IS IT A TIA OR A STROKE?

January 30, 2015

Richard S Jung, MDMedical Director, CoxHealth Stroke CenterVascular Neurology & Neurointerventional Surgery

DISCLOSURES

No relevant disclosures

CASE

52 yo left handed man with new onset of right face, arm and leg weakness with slurring of speech that lasted 30 minutes.

PMHx: Hypertension, Dyslipidemia, Diabetes mellitus

Anxiety, Depression, Bipolar Disorder

Chronic Total Body Pain

Syncopal Spells

Surgical Hx: Cholecystectomy, Appendectomy, Tonsillectomy, Vasectomy

CASE (CONTINUED)

Social Hx: Tobacco - Smokes 3 ppd Alcohol – “couplabeersaday” Remote illicit drug use – “you name it, I did it” Disabled (chronic pain and syncopal spells)

Family Hx: Mother and father both had heart attack and stroke in their 60’s. Brother died of heart attack in 40’s Sister with diabetes and heart disease.

ROS: Coughs continuously, occasional chest pain and dyspnea on

exertion Similar neurologic spell occurred 1 week prior to presentation.

CASE (CONTINUED)

Medications: Hydrocodone, alprazolam, clonazepam,

lorazepam, zolpidem as needed

Physical Examination: Vitals: 98.5F, 170/95, HR 88, RR 18, O2 Sat 92% RA General: Thin, disheveled, elderly appearing man in

no apparent distress. CVS: RRR, no murmurs, left carotid bruit. RESP: CTAB ABD: Soft, NT, ND ExT: No edema, some clubbing of the fingers b/l

NEUROLOGIC EXAM MS: Alert, oriented x3, no aphasia, no dysarthria CN:

II: Fundoscopic – copper wiring, no disc edema, cotton wool spot OS, VFF to confrontation

III, IV, VI: EOMI, pupils appear symmetric and reactive to light bilaterally.

V: Slightly diminished right lower facial perception to light touch and sharp

VII: face symmetric VIII/IX: hearing intact, VOR grossly normal X, XI, XII: palate elevates normally, tongue protrusion midline.

SCM/shoulder shrug 5/5. Motor:

5/5 all limbs, normal tone Sensory:

Intact to light touch bilaterally.

Reflexes: 2+ diffusely, toes downgoing

Coordination: Able to perform finger to nose and heel to shin with no significant

dysmetria Gait:

deferred

TESTS

CT Head – Report negative for acute hemorrhage

Labs – CBC normal, CMP (glucose 240, creatinine 1.4), troponin normal, urine drug screen normal, blood alcohol level 0.04.

CXR – no acute process, clear

EKG – sinus rhythm, normal axis

NON-CONTRASTED HEAD CT

DIAGNOSIS?

TIA? Ischemic Stroke? Reversible Ischemic Neurologic Deficit? Transient stroke? Cerebral infarct with transient symptoms? Transient symptoms with infarct? Conversion disorder? Alcoholism? Hypochondriasis? Hypertensive urgency? Other?

LOCALIZATION?

WHY DOES STROKE AND TIA MATTER? 795,000 strokes every year

>690,000 NEW ischemic strokes every year 240,000 TIAs per year

Every 4 minutes someone suffers stroke Every 4 seconds someone dies of stroke Now 5th leading cause of death in the US Still #1 cause of disability Short term risk for ischemic stroke

3-4% annual risk (historical low!) Prior numbers:

>10% in 90 days Of these that do occur, 25-50% occur in 2 days Greater Cincinnati and Kentucky Stroke Study cohort,

risk of MORTALITY after TIA in 1 year was 12%. 15% of ischemic stroke is heralded by TIA

Circulation. 2015;131:e29-e322.

Stroke. 2014;45:2160-2236

WHAT IS A TRANSIENT ISCHEMIC ATTACK?

OLD DEFINITION

A transient ischemic attack is a sudden focal neurologic deficit lasting for less than 24 hours, of presumed vascular origin, and confined to an area of the brain or eye perfused by a specific artery.

HISTORY

CM Fisher – described a TIA reported from 1950 – Right eye transient blindness in a man with transient left

arm and leg weakness. Ended up dying rather quickly of colon cancer. Autopsy revealed severe atherosclerotic plaque in the right carotid bulb.

Previously described TIA as “intermittent cerebral ischemia”

1958 – NIH Committee for Classification of Cerebrovascular

disease noted TIA could last up to several hours, but typically only few seconds up to 5-10 minutes.

1964 Acheson and Hutchinson – 1 hour separation for TIA and

Stroke Marshall – 24 hours for TIA (though most were <1 hour)

1965 4th Princeton Conference – 24 hours for TIA reinforced

CM Fisher. N Engl J Med, Vol. 347, No. 21 November 21, 2002

Neurology 1958;8:395-434.

N Engl J Med, Vol. 347, No. 21 · November 21, 2002

Fisher CM. Intermittent cerebral ischemia. In: Wright IS, Millikan CH, eds. Cerebral vascular disease. New York: Grune & Stratton, 1958:81-97.

1975 NIH Classification Document revision - TIA became

defined as a focal neurologic deficit/ischemic cerebral event lasting <24 hours

Reversible Ischemic Neurologic Deficit (RIND) >24 hours up to 7 days

Term phased out in the 1970’s, obsolete because these patients essentially had STROKE.

1991 “Cerebral infarction with transient signs” – Toole

Cerebral ischemic events with apparent infarction and rapid clinical recovery Stroke 1991;22:99-104.

PROBLEMS WITH OLD DEFINITION 1/3 of patients with classic definition <24 hours had POSITIVE

findings on MRI!

Delay treatment for IV tPA (wait and see) <1 in 6 with symptoms >1 hr in duration with reverse in 24 hours

Only 2% of placebo treated patients with disabling symptoms eligible for IV tPA recovered completely at 24 hours.

24 hour mark is arbitrary and insignificant.

Tissue based definition would improve diagnosis and treatment

Shah et al. Stroke. 2007;38:463

Neurology. 1988;38:674–677.

N Engl J Med. 1995;333:1581–1587.

N Engl J Med, Vol. 347, No. 21 · November 21, 2002

“…a TIA is a brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction.”

PROBLEMS WITH “NEW” 2002 DEFINITION

Imaging is required to satisfy new definition –variable resources in the communities

Stroke rates not comparable to prior studies (but encouraged as is more accurate)

Is it a TIA or is it a Stroke?! What about the “tweeners?” “Acute neurovascular syndrome” may be applied to

stroke like symptoms until diagnostic imaging is complete or not performed.

“Cerebral infarction with transient symptoms” or “transient symptoms with infarction” have also been proposed.

Time of “1 hour” is also not accurate, like 24 hours is not accurate. It is not possible to predict with certainty (high sensitivity and specificity)that ischemia will progress to infarct by any one time threshold.

RESPONSE TO NEW DEFINITION OF TIA Brown et al – UK

Impractical imaging requirement proposed leaving TIA a clinical diagnosis with time

constraint at 1 hour. Ballotta et al – Padua, Italy

rural patients don’t have MRI available, CT only. Difficult to distinguish. Misleading definition – “TIA without brain infarction is better than stroke”; proposed using “Transient stroke”

Bernstein and Alberts – Northwestern May prevent stroke patients from getting tPA

(subacute infarct on MRI precludes tPA) New definition – research Old definition - clinicians

n engl j med. 2003; 348;16

AHA/ASA PROPOSED DEFINITION OF TIA

…a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.

Stroke. 2009;40:2276-2293

PROPOSED DEFINITION OF CEREBRAL INFARCTION

“…brain or retinal cell death due to prolonged ischemia.”

Saver et al. Stroke. 2008;39:3110-3115

AHA-ASA DEFINITION OF ISCHEMIC STROKE

…brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury.

Stroke. 2014;45:2160-2236

PATHOPHYSIOLOGY OF ISCHEMIA

Reduced blood flow depletion of intracellular energy stores, membrane depolarization, release of extracelluar K+, concurrent increased O2 extraction and lactic acidosis VGCa2+ channels glutamate released activates NMDA receptor increased Na+ influx followed by H2O, cellular swelling increased intracellular calcium Increased NO free radical production damage mitochondria and cellular membrane eventual apoptosis.

Grotta. Journal of Stroke and Cerebrovascular Diseases, Vol. 8, No. 3 (May-June), 1999: pp 114-116

PATHOPHYSIOLOGY OF ISCHEMIA

Normal Cerebral blood flow (CBF) = 50-60 ml/100g/min

Benign oligemia CBF = 20-50 ml/100g/min

Ischemia (reversible) CBF < 23 ml/100g/min

Infarct (irreversible) CBF <10 ml/100g/min

EVALUATION OF STROKE AND TIA

Stroke. 2014;45:2160-2236

DETERMINE THE MECHANISM

Adams et al. Stroke 1993;24:35-41

WHAT IS THE MECHANISM OF ISCHEMIC STROKE?

Large artery, thrombotic Intracranial atherosclerosis

Large artery, embolic Carotid/vertebral atherosclerosis

Small vessel (lacunar)

Cardioembolic Atrial fibrillation

Aortic arch atheroma

Ventricular thrombus

MECHANISMS OF ISCHEMIC STROKE Others (not limited to below)

Vasculopathy from Drugs ie. Methamphetamines, cocaine Vasculitis Reversible vasoconstriction syndrome

Dissection Fat embolism Paradoxical embolism (DVT PFO Cerebral artery) Hypercoagulablility

Factor V leiden Prothrombin Gene mutation Protein C & S deficiency Antithrombin III deficiency + many, many more

Cryptogenic (unknown) ?PFO?

MORE IN THE DIFFERENTIAL –THANK YOU DR. FISHER

CM Fisher. N Engl J Med, Vol. 347, No. 21 November 21, 2002

EVALUATION OF STROKE AND TIA

Essentially no distinction for work up EVERY TIA OR STROKE should undergo

brain imaging with CT or MRI to distinguish from hemorrhage

Stroke. 2014;45:2160-2236

EVALUATION OF STROKE AND TIA

Evaluation should be enough to exclude high-risk modifiable conditions such as carotid disease or atrial fibrillation Carotid ultrasound

EKG

Echocardiogram (NOT necessary in clear lacunar stroke, unless etiology is not clear)

Stroke. 2014;45:2160-2236

EVALUATION OF STROKE AND TIA

All patients should probably be tested for DM Fasting glucose

HbA1c (most likely accurate post event)

Oral tolerance test

Stroke. 2014;45:2160-2236

EVALUATION OF STROKE AND TIA

All patients should be screened for dyslipidemia

Stroke. 2014;45:2160-2236

ANTITHROMBOTIC THERAPY

Aspirin daily (325mg or 81mg no difference)

May consider addition of clopidogrel 75mg to aspirin within 24 hours of symptoms for duration of 21 days (and then aspirin thereafter).

Stroke. 2014;45:2160-2236

STATIN THERAPY

It is recommended to start intensive lipid lower agents (statin) if atherosclerosis suspected along with LDL >100. (less level of evidence for LDL <100, but still recommended).

ABC…123…I?

2005 – ABCD Score – Rothwell et al Age Blood pressure Clinical features Duration of symptoms

2007 – ABCD2 – Johnston et al Addition of Diabetes Mellitus

2010 – ABCD3 and ABCD3-I – Merwick et al Addition of “dual TIA” (>= 2 TIA symptoms in 7 days) I = imaging (carotid stenosis or DWI restriction

Bottom line: TIA with ABCD2, ABCD3 or ABCD3-I score of 3 or

more, stroke risk moderate to high, admit and complete workup

REMEMBER OUR GUY? 52 yo man with the TRIFECTA (HTN, hyperlipidemia, diabetes

mellitus) and chronic smoker

Last known well: 07:30AM

Discovered: 08:28AM

Presented to community hospital with: Sudden onset R-sided facial droop

slurred speech

Right upper and lower extremity hemiplegia

NIHSS = 13

Rapid resolution of symptoms

DIAGNOSIS?

CASE

What’s his ABCD3 Score? 5 (age, blood pressure, clinical symptom,

diabetes) Moderate risk

7 day stroke risk is ~7%.

90 day risk ~12%

3 year risk ~25%

WHAT DO WE DO?

A) Send him home, he already got his head CT, what more does he want?

B) Sedate, paralyze, intubate and admit to the ICU

C) Start Coumadin

D) Give him IV tPA

E) Admit for observation and complete stroke/TIA workup

THIS GUY CAN’T WIN…

Neurologic Deterioration: 09:30AM Right face + arm > than leg weakness, left gaze

deviation, dense aphasia.

Blood pressure 150/90

NIHSS = 18

DIAGNOSIS?

CT HEAD

HyperdenseMCA sign

NOW WHAT DO WE DO?

A) Consult palliative care services

B) Lament loudly and contact next of kin

C) Put him on a boat and set it ablaze with fiery arrow to Vallhalla

D) Give him hugs until he gets better

E) __<the real answer>___?

WHAT DO WE REALLY DO?

A) Aspirin or Plavix or Aggrenox or Pletal (or any combo?) B) IV tPA C) Heparin infusion and Coumadin D) Mechanical Thrombectomy only E) IV + IA tPA + Mechanical Thrombectomy F) IA tPA only, no IV tPA G) Bivalrudin infusion H) IV + IA tPA I) Hemicraniectomy J) Hyperosmolar therapy (mannitol and hypertonic saline) K) Hypothermia L) Abxicimab infusion M) Back to the prior slide?

THE ONLY CORRECT ANSWER IS…

IV tPA

Total dose = 0.9mg/kg 10% bolus over 1 minute

Remaining 90% infused over 1 hour

Max dose 90mg total

BACK TO THE CASE…

IV tPA administered at 10:30AM (3 hrs after onset of symptoms).

Weakness was not improved But remember effect for functional independence

was measured in NINDS tPA trial at 90 days! Not in minutes or hours!

SO…WHAT NEXT?

Patient was emergently drip and shipped to Cox South

Emergent advanced imaging obtained for evaluation for endovascular therapy

MRI DWI/ADC

Small acute infarct already present in left striatum

MRA HEAD

Loss of signal in the LMCA and diminshed signal in LICA

ADVANCED IMAGING: MR PERFUSION

Large area of perfusion deficit in the entire LMCA vascular territory, (theoretically) not functioning, but not dead…yet.

OKAY…NOW WHAT?

Young guy, small core infarct <70cc, large vessel occlusion (LMCA or LICA), NIHSS >8, large perfusion deficit

Send him to neuroIR for angio!

Left Common Carotid Artery Injection:

Severe >85% stenosis of origin of left internal carotid artery with distal flow limitation

Also note the unstable plaque at the carotid bulb

Left ICA terminus Occlusion – bad news

ReoPro0.25mg/kg bolused.

Status post balloon angioplasty –improved intraluminal diameter

Status post placement of carotid stent –extends from the proximal left ICA to the distal left common carotid artery.

Oh right, still gotta fix that…

Penumbra aspiration catheter 5Max Ace navigated to LICA terminus.Direct aspiration performed with suction only.After a couple of minutes…

High FIVE!

LMCA and LACA revascularize.

Still some subocclusive branch occlusions in the posterior M2 division of the LMCA as well as the distal pericallosal artery

AND SO WE WAITED…

Let the tPA and the ReoPro marinate….

Put a fork in the man, he is DONE.

The End…

or is it?

MOST IMPORTANTLY…

No post tPA and post procedure symptomatic intracerebral hemorrhage (sICH)

Short hospital stay

Discharged to HOME on aspirin and plavix

NIHSS at Discharge = 1 (minor facial palsy)

SUMMARY

TIA: …a transient episode of neurological dysfunction

caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.

Ischemic Stroke: …brain, spinal cord, or retinal cell death

attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury.

SUMMARY

No more arbitrary time designation to distinguish TIA from stroke. Now tissue diagnosis.

In general, most TIAs last <10 minutes (up to 90%)

Neuroimaging will be helpful (and is essentially mandated for) diagnosis.

If symptoms are completely resolved after a short time and patient has an MRI positive lesion = STROKE (NOT TIA)

If symptoms are completely resolved after a short time and MRI is negative = TIA

If patient has persistent neurologic deficits but MRI negative = STROKE (or conversion reaction, or something else entirely; NOT TIA)

SUMMARY

If patient has MRI that shows prior infarct but clinically no history of symptoms = SILENT STROKE (NOT TIA)

There are going to be some in the middle: Lasting symptoms, CT head negative, but can’t

get MRI = probable STROKE (NOT TIA)

Treat and evaluate TIA like ischemic stroke. TIA can herald a big oncoming stroke.

THANK YOU