Introduction

Minor stroke is considered an acute ischemic stroke that has an NIHSS score ≤ 5 points, with the condition of a score of 0 on the cognitive section of the NIHSS scale [1–4]. Patients with minor stroke accounts for 30–50% of the general ischemic stroke population [5–8]. Although the initial clinical manifestations are mild neurological deficits, poor clinical outcomes rate (mRS 2–6) are for a very high rate of 23.5–38% [4, 9, 10]. Early neurological deterioration is related to reasonably expected poor clinical outcomes, accounting for 5–40% [11, 12]. Early neurological deterioration (END) in minor stroke is defined as a condition with progressive neurological deficit or an increase in NIHSS score of 2 points or more in the first 72 hours of illness [4, 11–14]. Therefore, identifying factors of minor stroke associated with END helps us offer appropriate treatment strategies to reduce the risk of poor clinical outcomes at day 90 [12].

In Vietnam, poor clinical outcome in minor stroke patients is related to initial NIHSS scores, clinical progression with NIHSS scores increasing above 4 in the first 24 hours, and intracranial artery stenosis [13]. However, the definition of END has not been made clear, and the minor stroke definition NIHSS ≤ 4 seems inappropriate. Outcomes, associated factors and frequency of minor stroke in Vietnam were not well characterised. There is a lack of research on minor stroke patients and also the END scale in Vietnam application leading to severe consequences in stroke management and treatment.

Therefore, in this study, we aim to determine the population of END subjects in a subgroup of minor stroke patients (NIHSS scores ≤ 5) hospitalized in the first 72 hours and determine factors (clinical and paraclinical characteristics, imaging, treatment) related to END based on regression analysis. This proposed case-control protocol for minor stroke is the first study conducted in Vietnam with 779 participants (a number estimated by statistical calculation).

Methods

Study design

The study design is an observational, descriptive study, with longitudinal follow-up of all patients with minor stroke (NIHSS ≤ 5 points, with the condition of a score of 0 in the cognitive section of the NIHSS scale) hospitalized within 24 hours. It will be at the comprehensive stroke centre of Bach Mai Hospital from December 1, 2023, to December 1, 2024. A study flow chart is illustrated in Fig 1. Exclusion criteria for mRS before stroke ≥ 2 points; Pregnant and breast-feeding women; co-existence of other brain injury: traumatic brain injury, intracranial hemorrhage, subarachnoid hemorrhage, and brain tumour. Further information on the eligibility criteria for this study can be found in Table 1.

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Fig 1. Flow chart of the study design.

END is Early neurological deterioration; mRS is the Modified Rankin Score; and NIHSS is the National Institutes of Health Stroke Scale.

https://doi.org/10.1371/journal.pone.0302822.g001

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Table 1. Eligibility criteria for the study, with mRS, is the Modified Rankin Score, and NIHSS is the National Institutes of Health Stroke Scale.

https://doi.org/10.1371/journal.pone.0302822.t001

Statistical analysis

We separated the data set of 779 subjects into two main groups, END and no-END. Demographic information, risk factors during stroke, NIHSS on admission, the etiology of stroke, and medications during hospitalization are compared between patients with and without END during the acute phase of stroke. All data inputs from the patients are recorded and reported in Table 2. The comparison is achieved by t-test (if normal distribution) or Kruskal-Wallis test (non-normal distribution) for continuous variables. The χ2 test is used to analyze categorical variables. Multivariate Logistic regression models after adjusting for potential confounders, including age, gender, hypertension, diabetes, NIHSS on admission, and other variables with P < 0.20 when analyze by univariate analysis. The p values are considered significant at 0.05. Statistical analyses are performed using SPSS 16.0 (IBM, Armonk, NY).

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Table 2. Clinical and subclinical characteristics of patients.

https://doi.org/10.1371/journal.pone.0302822.t002

Discussion

The significant contribution of the article is to determine the END rate and prognostic factors for END in a group of patients with minor stroke at a comprehensive stroke centre in Vietnam. From there, it helps guide clinical practice inappropriately approaching diagnosing and treating patients with minor strokes in the emergency room. The American Stroke Association recommends that patients with minor strokes with disabling neurological deficits be prescribed thrombolytic drugs, while groups without disabling neurological deficits will not be recommended for thrombolysis. Recently published research by Chen, et al. demonstrated that thrombolysis and antiplatelet drugs are effective in patients with minor strokes without neurological deficits—equal clinical benefits [16].

Patients with minor strokes with NIHSS ≤ 5 points are often excluded from mechanical thrombectomy studies. Recent studies have shown that mechanical thrombectomy in patients with minor stroke with low NIHSS scores in large artery occlusion might not demonstrate clinical benefit [17–19]. Research conducted across multiple centres and looking back at past cases has revealed that using endovascular mechanical thrombectomy does not provide any advantage over other treatment approaches for minor stroke patients with isolated M2 occlusion [20]. To reduce poor clinical outcomes and complications, early identification of risk factors and closely monitoring may help prevent complications and maximize the benefits of endovascular thrombectomy [21, 22]. Intracranial artery stenosis is more common in Asians than in Westerners. Is intracranial artery stenosis a risk factor for END? Our study will help to identify END risk factors and allow rational treatment choices for patients presenting within the reperfusion window (thrombolysis and mechanical thrombectomy).

In other research, in 2020, Sung SM, et al. demonstrated that Hemorrhagic transformation, initial NIHSS score, stenosis, or occlusion of the relevant artery were, respectively, prognostic factors for END in a group of minor strokes [12]. However, in Sung’s study, the criteria for minor stroke patients is NIHSS score ≤ 3. In 2021, Xiong, et al. found that patients with minor stroke had a rate of treatment outcomes, mortality, recurrent stroke, and myocardial infarction in two groups (NIHSS ≤ 3 points and NIHSS ≤ 5 points) are equivalent [23]. Therefore, an NIHSS score ≤ 5 is a more suitable criterion for a minor stroke [1, 3, 23]. This is also the first study on END (NIHSS ≥ 2) in patients with minor stroke (NIHSS ≤ 5) and including large artery occlusions or not different from N. Boulenoir only selected patients with large artery occlusions [15].

Our study determined the END rate in patients with minor stroke NIHSS ≤ 5 and prognostic factors for END. From there, it is proposed that patients at risk of END should be hospitalized early and treated with aggressive strategies such as reperfusion therapy. This study also can potentially extend to investigate further into risk factors to END and also early warning methods for stroke prevention in minor stroke patients.

Acknowledgments

We would like to thank Professor Andrew Farmery (University of Oxford) for thoroughly editing our final manuscript.