Urgent Demand of Network Access for Acute Ischemic Stroke Management in Taiwan.

Time is the major determinant in successful reperfusion therapy of acute ischemic stroke. The evolving diagnostic tools and treatment of acute stroke has made a great progress in the past 2 decades and is remolding current management practices. It demands a timely neurologic evaluation and a neuroimaging study to determine if stroke patients are appropriate candidates for reperfusion demands. Therefore, it is critical for the setting of stroke center accreditation levels and capabilities so that timely and appropriate treatment is initiated for the eligible stroke patients. Optimal acute ischemic stroke treatment requires all levels of stroke center network operating efficiently. In the future, Taiwan should revise the criteria of stroke center accreditation and set up the efficient acute stroke treatment network as soon as possible. Keywords: stroke, reperfusion, intra-arterial thrombectomy, intravenous recombinant tissue plasminogen activator.

Statins and the risk of bleeding in patients taking dabigatran.

OBJECTIVES: Dabigatran etexilate is a direct thrombin inhibitor that clinicians increasingly prescribe to prevent stroke in patients with non-valvular atrial fibrillation (NVAF). Clinicians also commonly prescribe statins for primary and secondary prevention of cardiovascular diseases. Little is known about the bleeding risk in patients taking a statin and dabigatran together. The aim of this study was to evaluate the safety and persistence of dabigatran after co-medication with statins. MATERIALS AND METHODS: We performed a prospective, multicenter registry study of stroke patients with NVAF who initiated dabigatran therapy within 3 months after a clinically evident ischemic cerebrovascular event between 2013 and 2017. The main outcome measure was symptomatic bleeding after 90, 180, and 360 days. RESULTS: In total, 652 patients (336 statin users, 316 non-users) were followed for 1 year after dabigatran therapy. Cox multivariate analysis demonstrated that male sex, prior use of aspirin, and concurrent use of an antiarrhythmic drug were associated with a higher risk of bleeding at 360 days. After adjusting time-dependent covariates, statin users had a significantly lower bleeding risk (adjusted hazard ratio: 0.11, P < 0.001) than non-users. Kaplan-Meier analysis indicated that patients prescribed with statins had a higher rate of bleeding-free survival (P = 0.028). CONCLUSION: For secondary prevention of stroke in patients with NVAF who are taking dabigatran etexilate, co-prescription with a statin was associated with a lower risk of bleeding complications. Future research is needed to determine the pharmacological mechanism underlying this effect.

Dynamic Cerebral Autoregulation Is an Independent Functional Outcome Predictor of Mild Acute Ischemic Stroke.

Background and Purpose- Cerebral autoregulation is impaired in patients with acute ischemic stroke. The purpose of this study was to investigate whether dynamic cerebral autoregulation (dCA) indices constitute an independent functional outcome predictor of acute ischemic stroke. Methods- In this study, 86 patients at days 3 to 7 after acute ischemic stroke and 40 age- and sex-matched controls were enrolled for assessing their dCA indices under spontaneous hemodynamic fluctuations. The dCA indices of patients with favorable outcomes (modified Rankin Scale score ≤1 at 3 months, n=65), patients with unfavorable outcomes (modified Rankin Scale score ≥2 at 3 months, n=21), and controls were compared. Results- The dCA indices, namely the phase shift at very low frequency band (phase_VLF), in the patients with unfavorable outcomes were significantly worse than those in the patients with favorable outcomes. However, the phase_VLF in the patients with favorable outcomes did not differ from those in the controls. Impaired dCA was associated with elevated mean arterial pressure and large infarction volume but was also present in patients with normal mean arterial pressure or small infarction volume. Phase_VLF was a predictor of outcomes in the receiver operating characteristic analysis (area under the curve: 0.722; P<0.001). Multivariate analysis revealed that a phase_VLF value of <61° was independently associated with unfavorable outcomes (odds ratio=4.90; P=0.024). Conclusions- Phase_VLF is an independent functional outcome predictor of acute ischemic stroke.

White matter hyperintensities in migraine: Clinical significance and central pulsatile hemodynamic correlates.

Background The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities in migraine patients has not been clarified. Methods Sixty patients with migraine (20-50 years old; women, 68%) without overt vascular risk factors and 30 demographically-matched healthy controls were recruited prospectively. Cerebral white matter hyperintensities volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure, carotid-femoral pulse wave velocity, and carotid augmentation index were measured by applanation tonometry. Carotid pulsatility index was derived from Doppler ultrasound carotid artery flow analysis. Results Compared to the controls, the migraine patients had higher white matter hyperintensities frequency (odds ratio, 2.75; p = 0.04) and greater mean white matter hyperintensities volume (0.174 vs. 0.049, cm3, p = 0.04). Multivariable regression analysis showed that white matter hyperintensities volume in migraine patients was positively associated with central systolic blood pressure ( p = 0.04) and carotid-femoral pulse wave velocity ( p < 0.001), but negatively associated with carotid pulsatility index ( p = 0.04) after controlling for potential confounding factors. The interaction effects observed indicated that the influence of carotid-femoral pulse wave velocity ( p = 0.004) and central systolic blood pressure ( p = 0.03) on white matter hyperintensities formation was greater for the lower-carotid pulsatility index subgroup of migraine patients. White matter hyperintensities volume in migraine patients increased with decreasing carotid pulsatility index and with increasing central systolic blood pressure or carotid-femoral pulse wave velocity. Conclusions White matter hyperintensities are more common in patients with migraine than in healthy controls. Increased aortic stiffness or central systolic blood pressure in the presence of low intracranial artery resistance may predispose patients with migraine to white matter hyperintensities formation.

Delayed diagnosis of atrial fibrillation after first-ever stroke increases recurrent stroke risk: a 5-year nationwide follow-up study.

BACKGROUND: Delayed detection of atrial fibrillation (AF) is common in patients with stroke. However, it is not well known whether delayed identification of AF in patients with stroke affects the prognosis of patients. AIMS: To evaluate the association between the timing of AF diagnosis after stroke and clinical outcomes. METHODS: We identified a cohort of all patients admitted with a primary diagnosis of first-ever ischaemic stroke, which was categorised into three groups, namely, non-AF, AF presenting with stroke and delayed AF diagnosis groups. The study patients were individually followed for 5 years to evaluate the occurrence of recurrent stroke and death. RESULTS: In total, 17 399 patients were hospitalised with first-ever ischemic stroke, of whom 16 261 constituted the non-AF group, 907 the AF presenting with stroke group and 231 the delayed AF diagnosis group. During the 5-year follow up, 2773 (17.1%), 175 (19.3%) and 68 (29.4%) patients in the non-AF, AF presenting with stroke and delayed AF diagnosis groups, respectively, were hospitalised for recurrent stroke. The delayed AF diagnosis group exhibited a 1.57-times higher risk of recurrent stroke than the AF presenting with stroke group, after adjustment for the CHA2DS2-VASc scores (adjusted hazard ratio (HR): 1.57; 95% confidence interval (CI) = 1.19-2.08; P = 0.002). In addition, delayed diagnosis of AF significantly increased the risk of recurrent stroke in men, but not in women, after adjustment for the CHA2DS2-VASc scores. CONCLUSION: Delayed diagnosis of AF after stroke increased the risk of recurrent stroke, particularly in men.

Extracranial and Intracranial Ultrasonographic Findings in Posterior Circulation Infarction.

OBJECTIVES: Patients with posterior circulation infarction are at higher risk of early recurrent stroke, especially those with vertebrobasilar stenosis or hypoplasia. The clinical presentations of this condition vary over a broad range, making diagnosis and treatment a challenge. Hemodynamic changes and stenosis detected by ultrasonography (US) are sensitive and important indicators for further evaluation. In this study, we correlated extracranial and intracranial US characteristics with brain magnetic resonance imaging (MRI) in patients with posterior circulation infarction. METHODS: Inpatients with acute ischemic stroke who received both MRI and US were enrolled. Baseline characters, underlying disorders, the ischemic territory, and vascular stenosis on MRI were recorded. Series of US data, including flow volume, diameter, mean velocity, and pulsatility index, were analyzed. Patients with new infarction over the medulla, pons, midbrain, or cerebellum were enrolled as the posterior circulation infarction group. Patients with pure anterior circulation infarction were also enrolled. RESULTS: A total of 210 patients with anterior circulation infarction (mean age ± SD, 66.24 ± 12.88 years) and 143 with posterior circulation infarction (mean age, 65.82 ± 11.39 years) were enrolled. Significant higher frequencies of vertebral artery hypoplasia and decreased intracranial vertebrobasilar velocity in the posterior circulation infarction group (44.75% and 64.33%, respectively) were documented (P < .0001; P = .035). Ischemic lesion distributions were correlated with vertebral artery hypoplasia (55.56 %) and low vertebral and basilar artery velocities (44.44% and 25.53%), as documented by US. A low vertebrobasilar velocity was highly correlated with MRI-documented vascular stenosis (53.06%). CONCLUSIONS: Vertebral artery hypoplasia and a low velocity in the intracranial vertebrobasilar system on US might change the treatment of patients with posterior circulation infarction for primary and secondary prevention.

Posterior Circulation Ischemic Stroke Caused by Arterial Dissection: Characteristics and Predictors of Poor Outcomes.

BACKGROUND: Posterior circulation ischemic stroke (PCS) caused by arterial dissection (AD-PCS) was rarely discussed. The present study aimed to evaluate the clinical characteristics and predictors of poor outcomes in AD-PCS patients. METHODS: A total of 286 PCS patients were recruited from Taipei Veterans General Hospital Stroke Registry (between January 1, 2012 and February 28, 2014). Clinical/image data of recruited PCS patients were reviewed by stroke specialists who reached a consensus on the stroke etiologies. Data of AD-PCS patients were analyzed. RESULTS: Seventy-four patients (65.8 ± 15.6 years, 56 (75.7%) men) were determined as AD-PCS. Headache and neck pain at admission were only presented in 18.9 and 6.8% of patients, respectively. The location of AD was initiated in the vertebral artery (66.2%), basilar artery (27.0%), posterior inferior cerebellar artery (5.4%) and posterior cerebral artery (1.4%). The involvement of intracranial arteries was present in the majority of patients (97.3%). Of the patients, 9.5% died, and 29.7% had poor functional outcomes (modified Rankin Scale ≥4) at 3-month. Conscious change independently predicted mortality at 3 months. Quadriparesis, National Institutes of Health Stroke Scale (NIHSS) score >8 and infarct lesions involving >1 category were independent predictors for poor functional outcomes at 3 months. CONCLUSION: AD is an important etiology of PCS. Physicians should be more vigilant in recognizing AD-PCS. Intracranial arteries are more important in AD-PCS; very few patients of AD-PCS had dissection solely in extracranial arteries. Short-term outcomes of AD-PCS were not favorable. Conscious change, quadriparesis, NIHSS score >8 and infarct lesions involving >1 category were independent predictors for poor outcomes. Patients presenting these factors should be monitored closely.

Chronic Influences of Obstructive Sleep Apnea on Cerebral Venous Flow.

OBJECTIVES: Evidence reveals a pathophysiologic link between sleep apnea syndrome and cerebrovascular diseases. It is known that obstructive sleep apnea (OSA) may cause serial hemodynamic changes and structural abnormalities in the cerebral and cardiac arterial systems, but its effect on the cerebral venous system has remained unclear. The purpose of this study was to compare internal jugular vein hemodynamics between patients with OSA and healthy individuals. METHODS: Patients with OSA and age-, body mass index-, and sex-matched healthy control participants were recruited for a jugular venous duplex study and neurologic examination. The luminal area of the internal jugular vein, jugular venous flow volume, time-averaged mean velocity, and presence of jugular venous reflux were recorded. These flow characteristics were obtained at different respiratory statuses, and we analyzed the differences between patients and controls. RESULTS: In the OSA group, there was an increasing flow volume in total internal jugular veins at rest. The frequency of venous reflux in patients compared with controls was significantly decreased (26.7% versus 53.3%, respectively; P < .05). The internal jugular vein drainage dominance was greater on the left side in the OSA group (right versus left: 48.8% versus 51.2%), whereas it was greater on the right side in the control group (right versus left: 61.7% versus 38.3%). CONCLUSIONS: Our data showed peculiar internal jugular vein hemodynamics at baseline and different respiratory statuses in patients with OSA. These characteristics imply that cerebral venous drainage conditions might be involved in the pathophysiologic mechanisms of OSA syndrome.

Bilateral Paramedian Thalamic Infarction Presenting as Status Epilepticus: A Case Report and Review of the Literatures.

PURPOSE: Occlusion of the artery of Percheron (AOP), a rare vascular variant of basilar artery branch, is presumed to cause bilateral paramedian thalamic infarction. We present a case of acute AOP infarction with status epilepticus. CASE REPORT: A 65-year-old woman had past history of hypertension, type 2 diabetes mellitus, and major depressive disorder. She was found to have altered mental status on awakening. She developed tonic convulsion and progressed to status epilepticus later. The brain magnetic resonance imaging (MRI) showed acute bilateral paramedian thalamic and interpeduncular mesencephalic infarction. The electroencephalography (EEG) showed continuous epileptiform discharges. After receiving antiplatelet and anticonvulsant agents, she regained her level of consciousness and has completely recovered to previous baseline. CONCLUSIONS: To our knowledge, this is the first case of AOP infarction presenting status epilepticus. Early recognition and treatment of seizure may reverse altered mental status in those patients.

Different doses of recombinant tissue-type plasminogen activator for acute stroke in Chinese patients.

BACKGROUND AND PURPOSE: The relationship between the dose of recombinant tissue-type plasminogen activator (r-tPA) and its safety/efficacy for ischemic stroke has not been well evaluated in the East Asian population. We assessed the safety/efficacy of different doses of r-tPA for acute ischemic stroke in Chinese patients. METHODS: A total of 1004 eligible patients were classified according to the dose of r-tPA received for managing acute ischemic stroke: 0.9 mg/kg (n=422), 0.8 mg/kg (n=202), 0.7 mg/kg (n=199), and 0.6 mg/kg (n=181). The safety outcome was symptomatic intracerebral hemorrhage and death within 3 months. The efficacy outcome was good functional outcome (modified Rankin Scale ≤1) at 3 months. RESULTS: There was a significant trend for symptomatic intracerebral hemorrhage with age (P=0.002). With multivariate logistic regression analysis, a dose of 0.9 mg/kg was a predictor of symptomatic intracerebral hemorrhage (P=0.0109), and a dose ≤0.65 mg/kg was a predictor of good functional outcome (P=0.0369). In patients aged 71 to 80 years, there was a significant trend of increasing symptomatic intracerebral hemorrhage (P=0.0130) and less good functional outcome (P=0.0179) with increasing doses of r-tPA. There was also a trend of increasing mortality (P=0.0971) at 3 months in these patients. CONCLUSIONS: These results did not support the dose of 0.9 mg/kg of r-tPA being optimal for all patients in the East Asian population. In elderly patients (71-80 years), a lower dose of 0.6 mg/kg is associated with a better outcome. Confirmation of the results through randomized trial is required.

Internal jugular venous abnormalities in transient monocular blindness.

BACKGROUND: The etiology of transient monocular blindness (TMB) in patients without carotid stenosis has been linked to ocular venous hypertension, for their increased retrobulbar vascular resistance, sustained retinal venule dilatation and higher frequency of jugular venous reflux (JVR). This study aimed to elucidate whether there are anatomical abnormalities at internal jugular vein (IJV) in TMB patients that would contribute to impaired cerebral venous drainage and consequent ocular venous hypertension. METHODS: Contrast-enhanced axial T1-weighted magnetic resonance imaging (MRI) was performed in 23 TMB patients who had no carotid stenosis and 23 age- and sex-matched controls. The veins were assessed at the upper IJV (at C1-3 level) and the middle IJV (at C3-5 level). Grading of IJV compression/stenosis was determined bilaterally as follows: 0 = normal round or ovoid appearance; 1 = mild flattening; 2 = moderate flattening; and 3 = severe flattening or not visualized. RESULTS: There was significantly more moderate or severe IJV compression/stenosis in the TMB patients at the left upper IJV level and the bilateral middle IJV level. Defining venous compression/stenosis scores ≥ 2 as a significant cerebral venous outflow impairment, TMB patients were found to have higher frequency of significant venous outflow impairment at the upper IJV level (56.5% vs. 8.7%, p = 0.0005) and the middle IJV level (69.6% vs. 21.7%, p=0.0011). CONCLUSIONS: TMB Patients with the absence of carotid stenosis had higher frequency and greater severity of IJV compression/stenosis which could impair cerebral venous outflow. Our results provide evidence supporting that the cerebral venous outflow abnormality is one of the etiologies of TMB.

Jugular venous reflux and brain parenchyma volumes in elderly patients with mild cognitive impairment and Alzheimer's disease.

BACKGROUND: To determine whether or not jugular venous reflux (JVR) is associated with structural brain parenchyma changes in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: 16 AD patients (mean (SD): 81.9 (5.8) years), 33 MCI patients (mean (SD): 81.4 (6.1) years) and 18 healthy elderly controls (mean (SD): 81.5 (3.4) years) underwent duplex ultrasonography and magnetic resonance imaging scans to quantify structural brain parenchyma changes. Normalized whole brain (WB), gray matter (GM) and white matter (WM) volumes were collected, together with CSF volume. RESULTS: JVR was strongly associated with increased normalized WB (p = 0.014) and GM (p = 0.002) volumes across all three subject groups. There was a trend towards increased WB and GM volumes, which was accompanied by decreased CSF volume, in the JVR-positive subjects in both the MCI and AD groups. When the MCI and AD subjects were aggregated together significant increases were observed in both normalized WB (p = 0.009) and GM (p = 0.003) volumes for the JVR-positive group. No corresponding increases were observed for the JVR-positive subjects in the control group. Through receiver operating characteristic analysis of the brain volumetric data it was possible to discriminate between the JVR-positive and negative AD subjects with reasonable accuracy (sensitivity = 71.4%; specificity = 88.9%; p = 0.007). CONCLUSIONS: JVR is associated with intracranial structural changes in MCI and AD patients, which result in increased WB and GM volumes. The neuropathology of this unexpected and counterintuitive finding requires further investigation, but may suggest that JVR retrogradely transmits venous hypertension into the brain and leads to brain tissues swelling due to vasogenic edema.

Jugular venous reflux and plasma endothelin-1 are associated with cough syncope: a case control pilot study.

BACKGROUND: Jugular venous reflux (JVR) has been reported to cause cough syncope via retrograde-transmitted venous hypertension and consequently decreased cerebral blood flow (CBF). Unmatched frequencies of JVR and cough syncope led us to postulate that there should be additional factors combined with JVR to exaggerate CBF decrement during cough, leading to syncope. The present pilot study tested the hypothesis that JVR, in addition to an increased level of plasma endothelin-1 (ET-1), a potent vasoconstrictor, is involved in the pathophysiology of cough syncope. METHODS: Seventeen patients with cough syncope or pre-syncope (Mean[SD] = 74.63(12.37) years; 15 males) and 51 age/gender-matched controls received color-coded duplex ultrasonography for JVR determination and plasma ET-1 level measurements. RESULTS: Multivariate logistic analysis showed that the presence of both-side JVR (odds ratio [OR] = 10.77, 95% confident interval [CI] = 2.40-48.35, p = 0.0019) and plasma ET-1 > 3.43 pg/ml (OR = 14.57, 95% CI = 2.95-71.59, p = 0.001) were independently associated with the presence of cough syncope/ pre-syncope respectively. There was less incidence of cough syncope/ pre-syncope in subjects with the absence of both-side JVR and a plasma ET-1 ≦3.43 pg/ml. Presence of both side JVR and plasma ET-1 level of > 3.43 pg/ml, increased risk for cough syncope/pre-syncope (p < 0.001). CONCLUSIONS: JVR and higher plasma levels of ET-1 are associated with cough syncope/ pre-syncope. Although sample size of this study was small, we showed a synergistic effect between JVR and plasma ET-1 levels on the occurrence of cough syncope/pre-syncope. Future studies should confirm our pilot findings.

Pneumocephalus associated with massive cerebral air embolism.

A 61-year-old man with critical aortic stenosis underwent aortic valve replacement. Mechanical ventilation was applied because of postoperative acute pulmonary edema accompanied by poor ventilation and poor oxygenation, and the patient was also recannulized to an extracorporeal membranous oxygenator. Bilateral pneumothorax was found 2 days later, and the right upper and left lower chest quadrants were drained with pigtail catheters. The patient did not regain consciousness 5 days after cessation of propofol. He remained in a deep coma; anisocoric pupils without light reflex and left upward eyeball deviation were observed. The brain computed tomography (CT) scan revealed cerebral air embolism that caused extensive cerebral infarction accompanied by a hypodense lesion located in the bilateral cerebral and cerebellar hemispheres, mainly on the right side; mass effect and midline shifting were observed (Figs. 1 and 2). The bone window image of brain CT scan revealed no evidence of fracture or bony lesion over the skull base or ethmoid sinus. The patient expired later and an autopsy was not obtained. Cerebral air embolism is mostly due to invasive vascular procedure like cardiosurgical procedure(1), angiography(2) or central venous catheterization(3). Besides, neurosurgeries, barotraumas, basilar skull fractures, sinus fractures, congenital skull defects, neoplasm, gas producing organism infections, epidural anaesthesia or even lumbar puncture had been reported(4,5). Massive cerebral air embolism is rare within most of the reported cases. Our case demonstrated an air embolism associated with large air pockets in the cerebral parenchyma and Virchow-Robin space. The interesting aspect of this case lies in the image of a peculiar pattern of massive cerebral air embolism with air in the carotid artery, as well as in the small cerebral arteries and leaking into the brain parenchyma. The latter is likely the result of breakdown of the blood-brain barrier after cerebral infarction.

Changes in cerebral autoregulation, stroke-related blood biomarkers, and autonomic regulation after patent foramen ovale closure in severe migraine patients.

AIMS: This study aimed to investigate changes in dynamic cerebral autoregulation (dCA), 20 stroke-related blood biomarkers, and autonomic regulation after patent foramen ovale (PFO) closure in severe migraine patients. METHODS: Patent foramen ovale severe migraine patients, matched non-PFO severe migraine patients, and healthy controls were included. dCA and autonomic regulation were evaluated in each participant at baseline, and within 48-h and 30 days after closure in PFO migraineurs. A panel of stroke-related blood biomarkers was detected pre-surgically in arterial-and venous blood, and post-surgically in the arterial blood in PFO migraineurs. RESULTS: Forty-five PFO severe migraine patients, 50 non-PFO severe migraine patients, and 50 controls were enrolled. The baseline dCA function of PFO migraineurs was significantly lower than that of non-PFO migraineurs and controls but was rapidly improved with PFO closure, remaining stable at 1-month follow-up. Arterial blood platelet-derived growth factor-BB (PDGF-BB) levels were higher in PFO migraineurs than in controls, which was immediately and significantly reduced after closure. No differences in autonomic regulation were observed among the three groups. CONCLUSION: Patent foramen ovale closure can improve dCA and alter elevated arterial PDGF-BB levels in migraine patients with PFO, both of which may be related to the preventive effect of PFO closure on stroke occurrence/recurrence.

More severe white matter changes in the elderly with jugular venous reflux.

OBJECTIVE: The etiology of age-related white matter changes is unclear. Cerebral white matter changes on magnetic resonance imaging (MRI) and progressive dementia have been reported in patients with dural arteriovenous fistulas of the sigmoid sinus. The frequency of jugular venous reflux, which mimics a dural arteriovenous fistula, significantly increases with age. We investigated whether jugular venous reflux was associated with the severity of age-related white matter changes in 97 persons (aged 55-90 years, mean [standard deviation]: 75.77 [8.19] years; 55 men) from a medical center memory clinic. METHODS: MRI (1.5T) and the semiquantitative Scheltens scale were used to investigate the severity of white matter changes. Subjects were classified into 3 groups (no, mild, and severe jugular venous reflux) by duplex ultrasonography. RESULTS: Subjects with severe jugular venous reflux had more severe age-related white matter changes in occipital subcortical, thalamus, pontine, and summed infratentorial regions compared with subjects with no jugular venous reflux (all corrected p < 0.0166), especially subjects aged ≥75 years (corrected p < 0.0166 in occipital subcortical; corrected p < 0.0001 in pontine and summed infratentorial regions). In subjects ≥75 years, we further noted that the whole brain age-related white matter changes rating scores were higher in the severe jugular venous reflux group than the no and mild jugular venous reflux groups (corrected p < 0.0166). INTERPRETATION: People with severe jugular venous reflux exhibit more severe age-related white matter changes, especially in caudal brain regions. We also demonstrate age-dependent jugular venous reflux effects on the severity of age-related white matter changes. These findings may provide new clues into the pathophysiology of age-related white matter changes.

Comparison of Different Dosages of Alteplase in Atrial Fibrillation-Related Acute Ischemic Stroke After Intravenous Thrombolysis: A Nationwide, Multicenter, Prospective Cohort Study in Taiwan.

Background Insufficient evidence is available for patients with acute ischemic stroke with atrial fibrillation (AF) to determine the efficacy and safety of different dosages of intravenous thrombolysis treatment. This study examined clinical outcomes in Chinese patients with stroke with and without AF after intravenous thrombolysis treatment with different intravenous thrombolysis doses. Methods and Results This multicenter, prospective cohort study recruited 2351 patients with acute ischemic stroke (1371 with AF and 980 without AF) treated with intravenous thrombolysis using alteplase. The Totaled Health Risks in Vascular Events score is a validated risk-scoring tool used for assessing patients with acute ischemic stroke with and without AF. We evaluated favorable functional outcome at day 90 and symptomatic intracranial hemorrhage within 24 to 36 hours and outcomes of the patients receiving different doses of alteplase. Compared with the non-AF group, the AF group exhibited a 2- to 3-fold increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (relative risk [RR], 2.10 [95% CI, 1.35-3.26]). Favorable functional outcome at 90 days and symptomatic intracranial hemorrhage rates according to the European Cooperative Acute Stroke Study II and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study standards did not significantly differ between the AF and non-AF groups. In addition, the low-dose alteplase subgroup exhibited an increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (RR, 2.84 [95% CI, 1.63-4.96]). A validation study confirmed these findings after adjustment for scores determined using different stroke risk-scoring tools. Conclusions Different alteplase dosages did not affect functional status at 90 days in the AF and non-AF groups. Thus, the adoption of low-dose alteplase simply because of AF is not recommended.

Triglyceride-Glucose Index and Intravenous Thrombolysis Outcomes for Acute Ischemic Stroke: A Multicenter Prospective-Cohort Study.

BACKGROUND: The triglyceride-glucose (TyG) index has recently been proposed as a reliable marker of insulin resistance. There is insufficient evidence to verify that the TyG index is correlated with functional outcomes and hemorrhagic transformation and in patients with stroke treated with intravenous thrombolysis (IVT). METHODS: We designed a multicenter cohort study, which enrolled patients with acute ischemic stroke treated with IVT between December 2004 and December 2016. The TyG index was divided into tertiles and calculated on a continuous scale. Unfavorable functional outcomes were defined by the modified Rankin Scale of 3-6 at 90 days and the incident rates of symptomatic intracranial hemorrhage (SICH) within 36 h of IVT onset were surveyed. Stroke severity was defined as mild (4-8), moderate (9-15), or high (≥16) based on the National Institutes of Health Stroke Scale (NIHSS) scores. RESULTS: Among 914 enrolled patients, the tertiles of the TyG index were 8.48 for T1, 8.48-9.04 for T2, and 9.04 for T3. T3 showed an increased risk of unfavorable functional outcomes at 90 days [odds ratio (OR): 1.76; P = 0.0132]. The TyG index was significantly associated with unfavorable functional outcomes at 90 days (OR: 1.32; P = 0.0431 per unit increase). No association was found between the TyG index and SICH. These findings were applicable for T3 with stroke of moderate (OR, 2.35; P = 0.0465) and high severity (OR: 2.57, P = 0.0440) patients with stroke. CONCLUSION: This study supports the strong association between the increased TyG index and increased unfavorable functional outcomes at 90 days in patients with acute ischemic stroke treated with IVT. These findings were found to be robust in patients with moderate and high stroke severity.

Jugular venous reflux could influence cerebral blood flow: a transcranial Doppler study.

PURPOSE: Studies have found significant associations between jugular venous reflux (JVR) and neurological disorders. However, there still lacks evidences that JVR could influence cerebral circulation. The aim of the present study is trying to provide evidences that the retrogradely-transmitted venous pressure of JVR could reach cerebral venous system and has an influence on cerebral blood flow (CBF). METHODS: We recruited 50 volunteers. Only 42 subjects' data (55.81 ± 19.96, 23 - 85 years; 9 women) were analyzed due to poor temporal windows in eight subjects. JVR was determined by color-coded Duplex sonography. Transcranial Doppler study was used to examine the CBF changes during Valsalva maneuver (VM) in each subject. RESULTS: All JVRs were detected during VM. We divided subjects into people with right JVR (n=12), left JVR (n=13) and no JVR (n=21) and four had bilateral JVR. There was a more decrease in CBF during and immediately after VM in right-JVR group than no-JVR group, though the baseline characteristics and arterial blood pressure changes were similar. There were no demographic and hemodynamic differences between left-JVR group and no-JVR group. CONCLUSION: We are the first to provide evidences that right JVR during VM could influence CBF. However, whether left JVR with or without right JVR may have similar effect on CBF deserves further study. The definite mechanism underlying this finding needs further studies.

Diagnosis of extracranial carotid stenosis by MRA of the brain.

Severe extracranial carotid stenosis (SECS) patients may present with nonspecific neurological symptoms that require intracranial magnetic resonance imaging (MRI) and time-of-flight (TOF)-MR angiography (MRA) to exclude intracranial pathology. Recognition of SECS on intracranial TOF-MRA findings is beneficial to provide a prompt carotid imaging study and aggressive stroke prevention. Patients with SECS (January 2016 to May 2019) undergoing percutaneous transluminal angioplasty and stenting (PTAS) were included. Differences in normalized signal intensities (SRICA) and diameters (DICA) between bilateral petrous internal carotid arteries (ICAs) were calculated 1 cm from the orifice. A hypothesized criterion describing the opacification grades (GOPH) of bilateral ophthalmic arteries was proposed. We correlated SRICA (p = 0.041), DICA (p = 0.001) and GOPH (p = 0.012), with the severity of extracranial carotid stenosis on digital subtractive angiography (DSA) in the examined group (n = 113), and all showed statistical significance in predicting percentages of ICA stenosis. The results were further validated in another patient group with SECS after radiation therapy (n = 20; p = 0.704 between the actual and predicted stenosis grades). Our findings support the evaluation of the signal ratio and diameter of intracranial ICA on TOF-MRA to achieve early diagnosis and provide appropriate management of SECS.