The impact factors on the cost and length of stay among acute ischemic stroke.

BACKGROUND: Understanding hospital costs and length of stay (LOS) can optimize the in-hospital management of acute stroke. We investigated cost and LOS in first-ever and recurrent stroke patients in Taiwan. METHODS: Data were examined in patients at Chang Gung Memorial Hospital in Chiayi County of Taiwan from April 1, 2008, to March 31, 2010 [corrected]. Predictors of hospital cost and LOS in these patients were studied. RESULTS: The study included 1021 patients with 1084 stroke episodes. Mean age was 68.1 ± 10.8 years (range: 32-93). The average cost was NTD$45,709.30 ± NTD$66,697.40 (US$1408.70 ± US$2084.30; US$1 = NTD$32) and average LOS was 13.9 ± 14.1 days (range: 1-129). After multivariate regression analysis, the significant predictive factors for cost were LOS, smoking, and medication for secondary prevention. The significant predictive factors for LOS were diabetes mellitus, atrial fibrillation, recurrence, and stroke subtype. CONCLUSIONS: Age 65 and over, atrial fibrillation, stroke treatment, and subtypes were the significant predictive factors affecting hospital costs and LOS. Compared to other countries, Taiwan spent the least while Canada had the highest expense. The United States had the shortest LOS (6 days) in contrast to Canada with the longest LOS (34-47 days). Regarding mean daily cost of stroke, the United States had the highest cost per day while China spent the least.

APOE and AßPP gene variation in cortical and cerebrovascular amyloid-ß pathology and Alzheimer's disease: a population-based analysis.

Cortical and cerebrovascular amyloid-ß (Aß) deposition is a hallmark of Alzheimer's disease (AD), but also occurs in elderly people not affected by dementia. The apolipoprotein E (APOE) ε4 is a major genetic modulator of Aß deposition and AD risk. Variants of the amyloid-ß protein precursor (AßPP) gene have been reported to contribute to AD and cerebral amyloid angiopathy (CAA). We analyzed the role of APOE and AßPP variants in cortical and cerebrovascular Aß deposition, and neuropathologically verified AD (based on modified NIA-RI criteria) in a population-based autopsy sample of Finns aged ≥ 85 years (Vantaa85 + Study; n = 282). Our updated analysis of APOE showed strong associations of the ε4 allele with cortical (p = 4.91 × 10-17) and cerebrovascular (p = 9.87 × 10-11) Aß deposition as well as with NIA-RI AD (p = 1.62 × 10-8). We also analyzed 60 single nucleotide polymorphisms (SNPs) at the AßPP locus. In single SNP or haplotype analyses there were no statistically significant AßPP locus associations with cortical or cerebrovascular Aß deposition or with NIA-RI AD. We sequenced the promoter of the AßPP gene in 40 subjects with very high Aß deposition, but none of these subjects had any of the previously reported or novel AD-associated mutations. These results suggest that cortical and cerebrovascular Aß depositions are useful quantitative traits for genetic studies, as highlighted by the strong associations with the APOE ε4 variant. Promoter mutations or common allelic variation in the AßPP gene do not have a major contribution to cortical or cerebrovascular Aß deposition, or very late-onset AD in this Finnish population based study.

FUS mutations in sporadic amyotrophic lateral sclerosis.

Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease.

A de novo missense mutation of the FUS gene in a "true" sporadic ALS case.

Mutations in the Cu/Zn superoxide dismutase (SOD1), transactive response (TAR)-DNA binding protein (TARDBP) and fused in sarcoma (FUS) genes account for approximately 1 third of familial amyotrophic lateral sclerosis (ALS) cases. Mutations in these genes have been found in 1% to 2% of apparently sporadic cases. We present the first case of an ALS patient carrying a de novo missense mutation of the FUS gene (c.1561C>T, p.R521C). This report highlights the importance of screening ALS patients, both familial and sporadic, for FUS mutations and also suggests that de novo mutations is a relevant mechanism underlying sporadic neurodegenerative disease.

Kinesin-associated protein 3 (KIFAP3) has no effect on survival in a population-based cohort of ALS patients.

It was recently reported that rs1541160 on chromosome 1q24.2 has a marked effect on survival of amyotrophic lateral sclerosis (ALS) patients by influencing KIFAP3 expression. The cohorts used in that study were collected from ALS specialty clinics. We attempted to replicate these findings in a population-based cohort of 504 Italian ALS patients. None of 140 SNPs genotyped within the KIFAP3 locus (including rs1541160) had an effect on survival (log-rank P value for rs1541160 = 0.47) or on gene expression in that region. These data illustrate the complexities associated with analyzing ALS phenotypes for association.

Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.

A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We present a set of integrated experiments that investigate the effects of common genetic variability on DNA methylation and mRNA expression in four human brain regions each from 150 individuals (600 samples total). We find an abundance of genetic cis regulation of mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation across the genome. We show peak enrichment for cis expression QTLs to be approximately 68,000 bp away from individual transcription start sites; however, the peak enrichment for cis CpG methylation QTLs is located much closer, only 45 bp from the CpG site in question. We observe that the largest magnitude quantitative trait loci occur across distinct brain tissues. Our analyses reveal that CpG methylation quantitative trait loci are more likely to occur for CpG sites outside of islands. Lastly, we show that while we can observe individual QTLs that appear to affect both the level of a transcript and a physically close CpG methylation site, these are quite rare. We believe these data, which we have made publicly available, will provide a critical step toward understanding the biological effects of genetic variation.

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.

Risk factors and subtype analysis of acute ischemic stroke.

BACKGROUND AND PURPOSE: Stroke risk factors and subtypes were examined for associations with mortality and recurrence rate in Taiwanese patients with first-ever and recurrent stroke. METHODS: This study examined patients with initial and recurrent stroke from 2003 to 2005 for risk factors, demographic data, Bamford subtypes and transient ischemic attack. RESULTS: One thousand and twenty-one patients with 1,085 stroke episodes were recruited. Significant factors associated with recurrent stroke were hyperlipidemia, atrial fibrillation and smoking. A significant incidence of lacunar infarction was noted in the patient population (37.82% in all patients; 41.02% in first stroke vs. 35.67% in recurrent stroke patients). Patients with diabetes mellitus were more likely to have lacunar rather than total anterior circulation infarction (TACI) or partial anterior circulation infarction (PACI). Hyperlipidemia was more often attributable to lacunar stroke than PACI. Atrial fibrillation was significantly associated with nonlacunar infarcts, TACI and PACI but not lacunar stroke. CONCLUSIONS: The incidence of lacunar infarction was significantly higher in initial rather than recurrent stroke patients. Diabetes mellitus or hyperlipidemia was highly associated with lacunar infarction. Atrial fibrillation was associated with nonlacunar infarction in Taiwan, similar to the result of White and Black populations in the UK.

Spontaneous intrapetrous internal carotid artery dissection: a case report and literature review.

Although hemodynamic change has been identified as the main mechanism of infarcts in intracranial internal carotid artery dissection, no report has utilized computed tomography perfusion study to evaluate the cerebral flow change in such cases. This report presents a rare case of intrapetrous internal carotid artery dissection with watershed infarction. Additionally, a literature review addresses the clinical profiles and related neuroimaging findings of such patients.

Avascular necroses inducing limb-girdle syndrome.

Disuse myopathy can be caused by many disorders. However, disuse myopathy with symmetrical weakness of the proximal muscles in the four limbs is rare. Here we report a 45-year-old man who presented with the appearance of myopathy similar to the clinical picture of limb-girdle syndrome with symmetrical weakness of proximal muscles in four limbs. A battery of intensive investigations confirmed that the patient had symmetric disuse myopathy induced by multiple avascular necroses of hip and shoulder joints. After the patient had received bilateral total hip replacement operations he had remarkable improvement in his muscle power in both lower limbs. This report highlights that some myopathies can be reversed if their underlying causes are correctable.

Bilateral common carotid artery occlusion--a case report and literature review.

Although unilateral common carotid artery (CCA) occlusion and bilateral internal carotid artery (ICA) occlusion have been reported in the past, bilateral CCA occlusion is rare. The management and mechanism of unilateral CCA occlusion and bilateral ICA occlusion are debatable, but those of bilateral CCA occlusion are largely unknown. Herein, we present a case of bilateral CCA occlusion that had an acceptable outcome with medical treatment. The literature regarding unilateral CCA occlusion, bilateral ICA occlusion and bilateral CCA occlusion is also discussed. Experience implies that the collateral circulation gives rise to the clinical presentation, and may affect the outcome of various managements. Our review and case study may provide new information for future studies of carotid artery occlusion.

Deleted 4977-bp mitochondrial DNA mutation is associated with sporadic amyotrophic lateral sclerosis: a hospital-based case-control study.

We investigated the relationship between the most common 4977-bp deleted mitochondrial DNA (mtDNA) mutations and the occurrence of sporadic amyotrophic lateral sclerosis (ALS). Primer-shift and quantitative polymerase chain reaction (PCR) were used to determine the 4977-bp deleted mtDNA in the muscle specimens from 36 patients with sporadic ALS and 69 age-matched controls with other neuromuscular disorders. We found that the 4977-bp deleted mtDNA mutations were significantly higher in the ALS patients than controls in both frequency (50.0% vs. 8.7%, P < 0.01) and amount (0.35 +/- 0.53% vs. 0.085 +/- 0.35%, P < 0.05). Subjects with, rather than without, deleted mtDNA were at a significantly higher risk for having ALS after adjustment for age and sex. Moreover, male subjects had a higher risk than female subjects of having sporadic ALS. This study suggested that 4977-bp deleted mtDNA is significantly associated with the occurrence of sporadic ALS.