Distribution Characteristics Of Cerebral Artery Stenosis And Histopathology Of Temporal Artery In Young Ischemic Stroke Patients With Undetermined Etiology

Part Ⅰ Distribution characteristics of cerebral artery stenosis in young ischemic stroke patients with undetermined etiologyObjective:Some young ischemic stroke patients have different degree of cerebral vascular stenosis but their etiology are undetermined. This paper is to investigate and comparie distribution characteristics of cerebral artery stenosis between patients with elevated and normal serum IgE level. At the mean time,we want to discuss their possible etiology.Methods:From March 2008 to August 2015. we selected the research subjects met the inclusion criteria who were young ischemic stroke patients hospitalized in our departmentin. All the patients included in the study should have a complete medical history and complete examination results. At the same time they should meet the following conditions:(1) Between 14-44 years old.(2) Diagnosed with cerebral infarction (CI) or transient ischemic attack (TIA) according to the clinical symptoms and cranial magnetic resonance imaging (CT and magnetic resonance imaging. MRI).(3) No cerebrovascular disease risk factors currently known, such as smoking, alcoholism, obesity, oral contraceptives, hypertension, diabetes, hyperlipidemia and and so on.(4) No evidence of cardiogenic embolism, tumor, blood system diseases, autoimmune diseases and infectious diseases.(5) Received whole brain digital subtraction angiography(DSA) examination and confirmed the presence of cerebral artery stenosis which were greater than or equal to 30%.(6) Except the serum IgE, all other relevant examination, including IgA, IgG, IgM, rheumatoid factor(RF), anti streptolysin O(ASO), complement 3 and 4(C3 and C4), erythrocyte sedimentation rate(ESR), C-reactive protein(CRP),its antibody spectrum and so on,were normal. According to whether the level of serum IgE increased, all the patients included in the study were divided into IgE elevated group and IgE normal group. At the same time, their general clinical data (including age, gender and allergies) and distribution characteristics of cerebral artery stenosis were recorded detailedly. The distribution characteristics of cerebral artery stenosis were judged by whole brain DSA.We recorded the site and the rate of cerebral artery stenosis. All the whole brain DSA were completed by two doctors who had rich experience of cerebrovascular intervention and images were read by two doctors who had rich experience of reading images in our department. The judgment standard of cerebral artery stenosis rate:(1) The standard of North American Symptomatic Carotid Endarterectomy Trial was used to analysis extracranial vessels.(2)The standard of Warfarin-Aspirin Symptomatic Intracranial Disease was used to analysis Intracranial vascular. All data were analyzed using SPSS statistical package 16.0(SPSS Inc.,Chicago,IL,U.S.A). Using Kolmogorov-Smirnov test to analysis the normal distribution of measurement data.For the comparison of the descriptive data, the Students T Test, Pearson Chi-Square Test or Fisher’s Exact Test was applied.A p value less than or equal to 0.05 was considered statistically significant.Result:During March 2008 to August 2015, there were 2382 young stroke patients hospitalized in our departmentin,including 459 patients (19.3%) whose etiology were undetermined. Excluding 127 patients (27.7%) without whole brain DAS examination and/or other relevant examination,168 patients (36.6%) with DSA showed the degree of cerebral artery stenosis less than 30%, only 164 patients (35.7%) were included in this study in the end. According to whether the level of serum IgE was increased, patients were divided into IgE elevated group and IgE normal group. IgE elevated group:41 patients,30 patients were male (73.2%),11 patients were female (26.8%), average age (31.8+8.3) years old. IgE normal group: 123 patients,87 patients were male (70.7%),36 patients were female (29.3%), average age (33.1+7.0) years old. There was no significant difference in the average age of patients in the two groups (t=-1.025 and P=0.307).A total of 307 stenosis in two groups, in which the IgE elevated group had 87, the IgE normal group had 220. Cerebral artery stenosis located in middle cerebral arteries (MCA):35 (40.2%) in IgE elevated group,58(26.4%)in IgE normal group, χ2=5.677, P=0.017. Cerebral artery stenosis located in internal carotid artery:18 (20.7%) in IgE elevated group,83(37.7%)in IgE normal group, x2=8.198, P=0.004. Cerebral artery stenosis located in anterior cerebral artery:5(5.7%)in IgE elevated group,9(4.1%)in IgE normal group, P=0.549. Cerebral artery stenosis located in vertebral artery:11(12.6%)in IgE elevated group,45(20.5%)in IgE normal group, χ2=2.550, P=0.110. Cerebral artery stenosis located in basilar artery:7 (8.0%) in IgE elevated group,11 (5.0%) in IgE normal group, χ2=1-048, P=0.306. Cerebral artery stenosis located in posterior cerebral artery:5 (5.7%) in IgE elevated group,9 (4.1%) in IgE normal group, P=0.549. Cerebral artery stenosis located in common carotid artery:3 (3.4%) in IgE elevated group,1 (0.5%) in IgE normal group, P=0.070. Cerebral artery stenosis located in external carotid artery:3(3.4%)in IgE elevated group,4 (1.8%) in IgE normal group, P=0.409. Cerebral artery stenosis located in anterior circulation:58(66.7%)in IgE elevated group,150(68.2%)in IgE normal group, =0.066, P=0.798. Cerebral artery stenosis located in posterior circulation: 23(26.4%)in IgE elevated group,65(29.5%)in IgE normal group, χ2=0.295,P=0.587. Cerebral artery stenosis located in intracranial vascular:74(85. 1%)in IgE elevated group,171(77.7%)in IgE normal group. Cerebral artery stenosis located in extracranial vascular:13(14.9%)in IgE elevated group,49(22.3%)in IgE normal group. The difference of cerebral artery stenosis in intracranial and extracranial was not statistically significant (χ2=2.079,P=0.149)The average rate of stenosis in IgE elevated group was (68.9+21.5)% and that in IgE normal group was (71.8+18.2)%. There was no significant difference in the average rate of stenosis in the two groups (t=-1.102 and P=0.272).Conclusion:Most of the cerebral artery stenosis were located in the anterior circulation vessels and intracranial vessels. It was considered that the etiology of these young patients maybe associated with cerebral vasculitis. Stenosis Located in middle cerebral artery in IgE elevated group was more common than that in IgE normal group and that located in internal carotid artery in IgE normal group was more common than that in IgE elevated group. It was not clear that whether the difference of distribution characteristics of cerebral vascular stenosis between the two groups was associated with serum IgE.Part Ⅱ Histopathology of temporal artery in young ischemic stroke patients with undetermined etiology and elevated serum-immunoglobulin EObjective:Some young ischemic stroke patients have different degrees of cerebral vascular stenosis, but relevant examination showed no abnormality except serum IgE increased, or all examination showed no abnormality (referred to as normal IgE). their etiology were undetermined. After treatment with glucocorticoid and/or immunosuppressive agents, part of the cerebral vascular stenosis rate was improved obviously. We considered their etiology associated with cerebral vasculitis, but lacking histological evidence. Under the current circumstances, to obtain specimens of cerebral vascular lesion in these patients is very difficult. Previous studies have shown that temporal artery biopsy can be used as a means of pathological diagnosis in some vasculitis. This study was to investigate the characteristics of vascular lesions and the possible etiology of these patients though temporal artery biopsy.Methods:From January 2013 to August 2015, we selected the research subjects met the inclusion criteria who were young ischemic stroke patients hospitalized in our departmentin. All the patients included in the study should have a complete medical history and complete examination results. At the same time they should meet the following conditions:(1) Between 14-44 years old.(2) Diagnosed with cerebral infarction (CI) or transient ischemic attack (TIA) according to the clinical symptoms and cranial magnetic resonance imaging (CT and magnetic resonance imaging,MRI).(3) No cerebrovascular disease risk factors currently known, such as smoking. alcoholism, obesity, oral contraceptives, hypertension, diabetes, hyperlipidemia and and so on.(4) No evidence of cardiogenic embolism, tumor, blood system diseases, autoimmune diseases and infectious diseases.(5) Received whole brain DSA examination and confirmed the presence of cerebral artery stenosis which were greater than or equal to 30%.(6) Except the serum IgE, all other relevant examination, including IgA, IgG, IgM,RF, ASI, C3 and C4, ESR, CRP, its antibody spectrum and so on,were normal. According to whether the level of serum IgE increased, all the patients included in the study were divided into IgE elevated group and IgE normal group. At the same time, their general clinical data (including age, gender and allergies) and distribution characteristics of cerebral artery stenosis were recorded detailedly.Temporal artery biopsy was performed under local anesthesia and then got a specimen about 10mm. After fixation, dehydration, clearing and paraffin paraffin embedding, sections of 4 mm thickness were cut from paraffin blocks. These sections were used for hematoxylin eosin(H-E) staining, toluidine blue staining. imrnunochemical examination of matrix metalloproteinase-9(MMP-9) and monocyte chemotaxis protein-1 (MCP-1)and IgE. Inflammatory cell infiltration lesions and the mast cells were observed by optical microscope. Image-pro plus 6.0 was to analysis vascular intima-media thickness in H-E staining sections, the main site of expression and the average optical density value of MMP-9, MCP-1 and IgE. All data were analyzed using SPSS statistical package 16.0(SPSS Inc.,Chicago,IL,U.S.A). Kolmogorov-Smirnov test was used to analysis the normal distribution of measurement data.For the comparison of the descriptive data, the Students T Test, Pearson Chi-Square Test or Fisher’s Exact Test was applied.A p value less than or equal to 0.05 was considered statistically significant.Result:Histopathology of temporal artery specimens examination was performed on 32 (male/female:23/9) young ischemic stroke patients with undetermined etiology (16 patients with serum IgE normal group and 16 patients with elevated group). Gender, age, lesion distribution, presence of allergens and equal average stenosis rate showed no significant difference between the two groups using Chi-Square Test or Fisher’s Exact Test (P>0.05). HE staining results showed that the membrane can meet the definition of the infiltration of inflammatory cells,2 cases (12.5%) in IgE normal group,7 cases (43.8%) in IgE elevated group.In IgE elevated group,there were still 2 case with inflammatory cell infiltration in the tunica media and 1 case with inflammatory cell infiltration in blood vessel walll. There was 1 case with focal fibrinous membrane necrosis and hemorrhage in IgE elevated group.Compared with IgE normal group, the infiltration of inflammatory cells, necrosis and fibrin exudation showed more common trends in temporal artery specimens of the serum IgE elevated group(P<0.01). The average thickness of the intima of temporal artery was (0.22 ± 0.06)mm in IgE normal group and (0.25 ± 0.06)mm in IgE elevated group, but their difference between the two groups weas not statistically significant (P>0.05). Number of mast cells between the two groups was also not statistically significant(P>0.05).The average optical density value of Monocyte chemotaxis protein-1 (MCP-1) in the temporal artery of the elevated group was higher than that in the normal group and the difference between the two groups was statistically significant[(9.25±5.79) ×10-5 vs (4.41 ±2.87) ×10-5, P<0.01]. The absolute values of the average optical density of matrix metalloproteinase 9 (MMP-9) were relatively high in the serum IgE elevated group, but their difference between the two groups were not statistically significant[(32.79±21.38) ×10-4 vs (25.23±12.78) x10-4, P>0.05]. Immunohistochemical staining results did not find the existence of IgE deposition temporal artery vessel wall specimens.Conclusion:The inflammatory cells infiltration, necrosis and fibrin exudation in the temporal artery of the serum IgE elevated group are likely to be a manifestation of vasculitis. MCP-1 may play a role in the pathogenesis of the disease. Although This conclusion needs responsible cerebral artery of patients with stroke to confirme,but perhaps we can infer that:there may be similar, even more serious pathological changes in young ischemic stroke patients with undetermined etiology and elevated serum-IgE.