The utility of prolonged outpatient ambulatory EEG

AbstractPurposeILAE guidelines recommend the use of prolonged EEG where the diagnosis of epilepsy or the classification of the seizure syndrome is proving difficult. Due to its limited provision, video EEG monitoring is unavailable to many patients under investigation1. The aim of this study was to examine the utility of the alternate investigation of outpatient ambulatory EEG.MethodsIn this retrospective study we analysed 324 consecutive prolonged outpatient ambulatory EEGs lasting 72–96h (4–5 days), without medication withdrawal. EEG data and the clinical record were reviewed to investigate the utility of the investigation.ResultsOf 324 studies: 219 (68%) studies gave positive data, 116 (36%) showed interictal epileptiform discharges (IEDs), 167 (52%) had events. 105 (32%) studies were normal. Overall 51% of studies changed management of which 22% of studies changed the diagnosis and 29% of studies refined the diagnosis by classifying the epilepsy into focal or generalised.ConclusionThe present study confirms the diagnostic utility of outpatient ambulatory EEG in the diagnosis of paroxysmal events

Impact of Visit-to-Visit Glycemic Variability on the Risks of Macrovascular and Microvascular Events and All-Cause Mortality in Type 2 Diabetes: The ADVANCE Trial

OBJECTIVE There is no consensus on the importance of visit-to-visit glycemic variability in diabetes. Therefore, we assessed the effects of visit-to-visit variability (VVV) in HbA1c and fasting glucose on major outcomes in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial. RESEARCH DESIGN AND METHODS ADVANCE was a factorial randomized controlled trial of intensive glucose control and blood pressure lowering in patients with type 2 diabetes. VVV in the intensive glucose treatment group was defined using the SD of five measurements of HbA1c and glucose taken 3–24 months after randomization. Outcomes were combined macro- and microvascular events and all-cause mortality occurring post 24 months. Sensitivity analyses were performed using other indices of variability and in the standard glucose treatment group. RESULTS Among 4,399 patients in the intensive group, an increase in VVV of HbA1c was associated with an increased risk of vascular events (P = 0.01) and with mortality (P < 0.001): highest versus lowest tenth hazard ratio (95% CI) 1.64 (1.05–2.55) and 3.31 (1.57–6.98), respectively, after multivariable adjustment. A clear association was also observed between VVV of fasting glucose and increased risk of vascular events (P < 0.001; 2.70 [1.65–4.42]). HbA1c variability was positively associated with the risk of macrovascular events (P = 0.02 for trend), whereas glucose variability was associated with both macro- and microvascular events (P = 0.005 and P < 0.001 for trend, respectively). Sensitivity analyses using other indices, and patients in the standard glucose treatment group, were broadly consistent with these results. CONCLUSIONS Consistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes

Validation of the simplified modified Rankin scale for stroke trials: Experience from the ENCHANTED alteplase-dose arm

Background and aims The structured, simplified modified Rankin scale questionnaire (smRSq) may increase reliability over the interrogative approach to scoring the modified Rankin scale (mRS) in acute stroke research and practice. During the conduct of the alteplase-dose arm of the international ENhanced Control of Hypertension ANd Thrombolysis StrokE stuDy (ENCHANTED), we had an opportunity to compare each of these approaches to outcome measurement. Methods Baseline demographic data were recorded together with the National Institutes of Health Stroke Scale (NIHSS). Follow-up measures obtained at 90 days included mRS, smRSq, and the 5-Dimension European Quality of life scale (EQ-5D). Agreements between smRSq and mRS were assessed with the Kappa statistic. Multiple logistic regression was used to identify baseline predictors of Day 90 smRSq and mRS scores. Treatment effects, based on Day 90 smRSq/mRS scores, were tested in logistic and ordinal logistic regression models. Results SmRSq and mRS scores had good agreement (weighted Kappa 0.79, 95% confidence interval (CI) 0.78–0.81), while variables of age, atrial fibrillation, diabetes mellitus, pre-morbid mRS (1 vs. 0), baseline NIHSS scores, and imaging signs of cerebral ischemia, similarly predicted their scores. Odds ratios for death or disability, and ordinal shift, 90-day mRS scores using smRSq were 1.05 (95% CI 0.91–1.20; one-sided P = 0.23 for non-inferiority) and 0.98 (95% CI 0.87–1.11; P = 0.02 for non-inferiority), similar to those using mRS. Conclusions This study demonstrates the utility of the smRSq in a large, ethnically diverse clinical trial population. Scoring of the smRSq shows adequate agreement with the standard mRS, thus confirming it is a reliable, valid, and useful alternative measure of functional status after acute ischemic stroke. Clinical Trial registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616

Incidence and Associations of Hemiplegic Shoulder Pain Poststroke: Prospective Population-Based Study

This author accepted manuscript (post print) is made available following a 12 month embargo from the date of publication (28 September 2014) in accordance with the publisher copyright policy

Ambient Temperature and Stroke Occurrence: A Systematic Review and Meta-Analysis

Abstract: Biologically plausible associations exist between climatic conditions and stroke risk, but study results are inconsistent. We aimed to summarize current evidence on ambient temperature and overall stroke occurrence, and by age, sex, and variation of temperature. We performed a systematic literature search across MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and GEOBASE, from inception to 16 October 2015 to identify all population-based observational studies. Where possible, data were pooled for meta-analysis with Odds ratios (OR) and corresponding 95% confidence intervals (CI) by means of the random effects meta-analysis. We included 21 studies with a total of 476,511 patients. The data were varied as indicated by significant heterogeneity across studies for both ischemic stroke (IS) and intracerebral hemorrhage (ICH). Pooled OR (95% CI) in every 1 degree Celsius increase in ambient temperature was significant for ICH 0.97 (0.94–1.00), but not for IS 1.00 (0.99–1.01) and subarachnoid hemorrhage (SAH) 1.00 (0.98–1.01). Meta-analysis was not possible for the pre-specified subgroup analyses by age, sex, and variation of temperature. Change in temperature over the previous 24 h appeared to be more important than absolute temperature in relation to the risk of stroke, especially in relation to the risk of ICH. Older age appeared to increase vulnerability to low temperature for both IS and ICH. To conclude, this review shows that lower mean ambient temperature is significantly associated with the risk of ICH, but not with IS and SAH. Larger temperature changes were associated with higher stroke rates in the elderly

Increased Plasma VEGF Levels in Patients with Cerebral Large Artery Disease Are Associated with Cerebral Microbleeds

Background/Purpose: Because atherosclerotic factors and antithrombotic agents sometimes induce cerebral microbleeds (CMBs), patients with cerebral large artery disease (CLAD) tend to have more CMBs than control subjects. On the other hand, VEGF contributes to the disruption of the blood-brain barrier, and it may induce parenchymal edema and bleeding. We conducted a study to evaluate the role of vascular endothelial growth factor (VEGF) in the occurrence of CMBs in patients with CLAD. Methods: CLAD is defined as stenosis or occlusion of either the carotid artery or the middle cerebral artery of 50% or more. We prospectively registered patients with CLAD who were hospitalized in our neurocenter. Biological backgrounds, atherosclerotic risk factors, administration of antithrombotics before hospitalization, and levels of cytokines and chemokines were evaluated. Susceptibility-weighted imaging or T2*-weighted MR angiography was used to evaluate CMBs. The Brain Observer MicroBleed Scale (BOMBS) was used for CMB assessments. Images were analyzed with regard to the presence or absence of CMBs. We also examined plasma VEGF concentrations using a commercial ELISA kit. Because more than half showed plasma VEGF levels below assay detection limits (3.2 pg/mL), the patients were dichotomized by plasma VEGF levels into two groups (above and below the detection limit). After univariate analyses, logistic regression analysis was conducted to determine the factors associated with the CMBs after adjustment for age, sex, the presence of hypertension, and administration of antithrombotic agents. A similar analysis with CMBs separated by location (cortex, subcortex, or posterior circulation) was also conducted. Results: Sixty-six patients (71.1 ± 8.9 years, 53 males and 13 females) were included in this study. Plasma VEGF levels were not correlated with age, sex, and atherosclerotic risk factors; however, patients with VEGF levels >3.2 pg/mL tended toward more frequent CMBs (60.0 vs. 32.6%, in the presence and absence of CMBs, p = 0.056). With regard to the location of CMBs, those in the cortex and/or at the gray-white junction were observed more frequently in the patients with VEGF levels >3.2 pg/mL after multivariable analyses (odds ratio: 3.80; 95% confidence interval: 1.07–13.5; p = 0.039). Conclusions: In patients with CLAD, elevated plasma VEGF might be associated with CMBs, especially those located in the cortex and/or at the gray-white junction

Ethnicity and Other Determinants of Quality of Functional Outcome in Acute Ischemic Stroke: The ENCHANTED Trial

Background and Purpose- Patient-centered outcomes are important. We aimed to determine predictors of health-related quality of life (HRQoL) and develop utility-weighted modified Rankin Scale (mRS) scores in thrombolyzed acute ischemic stroke patients from both arms of ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods- ENCHANTED was an international quasi-factorial clinical trial of different doses of intravenous alteplase and intensities of blood pressure control in acute ischemic stroke patients, with outcomes on the 5-Dimensional European Quality of Life Scale and mRS assessed at 90 days post-randomization. Logistic regression models were used to identify baseline predictors of poor HRQoL (≤mean 5-Dimensional European Quality of Life Scale utility scores). Ordinary least squares regression derived utility-weighted mRS scores. Results- In 4016 acute ischemic stroke patients with complete 5-Dimensional European Quality of Life Scale and mRS data, independent predictors of poor HRQoL were older age (odds ratio, 1.19 [95% CI, 1.12-1.27], per 10-year increase), non-Asian ethnicity (1.91 [1.61-2.27]), greater stroke severity on the National Institutes of Health Stroke Scale (1.11 [1.09-1.12]), diabetes mellitus (1.41 [1.18-1.69]), premorbid disability (mRS score 1 versus 0; 1.62 [1.33-1.97]), large vessel atheromatous pathogenesis (1.32 [1.12-1.54]), and proxy respondent (2.35 [2.01-2.74]). Sensitivity analyses indicate the ethnicity influence on HRQoL was driven by the high proportion of Chinese (62.9% of Asian) participants with better HRQoL compared with non-Chinese or other Asian groups. Derived utility values across mRS scores 0 to 5 were 0.977, 0.885, 0.748, 0.576, 0.194, and -0.174, respectively. Correlations between mRS and 5-Dimensional European Quality of Life Scale scores were stronger in Asians. Conclusions- HRQoL is worse after thrombolyzed acute ischemic stroke in the elderly, non-Asians, with greater initial severity, diabetes mellitus, premorbid disability, due to large vessel atheroma, and proxy assessment. The broader significance of better HRQoL in Asians is tempered by Chinese participants dominating analyses. From utility-weighted mRS scores indicating the greatest steps in mRS scores are between 5 and 3, treatments to avoid major disability provide the greatest benefits for patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616

Early Blood Pressure Lowering Does Not Reduce Growth of Intraventricular Hemorrhage following Acute Intracerebral Hemorrhage:Results of the INTERACT Studies

Background: Intraventricular hemorrhage (IVH) extension is common following acute intracerebral hemorrhage (ICH) and is associated with poor prognosis. Aim: To determine whether intensive blood pressure (BP)-lowering therapy reduces IVH growth. Methods: Pooled analyses of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and INTERACT2) computed tomography (CT) substudies; multicenter, open, controlled, randomized trials of patients with acute spontaneous ICH and elevated systolic BP, randomly assigned to intensive (Results: There was no significant difference in adjusted mean IVH growth following intensive (n = 228) compared to guideline-recommended (n = 228) BP treatment (1.6 versus 2.2 ml, respectively; p = 0.56). Adjusted mean IVH growth was nonsignificantly greater in patients with a mean achieved systolic BP ≥160 mm Hg over 24 h (3.94 ml; p trend = 0.26). Conclusions: Early intensive BP-lowering treatment had no clear effect on IVH in acute ICH

Stroke Epidemiology in an Australian Rural Cohort (SEARCH)

Copyright © 2016 World Stroke Organization. Reprinted by permission of SAGE PublicationsBackground Stroke rates in Australia and New Zealand have been declining since 1990 but all studies have been completed in large urban centers. Aim We report the first Australasian stroke incidence study in a rural population. Methods The authors applied the principle of complete ascertainment, used the WHO standard definition of stroke and classified ischemic stroke by the TOAST criteria. Data were collected from five rural centers defined by postcode of residence, over a 2-year period with 12 months of follow up of all cases. Results There were 217 strokes in 215 individuals in a population of 96,036 people, over 2 years, giving a crude attack rate of 113 per 100,000 per year. The 181 first-ever strokes (83% of total), standardized to the WHO world population, occurred at a rate of 50/100,000 (95% CI: 43–58). The 28-day fatality for first-ever strokes was 24% (95% CI: 18–31) and 77% (95% CI: 71–83) were classified as ischemic (140/181), 15% (95% CI: 10–21) intracerebral hemorrhage, 3% (95% CI: 1–6) due to subarachnoid hemorrhage and 5% (95% CI: 2–9) were unknown. A high proportion of first-ever ischemic strokes (44%) were cardioembolic, mostly (77%) due to atrial arrhythmias. Of the 38 with known atrial arrhythmias prior to stroke, only six (16%) were therapeutically anticoagulated. Conclusions This rural companion study of a recent Australian urban stroke incidence study confirms the downward trend of stroke incidence in Australia, and reiterates that inadequate anticoagulation of atrial arrhythmia remains a preventable cause of ischemic stroke