transient ischemic attack

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

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Review

Transient ischemic attack: Definitions and controversies

Vijayabala Jeevagan, MBBS1, Subathra Saravanabavananthan, MBBS

2, Harindra Karunathilake, MBBS,

MRCP, MD 3

National Hospital of Sri Lanka1, Teaching Hospital Jaffna

2, Teaching hospital Pollannaruwa, Sri Lanka

3.

Corresponding Author: Vijayabala Jeevagan , 165E, Vipulasena Mawatha Colombo 10, Sri Lanka. E-mail: [email protected].

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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Transient ischemic attack

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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.



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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