The Study Of Clinical And Imaging Characteristics Of Patients With Brainstem Infarction And Their Prognosis In One Year

Stroke is the leading cause of neurologic high morbidity and mortality worldwide.It is estimated that ischemic brain stem stroke(BSI)accounts for 11% of all first-episode ischemic strokes.Brainstem infarction(BSI),although small in size,may lead to serious neurological deficits.A thorough understanding of the etiology and pathogenesis of BSI is essential for its acute management,prognosis and risk assessment of recurrence.BSI can be caused by large artery disease(LAD),small artery disease(SAD),arterial to arterial embolism,cardiogenic embolism(CE)or other causes.Acute isolated pontine infarction is the most common type of infarction in the brainstem.Infarction in different vascular territories of the brainstem may have different etiology and clinical manifestations.The study on the pathogenesis of isolated brainstem infarction began in the 1960 s,and subsequent pathological studies confirmed that the cerebral infarction has different etiological mechanisms.Acute isolated pontine infarction can be resulted from branches blocking due to lipohyalinotic degeneration of perforators and orifice occlusion by perforator's proximal athroma or atherosclerotic plaque originated from parental artery.In recent years perforating artery diseases have attracted more and more attention.Studies have found that perforating artery disease associated with parental artery atherosclerosis are one of the major mechanisms of BSI.Although pathological findings suggest that perforating artery disease may be derived from parental artery atherosclerosis,current conventional angiographic techniques such as transcranial Doppler,CTA,MRA,cannot show them visually.In recent years,some studies on relationship between imaging Characteristic and etiology of BSI have tried to differentiate the etiology by analyzing it?s morphology.According to the shape and location of the lesion,the larger medial or paramedian infarction abuts on the basal surface of the brainstem is usually associated with branch obstruction caused by atherosclerotic plaques,while the smaller deep lesions that do not reach the ventral surface of the brainstem are mostly caused by lipohyalinotic degeneration of small artery.Since BSI associated with parental artery disease is an atherothrombotic disease,it more often shows characteristics of atherosclerosis than which caused by SAD.Studies have shown that compared with patients with SAD,patients with isolated subcortical infarcts associated with parental artery disease was more frequently related to atherosclerotic markers,such as coronary heart disease and asymptomatic cerebral artery atherosclerosis,but had a lower prevalence of SAD markers such as leukoaraiosis and microbleeds.However,there has not been a unified standards of etiology classification based on morphological for acute BSI at home and abroad and there is no consensus on whether perforator diseases should be included in small or large intracranial artery diseases.Isolated BSI,regardless of size,can be located in territory of single perforating artery or multiple groups of perforating arteries.The clinical manifestations of BSI with different etiology and location may vary greatly.The purpose of this subject is to study the anatomical distribution of BSI,the clinical and imaging features of BSI in different etiology and vascular regions and to analyze the impact of different imaging and clinical characteristics on the neurological deficits and disabilities of patients with BSI at discharge and prognosis in one year later.The study is divided into three parts,and the contents of each part are summarized as follows.Part one Study on clinical and imaging characteristics of patients with isolated brainstem infarctions.Objectives:By analyzing the clinical and imaging characteristics of patients with BSI,we compared the clinical and imaging differences of patients with LAD and SAD,paramedian infarction and non-paramedian infarction,single perforator and multiple perforators involvement.Methods:A total of 302 consecutive patients with non-cardiac isolated BSI within 7 days of onset were enrolled.Those patients who were unstable or dying,whose pre-admission m RS score >2,who have CE risk factors and who with unknown or other causes were excluded.We collect relevant clinical information of patients and evaluate the characteristics of patient's head MRI,including the lesion sites,Whether the lesion is located in the territory of the paramedian perforator artery or in the regions of multiple groups of brainstem perforators,size and volume of the focus and the etiological subtypes of infarcts.The risk factors of BSI patients were analyzed and statistical methods were used to compare clinical and imaging differences between patients with different etiology and perforator regions.Result:1.Baseline information:In our study,the top three risk factors were hypertension,abnormal lipid metabolism and diabetes.Dysfunction and dysarthria are the two most common symptoms,and sensory disorders are relatively common.The incidence of vertigo,dysphagia and diplopia was lower.2.Comparisons of etiological classification and related factors:The proportion of patients with LAD and SAD classification was similar,accounting for about 50% respectively.Female patients in LAD group were significantly higher than those in SAD group,and the difference between the two groups was significant(P=0.006).Although there were not many dysphagia patients in general,the proportion of 24(15.8%)dysphagia patients in LAD group was significantly higher than that 7(4.7%)in SAD group(P = 0.001).In LAD group,patients with hypertension,diabetes mellitus and abnormal lipid metabolism were more than those in SAD group.At admission,average NIHSS score and the number of patients with NIHSS ? 3 were higher than those in SAD group,but there was no significant difference.There was no significant difference in infarct size between the two groups.3.BSI distribution and related factors comparisonPontine infarcts were the most common type of BSI and 284(94.0%)cases were located in the pons.In 4(1.3%)patients the infarct was located in the medulla,8(2.6%)patients in the midbrain,and 6(2.0%)patients in the pons and midbrain.The mean volume of the BSI was 0.38 ml.In 156(51.7%)cases the lesions were located in single perforator territory.In 139 patients(46.0%)the paramedial artery regions were involved.NIHSS score was 5 points in the non-simple paramedian group,and 4 points in the paramedian group at admission.The difference between the two groups was significant(P = 0.018).In the non-simple median group,there were more risk factors such as hypertension,diabetes,abnormal lipid metabolism and smoking,and less number of patients whose NIHSS score ? 3 than that in paramedian group on admission.But the difference was not significant.Part two Study on influencing factors of functional outcome in patients with isolated brainstem infarction at dischargeObjective:By comparing the clinical and imaging characteristics of different subtypes of patients with BSI,we analyzed the related factors of severe neurological impairment when patients was discharged so as to provide basis for their early treatment and secondary prevention.Methods:A total of 302 newly isolated BSI patients from ICAS,who were aged 18-80 years and within 7 days after onset were enrolled.Patients with BSI due to cardiogenic embolism,unknown etiology or other causes were excluded.The clinical and imaging data of the patients were collected.All 302 patients completed the MRI examination.MRA was used to evaluate the presence of stenosis and the degree of stenosis in the intracranial artery.The etiology of BSI patients was assessment.According to the axial position,the location of the lesion was determined whether it was located in the pure paramedian branch or the non-simple paramedian branch,or whether it was located in the territory of single or multiple perforator branches.The lesion size was measured.The degree of leukoaraiosis was evaluated by Fazekas score,and the NIHSS score was used to evaluate the severity of stroke during hospitalization and discharge.NIHSS ? 3 is considered as a mild stroke,and NIHSS ? 4 is considered as a non-mild stroke.The m RS scale was used to evaluate the daily living ability of patients with BSI before and after discharge.Statistical analysis was put to use analyzing the effect of clinical and imaging factors on neurological function of patients with isolated BSI at discharge.Results:1.Baseline characteristicsThe median age of 302 patients with a newly brain infarction was 63 years old.112 patients(37.1%)were women.There are more patients over 65 years old,and the proportion is close to half.Hypertension,abnormal lipid metabolism,diabetes is still the most common risk factor and more than 80% of patients have hypertension and abnormal lipid metabolism.Nearly 50% of patients have diabetes.89.9% of patients had decreased muscle strength,nearly 70% of patients had dysarthria,and about 1/3 had sensory disturbances.Symptoms of the last four frequencies are dizziness,difficulty swallowing,diplopia,and disturbance of consciousness.The proportion of patients with lesions located in medulla oblongata,pons and midbrain was 1.3%,94.0% and 2.6% respectively.150(49.7%)patients were in the SAD subtype and 152(50.3%)were classified as LAD.In 156(51.7%)cases the lesions were located in single perforator territory.In 139 patients(46.0%)the paramedial artery regions were involved.2.Comparison of clinical and imaging characteristics between minor stroke and non-minor strokeThe information of two patients with pontine infarction was incomplete at the time of discharge so only 300 patients' discharge information were analyzed.Univariate analysis found that the severity of the illness at admission was different between the minor and non-non-minor groups.The mean NIHSS score of non-minor stroke patients was 8 and only 6 cases(5.9%)had NIHSS score ? 3,while that of minor stroke patients was 3 and 99 cases(52.4%)had NIHSS score ? 3.There were significant differences between the two subtype(P < 0.0001).92(89.3%)non-minor patients while 192(98.5%)minor patients were still taking antithrombotic drugs at discharge and the difference was very significant(P < 0.0001).The average score of MRS was 3 and 95(90.5%)cases with disability in non-minor patients,while average score of MRS was 1 and 59(30.3%)cases with disability in minor patients.The difference was significant(P < 0.0001).There was a significant difference in hospital stays.The average hospital stay was 17 days for non-light patients and 14 days for minor patients(P = 0.013).In minor BSI patients,99 cases(50.8%)with simple paramedian branch involvement,which were more than 40 cases(38.1%)with non-minor cases(P = 0.036).Among the non-minor patients,63(60.0%)were multiple perforator involvement and 65(61.9%)were LAD subtype which were significantly higher than those in the minor group(P = 0.003,P = 0.002 respectively).The volume of non-minor infarction was 0.72 ml,which was significantly larger than that of minor infarction(P < 0.0001).Those with severe neurological deficits at admission,first symptoms accompanied by decreased muscle strength,vertigo,dysarthria,dysphagia and conscious disturbance,no antithrombotic drugs were taken at discharge were closely related to serious neurological deficits(NIHSS score ? 4 at discharge.The imaging features of lesions located in the non-single paramedial branch territories,multiple groups of perforators involvement,lesion volume > 0.5 ml,etiological subtype of large artery atherosclerosis,and presence of leukoaraiosis were also related to serious neurological deficits(NIHSS score ? 4 points)at discharge.3.Risk factors related to severe neurological deficits of patients with BSI at dischargeMultivariate logistic regression showed that NIHSS score ? 4 points,initial symptoms of vertigo,lesion volume > 0.5 ml,etiological subtypes of LAD,and no antithrombotic drugs at discharge were risk factors for severe neurological deficits(NIHSS score ? 4 points).Part three Study on Prognosis of patients with isolated brainstem infarctions in one yearObjective:This study aimed at analyzing the influence of different clinical and imaging features on the prognosis of neurological deficits and disabilities in BSI patients.Methods:302 patients with new-onset isolated non-cardiogenic BSI within 7 days of onset were enrolled.Relevant clinical information and secondary prevention were collected.Assessing the information of cranial MRI included the specific location of the lesion in the brainstem and whether it was located in the territories of the paramedian perforators,whether it was involved in multiple groups of perforating arteries,the size and volume of the lesion,etiological subtypes,the severity of Leukoaraiosis,the number of asymptomatic lacunar infarctions,etc.The severity of neurological impairment during hospitalization and disability of patients in one year were followed up.Statistical analysis was used to analyze the influence of clinical and imaging features of isolated BSI on the prognosis of patients.Poor prognosis is defined as disability within 1 year of infarction.Results:1.Baseline information:see part one and two.2.Risk factors associated with disability of patients in one year.281 BSI patients were followed up in one year.Of the 281 patients,84(29.9%)were disabled at one-year follow-up.The median NIHSS score at admission was 6.Compared with BSI patients of LAD etiological subtype,patients with BSI of SAD subtype had a higher proportion of minor stroke at discharge(NIHSS score ? 3)while the incidence of dysphagia during hospitalization,disability at discharge and in 1 year were lower.patients with lesions located in territory of paramedian perforators were more likely to have severe leukoaraiosis and a large number of old lacunar infarctions.Their neurological deficits at admission and discharge were less severe and the infarct size was smaller.Some factors such as old age,Fazekas score ? 3,large number of old lacunar infarcts,the severity of neurological deficits at admission and discharge,disability at discharge,lesions located in pons and midbrain,multiple perforator arteries in brainstem involved,large size and volume of focus and conscious disturbance as one of initial symptoms were closely related to disability in 1 year.Multivariate logistic regression showed that Fazekas score ? 3,disability at discharge,multiple perforator artery involvement in brainstem,and no statin at discharge were high risk factors for disability in patients at 1 year of onset.Conclusions:1.In this study,further classification of lesions in patients with newly isolated BSI according to imaging characteristics is helpful to predict the prognosis of patients.2.In this study,We found that NIHSS score ? 4,disability at discharge,lesion volume > 0.5ml,etiological subtype of atherosclerosis,no antithrombotic drugs at discharge,and vertigo as one of onset symptoms were risk factors for severe neurological deficits(NIHSS score ? 4)in patients with BSI at discharge.3.In this study,Fazekas score ?3,disability at discharge,multiple perforator artery involvement in brainstem,and no statin at discharge were high risk factors for disability in patients at 1 year of onset.4.This study suggests that early antithrombotic and statin therapy as well as timely secondary prevention are necessary for the rehabilitation of patients with large BSI,which maybe LAD and may involve multiple groups of perforators.