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Journal of Symptoms and Signs 2012; Volume 1, Number 4

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146
Review
Transient ischemic attack: Definitions and controversies
Vijayabala Jeevagan, MBBS
1
, Subathra Saravanabavananthan, MBBS
2
, Harindra Karunathilake, MBBS,
MRCP, MD
3

National Hospital of Sri Lanka
1
, Teaching Hospital Jaffna
2
, Teaching hospital Pollannaruwa, Sri Lanka
3
.
Corresponding Author: Vijayabala Jeevagan , 165E, Vipulasena Mawatha Colombo 10, Sri Lanka. E-mail: jeevaganv@yahoo.com.
Abstract
The definition of TIA has always been a matter of debate. The traditional definition is time based and new
definition is tissue based. Both the time based and tissue based definition are not accurate. Here we propose
the universal term acute ischemic neurovascular syndrome (AINS) for all patients with symptoms suggestive
of focal neurological deficit of presumed ischemic origin. AINS can be further divided into transient ischemic
attack (TIA), transient symptoms with infarction (TSI) and ischemic stroke (IS) on the basis of clinical and
imaging findings. Each syndrome is associated with distinct clinical, imaging and prognostic features. Exten-
sive review that took clinical and imaging features into account suggests it might be more rational to consider
TSI as separate clinical syndrome. TSI is the most unstable syndrome, it is associated with the greatest risk of
recurrent stroke, which indicate that the underlying stroke mechanism is active.
Keywords: transient ischemic attack; stroke; transient symptoms with infarction.
Received: August 8, 2012; Accepted: September 23, 2012; Published: December 15, 2012

Introduction
Stroke is common and causes considerable morbidity and
mortality. Because transient ischemic attacks (TIA) pre-
cede approximately one third of strokes, treatment of TIA
offers an opportunity for prevention [1]. However TIAs
are often under recognized and under treated, due to in-
adequate appreciation of the gravity and the urgency
needed to intervene when TIAs occur.
The definition of TIA is always a matter of debate.
The traditional definition is time based and the new one
is tissue based. Since the larger medical community grew
up comfortably with the traditional definition, the new
tissue based definition is not widely accepted. In addition
the tissue based definition creates several new problems.
This article extensively reviews the problems of tissue
based definition and proposes a better way of classifying
ischemic cerebrovascular events.
Traditional Definition of TIA
Traditionally TIA is defined as sudden, focal neurologi-
cal deficit of presumed vascular origin that lasts for less
than 24 hours. It is based on the assumption that the tran-
sient symptoms disappear completely because permanent
brain injury has not occurred. This was formulated in
time when there were no proper neuroimaging modalities
to identify brain infarction or ischemia [2]. With the ad-
vent of diffusion weighted magnetic resonance imaging
[DWI MRI], it is now demonstrated that many transient
ischemic events are associated with infarction [3- 6].
Even though we are very familiar with this definition,
there are drawbacks. The 24 hour threshold is arbitrary.
In fact most of the TIAs typically resolve within 60
minutes. It does not help to determine which events in-
volve brain infarction. Both medical and non medical
personal do not realize the gravity of TIA and tend to
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consider TIA as benign whereas they regard stroke as
serious [2].
Tissue Based Definition of TIA
In tissue based definition, TIA is defined as transient
episode of neurological dysfunction caused by focal brain,
spinal cord, or retinal ischemia, without acute infarction
[7]. This new definition encourages the early use of neu-
roimaging (ideally DWI MRI) in the acute phase [7, 8].
The DWI MRI will help to differentiate TIA and TSI
(Transient symptoms with infarction) where both clini-
cally resolve within 24 hours. Since the new definition
requires DWI MRI, incidence of stroke and TIA will vary
depending on availability of imaging modalities.
Risk Prediction Models
The ABCD2 score which incorporates age, blood pres-
sure, clinical symptoms, and diabetes is used to identify
patients at high risk of developing ischemic stroke after a
TIA [9-12]. This score does not incorporate imaging
findings, which also predicts the recurrence. Patients with
TIA with positive DWI MRI finding (TSI) have 2 to
15-fold increase in subsequent short term risk of stroke
[13-16]. Risk prediction models that combine both imag-
ing and clinical features predict the early risk of stroke
after TIA with higher sensitivity and specificity [17-19].
The most compelling evidence comes from a recent
multicenter study by Giles, et al. which includes a total
of 4,574 patients with classically defined TIA [20].
Among the 3,206 patients who had a DWI MRI, 27.6%
had evidence of infarction. The 7-day stroke risk among
patients with acute infarction on DWI MRI (7.1%) was
substantially greater than those without acute infarction
on (0.4%). The ABCD2 score was predictive of early
stroke risk in those with and without infarction. Thus the
combination of both the imaging information as well as
the ABCD2 score is important in assessing short term
risk of stroke after TIA.
TSI is a Unique Syndrome
Studies which incorporated DWI MRI findings to risk
prediction model consistently showed that TSI has a
greater risk for recurrent IS (ischemic stroke) than TIA
without infarction. The risk of stroke during acute
hospitalization ranged from 8.3% to 14.8% [4, 21, 22].
In contrast, the short term risk of TIA or stroke among
those with true TIA (TIA without infarction) ranged
from 0.1% to 2% [20, 21]. Similarly IS patients have
substantially lower risk of early recurrent stroke: 1.2%
to 8.4% [23-26].
It is clear TSI behave distinctly from true TIA or IS.
TSI appears to be the most unstable event, it is associ-
ated with greater risk of IS and needs more urgent and
intensive care to prevent recurrent ischemic events.
According to the current definition TSI and IS are
considered to be the same. IS has permanent disability
and has low recurrent risk of ischemic events. The
only similarity between TSI and IS is the evidence of
infarction in the imaging. It is not justifiable to con-
sider TSI and IS as similar entity based on pathologi-
cal findings. It is reasonable to consider TSI as a
unique entity with distinct prognostic implications
compared with IS or true TIA. Some experts use the
term minor stroke instead of TSI [27]. We believe TSI
is more appropriate because the word minor stroke
merely means minor infarction and does not imply the
unique behavior of TSI (Table 1).
Table 1.
Clinical
syndrome
Definition
TIA Abrupt neurological dysfunction which
last less than 24 hours, caused by focal
brain, spinal cord, or retinal ischemia,
without acute infarction
TSI Abrupt neurological dysfunction which
last less than 24 hours, caused by focal
brain, spinal cord, or retinal ischemia,
with evidence of acute infarction
IS Abrupt neurological dysfunction which
last more than 24 hours, caused by focal
brain, spinal cord, or retinal infarction
AINS Abrupt neurological dysfunction caused
by focal brain, spinal cord or retinal is-
chemia of presumed vascular origin
Abbreviations: TIA-Transient ischemic attack; TSI
-Transient symptoms with infarction; IS- Ischemic stroke
AINS - Acute ischemic neurovascular syndrome.
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148
Is Tissue Based Definition the
Answer?
In the next paragraphs, we will critically review the
five arguments that are commonly used in favor of the
new definition, to see how realistic they are.
Argument 1: The classic 24 hours definition is mis-
leading in that many patients with transient < 24-hour
events actually have associated cerebral infarction.
There is no time limit which correctly differentiates
ischemia from infarction. It is not known whether the
differentiation based on time limit has clinical signifi-
cant especially in management or risk prediction.
Identifying the high risk patient for recurrence and
intensifying the treatment is crucial in the management
of TIA. Furthermore, TSI is more similar to TIA than
IS, that is in TSI symptoms are transient and the re-
current risk of stroke is greater. It is wise to consider
TSI as separate entity and not together with IS as in
the new definition.
Argument 2: The traditional definition suggests that
the transient symptoms are benign.
The risk of early stroke after true TIA is negligible
(<1%) even with high ABCD2 score [20]. True TIA is
a benign entity with a favorable prognosis. However
individual risk for recurrence depends on several other
factors, for example patient with atrial fibrillation has
high risk of recurrence irrespective of whether infarc-
tion has occurred or not. Presence or absence of in-
farction is not a sole discriminating factor to differen-
tiate benign from serious event. To the contrary, cur-
rent definition strengthens the concept that TIAs are
benign while they are not always. Considering all is-
chemic neurovascular events as a single entity may
resolve this problem. In addition both medical per-
sonnel and public should be educated about the seri-
ousness of TIA and need of urgent intervention irre-
spective of whether infarction is seen in DWI MRI or
not.
Argument 3: The traditional definition can impede the
acute stroke therapies.
It is said that the traditional definition has the poten-
tial to delay initiation of acute stroke therapies, partic-
ularly thrombolytic therapy which has a therapeutic
time window of 4.5 hours from the onset. However, in
patients with signs of improving neurological deficits
irrespective of DWI MRI finding, the risk benefit ratio
does not justify administrating thrombolytic therapy. It
is inescapable that few patients with TIA may receive
thrombolytic therapy without DWI MRI. However,
this is a minority since the majority of the TIAs are
brief, lasting less than an hour and brain infarction are
almost invariable in patients with symptoms lasting
longer. Furthermore currently there is no sufficient
evidence to use DWI MRI finding in selecting patients
for thrombolytic therapy [28, 29].
Argument 4: A 24-hour limit for transiently sympto-
matic cerebral ischemia is arbitrary and not reflective
of the typical duration of the events.
The traditional definition classifies stroke and TIA
depending on degree of disability and rate of subse-
quent recurrence. Even though the deficit is transient
in TIA, risk of early stroke is high and paradoxically,
the risk of subsequent ischemic stroke is less after
completed stroke. Almost all risk prediction models
incorporate 24 hour time limit to define TIA, despite
of TIAs typically last less than an hour [9-12, 17-19].
Therefore the 24 hour time limit has implication in
management and prognosis.
Argument 5: Disease definitions in clinical medicine,
including those for ischemic injuries, are most useful
when tissue based.
In modern day medicine nomenclature of disease
mainly based on current treatment and prognostic need
of the patients rather than pathology. Likewise in pa-
tient with acute coronary syndrome (ACS) the first
step is to differentiate the patients with ST elevation
ACS from non ST elevation ACS (not patient with
unstable angina from myocardial infarction) because it
has implication in immediate management. There is no
such thing as electrocardiography (ECG) in neurology
to differentiate patients who requires thrombolysis
from who do not. Therefore it is not convincing that
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the tissue based definition would harmonize cerebro-
vascular nosology with other ischemic conditions.
Acute Ischemic Neurovascular
Syndrome
Both the time based and tissue based definition are not
perfect. TIA and IS share common etiology, pathophysi-
ology and treatment. Broader acceptance of the concept
of acute ischemic neurovascular syndromes (AINS)
might be a good first step. AINS is defined as abrupt
neurological dysfunction caused by focal brain, spinal
cord or retinal ischemia of presumed vascular origin.
AINS can be further subdivided into TIA, TSI and IS on
the basis of duration of symptoms and whether infarction
occurs or not. However arbitrary it may be, we believe
that 24 hour time limit should be considered to differen-
tiate TIA or TSI from IS. The main aim of this differenti-
ation is to identify the patient with high risk of recurrence
for which available risk prediction models consider 24
hour time limit. The term Acute ischemic cerebrovascu-
lar syndrome already proposed as a universal term [30,
31]. We prefer neurovascular syndrome rather than cere-
brovascular syndrome, because neurovascular syndrome
is a broader term which will denote ischemic injury to
brain, retina and spinal cord.
The concept of AINS offers a number of important
advantages over prior terminology. The term AINS is in
a manner analogous to ACS, it will harmonize cerebro-
vascular nosology with cardiovascular nosology. It em-
phasizes the similar etiology, pathophysiology, and
prognosis for recurrence of any neurovascular ischemic
event. It also provides a frame work for patient triage,
further investigation and treatment. Because it serve as
umbrella term for all patient with presumed ischemic
neurovascular deficit, it is unlikely both medical and non-
medical professionals consider AINS as a benign entity.
Conclusions
Clinical and pathological correlation is the hallmark of
modern medical diagnosis. The new definition of TIA is
solely tissue based and lack clinical correlation. Acute
ischemic neurovascular syndrome is an umbrella term for
all patients with symptoms suggestive of focal neurolog-
ical deficit of presumed ischemic origin. This syndrome
is similar to acute coronary syndrome in cardiology.
Acute ischemic neurovascular syndrome can be further
separated into TIA, TSI and IS on the basis of clinical
and imaging findings. Whatever definition used it is ut-
most important to identify and treat the underlying
mechanism of each individual event.
Disclosure
There are no conflicts of interest.
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Copyright: 2012 Vijayabala Jeevagan, et al. This is an Open
Access article distributed under the terms of the Creative Com-
mons Attribution License, which permits unrestricted use, dis-
tribution, and reproduction in any medium, provided the original
work is properly cited.

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