Douglas Franz MD

Assistant Director, Banner Good Samaritan Stroke Center

July 2011

Stroke: Selected Diagnosis & Management Issues, & BGSMC's

Stroke Center

•1-1.5 Kg•100 Billion Neurons

32,000 neurons die per second during a stroke

Stroke 2006;37;263

Ischemic Penumbra

Core InfarctPenumbraBenign Oligemia

Cerebral Autoregulation

CNS Spectr 2007;12(1):35

•Autoregulation maintains constant perfusion for Mean Arterial Pressures between ~60-140 mm Hg

•Physiologic dysfunction with MAP ≲ 60 mm Hg•Ischemia with CBF ≲ 20 ml/min/100 g

Cerebral Perfusion Pressure

• CPP=MAP-ICP (or MAP-JVP if JVP>ICP)

• Normal: ICP ~7-15 mmHg, and MAP 50-150 mmHg

• Normal CPP ~70-90 mmHg– Perhaps as low as 50 mmHg in adults– Children require at least 60 mmHg

TINS 1999;22(9):391

Epidemiology of Stroke• Stroke WAS the third leading cause of death, behind

cardiovascular diseases and cancer• 150,000 deaths each year (US)• Approximately 780,000 strokes occur each year in the

USA and 450,000 strokes each year in Europe• 600,000 first strokes (US)• 180,000 recurrent strokes (US)• Leading cause of disability in US• 350,000 survivors each year (US)• 7.6% of ischemic strokes and 37.5% of hemorrhagic

strokes result in death within 30 days• Risk factors overlap significantly with cardiovascular

disease• Our best treatment is preventionAmerican Heart Association. 2003, 2008 Heart and Stroke Statistical Update.

ESH-ESC Guidelines Committee. J Hypertens 2003; 21 (6): 1011–1053.

Definitions• Stroke is the acute onset of a

focal neurologic deficit resulting from decreased perfusion to the brain, causing permanent tissue damage

• Strokes are usually the result of vascular disease

• The symptoms of a stroke depend on the part of the brain involved

• 85% are ischemic• 15% are hemorrhagic

Stroke Subtypes

Albers et al. Chest 2004; 126 (3 Suppl): 438S–512S.

15%

17%

21%17%

26%

4%

•Hemorrhagic Stroke•Atherosclerotic Cerebrovascular Disease•Small Vessel Disease (“lacunes”)•Cardiogenic Embolism

•Cryptogenic•Other

Ischemic Stroke

encephalomalacialacune

Ischemic Stroke

Hemorrhagic Stroke: Parenchymal Intracerebral Hemorrhage

(ICH)

Hemorrhagic Stroke

Other ICH locations:

A.Cortex (amyloidosis)

B.Basal GangliaC.ThalamusD.PonsE.Cerebellum

NEJM 2001;344(19):1450

Stroke Risk Factors

Stroke Risk Factors

• Older age• Male gender• Non-white genetic

background• Family history• Prior stroke or TIA

Non-modifiable risk factors Modifiable risk factors (PAR)

Previous TIA or stroke is the most importantrisk factor for stroke.

Hypertension is the most prevalent.

Hankey GJ. Cerebrovasc Dis 2003; 16 (Suppl 1): 14–19.Wolf PA. Adv Neurol 2003; 92: 165–172.

Sacco et al. Stroke 1997; 28 (7): 1507–1517.

• Hypertension (20-40%)• Diabetes mellitus (5-

27%)• Atrial fibrillation (1.5-

23.5%)• Carotid artery disease (2-

7%)• Dyslipidemia (10-15%)• Cardiac disease (1.1-

5.8%)• Cigarette smoking (12-

18%)• Obesity (12-20%)• Others…

Less Well Understood Risks

• Insulin resistance

• Sleep disordered breathing

• Na intake > 2300 mg/d

• Metabolic syndrome

• Alcohol abuse

• Hyperhomocysteinemia

• Drug abuse

• Hypercoagulable states

• OCP use

• Inflammatory processes– CMV, C. pneumoniae, periodontal disease, etc

• Migraine

• Lp(a) status

TIA: Transient Ischemic Attack

• Old Definition: stroke symptoms lasting less than 24 hours

• New Definition: “a brief episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction”

• TIA prevalence 7-40% in stroke patients, most in 30 days preceding first stroke, 41% lasting < 1 hour

• In another study: 17% TIAs on day of stroke, 9% previous day, 43% in previous week

Stroke 2009;40:2276

Cumulative Stroke Risk after TIA or Minor Stroke

Coull et al., BMJ 2004;328:326

Acute Stroke Risk After TIA• meta-analysis of 18 cohorts, 10126 TIAs

• 5.2% strokes in 7 days, 3.2% in 2 days• i.e., 1 in 20 patients will have a stroke soon after

their TIA

• TIA Management "Patchy"

• ½ of strokes after TIA occur in 24 hours

Lancet Neurol. 2007 Dec;6(12):1063

SettingPatients with

subsequent stroke (%)

95% CI

Non-urgent treatment 11 8.6 - 13.5

Urgent treatment 0.9 0.0-1.9 Neurology 2009;72:1941

New TIA Guidelines• Neuroimaging, preferably MRI with DWI within 24 hours

• Noninvasive cervicocephalic imaging

• Consider noninvasive cranial vessel imaging if management would be affected

• ECG ASAP after TIA

• TTE reasonable if no other causes, TEE if indicated

• CBC, CMP, PT/PTT, fasting lipids

• Hospitalize if <72 hours from event, and ABCD2 ≥ 3, or if work-up can’t be completed in 2 days

Stroke 2009;40:2276

Hypertension Risk and Prevalence

• JNC VII, 2003:• In patients > 50 years/age, SBP>140mmHg is a more important risk factor for

cardiovascular disease than DBP• Beginning with 115/75mmHg, CV disease risk doubles with each increment of

20/10mmHg• Individuals who are normotensive at age 55 have a 90% lifetime risk of

developing HTN• Odds ratio of developing HTN 4 at 50 years old

• NHANES, 1999-2002:

Hypertension Overall

•Lowering BP by 10/5 mmHg lowers CHD by ¼ and stroke by ⅓ regardless of starting BP, vascular risks, and how it was done

• Meta-analysis of 147 trials, 958,000 patients aged 60-69, over 42 years: ~40% reduction in stroke

• In patients with DBP > 90 mmHg, over 60% RRR with combination therapy

BMJ 2009;338:b1665

Lipids: SPARCL• 4731 patients with stroke/TIA 1-6 mo

before entry• LDL 100-190 mg/dl• atorvastatin 80mg vs placebo

– LDL: 73 vs 129 mg/dl– 5-year stroke risk 0.84 (0.71-0.99)– 5-year decrease in major cardiovascular

events:• ARR 2.2% (0.2-4.2), RRR 16%

– RRR ischemic stroke 22%– Increase in hemorrhagic stroke (2.3% vs. 1.4%)

• ARR 3.5%, RRR 20%

NEJM 2006; 355: 549

Lipids: SPARCL Net Benefit

Even

ts/5

Year

s (%

)

n=2,366 n=2,365

11.2%

2.3%

8.9%

13.1%

1.4%

11.7%

Prevent 22 events/1,000 treated/5 years

Carotid Stenosis Risk• Accounts for 15-20% of ischemic

strokes

• Carotid endarterectomy (CEA) surgery if symptomatic:• 70-99% stenosis: NNT 8 (2

years)• 50-69% stenosis: NNT 20

• Surgery if asymptomatic:• 60-99% stenosis: NNT 53 (3

years)

• In US ½ - ⅔ of carotid surgeries are still on asymptomatic patients

• <5% of asymptomatic patients will benefit from surgery, with 4-5% surgical risk

JAMA 1995;273:1421

NEJM 1991;325:445Lancet 2003;361:107

Patent Foramen Ovale• Detected incidentally in ~20% of

individuals

• Over-represented (>50%) in young people (<55) with cryptogenic stroke• PFO alone confers no statistical risk

(A)• PFO with septal aneurysm might (C)

Neurology 2004;62:1042

• Consensus: antiplatelet therapy if associated with cryptogenic stroke, antocoagulation for DVTs (U,A)

• CLOSURE trial

Acute Stroke

Specific Treatment Targets

• Blood Pressure:• SBP <185 after lytics• SBP < 160 in hemorrhage• SBP < 220 in general ischemia• Be aware of autoregulation, sudden changes

• Euvolemia

• Normoglycemia

• Normothermia

Stroke Mimics• Seizures, especially partial/focal ones

• Hyper/hypoglycemia

• Toxic/metabolic encephalopathy

• Decompensation of old deficits

• “Generalized” weakness

• Hemorrhage

• Tumors

IV tPA

SITS-MOST• 6,483 stroke patients in 285 European centers,

50% with little experience with tPA• Monitoring of safety profile of tPA in routine use

Lancet 2007;369:275

tPA Meta-Analysis

Lancet 2004; 363:768

•Pooled analysis of NINDS, ECASS, ATLANTIS trials

•OR 1.4 (1.05-1.85) for favorable outcomes with OTT 181-270 mins

ECASS-III

NEJM 2008;359(13):1317

• 821 pts; 403 placebo, 418 tPA (standard protocol) @ 3-4.5 hours

• Primary outcome: dichotomized mRS: 0-1 vs. 2-6

• Secondary outcomes: combined global scores

• Median administration time 3 hrs 59 mins

ECASS-III: Outcomes

NEJM 2008;359(13):1317

• Favorable 52.4% (tPA) vs. 45.2% (placebo)• OR 1.34 (95% CI: 1.02-1.76, p=0.04)

• Secondary outcomes: OR 1.28 (1.0-1.65, p<0.05)

• ICH higher with tPA: 27.0% vs. 17.6%, p=0.001• symptomatic 2.4% vs. 0.2%, p=0.001

• Mortality 7.7% vs. 8.4% (p=0.68)

SITS-ISTR

Lancet Online; 9/15/08

3: Moderate disability; requiring some

help, but able to walk without

assistance

Intra-Arterial TherapiesIndications: <6 hours, Significant disability,

Gross thrombus in large vessels (M1/M2, PCA, basilar, ACA)

Risks: 10-15% with complication/sICH

Options: thrombolysis, thrombectomy

Evidence: PROACT II, pending trials IMS III, MR RESCUE

MERCI Retrieval System™

Stroke 2004;35:A294

The Penumbra System™

Benefit of Revascularization

Saver / UCLA Stroke Center (MERCI)

90-day modified Rankin

53% 16% 31%

6% 32% 62%

Harm in Revascularization

Stroke Codes• Criteria:

• any patient you think clinically is having a stroke• time of onset/last-well < 6 hours ago• “meaningful” deficits

• Call 1-6666, ask for a “stroke alert”• On the floor, a SA is initiated by the MD or RRT, not the

nurses

• 6B/neuro-ICU nurse responds to guide process, gather data

• Decision on disposition made in ~45 mins and discussed (we may call you sooner)

• Calling office for doc-to-doc guarantees delays; if SA criteria are met, activate it

Acute Stroke Labs

• CBC

• BMP

• PT/INR/PTT

• lipid panel/HgBA1c (no so acute)

• Exotics: ESR/CRP, Hypercoagulable panels, vasculitis panels

Imaging Acute Stroke• Non-contrast CT head

• MR brain – obtained sub-acutely

• Vascular Imaging• CT angiogram head/neck• MRA neck/brain • Carotid U/S

• Acute Stroke <6 hours• CT angiogram/perfusion head and neck

• Telemetry

• TTE with bubbles, TEE in selected cases

• Cerebral Angiogram selected cases

Artery

VeinTissue

Perfusion Imaging

Cerebral Blood Volume (CBV)

• mL/100gm

• total volume of blood in a given unit volume of brain; including the blood in the tissues and the large capacitance vessels (arteries, capillaries and veins)

Cerebral Blood Flow (CBF)

• mL/100gm/min

• volume of blood moving through a given unit volume of brain per unit time

Mean Transit Time (MTT)

• seconds

• average time it takes for blood to travel from the arterial inlet, through the capillary bed, to the venous outlet

Blood Pressure Management

•>60% have at least transient SBP > 160

•Not clear if adjusting BP changes outcomes

•Not clear if home meds should be continued

•Consensus is permissive BP to 220/120 before lowering in ischemic stroke• IV boluses, labetalol, hydralazine• Nicardipine

•More aggressive lowering in ICH, generally to SBP <160 mmHg

Baseline BP and Outcomes in IST

Stroke 2002;33:1315

Medications

• Anti-platelets : ASA, Aggrenox, Plavix• Start <48 hours (unless tPA• ANY agent appropriate• ASA 325 mg initially/300 mg PR• ASA 81 mg long term

Platelet Inhibition

MJA 2003;178(11):568

Anti-thrombotics• DVT prophylaxis

• Lovenox 40 mg SQ Daily > SQ Heparin• Use SCD unless contraindicated

• Heparin Drips• Benefit not established, Risk known• Selected cases only: dissections, Cardiac

thrombus, Dural Venous thrombosis with stroke

• Coumadin• AFIB INR 2.5 (2-3)• LVEF < 35% -experimental • Rare indications: Hypercoagulable state,

dissection

Anti-Hypertensives• ACUTE GOAL < 200/100 mmHg Ischemia

• POST-tPA GOAL <185/110 mmHg

• ACUTE GOAL <160 mmHg ICH

• Restart outpatient meds prior to discharge

• Long term goal • <140/90 mmHg• <130/80 mmHg with DM, CKD

• Which agent?• Any but consider diuretic or diuretic/ACE-I

Statins• LDL goal <100mg/dL Uncomplicated

patients

• LDL goal <70mg/dL • In diabetics, identified atherosclerosis,

comorbidities

• Recommend atorvastatin first

• Be sure to continue outpatient statin

Hyperglycemia

• Treat with insulin sliding scale if BG > 140 mg/dL

JC Stroke Core Quality Measures

1. All patients given tPA when indicated2. Swallowing eval on all patients done or considered

• NPO means NPO

3. DVT prophylaxis within 48 hours4. Anti-thrombotic drugs within 48 hours5. Lipid profile on all stroke patients6. Anticoagulation for all a-fib patients considered7. Patients discharged on anti-thrombotic drugs8. Patients assessed for rehab needs9. Stroke education for patients and caregivers10. Smoking cessation

BGSMC Stroke Center

• “Acute” stroke: symptoms < 6 hours• In ED – “Stroke Alert”• On floor, in-house – Rapid Response Team• Elsewhere – CALL 911!

• Subacute or unclear stroke: routine neurology consult

• Clinic: 239-6515

• Stroke Program Office: 239-4531

Stroke Program Office: 239-4531

Thanks to Jeremy Payne