Background: As a common and high incidence of disease, the minor ischemic stroke (MIS) has become an important public health problem. The aim of this study was to address whether patients with MIS have different types and outcome in the elderly in northern China. Methods: A retrospective cohort of consecutive patients was selected for study; all registered neurologic outpatients of the tertiary teaching hospital in northern Jiangsu, China between February, 2011 and February, 2012. A total of 433 outpatients, clinically only having had an initial visit and a MRI study of the brain, were enrolled. Results: Of 433 outpatients, 247 (57.0%) patients with MIS were diagnosed. The clinical types of MIS included stable MIS in 58.3%, acute progressive MIS in 5.3%, and chronic progressive MIS in 36.4% of patients. After adjusted Odd ratio (OR), only aged (OR, 1.0; 95% confidence interval [CI], 1.007 - 1.087, p = 0.021), episode duration (OR, 1.8; 95% CI, 1.011 - 1.024, p = 0.001), initial number of MIS (OR, 1.1; 95% CI, 1.047 - 1.207, p = 0.001), and infarcts volume (OR, 1.8; 95% CI, 1.253 - 2.681, p = 0.002) were independently associated with stable MIS and progressive MIS. Total survival was favorable among groups ( p = 0.094), but the followed mRS score was significantly higher among those progressive MIS than those stable MIS (2.3 ± 1.0 vs 0.1 ± 0.3, p < 0.001). Conclusion: MIS had a very high prevalence and different clinical types. Stable MIS is a benign stroke, whereas those progressive MIS may have long-term instability or acute and chronic progressive trend. This information is important in prospectively determining outcome of MIS and in patient treatment.
With magnetic resonance imaging (MRI) advances, several epidemiological studies have reported that the incidence of minor ischemic stroke (MIS) is up to 55% - 74% in metropolitan regions [
From February 2011 to February 2012, a retrospective cohort of new patients was selected for study, all enrolled neurologic outpatients of the tertiary teaching hospital in northern Jiangsu, China. A total of 433 neurologic outpatients, clinically only having had their initial visit and having undergone the MRI studies of the brain, were prospective registered. The sample consisted of males and females, aged 40 years or older, residing in 38 villages or towns and one urban area in Shuyang. The study was approved by the Ethical Committee on Clinical Research of the Shuyang People’ hospital, China. All participants gave written informed consent to participate in the study. Clinical investigations were conducted according to the principles expressed in the Declaration of Helsinki.
We evaluated those outpatients who had an ischemic stroke based on the International Statistical Classification of Diseases, 10th Revision (ICD-10). In this study, the inclusion criteria of MIS were as follows: 1) first visit indicating minor brain symptoms, with or without minor positive signs of stroke, and measured as ≤3 on the National Institutes of Health Stroke Scale (NIHSS); 2) an MRI displaying visible MIS as a small infarcts within 24 hours of initial presentation, or lacunar lesions or increased brain signal using diffusion weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR), with a location in the subcortical white matter, the basal ganglia, or the brain stem. Exclusion criteria were as follows: 1) age < 25 years; 2) previous history of stroke diagnosed; 3) infarct size > 25 mm; or 4) an NIHSS score of >3 on first visit.
Information obtained from each patient at baseline included data on gender, age, body mass index (BMI), episode duration, clinical manifestations, and the imaging of brain MRI in initial visit. The following risk factors were obtained from outpatients registered: BMI measured at baseline was categorized as normal (BMI < 25 kg/m2), overweight (25 - 30 kg/m2), or obese (>30 kg/m2). Hypertension was defined if a patient had a clinical history of hypertension, or had two or more previously documented systolic blood pressures > 160 mm Hg or diastolic blood pressures > 90 mm Hg. Diabetes mellitus was deemed present if the patient gave a history of the condition that was confirmed in the medical records, or there was a random blood glucose concentration of >11 mmol/l. Dyslipidemia was deemed present if total venous plasma cholesterol level > 6.0 mmol/L, LDL fraction > 3.0 mmol/L, triglyceride level > 1.8 mmol/L. Coronary heart disease was defined as a history of acute myocardial infarction or angina pectoris. Atrial fibrillation indicated present when seen on an electrocardiogram during the initial visit or when it was reported in medical records. Cigarette smoking was defined as a last 5 years.
All MR (performed with 1.5-T equipment) studies were reviewed by a neuroradiologist and a neurologist who were blinded to the study. The examiners looked specifically for hyperintense lesions on FLAIR or DWI, measuring maximum diameters when present and attempting to correlate MR findings with clinical status. The number and location of lesions were recorded in detail for each patient.
A neurology specialist who made the baseline assessments followed patients until 6 months after their index event or the time of death if it occurred before that date. All patients were reassessed during the 6 months follow-up, and were classified as “no symptoms or minor symptoms” (score 0 or 1), “lifestyle restriction” [
The criteria of a clinical classification for subtypes of MIS were applied that combined clinical data (including the severity and duration of mRS score during the follow-up) with the results of MRI so that strokes could be classified into several “outcome distinct” groups. In accordance with clinical features and followed mRS score, two types of MIS were delineated: 1) Stable MIS: those MIS with a stable or benign course [
The transient symptoms included transient ischemic attack (TIA) and transient neurological attack (TNA). The newly proposed definition of TIA is a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction [
The syndromes classified by Fisher, namely pure sensory stroke, pure motor syndromes, ataxic hemiparesis, dysarthria clumsy hand, and sensorimotor stroke, were included in this study. The atypical, nonfocal or mixed symptoms such as headache or/and dizziness which can be attributed to a MIS, were summed as follow.
Headache/migraine is a common symptom and risk factor for cerebrovascular disease [
All numeric variables were expressed as the mean ± SD or median (interquartile range [IQR]). Fisher’s Exact test and Kruskal-Wallis test were used to explore the relationship among baseline patient variables. Continuous variables were compared using the t test. Univariate analyses were used to determine risk factors of MIS. Logistic regression analyses for risk factors between stable MIS and progressive MIS were used to calculate Odd ratios (OR), 95% confidence intervals (CI), and probability values. Kaplan-Meier method and test were used to estimate the differences in survival between groups. Multivariate regression analysis by Cox proportional hazards model was performed for each baseline factor. Data were analyzed using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA), with level of significance set at P < 0.05.
Of 433 outpatients, 247 (57%) patients with MIS were diagnosed according to findings on brain MRI. 90% of patients with MIS were released at home received aspirin treatment. The rest (about 10%) were admitted to a neurologic ward.
Features of subtype among patients with MIS
Baseline characteristics and types of MIS on out-patient clinic and during a follow-up are displayed in
Characteristics | Stable MIS (N = 144) | progressive | MIS | P Value |
---|---|---|---|---|
AP-MIS (N = 13) | CP-MIS (N = 90) | |||
Male gender (%) | 73 (50.7) | 9 (69.2) | 40 (44.4) | 0.460 |
Median age, years (range) | 57 (40 - 84) | 74 (65 - 83) | 61 (42 - 85) | 0.001 |
Residing in villages or towns | 135 (93.8) | 12 (92.3) | 85 (94.4) | 0.948 |
Residing in county urban | 9 (6.2) | 1 (7.7) | 5 (5.6) | 0.948 |
Median episode duration, days (range) | 8.6 (1017) | 2.5 (5) | 180 (2879) | 0.001 |
SBP | 151.3 ± 20.7 | 164.9 ± 23.3 | 150.6 ± 22.8 | 0.139 |
DBP | 96.3 ± 10.1 | 94.8 ± 10.2 | 95.4 ± 13.3 | 0.713 |
Blood glucose (mmol/l, mean ± SD) | 5.7 ± 1.6 | 5.6 ± 1.5 | 5.9 ± 2.3 | 0.649 |
Migraine/headache (%) | 34 (23.6) | 1 (7.7) | 21 (22.3) | 0.336 |
its TIAs or TNAs (%) | 30 (88.2) | 0 (0.0) | 21 (100.0) | 0.151 |
Dizziness/vertigo (%) | 52 (36.1) | 5 (38.5) | 18 (20.0) | 0.023 |
its TIAs or TNAs (%) | 46 (88.5) | 0 (0.0) | 18 (100.0) | 0.007 |
Headache and dizziness (%) | 34 (23.6) | 4 (30.8) | 31 (34.4) | 0.194 |
its TNAs (%) | 26 (76.5) | 0 (0.0) | 28 (90.3) | 0.009 |
Pure sensory stroke (%) | 16 (11.1) | 2 (15.4) | 15 (16.7) | 0.414 |
its TIAs | 13 (81.3) | 0 (0.0) | 10 (66.7) | 0.429 |
Pure motor hemiparesis (%) | 3 (2.1) | 6 (46.1) | 1 (1.1) | 0.001 |
Gait disorderss (%) | 8 (5.6) | 2 (15.4) | 9 (10.0) | 0.317 |
Miscellaneous (%) | 4 (2.8) | 0 (0.0) | 2 (2.2) | 0.787 |
Single LI (%) | 19 (15.0) | 0 (0.0) | 0 (0.0) | 0.001 |
Chronic lacunes (%) | 0 (0) | 0 (0) | 4 (4.4) | 0.024 |
Leukoaraiosis (%) | 2 (0.14) | 1 (7.7) | 13 (14.4) | 0.001 |
Normal pressure hydrocephalus (%) | 0 (0) | 0 (0) | 5 (5.6) | 0.009 |
Initial median lesions number (range) | 5.5 (18) | 25 (105) | 9 (80) | 0.001 |
Initial median infarcts volume (cm3, range) | 0.3 (4.5) | 4.1 (9) | 0.9 (8) | 0.001 |
Initial median NIHSS score (range) | 0.1 (3) | 1 (3) | 0.2 (3) | 0.001 |
Initial median ABCD2 score (range) | 4.5 (6) | 5.3 (6) | 4.8 (7) | 0.014 |
Followed median mRS score (range) | 0.2 (1) | 3.0 (6) | 2 (6) | 0.001 |
Mortality (%) | 0 (0) | 1 (7.7) | 1 (1.1) | 0.074 |
*MIS = Minor ischemic stroke; AP-MIS = Acute progressive MIS; CP-MIS = Chronic progressive MIS; TIA = Transient ischemic attack; TNA = Transient neurological attack; SBP = Systolic blood pressure; DBP = Diastolic blood pressure; NIHSS = national Institutes of Health Stroke Scale; ABCD2 = Age, blood pressure, clinical features, duration of symptoms, and presence or absence of diabetes; scores range from 0 to 7, with higher scores indicating greater risk of stroke; mRS = modified Rankin scale.
The acute progressive type of MIS (AP-MIS) was the least frequent (5.3%) and rapid deterioration was fairly typical, running a 2.5-day median course (range 5 days). Such lesions rapidly progressed, in a matter of hours or days, to affect multiple areas supplied by deep perforators, either individually or in aggregate as relatively large infarctions.
Chronic progressive type of MIS (CP-MIS) is the moderate frequency (36.4%), marked by an unstable clinical course and relatively slow progression (median course of 180 days). With this type of MIS, transient symptoms (TIAs or TNAs ) developed in 85.5% of those afflicted. On MRI, all instances were multifocal MIS and from one vascular supply slowly involves other sources. Eventually, many regions of the brain were affected, signaling anterior and posterior circulatory compromise.
Features of clinical symptoms in patient with MIS
There was no difference in gender, SBP, DBP, blood glucose, headache/ migraine, dizziness and headache, pure sensory stroke, gait disorders, miscellaneous, and mortality among stable MIS, AP-MIS, and CP-MIS. Single MIS and dizziness/vertigo were more prevalent in stable MIS than in progressive MIS (p < 0.05). Older age, pure motor hemiparesis, and high NIHSS score were significantly more prevalent in AP-MIS than in stable MIS and CP-MIS (p < 0.05). Longer episode duration, chronic lesion, leukoaraiosis, and normal pressure hydrocephalus were significantly more prevalent in CP-MIS than in stable MIS and AP-MIS (p < 0.05). The number of lesions, volume of infarcts, INHSS score, and ABCD2 score were significantly higher in AP and CP-MIS than in stable MIS (p < 0.05) (
Risk factors and early prediction in patient with MIS
Demographics and risk factor profiles in patients with stable MIS and those with progressive MIS were compared (
Outcome and survival rate among patients with MIS
The difference was significantly greater when the analysis was confined to followed median mRS score between the stable MIS and the progressive MIS (median 0.2 score versus 2 score, p = 0.001), and the respective mortality rates were 0% in stable MIS and 1.9% in progressive MIS (
Survival data were available for our patients with MIS (only two cases of pa-
Variable | Stable MIS (N = 144) | Progressive MIS (N = 103) | OR (95%CI for OR) | P Value |
---|---|---|---|---|
Male gender (%) | 73 (50.7) | 49 (47.6) | 1.4 (0.767 - 2.731) | 0.254 |
Age (y, mean ± SD) | 58.2 ± 10.5 | 63.7 ± 11.2 | 1.1 (1.025 - 1.081) | 0.001 |
BMI ( kg/m2, mean ± SD) | 23.9 ± 2.9 | 23.9 ± 3.4 | 1.0 (0.939 - 1.129) | 0.533 |
Hypertension (%) | 87 (60.4) | 59 (47.3) | 0.7 (0.396 - 1.225) | 0.209 |
Diabetes mellitus (%) | 9 (6.3) | 10 (9.7) | 1.7 (0.625 - 4.709) | 0.295 |
Coronary heart disease (%) | 5 (3.5) | 2 (1.9) | 0.4 (0.067 - 2.034) | 0.253 |
Atrial fibrillation (%) | 1 (0.7) | 1 (1.0) | 1.6 (0.089 - 28.77) | 0.749 |
Hyperlipidemia (%) | 83 (57.6) | 58 (56.3) | 0.8 (0.462 - 1.423) | 0.465 |
Heavy alcohol drinker (%) | 43 (29.9) | 17 (16.5) | 0.5 (0.222 - 1.036) | 0.061 |
Current smoking (%) | 41 (28.5) | 20 (19.4) | 0.6 (0.265 - 1.284) | 0.181 |
MIS = Minor ischemic stroke; OR = Odd ratio; CI = Confidence intervals; BMI = Body mass index.
Variable | Stable MIS (mean ± SD) | Progressive MIS (mean ± SD) | OR (95%CI for OR) | p Value |
---|---|---|---|---|
Age (y) | 58.2 ± 10.5 | 63.7 ± 11.2 | 1.0 (1.007 - 1.087) | 0.021 |
Episode duration (day) | 25.3 ± 87.0 | 321.7 ± 505.0 | 1.0 (1.011 - 1.024) | 0.001 |
Initial lesions number | 6.3 ± 4.0 | 16.4 ± 18.4 | 1.1 (1.047 - 1.207) | 0.001 |
Initial infarcts volume (cm3) | 0.6 ± 0.8 | 2.1 ± 2.2 | 1.8 (1.253 - 2.618) | 0.002 |
MIS = Minor ischemic stroke; OR = Odd ratio; CI = Confidence intervals.
tients lost to follow-up), with a mean follow-up of 180 days. A total of two patients due to the progress of MIS died during follow-up. Survival rate was slightly higher among patients with stable MIS than among those with progressive MIS, but the difference was small (Log rank 2.8; p = 0.094). In Cox proportional hazards analysis, the interaction between the effect of mRS score and type of MIS on survival was significant (OR = 2.6, 95% CI = 1.049 - 6.461, p = 0.039).
With increasing longevity, existing clinical data indicate a 55% - 74% incidence of MIS in metropolitan areas [
Some MIS with a stable course and a good prognosis have been reported [
Progressive MIS had been proposed by Bang [
Acute progressive type of MIS occurred in 4.5% - 6.8% of the patients with MIS [
Previous studied has been shown that the survival rate in MIS hospitalized was 97% at 1 year [
But then, this does not mean that the survival quality of MIS patients will be long-term stability and excellent health. Moreover, we have shown that the median mRS score in progressive MIS in the follow-up 6 months was significantly higher than those stable MIS. This finding suggests that progressive MIS may have long-term instability or acute and chronic progressive trend. Some studies have shown that the trends of prognosis for MIS related to the burden of atherosclerosis [
Some limitations of our study are conceded. Because the mRS gap for each of the subgroups were very narrow, misclassification between stable MIS and progressive MIS may be presented by the data on phone. In fact, these mRS scores were markedly differences between the “no symptoms or minor symptoms” (score 0 or 1) and “lifestyle restriction” (2 - 3). Therefore, we believe that at most a very small case would have misclassified in the inquiries. In addition, the absence of a repeated MRI or vascular imaging data from some patients may be affected the predictors for patients with progressive MIS as well as recurrent events.
MIS had a very high prevalence and different clinical types. Stable MIS is a benign stroke, whereas those progressive MIS may have long-term instability or acute and chronic progressive trend. This information is important in determining outcome of MIS and in patient treatment.
This work is supported by a grant from the Medical Research Council, affiliated Shuyang People’s Hospital, XuZhou Medical University, China.
Clinical Key Specialty Construction Project of Jiangsu Provence (20120013).
Wang, G.S., Tong, D.M., Chen, X.D., Yang, T.H. and Zhou, Y.T. (2017) Clinical Types and Outcome of Minor Ischemic Stroke in Northern China: A Retrospective Cohort Study. World Journal of Neuroscience, 7, 95-105. https://doi.org/10.4236/wjns.2017.71009