A functional MRI study of the relationship between naming treatment outcomes and resting state functional connectivity in post-stroke aphasia

Background: The majority of studies investigating the neural mechanisms underlying treatment in people with aphasia have examined task-based brain activity. However, the use of resting-state fMRI may provide another method of examining the brain mechanisms responsible for treatment-induced recovery, and allows for investigation into connectivity within complex functional networks Methods: Eight people with aphasia underwent 12 treatment sessions that aimed to improve object naming. Half the sessions employed a phonologically-based task, and half the sessions employed a semantic-based task, with resting-state fMRI conducted pre- and post-treatment. Brain regions in which the amplitude of low frequency fluctuations (ALFF) correlated with treatment outcomes were used as seeds for functional connectivity (FC) analysis. FC maps were compared from pre- to post-treatment, as well as with a group of 12 healthy older controls Results: Pre-treatment ALFF in the right middle temporal gyrus (MTG) correlated with greater outcomes for the phonological treatment, with a shift to the left MTG and supramarginal gyrus, as well as the right inferior frontal gyrus, post-treatment. When compared to controls, participants with aphasia showed both normalization and up-regulation of connectivity within language networks post-treatment, predominantly in the left hemisphere Conclusions: The results provide preliminary evidence that treatments for naming impairments affect the FC of language networks, and may aid in understanding the neural mechanisms underlying the rehabilitation of language post-stroke.

Changes in white matter connectivity following therapy for anomia post stroke

Background. The majority of studies investigating the neural mechanisms underlying treatment-induced recovery in aphasia have focused on the cortical regions associated with language processing. However, the integrity of the white matter connecting these regions may also be crucial to understanding treatment mechanisms. Objective. This study investigated the integrity of the arcuate fasciculus (AF) and uncinate fasciculus (UF) before and after treatment for anomia in people with aphasia. Method. Eight people with aphasia received 12 treatment sessions to improve naming; alternating between phonologically-based and semantic-based tasks, with high angular resolution diffusion imaging conducted pre and post treatment. The mean generalized fractional anisotropy (GFA), a measure of fiber integrity, and number of fibers in the AF and UF were compared pre and post treatment, as well as with a group of 14 healthy older controls. Results. Pre treatment, participants with aphasia had significantly fewer fibers and lower mean GFA in the left AF compared with controls. Post treatment, mean GFA increased in the left AF to be statistically equivalent to controls. Additionally, mean GFA in the left AF pre and post treatment positively correlated with maintenance of the phonologically based treatment. No differences were found in the right AF, or the UF in either hemisphere, between participants with aphasia and controls, and no changes were observed in these tracts following treatment. Conclusions. Anomia treatments may improve the integrity of the white matter connecting cortical language regions. These preliminary results add to the understanding of the mechanisms underlying treatment outcomes in people with aphasia post stroke.

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10 -11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.

Spatiotemporal transmission dynamics of hemorrhagic fever with renal syndrome in China, 2005-2012

Background Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by many serotypes of hantaviruses. In China, HFRS has been recognized as a severe public health problem with 90% of the total reported cases in the world. This study describes the spatiotemporal dynamics of HFRS cases in China and identifies the regions, time, and populations at highest risk, which could help the planning and implementation of key preventative measures. Methods Data on all reported HFRS cases at the county level from January 2005 to December 2012 were collected from Chinese Center for Disease Control and Prevention. Geographic Information System-based spatiotemporal analyses including Local Indicators of Spatial Association and Kulldorff's space-time scan statistic were performed to detect local high-risk space-time clusters of HFRS in China. In addition, cases from high-risk and low-risk counties were compared to identify significant demographic differences. Results A total of 100,868 cases were reported during 2005–2012 in mainland China. There were significant variations in the spatiotemporal dynamics of HFRS. HFRS cases occurred most frequently in June, November, and December. There was a significant positive spatial autocorrelation of HFRS incidence during the study periods, with Moran's I values ranging from 0.46 to 0.56 (P<0.05). Several distinct HFRS cluster areas were identified, mainly concentrated in northeastern, central, and eastern of China. Compared with cases from low-risk areas, a higher proportion of cases were younger, non-farmer, and floating residents in high-risk counties. Conclusions This study identified significant space-time clusters of HFRS in China during 2005–2012 indicating that preventative strategies for HFRS should be particularly focused on the northeastern, central, and eastern of China to achieve the most cost-effective outcomes.

Antithrombin III associated with fibrinogen predicts the risk of cerebral ischemic stroke

Background and purpose: The purpose of this study is to examine the feasibility of developing plasma predictive value biomarkers of cerebral ischemic stroke before imaging evidence is acquired. Methods: Blood samples were obtained from 198 patients who attended our neurology department as emergencies - with symptoms of vertigo, numbness, limb weakness, etc. - within 4.5 h of symptom onset, and before imaging evidence was obtained and medical treatment. After the final diagnosis was made by MRI/DWI/MRA or CTA in the following 24-72 h, the above cases were divided into two groups: stroke group and non-stroke group according to the imaging results. The levels of baseline plasma antithrombin III (AT-III), thrombin-antithrombin III (TAT), fibrinogen, D-dimer and high-sensitivity C-reactive protein (hsCRP) in the two groups were assayed. Results: The level of the baseline AT-III in the stroke group was 118.07 ± 26.22%, which was lower than that of the non-stroke group (283.83 ± 38.39%). The levels of TAT, fibrinogen, hsCRP were 7.24 ± 2.28 μg/L, 5.49 ± 0.98 g/L, and 2.17 ± 1.07 mg/L, respectively, which were higher than those of the non-stroke group (2.53 ± 1.23 μg/L, 3.35 ± 0.50 g/L, 1.82 ± 0.67 mg/L). All the P-values were less than 0.001. The D-dimer level was 322.57 ± 60.34 μg/L, which was slightly higher than that of the non-stroke group (305.76 ± 49.52 μg/L), but the P-value was 0.667. The sensitivities of AT-III, TAT, fibrinogen, D-dimer and hsCRP for predicting ischemic stroke tendency were 97.37%, 96.05%, 3.29%, 7.89%, but the specificity was 93.62%, 82.61%, 100% and 100%, respectively, and all the P-values were less than 0.001. High levels of D-dimer and hsCRP were mainly seen in the few cases with severe large-vessel infarction. Conclusions: Clinical manifestations of acute focal neurological deficits were associated with plasma AT-III and fibrinogen. These tests might help the risk assessment of acute cerebral ischemic stroke and/or TIA with infarction tendency in the superacute stage before positive imaging evidence is obtained.

A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to ischemic stroke risk

Background and Purpose Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles.We investigated epigenetic dysregulation for the MTHFR gene among ischaemic stroke patients. Methods Cases (n=297) and controls (n=110) were recruited after obtaining signed written informed consent, following a screening process against the inclusion/exclusion criteria. Serum vitamin metabolites (folate, vitamin B12 and homocysteine) were determined using immunoassays and methylation profiles for CpGs A and B in the MTHFR gene were determined using bisulfitepyrosequencing method. Results Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73 fold. CpGs A and B were not associated with either serum homocysteine levels or ischemic stroke severity. Conclusion CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke.

Aggressive surgical interventions for severe stroke: Impact on quality of life, caregiver burden and family outcomes

Introduction: Decompressive hemicraniectomy, clot evacuation, and aneurysmal interventions are considered aggressive surgical therapeutic options for treatment of massive cerebral artery infarction (MCA), intracerebral hemorrhage (ICH), and severe subarachnoid hemorrhage (SAH) respectively. Although these procedures are saving lives, little is actually known about the impact on outcomes other than short-term survival and functional status. The purpose of this study was to gain a better understanding of personal and social consequences of surviving these aggressive surgical interventions in order to aid acute care clinicians in helping family members make difficult decisions about undertaking such interventions. Methods: An exploratory mixed method study using a convergent parallel design was conducted to examine functional recovery (NIHSS, mRS & BI), cognitive status (Montreal Cognitive Assessment Scale, MoCA), quality of life (Euroqol 5-D), and caregiver outcomes (Bakas Caregiver Outcome Scale, BCOS) in a cohort of patients and families who had undergone aggressive surgical intervention for severe stroke between the years 2000–2007. Data were analyzed using descriptive statistics, univariate and multivariate analysis of variance, and multivariate logistic regression. Content analysis was used to analyze the qualitative interviews conducted with stroke survivors and family members. Results: Twenty-seven patients and 13 spouses participated in this study. Based on patient MOCA scores, overall cognitive status was 25.18 (range 23.4-26.9); current functional outcomes scores: NIHSS 2.22, mRS 1.74, and BI 88.5. EQ-5D scores revealed no significant differences between patients and caregivers (p=0.585) and caregiver outcomes revealed no significant differences between male/female caregivers or patient diagnostic group (MCA, SAH, ICH; p=""0.103).<"/span><"/span> Discussion: Overall, patients and families were satisfied with quality of life and decisions made at the time of the initial stroke. There was consensus among study participants that formal community-based support (e.g., handibus, caregiving relief, rehabilitation assessments) should be continued for extended periods (e.g., years) post-stroke. Ongoing contact with health care professionals is valuable to help them navigate in the community as needs change over time.

Using rowers’ perceptions of on-water stroke success to evaluate sculling catch efficiency variables via a boat instrumentation system

Aim An effective catch in sculling is a critical determinant of boat velocity. This study used rowers’ performance-based judgments to compare three measures of catch slip efficiency. Two questions were addressed: (1) would rower-judged Yes strokes be faster than No strokes? and (2) which method of quantifying catch slip best reflected these judgements? Methods Eight single scullers performed two 10-min blocks of sub maximal on-water rowing at 20 strokes per minute. Every 30 s, rowers reported either Yes or No about the quality of their stroke at the catch. Results It was found that Yes strokes identified by rowers had, on average, a moderate effect advantage over No strokes with a standardised effect size of 0.43. In addition, a quicker time to positive acceleration best reflected the change in performance; where the standardised mean difference score of 0.57 for time to positive acceleration was larger than the scores of 0.47 for time to PowerLine force, and 0.35 for time to 30% peak pin force catch slip measures. For all eight rowers, Yes strokes corresponded to time to positive acceleration occurring earlier than No strokes. Conclusion Rower judgements about successful strokes was linked to achieving a quicker time to positive acceleration, and may be of the most value in achieving a higher average boat velocity.

Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants

OBJECTIVE To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. METHODS We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. RESULTS We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 x 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 x 10(-20) for the CE score in MO). CONCLUSIONS Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.

The influence of OLR1 and PCSK9 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

It has been reported that both OLR1 and PCSK9 genes are related to various vascular diseases such as atherosclerosis, cardiovascular disease, peripheral artery disease and stroke, in particular ischemic stroke. The prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between OLR1 rs11053646 and PCSK9 rs505151 polymorphisms and the risk of ischemic stroke remains unclear and inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of genetic polymorphisms on ischemic stroke, by analyzing the complete coverage of all relevant studies. All eligible case-control and cohort studies that met the search term were retrieved in multiple scientific databases. Data of interest such as demographic data and genotyping methods were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. A total of seven case-control studies encompassing 1897 ischemic stroke cases and 2119 healthy controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR=1.33. 95%CI:1.11-1.58) and co-dominant models (OR=1.24, 95%CI:1.02-1.51) were significantly associated with ischemic stroke. For PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR=1.36, 95%CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G>C and PCSK9 rs505151 A>G may contribute to the susceptibility risk of ischemic stroke.

Clinical relevance of MTHFR, eNOS, ACE, and ApoE gene polymorphisms and serum vitamin profile among Malay patients with ischemic stroke

Background The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks. Methods Polymorphisms of these genes were analyzed in age-, sex-, and ethnicity-matched case–controls (n = 594); serum vitamin profiles were determined using immunoassays. Results The MTHFR 677C>T, 1298A>C, eNOS intron 4a/b, and ApoE polymorphisms were significantly associated with the increased risk of ischemic stroke. Elevated serum homocysteine and vitamin B12 levels were associated with MTHFR 677C>T and eNOS intron 4a/b polymorphisms. The ApoE and eNOS −786T>C polymorphisms were associated with increased serum vitamin B12 levels. However, none of the polymorphisms influenced serum folate levels except for the MTHFR 1298A>C. Different patterns of MTHFR and eNOS haplotypes tend to affect serum vitamin profiles to different degrees, which contribute to either different susceptibility risk or protective effect on ischemic stroke. Overall, increased levels of serum homocysteine and vitamin B12 levels were associated with higher risk of ischemic stroke in the investigated population. Conclusions The present study suggests that the genotypes and haplotypes of MTHFR 677C>T and eNOS intron 4a/b polymorphisms are potential serum biomarkers in the pathophysiological processes of ischemic stroke, by modulating homocysteine and vitamin B12 levels.

Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Following Stroke practice guidelines, update 2015

Every year, approximately 62 000 people with stroke and transient ischemic attack are treated in Canadian hospitals, and the evidence suggests one-third or more will experience vascular-cognitive impairment, and/or intractable fatigue, either alone or in combination. The 2015 update of the Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Module guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. The three consequences of stroke that are the focus of the this guideline (poststroke depression, vascular cognitive impairment, and fatigue) have high incidence rates and significant impact on the lives of people who have had a stroke, impede recovery, and result in worse long-term outcomes. Significant practice variations and gaps in the research evidence have been reported for initial screening and in-depth assessment of stroke patients for these conditions. Also of concern, an increased number of family members and informal caregivers may also experience depressive symptoms in the poststroke recovery phase which further impact patient recovery. These factors emphasize the need for a system of care that ensures screening occurs as a standard and consistent component of clinical practice across settings as stroke patients transition from acute care to active rehabilitation and reintegration into their community. Additionally, building system capacity to ensure access to appropriate specialists for treatment and ongoing management of stroke survivors with these conditions is another great challenge.