Dysphasia and platelet count associated with diffusion-weighted images lesions in patients with a clinical diagnosis of transient ischemic attack

Background Magnetic imaging is a mandatory tool in the diagnosis of a transient ischemic attack (TIA). Many patients cannot have an MRI in time. The clinical characteristics associated with DWI positivity after TIA are of great significance for the early diagnosis and urgent intervention of TIA and cerebral infarction. This study was conducted to investigate the clinical characteristics associated with DWI lesions in TIA patients. Methods We retrospectively identified patients who met the criteria of symptom duration <24 hours for a clinical diagnosis of TIA, and then screened out 302 patients underwent DWI within 7 days of admission. The patients were divided into DWI positive and DWI negative group. The clinical characteristics including risk factors, clinical manifestation, the laboratory blood tests, the auxiliary examination and the TIA scores were compared between the two groups. We aimed to identify the clinical characteristics associated with DWI lesions using logistic regression analysis. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were calculated to compare the predictive value of various scores such as ABCD2, ABCD3, ABCD3I, Dawson score and the Diagnosis of TIA (DOT) score for DWI lesions in TIA patients. Results A total of 302 patients (mean age, 62(54,70) years; 67.2 % men) were enrolled in this study. There were 89(29.5%) patients with DWI positivity. Logistic regression analysis showed that the clinical characteristics associated with DWI lesions were dysphasia (OR 2.129; 95%CI 1.215-3.729) and platelet count (OR 0.993; 95%CI 0.988-0.999). The AUCs 95%CI for Dawson score was 0.6100.543-0.678 and the DOT score was 0.6250.559-0.691. Conclusion DWI lesions were detected in 29.5% of patients with classically defined TIA and were associated with dysphasia and platelet count. Dawson score and DOT score seem to have the predictability of DWI lesions in TIA patients. of symptom for a clinical of We screened out the patients underwent DWI within 7 days of admission. We used 3.0-T MRI including T1, T2 and DWI sequences to evaluate whether acute ischemic lesions were present on admission. Acute DWI lesions were defined by areas of high signal intensity on DWI. All MRI scans were read by experienced neuroradiologists. Based on the results of DWI, patients were divided into DWI positive and DWI negative group. We collected a broad range of clinical, laboratory and radiological data from all patients based on a review of their medical records: baseline characterizations—age and gender, TIA symptoms, duration of symptoms, time from onset to MRI, vascular risk factors including hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, smoking and alcohol drinking, history of ischemic stroke and coronary artery disease, ABCD2[12], ABCD3, ABCD3I[13], Dawson score[14], the Diagnosis of TIA (DOT) score[15] at admission, results of the laboratory blood tests recorded for platelet count(PLT), albumin(ALB), prealbumin(PAB), cholesterol(CHOL), low density lipoprotein(LDL), triglyceride(TG), blood urea nitrogen(BUN), creatinine(Cr), uremic acid(URIC), calcium(Ca), phosphonium(P), fibrinogen(Fbg), glucose, degree of intracranial artery stenosis in magnetic resonance angiography(MRA) and computed tomography angiography(CTA), maximal plaque thickness in cervical vascular ultrasound and treatment after admission. We analyzed the associations of acute DWI lesions with clinical characteristics. Our results showed that acute DWI lesions were detected in 29.5% of patients classically defined TIA. Acute DWI lesions were associated with dysphasia and platelet count. The clinical characteristics associated with DWI lesions need to be confirmed in further studies. The association between clinical characteristics and DWI lesions is valuable for early evaluation of TIA patients. Additionally, the comparison of AUCs showed superiority of Dawson score and DOT score compared to ABCD2 score and ABCD3 score. Dawson score and DOT score may be useful for the diagnosis and management of TIA.


Introduction
A transient ischemic attack (TIA) is classically defined as an acute and focal neurologic deficit caused by temporary brain ischemia lasting less than 24 hours, irrespective of imaging findings [1]. Recent years, a new tissue-based definition of TIA was proposed [2]. It includes symptoms lasting less than 1 hour and the absence of a diffusion-weighted imaging (DWI) lesion detected by magnetic resonance imaging (MRI) [3,4]. DWI is highly sensitive to small acute ischemic lesions [5]. DWI become a mandatory tool in the diagnosis of a TIA. The frequency of positive DWI findings in TIA patients varied from 9 to 67% between studies [6]. Several studies have shown that DWI lesions were associated with high risk of recurrent ischemic stroke after TIA [5,7,8]. Clinical characteristics associated with DWI lesions after TIA are of great significance for the early diagnosis and urgent intervention of TIA and cerebral infarction [9]. Various studies have reported that the presence of DWI lesions in acute TIA is associated with motor weakness, aphasia, dysarthria, left hemispheric presenting symptoms, National Institutes of Health Stroke Scale (NIHSS) score of ≥10 at admission, time from onset to DWI longer than 24 hours, intracranial large artery atherosclerosis and old brain infarctions on MRI [3,10,11]. In this study, we aimed to further identify characteristics associated with the presence of acute DWI lesions in Chinses TIA patients.

Study design
From January 2016 to February 2019, we retrospectively identified patients admitted to the neurology department of Beijing Chao-Yang Hospital, Capital Medical University, who met the criteria of symptom duration <24 hours for a clinical diagnosis of TIA. We screened out the patients underwent DWI within 7 days of admission. We used 3.0-T MRI including T1, T2 and DWI sequences to evaluate whether acute ischemic lesions were present on admission. Acute DWI lesions were defined by areas of high signal intensity on DWI. All MRI scans were read by experienced neuroradiologists. Based on the results of DWI, patients were divided into DWI positive and DWI negative group.
We collected a broad range of clinical, laboratory and radiological data from all patients based on a review of their medical records: baseline characterizations-age and gender, TIA symptoms, duration of symptoms, time from onset to MRI, vascular risk factors including hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, smoking and alcohol drinking, history of ischemic stroke and coronary artery disease, ABCD2 [12], ABCD3, ABCD3I [13], Dawson score [14], the Diagnosis of TIA (DOT) score [15] at admission, results of the laboratory blood tests recorded for platelet count(PLT), albumin(ALB), prealbumin(PAB), cholesterol(CHOL), low density lipoprotein(LDL), triglyceride(TG), blood urea nitrogen(BUN), creatinine(Cr), uremic acid(URIC), calcium(Ca), phosphonium(P), fibrinogen(Fbg), glucose, degree of intracranial artery stenosis in magnetic resonance angiography(MRA) and computed tomography angiography(CTA), maximal plaque thickness in cervical vascular ultrasound and treatment after admission. We analyzed the associations of acute DWI lesions with clinical characteristics.

Ethics Statement
The study was approved by the ethics committee of Beijing Chaoyang Hospital and performed in accordance with the Declaration of Helsinki. All subjects provided written informed consent.

Statistics analysis
Statistical analyses were performed using IBM SPSS Statistics 21. All statistics were presented as mean ± standard deviation (SD) for continuous variables with normal distribution, median and interquartile range for continuous variables with non-normal distribution, and counts and proportions for categorical variables. We performed t test, chi-square test and the nonparametric Mann-Whitney U test to compare the clinical characteristics between the two groups. A P value of less than 0.05 was considered significant. Logistic regression analysis was applied to identify independent predictors of DWI lesions in TIA patients. A enter selection procedure was performed. The results were presented as estimates of relative risk by odds ratio (OR) with a 95% CI. Receiver operating characteristic curve analysis were used to compare the predictive values of various scores with regard to DWI lesions in TIA.

Results
We enrolled a total of 302 patients (mean age, 62(54,70) years; 67.2 % men) admitted for diagnostic TIA who met the criteria of symptom duration <24 hours and underwent DWI within 7 days of admission. DWI lesions were detected in 89 (29.5%) of the 302 patients. Table 1 shows the baseline clinical characteristics of patients with DWI lesions and those without. Results of blood pressure at admission, the laboratory blood tests, the auxiliary examination and the scores of the two groups are presented in Table 2.
There were differences in gender, dysphasia, motor weakness, Hyperlipidemia, smoking, alcohol drinking, systolic pressure, diastolic pressure, platelet count and glucose of the two groups. Logistic regression analysis ( count. There were significant differences in the severity of the stenosis in intracranial artery between the two groups. Patients with DWI lesions had more severe vascular stenosis. There were no differences in the location of vascular stenosis. Cervical vascular ultrasound showed thicker maximal plaque in patients with acute DWI lesions. In addition, treatment taken after admission was different between the two groups. The ABCD2, ABCD3, ABCD3I, Dawson score and DOT score were significantly higher with DWI lesions than those without DWI lesions. Based on receiver operating characteristic curve analysis In addition, most of the DWI lesions were located in the periventricular area, basal ganglia, cortical and subcortical region. Most lesions were diffused punctiformed lesions or lacunar infarcts. DWI lesions were more frequent in the anterior circulation.

Discussion
Our results showed that DWI lesions was detected in 29.5% of TIA patients. Characteristics associated with DWI lesions were dysphasia and platelet count. The ABCD2, ABCD3, ABCD3-I, Dawson score and DOT score were significantly higher with DWI lesions than those without DWI lesions.
According to the meta-analysis the pooled proportion of TIA patients with an acute DWI lesion was 34.3%, and there is a large variety in the prevalence of DWI lesions in acute TIA patients. The frequency of positive DWI findings varied from 9 to 67% between studies [6]. In young patients (median age 46 (40,51) years) with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI [11]. In our study, the frequency of an acute DWI lesion was 29.5% in TIA. A potential cause of heterogeneity may be the procedural TIA definition. In some studies, clinical TIA with acute lesions may be classified as stroke.
Otherwise, it is not clear to what extent TIAs without DWI lesions represent TIA mimics rather than being the result of a cerebrovascular event.
In agreement with previous investigations [3], acute DWI lesions were associated with dysphasia. Patients with dysphasia need to be taken seriously. The diagnosis of TIA is mainly based on the clinical history. Neurological signs usually disappear quickly. The diagnosis of TIA can be difficult and 50-60 % of patients seen in TIA clinics turn out to be nonvascular mimics [15]. The sign of dysphasia is not easy to imitate. The diagnosis of dysphasia is more accurate. This may explain why dysphasia is a related factor. Episodes of acute atypical or nonfocal neurological symptoms, referred to as transient neurological attack (TNA), are as prevalent as TIAs. It was reported that DWI shows acute ischemia in 23% of patients clinically diagnosed as TNA by experienced stroke neurologists [16]. This raises questions about the accuracy of the clinical diagnosis of TIA.
In addition, our study showed that DWI lesions were independently correlated with platelet count. Patients with DWI lesions had lower platelet count. Platelets have an important role in the initiation of atherosclerotic lesions and subsequent complications [17]. Ischemic stroke is associated with abnormal platelet activity and thrombus formation [18].
Inflammatory molecules secreted by platelets can induce the transition from chronic to acute disease, featuring increased instability of the atherosclerotic lesion that results in plaque rupture and thrombosis [19]. In a study of ischemic heart disease, patients with acute coronary syndrome had higher platelet volume indices and lower platelet counts.
Some studies have shown that decreases in platelet count may be a characteristic of the pre-thrombotic state and platelet consumption in the acute phase of clot formation and subsequent thrombosis [17]. Platelet volume indices such as mean platelet volume (MPV), platelet distribution width (PDW) and platelet large cell ratio (P-LCR) may be useful to show the association between platelet size and ischemic events. We collected some additional data including MPV, PDW and P-LCR of the two groups. There were no significant differences in MPV, PDW and P-LCR of the two groups. Results of them are presented in Table 5. Though MPV increased in unstable angina and myocardial infarction [17], we found that there were no differences between patients with acute DWI lesions and those without DWI lesions of TIA patients. With the support of further clinical studies, platelet count could be used for predicting acute DWI lesions of TIA patients.
Our result showed that ABCD2 ABCD3 ABCD3-I, Dawson score and DOT score were significantly higher with DWI lesions than those without DWI lesions. Acute DWI lesions were associated with the prognosis of TIA patients. Ay and co-workers found a higher predictive value of early risk of stroke for acute DWI lesion in TIA patients [20]. Early brain MRI examination is warranted in these patients. The use of DWI in all TIA patient assessments improved risk stratification from day 7 up to 3 months [21]. As for DWI lesions for stroke risk from 1 to 5 years, the study of Whilst Anticoli did not record any difference in stroke risk in patients with positive DWI lesions. This study showed the long-term follow-up study in TIA patients documents that both positive and negative DWI patients treated with fast-track had similar long-term risks of stroke [21]. We found that patients with acute DWI lesions had more severe vascular stenosis and thicker maximal plaque. We still need to pay close attention to the clinical course of these patients. Based on receiver operating characteristic curve analysis, the comparison of AUCs [95%CI] showed superiority of Dawson score and DOT score compared to the ABCD2 score and the ABCD3 score. Dawson score is a clinical scoring system that assists with diagnosis of TIA [14].
DOT Score is a new clinical diagnostic tool for both brain and retinal TIA [15]. With the use of Dawson and DOT score, the diagnosis of TIA wound be more accurate. It seems to be useful in predicting acute ischemic lesions on DWI with TIA.
Previous research found that most of the lesions were located in the cortical or subcortical region [11]. In our study, most of the DWI lesions were located in the periventricular area, basal ganglia, cortical and subcortical region. Most lesions were diffused punctiformed lesions or lacunar infarcts. DWI lesions were more frequent in the anterior circulation.
Havsteen I found that one-third of acute DWI lesions were completely reversed without persistent infarction signs, especially to the small cortical grey matter [22]. Further research is needed to analyze its characteristics.
In our study, there were no differences in the time from symptom onset to DWI examination (mean time, 5 (3,10) days) of the two groups. There was a study showed the time from symptom onset to DWI examination longer than 24 hours was independently associated with the presence of DWI lesions. In this study, 81.7% of patients underwent a DWI examination within the initial 24 hours after the symptom onset. They suggested that longer time from symptom onset to DWI examination was associated with more frequent lesions [10]. Brazzelli et al. found in a meta-analysis no evidence that the DWI-positive rate varied with time from symptom onset to DWI examination. They found that the DWI lesions were unstable. It may disappear within 24 hours or be undetectable on hyperacute imaging [6]. The study of Shono K also demonstrated that short latency (less than 2 hours) from TIA onset to initial DWI was an independent risk factor associated with false-negative findings on DWI[23]. A repeat DWI is recommended for these patients. Further research is needed to define the relationship between them.
Our study has several limitations. First, the number of patients was small. A study with a larger number of patients from multiple centers is needed to confirm the characteristics associated with DWI lesions. Second, our study only had DWI results. It was reported that perfusion-weighted imaging (PWI) is useful in defining whether or not the transient neurological symptoms in DWI-negative TIA are true vascular events. The presence of a focal perfusion abnormality is a strong predictor of new DWI lesions at follow-up in DWInegative TIA patients [24]. We need a variety of imaging tools to determine potential mechanisms underlying such events. Finally, our study population was based on hospital patients in a single center, and there might have been selection bias.

Conclusion
Our results showed that acute DWI lesions were detected in 29.5% of patients classically

Consent for publication
All patients agreed with the publication.

Availability of data and materials
The datasets used in the current study are available from the corresponding author upon reasonable request.

Competing interests
On behalf of all authors, the corresponding author states that there is no competing interest.