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BackgroundSodium-glucose co-transporter-2 inhibitors (SGLT2i) have cardiovascular (CV) benefits, particularly in reducing the risk of heart failure (HF). Pioglitazone (Pio) has shown potential in decreasing the risks of recurrent stroke, non-fatal myocardial infarction (MI), and all-cause mortality but increasing risks of HF. Our study aimed to examine the synergistic effects on CV outcomes in patients with type 2 diabetes mellitus (T2DM) who received the combined treatment of SGLT2i and Pio.Materials and methodsA total of 117,850 patients with T2DM and without a history of HF were selected as the observational study cohort from the Chang Gung Research Database (CGRD) in Taiwan between January 1, 2016, and December 31, 2019. The primary composite outcome was 4-point major adverse CV events (4P-MACE), including CV death, non-fatal MI, non-fatal ischemic stroke, and hospitalization for HF. The study was divided into four groups: a combined treatment group in which SGLT2i and Pio were used, two individual groups in which SGLT2i or Pio was used separately, and a reference group (non-study drugs).ResultsCombined treatment of SGLT2i and Pio had the lowest risk of 4P-MACE (adjusted hazard ratio [aHR], 0.66; 95% confidence interval [CI], 0.54–0.80) compared with the reference group after a mean follow-up of 2.2 years. There was no significant difference in risks of hospitalization for HF (adjusted subdistribution hazard ratio, 0.73; 95% CI, 0.49–1.07) compared with the reference group.ConclusionsIn T2DM patients without HF, the combined treatment with SGLT2i and Pio may synergistically provide CV benefits without increasing risks of HF.

Abstract Background To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods. Methods We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan–Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC. Results Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients’ images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan–Meier analysis revealed no significant difference between the NPC and non-NPC groups (p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3–7%) after both surgery and RT, 4% (95% CI = 2–6%) after surgery alone, and 5% (95% CI = 3–7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias.

Background An increased risk of recurrent stroke is noted in patients with atrial fibrillation despite direct oral anticoagulant (DOAC) use. We investigated the efficacy and safety of treatment with each of 4 different DOACs or warfarin after DOAC failure. Methods and Results We retrospectively analyzed patients with atrial fibrillation with ischemic stroke despite DOAC treatment between January 2002 and December 2016. The different outcomes of patients with DOAC failure were compared, including recurrent ischemic stroke, major cardiovascular events, intracranial hemorrhage and subarachnoid hemorrhage, mortality, and net composite outcomes according to switching to different DOACs or vitamin K antagonist after index ischemic stroke. We identified 3759 patients with DOAC failure. A total of 84 patients experienced recurrent ischemic stroke after switching to different oral anticoagulants, with a total follow‐up time of 14 years. Using the vitamin K antagonist group as a reference, switching to any of the 4 DOACs was associated with a 69% to 77% reduced risk of major cardiovascular events (adjusted hazard ratio [aHR], 0.25 [95% CI, 0.16–0.39] for apixaban, 0.23 [95% CI, 0.14–0.37] for dabigatran, 0.23 [95% CI, 0.09–0.60] for edoxaban, and 0.31 [95% CI, 0.21–0.45] for rivaroxaban), and a 69% to 83% reduced risk of net composite outcomes (aHR, 0.25 [95% CI, 0.18–0.35] for apixaban, 0.17 [95% CI, 0.11–0.25] for dabigatran, 0.31 [95% CI, 0.17–0.56] for edoxaban, and 0.31 [95% CI, 0.23–0.41] for rivaroxaban). Conclusions In Asian patients with DOAC failure, continuing DOACs after index stroke was associated with fewer undesirable outcomes than switching to a vitamin K antagonist. Alternative pharmacologic and nonpharmacologic strategies warrant investigation.

Autoimmune encephalitis is a rare but critical complication of COVID-19. The management of COVID-19-associated autoimmune encephalitis includes the use of steroids, intravenous immunoglobulin (IVIG), plasmapheresis, and monoclonal antibody therapy. This study presented a patient with critical COVID-19 autoimmune encephalitis who rapidly recovered after the initiation of corticosteroids and IVIG therapy. This study reviewed the current literature on the pathophysiological mechanisms, diagnosis, and management of COVID-19-associated autoimmune encephalitis.

Background: Patients with epilepsy have an increased risk of stroke. However, the detailed risk and characteristics of postepilepsy stroke have not been investigated. Methods: This study utilized the National Health Insurance Research Database in Taiwan. We classified adult patients with newly diagnosed epilepsy from 2003 to 2016 as the epilepsy cohort. Patients in the nonepilepsy cohort were selected with propensity score matching at a case–control ratio of 1:5. The incidence, hazard ratio (HR), period-specific HR, recurrent HR in the Wei-Lin-Weissfeld model, stroke severity index, complications, and mortality of all stroke, ischemic stroke (IS) and hemorrhagic stroke events in the two cohorts were analyzed. Results: We enrolled 23,810 patients in the epilepsy cohort and 119,050 persons in the nonepilepsy cohort. The period-specific HRs of all stroke, IS and hemorrhagic stroke peaked immediately after epilepsy diagnosis and trended downward [Adjusted HRs of all stroke: 4.88 (3.88–6.14), 4.47 (3.50–5.70), 3.17 (2.62–3.84), 2.81 (2.27–3.48), 2.81 (2.36–3.34) and 2.33 (2.07–2.62) in 0–0.5, 0.5–1, 1–2, 2–3, 3–5 and ≥5 years after epilepsy diagnosis, respectively]. The recurrent stroke HRs in the epilepsy cohort were >1 from the first [3.06 (2.71–3.34)] to the fourth events [6.33 (1.08–37.03)]. IS events in the epilepsy cohort were associated with a younger onset age, a higher IS severity index, a higher rate of urinary tract infection, a lower in-hospital mortality, while 90-day stroke mortality was similar between the 2 cohorts. Conclusion: Since the increased risk of stroke in epilepsy cohort peaked immediately after epilepsy diagnosis, early implementation of prevention strategies is considered.

Abstract Background To study whether oral presentation (OP) assessment could reflect the novice learners’ interpretation skills and reading behaviour on brain computed tomography (CT) reading. Methods Eighty fifth-year medical students were recruited, received a 2-hour interactive workshop on how to read brain CT, and were assigned to read two brain CT images before and after instruction. We evaluated their image reading behaviour in terms of overall OP post-test rating, the lesion identification, and competency in systematic image reading after instruction. Students’ reading behaviour in searching for the target lesions were recorded by the eye-tracking technique and were used to validate the accuracy of lesion reports. Statistical analyses, including lag sequential analysis (LSA), linear mixed models, and transition entropy (TE) were conducted to reveal temporal relations and spatial complexity of systematic image reading from the eye movement perspective. Results The overall OP ratings [pre-test vs. post-test: 0 vs. 1 in case 1, 0 vs. 1 in case 2, p

Background and objectivesLeukoaraiosis and infarcts are common in patients with carotid artery stenosis (CAS), and CAS severity, leukoaraiosis and infarcts all have been implicated in cognitive impairments. CAS severity was not only hypothesized to directly impede specific cognitive domains, but also transmit its effects indirectly to cognitive function through ipsilateral infarcts as well as periventricular leukoaraiosis (PVL) and deep white matter leukoaraiosis (DWML). We aimed to delineate the contributions of leukoaraiosis, infarcts and CAS to different specific cognitive domains.Materials and methodsOne hundred and sixty one participants with unilateral CAS (>50%) on the left (n = 85) or right (n = 76) side and 65 volunteers without significant CAS (

BackgroundStatins are frequently prescribed with direct oral anticoagulants (DOACs), and previous studies have raised concerns about the increased risk of intracerebral hemorrhage or other major bleeding in concurrent statins and DOACs use. The objective of this study is to evaluate the risk of major bleeding in non-valvular atrial fibrillation patients taking DOACs with or without statins.MethodsThis nationwide, retrospective cohort study used data from the Taiwan National Health Insurance Research Database, enrolled a total of 90,731 non-valvular atrial fibrillation patients receiving rivaroxaban, dabigatran, apixaban or edoxaban from January 1st, 2012 to December 31st, 2017. Major bleeding was defined as a hospitalization or emergency department visit with a primary diagnosis of intracerebral hemorrhage, gastrointestinal tract bleeding, urogenital tract bleeding, or other sites of bleeding. Adjusted incidence rate ratios (IRR) and differences of major bleeding between person-quarters of DOACs with or without statins were estimated using a Poisson regression and inverse probability of treatment weighting using the propensity score.Results50,854 (56.0%) of them were male with a mean age of 74.9 (SD, 10.4) years. Using DOACs without statins as a reference, the adjusted IRR for all major bleedings in concurrent use of DOACs and statins was 0.8 (95% CI 0.72–0.81). Lower major bleeding risk was seen in both low-to-moderate-intensity statins (IRR: 0.8, 95% CI 0.74–0.84) and high-intensity statins (IRR: 0.8, 95% CI 0.74–0.88). Concurrent use of DOACs and statins decreased the risk for intracerebral hemorrhage with an IRR of 0.8 (95% CI 0.66–0.93), and gastrointestinal tract bleeding with an IRR of 0.7 (95% CI 0.69–0.79). The protective effect of statins on intracerebral hemorrhage was observed only in female patients (IRR 0.67, 95% CI 0.51–0.89), but not in male patients (IRR 0.87, 95% CI 0.70–1.08).ConclusionsAmong non-valvular atrial fibrillation patients who were taking DOACs, concurrent use of statins decreased major bleeding risk, including intracerebral hemorrhage and gastrointestinal tract bleeding. Considering this and other cardioprotective effects, statins should be considered in all eligible patients prescribed with DOACs.

Abstract Atorvastatin 40 mg (ATOR 40) and ezetimibe 10 mg/simvastatin 20 mg (EZ-SIM 20) have similar reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond similar reductions of LDL-C, especially for extremely CV risk patients. Between January 1, 2007 and December 31, 2013, a total of 3,372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n = 1686) matched with EZ-SIM 20 group (n = 1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95–1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35–0.72), PCI (SHR, 0.82; 95% CI, 0.69–0.97) and CABG (SHR, 0.62; 95% CI, 0.40–0.97) than EZ-SIM 20 group. For T2DM patients after ACS or AIS, ATOR 40 and EZ-SIM 20 had similar major CV outcomes, which still supported the main driver for CV risk reductions is LDL-C lowering.

Kimura’s disease (KD) is a rare lymphoproliferative fibroinflammatory disorder that commonly affects the subcutaneous tissue and lymph nodes of the head and neck. The condition is a reactive process involving T helper type 2 cytokines. Concurrent malignancies have not been described. Differential diagnosis with lymphoma can be challenging without tissue biopsy. Here, we present the first reported case of coexisting KD and eosinophilic nodular sclerosis Hodgkin lymphoma of the right cervical lymphatics in a 72-year-old Taiwanese man.

Abstract Background Hypothyroidism (HT) and carotid artery stenosis (CAS) are complications of radiotherapy (RT) in patients with head and neck cancer (HNC). The impact of post-RT HT on CAS progression remains unclear. Methods Between 2013 and 2014, HNC patients who had ever received RT and were under regular follow-up in our hospital were initially screened. Patients were categorized into euthyroid (EU) and HT groups. Details of RT and HNC were recorded. Total plaque scores and degrees of CAS were measured during annual extracranial duplex follow-up. Patients were monitored for CAS progression to > 50 % stenosis or ischemic stroke (IS). Cumulative time to CAS progression and IS between the 2 groups were compared. Data were further analyzed based on the use or nonuse of thyroxine of the HT group. Results 333 HNC patients with RT history were screened. Finally, 216 patients were recruited (94 and 122 patients in the EU and HT groups). Patients of the HT group received higher mean RT doses (HT vs. EU; 7021.55 ± 401.67 vs. 6869.69 ± 425.32 centi-grays, p = 0.02). Multivariate Cox models showed comparable CAS progression (p = 0.24) and IS occurrence (p = 0.51) between the 2 groups. Moreover, no significant difference was observed in time to CAS progression (p = 0.49) or IS (p = 0.31) among patients with EU and HT using and not using thyroxine supplement. Conclusions Our results did not demonstrate significant effects of HT and thyroxine supplementation on CAS progression and IS incidence in patients with HNC after RT.

BackgroundTimely and accurate outcome prediction plays a vital role in guiding clinical decisions on acute ischemic stroke. Early condition deterioration and severity after the acute stage are determinants for long-term outcomes. Therefore, predicting early outcomes is crucial in acute stroke management. However, interpreting the predictions and transforming them into clinically explainable concepts are as important as the predictions themselves. ObjectiveThis work focused on machine learning model analysis in predicting the early outcomes of ischemic stroke and used model explanation skills in interpreting the results. MethodsAcute ischemic stroke patients registered on the Stroke Registry of the Chang Gung Healthcare System (SRICHS) in 2009 were enrolled for machine learning predictions of the two primary outcomes: modified Rankin Scale (mRS) at hospital discharge and in-hospital deterioration. We compared 4 machine learning models, namely support vector machine (SVM), random forest (RF), light gradient boosting machine (LGBM), and deep neural network (DNN), with the area under the curve (AUC) of the receiver operating characteristic curve. Further, 3 resampling methods, random under sampling (RUS), random over sampling, and the synthetic minority over-sampling technique, dealt with the imbalanced data. The models were explained based on the ranking of feature importance and the SHapley Additive exPlanations (SHAP). ResultsRF performed well in both outcomes (discharge mRS: mean AUC 0.829, SD 0.018; in-hospital deterioration: mean AUC 0.710, SD 0.023 on original data and 0.728, SD 0.036 on resampled data with RUS for imbalanced data). In addition, DNN outperformed other models in predicting in-hospital deterioration on data without resampling (mean AUC 0.732, SD 0.064). In general, resampling contributed to the limited improvement of model performance in predicting in-hospital deterioration using imbalanced data. The features obtained from the National Institutes of Health Stroke Scale (NIHSS), white blood cell differential counts, and age were the key features for predicting discharge mRS. In contrast, the NIHSS total score, initial blood pressure, having diabetes mellitus, and features from hemograms were the most important features in predicting in-hospital deterioration. The SHAP summary described the impacts of the feature values on each outcome prediction. ConclusionsMachine learning models are feasible in predicting early stroke outcomes. An enriched feature bank could improve model performance. Initial neurological levels and age determined the activity independence at hospital discharge. In addition, physiological and laboratory surveillance aided in predicting in-hospital deterioration. The use of the SHAP explanatory method successfully transformed machine learning predictions into clinically meaningful results.

Abstract Background The aim of this study is to investigate the associations between post-stroke cognitive impairment (PSCI) severity and reactive astrogliosis (RA) extent on normalized 18F-THK-5351 positron-emission tomography (PET) imaging in amyloid-negative patients with first-ever stroke. Methods We prospectively enrolled 63 amyloid-negative patients with first-ever stroke. Neurocognitive evaluation, MRI, 18F-THK-5351, and 18F-florbetapir PET were performed around 3 months after stroke. The 18F-THK-5351 uptake intensity was normalized using a signal distribution template to obtain the Z-SUM scores as the RA extent in the whole brain and cerebral hemisphere ipsilateral to stroke lesion. We evaluated stroke volume, leukoaraiosis, and brain atrophy on MRI. We used a comprehensive neurocognitive battery to obtain composite cognitive scores, and defined PSCI as a general cognitive function score < − 1. We analyzed the influence of Z-SUM scores on PSCI severity after adjusting for demographic, vascular, and neurodegenerative variables. Results Twenty-five of 63 stroke patients had PSCI. Patients with PSCI had older age, lower education, and more severe cortical atrophy and total Z-SUM scores. Total Z-SUM scores were significantly associated with general cognitive and executive functions at multiple regression models. Path analyses showed that stroke can exert cognitive influence directly by stroke itself as well as indirectly through RA, including total and ipsilateral Z-SUM scores, in patients with either right or left hemisphere stroke. Conclusion The patterns and intensity of 18F-THK-5351 uptake in amyloid-negative patients with first-ever stroke were associated with PSCI manifestations, which suggests that RA presents a modulating effect in PSCI development.

Abstract Background and aim Peroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have cardiovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS). However, whether there are additional benefits from intensive PPAR-γ modulating treatments in Asian patients with T2DM and hypertension (HTN) after IS remains unknown. Methods Between 2001 and 2013, patients admitted due to IS were identified from the National Health Insurance Research Database of Taiwan. Patients with T2DM and HTN using angiotensin receptor blockers were further included. Eligible patients were divided into two groups: (1) pioglitazone and (2) non-pioglitazone oral anti-diabetic agent groups. Propensity score matching (1:2) was used to balance the distribution of baseline characteristics, stroke severity and medications. The primary outcome was recurrent IS. Subgroup analysis for recurrent IS in pioglitazone and/or telmisartan users, the trend of IS risks across different PPAR-γ intensity treatments, and dose-dependent outcomes across different pioglitazone possession ratios were further studied. Statistical significance was set at p

Background: The occurrence of ischemic lesions is common in patients receiving carotid artery stenting (CAS), and most of them are clinically silent. However, few studies have directly addressed the cognitive sequelae of these procedure-related silent ischemic lesions (SILs).Objective: In this study, we attempted to investigate the effects of SILs on cognition using a comprehensive battery of neuropsychological tests.Method: Eighty-five patients with unilateral carotid stenosis and 25 age-matched healthy volunteers participated in this study. Brain MRI was performed within 1 week before and 1 week after CAS to monitor the occurrence of post-CAS SILs. A comprehensive battery tapping reading ability, verbal and non-verbal memory, visuospatial function, manual dexterity, executive function, and processing speed was administered 1 week before and 6 months after CAS. To control for practice effects on repeated cognitive testing, the reliable change index (RCI) derived from the healthy volunteers was used to determine the cognitive changes in patients with carotid stenosis.Results: Among the 85 patients with carotid stenosis, 21 patients received medical treatment (MED group), and procedure-related SILs were noted in 17 patients (SIL+ group) but not observed in 47 patients (SIL– group) after undergoing CAS. Two-way (group × phase) ANOVA revealed that the volunteer group showed improved scores in most cognitive tests while only limited improvement was noted in the SIL– group. The MED and control groups tended to show improvement in the follow-up cognitive testing than the SIL+ group. However, most of the cognitive changes for each patient group did not exceed the upper or lower limits (z = ±1.0) of the RCI.Conclusions: Although the occurrence of procedure-related SILs is common in patients undergoing CAS, their impacts on cognitive changes after CAS may be limited. The practice effect should be taken into consideration when interpreting cognitive changes following CAS.

Background and Objectives: Neurodegeneration and vascular burden are the two most common causes of post-stroke cognitive impairment. However, the interrelationship between the plasma beta-amyloid (Aβ) and tau protein, cortical atrophy and brain amyloid accumulation on PET imaging in stroke patients is undetermined. We aimed to explore: (1) the relationships of cortical thickness and amyloid burden on PET with plasma Aβ40, Aβ42, tau protein and their composite scores in stroke patients; and (2) the associations of post-stroke cognitive presentations with these plasma and neuroimaging biomarkers.Methods: The prospective project recruited first-ever ischemic stroke patients around 3 months after stroke onset. The plasma Aβ40, Aβ42, and total tau protein were measured with the immunomagnetic reduction method. Cortical thickness was evaluated on MRI, and cortical amyloid plaque deposition was evaluated by 18F-florbetapir PET. Cognition was evaluated with Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Dementia Rating Scale-2 (DRS-2).Results: The study recruited 24 stroke patients and 13 normal controls. The plasma tau and tau*Aβ42 levels were correlated with mean cortical thickness after age adjustment. The Aβ42/Aβ40 ratio was correlated with global cortical 18F-florbetapir uptake value. The DRS-2 and GDS scores were associated with mean cortical thickness and plasma biomarkers, including Aβ42/Aβ40, tau, tau*Aβ42, tau/Aβ42, and tau/Aβ40 levels, in stroke patients.Conclusion: Plasma Aβ, tau, and their composite scores were associated with cognitive performance 3 months after stroke, and these plasma biomarkers were correlated with corresponding imaging biomarkers of neurodegeneration. Further longitudinal studies with a larger sample size are warranted to replicate the study results.

BackgroundAngiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)-modulating effects, has additional benefits compared to other ARBs remains unclear.Methods and findingsBetween 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at p < 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97; p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data.ConclusionsThe current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population.

Background: Severe headaches, projectile vomiting, focal neurological deficits and early onset seizure are regarded as early warning symptoms of subarachnoid hemorrhage (SAH). Earlier diagnosis based on such warning symptoms theoretically would improve the clinical prognosis. However, it is still not clear whether the prognosis is correlated with early warning symptoms. Here, we reviewed warning symptoms and other predictive factors in the emergency room (ER) setting and examined their correlations with mortality. Methods: Ninety saccular aneurysmal SAH cases were reviewed in a single medical center between January 2011 and December 2013. We examined differences in mortality rate related to warning symptoms, SAH scales, onset-to-ER time, hydrocephalus, and aneurysm size, location, and complexity. Logistic regression analyses were performed to determine the correlations of warning symptoms and other predictive factors with mortality. Receiver operating characteristic (ROC) curve analysis was used to calculate the area the under curve (AUC) of SAH mortality prediction tools. Results: Warning headache, projectile vomiting, the Hunt and Hess scale, Fisher scale, World Federation of Neurological Surgeons (WFNS) grading scale, and modified WFNS (m-WFNS) scale, body mass index, aneurysm complexity and hydrocephalus were significantly different between the survivors and the decedents. The warning headache and WFNS grade were strongly correlated with mortality. The rate of prognostic prediction improved from 90.4% to 94.6% when warning headache was additionally evaluated. Conclusions: With growing healthcare costs and recognition of the value of palliative care, early identification via warning headache and a detailed clinical history review is necessary for cases of aSAH. Keywords: Warning headache, SAH, WFNS, Survival rate

Abstract Background Few systematic methods prioritize the image education in medical students (MS). We hope to develop a checklist of brain computerized tomography (CT) reading in patients with suspected acute ischemic stroke (AIS) for MS and primary care (PC) physicians. Methods Our pilot group generated the items indicating specific structures or signs for the checklist of brain CT reading in suspected AIS patients for MS and PC physicians. These items were used in a modified web-based Delphi process using the online software “SurveyMonkey”. In total 15 panelists including neurologists, neurosurgeons, neuroradiologists, and emergency department physicians participated in the modified Delphi process. Each panelist was encouraged to express feedback, agreement or disagreement on the inclusion of each item using a 9-point Likert scale. Items with median scores of 7–9 were included in our final checklist. Results Fifty-two items were initially provided for the first round of the Delphi process. Of these, 35 achieved general agreement of being an essential item for the MS and PC physicians. The other 17 of the 52 items in this round and another two added items suggested by the panelists were further rated in the next round. Finally, 38 items were included in the essential checklist items of brain CT reading in suspected AIS patients for MS and PC physicians. Conclusions We established a reference regarding the essential items of brain CT reading in suspected AIS patients. We hope this helps to minimize malpractice and a delayed diagnosis, and to improve competency-based medical education for MS and PC physicians.

Background: Breakthrough strokes during treatment with aspirin, termed clinical aspirin treatment failure (ATF), is common in clinical practice. The burden of cerebral small vessel disease (SVD) is associated with an increased recurrent ischemic stroke risk. However, the association between SVD and ATF remains unclear. This study investigated the prevalence and clinical characteristics of SVD in stroke patients with ATF.Methods: Data from a prospective, and multicenter stroke with ATF registry established in 2018 in Taiwan were used, and 300 patients who developed ischemic stroke concurrent with regular use of aspirin were enrolled. White matter lesions (WMLs) and cerebral microbleeds (CMBs) were identified using the Fazekas scale and Microbleed Anatomical Rating Scale, respectively. Demographic data, cardiovascular comorbidities, and index stroke characteristics of patients with different WML and CMB severities were compared. Logistic regression analyses were performed to explore the factors independently associated with outcomes after ATF.Results: The mean patient age was 69.5 ± 11.8 years, and 70.0% of patients were men. Among all patients, periventricular WML (PVWML), deep WML (DWML), and CMB prevalence was 93.3, 90.0, and 52.5%, respectively. Furthermore, 46.0% of the index strokes were small vessel occlusions. Severe PVWMLs and DWMLs were significantly associated with high CMB burdens. Patients with moderate-to-severe PVWMLs and DWMLs were significantly older and had higher cardiovascular comorbidity prevalence than did patients with no or mild WMLs. Moreover, patients with favorable outcomes exhibited significantly low prevalence of severe PVWMLs (p = 0.001) and DWMLs (p = 0.001). After logistic regression was applied, severe WMLs predicted less favorable outcomes independently, compared with those with no to moderate PVWMLs and DWMLs [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.25–0.87 for severe PVWMLs; OR, 0.40; 95% CI, 0.21–0.79 for severe DWMLs].Conclusions: SVD is common in stroke patients with ATF. PVWMLs and DWMLs are independently associated with functional outcomes in stroke patients with ATF. The burden of SVD should be considered in future antiplatelet strategies for stroke patients after ATF.

BackgroundTo identify predictors of carotid artery stenosis (CAS) progression in head and neck cancer (HNC) patients after radiation therapy (RT).MethodsWe included 217 stroke-naïve HNC patients with mild carotid artery stenosis after RT in our hospital. These patients underwent annual carotid duplex ultrasound (CDU) studies to monitor CAS progression. CAS progression was defined as the presence of ≥50% stenosis of the internal/common carotid artery on follow-up CDU. We recorded total plaque score (TPS) and determined the cut-off TPS to predict CAS progression. We categorized patients into high (HP) and low plaque (LP) score groups based on their TPS at enrolment. We analyzed the cumulative events of CAS progression in the two groups.ResultsThe TPS of the CDU study at enrolment was a significant predictor for CAS progression (adjusted odds ratio [aOR] = 1.69, p = 0.002). The cut-off TPS was 7 (area under the curve: 0.800), and a TPS ≥ 7 strongly predicted upcoming CAS progression (aOR = 41.106, p = 0.002). The HP group had a higher risk of CAS progression during follow-up (adjusted hazard ratio = 6.15; 95% confident interval: 2.29-16.53) in multivariable Cox analysis, and also a higher trend of upcoming ischemic stroke (HP vs. LP: 8.3% vs. 2.2%, p = 0.09).ConclusionsHNC patients with a TPS ≥ 7 in any CDU study after RT are susceptible to CAS progression and should receive close monitoring within the following 2 years.

Renal dysfunction is common after stroke. We aimed to investigate the clinical predictability of the ankle–brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) on poststroke renal deterioration. A total of 956 consecutive participants with acute ischemic stroke between 1 July 2016, and 31 December 2017 were enrolled and a final of 637 patients were recruited for final analysis. By using the group-based trajectory model (GBTM), the patients’ renal function trajectories were grouped into the low, intermediate, and high categories (LC, IC, and HC). Significant deterioration in the slope was noted in the IC (p < 0.001) and LC (p = 0.002) groups but was nonsignificant in the HC (p = 0.998) group. Abnormal ABI (ABI ≤ 0.9) was independently related to LC (adjusted odds ratio: 2.40; 95% CI, 1.16–4.95; p = 0.019) and was also independently associated with increased risks of a ≥30% decline in eGFR (adjusted hazard ratio [aHR], 2.28; 95% CI, 1.29–4.05; p = 0.005), a doubling of serum creatinine (aHR, 3.60; 95% CI, 1.93–8.34; p < 0.001) and ESRD (HR, 3.28; 95% CI, 1.23–8.74; p = 0.018). However, baPWV did not have a significant relationship with any of the renal outcomes. Patients with a lower ABI during acute stroke should receive regular renal function tests and should be closely monitored to improve poststroke renal care.

Background: Previous clinical trials showed a significant difference in efficacy and safety among antiplatelets in acute ischemic stroke (IS). The present study wished to compare the efficacy and safety head-to-head between cilostazol and clopidogrel in chronic IS. Methods: This open prospective cohort study recruited chronic IS patients with an index hospitalization between 2001 and 2013 from Taiwan National Health Insurance Research Database. In the 504,191 hospitalized patients, patients who had missing information and history of atrial fibrillation or rheumatic heart disease, received mechanical valve replacement or anticoagulants, expired during the index hospitalization, received follow-up ⩽6 months, or had recurrent stroke within 6 months after index stroke were excluded. Results: Among the 15,968 eligible patients, 502 patients who consistently received either cilostazol or clopidogrel from the 7th month after the index stroke were included for analysis after propensity score matching. The 3-year primary outcomes showed similar frequency of recurrent IS, all-cause mortality, and acute myocardial infarction (AMI), and similar frequency of intracerebral hemorrhage, gastrointestinal bleeding, and major bleeding between the cilostazol and clopidogrel groups. Subgroup analysis revealed that patients with a history of hypertension or gastrointestinal bleeding had a trend of having lower frequency of recurrent IS or major bleeding, respectively, in the cilostazol group. Conclusion: The present real-world study demonstrated no significant difference in efficacy and safety between cilostazol and clopidogrel in chronic IS. However, cilostazol might be better than clopidogrel in patients with a history of hypertension or gastrointestinal bleeding.

BackgroundStroke is prevalent in patients with chronic kidney disease (CKD) and is associated with high mortality, but the causes of death after stroke among different CKD stages are not well known.AimsWe aimed to investigate whether the severity of CKD would impact on the causes of death after first-ever stroke.MethodsThis retrospective multicenter cohort study included stoke patients with CKD between 2007 and 2012. The cause of death and date of death were ascertained by linking the National Death Registry Database of Taiwan. Clinical outcomes, 1-month, and 1-year mortality rates, and major causes of death were compared according to five CKD stages (G1 to G5) in the ischemic and hemorrhagic stroke separately.ResultsOf these patients, 9,878 were first-ever ischemic stroke (IS) patients, and 1,387 were first-ever hemorrhagic stroke (HS) patients. Patients with CKD G5 had the highest one-year mortality rate with hazard ratio 5.28 [95%CI, 3.94-7.08] in IS and 3.03 [95%CI, 2.03-4.54] in HS when compared to G1 patients. Leading causes of one-year death after IS were stroke, cancer, and pneumonia in early (G1-3) CKD patients, while diabetes mellitus, CKD, and stroke itself contributed to the major mortality in CKD G5 patients. An inverse association between eGFR decrement and the proportion of deaths caused by stroke itself was observed in CKD G2-5 patients after IS. Stroke was the leading cause of one-year death among all CKD patients after HS.ConclusionsAsides from high mortality, late-stage CKD patients had different causes of death from early CKD patients after stroke. This study highlights the need to imply different treatment strategies in late-stage CKD post-stroke patients to improve their prognosis.

Abstract Background The 18F-THK-5351 radiotracer has been used to detect the in vivo tau protein distribution in patients with tauopathy, such as Alzheimer’s disease and corticobasal syndrome. In addition, 18F-THK-5351 can also monitor neuroinflammatory process due to high affinity to astrogliosis. We aimed to explore 18F-THK-5351 distribution patterns and characteristics in patients with recent ischemic stroke. Results Fifteen patients received 18F-THK-5351 positron emission tomography (PET) and diffusion tensor imaging (DTI) approximately 3 months after ischemic stroke. A region of interest (ROI) was placed in the peri-ischemic area and was mirrored on the contralateral side as the control, and a proportional value was derived from the ratio of the peri-ischemic ROI value over the mirrored ROI value. Increased 18F-THK-5351 retention was observed in the areas around and remote from the stroke location. The proportional 18F-THK-5351 values were negatively correlated with the proportional fractional anisotropy values (r = − 0.39, P = 0.04). Conclusion 18F-THK-5351 PET imaging provides a potential tool for in vivo visualization of the widespread ischemia-related changes associated with a microstructural disruption in recent ischemic stroke patients.

Objective: Neural disruption and cognitive impairment have been reported in patients with carotid stenosis (CS), but carotid artery stenting (CAS) may not contribute to the cognitive recovery. Although functional hyper-connectivity is one of the physiological over-compensation phenomena in neurological diseases, the literature on the cognitive influence of functional hyper-connectivity in CS patients is limited. We aimed to investigate the longitudinal changes of hyper-connectivity after CAS and its association with cognition in CS patients. Methods: Thirteen patients with unilateral CS and 17 controls without CS were included. Cognitive function was evaluated at baseline, and resting-state functional MRI was performed 1 week before and 1 month and 1 year after CAS. Comparisons of functional connectivity (FC) between CS patients and controls in multiple brain networks were performed. Results: In patients before CAS, FC in the cerebral hemispheres ipsilateral and contralateral to CS was mainly decreased and increased, respectively, compared with normal controls. Part of the FC alterations gradually recovered to the normal condition after CAS. The stronger FC abnormality (both hypo- and hyper-connectivity compared with normal controls) was associated with poorer cognitive performances, especially in memory and executive functions. Conclusion: The study demonstrated the lateralization of hyper-connectivity and hypo-connectivity in patients with unilateral CS in contrast to the FC in normal controls. These FC alterations were associated with poor cognitive performances and tended to recover after CAS, implying that hyper-connectivity is served as a compensation for neural challenge. Keywords: Stroke, Carotid artery stenosis, Resting-state fMRI, Functional connectivity, Hyper-connectivity

Abstract Background Hepatitis C virus (HCV)-infected patients with chronic kidney disease (CKD) have rarely been studied because they rarely accept interferon-based therapy (IBT) and have been difficult to follow up. We investigated long-term outcomes of IBT on the population. Methods This population-based cohort study used the Taiwan National Health Insurance Research Database as its data source. HCV patients diagnosed with CKD between Jan. 1, 2003, and Dec. 31, 2013, were selected. They were then divided into two groups based on whether they had undergone IBT. All-cause mortality, acute myocardial infarction (AMI), ischemic stroke (IS), hemorrhagic stroke, and new-onset dialysis were evaluated using a Cox proportional hazard regression analysis after propensity score matching. Results We enrolled 9872 HCV patients with CKD: 1684 patients in the treated cohort and 8188 patients in the untreated cohort. The annual incidence of all-cause mortality (19.00 vs. 42.89 events per 1000 person-years; p

Objective: To test whether strokes increase around the time of cancer diagnosis, we comprehensively examined the correlations of cancer and stroke by employing a population-based cohort study design.Methods: One million people insured under the Taiwan's National Health Insurance program in 2005 were randomly sampled to create the study's dataset. According to the presence of cancer and/or stroke, patients were separated into cancer and stroke, cancer-only, and stroke-only groups. Diagnoses of cancer, stroke, and comorbidities were defined according to ICD9-CM codes. Cancer and non-cancer populations were matched by age at cancer diagnosis, gender, and stroke risk factors, and each patient with cancer was matched with two non-cancer controls nested in the same year of cancer diagnosis. The hazards of stroke and cumulative incidences within a year after cancer diagnosis were evaluated using Fine and Gray's subdistributional hazard model.Results: The temporal distribution of first-ever stroke in patients with both cancer and stroke was a sharpened bell shape that peaked between 0.5 years before and after cancer diagnosis. Frequencies of stroke were further adjusted by number of cancer survivors. The monthly event rate of stroke remained nested around the time of cancer diagnosis in all strokes. Brain malignancies, lung cancer, gastric cancer, prostate cancer, and leukemia patients obtained higher ratio of stroke, while breast cancer and thyroid cancer patients had low percentage of combining stroke. When compared to non-cancer matched control, the hazard of stroke within one year after cancer diagnosis was increased by cancer at a subdistributional hazard ratio of 1.72 (95% confident interval 1.48 to 2.01; p < 0.0001).Conclusions: Cancer increased the risk of stroke and stroke events were nested around the time of cancer diagnosis, occurring 0.5 years prior to cancer on average regardless of stroke type.

Background: Brain 18F-AV-45 amyloid positron emission tomography (PET) in Taiwanese patients with familial Alzheimer's disease with the amyloid precursor protein (APP) p.D678H mutation tends to involve occipital and cerebellar cortical areas. However, tau pathology in patients with this specific Taiwan mutation remains unknown. In this study, we aimed to study the Tau PET images in these patients.Methods: Clinical features, brain magnetic resonance imaging/computed tomography (MRI/CT), and brain 18F-THK-5351 PET were recorded in five patients with the APP p.D678H mutation and correlated with brain 18F-AV-45 PET images. We also compared the tau deposition patterns among five patients with familial mild cognitive impairment (fMCI), six patients with sporadic amnestic mild cognitive impairment (sMCI), nine patients with mild to moderate dementia due to Alzheimer's disease (AD), and 12 healthy controls (HCs). All of the subjects also received brain 18F-AV-45 PET.Results: The nine patients with sAD and six patients with sMCI had a positive brain AV-45 PET scans, while the 12 HCs had negative brain AV-45 PET scans. All five patients with fMCI received a tau PET scan with the age at onset ranging from 46 to 53 years, in whom increased standard uptake value ratio (SUVR) of 18F-THK-5351 was noted in all seven brain cortical areas compared with the HCs. In addition, the SUVRs of 18F-THK-5351 were increased in the frontal, medial parietal, lateral parietal, lateral temporal, and occipital areas (P < 0.001) in the patients with sAD compared with the HCs. The patients with fMCI had a significant higher SUVR of 18F-THK-5351 in the cerebellar cortex compared to the patients with sMCI. The correlations between regional SUVR and Mini-Mental State Examination score and between regional SUVR and clinical dementia rating (sum box) scores within volumes of interest of Braak stage were statistically significant.Conclusion: Tau deposition was increased in the patients with fMCI compared to the HCs. Increased regional SUVR in the cerebellar cortical area was a characteristic finding in the patients with fMCI. As compared between amyloid and tau PET, the amyloid deposition is diffuse, but tau deposition is limited to the temporal lobe in the patients with fMCI.

In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer’s disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.

Background: To compare the long-term clinical outcomes of different antihypertensive drugs in stable patients after acute hemorrhagic stroke (HS). Methods: From January 2001 to December 2013, patients with first-ever primary HS were identified in the National Health Insurance Research Database, Taiwan. Patients with traumatic intracerebral hemorrhage and secondary HS were excluded. Those with first-ever HS were recruited and classified into three groups: (1) angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB); (2) calcium channel blocker (CCB); and (3) other antihypertensive drugs (comparison) groups. Propensity score matching was used to balance the distribution of baseline characteristics, stroke severity, and medications between any two of the three groups. A validation study was performed using the databank of the Stroke Registry in Chang-Gung Healthcare System to reduce the bias. Primary outcomes were recurrent HS, ischemic stroke, any stroke, and all-cause mortality. Results: Compared to the comparison group, the ACEI/ARB group [35.4% versus 39.3%; hazard ratio (HR), 0.84; 95% confidence interval (CI), 0.74–0.95] and CCB group (33.0% versus 41.9%; HR, 0.72; 95% CI, 0.64–0.81) had a lower risk of all-cause mortality during long-term follow up. The CCB group had a similar risk of all-cause mortality to the ACEI/ARB group. Risks of recurrent HS, ischemic stroke, or any stroke were not different between the study groups. Conclusions: Antihypertensive drug class could be important to long-term outcomes in HS patients in addition to the target control of blood pressure. Both ACEIs/ARBs and CCBs are associated with lower risks of all-cause mortality. Our results may be applied to inform future research on hypertensive control in HS patients.

Background: Low lipid level is associated with better cardiovascular outcome. However, lipid paradox indicating low lipid level having worse outcomes could be seen under acute injury in some diseases. The present study was designed to clarify the prognostic significance of acute-phase lipid levels within 1 day after admission for stroke on mortality in first-ever statin-naïve acute ischemic stroke (IS) and hemorrhagic stroke (HS).Methods: This observational study was conducted using the data collected from Stroke Registry In Chang-Gung Healthcare System (SRICHS) between 2009 and 2012. Patients with recurrent stroke, onset of symptoms >1 day, and history of the use of lipid-lowering agents prior to index stroke were excluded. Stroke was classified into IS and hypertension-related HS. The primary outcomes were 30-day and 1-year mortality identified by linkage to national death registry for date and cause of death. Receiver operating characteristic (ROC) curve analysis and multivariate Cox proportional hazard models were used to examine the association of lipid profiles on admission with mortality.Results: Among the 18,268 admitted stroke patients, 3,746 IS and 465 HS patients were eligible for analysis. In IS, total cholesterol (TC)

BACKGROUND:With the evolution of treatments for neurological diseases, the contents of core neurological examinations (NEs) for medical students may need to be modified. We aimed to establish a consensus on the core NE items for neurology clerks and compare viewpoints between different groups of panelists. METHODS:First, a pilot group proposed the core contents of NEs for neurology clerks. The proposed core NE items were then subject to a modified web-based Delphi process using the online software "SurveyMonkey". A total of 30 panelists from different backgrounds (tutors or learners, neurologists or non-neurologists, community hospitals or medical centers, and different academic positions) participated in the modified Delphi process. Each panelist was asked to agree or disagree on the inclusion of each item using a 9-point Likert scale and was encouraged to provide feedback. We also compared viewpoints between different groups of panelists using the Mann-Whitney U test. RESULTS:Eighty-three items were used for the first round of the Delphi process. Of them, 18 without consensus of being a core NE item for the neurology clerks in the first round and another 14 items suggested by the panelists were further discussed in the second round. Finally, 75 items with different grades were included in the recommended NE items for neurology clerks. CONCLUSIONS:Our findings provide a reference regarding the core NE items for milestone development for neurology clerkships. We hope that prioritizing the NE items in this order can help medical students to learn NE more efficiently.

BackgroundAtrial flutter (AFL) has been identified to be equivalent to atrial fibrillation (AF) in terms of preventing ischemic stroke, although differences exist in atrial rate, substrate, and electrophysiological mechanisms. This study aimed to investigate differences in clinical outcomes between nonvalvular AF and AFL. Methods and ResultsAF and AFL patients without any prescribed anticoagulation were enrolled from a 13‐year national cohort database. Under series exclusion criteria, ischemic stroke, heart failure hospitalization, and all‐cause mortality were compared between the groups in real‐world conditions and after propensity score matching. We identified 175 420 patients in the AF cohort and 6239 patients in the AFL cohort, and the prevalence of most comorbidities and frequency of medications were significantly higher in the AF group than the AFL group. In the real‐world setting the AF patients had higher incidence rates of ischemic stroke, heart failure hospitalization, and all‐cause mortality than the AFL patients (all P

Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.

The clinical analyses and prognoses of mitochondrial diseases with A3243G mutation are rarely documented in Taiwan. Our study investigated the clinical phenotypes and the outcomes of patients with mitochondrial disease and the A3243G mutation of mtDNA in a Taiwanese population, and compared these with previous reports. Methods: We retrospectively studied 22 consecutive patients with mitochondrial disease and the A3243G mutation of mtDNA in Chang Gung Memorial Hospital between 1988 and 2009. All patients underwent a detailed demographic registration, neurological examinations, a muscle biopsy, and mitochondrial DNA analysis. Modified Rankin scale, the presence of recurrent strokes or seizures, critical medical complications, and death were monitored during the follow-up period. Results: Of the 22 patients, seizures and stroke-like episodes were found in 12 (55%). Visceral involvement, including cardiomyopathy, nephropathy, and pulmonary hypertension, were noted in five patients (23%). Patients with seizures had a high frequency of status epilepticus (92%) and a younger age of onset (21.3±7.2 years). Both the Kaplan–Meier survival analysis and the Cox-regression model showed a marked deterioration in patients with seizures after 7 years of follow-up. Conclusion: Our study found that seizures and status epilepticus are the most important predictive values for a poor outcome in patients with the mtA3243G mutation of mtDNA. Age of onset and visceral organ involvement had no prominent influence on the prognosis. Some medical complications could be well controlled or even reversed after management.

BackgroundCoronary artery disease (CAD) may coexist with extracranial carotid artery stenosis (ECAS), but the influence of CAD on procedure-related complications after carotid artery stenting (CAS) has not been well investigated. The study aimed to determine the impact of CAD on the occurrence of peri-CAS cerebral ischemic lesions on diffusion-weighted imaging (DWI) scanning.MethodsCoronary angiography was performed within six months before CAS. DWI scanning was repetitively done within 1 week before and after CAS. Clinical outcome measures were stroke, angina, myocardial infarction and death within 30 days.ResultsAmong 126 patients (69.5±9.0 years) recruited for unilateral protected CAS, 33 (26%) patients had peri-CAS DWI-positive lesions. CAD was noted in 79% (26 in 33) and 48% (45 in 93) of patients with and without peri-CAS DWI-positive lesions (OR, 4.0; 95% CI, 1.6-10.0; P = .0018), and the number of concomitant CAD on coronary angiography was positively correlated with the risk for peri-CAS DWI-positive lesions (P = .0032). In patients with no CAD (n = 55), asymptomatic CAD (n = 41) and symptomatic CAD (n = 30), the occurrence rates of peri-CAS DWI-positive lesions were 13%, 41% and 30% (P = .0048), and the peri-CAS stroke rates were 2%, 7% and 0% (P = .2120).ConclusionsThe severity of morphological CAD and the presence of either symptomatic or asymptomatic CAD are associated with the occurrence of peri-CAS cerebral ischemic lesions.