Etiologic subtype predicts outcome in mild stroke: prospective data from a hospital stroke registry

It is very common that acute ischemic stroke patients have mild symptoms or rapidly improving stroke symptoms, which makes the decisions of treatment in dilemma. Intravenous thrombolysis with recombinant tissue plasminogen activator (IV rtPA) is proven to be the most effective treatment for acute ischemic stroke [1, 2]. However, only 1%-5% patients are treated with IV rtPA. In addition to the narrow time window for treatment, not treat patients with mild or rapidly improving symptoms is one important reason [3]. In studies evaluating eligibility for thrombolysis, up to 43% of patients with mild or improving stroke symptoms do not receive thrombolytic therapy because of clinicians think the natural course of these patients is benign [4]. However, according to recent reports, 15%–31% of patients with mild or rapidly improving symptoms have dependent or dead during hospital admission without thrombolysis [3, 5–7]. Therefore, early identification of these patients with poor outcome will contribute to the choice of early intervention to prevent the occurrence of poor outcomes. Studies suggest that mild stroke patients with large vessel occlusion are at a high risk for early neurological deterioration or poor outcome [8]. Imaging with advanced MRI is one possibility to guide treatment decision in mild stroke [9–11]. Therapies directed at the underlying mechanism will be more effective. But there is still lack of clinical outcomes in patients with different etiologic subtype. This study aims to observe clinical characteristics and explore the effect of different etiologic subtype on prognosis of mild stroke.

In this study, we found patients with mild stroke accounted for 41.1% in our cohort. The proportion of case fatality and death/disability was 2.2% and 10.1% respectively at 3 month. Different etiologic subtype can predict the outcome in these patients.

Previous studies showed the proportion of mild stroke veried from 5.8% to 62.3% based on different criteria, which in accordance with our study [16, 17]. Khatri et al. suggests that approximately one third of so-called mild strokes have significant disability (mRS 2–6) that persists at 3 months [7]. In contrast, we found 10.1% of minor stroke had death or disability. The reasons of low proportion of our study may be as follows: (1) they used the NIHSS≦5 as criteria whereas we used NIHSS≦3, which indicates they included participants more severer than ours; (2) they measured disability with mRS > 1 whereas we defined it as mRS > 2; (3) they enrolled patients within 24 hours whereas we included them within 30 days, which means their participants may be prone to have early worsening or early recurrence than ours; (4) In general, the death or disability of acute ischemic stroke patients in China is lower than abroad [18, 19], so may be minor stroke no exception.

Several studies reported the predictors of poor outcome of mild stroke, such as age, diabetes, coronary heart disease, smoking, and vessel stenosis or occlusion were predictor of death or disability or recurrence at the end of follow up period [20–25]. Ferrari J et al. found hypertension, diabetes, cardiac decompensation, acute infection, and stroke etiology (LAA and CE) emerged as independent risk predictors for early deterioration in patients with a transient ischaemic attack (TIA) or minor ischemic stroke, defined by an NIHSS score <4 [26]. In our cohort, age, history of intracerebral hemorrhage, infections and etiologic subtype (CE and SAO) were the independent predictors of death or disability at 3rd month. Our finding of etiologic subtype can predict outcome in mild stroke is more compelling, because consecutive subjects that were assessed beyond hospital discharge at 90 days. So far, although there are no identical variates for predicting the poor outcome of patients with minor stroke, future studies are needed to focus on how to really identify minor stroke patients with poor outcome by clinical features combined with imaging features. Recently, Strbian D et al. indicates that half of patients presenting with NIHSS 0–6 developed an infarction despite thrombolysis, and 40% had poor outcome. Perhaps, urgent multimodal imaging can help to identify mild stroke at risk of worsening [27]. As we known, etiologic subtype help stratify patients for secondary prevention and it may also be used for identifing poor outcome in patients with mild stroke.

At present, whether patients presenting with mild stroke should or should not be treated with intravenous rtPA is still unclear. In our study, 3.8% (26/680) of cases admitted within 3 hours and 4.7% (32/680) admitted within 4.5 hours. However, no patient received intravenous thrombolysis. In the light of the natural history of course of mild stroke is not always benign, before a large randomized trial proving its lack of benefit in mild stroke patients, IV t-PA should be considered in these patients.

Our study has several limitations. (1) It was performed in a single-center, which may not represent for whole Chinese population; (2) there is no consensus definition of mild stroke. The National Institute of Neurological Disorders and Stroke (NINDS) rtPA study and the European Cooperative Acute Stroke Study (ECASS) III both excluded patients with mild stroke, but they failed to clearly define a certain threshold for a mild stroke. We used diagnostic criteria NIHSS score ≦3, which be evaluated as the more suitable cutoff point [13]; (3) The effects of potential unknown confounders cannot be ruled out in our cohort. Despite these limitations, our study explored the relationship between etiologic subtype and outcomes by inclusion of propectively consecutive patients and the blind evaluation of the study outcome.

In conclusion, our study indicates that different etiologic subtype can predict the outcome in patients with minor stroke it can help to stratify these patients for individual decision-making.