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