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Background: The Cognitive Abilities Screening Instrument (CASI) is widely used to assess global cognitive function in patients with dementia. It contains nine cognitive domains, namely long-term memory, short-term memory, attention, mental manipulation, orientation, abstraction and judgment, language, visual construction, and list-generating fluency. However, test-retest reliability and minimal detectable change (MDC) of the CASI are largely unknown in patients with dementia, which limits its utility and the explanation of a score change. Purpose: The purpose of this study was to examine test-retest reliability and calculate MDC of the CASI in patients with dementia. Methods: Fifty-two patients with dementia completed the CASI twice with a two-week interval. The frequencies of the scores in the Clinical Dementia Rating (0.5, 1, and ≥ 2) were 38.5, 36.5, and 25.0, respectively. Test-retest reliability was examined using intraclass correlation coefficient (ICC) for the total score and nine domains of the CASI. The MDC was calculated based on standard error of measurement. Results: The ICC value of the CASI total score was 0.97 while the ICC value for the nine domains were 0.65–0.92. The MDC values (MDC%) were 11.6 (12.9%), 2.8 (23.2%), 4.5 (41.2%), 3.4 (42.1%), 4.9 (49.2%), 5.3 (29.2%), 3.4 (28.8%), 2.2 (22.3%), 3.2 (32.1%), and 3.1 (30.7%) for CASI total score, long-term memory, short-term memory, attention, mental manipulation, orientation, abstraction and judgment, language, visual construction, and list-generating fluency, respectively. Conclusion: Our results revealed that the CASI has sufficient test-retest reliability. The MDC values are useful in determining a real change (i.e., improvement or deterioration) between two assessments of an individual patient. However, four domains (i.e., short-term memory, attention, mental manipulation, and list-generating fluency) demonstrated lower ICC values and substantial random measurement errors. Clinicians and researchers should be cautious while using these four domains to explain score changes between repeated assessments of patients with dementia. [ABSTRACT FROM AUTHOR]

Objectives:Caregivers’ perceived stress and reactions to patients’ memory and behavior problems have been commonly regarded as outcomes in caregiving research; however, these variables may also serve as predictors of caregivers’ depressive symptoms. The current study investigated the relationship between perceived stress and reactions to patients’ problems and depression among the family caregivers of persons with Alzheimer’s disease. Additionally, we examined caregiving self-efficacy and sleep quality as possible mediators in the relationship between perceived stress and reactions to patients’ memory and problem behaviors and depression. Methods:This study is a cross-sectional study. The study sample consisted of 72 family members caring for a loved one with Alzheimer’s disease who completed a set of questionnaires that included the Perceived Stress Scale, the Chinese Pittsburg Sleep Quality Index, the Revised Scale for Caregiving Self-efficacy, and the Revised Memory and Behavior Checklist (RMBPC). Results:The results indicated that both higher perceived stress and RMBPC reaction scores were directly and indirectly associated with higher depressive symptoms. A specific domain of caregivers’ self-efficacy and sleep quality mediated the indirect path. Conclusion:These findings suggest that caregiving self-efficacy and sleep quality may function as mechanisms through which perceived stress and reactions influence depressive symptoms and that this mechanism may be domain specific. [ABSTRACT FROM AUTHOR]

Distinguishing stenosis and hypoplasia of the extracranial vertebral artery (VA) is clinically important, but there is no agreement in defining VA hypoplasia. We endeavored to attain reference values for VA flow volume by color Doppler ultrasonography (CDU), analyze age and gender effects on VA flow volume and develop a definition of VA hypoplasia. CDU was performed in 447 subjects free of cerebrovascular diseases or carotid stenosis. The VA diameter, peak systolic velocity, end-diastolic velocity, time-averaged mean velocity, resistance index (RI) and flow volume were recorded bilaterally. We found significant asymmetries in diameter, flow velocities and flow volume with left-sided dominance. Diameters were different on left (0.297 ± 0.052 cm) and right (0.323 ± 0.057) sides (p < 0.001). Flow volume was different on right (83.0 ± 36.9 mL/min) and left (96.6 ± 42.4) sides (p < 0.001). Women had significantly smaller diameters, higher flow velocities and lower RIs than men. VA flow volume did not change with aging. We defined hypoplasia as a significant decrease in flow velocities and increase in RI for VA diameters < 0.22 cm. This definition is supported by findings of an increase in ipsilateral flow resistance (RI ≥ 0.75), contralateral diameter (side-to-side diameter difference ≥ 0.12 cm), and flow volume (side-to-side flow volume ratio ≥ 5). This definition and these reference values may lead to better differentiation between congenital variation and steno-occlusion clinically. (E-mail: ) [Copyright &y& Elsevier]

Muscular dystrophy (MD) is a genetic disorder that causes progressive muscle weakness and degeneration. Limb‐girdle muscular dystrophy (LGMD) is a type of MD that mainly causes muscle atrophy within the shoulder and pelvic girdles. LGMD is classified into autosomal dominant (LGMD‐D) and autosomal recessive (LGMD‐R) inheritance patterns. Mutations in the Dysferlin gene (DYSF) are common causes of LGMD‐R. However, genetic screening of DYSF mutations is rare in Taiwan. Herein, we identified a novel c.2867_2871del ACCAG deletion and a previously reported c.937+1G>A mutation in DYSF from a Taiwanese family with LGMD. The primary symptoms of both siblings were difficulty climbing stairs, walking on the toes, and gradually worsening weakness in the proximal muscles and increased creatine kinase level. Through pedigree analysis and sequencing, two siblings from this family were found to have compound heterozygous DYSF mutations (c. 937+1G>A and c. 2867_2871del ACCAG) within the separated alleles. These mutations induced early stop codons; if translated, truncated DYSF proteins will be expressed. Or, the mRNA products of these two mutations will merit the nonsense‐mediated decay, might result in no dysferlin protein expressed. To our knowledge, this is the first report of a novel c.2867_2871del ACCAG deletion in DYSF. Further research is required to examine the effects of the novel DYSF mutation in Taiwanese patients with LGMD. [ABSTRACT FROM AUTHOR]

Background Increasing evidence shows that bilingualism or multilingualism may have beneficial effects on preventing dementia. We performed a cross-sectional, community-based study in Taiwan. Some elders (older than 70 years) in Taiwan can speak Japanese because of the formal Japanese education they received before World War II, when Taiwan was under Japanese rule. After the war, Mandarin Chinese was adopted as the official language of Taiwan. We assessed whether constantly using three languages had an effect on dementia prevalence and cognitive function. Methods We defined multilingualism as the ability to fluently speak Taiwanese (T), Japanese (J), and Mandarin Chinese (C) in daily life. We evaluated the Mini-Mental State Examination and AD8 questionnaire results of 514 community-dwelling people older than 70 years in Taishan, Taiwan. Results Seventy-three of the subjects (14.2%) were multilingual (T, J, C) and 441 (85.8%) were bilingual (T, C). No difference was noted in dementia prevalence between multilingual (6.8%) and bilingual (7.4%) populations, but multilinguals were older than bilinguals (mean age: 79.9 vs 77.3 years). Multilinguals had higher Mini-Mental State Examination scores than bilinguals (mean: 24.6 vs. 22.7). However, after the subjects were stratified into low and high education level groups, the Mini-Mental State Examination difference was found to be significant in only the low education level group. Conclusions Dementia prevalence did not significantly differ between the multilingual (T, J, C) and bilingual (T, C) groups. However, given that the average age of the multilingual group was approximately 2 years older than that of the bilingual group, there may have been minor effects in the multilingual group. [ABSTRACT FROM AUTHOR]

Background: Chinese populations have been reported higher incidence of all strokes and intracerebral hemorrhage. However, few large-scale studies have evaluated changes of stroke epidemiology in the 21st century. Methods: We explored the rates of incidence of all first-ever strokes, subtypes, and 1-month case fatality by using data from the Taiwan National Health Insurance Research Database since 2004. Also, we investigated sex differences in stroke. Time-trend analysis was performed for incidence and case fatality rates of all strokes and subtypes in both sexes. Results: The age-adjusted incidence of all strokes per 100,000 person-years decreased by 16%, from 251 (95% confidence interval [CI] 249–253) in 2004 to 210 (95% CI 209–212) in 2011 (p<0.001); it was always higher in Chinese men than in women. Among pathological subtypes, the incidence of intracerebral hemorrhage markedly decreased by 26% over the years (p<0.001), while that of ischemic stroke slightly decreased by 8%. However, when stratified by sex, the incidence of ischemic stroke decreased significantly in only women, not in men (men: p = 0.399, women: p = 0.004). Regarding the incidence of subarachnoid hemorrhage, it remained unchanged. Furthermore, the rate of 1-month case fatality decreased significantly for all strokes in both sexes (p<0.001). Conclusions: In Taiwan, the incidence rate of first-ever stroke decreased in both Chinese men and women in the early 21st century. Men had a higher incidence rate than women. Furthermore, a marked decrease was noted in the incidence of intracerebral hemorrhage, while a slight decrease was noted in that of ischemic stroke; however, the decreased incidence of ischemic stroke was significant in only women. [ABSTRACT FROM AUTHOR]

Background: Language impairment and behavioral symptoms are both common phenomena in dementia patients. In this study, we investigated the behavioral symptoms in dementia patients with different language backgrounds. Through this, we aimed to propose a possible connection between language and delusion. Methods: We recruited 21 patients with Alzheimer’s disease (AD), according to the DSM-IV and NINCDS-ADRDA criteria, from the memory clinic of the Cardinal Tien Hospital in Taipei, Taiwan. They were classified into two groups: 11 multilinguals who could speak Japanese, Taiwanese and Mandarin Chinese, and 10 bilinguals who only spoke Taiwanese and Mandarin Chinese. There were no differences between age, education, disease duration, disease severity, environment and medical care between these two groups. Comprehensive neuropsychological examinations, including Clinical Dementia Rating (CDR), Mini-Mental Status Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), Verbal fluency, Chinese version of the Boston naming test (BNT) and the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD), were administered. Results: The multilingual group showed worse results on the Boston naming test. Other neuropsychological tests, including the MMSE, CASI and Verbal fluency, were not significantly different. More delusions were noted in the multilingual group. Three pairs of subjects were identified for further examination of their differences. These three cases presented the typical scenario of how language misunderstanding may cause delusions in multilingual dementia patients. Consequently, more emotion and distorted ideas may be induced in the multilinguals compared with the MMSE-matched controls. Conclusion: Inappropriate mixing of language or conflict between cognition and emotion may cause more delusions in these multilingual patients. This reminds us that delusion is not a pure biological outcome of brain degeneration. Although the cognitive performance was not significantly different between our groups, language may still affect their delusion. [ABSTRACT FROM AUTHOR]

This study investigated changes in cognitive function in acute and delayed carbon monoxide (CO) poisoning groups with comprehensive neuropsychological tests at 1 month and 6 months after therapy. For this study, 11 patients with acute and 14 with delayed CO poisoning were recruited. The neuropsychological tests included psychomotor speed, visual-spatial ability, language, logical memory, working memory, and executive function. The results showed that patients with delayed neuropsychiatric syndrome (DNS) had poorer performance on neuropsychological tasks than did those with acute CO poisoning at the 1st month and reached almost the same level as the acute group on the neuropsychological tasks at the 6-month follow-up assessment. The DNS group had more significant progress on general cognitive function, psychomotor speed, and visual-spatial ability than did the acute group after continuous hyperbaric-oxygen therapy. [ABSTRACT FROM PUBLISHER]

Abstract: Isolated middle cerebral artery dissection (MCAD) has rarely been encountered clinically and few have reviewed it systemically. The etiologies, clinical manifestations, natural clinical course and prognosis of MCAD remain poorly understood. From 1995 to 2004, there were 5 cases diagnosed clinically and angiographically to have MCAD (isolated MCAD in 1, ICAD-MCAD in 4) from a medical center in Taiwan. MEDLINE (1966–2003) was searched for published articles in English that concerned the diagnosis of MCAD. Clinical presentations, stroke types, angiographic findings, etiologies, treatment strategies and outcomes were compared between cases with isolated MCAD or ICAD-MCAD. There were 23 cases (male, 46%; mean age, 22.9±19.5 years) with 24 events of isolated MCAD and 31 cases (male, 47%; mean age, 22.2±12.9 years) with 35 events of ICAD-MCAD. The types of stroke in isolated MCAD group included subarachnoid hemorrhage (12%) and cerebral infarction (88%); and in ICAD-MCAD group were subarachnoid hemorrhage (6%) and cerebral infarction (94%). The presenting symptoms were similar between both groups. Fluctuating course was more often in isolated MCAD than in ICAD-MCAD (17% vs. 3%, p =0.061). Recurrence of dissection events in both groups was infrequent (4% vs. 9%, p =0.56). Both groups had high case-fatality rates (MCAD, 48%; ICAD-MCAD, 58%). The cause of dissection in both groups was idiopathic in the majority. Congenital vessel wall defects were found in 26% of ICAD-MCAD, but in only 4% of isolated MCAD (p =0.066). In contrast, preceded trauma was more often found in isolated MCAD than ICAD-MCAD (35% vs. 19%, p =0.085). Arteritis was noted in 16% of ICAD-MCAD patients, but none in isolated MCAD. Angiography revealed segmental stenosis in 72% of isolated MCAD and 96% of ICAD-MCAD. Aneurysmal dilatation of the involved cerebral arteries was noted in 28% of isolated MCAD, but none in MCAD-ICAD. Both isolated MCAD and ICAD-MCAD can cause vascular events with high mortality rates. Several aspects differed between 2 groups, including clinical course, underlying etiologies and angiographic findings. [Copyright &y& Elsevier]

Pregnancy may increase the risk of stroke. However, few studies have compared strokes in women of reproductive age that occur in pregnancy or the puerperium (pregnancy-related stroke, PRS) with those unrelated to pregnancy. This study assesses risk factors and etiologies of stroke in these women based on relationship to pregnancy. From 1984 to 2002, all female patients 15 through 40 years of age with a first-ever stroke at National Taiwan University Hospital were included in this study. PRS was defined as patients who had stroke occurrence during pregnancy or within 6 weeks postpartum. Stroke was categorized as cerebral infarction (CI), cerebral hemorrhage (CH), or subarachnoid hemorrhage (SAH) and divided into subtype according to etiology. Risk factors and etiologies were compared for patients with PRS and stroke unrelated to pregnancy. We identified 49 patients with PRS, and 353 patients with stroke unrelated to pregnancy. There was no statistically significant difference in distribution of CI subtypes. Cerebral venous thrombosis (CVT) was more common in PRS than stroke unrelated to pregnancy (39% vs. 7%, P<0.001), and 73% of these cases occurred postpartum. Preeclampsia–eclampsia was an important cause of peripartum CH (37%), but not CI (4%). Among PRS cases, postpartum cerebral venous thrombosis and preeclampsia–eclampsia were the major causes of CI and CH, respectively. [Copyright &y& Elsevier]

Background and Objectives Improving quality of life for community-dwelling older persons with dementia symptoms (PWDS) and family caregivers requires promoting dementia-friendly communities (DFC). However, little is known regarding older Taiwanese Aboriginal PWDS' experiences of living in the community. We explored these experiences for older Atayal PWDS and their families in Taiwan. Research Design and Methods This grounded theory research used in-depth interviews to explore the perspectives of older PWDS (n = 4), their family members (n = 3), and key persons (n = 10) in an Atayal community in northern Taiwan. Data were analyzed using constant comparative analysis. Participants were interviewed between January and May 2015. Results Participants' experiences were captured by the overarching concept of "low dementia awareness, high family-like ambience in the community." Despite the low/absent community awareness of dementia, older Atayal PWDS functioned as freely in the community as at home due to a family-like supportive environment. Aboriginal PWDS and their families also faced environmental challenges, e.g., environmental constraints and barriers to transportation access. Discussion and Implications Our results suggest that this Aboriginal community and culture offer important DFC components, and these strengths could be further studied to enhance DFC models elsewhere. Despite these strengths in supporting PWDS, environmental challenges to transportation access still cause difficulties for PWDS and their families and need improvement. The Atayal community's low dementia awareness suggests that services introduced must be culturally appropriate and nondisruptive to existing supportive helping systems. Our study can be a model for future studies to understand and identify PWDS' needs in Indigenous communities. [ABSTRACT FROM AUTHOR]

Aim: To determine whether giving dementia caregivers active psychoeducational intervention is more efficacious than passive intervention for improving their caregiving skills and reducing their caregiving burden. Methods: This study was a prospective, single‐blinded, controlled trial with 43 caregiver/person‐with‐dementia dyads. The dyads were randomly assigned to the active psychoeducational intervention (AP) group, which used role‐play, discussion, and development of problem‐solving capacity to build up their caregiving skills and competence, or the passive psychoeducational intervention (PP) group, which gave caregivers educational materials on common caregiving strategies. Primary outcomes were the levels of caregiver competence (Care Skill Inventory [CSI]), burden (Chinese Zarit Burden Inventory [CZBI]), and distress caused by the behavioral and psychological symptoms of dementia (Neuropsychiatric Inventory‐Questionnaire [NPI‐Q]). Outcomes were assessed pre‐test, post‐test and after 3 months. Repeated measures one‐way analysis of variance was used to compare mean‐change scores between time‐points, and generalized estimating equations (GEE) were used to compare groups. Results: Post‐test or 3‐month (or both) Care Skill Inventory, Chinese Zarit Burden Inventory and Neuropsychiatric Inventory‐Questionnaire distress levels were significantly (p < 0.05) better in the AP but not in the PP group. The generalized estimating equation intergroup comparison, adjusted for potential confounders, showed that Care Skill Inventory in the AP group was more significantly improved than in the PP group, and that Chinese Zarit Burden Inventory nearly reached significance. Conclusions: Active rather than passive psychoeducation, even in a short (3 months) intervention of six visits, was more efficacious for improving caregiving competence. Future studies will require larger samples. Geriatr Gerontol Int 2018; 18: 750–757. [ABSTRACT FROM AUTHOR]

Introduction Religious affiliations vary across ethnic groups because of different cultural backgrounds. Some studies have explored the association between religious affiliation and cognitive decline. Only a small portion of patients with cognitive decline progress to dementia. However, the association between religious affiliation and dementia risk remains unclear. Methods In this case–control study, we recruited 280 patients with Alzheimer's disease (AD) and 138 with vascular dementia (VaD) (both aged ≥60 years) from three teaching hospitals in northern Taiwan between 2007 and 2010. Age-matched healthy controls ( n = 466) were recruited from an elderly health checkup program and from volunteers visiting the hospital during the same period. Three religious affiliations—Taoism, Buddhism, and Christianity—were evaluated. The study also assessed the effect of important factors such as gender or leisure activities on the association of religious affiliation with dementia risk. Results Participants with Christianity affiliation showed decreased AD risk (adjusted odds ratio [AOR] = 0.46, 95% confidence interval [CI] = 0.25–0.87) compared with those without any religious affiliation. Moreover, this effect was stronger in women (AOR = 0.38, 95% CI = 0.15–0.92) and in participants who exercised regularly (>3 times/week; AOR = 0.33, 95% CI = 0.14–0.77). No significant association was observed among participants with Taoism and Buddhism affiliations. Affiliation to none of the religions was associated with VaD risk. Conclusions Thus, Chinese participants having Christianity affiliation showed decreased AD risk. Moreover, the protective effect was more evident in women and in participants who exercised regularly. [ABSTRACT FROM AUTHOR]

Background: CHRNA7 encodes the α7 nicotinic acetylcholine receptor subunit, which is important to Alzheimer's disease (AD) pathogenesis and cholinergic neurotransmission. Previously, CHRNA7 polymorphisms have not been related to cholinesterase inhibitors (ChEI) response. Methods: Mild to moderate AD patients received ChEIs were recruited from the neurology clinics of three teaching hospitals from 2007 to 2010 (n = 204). Nine haplotype-tagging single nucleotide polymorphisms of CHRNA7 were genotyped. Cognitive responders were those showing improvement in the Mini-Mental State Examination score ≧2 between baseline and 6 months after ChEI treatment. Results: AD women carrying rs8024987 variants [GG+GC vs. CC: adjusted odds ratio (AOR) = 3.62, 95% confidence interval (CI) = 1.47–8.89] and GG haplotype in block1 (AOR = 3.34, 95% CI = 1.38–8.06) had significantly better response to ChEIs (false discovery rate <0.05). These variant carriers using galantamine were 11 times more likely to be responders than female non-carriers using donepezil or rivastigmine. Conclusion: For the first time, this study found a significant association between CHRNA7 polymorphisms and better ChEI response. If confirmed by further studies, CHRNA7 polymorphisms may aid in predicting ChEI response and refining treatment choice. [ABSTRACT FROM AUTHOR]

Abstract: Background: Familial hemiplegic migraine (FHM) is a rare type of migraine. Correct diagnosis is challenging for emergency physicians (EPs) due to its variable clinical picture, as well as its lack of diagnostic biological markers. Objectives: To raise awareness among EPs regarding FHM''s diverse clinical picture, and to highlight FHM''s diagnostic criteria to facilitate an accurate and timely diagnosis of FHM in patients presenting to the emergency department (ED) with indicative symptomatology. Case Report: A 24-year-old male student presented to the ED complaining of dizziness, general weakness, and blurred vision that had developed the previous night. The initial physical examination revealed drowsiness, slow speech production, and slight weakness with paresthesia in all limbs. Detailed communication with the patient''s aunt revealed that he had experienced several similar attacks since the age of 12 years, and that there was also an extensive family history of the same symptoms. In addition, 2 h after arrival, the patient experienced severe throbbing headache, vomiting, severe dysphasia, and the weakness shifted to the right side. A computed tomography scan of the brain showed no anomalies. He was admitted with a tentative diagnosis of FHM. Conclusion: A diagnosis of FHM should be considered if the patient''s clinical features include headache and weakness, with a family history of similar symptomatology. However, atypical symptoms of FHM may present as recurrent episodes of unexplained encephalopathy. Crucial elements for making an accurate and timely diagnosis of FHM include a detailed knowledge of weakness-related diseases and an ability to consider FHM in the differential diagnosis, as well as obtaining a thorough family history with repeated neurologic assessments. [Copyright &y& Elsevier]

Abstract: BMI change and BMI at an early age have not been investigated as risks for dementia. This case-control study included 286 dementia patients and 268 controls from two medical centers between 2007 and 2009. BMI information was collected from medical records and questionnaires. Men and women with low BMIs at the time of the study, in their 20s, and in their 40s had significantly increased risks of Alzheimer''s disease (AD) (odds ratio = OR = 2.62–3.97) and increased vascular dementia (VaD) risk (20s and 40s: OR = 6.23–11.11) compared with those with normal BMIs. High BMI in the 20s and 40s was associated with increased VaD risk (OR = 15.29 and 10.32) among women. For BMI changes from the 20s or 40s, the second and third tertiles were significantly associated with decreased AD risk among women (OR = 0.15–0.35) compared to the first tertile. The third tertile of BMI change from the 20s or 40s was associated with decreased VaD risk among women (OR = 0.06 and 0.14). Low BMIs in the 20s and 40s were stronger predictors of AD and VaD. There was a U-shaped association between BMI at different ages and dementia among participants with VaD. [Copyright &y& Elsevier]

Abstract: Dysphagia increases the risk of pneumonia in stroke patients. This study aimed to evaluate bedside swallowing screening for prevention of stroke-associated pneumonia (SAP) in acute stroke patients admitted to the intensive care unit (ICU). Consecutive acute stroke patients admitted to the stroke ICU from May 2006 to March 2007 were included. Patients were excluded if they were intubated on the first day of admission or had a transient ischemic attack. A 3-Step Swallowing Screen was introduced since October 2006 and therefore patients were divided into pre-screen and post-screen groups. A binary logistic regression model was used to determine independent risk factors for SAP and in-hospital death. There were 74 and 102 patients included in the pre- and post-screen groups, respectively. Pneumonia was associated with higher National Institutes of Health Stroke Scale (NIHSS) score, older age, nasogastric and endotracheal tube placement. After adjusting for age, gender, NIHSS score and nasogastric and endotracheal tube insertion, dysphagia screening was associated with a borderline decrease in SAP in all stroke patients (odds ratio, 0.42; 95% CI, 0.18–1.00; p =0.05). However, dysphagia screening was not associated with reduction of in-hospital deaths. Systematic bedside swallowing screening is helpful for prevention of SAP in acute stroke patients admitted to the ICU. [Copyright &y& Elsevier]

Abstract: Stroke centers and intravenous tissue plasminogen activators (tPA) are effective management for acute ischemic stroke. This study aimed to analyze stroke center characteristics on the administration of thrombolytic therapy. A national survey of stroke centers in academic medical centers and regional teaching hospitals in Taiwan was conducted. The survey questions included the number of tPA or other thrombolytic therapies, presence of stroke intensive care units and wards, initiation of rehabilitation, and 15 criteria for establishment of stroke centers adopted from the Brain Attack Coalition''s recommendation. Factors influencing administration of thrombolytic therapy were analyzed. Intravenous tPA increased from 135 cases in 2004 to 246 cases in 2006, accounting for approximately 0.4% and 0.8% of all acute ischemic stroke patients in Taiwan, respectively. The frequency of thrombolytic therapy administration significantly correlated with stroke center criteria (Spearman''s rho=0.731, P <0.001). Multivariate analysis showed routine intravenous tPA protocol in the emergency room (odds ratio=4.6, P =0.042) and supervision by the stroke center director (odds ratio=3.7, P =0.031) significantly influenced the administration of thrombolytic therapy. Well-organized stroke centers, routine use of thrombolytic therapy protocols in the emergency room, and guidance by a stroke center director are important for enhancing thrombolytic therapy in patients with acute ischemic stroke. [Copyright &y& Elsevier]

Long-term exposure to inorganic arsenic from artesian drinking well water is associated with carotid atherosclerosis in the Blackfoot Disease (BFD)-hyperendemic area in Taiwan. The current study examined the arsenic methylation capacity and its risk on carotid atherosclerosis. A total of 304 adults (158 men and 146 women) residing in the BFD-hyperendemic area were included. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Chronic arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE) and the duration of artesian well water consumption. Urinary levels of inorganic arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)] were determined by high performance liquid chromatography linked on-line to a hydride generator and atomic absorption spectrometry (HPLC-HG-AAS). The percentage of arsenic species, primary methylation index [PMI=MMA(V)/(As(III)+As(V)] and secondary methylation index [SMI=DMA(V)/MMA(V)] were calculated and employed as indicators of arsenic methylation capacity. Results showed that women and younger subjects had a more efficient arsenic methylation capacity than did men and the elderly. Carotid atherosclerosis cases had a significantly greater percentage of MMA(V) [%MMA(V)] and a lower percentage of DMA [%DMA (V)] compared to controls. Subjects in the highest two tertiles of PMI with a median of CAE >0 mg/L-year had an odds ratio (OR) and a 95% confidence interval (CI) of carotid atherosclerosis of 2.61 and 0.98–6.90 compared to those in the highest two tertiles of PMI with a CAE=0 mg/L-year. We conclude that individuals with greater exposure to arsenic and lower capacity to methylate inorganic arsenic may be at a higher risk to carotid atherosclerosis. [Copyright &y& Elsevier]

Abstract: Multivariate models have not been widely used to predict the outcome of acute stroke patients admitted to the intensive care unit (ICU). The purpose of this study was to determine potential measures observed in the first 12 h post-stroke that predict early mortality and functional outcomes in ICU-admitted stroke patients. Eight hundred and fifty acute stroke patients (ischemic stroke, 508; intracerebral hemorrhage, 342) were included in this analysis between November 2002 and December 2006. Measures of interest were obtained in the first 12 h after onset of stroke were analyzed for three types of outcome: 3-month mortality, 3-month mortality or institutional care, and poor functional outcomes at discharge. Poor functional outcomes were defined as a Barthel index <80 or a Rankin scale >2. Multivariate regression models were used to determine the predictive value of the observed measures. After 3 months, 17% of patients had died; 21% were alive but being cared for in institutional settings; and 62% were alive and living at home. Functional status at discharge indicated 16% of patients had died, poor function in 50%, and good function in 34% of patients. Initial stroke severity, measured by National Institute of Health Stroke Scale, and dependence on a ventilator predicts 3-month mortality and poor outcome in all stroke patients. In addition, old age, previous stroke, and total anterior circulatory infarct were associated with poor outcome in ischemic stroke patients; old age, low body mass index and the presence of intraventricular hemorrhage were associated with poor outcomes in intracerebral hemorrhage patients. In conclusion, early stroke mortality and outcome at discharge can be predicted in the first few hours following an acute stroke for moderate to severe ICU-admitted stroke patients. [Copyright &y& Elsevier]

Objectives: This study sought to report technical details and clinical results of the first series of endovascular recanalization for cervical internal carotid artery (ICA) occlusion. Background: Cervical ICA occlusion is associated with impaired cerebral perfusion, which may lead to ischemic cerebral symptoms and hemodynamic infarcts. Neither surgical nor endovascular revascularization has been shown to benefit this population. Methods: Endovascular recanalization was attempted in 30 patients with ICA occlusions (27 men; age 72.1 ± 8.0 years, range 48 to 85 years). Recurrent neurologic deficit or cerebral ischemia by perfusion study, after known ICA occlusion, was noted in all patients. Strategies and devices for coronary occlusion intervention were applied, including microcatheter-supported tapered-tip stiff coronary guidewires. Contralateral ICA stenosis was found in 9 patients (30%). All patients underwent independent neurologic and duplex ultrasound follow-up. Results: The overall technical success rate was 73% (22 of 30). No neck hematoma, intracranial hemorrhage, or hyperperfusion was noted. One (3.3%) fatal brainstem infarction occurred 1 day after a successful ICA procedure, with angiographically proven acute basilar artery occlusion and patent ICA stent. Baseline ophthalmic artery flow was reversed in 15 of the 22 successfully recanalized patients, and was normalized in 12 after the procedure. There was no new cerebral ischemic event or neurologic death for a mean follow-up of 16.1 ± 18.5 months. Conclusions: Endovascular recanalization for cervical ICA occlusion is feasible with acceptable midterm clinical results. [Copyright &y& Elsevier]

Abstract: The phenotype and genotype of cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (CADASIL) in Caucasians have been well characterized, but CADASIL is less recognized in Asian populations. Here we investigated the first known Taiwanese family affected by CADASIL and identified an uncommon NOTCH3 mutation. The family had clinical manifestations in affected members including recurrent strokes, early dementia, and depression, but not migraine. A skin biopsy in the proband patient showed characteristic pathological findings of CADASIL on electron microscopy. Afterward, genetic analysis found an Arg332Cys mutation at exon 6 of NOTCH3. Neuropsychological evaluation showed vascular dementia in two of four affected people. Head MRI showed multiple infarcts in bilateral basal ganglia, thalami, periventricular white matter, external capsules, and brainstem, but involvement of the anterior temporal pole was found only in two people with milder symptoms. To our knowledge, the Arg332Cys NOTCH3 mutation at exon 6, which was identified in the studied family, has not been reported in Asian populations. Our findings emphasize the importance of genetic analysis of NOTCH3 for Asians with a phenotype typical of CADASIL. [Copyright &y& Elsevier]

Stenting is a potential alternative treatment for carotid artery stenosis. Direct stenting may, theoretically, reduce the risk of embolism by minimizing plaque manipulation before tissue scaffolding is achieved. The results of direct carotid stenting are reported and compared with those of stenting with predilatation. One hundred and seventy-four carotid artery stenoses were treated from July 1998 to February 2002, with 84 lesions directly stented (Group 1) and the other 90 lesions stented after predilatation (Group 2). The criteria for direct stenting were minimal luminal diameter (MLD) > 1 mm and no visible thrombus angiographically. Technical success rates of the two groups were both 100%, without any cross-over. Reference vessel diameter and lesion length did not differ between the two groups. In Group 1, diameter stenosis was lower (79 ± 8 vs 92 ± 7%,P < 0.001) and MLD was larger (1.1 ± 0.5 vs 0.4 ± 0.4 mm,P < 0.001) than that in Group 2, but the final MLD (4.7 ± 0.9 vs 4.7 ± 0.9 mm,P = 0.94) of the two groups were not statistically different. The periprocedural ipsilateral stroke or death rates were also similar in the two groups (2/84 vs 4/90,P = 0.68). It was concluded that if the MLD of carotid stenosis is larger than 1 mm and no thrombus is present, direct stenting could be carried out safely with results comparable to that of stenting after predilatation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association of intima media thickness (IMT) and plaque with risk factors for atherosclerosis in asymptomatic subjects in Taiwan. Between 1998 and 2001, the study recruited 1781 asymptomatic subjects (1131 men and 650 women [mean age, 49 years; range 18–85 years]). These were examined by B-mode ultrasound to measure the IMT at the far wall of the common carotid artery (CCA) and the extent of plaque formation. A wide range of vascular risk factors including age, gender, smoking, body mass index, blood chemistry, and previous history were surveyed. The mean (±S.D.) IMT observed was 0.68 (±0.12) and 0.66 (±0.11) mm for men and women, respectively, (P=0.0008). The mean (S.D.) IMT of the CCA was 0.66 (±0.12) mm on the right side and 0.68 (±0.12) mm on the left side (P=0.0004). IMT increased with aging, according to the equation IMT=(0.005×age in years)+0.043. Higher IMT was associated with male gender, and IMT was greater in the left CCA. About 36.9% of subjects had carotid plaques. The percentage of plaque increased with aging. The plaque prevalence was positively associated with IMT. The value of IMT over the cut point of 0.68 mm correlated with obviously increased risk of carotid atherosclerosis. Age, systolic blood pressure and fasting blood sugar were independent risk factors related to both carotid atherosclerosis and thick IMT. [Copyright &y& Elsevier]

• A link exists between NPC treated with RT and dementia development. • A 1.97-fold higher risk of dementia exists in NPC patients than in controls. • The occurrence of dementia seems earlier in NPC patients than in the controls. We evaluated the risk of dementia in patients with nasopharyngeal cancer (NPC) after undergoing radiation therapy (RT). Between January 1, 2000, and December 31, 2015, 594 patients newly diagnosed with NPC and treated with RT (NPC cohort) were identified from the Longitudinal Health Insurance Database (LHID) for this nationwide population-based matched cohort study. LHID is a subset of the National Health Insurance Research Database of Taiwan. We selected 2376 controls (non-NPC comparison cohort) using a four-fold propensity score-matched by sex, age, comorbidities, education level, tobacco abuse, and index date (the date when the patient received first RT). After adjusting for confounding factors, Fine and Gray's competing risk analysis compared dementia development between the NPC study cohort and non-NPC comparison cohort over the observation period from 2000 to 2015. Dementia development was 6.57% (39 of 594) and 4.42% (105 of 2376) in the NPC study cohort and non-NPC comparison cohort, respectively. Patients with NPC receiving RT were more likely to develop dementia than the comparison cohort, with a crude hazard ratio (HR) of 1.63 [95% confidence interval (CI) = 1.25–2.13, P < 0.001]. After adjusting for age, sex, education level, tobacco abuse, comorbidity, geographic area, urbanization level of the residence, and care level, the adjusted HR was 1.91 (95% CI = 1.42–2.51, P < 0.001). Patients with NPC receiving RT had a 1.91-fold higher risk of dementia than the non-NPC comparison controls. [ABSTRACT FROM AUTHOR]

Abstract: Vascular lesions are infrequently recognized as manifestations of neurofibromatosis 1 (NF1), but they can produce serious complications and contribute to mortality at younger ages. Here we report the case of a young female patient with NF1 who suffered from a fatal middle cerebral artery (MCA) infarct. In addition to the MCA infarct, head MRI also disclosed old infarcts at bilateral cerebella and multiple intracranial arterial steno-occlusions. Stroke related to NF1 cerebral vasculopathy was highly suggested after other diseases were excluded. Additionally, genetic analysis of the patient identified a novel mutation at the splicing donor site, c. 2409+2T>G that resulted in a splicing aberration. [Copyright &y& Elsevier]

Previous genome-wide association studies using P-values to select single nucleotide polymorphisms (SNPs) have suffered from high false-positive and false-negative results. This case-control study recruited 713 late-onset Alzheimer's disease (LOAD) cases and controls aged ≥65 from three teaching hospitals in northern Taiwan from 2007 to 2010. Performance metrics were used to select SNPs in stage 1, which were then genotyped to another dataset (stage 2). Four SNPs (CPXM2 rs2362967, APOC1 rs4420638, ZNF521 rs7230380, and rs12965520) were identified for LOAD by both traditional P-values (without correcting for multiple tests) and performance metrics. After correction for multiple tests, no SNPs were identified by traditional P-values. Simultaneous testing of APOE e4 and APOC1 rs4420638 (the SNP with the best performance in the performance metrics) significantly improved the low sensitivity of APOE e4 from 0.50 to 0.78. A point-based genetic model including these 2 SNPs and important covariates was constructed. Compared with elders with low-risks score (0-6), elders belonging to moderate-risk (score = 7-11) and high-risk (score = 12-18) groups showed a significantly increased risk of LOAD (adjusted odds ratio = 7.80 and 46.93, respectively; Ptrend < 0.0001). Performance metrics allow for identification of markers with moderate effect and are useful for creating genetic tests with clinical and public health implications. [ABSTRACT FROM AUTHOR]

Mutations in the TBK1 gene were just recently identified to cause amyotrophic lateral sclerosis (ALS), and their role in ALS in various populations remains unclear. The aim of this study was to determine the frequency and spectrum of mutations in TBK1 in a Taiwanese ALS cohort of Han Chinese origin. Mutational analyses of TBK1 were carried out by direct nucleotide sequencing in a cohort of 207 unrelated patients with ALS. Among them, the genetic diagnoses of 168 patients remained elusive after mutations in SOD1 , C9ORF72 , TARDBP , FUS , ATXN2 , OPTN , VCP , UBQLN2 , SQSTM1 , PFN1 , HNRNPA1 , HNRNPA2B1 , MATR3 , CHCHD10 , and TUBA4A had been excluded. We identified one nonsense mutation, p.R444X (c.1330C>T), in one patient with apparently sporadic ALS-frontotemporal dementia. In vitro functional study demonstrated the p.R444X mutation resulting in a truncated TANK-binding kinase 1 (TBK1) protein product, low protein expression, and loss of kinase function and interaction with optineurin. The frequency of TBK1 mutations in ALS patients in Taiwan is, therefore, approximately 0.5% (1/207). This study reports a novel TBK1 mutation and stresses on the importance to consider TBK1 mutation as a possible etiology of ALS. [ABSTRACT FROM AUTHOR]