Kuo-Lun Huang

Dehydration is an independent predictor of discharge outcome and admission cost in acute ischaemic stroke

Our aim was to investigate the influence of admission dehydration on the discharge outcome in acute ischaemic and hemorrhagic stroke.

Coexisting Diseases of Moyamoya Vasculopathy

BACKGROUND Several coexisting diseases have been reported in patients with moyamoya vasculopathy (MMV), but studies of quasi-moyamoya disease (quasi-MMD) are rare. This study aims to investigate the frequency of known coexisting diseases in patients with quasi-MMD and to compare quasi-MMD with moyamoya disease (MMD). METHODS Between 2000 and 2011, we retrospectively screened patients with International Classification of Diseases, Ninth Revision, code of 4375 (MMD) in the Health Information System of our hospital. The vascular images of each patient were confirmed by 2 neurologists and 1 neuroradiologist based on the diagnostic criteria of Japan Ministry of Health and Welfare. We excluded the patients with missing images and erroneous diagnosis. Demographics, coexisting diseases, laboratory data, treatment, and recurrent strokes were recorded. The eligible patients were divided into quasi-MMD and MMD groups according to the presence or absence of coexisting diseases. RESULTS MMV was found in 90 patients including 37 (41.1%) quasi-MMD and 53 (58.9%) MMD. Atherosclerosis (32.4%) and thyroid disease (29.7%) were the leading coexisting diseases in quasi-MMD. Patients with MMD became symptomatic in a bimodal age distribution, whereas patients with quasi-MMD became symptomatic in a single-peak distribution. The prognosis of recurrent strokes was similar between quasi-MMD and MMD based on Kaplan-Meier analysis. CONCLUSIONS A bimodal distribution of onset age was noted in MMD, whereas a single-peak distribution was found in quasi-MMD. Coexisting diseases were usually underevaluated but were more common than expected in patients with MMV. Atherosclerosis and thyroid diseases were the leading coexisting diseases in different preferential age.

Graph theoretical analysis of functional networks and its relationship to cognitive decline in patients with carotid stenosis

Significant carotid stenosis compromises hemodynamics and impairs cognitive functions. The interplay between these changes and brain connectivity has rarely been investigated. We aimed to discover the changes of functional connectivity and its relation to cognitive decline in carotid stenosis patients. Twenty-seven patients with unilateral carotid stenosis (≥60%) and 20 age- and sex-matched controls underwent neuropsychological tests and resting-state functional magnetic resonance imaging. The patients also received perfusion magnetic resonance imaging. The relationships between cognitive function and functional networks among the patients and controls were evaluated. Graph theory was applied on resting-state functional magnetic resonance imaging network analysis, which revealed that the hemispheres ipsilateral to the stenosis were significantly impaired in “degree” and “global efficiency.” The neuropsychological performances were positively correlated with degree, clustering coefficient, local efficiency, and global efficiency, and negatively correlated with characteristic path length, modularity, and small-worldness in the patients, whereas these relationships were not observed in the controls. In this study, we identified the networks that were impaired in the affected hemispheres in patients with carotid stenosis. Specific indices (global efficiency, characteristic path length, and modularity) were highly correlated with neuropsychological performance in our patients. Analysis of brain connectivity may help to elucidate the relationship between hemodynamic impairment and cognitive decline.

Correlation between the flow pattern of the circle of Willis and segmental perfusion asymmetry after carotid artery revascularization

Background:  To correlate cerebral perfusion and flow patterns after carotid artery revascularization within the circle of Willis (CoW).

Identification of PTCSC3 as a Novel Locus for Large‐Vessel Ischemic Stroke: A Genome‐Wide Association Study

Background Ischemic stroke is a major cause of death and disability in the world. A major ischemic stroke subtype, large‐vessel ischemic stroke (large artery atherosclerosis; LAA), has been shown to have some genetic components in individuals of European ancestry. However, it is not clear whether the genetic predisposition to LAA stroke varies among ethnicities. We sought to identify genetic factors that contribute to LAA stroke in 2 independent samples of Han Chinese individuals. Methods and Results Novel genetic variants that predispose individuals to LAA stroke were identified using a genome‐wide association study (GWAS) of 444 individuals with LAA stroke and 1727 controls in a Han Chinese population residing in Taiwan. The study was replicated in an independent Han Chinese population comprising an additional 319 cases and 1802 controls. We identified 5 single‐nucleotide polymorphisms, including rs2415317 (P=3.10×10−8), rs934075 (P=4.00×10−9), rs944289 (P=3.57×10−8), rs2787417 (P=1.76×10−8), and rs1952706 (P=2.92×10−8), at one novel locus on chromosome 14q13.3 within PTCSC3 (encoding papillary thyroid carcinoma susceptibility candidate 3) that were associated with LAA stroke at genome‐wide significance (P<5×10−8). Conclusions Our data provide strong support for future studies on the role of PTCSC3 in the pathogenesis of LAA stroke and the association between LAA stroke development and thyroid function. In addition, these findings provide insights into the genetic basis of LAA stroke and identify a novel pathway that might be applicable for future therapeutic intervention.

A genome-wide association study links small-vessel ischemic stroke to autophagy

Genome-wide association studies (GWAS) can serve as strong evidence in correlating biological pathways with human diseases. Although ischemic stroke has been found to be associated with many biological pathways, the genetic mechanism of ischemic stroke is still unclear. Here, we performed GWAS for a major subtype of stroke—small-vessel occlusion (SVO)—to identify potential genetic factors contributing to ischemic stroke. GWAS were conducted on 342 individuals with SVO stroke and 1,731 controls from a Han Chinese population residing in Taiwan. The study was replicated in an independent Han Chinese population comprising an additional 188 SVO stroke cases and 1,265 controls. Three SNPs (rs2594966, rs2594973, rs4684776) clustered at 3p25.3 in ATG7 (encoding Autophagy Related 7), with P values between 2.52 × 10−6 and 3.59 × 10−6, were identified. Imputation analysis also supported the association between ATG7 and SVO stroke. To our knowledge, this is the first GWAS to link stroke and autophagy. ATG7, which has been implicated in autophagy, could provide novel insights into the genetic basis of ischemic stroke.

Carotid Artery Stenting Improves Cerebral Hemodynamics Regardless of the Flow Direction of Ophthalmic Artery

We enrolled 221 patients with elective carotid artery stenting (CAS). Patients with contralateral carotid stenosis exceeding 50%, insufficient vertebral artery (VA) flows, or angioplasty at subclavian artery were excluded. All patients underwent serial cerebral ultrasound studies. Of the 116 included patients, the direction of ophthalmic artery (OA) flow was forward in 74 patients while reversed in 42. The reversed flow group had worse ipsilateral stenosis, higher hemoglobin, and cardiac output. After CAS, the reversed flow group had an immediate recovery of ipsilateral internal carotid artery flow volume (FV; P < .0001), time average velocity (TAV) of middle cerebral artery (P = .02), and normalization of OA flow. The forward flow group had gradual decrement in TAV of contralateral anterior cerebral artery (P = .01) and total FV of VA (P = .001). Our results suggest CAS improves cerebral hemodynamics through different ways regardless of the direction of OA flow.

Changes in E-Selectin Levels Predict Carotid Stenosis Progression after Carotid Artery Stenting

BACKGROUND We hypothesized that the inflammatory markers (IM) could be the independent predictors of Carotid Stenosis Progression (CSP) after Carotid Artery Stenting (CAS). METHODS Between 2010 and 2012, 122 patients undergoing cervicocranial revascularization in our hospital were prospectively recruited. Patients undergoing revascularizations other than CAS were excluded. Carotid duplex ultrasonography was performed before and at 1 week, 6 months (6M), 1 year, and 2 years after CAS. IM levels were recorded before CAS and were followed up immediately and 6M after CAS. The data was analyzed retrospectively. Patients were categorized into the Progression Group (PG) and Nonprogression Group (NPG) based on the presence or absence of CSP, including in-stent restenosis (ISR) and worsening contralateral carotid stenosis. Receiver operating characteristic and multivariate logistic regression analyses were conducted. RESULTS In Total, 77 patients were enrolled. The frequency of CSP was 24.7% (ISR: 14.3%; worsening contralateral carotid stenosis: 14.3%). Compared with the NPG, the PG had lower E-selectin levels before CAS [PG vs. NPG, 47.90 (42.80, 64.90) vs. 68.25 (52.08, 92.30); p = .01] and a nonreduced E-selectin levels at 6M after CAS [PG vs. NPG, 7.65 (-2.45, 25.75) vs. -16.10 (-33.45, 1.65); p = .002]. The E-selectin changes between 6M after and before CAS had highest predictive accuracy on CSP (area under the curve = 0.74, p = .002). The optimal cut-off level was a 2.95 ng/mL decrease and the adjusted odds ratio for CSP was 10.16 (p = .001). CONCLUSION The E-selectin changes between 6M after and before CAS are independent predictors of CSP.

Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients Receiving Thrombectomy: Standard or Low Dose Therapy?

BACKGROUND We compared the clinical outcomes of low and standard dose recombinant tissue Plasminogen Activator (rtPA) treatment in Acute Ischemic Stroke (AIS) patients receiving Endovascular Mechanical Thrombectomy (EVT). METHODS Between April 01, 2015 and September 30, 2017, all AIS patients admitted to the Linkou and Chiayi Chang Gung Memorial Hospital were retrospectively reviewed. Patients with large vessel occlusions, who underwent bridging therapy with rtPA and EVT, were further enrolled. The enrolled patients were categorized into low (0.6-0.7 mg/kg; LD) or standard dose (0.9 mg/kg; SD) group based on the dose of rtPA they received. Baseline characteristics, reperfusion status, and clinical outcomes were compared between the two groups. RESULTS Forty-two patients were enrolled in the final analyses, including 13 in the LD and 29 in the SD group. In all groups analyzed, the frequencies of moderate to severe and severe stroke at discharge were significantly decreased compared to those at stroke onset (p < 0.01). Compared to the SD group, patients of the LD group had a similar rate of mortality (LD vs. SD; 0% vs. 3.4%, p = 1.00), and comparable frequencies of functional independence at 3 months after stroke onset (LD vs. SD; 33.3% vs. 44.8%, p = 0.50). The rates of symptomatic intracerebral hemorrhage were also similar between the two groups (LD vs. SD; 0% vs. 6.9%, p =1.00). CONCLUSIONS Compared to standard dose treatment, low dose rtPA may have similar clinical efficacy and safety outcomes in AIS patients receiving bridging therapy.

Asymmetric Cerebrovascular Collateral Supply Affects Cognition in Patients with Unilateral Carotid Artery Stenosis

BACKGROUND The time to maximum of the residue function (TMax) has been employed to identify the penumbra in acute ischemic stroke. Cognitive impairment in patients with Carotid Artery Stenosis (CAS) has been attributed to chronic cerebral hypoperfusion. The study aimed to examine whether cognitive impairment can be detected based on a preliminary TMax cutoff in patients with unilateral CAS. METHODS Fifty unilateral CAS patients underwent dynamic susceptibility contrast MR perfusion. The preliminary TMax cutoff (3 seconds) was derived on the basis of the upper limit of 95% confidence interval of TMax in the Middle Cerebral Artery (MCA) contralateral to the CAS side. All patients were allocated to the Right-delayed group (n=18), Left-delayed group (n=12), and Nondelayed group (n=20) by the cutoff. Cognitive assessment was also administered on all patients and 22 healthy volunteers. RESULTS No significant interhemispheric mean TMax differences of the Non-delayed group were noted (p=0.75), but the mean TMax of ipsilateral MCA was significantly longer than that of the contralateral MCA of the Left- and Right-delayed groups (ps<0.001), respectively. Compared to healthy volunteers, the Right-delayed group performed significantly worse on most of the visuospatial tests (ps<0.04), while the Left-delayed group performed significantly worse on most of the verbal tests (ps<0.05). The performance of the Non-delayed group on all cognitive domains was similar to that of healthy volunteers (ps>0.07). CONCLUSION TMax can be used to differentiate the chronic hypoperfusion state in unilateral CAS patients. Prolonged TMax in the MCA of either hemisphere may lead to lateralized impairment in cognition functions in patients with unilateral CAS.