Hung-Yi Hsu

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.

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.

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.

Decreased Jugular Venous Distensibility in Migraine

It has been demonstrated that internal jugular vein (IJV) compression aggravates headache intensity in patients of migraine. We hypothesized that patients with migraine may have veins that are less distensible; consequently, these veins are more likely to develop and transmit venous hypertension caused by the increased venous blood volume during IJV compression. We used ultrasonography to measure the extent of venodilatation and distensibility of IJV in response to increased transmural pressure, which was produced by a Valsalva maneuver. The extent of venodilatation were compared between 23 migraine patients (5 men, 18 women; mean age: 40.22+/-12.71 years, range: 27-7 years) and 23 age- and gender-matched normal individuals (5 men, 18 women; mean age: 40.23+/-12.04 years, range: 27-7 years). In the result, the venodilatation of IJV in response to each level of Valsalva pressure in patients with migraine was significantly less than that in normal individuals. Our results suggest that patients with migraine have less compliant IJVs, which makes them susceptible to cerebral venous hypertension. Further studies are needed to elucidate the clinical implications of decreased venous distensibility in migraine patients. (E-mail: hhhu@vghtpe.gov.tw).

Mechanisms of cough syncope as evaluated by valsalva maneuver.

Successful treatment of cough syncope depends on the correction of various pathogenetic mechanisms among different patients. The valsalva maneuver (VM), which elicits hemodynamic responses mimicking coughs, has potential for investigating the individual pathogenesis of cough syncope. Eighteen consecutive patients suffering from cough‐induced syncope were examined. All patients were asked to cough and to perform VM several times under continuous cerebral blood‐flow velocity and blood pressure (BP) monitoring by transcranial Doppler and finger plethysmography. Eight patients demonstrated abnormal VM characterized by the absent BP overshoot following the relief of straining. Patients demonstrating abnormal VM had delayed BP recovery after cough (median, 16.4; range, 8.7–25.6 seconds) compared to those demonstrating normal VM (2.6, 1.3–3.8 seconds, p < 0.001). Seven of the 10 patients exhibiting normal BP overshoot during VM had stenotic arterial lesions in the cerebral or coronary circulation, whereas only one of the eight patients demonstrating absent BP overshoot had coronary artery disease (70% vs. 12.5%, p = 0.025). Other clinical profiles, body mass index, frequency of obstructive pulmonary disease and valsalva ratio did not differ between patients featuring normal and absent BP overshoot. In conclusion, the pathogenesis of cough syncope could be different between patients with normal and abnormal VM responses. Patients who had no BP overshoot during VM sustained prolonged hypotension after cough. The VM helps in discriminating among pathogenic mechanisms and guiding investigation and treatment for cough syncope patients.

Altered Retrobulbar Hemodynamics in Patients Who Have Transient Monocular Blindness Without Carotid Stenosis

Background and Purpose— This study was to evaluate the retrobulbar hemodynamics in patients who have transient monocular blindness (TMB) without carotid stenosis. Methods— Fifty-nine patients who have TMB without carotid stenosis were studied along with 59 age- and sex-matched controls. Color Doppler–imaging was used to study the retrobulbar hemodynamic by measuring the flow velocities (peak-systolic velocity, and end-diastolic velocity), vascular resistance indices (pulsatility index, and resistance index) in central retinal arteries, short posterior ciliary arteries, and ophthalmic arteries. The patients were divided into 2 groups according to the attack frequency: group 1 (occasional TMB, 2 or fewer attacks, 26 patients) and group 2 (frequent TMB, 3 or more attacks, 33 patients). Results— The risk factors for atherosclerosis were similar between the cases and controls. The means of end-diastolic velocity were significantly lower in central retinal arteries and ophthalmic arteries, and the pulsatility index and resistance index were significantly higher in all the 3 retrobulbar vessels in TMB patients than for the controls. The differences between patients and controls were greater for the group-2 patients. Conclusion— Patients who have TMB without carotid stenosis had altered retrobulbar hemodynamics with a generalized increase in vascular resistance in the retrobulbar arteries. The role of venous hypertension as an etiology needs further study.

Stroke etiology is associated with outcome in posterior circulation stroke.

Stroke research and clinical trials have focused mainly on anterior circulation stroke (ACS). Since clinical characteristics, mechanisms, and outcomes of posterior circulation stroke (PCS) have been reported different from ACS, more PCS studies are required, particularly researching the etiologies, to help establish an optimal management strategy.

Collapsed Jugular Vein and abnormal cerebral blood flow changes in patients of Panic Disorder

OBJECTIVE Panic disorder (PD) is characterized by panic attacks accompanied with respiratory symptoms. Internal jugular vein (IJV) alters its hemodynamics in response to respiration and which might cause cerebral blood flow (CBF) changes. In the present study, we compared (1) respiratory-related IJV hemodynamics and (2) CBF changes during Valsalva maneuver (VM) between PD and normal subjects. METHODS 42 PD patients and age/gender-matched controls (14 men; 52.3 ± 11.4 years) were recruited. Duplex ultrasonography measured time-averaged mean velocity (TAMV) and lumen in IJV at baseline and deep inspiration. Lumen area <0.10 cm(2) at deep inspiration was defined as IJV collapse. CBF changes during VM were recorded by transcranial Doppler (TCD). RESULTS Compared with normal group, PD patients had significantly higher frequency of IJV collapse at deep inspiration (Left: 40.0% vs. 7.0%, p = 0.0003, Right: 17.0% vs. 0%, p = 0.0119). IJV collapse was associated with symptoms of respiratory subtype in our PD patients. PD group also had smaller lumen (Left: 0.53 ± 0.29 vs. 0.55 ± 0.26 cm(2), p = 0.8296, Right: 0.63 ± 0.36 vs. 0.93 ± 0.45 cm(2), p = 0.0014) and slower TAMV of IJV at baseline (Left: 11.8 ± 8.43 vs. 20.6 ± 16.5 cm/s, p = 0.0003, Right: 15.9 ± 9.19 vs. 24.1 ± 15.7 cm/s, p = 0.0062). PD patients with inspiration-induced IJV collapse had more decreased CBF during VM compared with the other PD patients and normal individuals respectively. INTERPRETATION We are the first to show that PD have less IJV flow at baseline and more frequent collapse at deep inspiration. Inspiration-induced IJV collapsed was associated with CBF decrement during VM in PD patients. These results suggest that venous drainage impairment might play a role in the pathophysiology of PD by influencing CBF.

Obstruction of Venous Drainage Linked to Transient Global Amnesia

Abnormal extracranial venous drainage modality has been considered an etiology of transient global amnesia (TGA). Evidence suggests that the transmission of the intrathoracic/intraabdominal pressure during a Valsalva maneuver (VM) is mainly through the vertebral venous system, and patency of internal jugular vein (IJV) is essential for venous drainage and pressure releasing. We hypothesize that obstruction of IJV venous drainage is a contributing factor in TGA pathogenesis. A magnetic resonance (MR) imaging protocol was used in 45 TGA patients and 45 age- and sex-matched controls to assess the morphologies of IJV, brachiocephalic vein (BCV) and asymmetry of transverse sinus (TS). The IJV was divided into the upper- and middle-IJV segments. Compared to the controls, TGA patients had significantly higher rates of moderate and severe compression/stenosis at the bilateral upper-IJV segment (left: 37.8% vs. 17.8%, P = 0.0393; right: 57.8% vs.15.6%, P<0.0012), in left BCV (60% vs. 8.9%, P<0.0004), and in TS hypoplasia (53.3%% vs. 31.1%, P = 0.0405). The prevalence of at least one site of venous compression/stenosis in IJV or BCV was significantly higher in patients than in controls (91.1% vs. 33.3%, P<0.0004). The diameter of the left TS in MRV, but not in T1 contrast imaging, was significantly smaller in TGA patients than in controls (0.31±0.21 vs. 0.41±0.19, P = 0.0290), which was compatible with downstream venous stenosis/obstruction. TGA patients have a higher prevalence of compression/stenosis of the bilateral IJV and the left BCV and TS hypoplasia, which is new evidence that supports the role of extracranial veins in TGA pathogenesis.