moderate intensity in age >75 yrs) • Carotid Imaging • Consider Transthoracic echocardiogram • Consider 30-day ambulatory cardiac monitor • Encourage smoking cessation

Acute Ischemic Stroke

Yes

TISSUE-BASED SELECTION (PENUMBRAL CTP IMAGING DAWN Protocol 6-24hr window)

Case

• 79 y/o man presents to ED with:

• Left face and arm weakness, neglect

• Onset 1hour ago (witnessed, LSN, LKN)

• PMH: diabetes, hypertension, sleep apnea, hyperlipidemia

• Meds: amlodipine

• Vitals: Afebrile; BP 184/75 mmHg; P 100/min irreg irreg rhythm; RR 18/min; O2sat 100%

• NIHSS 20

• General physical exam unremarkable

• Bedside blood sugar check 120 g/dl

Noncontrast head CT Right MCA L.V.O. Large Vessel Occlusion

Contraindications for use of IV t-PA

0-3 hrs

AHA/ASA 2013 guidelines 2015 FDA guidelines

Prior stroke within 3 months Removed

Seizure at onset Removed

Bleeding Diathesis Platelet count < 100,000/mm Abnormal PTT on heparin Anticoagulant with INR > 1.7 Current use of DOAC

Bleeding diathesis remains a contraindication, but all laboratory values and specific examples removed

History of ICH Warning for recent ICH

SBP > 185/110 mmHg Remains a warning, but specific BP values removed

Blood glucose < 50 mg/dL (2.8mmol/L)

Removed

Severe Stroke Removed

Mild or rapidly improving symptoms

Removed

Symptoms suggestive of SAH Confirmed SAH

ECASSIII: IV t-PA 3.0 – 4.5

hrs

Additional inclusion between 3 - 4.5 hrs

Meet all criteria of < 3 hour since onset of stroke

Age ≤ 80 years of age

No anticoagulant use, regardless of INR

NIHSS ≤ 25

No combined history of prior stroke and diabetes

Case

• < 3 hours from onset

• NIHSS 20

• Bedside blood sugar check normal

• Noncontrast head CT without hemorrhage

• No contraindications

• BP < 185/110

Neurocrit Care. 2015 Dec;23 Suppl 2:S94-102. doi:

10.1007/s12028-015-0159-0.

IV t-PA Delivery

Two peripheral IV lines (one for TPA, one for PRNs)

Calculate actual body weight

can be estimated by two experienced providers, or scale in ED minus stretcher weight

0.9 mg/kg (MAX 90 mg)

10% given in bolus over 1st minute

The rest given over a 1 hour infusion

Stop immediately if neurological deterioration

Think hemorrhagic conversion

Risk of Intracerebral Hemorrhage with IV t-PA 0-3 hrs

NIHSS Risk of ICH

0-10 2-3%

11-20 4-5%

>20 17%

The higher the NIHSS the higher the risk of ICH

Deterioration During or After IV t-PA

STOP t-PA infusion

Vital signs every 15 mins

Consider non-invasive interventions to lower ICP (e.g., mannitol)

Obtain STAT non-contrast CT scan

Notify the neurosurgeon on call If not available, begin the process of transfer

Stat Labs: PT, PTT, platelets, fibrinogen, type and cross

Give cryoprecipitate if confirmed hemorrhage

Consider one unit of platelets

Endovascular Treatment

Intra-arterial thrombolysis or thrombectomy

• Large vessel occlusion

• Allows later time window of therapy up to 6 – 8 hours

• Continually defining best patient inclusion and exclusion

• Continually developing newer devices

Yes

Neurocrit Care. 2015 Dec;23 Suppl 2:S94-102. doi:

10.1007/s12028-015-0159-0.

TISSUE-BASED SELECTION (PENUMBRAL CTP IMAGING DAWN Protocol 6-24hr window)

Thombectomy Devices

Trevo

Trevo

Solitaire

Recommendations for Thrombectomy (LVO)

Give IV t-PA if eligible

Endovascular Therapy indicated if the following criteria are met:

Prestroke mRS score 0 to 1

LVO of the ICA or proximal MCA (M1)

Age ≥ 18 (no upper age limit)

NIHSS ≥ 8

ASPECTS score ≥ 6

Groin puncture within 6 hours of LKW

Case • He received IV t-PA

• CTA confirms right MCA-M1 LVO

• He is taken for thrombectomy

CBF CBV

TTP TTD MTT

CBF= CPP/CVR Thus CBF= CBV/MTT

Neuroimaging Clin N Am.

2011 May ; 21(2): 259–283.

Pre intervention Angio

Post intervention Angio

Red Clot embolus

Freeman WD, Brott TG. Neurovascular Surgery. 2nd Ed. Thieme; 2015. p. 337-350.

Case of Reperfusion Therapy

• Patient NIHSS went from 20 to 3

• Admitted to the ICU for post IV t-PA and endovascular care protocols

Yes

PENUMBRA

MCA model, CBF values = ml/100g/min

Red= core infarct, Blue = Penumbra, Grey=normal

Ischemic Core

• Nonsalvagable tissue (<4min to rescue)

• Electrically silent

• Irreversible damage at cellular level, loss of ion pump function/cellular integrity1

• Core volume closely related to admission neurological deficit2

1 Moustafa R, Baron JC. British J of Pharm 2 Marchal et al 1999. Brain 122 (Pt 12): 2387-2400

Recent Trials: CT Penumbral Selection vs Time-Based Selection or both

More Selective LVO

Small core infarct

Less Selective LVO

MR CLEAN: 13% REVASCAT: 15% THRACE: 11%

EXTEND-IA: 31% SWIFT PRIME: 24% ESCAPE: 25%

Effect size

Late Window Treatment

DWI/PWI and CTP Assessment in the Triage of

Wake-Up and Late Presenting Strokes Undergoing

Neurointervention (DAWN) Multicenter randomized controlled trial, funded by industry

6-24 hours, NIHSS 10+ Perfusion evaluation for core volume, graded by age

Primary outcome: 90 day mRS

Stopped early due to pre-specified endpoint

Endovascular Therapy Following Imaging

Evaluation for Ischemic Stroke 3 (DEFUSE 3) Multicenter randomized controlled trial, funded by StrokeNet

6-16 hours, NIHSS 6+ RAPID software for automated evaluation of penumbra

Primary outcome: 90 day mRS

Completed

PMID: 29129157

DAWN Time (6-24hrs) + penumbral selection

TICI- Thrombolysis in Cerebral Infarction “TICI 2B (or better) is where you want to be” (reperfusion)

DEFUSE 3 TICI score Predicts mRS outcome

• Size of core determines

outcome.

• Collaterals determine

core, since patients with

poor collaterals are time

sensitive

• TICI 2B+ determines

outcome

“2B or not 2B”

T. Lesli-Mazwi - DEFUSE 3

Example#1- Core Small, Large Penumbra, not reperfused =Large infarct

Hakimelahi R. Exp Rev C Ther. 7(1),29-28 (2009)

Example #2- moderate core infarct, Large penumbra (salvaged)

Hakimelahi R. Exp Rev C Ther. 7(1),29-28 (2009)

What if I don’t have CT perfusion? Use ASPECTS!–Alberta Stroke Program Early CT Score

Hypodense brain or sulcal edema = 1 point You want to be a perfect 10! ASPECTS > 7 better Outcomes in several Thrombectomy trials

Can’t remember ASPECTS? There’s an APP for that!

Handoff Checklist ☐ Age, gender, pertinent comorbids

☐ ABC’s

☐ Time of symptom onset

☐ NIHSS pre therapy, post

☐ CT/CTA or MRI/MRA results

☐ IV t-PA administration or contraindication(s) to IV t-PA

☐ Endovascular intervention(s) if applicable, TICI scale if known (recanalization)

Admission/Transfer • Continuous telemetry

• IV normal saline – euvolemia

• Keep glucose 140-180 mg/dl (7.8-10 mmol/L)

• Aggressive fever workup and control

• If t-PA administered,

• no anticoagulation or antiplatelets for 24 hours

• avoid indwelling urinary catheters, nasogastric tubes and intra-arterial catheters for 4 hours-if possible

• Swallow assessment/document before PO!

Conclusion

PMID: 27673305

Remember the Time (<4.5hr) and Tissue-based (Penumbra) Paradigms for acute stroke management (tPA-treated patients and thrombectomy candidates)

Think: Do I have a salvageable penumbra? If so, consider acute endovascular intervention - risk vs benefit:

• LVO time based < 6 - 7.3 hrs (HERMES)

• DAWN 6-24hrs if mismatch still present

Thank you - Sept 26-28th Amelia Island https://ce.mayo.edu/neurology-and-neurologic-surgery/content/11th-annual-stroke-and-cerebrovascular-disease-review-2019

Questions?