A-Ching Chao

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.

Noninvasive Assessment of Spontaneous Baroreflex Sensitivity and Heart Rate Variability in Patients with Carotid Stenosis

Background: Previous limited observations have suggested that atherosclerosis may affect the distensibility of the carotid sinus and then impair the baroreflex sensitivity (BRS). No studies have been done to compare the BRS and heart rate variability (HRV) in patients with carotid stenosis and normal controls. Methods: A convenience-consecutive sample of 118 patients with transient ischemic attack or minor stroke 3 months to 1 year before (mean 6 months) who met the study criteria were referred to the neurovascular laboratory of the study hospital. Forty-three age-matched healthy adults were recruited as the normal controls. The inclusion criteria for participation were (1) no diabetes mellitus, (2) no history, symptoms or ECG signs of coronary artery disease or myocardial infarction, and (3) presence of carotid stenosis greater than or equal to 50%. The diagnosis of carotid stenosis was made using color-coded duplex ultrasound with published criteria. We categorized the patients into two groups: group 1 had moderate stenosis (50–75%) and group 2 had high-grade stenosis (75–99%). Instantaneous systolic blood pressure (SBP) and heart rate of all participants were assessed noninvasively using servo-controlled infrared finger plethysmography. The fluctuation in SBP as well as the interpulse interval (IPI) was divided into three components at specific frequency ranges by fast Fourier transform as high frequency (HF; 0.15–0.4 Hz), low frequency (LF; 0.04–0.15 Hz) and very low frequency (VLF; 0.004–0.04 Hz). The BRS was expressed as (1) transfer function with its magnitude in the HF and LF ranges, (2) BRS index alpha, and (3) regression coefficient by sequence analysis. The HRV was expressed as total power and power in the three frequency ranges (HF, LF and VLF). Results: The final analysis included 99 patients (mean age 72 ± 6 years, 79 male) and 43 healthy controls (mean age 68 ± 7 years, 30 male). Forty-three patients were classified as group 1 (stenosis 50–75%) and 56 as group 2 (stenosis 75–99%). There was no significant difference in the IPI between patients and controls (p value = 0.8637). We observed a significant decrease in all three HRV components (VLF, LF and HF) in the patients; however, there were no differences between the two patient groups with various degrees of stenosis. All the indices of BRS, including the magnitude of SBP-IPI transfer function at LF and HF, the computed BRS index alpha and the regression coefficient of sequence analysis, revealed similar results. Patients exhibited a significant reduction in the BRS (p < 0.001) compared with controls, and no difference was found between the two groups of patients. Conclusions: Our study linked significant carotid stenosis to two important autonomic markers (BRS and HRV) that may have prognostic value for patients with cardiovascular events. Further prospective studies are needed to explore whether or not the decreased BRS and HRV can be predictors for poor cardiovascular prognosis, or even for shortened life span in general, in patients with significant carotid stenosis.

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).

Effects of atenolol and losartan on baroreflex sensitivity and heart rate variability in uncomplicated essential hypertension

Baroreflex sensitivity (BRS) and heart rate variability (HRV) are potential therapeutic targets. The present study was conducted to assess changes in BRS and HRV after monotherapy with losartan versus that of atenolol in uncomplicated essential hypertension. Thirty subjects with uncomplicated essential hypertension were randomized to receive atenolol 50 mg to 100 mg (n = 15) or losartan 50 mg to 100 mg (N = 15) daily for 6 months. Instantaneous systolic blood pressure (SBP) and heart rate were assessed using servo-controlled infrared finger plethysmography before treatment and at the end of 3 months and 6 months after treatment. The fluctuation in SBP and interpulse interval (IPI) was divided into three specific frequency ranges by fast Fourier transform as high frequency (HF; 0.15 Hz-0.4 Hz), low frequency (LF; 0.04 Hz-0.15 Hz), and very low frequency (VLF; 0.004 Hz-0.04 Hz). The BRS was expressed as (1) SBP-IPI transfer function with its magnitude in the HF and LF ranges and (2) BRS index alpha. The HRV was expressed as total power and power in the LF and HF ranges of interpulse interval. Blood pressure was reduced to a similar extent in both groups. Compared with the baseline, BRS did not improve in both groups at month 3. However, BRS was significantly improved in the losartan group (P < 0.05) but not in the atenolol group at month 6. In addition, BRS was significantly higher in the losartan group than the atenolol group at month 3 and month 6 (P < 0.05). Moreover, heart rate variability was significantly reduced in the atenolol group at month 6 (P < 0.05), but not in the losartan group. The HRV in the losartan group was significantly higher than that in the atenolol group at month 6 (P < 0.05). These findings suggest superior effects of losartan on BRS and HRV than atenolol in uncomplicated essential hypertension, which may be beyond blood pressure reduction/resetting.

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.

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).

Internal jugular venous abnormalities in transient monocular blindness

BackgroundThe 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.MethodsContrast-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.ResultsThere 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).ConclusionsTMB 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.

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.

Central nervous system tuberculosis: a forgotten diagnosis.

Introduction:Early diagnosis and treatment of central nervous system (CNS) tuberculosis (TB) are very important because of its high morbidity and mortality characteristics. However, the clinical symptoms, laboratory and neuroimaging findings of CNS TB are nonspecific, no matter whether they are the common form, tuberculous meningitis (TBM), or the rare form, intracranial tuberculomas. We report a case of TBM with miliary pattern of intracranial tuberculomas, although the initial diagnosis was masked by an atypical neuropsychiatric presentation, cerebrospinal fluid (CSF) finding, and other medical comorbidity. Case Report:A 51-year-old man was brought to the emergency room due to a traffic accident. The initial impression was Wernicke encephalopathy due to his alcohol use history and the clinical triad. After admission, fever and mental confusion lead to the suspicion of CNS infection. Although the initial CSF analysis was inconclusive, the miliary pattern of intracranial tuberculomas was highly suspected by brain magnetic resonance imaging finding. The diagnosis of TBM and miliary TB was finally confirmed by positive CSF and sputum culture of Mycobacterium tuberculosis. The patient had a good response to standard antituberculous therapy, although paradoxical expansion of cerebral tuberculomas occurred during treatment. Conclusions:TB is still a major public health problem in the world, and there is a rising tendency of extrapulmonary TB incidences in the developed countries. Because of the high mortality and treatable characteristics of CNS TB, physicians should be familiar with it and keep the diagnosis in mind.