Nai-Fang Chi

• MD
• Professor (Associate) at National Yang Ming Chiao Tung University

Objective: To investigate the risk of stroke in patients clinically diagnosed with Alzheimer disease (AD) compared with non-AD patients with similar vascular risk factors. Methods: Using data obtained from Taiwan's National Health Insurance Research Database, we evaluated the risk of ischemic stroke (IS) and intracerebral hemorrhage (ICH) in pat...

Transcranial Doppler ultrasonography of the middle cerebral artery (MCA) is frequently used to assess dynamic cerebral autoregulation (dCA); however, this is difficult in patients with poor temporal bone windows. In the study described here, we investigated the agreement and sensitivity of dCA indices determined from the extracranial internal carot...

Background and Purpose— Cerebral autoregulation is impaired in patients with acute ischemic stroke. The purpose of this study was to investigate whether dynamic cerebral autoregulation (dCA) indices constitute an independent functional outcome predictor of acute ischemic stroke. Methods— In this study, 86 patients at days 3 to 7 after acute ischem...

Sixty-seven patients with first acute ischemic stroke onset between 3 to 7 days and 25 age- and sex- matched controls were analyzed for the performance of a resting-state functional MRI to investigate whether the functional connectivity (FC) of the motor network in acute ischemic stroke is independently associated with functional outcomes. The FC o...

Objective To investigate whether dynamic cerebral autoregulation (CA) and neuroimaging characteristics are determinants of poststroke cognitive impairment (PSCI). Methods Eighty patients within 7 days of acute ischemic stroke and 35 age‐ and sex‐matched controls were enrolled. In the patients with stroke, brain magnetic resonance imaging and dynam...

DNA sequencing of patients with rare disorders has been highly successful in identifying ''causal variants'' for numerous conditions. However, there are many reports of healthy individuals who harbor these deleterious variants, leading to the concept of incomplete penetrance and doubt about the utility of genetic testing in clinical practice and po...

Purpose Odatroltide (LT3001), a novel small synthetic peptide molecule designed to recanalize occluded blood vessels and reduce reperfusion injury, is safe and efficacious in multiple embolic stroke animal models. This study aimed to investigate the safety and tolerability of intravenous administration of odatroltide in patients with acute ischemic...

Background Half of the sufferers of reversible cerebral vasoconstriction syndrome (RCVS) exhibit imaging-proven blood-brain barrier disruption. The pathogenesis of blood-brain barrier disruption in RCVS remains unclear and mechanism-specific intervention is lacking. We speculated that cerebrovascular dysregulation might be associated with blood-bra...

Aim: This study compared the effectiveness, safety, and mortality risks between cilostazol plus aspirin and clopidogrel plus aspirin treatment for patients with acute minor ischemic stroke or transient ischemic attack (TIA). Methods: This retrospective cohort study employed a new-user design and utilized data from the nationwide Health and Welfare...

Increased medical attention is needed as the prevalence of autism spectrum disorder (ASD) rises. Both cardiovascular disorder (CVD) and hyperlipidemia are closely associated with adult ASD. Shank3 plays a key genetic role in ASD. We hypothesized that Shank3 contributes to CVD development in young adults with ASD. In this study, we investigated whet...

Objectives To investigate whether utilizing a convolutional neural network (CNN)-based arterial input function (AIF) improves the volumetric estimation of core and penumbra in association with clinical measures in stroke patients. Methods The study included 160 acute ischemic stroke patients (male = 87, female = 73, median age = 73 years) with app...

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke especially in Asian populations, which has a high risk of recurrent stroke and cardiovascular comorbidities. The present guidelines aim to provide updated evidence-based recommendations for diagnosis and management of patients with ICAD. Taiwan Stroke Society guideline...

Cognitive performance was measured under non-defecated, non-magnesium defecated, and magnesium defecated conditions among thirteen elite triathletes in a counter-balanced order. Real-time hemodynamic changes in the prefrontal brain and sub-navel regions proximal to rectum were also measured using near-infrared spectroscopy (NIRS), where both detect...

Whole exome sequencing (WES) has been used to detect rare causative variants in neurological diseases. However, the efficacy of WES in genetic diagnosis of clinically heterogeneous familial stroke remains inconclusive. We prospectively searched for disease-causing variants in unrelated probands with defined familial stroke by candidate gene/hotspot...

The 2020 Taiwan Stroke Society (TSS) guidelines for blood pressure (BP) control related to ischemic stroke update the 2015 TSS BP guidelines. The early management of acute ischemic stroke has evolved rapidly in the previous two decades. Since the publication of the previous version of the TSS BP guidelines, many studies have addressed BP management...

To determine how brain oxygenation is stably maintained during advancing age, cerebral oxygenation and hemoglobin were measured real-time at 10 Hz using near-infrared spectroscopy (NIRS) at rest (30 seconds) and during a 10-repeated handgrip strength test (30 seconds) for 834 adults (M/F = 45/55%) aged 20-88 y. The amplitude of cerebral hemodynamic...

Background: Since the publication of the 2015 Taiwan Stroke Society Blood Pressure for Treatment and Prevention of Stroke Guideline (2015 TSS BP Guideline), several new clinical studies have addressed whether a stricter blood pressure (BP) target would be effective for stroke prevention. Methods: TSS guideline consensus group provides recommenda...

Background Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzheimer’s disease (AD) in elderly population. Objective We wondered about the relationship between vascular health and cognitive performance in middle-aged adults. The present study aims to evaluate whether and which brain vascular hemodynamic parameters...

Background: Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed to construct a hyperglycemia/diabetes-derived polygenic risk score (PRS) to improve the predictive performance for poor outcome risks after a stroke and to evaluate its potential clinical application. Methods: A hospital-based cohort study...

Background: Young stroke incidence has increased worldwide with lifestyle changes. Etiology and risk factors for both ischemic and hemorrhagic stroke in young Asians remain underexplored. Methods: We retrospectively reviewed consecutive acute stroke patients aged 16-45 years admitted to the Taipei Veterans General Hospital between 2009 and 2019...

Background: Clinical and radiological outcomes of endovascular thrombectomy (EVT) are related to etiologies of large vessel occlusion (LVO) in acute stroke. However, preprocedural computed tomography angiography (CTA) or CT perfusion imaging can hardly distinguish embolic occlusion from atherosclerotic occlusion. We hypothesized that quantitative...

Background: Endovascular thrombectomy (EVT) has become the standard treatment for acute ischemic stroke with large vessel occlusion. Atrial fibrillation (AF) is one of the major causes. However, the impact of AF on the treatment has not yet been clearly discussed. This study is to evaluate the influence of AF on the outcomes of EVT in patients wit...

Ischemic preconditioning with non‐lethal ischemia can be protective against lethal forebrain ischemia. We hypothesized that aging may aggravate ischemic susceptibility and reduce brain plasticity against preconditioning. Magnetic resonance diffusion tensor imaging (DTI) is a sensitive tool to detect brain integrity and white matter architecture. Th...

Background: The current study compared the efficacy and safety of clopidogrel vs aspirin in the secondary prevention of ischemic stroke (IS). Methods: We included patients from the Taiwan National Health Insurance Research Database who were aged between 20 and 80 years, had their first ever IS, had no diagnosis of atrial fibrillation, and had no...

Background/purpose Metabolites in blood have been found associated with the occurrence of vascular diseases, but its role in the functional recovery of stroke is unclear. The aim of this study is to investigate whether the untargeted metabolomics at the acute stage of ischemic stroke is able to predict functional recovery. Methods One hundred and...

Background Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia‐associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia‐induced unfavorable stroke outcomes and further va...

Objective: To evaluate the effects of home-based rehabilitation on improving physical function in home-dwelling patients after a stroke. Data sources: Various electronic databases, including PubMed, CINAL, Embase, the Cochrane Central Register of Controlled Trials, and two Chinese datasets (i.e., Chinese Electronic Periodical Services and China...

Stroke is the third cause of death and the leading cause of adult disability in Taiwan. More than half of acute ischemic stroke patients had hyperglycemia, which is one of the major reason for unfavorable outcomes. However, the physiopathology is remain unclear and better knowledge of underlying genetic mechanisms is needed to improve prognosis. Th...

Objectives: Post-stroke cognitive impairment (PSCI) is a common disease that may occur within 3 months after a stroke or even later. However, the mechanism of PSCI development is unclear. The present study investigated whether the levels of plasma amyloid beta-42 (Aβ42) and tau are associated with the onset of PSCI. Methods: Fifty-five patients adm...

Background Early-onset adult stroke has not been fully characterized in Asians. Objectives We investigated the etiologic subtypes, risk factors and 1-year outcomes of early-onset stroke (16 – 55 years of age) in a Taiwanese cohort. Methods We retrospectively reviewed consecutive patients with acute stroke admitted to the Taipei Veterans General Hos...

Percutaneous coronary intervention (PCI) is suggested for treating patients with non-ST-elevation myocardial infarction (NSTEMI) to reduce adverse cardiovascular events. However, the short- and long-term effects of PCI on the risk of postdischarge ischemic stroke (IS) in patients hospitalized for NSTEMI remain unclear. This study investigated the a...

Objectives: Association between net vertebral artery flow volume (NVAFV) and stroke types remains unclear. We hypothesize NVAFV is low in patients with posterior circulation infarction (PCI) and an ideal cut-off value for discriminating PCI from anterior circulation infarction (ACI) and controls may be present. Materials and Methods: As study candi...

Background This study assessed whether serum lipid levels are associated with the risk of symptomatic intracerebral hemorrhage (sICH) and functional outcomes in patients with acute ischemic stroke after receiving intravenous thrombolysis. Methods We retrospectively analyzed consecutive ischemic stroke patients who were treated with intravenous tis...

Raw data for selected patients in the entire study

Objective Features of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70% of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544C mutation in stroke patients i...

Intravenous thrombolysis with the tissue plasminogen activator (tPA) is the gold standard for acute ischemic stroke. However, its application is limited because of the concern of the post-tPA intracranial hemorrhage (ICH). Low low-density lipoprotein (LDL) has been speculated to increase the risk of hemorrhagic transformation after ischemic stroke....

Background Clopidogrel was thought to be superior to aspirin for secondary prevention of vascular diseases in clinical trials. In this study we assessed the safety and efficacy of clopidogrel versus aspirin in real‐world practice by using the Taiwan Stroke Registry. Methods and Results Patients with ischemic stroke (2006–2016) on aspirin or clopid...

Appendix S1. List of Taiwan Stroke Registry Investigators. Table S1. Correlation Matrices of the Variables for 1‐Year Mortality by Cox Model Table S2. Correlation Matrices of the Variables for 1‐Year Stroke Recurrence by Cox Model

Objective This study aimed to develop and validate a prognostic model for the 1-year risk of late poststroke epilepsy (PSE). Materials and methods We included patients initially diagnosed with ischemic stroke between 2003 and 2014 in a National Health Insurance claims-based cohort in Taiwan. Patients were further divided into development and valid...

The effect of RA on recurrent stroke is unknown. Therefore, we examined effects of rheumatoid arthritis (RA) on risk of stroke recurrence and investigated the interaction between RA and traditional cardiovascular risk factors on recurrence risk after ischemic stroke (IS) or transient ischemic attack (TIA). Of 3190 patients with IS or TIA recruited...

Background: Only a few studies have investigated the affect of rheumatoid arthritis (RA) on the risk of cerebrovascular disease (CVD)/coronary artery disease (CAD) in young adults. This study, therefore, examined the association between RA and the risk of CVD/CAD in young adults and the interaction effects between cardiovascular risk factors and R...

Background: It remains unclear whether the use of new oral anticoagulants, compared with warfarin, is economically beneficial in Asian countries. Objective: The objective of this study is to compare the health care costs and utilization between dabigatran and warfarin in a real-world nonvalvular atrial fibrillation (NVAF) population. Research d...

We compared the dynamic cerebral autoregulation (dCA) indices between 5- and 10-minute data lengths by analyzing 37 patients with ischemic stroke and 51 controls in this study. Correlation coefficient ( Mx ) and transfer function analysis were applied for dCA analysis. Mx and phase shift in all frequency bands were not significantly different betwe...

Supplementary Table Agreements between dCA assessed for 5 and 10 minutes in (A) patients with stroke and (B) controls.

Background Estrogen plays an important role as an anti-inflammatory and neuroprotective agent in ischemic stroke. In this study, we analyzed the effect of a polygenic risk score (PRS) constructed using inflammatory genes and estradiol levels on the risk of ischemic stroke. Methods This case-control study was conducted with 624 ischemic stroke patie...

Background and aims: Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods: From the Taiwan Stroke Regi...

Background The presence of an intracranial aneurysm is contraindicated to recombinant tissue plasminogen activator (r-tPA) treatment for acute ischemic stroke. However, it is difficult to exclude asymptomatic intracranial aneurysms by using conventional, noncontrast head computed tomography (CT), which is the only neuroimaging suggested before r-tP...

Image of a 72 years old man, post r-tPA ICH with unruptured aneurysm. (TIF)

Image of a 77 years old woman, post r-tPA ICH with unruptured aneurysm. (TIF)

The correlation between the present of unruptured cerebral aneurysm and post r-tPA ICH. (PDF)

Aims: To investigate the association between early percutaneous coronary intervention (PCI) and pneumonia risk in patients with acute myocardial infarction (AMI) by using Taiwan's National Health Insurance Research Database. Methods and results: In total, 4,732 patients with non-ST-elevation myocardial infarction (NSTEMI) and 5,465 with ST-eleva...

Depression and dementia are common mental health problems and are associated in several ways. Early-life depression is associated with increased risk of later life dementia, and depression can present as a preclinical symptom or consequence of dementia. Despite the plausible relationship between these two clinical entities, the potential associatio...

The plot of log(-log(survival function)) versus log of survival time. (TIF)

Kaplan-Meier estimates of study and control group patients who developed dementia after 5 years of index date. (TIF)

Background Hyperglycemia is a known predictor of negative outcomes in stroke. Several glycemic measures, including admission random glucose, fasting glucose, and glycated hemoglobin (HbA1c), have been associated with bad neurological outcomes in acute ischemic stroke, particularly in nondiabetic patients. However, the predictive power of these glyc...

Raw data

Patients with schizophrenia have a higher risk of cardiovascular diseases and higher mortality from them than does the general population; however, the underlying mechanism remains unclear. Impaired cerebral autoregulation is associated with cerebrovascular diseases and their mortality. Increased or decreased cerebral blood flow in different brain...

Background: The association between chronic obstructive pulmonary disease (COPD) and the risk of recurrent peptic ulcer bleeding (PUB) remains unclear. In this study, we compared the risk of recurrent PUB between patients with and those without COPD. Methods: Using the Taiwan National Health Insurance Research Database, we first selected patient...

Objective: We recently described TURN (Thrombolysis risk Using mRS and NIHSS), a computationally simple tool for predicting symptomatic intracerebral hemorrhage (sICH) after IV thrombolysis (rt-PA). Our objective was to compare TURN to existing scores for predicting sICH. Methods: Our internal dataset consisted of 210 ischemic stroke patients re...

The objectives of this study were to develop a cross-cultural Chinese version of the Emotional and Social Dysfunction Questionnaire (ESDQ-C) and test its validity and reliability among Chinese-speaking stroke patients. Various methods were used to develop the ESDQ-C. A cross-sectional study was used to examine the validity and reliability of the de...

Purpose: Obstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepiness (EDS), and sympathetic hyperactivation. Continuous positive airway pressure is the first-line treatment for OSA. However, some patients may have residual EDS. Modafinil and its R-enantiomer, armodafinil, are wakefulness-promoting agents know...

Introduction: Cerebral hyperperfusion syndrome (CHS) is a devastating complication after carotid revascularization procedure such as carotid angioplasty and stenting (CAS). Although there is no reliable predictor of CHS after CAS, it is believed CHS is caused by impaired cerebral autoregulation (CA). However, there is no study using CA assessment a...

Background: The symptom onset-to-treatment (OTT) duration predicts symptomatic intracerebral hemorrhage (sICH) and adverse outcomes after ischemic stroke. Previous studies found disparities in OTT durations and clinical outcomes between stroke patients with symptom onset during on-hours versus off-hours, which led to the initiation of nationwide e...

Val66Met polymorphism on the brain-derived neurotrophic factor (BDNF) gene is associated with hippocampal pathology and impaired episodic memory. However, the influence of this polymorphism on working memory (WM) performance and patterns of brain activation is controversial. This study investigated the effects of BDNF Val66Met polymorphism on funct...

To assess the efficacy of various antiepileptic drugs (AEDs) for controlling post-stroke epilepsy. This nationwide cohort study was conducted by using data from 2004 to 2008 on new occurrence of post-stroke epilepsy obtained from the National Health Insurance Research Database of Taiwan. The examined AEDs were phenytoin (PHT), valproic acid (VPA),...

IV Thrombolysis (rt-PA) for ischemic stroke treatment carries a substantial risk for symptomatic intracerebral hemorrhage (sICH). Our purpose was to develop a computationally simple and accurate sICH predictor METHODS : Our derivation dataset consisted of 210 ischemic stroke patients receiving IV rt-PA from January 2009 until July 2013 at Yale-New...

Symptomatic intracranial hemorrhage (sICH) is a serious complication of IV rt-PA therapy after acute ischemic stroke. Independent sICH predictors have been previously derived using case-control studies. Here we utilized a novel cohort-based comparison to identify additional independent predictors of sICH. We included 210 patients receiving IV rt-PA...

Thirty- and 90-day modified Rankin Scale (mRS) scores are used to monitor adverse outcome or symptomatic intracerebral hemorrhage (sICH) in ischemic stroke patients after intravenous (IV) thrombolytic therapy. Discharge mRS scores are more readily available and could serve as a proxy for 30- or 90-day mRS data. Our goal was to evaluate agreement be...

BNG-1 is a herb complex used in traditional Chinese medicine to treat stroke. In this study, we attempted to identify the neuroprotective mechanism of BNG-1 by using neuroimaging and neurotrophin analyses of a stroke animal model. Rats were treated with either saline or BNG-1 for 7 d after 60-min middle cerebral artery occlusion by filament model....

Background: Glaucoma is the leading cause of irreversible blindness worldwide and primary open-angle glaucoma (POAG) is the most common type of glaucoma. An association between POAG and the subsequent risk of Alzheimer's disease (AD) and Parkinson's disease (PD) was unclear. Objective: To investigate the association between POAG (including norma...

Background: Intracerebral hemorrhage is a feared complication of IV thrombolytic (rt-PA) therapy. In recent years, at least 8 clinical scores have been proposed to predict either adverse outcome or symptomatic intracerebral hemorrhage (sICH) in patients undergoing rt-PA therapy. The purpose of this study was to evaluate the ability of these 8 scor...

Aims and objectivesTo explore varied forms of psychological distress and to determine the mediating influence of psychological distress on functional outcomes in stroke patients.Background Previous studies attest to the influence of depression on poststroke functional recovery. While there is evidence for neuropathological deficits that occur after...

To evaluate the long-term risk of ischemic heart disease (IHD) following total knee arthroplasty (TKA), we conducted a retrospective cohort study using data from the National Health Insurance Research Database of Taiwan. We evaluated 3599 primary TKA patients and 14 396 matched control patients. We further classified all patients into those with an...

Introduction: Symptomatic intracranial hemorrhage (sICH) is a concerning complication after the administration of IV r-tPA for treatment of acute ischemic stroke. Results from the NINDS trial demonstrated a 6.2% sICH rate. As such, acute stroke teams have used this data as a benchmark to compare their program’s complication rate related to IV r-tPA...

Introduction: Hemorrhagic transformation (HT) is a major complication of IV r-tPA therapy following ischemic stroke. At least 8 scores have been proposed to predict HT in patients undergoing IV thrombolytic therapy; however, studies comparing these 8 scores in an independent dataset are missing. Hypothesis: We tested the hypothesis that stroke metr...

Background: longitudinal myelitis (LM) is defined by the continuous lesion of more than four spinal cord segments. LM is a rare variant of acute transverse myelitis and it frequently presented poor responses to immunomodulatory therapy, which resulted in severe and disabling sequelae. We reported a case of acute longitudinal myelitis involving ext...

Controversies and interest are present in the associations between specific brain locations and depression or anxiety. This study investigated the association between stroke location and emotional changes in stroke patients. This prospective observational study analyzed the neuroimages and neuropsychiatric conditions of 26 patients with acute middl...

Background: Chronic central nervous system (CNS) infections have been found to associate with cerebrovascular complications. Acute CNS infections are more common than chronic CNS infections, but whether they could increase the risk of vascular diseases has not been studied. Methods: The study cohort comprised all adult patients with diagnoses of...

Sleep disorders are frequently seen in patients with Parkinson disease (PD), including rapid eye movement (REM) behavior disorder and periodic limb movement disorder. However, knowledge about changes in non-REM sleep in patients with PD is limited. This study explored the characteristics of electroencephalography (EEG) during sleep in patients with...

Background: Sleep structure disruption and rapid eye movement (REM) sleep behavior disorders (RBD) have been previously reported in patients with neurodegenerative diseases. However, similar studies have rarely been quantitatively conducted in type 3 spinocerebellar ataxia (SCA3). Methods: Fifteen patients with SCA3 and 16 healthy controls were...

BACKGROUND AND PURPOSE:APOE4 is the best-documented genetic risk factor for sporadic AD. Previous research showed that APOE4 is associated with increased risk of occurrence and earlier onset of AD in a gene dose-dependent manner. However, the specific role of APOE4 in processing of brain functions requires further investigation. Investigators have...