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Background@#and Purpose Various mechanisms are involved in the etiology of stroke caused by atherosclerosis of the middle cerebral artery (MCA). Here, we compared differences in plaque nature and hemodynamic parameters according to stroke mechanism in patients with MCA atherosclerosis. @*Methods@#Consecutive patients with asymptomatic and symptomatic MCA atherosclerosis (≥50% stenosis) were enrolled. MCA plaque characteristics (location and plaque enhancement) and wall shear stress (WSS) were measured using high-resolution vessel wall and four-dimensional flow magnetic resonance imaging, respectively, at five points (initial, upstream, minimal lumen, downstream, and terminal). These parameters were compared between patients with asymptomatic and symptomatic MCA atherosclerosis with infarctions of different mechanisms (artery-to-artery embolism vs. local branch occlusion). @*Results@#In total, 110 patients (46 asymptomatic, 32 artery-to-artery embolisms, and 32 local branch occlusions) were investigated. Plaques were evenly distributed in the MCA of patients with asymptomatic MCA atherosclerosis, more commonly observed in the distal MCA of patients with artery-to-artery embolism, and in the middle MCA of patients with local branch occlusion. Maximum WSS and plaque enhancement were more prominent in the minimum lumen area of patients with asymptomatic MCA atherosclerosis or those with local branch occlusion, and were more prominent in the upstream area in those with artery-to-artery embolism. The elevated variability in the maximum WSS was related to stroke caused by artery-to-artery embolism. @*Conclusion@#Stroke caused by artery-to-artery embolism was related to plaque enhancement and the highest maximum WSS at the upstream point of the plaque, and was associated with elevated variability of maximum WSS.
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Background@#There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data. @*Methods@#Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018. @*Results@#The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL. @*Conclusion@#For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.
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Background@#To validate the treatment target of low-density lipoprotein cholesterol (LDL-C) level according to the cardiovascular disease (CVD) risk which was recommended by Korean dyslipidemia guideline. @*Methods@#We used the Korean National Health Insurance Service database which included 3,958,048 people aged 20 to 89 years who underwent regular health screening. The primary outcome was incident CVD, defined as a composite of myocardial infarction and stroke during the follow-up period from 2009 to 2018. @*Results@#The risk of CVD increased from LDL-C level of 70 mg/dL in very high-risk and high-risk groups and from 130 mg/dL in moderate-risk and low-risk groups. Adjusted hazard ratios (HRs) of LDL-C ranges 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL were 1.20 (95% confidence interval [CI], 1.08–1.33), 1.27 (1.15–1.42), 1.39 (1.23–1.56), 1.69 (1.45–1.96), and 1.84 (1.49– 2.27) in very high-risk group, and 1.07 (1.02–1.13), 1.16 (1.10–1.21), 1.29 (1.22–1.36), 1.45 (1.36–1.55), and 1.73 (1.58–1.90) in high-risk group. Adjusted HRs (95% CI) of LDL-C ranges 130–159, 160–189, and ≥190 mg/dL were 1.15 (1.11–1.20), 1.28 (1.22– 1.34), and 1.45 (1.36–1.54) in moderate-risk group and 1.07 (1.02–1.13), 1.20 (1.13–1.26), and 1.47 (1.37–1.57) in low-risk group. @*Conclusion@#We confirmed the incidence of CVD was increased in higher LDL-C range. The risk of CVD increased from ≥70 mg/dL of LDL-C in very high-risk and high-risk groups, and from ≥130 mg/dL of LDL-C in moderate-risk and low-risk groups in Korean adults.
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Purpose@#To propose standardized and feasible imaging protocols for constructing artificial intelligence (AI) database in acute stroke by assessing the current practice at tertiary hospitals in South Korea and reviewing evolving AI models. @*Materials and Methods@#A nationwide survey on acute stroke imaging protocols was conducted using an electronic questionnaire sent to 43 registered tertiary hospitals between April and May 2021. Imaging protocols for endovascular thrombectomy (EVT) in the early and late time windows and during follow-up were assessed. Clinical applications of AI techniques in stroke imaging and required sequences for developing AI models were reviewed. Standardized and feasible imaging protocols for data curation in acute stroke were proposed. @*Results@#There was considerable heterogeneity in the imaging protocols for EVT candidates in the early and late time windows and posterior circulation stroke. Computed tomography (CT)-based protocols were adopted by 70% (30/43), and acquisition of noncontrast CT, CT angiography and CT perfusion in a single session was most commonly performed (47%, 14/30) with the preference of multiphase (70%, 21/30) over single phase CT angiography. More hospitals performed magnetic resonance imaging (MRI)-based protocols or additional MRI sequences in a late time window and posterior circulation stroke. Diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) were most commonly performed MRI sequences with considerable variation in performing other MRI sequences. AI models for diagnostic purposes required noncontrast CT, CT angiography and DWI while FLAIR, dynamic susceptibility contrast perfusion, and T1-weighted imaging (T1WI) were additionally required for prognostic AI models. @*Conclusion@#Given considerable heterogeneity in acute stroke imaging protocols at tertiary hospitals in South Korea, standardized and feasible imaging protocols are required for constructing AI database in acute stroke. The essential sequences may be noncontrast CT, DWI, CT/MR angiography and CT/MR perfusion while FLAIR and T1WI may be additionally required.
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Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a genetic disorder caused by mutation in mitochondrial DNA. Patients with stroke-like episodes show restrictive lesions in diffusion weighted image, whereas magnetic resonance angiography images show both vasodilation or vasoconstriction. Vasodilation may lead to hyperperfusion and cerebral edema, which may worsen clinical outcome. Here, we report a 25-year-old male patient diagnosed as MELAS, who presented with stroke-like episodes and seizures and showed cerebral edema with vasodilation which was normalized after steroid treatment.
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Objective@#The role of low-density lipoprotein cholesterol (LDL-C) after carotid artery stenting (CAS) is not well known with respect to stented-territory infarction (STI) and instent restenosis (ISR). We hypothesized that LDL-C levels after CAS might be independently associated with STI and ISR. @*Methods@#We conducted a retrospective study for patients with significant extracranial carotid stenosis who were subjected to CAS between September 2013 and May 2021. LDL-C levels were measured after 6 and 12 months following CAS. The association between STI and ISR, and LDL-C was explored using Cox proportional-hazard model. @*Results@#Of 244 patients enrolled, STI and ISR were observed in 11 (4.5%) and 10 (4.1%) patients, respectively. In multivariable analysis, higher white blood cell count (hazard ratio [HR], 1.408 per 103 /mm3 ; 95% confidence interval [CI], 1.085–1.828; p=0.010), higher LDL-C levels after 12 months (HR, 1.037 per 1 mg/dL; 95% CI, 1.011–1.063; p=0.005), and ISR (HR, 13.526; 95% CI, 3.405–53.725; p<0.001) were independent predictors of STI. Diabetes (HR, 4.746; 95% CI, 1.026–21.948; p=0.046), smaller stent diameter (HR, 0.725 per 1 mm; 95% CI, 0.537–0.980; p=0.036), and higher LDL-C levels after 12 months (HR, 1.031 per 1 mg/dL; 95% CI, 1.007–1.055; p=0.011) were independent predictors of ISR. @*Conclusion@#We showed that LDL-C levels after 12 months independently predict STI and ISR after CAS. It is necessary to investigate the optimal target LDL-C level for STI prevention through well designed research in the future.
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Background@#and Purpose The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) scores have been validated in estimating the risks of ischemic stroke and major bleeding, respectively, in patients with atrial fibrillation (AF). This study investigated stroke-specific predictors of major bleeding in patients with stroke and AF who were taking oral anticoagulants (OACs). @*Methods@#Subjects were selected from patients enrolled in the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) nationwide multicenter registry between 2013 and 2015. Patients were excluded if they were not taking OACs, had no brain imaging data, or had intracranial bleeding directly related to the index stroke. Major bleeding was defined according to International Society of Thrombosis and Haemostasis criteria. Cox regression analyses were performed to assess the associations between clinical variables and major bleeding and Kaplan-Meier estimates were performed to analyze event-free survival. @*Results@#Of a total of 3,213 patients, 1,414 subjects (mean age of 72.6 years, 52.5% males) were enrolled in this study. Major bleeding was reported in 34 patients during the median follow-up period of 1.73 years. Multivariable analysis demonstrated that initial National Institutes of Health Stroke Scale scores (hazard ratio [HR] 1.07, p=0.006), hypertension (HR 3.18, p=0.030), persistent AF type (HR 2.51, p=0.016), and initial hemoglobin level (HR 0.74, p=0.001) were independently associated with major bleeding risk. Except for hypertension, these associations remained significant after adjusting for the HAS-BLED score. Intracranial atherosclerosis presented a trend of association without statistical significance (HR 2.21, p=0.050). @*Conclusions@#This study found that major bleeding risk was independently associated with stroke-specific factors in anticoagulated patients with stroke and AF. This has the clinical implication that baseline characteristics of patients with stroke and AF should be considered in secondary prevention, which would bring the net clinical benefit of balancing recurrent stroke prevention with minimal bleeding complications.
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Background@#and Purpose Ischemic stroke recurs despite the use of antiplatelet agents. Various mechanisms are involved in recurrence due to intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS). High-on-aspirin platelet reactivity (HAPR) may differ between recurrent stroke due to ICAS and ECAS. @*Methods@#Patients with recurrent ischemic stroke as a result of large-artery atherosclerosis despite taking aspirin were enrolled consecutively. Ischemic stroke was classified as stroke due to ICAS or ECAS according to the location of the culprit stenosis. An aspirin reaction units (ARU) value of >550 IU was defined as HAPR. HAPR and its associated factors were compared between the two groups and also considering the mechanism of stroke. @*Results@#Among the 190 patients with recurrent stroke (111 with ICAS and 79 with ECAS), 36 (18.3%) showed HAPR. The ARU value was higher in the ECAS than the ICAS group (492± 83 vs. 465±78, mean±standard deviation; p=0.028), as was the proportion of patients with HAPR (27.8% vs. 12.6%, p=0.008). Being male and having stroke due to ECAS (reference = stroke due to ICAS: odds ratio=5.760; 95% confidence interval=2.154–15.403; p<0.001) was independently associated with HAPR. The ARU value differed according to the stroke mechanism, and was highest in those with artery-to-artery embolism. Artery-to-artery embolism was independently associated with HAPR in both the ICAS and ECAS groups. @*Conclusions@#Recurrent stroke due to ECAS was more strongly associated with HAPR and insufficient antiplatelet inhibition than was that due to ICAS. Artery-to-artery embolism was associated with HAPR in recurrent ischemic stroke as a result of ICAS or ECAS.
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Background@#and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. @*Methods@#This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). @*Results@#Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. @*Conclusions@#Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
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Background@#and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. @*Methods@#This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). @*Results@#Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. @*Conclusions@#Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
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Background@#and Purpose To evaluate the outcome events and bleeding complications of the European Society of Cardiology (ESC) guideline-matched oral anticoagulant therapy for patients with acute ischemic stroke and atrial fibrillation (AF). @*Methods@#Patients with acute ischemic stroke and AF from a nationwide multicenter registry (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts [K-ATTENTION]) between January 2013 and December 2015 were included in the study. Patients were divided into the ESC guideline-matched and the non-matched groups. The primary outcome was recurrence of any stroke during the 90-day follow-up period. Secondary outcomes were major adverse cerebrovascular and cardiovascular events, ischemic stroke, intracranial hemorrhage, acute coronary syndrome, allcause mortality, and major hemorrhage. Propensity score matching and logistic regression analyses were performed to assess the effect of the treatments administered. @*Results@#Among 2,321 eligible patients, 1,126 patients were 1:1 matched to the ESC guidelinematched and the non-matched groups. As compared with the non-matched group, the ESC guideline-matched group had a lower risk of any recurrent stroke (1.4% vs. 3.4%; odds ratio [OR], 0.41; 95% confidence interval [CI], 0.18 to 0.95). The risk of recurrent ischemic stroke was lower in the ESC guideline-matched group than in the non-matched group (0.9% vs. 2.7%; OR, 0.32; 95% CI, 0.11 to 0.88). There was no significant difference in the other secondary outcomes between the two groups. @*Conclusions@#ESC guideline-matched oral anticoagulant therapy was associated with reduced risks of any stroke and ischemic stroke as compared with the non-matched therapy.
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Acute cerebral infarction secondary to glioblastoma is rarely reported, and its mechanism is still controversial. Vascular infiltration of malignant cell, direct mass effect and local procoagulant effect were considered as main pathophysiology. We report a case of glioblastoma-related cerebral infarction documented by high resolution vessel wall magnetic resonance imaging, which reveals concentric enhancement of arterial wall and intraluminal thrombus without direct compression. These findings suggest tumor cell infiltration of intracranial vessels is one of the important mechanisms of glioblastoma-related cerebral infarction.
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Carotid stenosis is an important etiology of ischemic stroke. Most of the strokes associated with carotid stenosis are caused by artery-to-artery embolism. The risk of embolism highly depends on the stenosis degree and the vulnerability of the carotid plaque. Carotid ultrasonography is useful for evaluating the characteristics of carotid plaque. This review aims to provide information on performing and interpreting the result of carotid ultrasonography and the treatment of carotid artery disease based on the current guidelines. The degree of stenosis can be measured by the diameter reduction and flow velocity criteria. The risk of embolism is highest when the stenosis degree is around 70% to 80%. A heterogeneous echolucent plaque with an irregular surface or an ulcer shows a high risk of embolism. Appropriate treatment is important for the patients with carotid stenosis. In symptomatic patients, a potent antiplatelet treatment, especially during the acute stage, is beneficial. Patients with asymptomatic stenosis over 50% can also be considered for antiplatelet treatments. The associated risk factors should be managed according to the targets. Medically intractable cases or patients with high risk of embolism may receive carotid endarterectomy or carotid artery stenting depending on the concomitant disease and the degree of carotid stenosis. Considering the safety of ultrasound imaging, treatment may be followed-up by carotid ultrasonography.
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Background@#and Purpose The outcome of endovascular treatment (EVT) may differ depending on the etiology of arterial occlusion. This study aimed to assess the differences in EVT outcomes in patients with intracranial arterial steno-occlusion (ICAS-O), artery-to-artery embolism (AT-O), and cardiac embolism (CA-O). @*Methods@#We retrospectively analyzed 330 patients with ischemic stroke who underwent EVT between January 2012 and August 2017. Patients were classified according to the etiology. The clinical data, EVT-related factors, and clinical outcomes were compared. The modified Rankin Scale (mRS) score at 3 months, determined using ordinal logistic regression (shift analysis), was the primary outcome. @*Results@#CA-O (n=149) was the most common etiology, followed by ICAS-O (n=63) and AT-O (n=49). Age, initial National Institutes of Health Stroke Scale (NIHSS) score, and rate of hemorrhagic transformation were significantly higher in patients with CA-O compared to AT-O and ICAS-O. The time from onset-to-recanalization was the shortest in the CA-O (356.0 minutes) groups, followed by the AT-O (847.0 minutes) and ICAS-O (944.0 minutes) groups. The rates of successful recanalization, mRS distribution, and favorable outcomes at 3 months (mRS 0–2; CA-O, 36.9%, AT-O, 53.1%; and ICAS-O, 41.3%) did not differ among the three groups. Baseline NIHSS score (odds ratio, 0.87; 95% confidence interval, 0.83 to 0.91) could independently predict a favorable shift in mRS distribution. @*Conclusions@#The functional outcomes of ICAS-O and AT-O were similar to those of CA-O, despite the delay in symptom onset-to-recanalization, suggesting that the therapeutic time window may be extended in these patients.
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Background@#and Purpose: The incidence of ischemic stroke (IS) in young adults is increasing, and the associated large socioeconomic impact makes understanding IS in young adults important. We investigated the causes of and risk factors for IS in young adults, and their impact on outcomes. @*Methods@#The Stroke in Korean Young Adults (SKY) study is a standardized multicenter prospective study involving eight medical centers of the Republic of Korea. First-ever IS patients aged 18 years to 44 years were prospectively included in this study within 7 days of stroke onset.Their outcomes at 3 months were analyzed. @*Results@#This study enrolled 270 patients from April 2014 to December 2018, most (67.8%) of whom were male. About 41.5% of the patients had one or more vascular risk factors from among hypertension, diabetes mellitus, and dyslipidemia. However, only half of them had received regular treatment. Arterial dissection was more common in males, and systemic lupus erythematosus (SLE) and Moyamoya disease were more common in females. The outcome was favorable (modified Rankin Scale score of 0 or 1) in 81.9% of the patients at 3 months after stroke onset. More severe initial symptoms, higher initial glucose level, and SLE as a comorbidity were associated with unfavorable outcomes. @*Conclusions@#Young adult IS patients in Korea exhibit low awareness and poor management of their risk factors. Although the short-term outcome was relatively favorable in those patients, having SLE was associated with unfavorable outcomes. More attention needs to be paid for improving awareness and controlling risk factors in this population.
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Purpose@#Specific IgG4 (sIgG4) increases with allergen specific immunotherapy and may reflect a state of immune tolerance in food allergy. While ImmunoCAP® has been widely used to measure sIgG4 to a single allergen, PROTIATM Specific IgG4® has been designed as a multiplex assay for measuring sIgG4. This study sought to validate this assay in comparison to ImmunoCAP®. @*Materials and Methods@#Measurements of sIgG4 were compared between PROTIATM Specific IgG4® and ImmunoCAP® using sera from 519 allergy patients (asthma: 114, allergic rhinitis: 318, food allergy: 146) with 731 paired tests. sIgG4 was measured against nine inhalant allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat dander, dog dander, birch pollen, oak pollen, ragweed pollen, mugwort pollen, and Alternaria alternata spores) and nine food allergens (egg white, casein, wheat, peanut, walnut, crab, shrimp, apple, and peach). @*Results@#PROTIATM Specific IgG4® showed 95.6% agreement rate with ImmunoCAP® in the positivity comparison. For sIgG4 positivity to each individual allergen, an agreement rate of more than 84.8% was observed. In Cohen’s kappa analysis, these assays displayed substantial correlations [Cohen’s kappa coefficient (κ) ≥0.699], except for shrimp (κ=0.448). Furthermore, both assays displayed strong correlations in quantitative comparisons [correlation coefficients value (ρ) ≥0.8014], except for apple (ρ=0.6571, p=0.175). Serial dilution tests also showed consistency between the assays. @*Conclusion@#PROTIATM Specific IgG4® showed high consistency with ImmunoCAP® in measuring sIgG4. This assay is applicable to various clinical fields, including allergen immunotherapy and food allergy.
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Influenza is an epidemical acute respiratory disease caused by viral infection. Several complications in the respiratory tract, such as pneumonia can occur. However, rare but serious neurological complications are also observed. Here, we described the prevalence, characteristics and suggestive pathomechanism of syncope after influenza infection season. Of 2.2% of patients diagnosed as influenza experienced syncope. None of the patients had severe cough, low blood pressure (BP) or dehydration. Patients suffered with frequent dizziness before syncope. Patient with long duration of loss of consciousness was more observed in those with high fever or positive orthostatic BP drop.
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The myelination of axons in the vertebrate nervous system through oligodendrocytes promotes efficient axonal conduction, which is required for the normal function of neurons. The central nervous system (CNS) can regenerate damaged myelin sheaths through the process of remyelination, but the failure of remyelination causes neurological disorders such as multiple sclerosis. In mammals, parenchymal oligodendrocyte progenitor cells (OPCs) are known to be the principal cell type responsible for remyelination in demyelinating diseases and traumatic injuries to the adult CNS. However, growing evidence suggests that neural stem cells (NSCs) are implicated in remyelination in animal models of demyelination. We have previously shown that olig2+ + radial glia (RG) have the potential to function as NSCs to produce oligodendrocytes in adult zebrafish. In this study, we developed a zebrafish model of adult telencephalic injury to investigate cellular and molecular mechanisms underlying the regeneration of oligodendrocytes. Using this model, we showed that telencephalic injury induced the proliferation of olig2+ + RG and parenchymal OPCs shortly after injury, which was followed by the regeneration of new oligodendrocytes in the adult zebrafish. We also showed that blocking Notch signaling promoted the proliferation of olig2+ RG and OPCs in the normal and injured telencephalon of adult zebrafish. Taken together, our data suggest that Notch-regulated proliferation of olig2+ RG and parenchymal OPCs is responsible for the regeneration of oligodendrocytes in the injured telencephalon of adult zebrafish.
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The myelination of axons in the vertebrate nervous system through oligodendrocytes promotes efficient axonal conduction, which is required for the normal function of neurons. The central nervous system (CNS) can regenerate damaged myelin sheaths through the process of remyelination, but the failure of remyelination causes neurological disorders such as multiple sclerosis. In mammals, parenchymal oligodendrocyte progenitor cells (OPCs) are known to be the principal cell type responsible for remyelination in demyelinating diseases and traumatic injuries to the adult CNS. However, growing evidence suggests that neural stem cells (NSCs) are implicated in remyelination in animal models of demyelination. We have previously shown that olig2+ + radial glia (RG) have the potential to function as NSCs to produce oligodendrocytes in adult zebrafish. In this study, we developed a zebrafish model of adult telencephalic injury to investigate cellular and molecular mechanisms underlying the regeneration of oligodendrocytes. Using this model, we showed that telencephalic injury induced the proliferation of olig2+ + RG and parenchymal OPCs shortly after injury, which was followed by the regeneration of new oligodendrocytes in the adult zebrafish. We also showed that blocking Notch signaling promoted the proliferation of olig2+ RG and OPCs in the normal and injured telencephalon of adult zebrafish. Taken together, our data suggest that Notch-regulated proliferation of olig2+ RG and parenchymal OPCs is responsible for the regeneration of oligodendrocytes in the injured telencephalon of adult zebrafish.
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PURPOSE: Component-resolved diagnostics (CRD) is expected to provide additional diagnostic information in allergic patients. PROTIA™ Allergy-Q 64 Atopy®, a recently developed CRD-based multiplex specific immunoglobulin E (sIgE) assay, can quantitatively measure sIgE to major allergen components. METHODS: The sIgE detection by PROTIA™ Allergy-Q 64 Atopy® and ImmunoCAP® assays was compared using the sera of 125 Korean allergic patients. Group 1 and 2 allergens of house dust mites (HDMs; Dermatophagoides farinae (Der f) 1 and Der f 2 in PROTIA™ Allergy-Q 64 Atopy®, Dermatophagoides pteronyssinus (Der p) 1 and Der p 2 in ImmunoCAP®), Bet v 1, Fel d 1, Que a 1, ω-5 gliadin, α-lactalbumin, β-lactoglobulin, casein and α-Gal were measured by both assays. RESULTS: Comparing the results from the 2 assays, the agreement rate for all the 10 allergens was > 88% (group 1 HDM allergen, 100%; group 2 HDM allergen, 94.6%; Bet v 1, 97.4%; Fel d 1, 90.5%; Que a 1, 89.2%; α-lactalbumin, 96%; β-lactoglobulin, 88%; casein, 88%; ω-5 gliadin, 96%; α-Gal, 100%). Correlation analysis indicated that, all the 10 allergen sIgEs showed more than moderate positive correlation (Pearson correlation coefficients > 0.640). Additionally, intra-class comparison showed more than high correlation for all the 10 allergens (Spearman's rank correlation coefficients > 0.743). CONCLUSIONS: PROTIA™ Allergy-Q 64 Atopy® is reliable and comparable to the ImmunoCAP® assay for component-resolved diagnosis.