Functional recovery of stroke patients with postacute care: a retrospective study in a northern medical center.

BACKGROUND: Taiwan's NHI Administration proposed a nationwide postacute care-cerebral vascular disease (PAC-CVD) program, which transfers stroke patients at postacute phase in medical centers to community hospitals. Its aim is mainly to prevent a prolonged stay in medical centers, which usually results in higher medical costs. The present study evaluated the 3-months functional outcomes of stroke patients receiving PAC-CVD. METHODS: We retrogradely retrieved patients' data from Stroke Registry of a Northern medical center. Patients admitted between January 2014 and March 2018 were screened. We included patients receiving PAC-CVD and age/sex/stroke severity/functional status-matched acute stroke patients (regular rehabilitation group). Baseline clinical characteristics and 3-months functional outcomes were analyzed. We defined 3-months mRS 0 to 2 as better, 3 to 4 as same, and 5 to 6 as worse functional recovery. RESULTS: One-hundred-and-seventy-three patients receiving PAC-CVD and 173 matched controls (68.2 ± 14.0-years-old, 68.5% ± 11.22% men) were recruited. All patients were with mRS 3 to 4 at discharge from our medical center. The distributions of 3-months functional recovery in two groups were as follows: better/same/worse 3-months functional outcomes, PAC-CVD = 40.4%/57.8%/1.8%; controls (regular rehabilitation) = 33.9%/50.3%/5.8%. Multivariate analyses adjusted for age, sex, NIHSS, and cardiovascular risk factors were performed to evaluate whether PAC-CVD predicted better or poor functional outcomes. The results showed that compared with controls, PAC-CVD group had similar frequency of better functional recovery (odds ratio [OR] = 0.97, 95% CI = 0.54-1.74, p = 0.924) but less frequency of worse functional outcomes (OR = 0.08, 95% CI = 0.008-0.84, p = 0.035). CONCLUSION: About one-third of patients with mRS 3 to 4 recovered well in 3-months after stroke in both PAC-CVD and regular rehabilitation groups. Our results showed that PAC-CVD program can significantly decrease functional decline after acute stroke.

Transient Global Amnesia Linked to Impairment of Brain Venous Drainage: An Ultrasound Investigation.

Background: Previous neuroimaging and ultrasound studies suggested that compression and stenosis of the internal jugular vein (IJV) in patients with transient global amnesia (TGA) may impair IJV drainage, while a patent IJV releases intracranial pressure caused by the Valsalva maneuver (VM). Methods: Seventy-nine TGA patients with complete ultrasound examination data during admission were recruited prospectively to evaluate IJV drainage, which included the time-averaged mean velocity, and the cross-sectional lumen area of the IJV at the vein's middle (J2) and distal (J3) segments and the cross-sectional area during a 10-s VM to test for any retrograde or anti-grade flow. Forty-five TGA patients and 45 age- and sex-matched control subjects underwent complete contrast-enhanced magnetic resonance (MR) venous studies, which included time-resolved imaging of contrast kinetics, contrast-enhanced axial T1-weighted MR imaging, and phase-contrast-based non-contrast enhanced magnetic resonance venography (MRV). Results: In those subjects with complete MRV studies, the flow volumes exhibited at both the J2 and J3 segments of the left IJV and left vertebral vein (VV) were significantly lower in the TGA patients than in the control subjects. Although there was no significant difference in the flow volume of right IJV, the total of bilateral IJV, and VV flow volumes was still significantly lower in the TGA patients. As compared with the control subjects, the TGA patients exhibited significantly higher prevalence of completely blocked right IJV drainage at the J3 segment during the VM, but non-significantly higher for the left IJV at the J3 segment and for the right IJV at the J2 segment. Conclusion: Our results confirmed that the total venous flow decreases in the IJVs and VVs of the patients with TGA. This is consistent with the findings of previous MR imaging studies that have reported about compression and stenosis of the draining veins. We also found that IJV drainage is relatively compromised during the VM in the patients with TGA.

Ultrasound diagnosis of transverse sinus hypoplasia using flow profiles of the internal jugular vein.

Accurate diagnosis of subtypes of transverse sinus (TS) hypoplasia requires more expensive methods like magnetic resonance (MR) imaging. We hypothesized ultrasound findings of the internal jugular vein (IJV) can be surrogate indicators for diagnosis of TS hypoplasia. MR images were reviewed in 131 subjects to evaluate TS diameter and the location and degree of venous flow stenosis and obstruction. Ultrasound parameters including the cross-sectional lumen area (CSA), time-average-mean velocity (TAMV), and flow volume (FV) at each IJV segment were also evaluated. Sixty-nine subjects had TS hypoplasia based on MRV criteria, of which 39 TS hypoplasia were considered a subtype of TS hypoplasia, which is secondary to the downstream venous compression/stenosis or left brachiocephalic vein. In the ultrasound study, the CSA of the IJV ipsilateral to TS hypoplasia was significantly smaller. Further, a contralateral/ipsilateral IJV CSA ratio >1.55 provided good sensitivity, specificity, and positive predictive value for discriminating TS hypoplasia.

Vertebral artery terminating in posterior inferior cerebellar artery: A normal variation with clinical significance.

A vertebral artery (VA) terminating in a posterior inferior cerebellar artery (PICA) is often considered to be a normal variation associated with VA hypoplasia. We aimed to investigate the clinical significance of this cerebrovascular variant. A total of 80 patients with clinically evident cerebrovascular events in posterior circulation were examined by duplex sonography and magnetic resonance angiography (MRA). Eighty healthy subjects who had MRA check-up were recruited as controls. PICA termination of the VA (PICA-VA) was identified as the VA not communicating with the basilar artery (BA) but ending into a PICA. We compared the prevalence of PICA-VA and associated hemodynamic parameters between the patients with and without PICA-VA, and investigated their relationships with VA hypoplasia. The prevalence of PICA-VA was higher in the patient group than in the controls (18.7% vs. 6.3%, p = 0.015). Most measurements (73.3%) of PICA-VA did not fit the criteria of VA hypoplasia. In comparison with the non-PICA-terminating group, the PICA-VA has a smaller diameter (3.7 ± 0.7 mm vs. 3.0 ± 0.5 mm, p < 0.001), lower mean velocity (241 ± 100 mm/sec vs. 164 ± 88 mm/sec, p < 0.01), and higher pulsatility index (1.3 ± 0.5 vs. 1.9 ± 0.6, p < 0.001). Moreover, a smaller diameter of the BA (3.2 ± 0.5 mm vs. 2.5 ± 0.9 mm, p = 0.004) and the posterior cerebral artery (PCA) (2.0 ± 0.1 mm vs. 1.6 ± 0.1 mm, p = 0.006) were also noted in the PICA-VA group. The higher prevalence of PICA-VA in the patient group with smaller diameter of VA, BA and PCA reflected its clinical significance, suggesting that PICA-VA may have a detrimental impact on cerebral hemodynamics. However, the sample is small, and further studies are needed with larger sample size for confirmation.

Diagnosis of Transverse Sinus Hypoplasia in Magnetic Resonance Venography: New Insights Based on Magnetic Resonance Imaging in Combined Dataset of Venous Outflow Impairment Case-Control Studies: Post Hoc Case-Control Study.

In previous studies of transverse sinus (TS) hypoplasia, discrepancies between TS diameter measured by magnetic resonance venography (MRV) and contrast T1-weighted magnetic resonance (contrast T1) were observed. To investigate these discrepancies, and considering that TS hypoplasia is associated with neurological disorders, we performed a post hoc analysis of prospectively collected data from 3 case-control studies on transient global amnesia (TGA), transient monocular blindness (TMB), and panic disorders while retaining the original inclusion and exclusion criteria. Magnetic resonance (MR) imaging of 131 subjects was reviewed to evaluate TS diameter and the location and degree of venous flow stenosis and obstruction.MRV without contrast revealed that TS hypoplasia was observed in 69 subjects, whom we classified into 2 subgroups according to the concordance with contrast T1 observations: concordance indicated anatomically small TS (30 subjects), and discrepancy indicated that the MRV diagnosis is in fact flow-related and that TS is not anatomically small (39 subjects). The latter subgroup was associated with at least 1 site of venous compression/stenosis in the internal jugular vein (IJV) or the left brachiocephalic vein (BCV) (P < 0.001), which was significantly larger in patients than controls. Compensatory dilatation of contralateral TS diameter was only observed with MRV, not with contrast T1 imaging.The clinical implication of these results is that using MRV only, IJV/BCV compression/stenosis may be misdiagnosed as TS hypoplasia. And contralateral TS have no compensatory dilatation in its diameter in contrast T1 imaging, just compensatory increased flow volume.

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.

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.

Body positions in the diagnosis of right-to-left shunt by contrast transcranial Doppler.

Contrast transcranial Doppler (c-TCD) is sensitive in detecting right-to-left shunt (RLS). However, the methodology and ideal posture are controversial. Consecutive migraine patients were prospectively examined for RLS using c-TCD. Each patient was examined while at rest and subsequently with the Valsalva maneuver (VM) in three positions: supine, left lateral decubitus and right lateral decubitus. RLS was diagnosed with at least one microbubble detected at any position. RLS was highest in the left lateral decubitus position, both during rest and with VM. The left lateral decubitus position was associated with the highest total number of microbubbles and greater shunt grades. Patients who tested positive in the other two positions had the lowest index position failure rate during rest in the left lateral decubitus position. In some patients in whom RLS is detected at rest, it may not be detected (false negative) under VM. To ensure c-TCD's the sensitivity to RLS, testing in the left lateral decubitus position at rest and under VM is suggested; testing in other positions is necessary to avoid false negatives.

Stroke etiology is associated with outcome in posterior circulation stroke.

OBJECTIVE: 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. METHODS: The present study analyzed patients of PCS who were consecutively admitted and registered in Taipei Veterans General Hospital Stroke Registry between 1 January 2012 to 28 February 2014. We demonstrated the distribution of etiologies, compared the clinical characteristics/outcomes among different etiology groups, and used univariate/multivariate analyses to identify the predictors for poor functional outcome (modified Rankin Scale ≥5) at discharge and 3 month. RESULTS: About 286 patients of PCS were included for analyses. Basilar artery atheromatous branch occlusive disease (BABO, 28.0%) and large artery dissection (25.9%) were the two most common etiologies, followed by large artery atherosclerotic stenosis/occlusion (LAA, 20.6%), cardioembolism (CE, 18.5%) and small vessel disease (7.0%). Age, vascular risk factors, infarct locations and patterns, and outcomes were different among these five etiology groups. Multivariate analyses showed that age >70 y/o (discharge/3 month, OR, 95% CI: 3.05, 1.23-7.56/8.39, 2.32-30.33), admission NIH Stroke Scale >9 (19.50, 8.69-43.75/13.45, 5.59-32.39), and etiology (LAA versus BABO: 5.00, 1.58-15.83/4.00, 1.19-13.4; CE versus BABO: 3.36, 1.02-11.09/4.66, 1.40-15.46) were independently associated with poor functional outcome. INTERPRETATION: The etiologies of PCS are heterogeneous and shown to be associated with functional outcomes. Our results have shed lights on future pathophysiological research and designs of clinical trials for PCS.

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.

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.

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.

Transcranial Doppler studies on cerebral autoregulation suggest prolonged cerebral vasoconstriction in a subgroup of patients with orthostatic intolerance.

We studied the cerebral autoregulation in a subgroup of patients with orthostatic intolerance, who exhibited excessively decreased middle cerebral artery flow velocity (MCAFV) on transcranial Doppler sonography (TCD) during head-up tilt (HUT) test but without orthostatic hypotension or postural tachycardia. Twenty patients and 20 age- and sex-matched controls underwent Valsalva maneuver (VM) and HUT test with simultaneous monitoring of MCAFV by TCD and blood pressure, heart rate recordings. The pulsatility index (PI), cerebrovascular resistance (CVR) and autoregulatory indices were calculated. During HUT, patients had marked MCAFV reduction (-29.0 ± 5.25% vs. -8.01 ± 4.37%), paradoxically decreased PI (0.68 ± 0.17 vs. 0.96 ± 0.28) but increased CVR (45.7 ± 16.7% vs. 14.3 ± 12.6%). The MCAFV decreased similarly during early phase II of VM in both groups but did not recover to baseline in patients during late phase II, phase III and less overshoot in phase IV (-11 ± 16.7% vs. +2.2 ± 17.9 %; -15.4 ± 16.5% vs. -2.4 ± 17.8% and 16.7 ± 22.9% vs. 38.7 ± 26.5%, respectively). We concluded that in these patients, cerebrovascular vasoconstriction in response to physiologic stimulation was normal but relaxation during and after stimulation were impaired, indicating prolonged cerebral vasoconstriction.

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.

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.

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 + or - 0.02 mg/kg, n=125) and lower dose (0.72 + or - 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 > or = 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.

OBJECTIVE: 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. METHODS: Duplex ultrasonography and Doppler-flow measurement of jugular and retrobulbar veins were performed in 134 consecutive patients with TMB and 134 age- and sex-matched control subjects. All recruited patients received thorough examinations to screen for possible underlying causes. RESULTS: Of the 134 patients with TMB, 48 patients had ipsilateral carotid arterial lesion and 7 patients had TMB attack(s) caused by cardiac embolism. Of the remaining 79 patients with undetermined cause, 46 had 3 or more TMB attacks (undetermined-frequent group) and 33 had fewer than 3 attacks. In comparison with the control subjects, the TMB patients had greater frequencies of jugular venous reflux (57 vs 30%; p < 0.0001; odds ratio [OR]: 3.079, 95% confidence intervals [CI]: 1.861-5.096) and flow reversal in the superior ophthalmic vein (RSOV; 37 vs 9%; p < 0.0001; OR: 6.052, CI: 3.040-12.048). The undetermined-frequent group had the greatest frequencies of jugular venous reflux (74%, 34 patients; OR: 6.66, CI: 3.13-14.17) and RSOV (59%, 27 patients; OR: 6.51, CI: 3.12-13.58). Of the 50 patients with RSOV, 47 (94%) had RSOV on the side of the TMB attacks. INTERPRETATION: The increased incidences of jugular and orbital venous reflux in TMB patients suggest that disturbance of cerebral and orbital venous circulation is involved in the pathogenesis of TMB, especially among patients with frequent attacks of undetermined cause.

Transient global amnesia: cerebral venous outflow impairment-insight from the abnormal flow patterns of the internal jugular vein.

Cerebral venous reflux is found frequently in transient global amnesia (TGA) patients. The cerebral venous reflux mostly results from left brachiocephalic venous obstruction, and the level of reflux depends on different respiratory status. For further understanding of the role of venous outflow impairment in the pathogenesis of TGA, we used color duplex sonography to reveal the flow patterns in the internal jugular vein (IJV) and its branches (JB) under different respiratory conditions. We compared the frequency of abnormal venous flow of IJV and/or JB on color duplex sonography between 17 TGA patients and 17 age- and gender-matched normal individuals both at rest (regular breathing) and at deep inspiration. Further, these venous-flow abnormalities in IJV and JB were well described. Cranial 3-D time-of-flight magnetic resonance arteriography (MRA) were performed in all patients three to seven days after their TGA attacks and in all normal individuals to analyze the abnormal flow signals in the intracranial venous structures. In the result, abnormal flow-patterns in the left IJV and/or left JB during regular breathing were found more frequently in TGA patients than normal individuals (65% vs. 6%; p < 0.001). These abnormalities in TGA patients were (1) isolated reversed flow in the left JB, (2) segmental reversed flow in the left distal IJV and (3) continuous reversed flow in the left IJV and JB. The MRA study revealed that only the most severe reflux in the IJV causes intracranial venous reflux; six were in the group of continuous reversed flow in left IJV and one was in the group of segmental reversed flow in left distal IJV. These findings suggest that TGA might be one of the clinical manifestations of the "cerebral-type intermittent venous claudication," which stems from cerebral venous outflow impairment, insufficient venous collaterals and specific precipitating factors.

Pharmacoeconomics of therapy for Guillain-Barré syndrome: plasma exchange and intravenous immunoglobulin.

Guillain-Barré syndrome (GBS) is an acute neuropathy and a clinical syndrome that includes a number of pathological and electrophysiological subtypes. Intravenous immunoglobulin (IVIG) and plasma exchange (PE) are both equally efficacious for the treatment of GBS; however, the cost of IVIG may be lower for both the patient and the healthcare system. To compare the pharmacoeconomics of PE and IVIG in GBS, a retrospective study was done from 1999 to 2004, which included a total of 24 patients with GBS who were admitted to Taipei Veterans General Hospital. This showed that except for the costs of the drugs used in IVIG, treatment of GBS with IVIG was more cost-effective (p=0.057) than that with PE in total length of hospitalization and the cost of procedures and hospitalization. The study also showed that the total costs were higher for patients on ventilators than those not requiring ventilators (p=0.008, t-test) and the length of hospitalization showed a very strong linear relationship to total costs (Pearson correlation coefficient=0.907). The regression analysis showed that each additional day of hospitalization increased the hospitalization costs by an average of 5599 New Taiwan Dollars (NT) (US$1.00=NT$33.50 in 2005).