Transient ischemic attack: definitional evolution, clinical manifestations, diagnostic evaluation, and treatment strategies

Neuro Times

Transient ischemic attack (TIA) is one of the acute ischemic cerebrovascular diseases and is a high-risk signal
for ischemic stroke.
Numerous studies have shown that patients with TIA are at high risk
of stroke in the near future.
Related meta-analyses indicate that the risk of stroke on days 2, 7, 30 and 90 after TIA is 3.
5%, 5.
2%, 8.
0% and 9.
2%,
respectively.
Early intervention and treatment of TIA patients can significantly reduce the risk of stroke recurrence and reduce the burden
of stroke disease.

The evolution of the TIA definition

In 1958, the famous neurology professor Miller Fisher proposed the prototype of the concept of TIA, and proposed the clinical characteristics of TIA for the first time: symptoms can last for minutes to hours, but most attacks are 5~10 minutes
.

The Fourth Princeton Conference in 1965 and the Classification of Cerebrovascular Diseases issued by the National Institutes of Health in 1975 established the traditional "time-symptomatic" definition of TIA: sudden onset of focal or brain-wide neurological dysfunction lasting no more than 24 hours, excluding non-vascular causes
.

In 2002, the US TIA working group proposed a new definition: transient neurological deficit due to local brain or retinal ischemia, typical clinical symptoms lasting no more than 1 h, and no evidence
of acute cerebral infarction on imaging.

In 2009, the American Stroke Association (ASA) again updated the definition of TIA as transient neurologic deficit
caused by focal ischemia of the brain, spinal cord, or retina without acute infarction.

The evolution of the definition of TIA reflects the gradual deepening
of people's understanding of TIA as a disease.
Before the 70s of the 20th century, when imaging examination was not yet developed, people relied more on symptoms and symptom duration to define TIA, but with the development of neuroimaging, the gradual popularization of magnetic resonance examination techniques such as DWI has challenged
the traditional definition of "time-symptomatic" TIA 。 Studies have shown that 30%~50% of TIA patients diagnosed by the traditional "time-symptom" definition have new cerebral infarction in DWI, in view of this, in 2009, the new TIA definition believes that the presence or absence of infarction lesions is the only basis for differential diagnosis of TIA and cerebral infarction, regardless of the duration of symptoms, and the new definition dilutes the concept of "time-symptoms" and emphasizes "histological damage"
.
In addition, the new definition also includes acute transient neurological deficits caused by spinal cord ischemia under the category
of TIAs.

Table 1 Clinical manifestations of TIA compared between the traditional definition of TIA and the new definition

1.
General features

TIA tends to occur in middle-aged and elderly people, more men than women, and patients are often associated with risk factors
for vascular diseases such as hypertension, atherosclerosis, diabetes or hyperlipidemia.
The onset is sudden, often recurrent, and local brain or retinal dysfunction lasts briefly, with a maximum < of 24 h without leaving sequelae
.

TIA due to hemodynamic changes is clinically similar or rigid
because the ischemic site is basically the same for each attack.
TIA due to microembolism has a variable
clinical presentation depending on the blood vessels and sites affected by each attack.

2.
TIA of the internal carotid artery system

The median duration of neurological deficit was 14 minutes
.
Clinical manifestations are related
to the distribution of affected vessels.

(1) TIA in the middle cerebral artery blood supply area: monopalsis, hemiparesis, facial paralysis and tongue paralysis of the opposite limb of ischemia can occur, which can be accompanied by hemisensory impairment and contralateral homologous hemianopia, aphasia and apraxia often occur when the dominant hemisphere is damaged, and spatial disorientation can occur when the non-dominant hemisphere is damaged
.

(2) TIA in the anterior cerebral artery supply area: personality and affective disorders, contralateral lower limb weakness
may occur.

(3) Ischemia in the blood supply area of the ocular branch of the internal carotid artery shows gray sensation, cloudy or blurred vision in front of the eyes, and even transient blackness and blindness
in one eye.

(4) Ischemia in the main blood supply area of the internal carotid artery can be manifested as ophthalmic artery cross paralysis (transient amaurosis of the affected side, blindness and/or contralateral hemiplegia and sensory impairment), Homner cross paralysis (Horner sign on the affected side, contralateral hemiplegia).

3.
Vertebrobasilar system TIA

The median duration of neurological deficit was 8 minutes
.
The most common presentations are vertigo, balance disturbances, eye movement abnormalities, and diplopia
.
There may be unilateral or bilateral facial and perioral numbness, isolated or accompanied by contralateral limb paralysis, sensory impairment, and typical or atypical brainstem ischemic syndrome
.

In addition, TIA of the vertebrobasilar artery system can also have the following clinical syndromes with specific manifestations:

(1) Fall seizure: manifested as a sudden loss of tension in the lower limbs and falling, unconscious loss, often can quickly stand up on its own, caused by
ischemia of the lower reticular structure of the brain stem.
Sometimes seen when
the person turns or tilts his or her head.

(2) Transient global amnesia: short-term memory loss at the time of the attack, disorientation to time and place, but normal conversation, writing and calculation skills, general symptoms last for several hours, and then completely improve, leaving no memory damage
.
The pathogenesis is still unclear, and some of the pathogenesis may be due to
ischemia of the posterior cerebral artery temporal branch involving the temporal hippocampus, parahippocampal gyrus, and fornix of the limbic system.

(3) Onset of binocular visual impairment: bilateral posterior cerebral artery talar branch ischemia leads to occipital lobe visual cortex involvement, causing temporary cortical blindness
.

Of note, patients with TIA of the vertebrobasilar system rarely present with isolated symptoms of vertigo, tinnitus, nausea, syncope headache, urinary and fecal incontinence, lethargy, or seizures, often with symptoms and/or signs
of ischemia in other brainstem or posterior cerebral artery supply areas.

Early diagnosis and evaluation of TIA

The high-risk period of stroke is within 2~7 days after the onset of TIA, and urgent evaluation and intervention of patients can reduce the occurrence of
stroke.
Clinicians should also make relevant preparations in advance, once the TIA is transformed into cerebral infarction, do not delay thrombolytic therapy
by waiting for results such as coagulation function.

New-onset TIA is treated as an emergency, and if the patient is within 72 hours of symptom onset and has one of the following conditions, hospital admission is recommended: (1) ABCD2 score ≥ 3; (2) Patients with ABCD2 score of 0~2 points, but cannot guarantee that they can complete the system examination in the outpatient clinic within 2 days; (3) ABCD2 score 0~2 points, and other evidence suggests that symptoms are caused by
ischemia.

Table 2 ABCD2 Rating Scale

Note: ABCD2 score 0~3 is judged as a low-risk group; 4~5 is divided into medium risk groups; 6~7 is divided into high-risk groups
.

Patients with new-onset TIA are examined and evaluated as follows:

1.
General examination: evaluation includes electrocardiogram, complete blood count, coagulation function, blood electrolytes, renal function, and rapid blood glucose and lipid measurement
.

2.
Vascular examination: CT angiography (CTA), magnetic resonance angiography (MRA), angiography, and pan-cerebral angiography (DSA) can detect important intracranial and extracranial vascular lesions
.
DSA is the gold standard
for preoperative evaluation of carotid endarterectomy (CEA) and carotid artery stent therapy (CAS).

3.
Collateral circulation compensation and cerebral blood flow reserve assessment: the use of DSA, cerebral perfusion imaging and/or transcranial color Doppler ultrasound (TCD) examination to evaluate collateral circulation compensation and cerebral blood flow reserve is necessary
to identify hemodynamic TIA and guide treatment.

4.
Examination of vulnerable plaques: Vulnerable plaques are an important source of
arterial emboli.
Vascular ultrasound, endovascular ultrasound, high-resolution MRI, and TCD microemboli monitoring are helpful in evaluating vulnerable plaques in
atherosclerosis.

5.
Cardiac evaluation: if cardioembolism is suspected, or if the cause cannot be identified by neck and cerebrovascular examination and hematological screening under 45 years of age, transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TEE) examination is recommended, which may find multiple embolus sources
such as cardiac wall thrombosis, abnormalities of atrial septum (atrioventricular aneurysm, patent foramen ovale, atrial septal defect), mitral valve vegetation, and aortic toxosclerosis.

6.
Do other relevant tests
according to the medical history.

Fig.
1 Triage process of stroke patients

Treatment of TIA

1.
Drug treatment

(1) Antiplatelet therapy

Noncardioembolic TIAs recommend antiplatelet therapy
.

Patients with acute non-cardiac TIA or mild ischemic stroke (NIHSS score ≤3) who are at high risk of stroke recurrence (ABCD2 score ≥4) within 24 hours of onset should be given aspirin plus closengrel as soon as possible for 21 days
.

Patients with TIA with symptomatic intracranial artery stenosis (stenosis rate 70%~99%) within 30 days of onset should be treated with aspirin combined with clopidogrel for 90 days
as soon as possible.

Other TIAs or small strokes are generally used alone: (1) aspirin (50~325 mg/d); (2) clopidogrel (75 mg/d); (3) Aspirin and extended-release dipyridamole (25 mg and 200 mg, 2 times/day, respectively).

(2) Anticoagulant therapy

Anticoagulation is generally recommended for cardioembolic TIAs, which can be started as early as possible after neuroimaging has ruled out intracerebral haemorrhage
.

It mainly includes heparin, low molecular weight heparin, warfarin and new oral anticoagulants (such as dabigatran rivaroxaban, apixaban, edoxaban, etc.
).

Generally, short-term use of heparin is changed to oral anticoagulant warfarin treatment, and the goal of warfarin treatment is to reach the international normalized ratio (INR) of 2~3, and the dosage is adjusted
according to the results.

Patients with TIA at high risk of stroke should be treated with heparin with a shorter half-life and easier neutralization of anticoagulant strength; Once TIA is transformed into cerebral infarction, the abnormality of coagulation function can be quickly corrected to meet the criteria
for thrombolytic therapy.

Frequent episodes of TIA or vertebrobasilar system TIA, and cases that do not respond to antiplatelet therapy
, may also be considered for anticoagulation.
Low-dose aspirin or dipyridamole may also be added
to patients with TIA who are at high risk of stroke, such as after prosthetic heart valve replacement, when oral anticoagulant therapy is not effective.

(3) Expansion therapy

Corrects hypoperfusion, suitable for hemophilia-type TIA
.

(4) Thrombolytic therapy

In patients who have recently developed and meet the traditional definition of TIA, even if neuroimaging reveals a clear focus of responsibility for cerebral infarction, it is not currently a contraindication to thrombolytic therapy
.
If the TIA recurs, there is a clinical possibility of a diagnosis of cerebral infarction, and should not wait, and thrombolytic therapy
should be actively carried out according to stroke guidelines.

(5) Others

Patients with TIA with hyperfibrinogenemia are treated with fibrase as an option
.
Chinese herbal preparations may also have certain therapeutic effects
on TIA patients.

2.
Surgical treatment and vascular interventional treatment

For those who are suitable for CEA or CAS, it is best to operate within 48 hours and should not delay treatment
.

3.
Control risk factors

Regulate modifiable risk factors including: hypertension, smoking, diabetes, atrial fibrillation, other heart disease, dyslipidemia, asymptomatic carotid stenosis, sickle cell anemia, postmenopausal estrogen replacement therapy, diet and nutrition, exercise and exercise, obesity, excessive alcohol consumption, etc
.

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