VASCULAR EMERGENCIES
| ACUTE STROKE TREATMENT —Justin A. Sattin, MD, Stroke Fellow, University of California, San Diego, School of
Medicine
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| Acute ischemic stroke: 80% of strokes ischemic, 20% hemorrhagic; frontotemporal brain lesions cause speech problems;
cerebellar lesions cause balance problems; number of functions mediated by brain pose clinical challenge, compared
to diseases with target pain and specific symptoms; patients with insensate brain often unaware of deficit
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| American Heart Association/American Stroke Association: stroke warning signs—sudden onset of 1)
numbness and weakness, 2) confusion (covers fluent aphasia, ie, speaking gibberish), 3) visual loss in one or both eyes
(visual field cut usual but monocular vision loss less common), 4) dizziness (suspicious if accompanied by dysarthria,
diplopia, weakness, and sensory changes), 5) severe headache (intracerebral hemorrhage causes pain)
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| Left hemisphere stroke: causes aphasia; gaze deviation on left side; left hemisphere stroke sometimes followed by seizure
that pins eyes to right side (eyes drift back to left when seizure ends); eyes will drift toward side of lesion in hemispheric infarction
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| Right hemisphere stroke: eyes drift right; left-sided visual field cut, weakness, sensory disturbance; issue of neglect
unique to right hemisphere stroke; patient loses concept of leftness; rehabilitation difficult and patients do not do as well
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| Cerebellar stroke: causes dysarthria and ataxia
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| Brainstem stroke: associated with crossed signs; weakness and sensory loss on one side of face and opposite side of
body concerning for brainstem stroke; illustrated by lateral medullary syndrome; presents with routine stroke signs
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| Hemorrhagic stroke: not qualitatively different from ischemic stroke; very high blood pressure (BP), eg, 260 mm Hg,
and rapid decline in consciousness; flexor or extensor posturing
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| Medical emergency: need to recognize stroke as emergency like cardiac arrest; “code of a different flavor”
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| Clinical work-up: fresh set of vital signs, finger-stick glucose, electrocardiography (ECG), and noncontrast head computed
tomography (CT)
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| Evaluation of stroke patient: seizure mimics stroke in ocular motility, so important for physician to obtain good history
to rule out convulsion or epilepsy; also exclude hypoglycemia (can mimic stroke) and migraine; anamnestic
response—symptoms of past stroke re-emerging due to another problem, eg, UTI; severity of new problem does not outstrip
original problem; psychiatric symptoms may be present
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| Time of onset: ask relatives, witnesses; if “911” call placed, obtain time of call from emergency medical technician;
sometimes detective work necessary (eg, man’s receipt from store issued hours before stroke enabled physicians to estimate
time of onset)
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| Computed tomography: confirms diagnosis (hemorrhagic or ischemic); in hyperacute settings, CT often normal
(usual in patient with no history of stroke)
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| Proven treatments: intravenous (IV) tissue plasminogen activator (tPA)—National Institute of Neurological Disorders
and Stroke (NINDS) ≈10 yr ago funded pivotal study in which tPA given as 10% bolus and 90% over 1 hr; results
showed 10-fold higher hemorrhage rate in treatment arm than placebo arm; outcomes data in National Institutes of Health
(NIH) Stroke Scale (NIHSS) showed tPA beneficial across board; relative benefit 50% on Modified Rankin scale (outcome
measure used most by neurologists); number needed to treat (NNT) 7.7 (compares favorably with other medical interventions);
mortality rate little lower for tPA but not statistically significant; aspirin—2 trials (40,000 patients)
showed aspirin can prevent death or nonfatal stroke in 1 of every 111 treated; does not compare to tPA result, so aspirin
not viable alternative
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| Other treatments: heparin—not shown useful for acute stroke; study showed slight decrease in stroke recurrence offset
by increase of same magnitude in hemorrhagic stroke
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| Neuroprotection: hypothermia—well-known neuroprotector; good data in cardiac arrest, conflicting data in traumatic
brain injury; used in some surgical procedures; preclinical data available on brains with large infarctions not exposed
to hypothermia and very small infarctions in brains exposed to hypothermia; pilot studies include one using surface
cooling with blankets and one using catheter in femoral vein (catheter cools core temperature)
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 | Intravascular Cooling for the Treatment of Stroke–Longer window (ICTus-L) trial: ongoing at speaker’s center; patient
presenting within 3 hr receives tPA (standard of care), then randomized to receive hypothermia or not; testing hypothesis
that hypothermia will extend window for giving tPA and reduce bleeding risk
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| NXY 059: neuroprotective strategy under investigation; free radical scavenger made by AstraZeneca; testing for ischemic
stroke and intracerebral hemorrage; Stroke Acute Ischaemic NXY-059 Treatment (SAINT) I and II—Saint I
European version and Saint II US version of trial for ischemic stroke; data show adverse and serious events same for
drug and placebo
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| Safety of tPA administration: recent study suggested one major impediment to stroke patients receiving tPA was clinicians’
fear of hemorrhage risk; emergency department (ED) physicians, when polled, stated hemorrhage rate of 2% or
3% would make them more comfortable with using drugs
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| Magnetic resonance imaging (MRI) technologies: trial under way in which patients receive MRI, then device
used for removal of clot; using Merci Retrieval (system), insert catheter, inflate balloon to occlude forward flow, snag
clot on corkscrew-shaped device, retract it inside catheter, deflate balloon, and pull clot out
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| Intra-arterial thrombolysis: Prolyse in Acute Cerebral Thromboembolism (PROACT) trial—prourokinase (plasminogen
activator) used within 6-hr window; agent squirted directly onto clot; had to have occlusion in M1 or M2 segments;
results showed hemorrhage risk 10% at 24 hr up to 10 days, compared to risk of 2% rising over time in placebo
arm; much higher than hemorrhage rate (0.6%) in IV tPA trial (attributed to more severe strokes in PROACT subjects);
overall, positive trial on par with tPA trial; Food and Drug Administration (FDA) required second trial due to relatively
small numbers
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| Hemicraniectomy: not proven therapy; in review of 140 patients, those <50 yr of age had reasonable chance of good outcome;
all studies observational; physician can try approach if patient young, deteriorating, and family wants to pursue all avenues
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| Transcranial ultrasonography (US): can potentiate tPA; study pending
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| Laser therapy: appears to improve outcomes when delivered to brain, but reasons unclear; some animal data
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| Hypobaric O2 : in early testing stage
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| UPDATES IN STROKE AND TIA—Wade S. Smith, MD, Professor of Neurology, and Director, Neurovascular Service,
University of California, San Francisco, School of Medicine
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| Stroke after transient ischemic attack (TIA): clinical view of TIA now as “unstable angina of the brain”
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| Clinical factors enhancing likelihood of stroke after TIA: 1) age >60 yr; 2) motor weakness (objective finding);
3) duration of TIA >10 min; 4) speech or language problem of any kind (eg, garbled speech); 5) diabetes; if none of
5 factors present at 90 days, no patient had stroke; when 5 present, 35% of patients had stroke within 90 days
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| What can be done for TIA patient: clinician should not miss 1) atrial fibrillation (ECG combined with review of systems
questions sufficient to rule out in ED) or 2) carotid disease (not all settings have technology to noninvasively image carotid
artery); for all other patients, give angiotensin-converting enzyme (ACE) inhibitor, statin, and antithrombotic agent
(eg, aspirin, dipyridamole and aspirin [Aggrenox], clopidogrel [Plavix])
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| Standard of care: if no contraindication for antithrombotic drug, start with aspirin; if patient already on aspirin, change to
clopidogrel 75 mg/day or Aggrenox (one tablet bid); ongoing trial (Prevention Regimen For Effectively avoiding Second
Strokes [PRoFESS]) investigating whether clopidogrel or Aggrenox best therapeutic route; atrial fibrillation—put patients
on warfarin (Coumadin); explain to patient Coumadin drug of choice
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| Outcome modification: if TIA related to carotid artery, risk for stroke within 30 days as high as 20%; do not wait
weeks for carotid US and specialist follow-up; need to identify modifiable factors such as high BP and age early; clinician
can revascularize, lower BP over time, treat glucose, keep temperature down, and utilize advanced rehabilitation
techniques and stroke facilities to modify stroke outcome; identifying blood vessel blocked in brain now target issue (important
outcome determinant in ischemic stroke [85% of all strokes] in light of new revascularization techniques for large
vessel occlusions)
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| Bleeding in brain or ischemia: first question in traditional approach; heavily based on imaging; speaker advocates
use of spiral CT followed by CT perfusion scan, which allows patients to be imaged with protocol lasting 25 min; can
produce perfusion map of brain
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| CT angiography (CTA): gaining ground as standard of care; can go from vertex of skull through aortic arch down to
diaphragm with single bolus of contrast (70 mL); study—speaker’s experience of 2100 imaging studies using protocol;
data on ≈1000 with follow-up creatinine; of ≈2,000 patients imaged, 2 required temporary hemodialysis due to contrast
nephropathy (deemed “measurable risk” and practice continued for benefits of large-scale data collection); reconstruction
images—data “phenomenal”; can peel bone away to view vessels; speaker’s team prefers “thick nip” reconstruction images;
black and white; sufficient to rule out carotid disease; can produce perisagittal reconstructions; can measure degree
of stenosis accurately on cross-sectional images for which good correlation with catheter-based angiography; negative
predictive value 100%; calcification of plaque may necessitate additional imaging studies; speaker endorses CTA screening
for uncomplicated carotid disease; emerging use of angioplasty for risky intracranial vessels
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| Aneurysms: subarachnoid hemorrhage should be treated as emergency; never submitted for randomized trial; large
movement to adopt endovascular route for treating aneurysm by putting coil inside aneurysm to thrombose it; avoids
craniotomy but requires additional angiography
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| International Subarachnoid Aneurysm Trial (ISAT): published 2 yr ago, follow-up published recently in Lancet
; investigated surgical vs endovascular treatment in randomized trial; surgery associated with higher mortality; study
stopped due to mortality; rebleeding rates similar between 2 arms; more neurosurgeons starting to use coil on aneurysms, but
still need to treat some aneurysms surgically; ideal to offer both treatment options
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| Intracranial hemorrhage due to hypertension: phase 2 trial published in New England Journal of Medicine investigated
use of coagulation factor VIIa (NovoSeven) in patients with hypertensive intracranial bleed; hematoma expansion
primary outcome; if CT performed within few hours of onset (eg, 3 hr), one third of patients have larger hematoma
detected on CT at 6 hr; another trial explored prevention of hematoma expansion; showed hematoma expansion and mortality
reduced if NovoSeven given within 4 hr (surprising outcome); speaker’s group not using NovoSeven because not
yet proven (phase 3 trial ongoing); may see development in this area
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| Ischemic stroke and tPA window: start secondary prevention at time of arrival; for thrombolysis and thrombectomy,
can invoke time window of 0 to 3 hr used to study IV tPA; New England Journal of Medicine published results of trial in
1995 that showed patients randomized to tPA vs placebo within 3 hr have improved neurologic outcome at 90 days; number of
scales indicated neurologic recovery improved if tPA given to proper patient, but not without risk; intracranial hemorrhage rate
6% in patients who received tPA, compared to 0.6% for placebo arm (10-fold increase; half of events fatal, and no difference in
mortality)
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| Informed consent: speaker’s group informs patients and their families about trial results; most patients elect tPA; if use
off-label, inform patients; aim to foster medical system that can respond quickly and carry out ancillary testing and where
patients can opt to “say no” to tPA
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| Use of tPA: emergency medical societies state tPA not standard of care; >50% of EDs in United States not giving tPA; liability
issue; rare for ED physician to take on responsibility; key elements radiology and having neurologist willing to assist in
protocol
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| Primary stroke centers: credentialed by Joint Commission on Accreditation of Healthcare Organizations (JCAHO);
credential improves level of care in institution treating stroke; of >5000 major hospitals in United States, 500 to 600 have
made application; next level comprehensive stroke center with interventional capabilities
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| Intra-arterial prourokinase: PROACT II randomized trial of intra-arterial recombinant prourokinase included patients
that arrived in 3- to 6-hr window; aimed to safely open middle cerebral artery occlusion; 40% of patients achieved
clinical end point, 25% did not (absolute clinical benefit 15%); problem intracranial hemorrhage; FDA has not approved
prourokinase, so most centers using off-label intra-arterial tPA and urokinase to try to open vessels; difficult where large
clot burden exists
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| Thrombectomy: next step; attempted in 1960s but morbid procedure so not pursued; longer catheters can now access all
large vessels in neurovasculature; case report—young man with touch football injury and subsequent embolus; beyond
tPA window on admission; patient underwent attempted thrombectomy for basilar artery occlusion (if untreated, mortality
90%); procedure carries risk of traumatizing vessels (requires blind stick to go through clot); technique—use balloon-guided
catheter to introduce microwire through carotid into blocked vessel; pierce clot with wire; deliver nitinol
memory wire which has distal corkscrew, and embed into clot; proximally, inflate balloon to arrest flow and fragmentation;
pull back and use 100 mL syringe to vacuum out clot
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| Summary: catheter techniques work 48% of time; tPA intra-arterially can achieve opening 60% to 70% of time; pretreating
with tPA, then using device known to be safe; most stroke neurologists believe IV tPA proven to improve outcome,
and FDA approved label change to allow for acute ischemic stroke; prourokinase believed to work but not approved;
thrombectomy not proven and not tested in randomized trial, so can be said to restore perfusion in ischemic stroke but not
treat ischemic stroke (approved because device not drug)
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Educational Objectives
| The goal of this program is to educate the listener about emergency care for stroke and new diagnostic and treatment issues
in transient ischemic attack (TIA) and stroke. After hearing and assimilating this program, the clinician will be better able
to:
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| 1. Evaluate a stroke patient using key diagnostic criteria.
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| 2. Discuss the findings of the National Institute of Neurological Disorders and Stroke (NINDS) trial of tissue plasminogen
activator (tPA) therapy and the implications for patients and families making decisions about stroke treatment.
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| 3. List 5 clinical factors that enhance the likelihood of stroke after a transient ischemic attack (TIA).
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| 4. Identify the risk factors and modifiable risk factors in determining a course of treatment for a patient with acute
stroke.
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| 5. Become aware of new uses of catheter techniques and computed tomography angiography in stroke.
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Discussed on This Program
Aspirin (acetylsalicylic acid; ASA) [several trade names]
Coagulation factor VIIa (recombinant) [NovoSeven]
Clopidogrel bisulfate [Plavix]
Dipyridamole and aspirin [Aggrenox]
PROACT (Prolyse {recombinant prourokinase} in acute cerebral thromboembolism) (investigational)
Tissue plasminogen activator, recombinant (tPA)
Warfarin sodium [Coumadin]
Suggested Reading
Adams HP Jr: Treatment of acute ischemic stroke: selecting th.right treatment for the right patient. Eur Neurol 45:61,
2001; Ay H et al: Transient ischemic attack: are there different types or classes? Risk of stroke and treatment options.
Curr Treat Options Cardiovasc Med 8:193, 2006; Berthet JP et al: Acute carotid artery thrombosis: description of 12
surgically treated cases. Ann Vasc Surg 19:11, 2005; Brown DL et al: Survey of emergency physicians about recombinant
tissue plasminogen activator for acute ischemic stroke. Ann Emerg Med 46:56, 2005; Bruno A: Predicting rtPA associated
ICH in acute stroke. Stroke 35:2762; author reply 2762, 2004; Epub 2004 Oct 28. Chuang YM et al: Use of
CT angiography in patient selection for thrombolytic therapy. Am J Emerg Med 21:167, 2003; Deshmukh VR et al:
Intra-arterial thrombolysis for acute ischemic stroke: preliminary experience with platelet glycoprotein IIb/IIIa inhibitors as
adjunctive therapy. Neurosurgery 56:46, 2005; Frey JL: Recombinant tissue plasminogen activator (rtPA) for stroke.
The perspective at 8 years. Neurologist 11:123, 2005; Furlan AJ et al: When is thrombolysis justified in patients with
acute ischemic stroke? A bioethical perspective. Stroke 28:214, 1997; Giles MF et al: Patient behavior immediately after
transient ischemic attack according to clinical characteristics, perception of the event, and predicted risk of stroke.
Stroke 37:1254, 2006; Epub 2006 Mar 30. Gutierrez M et al: Thrombolysis and neuroprotection in cerebral ischemia.
Cerebrovasc Dis 21 Suppl 2:118, 2006; Epub 2006 May 2. Imai K et al: Successful thrombectomy in acute terminal internal
carotid occlusion using a basket type microsnare in conjunction with temporary proximal occlusion: a case report.
AJNR Am J Neuroradiol 26:1395, 2005; Kent DM et al: Sex-based differences in response to recombinant tissue plasminogen
activator in acute ischemic stroke: a pooled analysis of randomized clinical trials. Stroke 36:62, 2005; Epub 2004
Nov 29. Kwiatkowski T et al: National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen
Activator Stroke Study Group. The impact of imbalances in baseline stroke severity on outcome in the National Institute
of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study. Ann Emerg Med
45:377, 2005; Pomerantz SR et al: Computed tomography angiography and computed tomography perfusion in ischemic
stroke: A step-by-step approach to image acquisition and three-dimensional postprocessing. Semin Ultrasound CT
MR 27:243, 2006; Reeves MJ et al: Acute stroke care in the US: results from 4 pilot prototypes of the Paul Coverdell
National Acute Stroke Registry. Stroke 36:1232, 2005; Epub 2005 May 12. Erratum in: Stroke. 2005 Aug;36(8):1820.
Smith WS: Safety of mechanical thrombectomy and intravenous tissue plasminogen activator in acute ischemic stroke.
Results of the multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial, part I. AJNR Am J Neuroradiol
27:1177, 2006; Suzuki S et al: Use of multimodal MRI and novel endovascular therapies in a patient ineligible for intravenous
tissue plasminogen activator. Stroke 36: e77, 2005; Epub 2005 Jul 28. Sylaja PN et al: Role of CT angiography
in thrombolysis decision-making for patients with presumed seizure at stroke onset. Stroke 37:915, 2006; Epub 2006 Feb 2.
Tanne D et al: Hemostatic activation and outcome after recombinant tissue plasminogen activator therapy for acute ischemic
stroke. Stroke 37:1798, 2006; Epub 2006 Jun 8. Toni D et al: Specific therapies for ischaemic stroke: rtPA and
others. Neurol Sci 26 Suppl 1:S26, 2005; Zaidat OO et al: Thrombolytic therapy of acute ischemic stroke: correlation
of angiographic recanalization with clinical outcome. AJNR Am J Neuroradiol 26:880, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Sattin spoke at Critical Care, held July 21-23, 2005, in San Diego, CA, and sponsored by the University of California,
San Diego, School of Medicine. Dr. Smith spoke at Topics in Emergency Medicine, held October 24-27, 2005,
in San Francisco, CA, and sponsored by the University of California, San Francisco, School of Medicine. The Audio-
Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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