Publications by authors named "Deidre A De Silva"

51 Publications

Stroke Patients Without COVID-19 Symptoms: Is There a Need to Screen?

Neurologist 2021 Mar 4;26(2):73-74. Epub 2021 Mar 4.

Department of Neurology, National Neuroscience Institute, Singapore General Hospital.

Introduction: COVID-19 patients who present with strokes but without typical COVID-19 symptoms have been described in small numbers. Despite the paucity of fever and respiratory symptoms, they remain capable of infecting others. The patient we discuss herein highlights the important issues of strokes as presenting events of COVID-19 infections, and how testing for COVID-19 in stroke patients, even when asymptomatic for COVID-19, can play an important role in infection control, clinical management and outcomes amidst this global pandemic.

Case Report: A 45-year-old male resident of a dormitory presented to our unit with acute vertigo and left-sided dysmetria. NIHSS was 2. The initial magnetic resonance imaging demonstrated infarction of the left cerebellar hemisphere, middle cerebellar peduncle and hemipons. An extensive work-up for stroke etiologies was unremarkable. Despite having no fever, respiratory symptoms, anosmia or ageusia, he was isolated and screened for COVID-19 due to his epidemiologic risks, with multiple residents from his dormitory being recently diagnosed with COVID-19. Confirming our suspicion, his respiratory samples returned positive for COVID-19. His D-dimer levels returned normal. Thereafter, the patient underwent posterior decompression surgery due to worsening edema caused by the cerebellar infarct. He was started on antiplatelet therapy and recovered significantly a month from presentation with an modified Rankin Sore of 2. He remained without typical COVID-19 symptoms.

Conclusion: Our patient's case clearly supports the screening for COVID-19 in stroke patients who are without COVID-19 symptoms, appreciating the significant value it adds to infection control, clinical management, and outcomes amidst this global pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NRL.0000000000000305DOI Listing
March 2021

Association of Reperfusion After Thrombolysis With Clinical Outcome Across the 4.5- to 9-Hours and Wake-up Stroke Time Window: A Meta-Analysis of the EXTEND and EPITHET Randomized Clinical Trials.

JAMA Neurol 2021 Feb;78(2):236-240

Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.

Importance: Intravenous alteplase reduces disability after ischemic stroke in patients 4.5 to 9 hours after onset and with wake-up onset stroke selected using perfusion imaging mismatch. However, whether the benefit is consistent across the 4.5- to 6-hours, 6- to 9-hours, and wake-up stroke epochs is uncertain.

Objective: To examine the association of reperfusion with reduced disability, including by onset-to-randomization time strata in the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) randomized clinical trials.

Design, Setting, And Participants: Individual patient meta-analysis of randomized clinical trials performed from August 2001 to June 2018 with 3-month follow-up. Patients had acute ischemic stroke with 4.5-to 9-hours poststroke onset or with wake-up stroke were randomized to alteplase or placebo after perfusion mismatch imaging. Analysis began July 2019 and ended May 2020.

Exposures: Reperfusion was defined as more than 90% reduction in time to maximum of more than 6 seconds' lesion volume at 24- to 72-hour follow-up.

Main Outcomes And Measures: Ordinal logistic regression adjusted for baseline age and National Institutes of Health Stroke Scale score was used to analyze functional improvement in day 90 modified Rankin Scale score overall, including a reperfusion × time-to-randomization multiplicative interaction term, and in the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata. Symptomatic hemorrhage was defined as large parenchymal hematoma with a National Institutes of Health Stroke Scale score increase of 4 points or more.

Results: Reperfusion was assessable in 270 of 295 patients (92%), 68 of 133 (51%) in the alteplase group, and 38 of 137 (28%) in the placebo reperfused group (P < .001). The median (interquartile range) age was 76 (66-81) years in the reperfusion group vs 74 (64.5-81.0) years in the group with no reperfusion. The median (interquartile range) baseline National Institutes of Health Stroke Scale score was 10 (7-15) in the reperfusion group vs 12 (8.0-17.5) in the no reperfusion group. Overall, reperfusion was associated with improved functional outcome (common odds ratio, 7.7; 95% CI, 4.6-12.8; P < .001). Reperfusion was associated with significantly improved functional outcome in each of the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata, with no evidence of association between time to randomization and beneficial effect of reperfusion (P = .63). Symptomatic hemorrhage, assessed in all 294 patients, occurred in 3 of 51 (5.9%) in the 4.5- to 6-hours group, 2 of 28 (7.1%) in the 6- to 9-hours group, and 4 of 73 (5.5%) in the wake-up stroke in patients treated with alteplase (Fisher P = .91).

Conclusions And Relevance: Strong benefits of reperfusion in all time strata without differential risk in symptomatic hemorrhage support the consistent treatment effect of alteplase in perfusion mismatch-selected patients throughout the 4.5- to 9-hours and wake-up stroke time window.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2020.4123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607491PMC
February 2021

Ischaemic stroke.

Nat Rev Dis Primers 2019 10 10;5(1):70. Epub 2019 Oct 10.

Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.

Stroke is the second highest cause of death globally and a leading cause of disability, with an increasing incidence in developing countries. Ischaemic stroke caused by arterial occlusion is responsible for the majority of strokes. Management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy, which both reduce disability but are time-critical. Accordingly, improving the system of care to reduce treatment delays is key to maximizing the benefits of reperfusion therapies. Intravenous thrombolysis reduces disability when administered within 4.5 h of the onset of stroke. Thrombolysis also benefits selected patients with evidence from perfusion imaging of salvageable brain tissue for up to 9 h and in patients who awake with stroke symptoms. Endovascular thrombectomy reduces disability in a broad group of patients with large vessel occlusion when performed within 6 h of stroke onset and in patients selected by perfusion imaging up to 24 h following stroke onset. Secondary prevention of ischaemic stroke shares many common elements with cardiovascular risk management in other fields, including blood pressure control, cholesterol management and antithrombotic medications. Other preventative interventions are tailored to the mechanism of stroke, such as anticoagulation for atrial fibrillation and carotid endarterectomy for severe symptomatic carotid artery stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41572-019-0118-8DOI Listing
October 2019

Home-based tele-rehabilitation presents comparable positive impact on self-reported functional outcomes as usual care: The Singapore Tele-technology Aided Rehabilitation in Stroke randomised trial.

J Telemed Telecare 2019 Aug 28:1357633X19868905. Epub 2019 Aug 28.

National University of Singapore, Saw Swee Hock School of Public Health, Singapore.

Introduction: The aim of this research was to evaluate the impact of a novel tele-rehabilitation system on self-reported functional outcomes compared to usual care during the first three months after stroke.

Methods: A parallel, two-arm, evaluator-blinded, randomised controlled trial was conducted. Adults aged ≥40 years who had suffered a stroke within four weeks of the start of the study were recruited from the general community. The intervention group received access to a novel tele-rehabilitation system and programme for three months. The primary outcome measures utilised were the frequency and limitation total scores of the Late-Life Function and Disability Instrument (LLFDI) at three months.

Results: A total of 124 individuals were recruited. The mean differences in the LLDFI frequency and limitation total scores at three months comparing the intervention and control groups were -3.30 (95% confidence interval (CI) -7.81 to 1.21) and -6.90 (95% CI -15.02 to 1.22), respectively. Adjusting for the respective baseline covariates and baseline Barthel Index also showed no significant difference between interventions in the LLFDI outcomes.

Discussion: The intervention and control groups self-reported similar improvements in functional outcomes. Tele-rehabilitation may be a viable option to provide post-stroke rehabilitation services in Singapore while reducing barriers to continue rehabilitation conventionally after discharge from hospital and encouraging more participation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1357633X19868905DOI Listing
August 2019

Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data.

Lancet 2019 07 22;394(10193):139-147. Epub 2019 May 22.

Department of Medicine and Neurology, Melbourne Brain Centre, University of Melbourne, Melbourne, VIC, Australia; Royal Melbourne Hospital, and Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia. Electronic address:

Background: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.

Methods: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036.

Findings: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66).

Interpretation: Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

Funding: None.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(19)31053-0DOI Listing
July 2019

Health-related quality of life loss associated with first-time stroke.

PLoS One 2019 28;14(1):e0211493. Epub 2019 Jan 28.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

Objectives: This study aimed to quantify health-related quality of life (HRQoL) loss associated with first episode of stroke by comparing patient-reported HRQoL before and after stroke onset. The impact of stroke in local population was also evaluated by comparing the pre- and post-stroke HRQoL with that of the general population.

Methods: The HRQoL of stroke survivors was assessed with the EQ-5D-3L index score at recruitment, for recalled pre-stroke HRQoL, and at 3 and 12 month post-stroke. Change in HRQoL from pre-stroke to 3 and 12 month was self-reported by 285 and 238 patients, respectively. Mean EQ index score at each time point (baseline: 464 patients; 3 month post-stroke: 306 patients; 12 month post-stroke: 258 patients) was compared with published population norms for EQ-5D-3L.

Results: There was a significant decrease in HRQoL at 3 (0.25) and 12 month (0.09) post-stroke when compared to the retrospectively recalled patients' mean pre-stroke HRQoL level (0.87). The reduction at 3 month was associated with the reduction in all EQ-5D-3L health dimensions; reductions remaining at 12 month were limited to dimensions of mobility, self-care, usual activities, and anxiety/depression. Stroke patients had a lower mean EQ index than the general population by 0.07 points pre-stroke (0.87 vs. 0.94), 0.33 points at 3 month (0.61 vs. 0.94) and 0.18 points at 12 month (0.76 vs. 0.94) post-stroke.

Conclusions: Stroke has a substantial impact on HRQoL in Singapore, especially in the first three months post-stroke. Compared to the general population, stroke survivors have lower HRQoL even before stroke onset. This pre-stroke deficit in HRQoL should be taken into account when quantifying health burden of stroke or setting goals for stroke rehabilitation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211493PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349359PMC
November 2019

Can acute clinical outcomes predict health-related quality of life after stroke: a one-year prospective study of stroke survivors.

Health Qual Life Outcomes 2018 Nov 21;16(1):221. Epub 2018 Nov 21.

Saw Swee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, Block MD1, 12 Science Drive 2, Singapore, 117549, Singapore.

Background: Health-related quality of life (HRQoL) is a key metric to understand the impact of stroke from patients' perspective. Yet HRQoL is not readily measured in clinical practice. This study aims to investigate the extent to which clinical outcomes during admission predict HRQoL at 3 months and 1 year post-stroke.

Methods: Stroke patients admitted to five tertiary hospitals in Singapore were assessed with Shah-modified Barthel Index (Shah-mBI), National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), and Frontal Assessment Battery (FAB) before discharge, and the EQ-5D questionnaire at 3 months and 12 months post-stroke. Association of clinical measures with the EQ index at both time points was examined using multiple linear regression models. Forward stepwise selection was applied and consistently significant clinical measures were analyzed for their association with individual dimensions of EQ-5D in multiple logistic regressions.

Results: All five clinical measures at baseline were significant predictors of the EQ index at 3 months and 12 months, except that MMSE was not significantly associated with the EQ index at 12 months. NIHSS (3-month standardized β = - 0.111; 12-month standardized β = - 0.109) and mRS (3-month standardized β = - 0.122; 12-month standardized β = - 0.080) were shown to have a larger effect size than other measures. The contribution of NIHSS and mRS as significant predictors of HRQoL was mostly explained by their association with the mobility, self-care, and usual activities dimensions of EQ-5D.

Conclusions: HRQoL at 3 months and 12 months post-stroke can be predicted by clinical outcomes in the acute phase. NIHSS and mRS are better predictors than BI, MMSE, and FAB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12955-018-1043-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249770PMC
November 2018

The Relationship Between Ambient Air Pollution and Acute Ischemic Stroke: A Time-Stratified Case-Crossover Study in a City-State With Seasonal Exposure to the Southeast Asian Haze Problem.

Ann Emerg Med 2018 11 29;72(5):591-601. Epub 2018 Aug 29.

Health Services and Systems Research, Duke-NUS Medical School, Singapore; Department of Emergency Medicine, Singapore General Hospital, Singapore.

Study Objective: Studies are divided on the short-term association of air pollution with stroke. Singapore is exposed to seasonal transboundary haze. We aim to investigate the association between air pollution and stroke incidence in Singapore.

Methods: We performed a time-stratified case-crossover analysis on all ischemic stroke cases reported to the Singapore Stroke Registry from 2010 to 2015. Exposure on days was compared with control days on which exposure did not occur. Control days were chosen on the same day of the week earlier and later in the same month in the same year. We fitted a conditional Poisson regression model to daily stroke incidence that included Pollutant Standards Index and environmental confounders. The index was categorized according to established classification (0 to 50=good, 51 to 100=moderate, and ≥101=unhealthy). We assessed the relationship between stroke incidence and Pollutant Standards Index in the entire cohort and in predetermined subgroups of individual-level characteristics.

Results: There were 29,384 ischemic stroke cases. Moderate and unhealthy Pollutant Standards Index levels showed association with stroke occurrence, with incidence risk ratio 1.10 (95% confidence interval 1.06 to 1.13) and 1.14 (95% confidence interval 1.03 to 1.25), respectively. Subgroup analyses showed generally significant association, except in Indians and nonhypertensive patients. The association was significant in subgroups aged 65 years or older, women, Chinese, nonsmokers and those with history of diabetes, hypertension, and hyperlipidemia. Stratified by age and smoking, the risk diminished in smokers of all ages. Risk remained elevated for 5 days after exposure.

Conclusion: We found a short-term elevated risk of ischemic stroke after exposure to air pollution. These findings have public health implications for stroke prevention and emergency health services delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.annemergmed.2018.06.037DOI Listing
November 2018

Two decades of nation-wide community-based stroke support - The Singapore National Stroke Association.

Int J Stroke 2017 04 24;12(3):297-301. Epub 2016 Oct 24.

3 Department of Neurology, National Neuroscience Institute, Singapore General Hospital Campus, Singapore, Singapore.

The Singapore National Stroke Association, registered in 1996, offers support and information to stroke survivors and caregivers, and aims to raise public stroke awareness. In the last 20 years, we have developed programs to equip stroke survivors and caregivers with knowledge, life skills, comfort, and opportunities for socialization and reintegration. We have on-going public education and advocacy initiatives. Obtaining funding, member recruitment, volunteer retention, and leadership renewal are on-going challenges. Singapore National Stroke Association will continue to strive for the betterment of stroke survivors, their caregivers, and the public.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493016676620DOI Listing
April 2017

Asian venous thromboembolism guidelines: updated recommendations for the prevention of venous thromboembolism.

Int Angiol 2017 Feb 8;36(1):1-20. Epub 2016 Sep 8.

Department of Hematology, Singapore General Hospital, Singapore.

The Asian venous thromboembolism (VTE) prophylaxis guidelines were first published in 2012. Since its first edition, the Asian Venous Thrombosis Forum (AVTF) working group have updated the Asian VTE epidemiology and reviewed issues that were not addressed in the previous guidelines. The authors noted that the rising incidence of VTE across Asia may be attributable to aging population, dietary changes, and increasing incidence of obesity and diabetes. The new additions in the guideline include role of thrombophilia in VTE, bleeding risk in Asians, individual risk assessment, updates in the prevention of VTE in medically ill, bariatric surgery, cancer, orthopedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors, however, are similar between Asians and Caucasians. The group found no evidence of increased risk of bleeding while using pharmacological agents, including the use of novel anti-coagulants. At present, Caprini risk assessment model is widely used for individual risk assessment. Further validation of this model is needed in Asia. In medically ill patients, pharmacological agents are preferred if there is no bleeding risk. Intermittent pneumatic compression device (IPC) is recommended in patients with bleeding risk but we do not recommend using graduated compressive stockings. In bariatric patients, data on VTE is lacking in Asia. We recommend following current international guidelines. A high index of suspicion should be maintained during postbariatric surgery to detect and promptly treat portomesenteric venous thrombosis. Different cancer types have different thrombotic risks and the types of surgery influence to a large extent the overall VTE risk. Cancer patients should receive further risk assessment. In patients with higher thrombotic risk, either due to predisposing risk or concomitant surgery, low molecular weight heparin is indicated. Different countries appear to have different incidence of VTE following trauma and major orthopedic surgery. We recommend mechanical prophylaxis using IPC as the main method and additional pharmacological prophylaxis if the thrombotic risk is high. As for obstetric practice, we propose adherence to the UK Greentop guideline that is widely accepted and utilized across Asia. To improve VTE thromboprophylaxis implementation in the region, we propose that there should be better health education, establishment of hospital-based guidelines and multidisciplinary collaboration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0392-9590.16.03765-2DOI Listing
February 2017

Cultural issues of the National Institutes of Health Stroke Scale dysphasia and dysarthria components in Singapore - A survey of healthcare workers.

Int J Stroke 2016 12 12;11(9):NP93. Epub 2016 Jul 12.

Singapore General Hospital, National Neuroscience Institute, Singapore

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493016660097DOI Listing
December 2016

Prognostic factors and treatment effect in the CHIMES study.

J Stroke Cerebrovasc Dis 2015 Apr 11;24(4):823-7. Epub 2015 Feb 11.

Department of Pharmacology, National University of Singapore, Clinical Research Centre, Singapore. Electronic address:

Background: Stroke trials often analyze patients with heterogeneous prognoses using a single definition of outcome, which may not be applicable to all subgroups. We aimed to evaluate the treatment effects of MCL601 among patients stratified by prognosis in the Chinese Medicine Neuroaid Efficacy on Stroke Recovery (CHIMES) study.

Methods: Analyses were performed using data from the CHIMES study, an international, randomized, placebo-controlled, double-blind trial comparing MLC601 with placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. All subjects with baseline data and the modified Rankin Scale (mRS) score at 3 months were included.

Results: Data from 1006 subjects were analyzed. The predictive variables for mRS score greater than 1 at month 3 were age older than 60 years (P < .001), baseline National Institutes of Health Stroke Scale score 10-14 (P < .001), stroke onset to initiation of study treatment of more than 48 hours (P < .001), and female sex (P = .026). A higher number of predictors was associated with poorer mRS score at month 3 for both placebo (P < .001) and treatment (P < .001) groups. The odds ratio (OR) for achieving a good outcome increased with the number of predictors and reached statistical significance in favor of MLC601 among patients with 2 to 4 predictors combined (unadjusted OR = 1.44, 95% confidence interval, 1.02-2.03; adjusted OR = 1.60, 95% confidence interval, 1.10-2.34).

Conclusions: Age, sex, baseline National Institutes of Health Stroke Scale score, and time to first dose are predictors of functional outcome in the CHIMES study. Stratification by prognosis showed that patients with 2 or more predictors of poorer outcome have better treatment effect with MLC601 than patients with single or no prognostic factor. These results have implications on designing future stroke trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.11.017DOI Listing
April 2015

Disability impacts length of stay in general internal medicine patients.

J Gen Intern Med 2014 Jun;29(6):885-90

Duke - National University of Singapore (NUS) Graduate Medical School, Singapore, Singapore.

Background: Disability is prevalent among patients treated in Internal Medicine (IM), but its impact on length of inpatient stay (LOS) is unknown. Current systems of patient management and resource allocation are disease-focused with scant attention paid to functional impairment. Earlier studies in selected cohorts suggest that disability prolongs LOS.

Objective: To investigate the relationship of disability with LOS in IM, controlling for comorbidity.

Design: Prospective cohort study.

Patients: We charted 448 patients from an IM team admitted between 2008 and 2012 for sociodemographic, disease, biochemical and functional characteristics. Each IM team is on duty for one month annually, and patients were hence recruited for one month each year.

Main Measures: Disability was measured using the Functional Independence Measure (FIM) recorded at discharge. Comorbidity was measured using the Charlson Comorbidity Index (CCI).

Key Results: Of the 448 patients, 57.4 % were male with mean age 68.6 years. The mean LOS was 9.58 days. The mean motor and cognitive FIM scores were 57.1 and 25.7, respectively. The mean CCI score was 2.69. Thirty-four percent had major social issues impacting discharge plans. The five most common diagnoses for admission were pneumonia (8.9 %), urinary tract infection (7.8 %), cellulitis (7.6 %), heart failure (7.1 %) and falls (6.0 %). Both cognitive and motor FIM scores were negatively correlated with longer LOS (P < 0.001). On multivariate analysis, variables independently associated with longer LOS included the motor FIM score (P < 0.001), presence of social issues such as caregiver unavailability (P < 0.001), non-realistic patient expectations (P = 0.001) and administrative issues impeding discharge (P = 0.016).

Conclusion: Disability predicts LOS in IM patients, and thus their comprehensive care should involve functional assessment. As social and administrative factors were also independently associated with LOS, there is a need to involve social workers and administrators in a multidisciplinary approach towards optimizing LOS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11606-014-2815-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026504PMC
June 2014

Patients with single distal MCA perfusion lesions have a high rate of good outcome with or without reperfusion.

Int J Stroke 2014 Feb 23;9(2):156-9. Epub 2013 Dec 23.

Stanford University, Stanford, CA, USA.

Background: Reperfusion is associated with good functional outcome after stroke. However, minimal data are available regarding the effect of reperfusion on clinical outcome and infarct growth in patients with distal MCA branch occlusions.

Aim: The aim of this study was to evaluate this association and to determine the impact of the perfusion-diffusion mismatch.

Methods: Individual patient data from three stroke studies (EPITHET, DEFUSE and DEFUSE 2) with baseline MRI profiles and reperfusion status were pooled. Patients were included if they had a single cortical perfusion lesion on their baseline MRI that was consistent with a distal MCA branch occlusion. Good functional outcome was defined as a score of 0-2 on the modified Rankin Scale at day 90 and infarct growth was defined as change in lesion volume between the baseline DWI and the final T2/FLAIR.

Results: Thirty patients met inclusion criteria. Eighteen (60%) had a good functional outcome and twenty (67%) had reperfusion. Reperfusion was not associated with good functional outcome in the overall cohort (OR: 1·0, 95% CI 0·2-4·7) and also not in the subset of patients with a PWI-DWI mismatch (n = 17; OR: 0·7, 95% CI 0·1-5·5). Median infarct growth was modest and not significantly different between patients with (0 ml) and without reperfusion (6 ml); P = 0·2.

Conclusions: The overall high rate of good outcomes in patients with distal MCA perfusion lesions might obscure a potential benefit from reperfusion in this population. A larger pooled analysis evaluating the effect of reperfusion in patients with distal MCA branch occlusions is warranted as confirmation of our results could have implications for the design of future stroke trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907940PMC
February 2014

Retinal microvascular changes and risk of stroke: the Singapore Malay Eye Study.

Stroke 2013 Sep 18;44(9):2402-8. Epub 2013 Jul 18.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

Background And Purpose: To examine the relationship between retinal microvascular measures and incident stroke in an Asian Malay population.

Methods: We conducted a prospective, population-based cohort study of Asian Malay persons 40 to 80 years at baseline. Retinal microvascular signs were assessed from baseline retinal photographs including quantitative retinal microvascular parameters (caliber, branching angle, tortuosity, and fractal dimension) and qualitative retinopathy signs. Incident stroke cases were identified during the follow-up period. Cox proportional-hazards regression and incremental usefulness analysis (calibration, discrimination, and reclassification) were performed.

Results: A total of 3189 participants were free of prevalent stroke at baseline. During the follow-up (median, 4.41 years), 51 (1.93%) participants had an incident stroke event. In Cox proportional-hazards models adjusting for established stroke predictors (age, sex, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, smoking, glycosylated hemoglobin, and antihypertensive medication), retinopathy (hazard ratio, 1.94; 95% confidence interval, 1.01-3.72) and larger retinal venular caliber (hazard ratio, 3.28; 95% confidence interval, 1.30-8.26, comparing fourth versus first quartiles) were associated with risk of stroke. Compared with the model with only established risk factors, the addition of retinal measures improved the prediction of stroke (C-Statistic 0.826 versus 0.792; P=0.017) and correctly reclassified 5.9% of participants with incident stroke and 3.4% of participants with no incident stroke.

Conclusions: Retinal microvascular changes are related to an increased risk of stroke in Asian Malay, consistent with data from white populations. Retinal imaging improves the discrimination and stratification of stroke risk beyond that of established risk factors by a significant but small margin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.113.001738DOI Listing
September 2013

Microvascular structure and network in the retina of patients with ischemic stroke.

Stroke 2013 Aug 28;44(8):2121-7. Epub 2013 May 28.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.

Background And Purpose: Microvascular disease has been implicated in the pathogenesis of stroke. The retina provides a window to assess microcirculation noninvasively. We studied the association between quantitatively measured retinal microvascular characteristics and acute ischemic stroke.

Methods: We conducted a case-control study with acute ischemic stroke patients recruited from a tertiary hospital in Singapore and controls from the Singapore Epidemiology of Eye Disease program matched by 10-year age strata, sex, and race. Strokes were classified using modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Retinal vascular parameters were measured from retinal fundus photographs using a computer program. Logistic regression models for stroke were constructed adjusting for age, sex, race, and additionally for smoking, hypertension, diabetes mellitus, and hypercholesterolemia.

Results: We included 557 ischemic stroke cases (261 lacunar, 185 large artery, and 54 cardioembolic stroke) and 557 controls. After adjusting for vascular risk factors, decreased arteriolar fractal dimension (odds ratio [OR] per standard deviation [SD] decrease, 2.28; 95% confidence interval [CI], 1.80-2.87) and venular fractal dimension (OR per SD decrease, 1.80; 95% CI, 1.46-2.23), increased arteriolar tortuosity (OR per SD increase, 1.56; 95% CI, 1.25-1.95), and venular tortuosity (OR per SD increase, 1.49; 95% CI, 1.27-1.76), narrower arteriolar caliber (OR per SD decrease, 2.79; 95% CI, 2.21-3.53), and wider venular caliber (OR per SD increase, 1.57; 95% CI, 1.27-1.95) were associated with stroke. Stratification by stroke subtypes and further adjustment for retinopathy signs revealed similar results.

Conclusions: Patients with ischemic stroke have a sparser and more tortuous microvascular network in the retina. These findings provide insight into the structure and pattern of microcirculation changes in stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.113.001741DOI Listing
August 2013

Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation.

Int J Stroke 2015 Jun 12;10(4):534-40. Epub 2013 Mar 12.

Department of Medicine and Neurology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic, Australia.

Background: Atrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies.

Methods: Echoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at three to six hours following symptom onset. Patients underwent multimodal magnetic resonance imaging before treatment, at three to five days and three-months after stroke in Echoplanar Imaging Thrombolytic Evaluation Trial; before treatment, three to six hours after treatment and one-month after stroke in Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution. Patients were assessed with the National Institutes of Health Stroke Scale and the modified Rankin scale before treatment and at three-months after stroke. Patients were categorized into definite atrial fibrillation (present on initial examination), probable atrial fibrillation (history but no atrial fibrillation on initial examination), and no atrial fibrillation. Perfusion data were reprocessed with automated magnetic resonance imaging analysis software (RAPID, Stanford University, Stanford, CA, USA). Hypoperfusion volumes were defined using time to maximum delays in two-second increments from >4 to >8 s. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Studies criteria.

Results: Of the 175 patients, 28 had definite atrial fibrillation, 30 probable atrial fibrillation, 111 no atrial fibrillation, and six were excluded due to insufficient imaging data. At baseline, patients with definite atrial fibrillation had more severe hypoperfusion (median time to maximum >8 s, volume 48 vs. 29 ml, P = 0.02) compared with patients with no atrial fibrillation. At outcome, patients with definite atrial fibrillation had greater infarct growth (median volume 47 vs. 8 ml, P = 0.001), larger infarcts (median volume 75 vs. 23 ml, P = 0.001), more frequent parenchymal hematoma grade hemorrhagic transformation (30% vs. 10%, P = 0.03), worse functional outcomes (median modified Rankin scale score 4 vs. 3, P = 0.03), and higher mortality (36% vs. 16%, P = 0·.3) compared with patients with no atrial fibrillation. Definite atrial fibrillation was independently associated with increased parenchymal hematoma (odds ratio = 6.05, 95% confidence interval 1.60-22.83) but not poor functional outcome (modified Rankin scale 3-6, odds ratio = 0.99, 95% confidence interval 0.35-2.80) or mortality (odds ratio = 2.54, 95% confidence interval 0.86-7.49) three-months following stroke, after adjusting for other baseline imbalances.

Conclusion: Atrial fibrillation is associated with greater volumes of more severe baseline hypoperfusion, leading to higher infarct growth, more frequent severe hemorrhagic transformation and worse stroke outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688700PMC
June 2015

Inflammatory markers and their association with post stroke cognitive decline.

Int J Stroke 2015 Jun 12;10(4):513-8. Epub 2013 Mar 12.

Department of Pharmacology, National University of Singapore, Singapore.

Background: Population-based studies have demonstrated the association of inflammation and cognitive impairment. However, few studies to date have examined this association in ischemic stroke patients.

Aims: The study aims to determine the association between inflammatory markers and cognitive impairment.

Methods: Ischemic stroke patients with baseline neuropsychological assessments at three-months poststroke were followed up with annual neuropsychological assessments for up to five-years. Inflammatory markers (C-reactive protein, interleukin 1β, interleukin 6, interleukin 8, interleukin 10, interleukin 12, and tumor necrosis factor-α) were assayed, and logistic regression analyses were performed to determine associations between inflammatory markers and both baseline cognitive status and subsequent cognitive decline.

Results: There were 243 ischemic stroke patients in the study. In multivariable ordinal logistic regression analysis, age, education, ethnicity, stroke subtype, and interleukin 8 (OR 1.23 CI 1.05-1.44) levels were independently associated with baseline cognitive status. In multivariable logistic regression analyses, age, gender, recurrent strokes, and interleukin 12 (OR 25.02 CI 3.73 to 168.03) were independent predictors of subsequent cognitive decline.

Conclusions: Following ischemic stroke, higher serum interleukin 8 is independently associated with baseline cognitive impairment while higher serum interleukin 12 is associated with subsequent cognitive decline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12001DOI Listing
June 2015

Advanced imaging improves prediction of hemorrhage after stroke thrombolysis.

Ann Neurol 2013 Apr 26;73(4):510-9. Epub 2013 Feb 26.

Departments of Medicine and Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.

Objective: Very low cerebral blood volume (VLCBV), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion.

Methods: The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging (MRI) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator (tPA) or placebo, and all DEFUSE patients received tPA. VLCBV was defined as cerebral blood volume<2.5th percentile of brain contralateral to the infarct. Parenchymal hematoma (PH) was defined using European Cooperative Acute Stroke Study criteria. Reperfusion was assessed using subacute perfusion MRI coregistered to baseline imaging.

Results: In DEFUSE, 69 patients were analyzed, including 9 who developed PH. The >2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH), regression models using VLCBV (p<0.001) and tPA (p=0.02) predicted PH independent of clinical factors better than models using diffusion or time to maximum>8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis.

Interpretation: VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post-thrombolysis PH. VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.23837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665631PMC
April 2013

The effects of alteplase 3 to 6 hours after stroke in the EPITHET-DEFUSE combined dataset: post hoc case-control study.

Stroke 2013 Jan 18;44(1):87-93. Epub 2012 Dec 18.

FRACP, Level 2 Alan Gilbert Bldg, 161 Barry St, Carlton S Victoria 3053, Australia.

Background And Purpose: Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques.

Methods: The EPITHET-DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay >6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures.

Results: From 165 patients with adequate MR scans in the EPITHET-DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo (P=0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P=0.003). Mortality and clinical outcomes were not different between groups.

Conclusions: The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.112.668301DOI Listing
January 2013

Multiparametric MRI and CT models of infarct core and favorable penumbral imaging patterns in acute ischemic stroke.

Stroke 2013 Jan 11;44(1):73-9. Epub 2012 Dec 11.

Building D, Suite 150, Georgetown University, 4000 Reservoir Road NW, Washington, DC 20007, USA.

Background And Purpose: Objective imaging methods to identify optimal candidates for late recanalization therapies are needed. The study goals were (1) to develop magnetic resonance imaging (MRI) and computed tomography (CT) multiparametric, voxel-based predictive models of infarct core and penumbra in acute ischemic stroke patients, and (2) to develop patient-level imaging criteria for favorable penumbral pattern based on good clinical outcome in response to successful recanalization.

Methods: An analysis of imaging and clinical data was performed on 2 cohorts of patients (one screened with CT, the other with MRI) who underwent successful treatment for large vessel, anterior circulation stroke. Subjects were divided 2:1 into derivation and validation cohorts. Pretreatment imaging parameters independently predicting final tissue infarct and final clinical outcome were identified.

Results: The MRI and CT models were developed and validated from 34 and 32 patients, using 943 320 and 1 236 917 voxels, respectively. The derivation MRI and 2-branch CT models had an overall accuracy of 74% and 80%, respectively, and were independently validated with an accuracy of 71% and 79%, respectively. The imaging criteria of (1) predicted infarct core ≤90 mL and (2) ratio of predicted infarct tissue within the at-risk region ≤70% identified patients as having a favorable penumbral pattern with 78% to 100% accuracy.

Conclusions: Multiparametric voxel-based MRI and CT models were developed to predict the extent of infarct core and overall penumbral pattern status in patients with acute ischemic stroke who may be candidates for late recanalization therapies. These models provide an alternative approach to mismatch in predicting ultimate tissue fate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.112.670034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558033PMC
January 2013

Differing associations of white matter lesions and lacunar infarction with retinal microvascular signs.

Int J Stroke 2014 Oct 18;9(7):921-5. Epub 2012 Sep 18.

Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia.

Background: White matter lesions (WML) and lacunar infarcts (LI) are believed to have microvascular etiologies but the exact microvascular changes occurring in each is unclear.

Aim: Using the retina as a proxy, we assessed retinal microvascular changes in WML and LI.

Methods: We prospectively recruited 1211 acute stroke patients. Four subgroups were identified from neuroimaging: WML alone, LI alone, both WML and LI, neither WML nor LI. Masked retinal photographs identified retinopathy and retinal arteriolar wall signs and measured retinal vascular caliber.

Results: Compared with 448 controls with neither WML nor LI, 384 patients with only WML were more likely to have retinopathy [odds ratio (OR) 1·5, 95% confidence interval (CI) 1·1 to 2·1] and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·1 to 2·3); 200 patients with only LI were more likely to have arteriolar narrowing (OR 1·6, 95% CI 1·1 to 2·3) and enhanced arteriolar light reflex (OR 1·6, 95% CI 1·0 to 2·4); and 179 patients with both WML and LI were more likely to have arteriovenous nicking (OR 1·7, 95% CI 1·1 to 2·6), enhanced arteriolar light reflex (OR 2·0, 95% CI 1·3 to 3·2) and wider venules (OR 2·3, 95% CI 1·4 to 3·6). All analyses were adjusted for age, gender, study site and cardiovascular risk factors.

Conclusion: Both WML and LI were associated with retinal microvascular signs, supporting a microvascular etiology. Differing patterns of association suggest different mechanisms may predominate, e.g. greater endothelial permeability in WML, and ischemia associated with arteriolar wall disease in LI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1747-4949.2012.00865.xDOI Listing
October 2014

Associations of ankle-brachial index (ABI) with cerebral arterial disease and vascular events following ischemic stroke.

Atherosclerosis 2012 Jul 11;223(1):219-22. Epub 2012 May 11.

Singapore General Hospital Campus, National Neuroscience Institute, Department of Neurology, Singapore General Hospital, Singapore.

Objectives: Low ankle-brachial index (ABI), indicative of peripheral arterial disease (PAD), is a risk factor for stroke. ABI has been shown to be associated with cerebral arterial disease and prognosis following stroke. We studied the associations of the degree of ABI lowering with extracranial carotid disease (ECD), intracranial large artery disease (ICLAD), and subsequent vascular events in a prospective cohort of acute ischemic stroke patients.

Methods: ABI, extracranial and intracranial cerebral arteries were assessed in a blinded manner. ABI was categorized into 0.9-1.3 (normal), 0.8-0.89 (mildly lowered) and <0.8 (severely lowered). Follow-up data at 1 year were obtained from standardized telephone interviews and verified with medical records.

Results: Among the 1311 patients, 73% had normal ABI, 13% had ABI 0.8-0.89 and 13% had ABI <0.8. Compared to patients with normal ABI, those with ABI<0.8 had higher prevalence of severe ECD (15% vs. 5%, p = 0.006) and ICLAD (72% vs. 48%, p = 0.003), even after adjustment for age, gender, hypertension, diabetes, hyperlipidemia, smoking, ischemic heart disease and atrial fibrillation (severe ECD p < 0.001, ICLAD p < 0.001). At 1 year, patients with ABI <0.8 had a higher incidence of composite vascular events (19% vs. 11%, p = 0.02), stroke (15% vs. 10%, p = 0.06) and myocardial infarction (4% vs. 2%, p = 0.07) than patients with normal ABI.

Conclusion: Among ischemic stroke patients, large cerebral arterial disease and incidence of subsequent vascular events at 1 year were associated with severe ABI lowering <0.8, but not with mild ABI lowering (0.8-0.89).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2012.04.009DOI Listing
July 2012

Greater effect of stroke thrombolysis in the presence of arterial obstruction.

Ann Neurol 2011 Oct;70(4):601-5

Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore.

Objective: Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth.

Methods: We analyzed 175 ischemic stroke patients treated in the 3-6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA).

Results: Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1-50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, -3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21-43, p < 0.001).

Interpretation: The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.22444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205432PMC
October 2011

Fluid-attenuated inversion recovery hyperintensity in acute ischemic stroke may not predict hemorrhagic transformation.

Cerebrovasc Dis 2011 8;32(4):401-5. Epub 2011 Oct 8.

Department of Medicine and Neurology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Vic., Australia.

Background: Fluid-attenuated inversion recovery (FLAIR) hyperintensity within an acute cerebral infarct may reflect delayed onset time and increased risk of hemorrhage after thrombolysis. Given the important implications for clinical practice, we examined the prevalence of FLAIR hyperintensity in patients 3-6 h from stroke onset and its relationship to parenchymal hematoma (PH).

Methods: Baseline DWI and FLAIR imaging with subsequent hemorrhage detection (ECASS criteria) were prospectively obtained in patients 3-6 h after stroke onset from the pooled EPITHET and DEFUSE trials. FLAIR hyperintensity within the region of the acute DWI lesion was rated qualitatively (dichotomized as visually obvious or subtle (i.e. only visible after careful windowing)) and quantitatively (using relative signal intensity (RSI)). The association of FLAIR hyperintensity with hemorrhage was then tested alongside established predictors (very low cerebral blood volume (VLCBV) and diffusion (DWI) lesion volume) in logistic regression analysis.

Results: There were 49 patients with pre-treatment FLAIR imaging (38 received tissue plasminogen activator (tPA), 5 developed PH). FLAIR hyperintensity within the region of acute DWI lesion occurred in 48/49 (98%) patients, was obvious in 18/49 (37%) and subtle in 30/49 (61%). Inter-rater agreement was 92% (κ = 0.82). The prevalence of obvious FLAIR hyperintensity did not differ between studies obtained in the 3-4.5 h and 4.5-6 h time periods (40% vs. 33%, p = 0.77). PH was poorly predicted by obvious FLAIR hyperintensity (sensitivity 40%, specificity 64%, positive predictive value 11%). In univariate logistic regression, VLCBV (p = 0.02) and DWI lesion volume (p = 0.03) predicted PH but FLAIR lesion volume (p = 0.87) and RSI (p = 0.11) did not. In ordinal logistic regression for hemorrhage grade adjusted for age and baseline stroke severity (NIHSS), increased VLCBV (p = 0.002) and DWI lesion volume (p = 0.003) were associated with hemorrhage but FLAIR lesion volume (p = 0.66) and RSI (p = 0.35) were not.

Conclusions: Visible FLAIR hyperintensity is almost universal 3-6 h after stroke onset and did not predict subsequent hemorrhage in this dataset. Our findings question the value of excluding patients with FLAIR hyperintensity from reperfusion therapies. Larger studies are required to clarify what implications FLAIR-positive lesions have for patient selection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000331467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214893PMC
March 2012

The infarct core is well represented by the acute diffusion lesion: sustained reversal is infrequent.

J Cereb Blood Flow Metab 2012 Jan 20;32(1):50-6. Epub 2011 Jul 20.

Department of Medicine and Neurology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.

Diffusion-weighted imaging (DWI) is commonly used to assess irreversibly infarcted tissue but its accuracy is challenged by reports of diffusion lesion reversal (DLR). We investigated the frequency and implications for mismatch classification of DLR using imaging from the EPITHET (Echoplanar Imaging Thrombolytic Evaluation Trial) and DEFUSE (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) studies. In 119 patients (83 treated with IV tissue plasminogen activator), follow-up images were coregistered to acute diffusion images and the lesions manually outlined to their maximal visual extent in diffusion space. Diffusion lesion reversal was defined as voxels of acute diffusion lesion that corresponded to normal brain at follow-up (i.e., final infarct, leukoaraiosis, and cerebrospinal fluid (CSF) voxels were excluded from consideration). The appearance of DLR was visually checked for artifacts, the volume calculated, and the impact of adjusting baseline diffusion lesion volume for DLR volume on perfusion-diffusion mismatch analyzed. Median DLR volume reduced from 4.4 to 1.5 mL after excluding CSF/leukoaraiosis. Visual inspection verified 8/119 (6.7%) with true DLR, median volume 2.33 mL. Subtracting DLR from acute diffusion volume altered perfusion-diffusion mismatch (T(max)>6 seconds, ratio>1.2) in 3/119 (2.5%) patients. Diffusion lesion reversal between baseline and 3 to 6 hours DWI was also uncommon (7/65, 11%) and often transient. Clinically relevant DLR is uncommon and rarely alters perfusion-diffusion mismatch. The acute diffusion lesion is generally a reliable signature of the infarct core.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/jcbfm.2011.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323290PMC
January 2012

RAPID automated patient selection for reperfusion therapy: a pooled analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study.

Stroke 2011 Jun 14;42(6):1608-14. Epub 2011 Apr 14.

Stanford University,Stanford Stroke Center, 780 Welch Road, Suite 205, Palo Alto, CA 94304, USA.

Background And Purpose: The aim of this study was to determine if automated MRI analysis software (RAPID) can be used to identify patients with stroke in whom reperfusion is associated with an increased chance of good outcome.

Methods: Baseline diffusion- and perfusion-weighted MRI scans from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE; n=74) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; n=100) were reprocessed with RAPID. Based on RAPID-generated diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, patients were categorized according to 3 prespecified MRI profiles that were hypothesized to predict benefit (Target Mismatch), harm (Malignant), and no effect (No Mismatch) from reperfusion. Favorable clinical response was defined as a National Institutes of Health Stroke Scale score of 0 to 1 or a ≥ 8-point improvement on the National Institutes of Health Stroke Scale score at Day 90.

Results: In Target Mismatch patients, reperfusion was strongly associated with a favorable clinical response (OR, 5.6; 95% CI, 2.1 to 15.3) and attenuation of infarct growth (10 ± 23 mL with reperfusion versus 40 ± 44 mL without reperfusion; P<0.001). In Malignant profile patients, reperfusion was not associated with a favorable clinical response (OR, 0.74; 95% CI, 0.1 to 5.8) or attenuation of infarct growth (85 ± 74 mL with reperfusion versus 95 ± 79 mL without reperfusion; P=0.7). Reperfusion was also not associated with a favorable clinical response (OR, 1.05; 95% CI, 0.1 to 9.4) or attenuation of lesion growth (10 ± 15 mL with reperfusion versus 17 ± 30 mL without reperfusion; P=0.9) in No Mismatch patients.

Conclusions: MRI profiles that are associated with a differential response to reperfusion can be identified with RAPID. This supports the use of automated image analysis software such as RAPID for patient selection in acute stroke trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.110.609008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104106PMC
June 2011

Refining the definition of the malignant profile: insights from the DEFUSE-EPITHET pooled data set.

Stroke 2011 May 7;42(5):1270-5. Epub 2011 Apr 7.

Department of Neurology and Neurological Sciences, Stanford Stroke Center, 780 Welch Road, Suite 205, Stanford, Stanford, CA, USA.

Background And Purpose: To refine the definition of the malignant magnetic resonance imaging profile in acute stroke patients using baseline diffusion-weighted magnetic resonance imaging (DWI) and perfusion-weighted magnetic resonance imaging (PWI) findings from the pooled DEFUSE/EPITHET database.

Methods: Patients presenting with acute stroke within 3 to 6 hours from symptom onset were treated with tissue plasminogen activator or placebo. Baseline and follow-up DWI and PWI images from both studies were reprocessed using the same software program. A receiver operating characteristic curve analysis was used to identify Tmax and DWI volumes that optimally predicted poor outcomes (modified Rankin Scale 5-6) at 90 days in patients who achieved reperfusion.

Results: Sixty-five patients achieved reperfusion and 46 did not reperfuse. Receiver operating characteristic analysis identified a PWI (Tmax>8 s) volume of >85 mL as the optimal definition of the malignant profile. Eighty-nine percent of malignant profile patients had poor outcome with reperfusion versus 39% of patients without reperfusion (P=0.02). Parenchymal hematomas occurred more frequently in malignant profile patients who experienced reperfusion versus no reperfusion (67% versus 11%, P<0.01). DWI analysis identified a volume of 80 mL as the best DWI threshold, but this definition was less sensitive than were PWI-based definitions.

Conclusions: Stroke patients likely to suffer parenchymal hemorrhages and poor outcomes following reperfusion can be identified from baseline magnetic resonance imaging findings. The current analysis demonstrates that a PWI threshold (Tmax>8 s) of approximately 100 mL is appropriate for identifying these patients. Exclusion of malignant profile patients from reperfusion therapies may substantially improve the efficacy and safety of reperfusion therapies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00238537.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.110.601609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248048PMC
May 2011