2008 Clinical Decisions in Emergency Medicine
“Transient Ischemic Attack Patient Update:
The Optimal Management of Emergency Department Patients
With Suspected Cerebral Ischemia”
Cerebral Ischemia and Transient Ischemic Attacks:
Definitions and a Historical Perspective
J Stephen Huff, MD, FACEP
Associate Professor of Emergency Medicine & Neurology
University of Virginia
Charlottesville, VA
Learning Objective and Key Clinical Questions
Assess the clinical significance of how the definition of cerebral
ischemia and transient ischemic attacks has evolved over time.
How are TIA, RIND, cerebral ischemia, and cerebral stroke defined?
What are the epidemiology and outcomes of patients with cerebral
ischemia?
How have these definitions changed over time and for what reasons,
including the progress of advanced neuroimaging?
Has the outcomes of these cerebral ischemia patients changed over
time as the definitions have changed?
Optimizing ED TIA Patient Management:
TIA Definitions & Historical Perspectives
2008 FERNE / Clinical Decisions in Emergency Medicine
J. Stephen Huff MD, FACEP
Page 2 of 7
Key Clinical Questions and Learning Points
How are TIA, RIND, cerebral ischemia, and cerebral stroke defined?
Definitions are changing for TIA and stroke. TIA, or transient ischemic attack, has
traditionally been defined as a stroke syndrome that is time-limited with complete
resolution. Even though it has long been recognized that most TIAs resolve over
minutes, and that the longer ischemic symptoms persist, the more likely a stroke is
present, research criteria and consensus opinion arbitrarily defined a TIA as having
resolution of signs and symptoms within 24 hours of onset.
Implicit in the definition is that there must be some pre-test probability assessment of a
transient symptom or sign having ischemic pathophysiology. Symptoms lasting seconds
are unlikely to be ischemic in etiology. Simple dizziness or vertigo, without associated
signs and symptoms, is unlikely to be ischemic in origin. Transient loss of
consciousness (syncope) or seizures are not TIA syndromes. The symptoms of
ischemia are usually negative in nature, that is neurologic deficits, rather than positive
symptoms such as shaking. “Marching” of symptoms up an extremity, such as
progression of a deficit or paresthesias, also suggests non-ischemic pathophysiology.
RIND, or reversible ischemic neurologic deficit, was defined in the past by consensus as
a stroke syndrome with resolution of signs and symptoms within 6 weeks. RIND has
fallen from clinical usage.
An ischemic stroke is an enduring neurologic syndrome with pathophysiology from
embolic or thrombotic causes.
What are the epidemiology and outcomes of patients with transient
ischemic attack?
It is estimated that there are 200,000-500,000 patients with transient ischemic attack in
the United States each year. Outcomes data is still being accumulated especially as
definitions are revised. It is estimated that somewhere between 2-13% of patients with
transient ischemic attack will develop a stroke within one month, and up to one-third
within 5 years.
In some studies, high early risk of stroke following TIA has been found with up to onehalf of the strokes occurring within 48 hours.
Optimizing ED TIA Patient Management:
TIA Definitions & Historical Perspectives
2008 FERNE / Clinical Decisions in Emergency Medicine
J. Stephen Huff MD, FACEP
Page 3 of 7
How have these definitions changed over time and for what reasons,
including the progress of advanced neuroimaging?
Definition of transient ischemic attack is blurring with that of stroke. With advances in
neuroimaging, TIA patients are increasingly identified whom have clinically transient
events with resolution of deficits, but with abnormalities found on special neuroimaging.
Diffusion-weighted MRI is an increasingly employed technology for patients with stroke
and TIA. A new syndrome of TIA with DWI abnormality is being defined.
The definition of TIA is being revised to reflect tissue-based pathology instead of a timereferenced definition. This implies that advanced neuroimaging is necessary to
distinguish TIA patients with and without neuroimaging (MRI-DWI) abnormalities.
Has the outcomes of these cerebral ischemia patients changed over
time as the definitions have changed?
Clearly the natural history of TIA patients is being further delineated with improved
neuroimaging. The hope would be that subsets of patients might be identified where
interventions might moderate stroke rate following TIA. Outcomes data is lagging.
Antiplatelet agents, notably aspirin, seem to show risk reduction of stroke and other
vascular events following TIA of approximately 20%. Other antiplatelet regimens
including clopidegrel, ticlopidine, or combination treatments may be slightly better
though arguably definitive data is lacking.
A few sub-groups have been identified where interventions do limit subsequent stroke
risk. Patients with TIA and significant carotid stenosis > 70% do have reduction in stroke
risk following endarterectomy. For patients with carotid stenosis < 70%, antiplatelet
medical treatment seems to be equal to surgical management.
In patients with atrial fibrillation and TIAs, anticoagulation with warfarin has been shown
to be superior to antiplatelet therapy in preventing strokes.
Optimizing ED TIA Patient Management:
TIA Definitions & Historical Perspectives
2008 FERNE / Clinical Decisions in Emergency Medicine
J. Stephen Huff MD, FACEP
Page 4 of 7
Are there publications that help the emergency physician
with the approach to assessment of TIA patients?
___________________________________________________________
TIA, RIND, minor stroke: a continuum, or different
subgroups?
Koudstall PJ, van Gijn J, Frenken CWGM, Hijdra A, Lodder A,
Vermeulen M, Bulens C, Franke CL (for the Dutch TIA Study Group)
J Neurol, Nsurg, Psych 1992;55:95-97.
One of the first articles to advance the argument that these time-defined
clinical entities should be thought of as existing along a continuum rather
than as separate groups. Cranial CTs were obtained more than 24 hours
after the neurologic event. CT abnormalities showed relevant ischemic
lesions in 13% of patients with clinical TIA (<24 hour definition), 35% of
patients with RIND, and 49% of patients with minor stroke. CT infarction
patterns were present more often with longer symptom duration but were
also found in some patients with symptoms lasting less than a minute.
___________________________________________________________
The duration of symptoms in transient ischemic attack
Kimura K, Minematsu K, Yasaka M, Wada K, Yamaguchi T
Neurology 1999;52:976-980.
Clinical records were reviewed of 81 patients with carotid distribution TIA.
Patients were investigated with brain imaging (CT or MR) , EKG
monitoring, and transthoracic echocardiography, and carotid ultrasound.
TIA of longer duration (> 60 minutes) was associated with the presence of
emboligenic cardiac disease or arterial disease. Recent infarcts on CT
were seen more frequently in patients with longer duration TIA.
Optimizing ED TIA Patient Management:
TIA Definitions & Historical Perspectives
2008 FERNE / Clinical Decisions in Emergency Medicine
J. Stephen Huff MD, FACEP
Page 5 of 7
___________________________________________________________
Timing of TIAs preceding stroke: time window for prevention
is very short
Rothwell PM, Warlow CP
Neurology 2005;64:817-820
Retrospective review of patients with acute ischemic stroke from two
studies who reported preceding TIA symptoms. 23% of patients gave a
history of TIA before their stroke with 17% of those TIAs occurring the day
of infarction, 9% on the previous day, and 43% at some point during the
prior 7 days.
___________________________________________________________
Head computed tomography findings predict short-term
stroke risk after transient ischemic attack
Douglas VC, Johnston CM, Elkins J, Sidney S, Gress D, Johnston SC
Stroke 2003;34:2894-2899
67% of patients presenting to EDs that received a diagnosis of TIA had CT
scans performed within 48 hours. Evidence of new infarct was found in 4%.
A nonischemic cause of TIA was found in 1.2% (tumors, chronic subdural
hematoma). Risk of stroke during 90 day followup was higher in TIA
patients that had a new infarct on CT. Patients with TIA and resolved
symptoms with evidence of acute infarction on head CT may make up a
population especially vulnerable to stroke.
Optimizing ED TIA Patient Management:
TIA Definitions & Historical Perspectives
2008 FERNE / Clinical Decisions in Emergency Medicine
J. Stephen Huff MD, FACEP
Page 6 of 7
___________________________________________________________
DWI abnormalities and clinical characteristics in TIA patients
Inatomi Y, Kimura K, Yonehara T, Fujioka S, Uchino M
Neurology 2004;62:376-380
129 consecutive patients with TIA had MRI with DWI performed within 14
days. DWI demonstrated recent ischemic lesions in 44%. Prolonged TIA
duration (> 30 minutes) and symptoms or signs of disturbances of higher
brain function (aphasia, hemianopia, unilateral spatial neglect) were
significant and independent factors associated with DWI abnormalities.
___________________________________________________________
Transient ischemic attack and stroke can be differentiated by
analyzing early diffusion-weighted imaging signal intensity
changes
Winbeck K, Bruckmaie K, Etgen T, von Einsiedel HG, Rottinger M,
Sander D
Stroke 2004;34:1095-1099
DWI was performed within 24 hours after symptom onset in 60 patients
with TIA and 37 patients with stroke. Patients with stroke had significantly
higher DWI signal than that of patients with TIA. The authors suggest that
DWI can differentiate stroke from TIA in patients as little as 6 hours from
syndrome onset.
Optimizing ED TIA Patient Management:
TIA Definitions & Historical Perspectives
2008 FERNE / Clinical Decisions in Emergency Medicine
J. Stephen Huff MD, FACEP
Page 7 of 7
___________________________________________________________
Transient ischemic attack – proposal for a new definition
Albers GW, et al for the TIA Working Group
N Engl J Med 2002;347:1715-1716
The redefinition of TIA: the uses and limitations of DWI in
acute ischemic cerebrovascular syndromes
Warach S, Kidwell CS
Neurology 2004;62:359-360
Albers et al state the proposal for tissue-based new definition of TIA,”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.” Stroke / infarction is defined by
persistent clinical signs or characteristic imaging abnormalities. The
arbitrary time criterion of 24 hours is dismissed in this new definition. The
second reference above discusses some advantages and limitations of
DWI use.
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