Chih-Ping Chung

Outcomes of Thrombolytic Therapy for Acute Ischemic Stroke in Chinese Patients The Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study

Background and Purpose— The safety and efficacy of alteplase for ischemic stroke has not been examined in Chinese patients. We assessed the safety and efficacy of alteplase for acute ischemic stroke in daily clinical practice in Taiwan. Methods— A prospective, multicenter, observational study was conducted in Taiwan from December 2004 to July 2008. Eligible patients (241) receiving alteplase were recruited and divided into 2 groups: standard dose (0.90±0.02 mg/kg, n=125) and lower dose (0.72±0.07 mg/kg, n=116). Primary outcome measures were safety: symptomatic intracerebral hemorrhage and death within 3 months. The secondary outcome measure was efficacy a modified Rankin scale of 0 to 2 after 3 months. Results— The standard-dose group had higher rates of symptomatic intracerebral hemorrhage using National Institute of Neurological Diseases and Stroke, European Cooperative Acute Stroke Study, and Safe Implementation of Thrombolysis in Stroke-Monitoring Study definitions (10.4% versus 5.2%, 8.0% versus 2.6%, and 5.6% versus 1.7%, respectively) and mortality within 3 months (12.8% versus 6.9%), twice that of the lower-dose group. This pattern was more prominent in older patients. Significantly higher rates of symptomatic intracerebral hemorrhage per European Cooperative Acute Stroke Study (15.4% versus 3.3%, P=0.0257) and mortality (21.1% versus 5.0%, P=0.0099) and significantly lower independence rate (32.6% versus 53.6%, P=0.0311) were observed among patients ≥70 years old receiving the standard dose than those receiving the lower dose. Conclusions— This study suggests that the standard dose of 0.9 mg/kg alteplase may not be optimal for treating aged Chinese patients. However, the dose of recombinant tissue plasminogen activator for ischemic stroke in Chinese patients should be based on more broad and convincing evidences and randomized trials of lower versus higher doses are needed.

Reflux of jugular and retrobulbar venous flow in transient monocular blindness

Transient monocular blindness (TMB) attacks may occur during straining activities that impede cerebral venous return. Disturbance of cerebral and orbital venous circulation may be involved in TMB.

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

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.

Jugular Venous Hemodynamic Changes with Aging

Cerebral venous outflow insufficiency via the internal jugular vein (IJV) is associated with several neurological disorders. However, a normal reference set of IJV hemodynamic parameters derived from a large, healthy population over a wide range of age has, until now, been lacking. Color-coded duplex sonography was performed on the IJVs of 349 subjects (55.60 ± 17.49,16 to 89 y; 167 M/182 F). With increasing age, increased lumen area and decreased time-averaged mean velocity of bilateral IJV and a decreased proportion of total flow volume, drainage in the left IJV were found. The frequency of left jugular venous reflux (JVR) also increased with aging. We report IJV hemodynamic parameters across a large population, which could be used as a normal reference for clinical and research purposes. Furthermore, we found a decreased proportion of venous drainage, increased JVR prevalence, dilated lumen and slowed flow velocity in the left IJV, all of which suggest increased left IJV outflow impedance with aging.

Vertebral Artery Hypoplasia is Associated With A Decrease in Net Vertebral Flow Volume

The definition and clinical significance of vertebral artery hypoplasia (VAH) remain inconclusive. VAH has been proposed as a predisposing factor of posterior circulation ischemic stroke. The aim of this study was to determine a best cut-off diameter of vertebral artery (VA) for VAH and to investigate if unilateral VAH is associated with a decrease in net vertebral flow volume. Retrospective data of 1000 presumably healthy subjects free of cerebrovascular disease or apparent carotid atherosclerosis were analysed. We found that a VA diameter </=2.5mm is an ideal value to define VAH. The flow volume of the identified hypoplastic VA was remarkably low and the contralateral VA had only a slightly increased compensatory flow volume. The net VA flow volumes remained significantly and markedly lower in subjects with unilateral VAH (140.7+/-46.2mL/min) than those in subjects without VAH (190.1+/-54.5mL/min, p<0.001). Flow volume insufficiency of VA (defined as a net VA flow volume less than 100mL/min) occurred more frequently in individuals with VAH than in those without VAH (22.1% vs. 2.4%, p<0.001). Our study suggested that asymptomatic subjects with VAH had a significantly lower net VA flow volume and a higher frequency of VA flow insufficiency than the control group. (E-mail: hhhu@vghtpe.gov.tw).

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.

Potential involvement of the extracranial venous system in central nervous system disorders and aging

BackgroundThe role of the extracranial venous system in the pathology of central nervous system (CNS) disorders and aging is largely unknown. It is acknowledged that the development of the venous system is subject to many variations and that these variations do not necessarily represent pathological findings. The idea has been changing with regards to the extracranial venous system.DiscussionA range of extracranial venous abnormalities have recently been reported, which could be classified as structural/morphological, hemodynamic/functional and those determined only by the composite criteria and use of multimodal imaging. The presence of these abnormalities usually disrupts normal blood flow and is associated with the development of prominent collateral circulation. The etiology of these abnormalities may be related to embryologic developmental arrest, aging or other comorbidities. Several CNS disorders have been linked to the presence and severity of jugular venous reflux. Another composite criteria-based vascular condition named chronic cerebrospinal venous insufficiency (CCSVI) was recently introduced. CCSVI is characterized by abnormalities of the main extracranial cerebrospinal venous outflow routes that may interfere with normal venous outflow.SummaryAdditional research is needed to better define the role of the extracranial venous system in relation to CNS disorders and aging. The use of endovascular treatment for the correction of these extracranial venous abnormalities should be discouraged, until potential benefit is demonstrated in properly-designed, blinded, randomized and controlled clinical trials.Please see related editorial: http://www.biomedcentral.com/1741-7015/11/259.

Jugular venous reflux and white matter abnormalities in Alzheimer's disease: a pilot study.

To determine whether jugular venous reflux (JVR) is associated with cerebral white matter changes (WMCs) in individuals with Alzheimers disease (AD), we studied 12 AD patients 24 mild cognitive impairment (MCI) patients, and 17 elderly age- and gender-matched controls. Duplex ultrasonography and 1.5T MRI scanning was applied to quantify cerebral WMCs [T2 white matter (WM) lesion and dirty-appearing-white-matter (DAWM)]. Subjects with severe JVR had more frequently hypertension (p = 0.044), more severe WMC, including increased total (p = 0.047) and periventricular DAWM volumes (p = 0.008), and a trend for increased cerebrospinal fluid volumes (p = 0.067) compared with the other groups. A significantly decreased (65.8%) periventricular DAWM volume (p = 0.01) in the JVR-positive AD individuals compared with their JVR-negative counterparts was detected. There was a trend for increased periventricular and subcortical T2 WMC lesion volumes in the JVR-positive AD individuals compared with their JVR-negative counterparts (p = 0.073). This phenomenon was not observed in either the control or MCI groups. In multiple regression analysis, the increased periventricular WMC lesion volume and decreased DAWM volume resulted in 85.7% sensitivity and 80% specificity for distinguishing between JVR-positive and JVR-negative AD patients. These JVR-WMC association patterns were not seen in the control and MCI groups. Therefore, this pilot study suggests that there may be an association between JVR and WMCs in AD patients, implying that cerebral venous outflow impairment might play a role in the dynamics of WMCs formation in AD patients, particularly in the periventricular regions. Further longitudinal studies are needed to confirm and validate our findings.

Jugular Venous Reflux Affects Ocular Venous System in Transient Monocular Blindness

Background: The frequency of jugular venous reflux (JVR) is higher in patients with transient monocular blindness (TMB). We hypothesize that JVR influences ocular venous outflow, and resulting disturbances in cerebral and ocular venous circulation might be a cause of TMB. To substantiate this hypothesis, we aimed to demonstrate that: (1) TMB patients have vasculature changes in their retinal venules, and (2) JVR could influence ocular venous outflow, as revealed by dilated retinal venules. Methods: This study has 2 parts. The case-control study included 31 TMB patients and 31 age/gender-matched normal individuals, who all received fundus photography for retinal venule diameter comparisons. The Valsalva maneuver (VM) experiment included 30 healthy volunteers who received both color Doppler imaging of the internal jugular vein and fundus photography for retinal venule diameter measurement. Results: In the case-control study, TMB patients had a wider retinal venule diameter (184.5 ± 17.5 vs. 174.3 ± 16.2 µm, right eye, p = 0.023; 194.20 ± 24.6 vs. 176.6 ± 19.5 µm, left eye, p = 0.017), especially TMB patients with JVR. The VM experiments showed that the presence of JVR was associated with a greater increase in retinal venule diameters during VM in the subjects’ right eye (14.27 ± 11.16 vs. 2.75 ± 3.51%, JVR vs. non-JVR, p = 0.0002) and left eye (10.06 ± 6.42 vs. 1.80 ± 2.03%, p = 0.0003). Conclusions: These findings provide evidence that frequently occurring JVR associated with TMB impedes ocular venous outflow, and the subsequent disturbances in ocular venous circulation may be a cause of TMB.

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

BackgroundJugular 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.MethodsSeventeen 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.ResultsMultivariate 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).ConclusionsJVR 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.