Advances in thrombolytic therapy in patients with mild stroke

From 1990 to 2017, the prevalence and incidence of stroke in China showed a continuous upward trend, and the demand for inpatient medical services in China increased by nearly 6 times from 2005 to 2015 (66.

01 Definition and epidemiology of mild stroke

At present, the definition and standards of light stroke are not uniform
.

Other scholars have proposed the use of imaging methods to define light stroke
.

A comparative study of Phase I (2007-2008) and Phase II (2012-2013) of the National Stroke Registry of China (China National Stroke Registry (CNSR) showed that the NIHSS score of stroke patients in China was lower than before (median NIHSS score of 5 points vs 4 points), suggesting that the proportion of patients with mild stroke may increase
。 Of the 430,000 inpatient stroke patients in 1,576 hospitals nationwide registered for CSCA, 350,000 (81%) were ischemic strokes, of which up to 50% were mild strokes (NIHSS score ≤3).

02Current status of thrombolytic therapy for mild stroke

The International TIA Registered Cohort (TIA registry.

Intravenous thrombolytic therapy is the treatment of choice in patients with acute ischemic stroke within 4.

Multiple studies have shown that the benefits of thrombolytic therapy in patients with mild stroke outweigh the disadvantages, but some studies disagree
.

Given the current findings and conclusions, the American Heart Association's (AHA)/American Stroke Association (ASA) "Early Management Guidelines for Patients with Acute Ischemic Stroke 2019" and the European Stroke Organisation's (ESO) "Guidelines for Venous Thrombolysis in Acute Ischemic Stroke Stroke 2021" rt-PA is recommended for patients with mild stroke with disabling symptoms, and thrombolytic therapy
is not recommended for patients with non-disabling mild stroke.

Most of the current clinical studies of thrombolytic therapy for mild stroke are limited to retrospective analysis and have small
sample sizes.

It has also been suggested that tenectase may be a more desirable thrombolytic agent
for mild stroke.

03Influencing factors in the prognosis of thrombolysis in light stroke

The use of thrombolytic therapy in patients with mild stroke is still highly controversial
.

3.

Generally, the time window of thrombolytic treatment is divided into 0-3 h and 3-4.

3.

In clinical decision-making, the thrombolysis of a mild stroke depends largely on whether the patient's
symptoms are disabling.

There are currently no studies to support the benefit of intravenous thrombolytic therapy in patients with non-disabling mild stroke
.

3.
3 NIHSS score

Acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes, Secondary analysis of the SOCRATES) trial proved that the NIHSS score is a predictor
of disability after thrombolytic therapy in patients with mild stroke (NIHSS score 0 to 5).
Studies such as Romano have also shown that NIHS S-scores in patients with mild stroke (NIHSS score 0 to 5) are inversely associated with discharge outcomes (independent walking, homecoming, length of hospital stay≥3 d) after thrombolytic therapy, and are not associated with sICH and other complications (malignant edema, angioedema, stroke recurrence, and other complications requiring additional medical intervention or prolonged hospital stay
).
。 Leira et al.
found that the NIHSS score of patients with mild stroke (NIHSS score 0 to 6) was negatively correlated
with the good prognosis outcome of thrombolytic therapy in 3 months (GCS score of 1 and Barthel index score of 19 to 20).
But there are also studies that show that even with an NIHSS score of 0, patients may still experience a recurrence of stroke within 12 months and worsen
symptoms.
There is currently no consensus on the effect of the NIHSS subscore on prognosis
.
The SOCRATES trial showed that the correlation between limb weakness subterm score and disability rate was higher than other subterms, but Leira et al.
believed that the NIHSS subterm score was not an independent predictor of long-term prognosis in patients with mild stroke, and the NIHSS score still had a certain predictive effect on thrombolysis prognosis in patients with mild stroke even in the range of 0 to 5 points, but the effect of NIHSS subterm score on thrombolysis prognosis in mild stroke is currently controversial
.

3.
4 Etiological classification

The etiological classification of mild stroke is currently controversial
.
NINDS found that the proportion of patients with mild stroke and other types (6.
9% vs 3.
2%) was significantly higher than that of all stroke patients, and the proportion of patients with atherosclerosis (13.
8% vs 21.
6%), cardiac origin (29.
3% vs 39.
6%), and unknown cause (20.
7% vs 27.
9%) was significantly reduced
.
The PRISMS findings also support that the most common pathogenesis of mild stroke is cerebral small vessel disease (36.
6%)
.
Two studies from Asia concluded that atherosclerosis was the most common subtype
of cause of mild stroke (46.
5%, 33.
2%).

Multiple studies support that patients with aortic atherosclerotic mild stroke are at higher risk of recurrence and may benefit more
after intravenous RT-PA therapy.
Wang et al.
have found that rt-PA thrombolytic therapy is more beneficial for patients with light atherosclerotic stroke of the aorta without tandem stenosis occlusion and improves their 90-day prognosis (64.
4% vs 88.
4% for unthrombolytic therapy versus thrombolytic therapy).

3.
5 Other influencing factors

In addition to the currently studied factors such as thrombolytic treatment time window, disabling symptoms and signs, NIHSS score, and etiological classification, there are other factors related
to thrombolytic prognosis in patients with mild stroke 。 Demographics: age, female, African American; Arrival at the hospital: by ambulance, non-working hours; Past medical history: diabetes, hypertension, dysliposis, internal carotid artery stenosis, coronary heart disease, persistent or paroxysmal atrial fibrillation or atrial flutter, heart failure, previous stroke; Clinical manifestations: impaired consciousness, ABCD2 score of ≥6, multiple cerebral infarction, acute infection, recurrent stroke and concomitant myocardial infarction are also influencing factors
for poor prognosis of thrombolytic therapy in patients with mild stroke.
Comprehensive exploration of a variety of influencing factors can help to identify patients with mild stroke with poor prognosis early and improve clinical outcomes
.

In this paper, the definition, epidemiology, status quo of thrombolytic therapy, and prognostic influencing factors are summarized, and it is found that the efficacy and safety of thrombolytic therapy in patients with mild stroke are highly controversial
in the current study.
Most studies were limited by small sample sizes and the conclusions drawn for retrospective studies were not highly informative, and the only randomised controlled trial was unable to provide high-level evidence
due to early termination.
Therefore, it is expected that more large-scale, multicenter, prospective, randomized clinical trials will be held in the future to provide more evidence-based medical evidence
for the clinical practice of thrombolytic therapy in patients with mild stroke.