Leonid Churilov

The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia

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Publications (153)407.59 Total impact

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    ABSTRACT: Background Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. Methods We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. Results The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. Conclusions In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725 , and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965 .).
    New England Journal of Medicine 02/2015; DOI:10.1056/NEJMoa1414792 · 54.42 Impact Factor
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    ABSTRACT: Background Older adults who have received inpatient rehabilitation often have significant mobility disability at discharge. Physical activity levels in rehabilitation are also low. It is hypothesized that providing increased physical activity to older people receiving hospital-based rehabilitation will lead to better mobility outcomes at discharge.Methods/DesignA single blind, parallel-group, multisite randomized controlled trial with blinded assessment of outcome and intention-to-treat analysis. The cost effectiveness of the intervention will also be examined. Older people (age >60 years) undergoing inpatient rehabilitation to improve mobility will be recruited from geriatric rehabilitation units at two Australian hospitals. A computer-generated blocked stratified randomization sequence will be used to assign 198 participants in a 1:1 ratio to either an `enhanced physical activity¿ (intervention) group or a `usual care plus¿ (control) group for the duration of their inpatient stay. Participants will receive usual care and either spend time each week performing additional physical activities such as standing or walking (intervention group) or performing an equal amount of social activities that have minimal impact on mobility such as card and board games (control group). Self-selected gait speed will be measured using a 6-meter walk test at discharge (primary outcome) and 6 months follow-up (secondary outcome). The study is powered to detect a 0.1 m/sec increase in self-selected gait speed in the intervention group at discharge. Additional measures of mobility (Timed Up and Go, De Morton Mobility Index), function (Functional Independence Measure) and quality of life will be obtained as secondary outcomes at discharge and tertiary outcomes at 6 months follow-up. The trial commenced recruitment on 28 January 2014.DiscussionThis study will evaluate the efficacy and cost effectiveness of increasing physical activity in older people during inpatient rehabilitation. These results will assist in the development of evidenced-based rehabilitation programs for this population.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12613000884707 (Date of registration 08 August 2013); ClinicalTrials.gov Identifier NCT01910740 (Date of registration 22 July 2013).
    Trials 01/2015; 16(1):13. DOI:10.1186/s13063-014-0531-y · 2.12 Impact Factor
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    ABSTRACT: Spinal cord injury (SCI) leads to a profound muscular atrophy, bone loss and bone fragility. While there is evidence that exercising paralysed muscles may lead to reversal of muscle atrophy in the chronic period after SCI, there is little evidence that exercise can prevent muscle changes early after injury. Moreover, whether exercise can prevent bone loss and microarchitectural decay is not clear.Methods/design: A multi-centre, parallel group, assessor-blinded randomised controlled trial will be conducted. Fifty participants with acute spinal cord injury will be recruited from four SCI units in Australia and New Zealand. Participants will be stratified by site and AIS status and randomised to an experimental or control group. Experimental participants will receive a 12-week programme of functional electrical stimulation (FES)-assisted cycling. Control participants will receive a 12-week programme of passive cycling. The primary outcome is muscle cross-sectional area of the thigh and calf measured using magnetic resonance images (MRI) of the leg. Secondary outcomes include serum biomarkers of SCI osteoporosis (sclerostin, P1NP and beta-CTX), markers of immune function (IL-6, IL-10, FGF2, INF-gamma, TNF-alpha), neurological function, body composition, depression and quality of life. Leg MRIs will be measured by a single blinded assessor based in Melbourne. Serum samples will be analysed in a central laboratory. All other characteristics will be measured at baseline and 12 weeks by blinded and trained assessors at each site. The first participant was randomised on 27 November 2012. The results of this trial will determine the relative effectiveness of a 12-week programme of FES-assisted cycling versus passive cycling in preventing muscle atrophy and maintaining skeletal integrity after spinal cord injury.Trial registration: ACTRN12611001079932 (18 October 2011).
    Trials 01/2015; 16(1):7. DOI:10.1186/1745-6215-16-7 · 2.12 Impact Factor
  • International Journal of Stroke 01/2015; 10(1). DOI:10.1111/ijs.12423 · 4.03 Impact Factor
  • Cerebrovascular Diseases 11/2014; 38(5):393-394. DOI:10.1159/000369118 · 3.70 Impact Factor
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    ABSTRACT: Background Large vessel occlusion (LVO) is associated with poor functional outcome in acute ischemic stroke. Given the uncertainty whether LVO has the same significance in mild and severe stroke, we compared functional outcomes after intravenous thrombolysis, based on severity and LVO. Methods Ischemic stroke patients were thrombolyzed in less than 4.5 hours after onset between 2007 and 2013. LVO was defined as occlusion of one of the following arteries: internal carotid, middle cerebral (M1/M2), anterior cerebral (A1), posterior cerebral (P1), basilar, or vertebral (V4) arteries on prethrombolysis computed tomography angiography. Mild stroke was defined as baseline National Institutes of Health Stroke Scale (NIHSS) score 0-6. Favorable outcome was defined as modified Rankin Scale (mRS) score 0-1 at 3 months or equal to the prestroke mRS. Results There were 175 acute stroke patients, median age 74 years (interquartile range [IQR], 64-83), median baseline NIHSS = 11 (IQR, 5-16), and 63 of 175 patients (36%) with mild stroke. LVO was associated with worse outcome in severe stroke (age-adjusted odds ratio [OR] of favorable outcome, .42; 95% confidence interval [CI], .19-.93; P = .033) and mortality (age-adjusted OR, 3.52; 95% CI, 1.08-11.48; P = .037). Although the difference in favorable outcome between mild stroke patients with and without LVO was not significant (55.6% vs. 74.1%, P = .262; age-adjusted OR of favorable outcome, .42; 95% CI, .1-1.84; P = .251), the similarity of effects across both subgroups cannot be excluded (LVO-by-stroke severity interaction test, P = .906). Conclusions LVO is associated with worse functional outcome and mortality in severe stroke after intravenous thrombolysis. Although significant association between LVO and outcome in mild stroke was not found, there were similar effects on outcome and a larger study might well confirm a relationship.
    Journal of Stroke and Cerebrovascular Diseases 11/2014; 23(10). DOI:10.1016/j.jstrokecerebrovasdis.2014.07.018 · 1.99 Impact Factor
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    ABSTRACT: Advanced imaging may refine patient selection for ischemic stroke treatment but delays to acquire and process the imaging have limited implementation.
    International Journal of Stroke 10/2014; 10(1). DOI:10.1111/ijs.12381 · 4.03 Impact Factor
  • Yuan Gao, Leonid Churilov, Sarah Teo, Bernard Yan
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    ABSTRACT: Remote intracerebral haemorrhage (rICH) is defined as intracerebral haemorrhage (ICH) post thrombolysis in brain regions without visible ischaemic changes. There is uncertainty that clinical outcomes and risk factors for rICH are different to those for local ICH. We investigated the morbidity, mortality and factors associated with rICH. We hypothesised that a previous history of cerebral ischaemic events is associated with increased risk of rICH. We included consecutive acute ischaemic stroke patients from 2003 to 2012 who were treated with intravenous thrombolysis. Clinical data included demographics, stroke classification, vascular risk factors and laboratory results. Clinical outcome was defined by modified Rankin Scale (mRS) score at 3 months. Baseline and follow-up CT scans were analysed for all ICH, and further dichotomised to rICH and local ICH. Clinical outcomes between rICH and local ICH were compared after adjustment for confounding factors. Four hundred and two patients were included in the study. The median age was 71 (interquartile range 60–79) years, and 54% were male. ICH (local ICH and rICH) was detected in 21.6% (87/402) of all patients post thrombolysis. The incidence of rICH was 2.2% (9/402). Most rICH were classified as haemorrhagic infarct category 2 (HI2) (p = 0.002). The proportion of patients with previous transient ischaemic attacks was significantly higher in the rICH group (33.33% versus 2.56%; odds ratio [OR] 18.75, 95% confidence interval [CI] 3.06–114.38; p = 0.007). The proportion of mRS scores 0–2 at 3 months was significantly higher in the rICH group (50% versus 28%; adjusted OR 10.469, 95%CI 1.474–74.338; p = 0.019). The 3 month mortality rate was 22.2% (2/9) in the rICH group and 36% (27/75) in the local ICH group (OR 0.53, 95%CI 0–2.51, p = 0.703). rICH was an infrequent complication after intravenous thrombolysis in our series. The clinical outcome of rICH was significantly better than local ICH. Of note, previous episodes of transient ischaemic attack were significantly higher in the rICH group, suggesting previous ischaemic injury as an underlying mechanism.
    Journal of Clinical Neuroscience 10/2014; 22(2). DOI:10.1016/j.jocn.2014.07.009 · 1.32 Impact Factor
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    ABSTRACT: Background: Early decompressive hemicraniectomy following malignant middle cerebral artery (MCA) infarction reduces mortality and improves clinical outcome. Imaging predictors of malignant infarction may serve as 'red flags', prompting intensive neurological monitoring and timely intervention. Our objective is to investigate whether lower ASPECTS (Alberta Stroke Program Early CT Score) is associated with malignant MCA infarction. Methods: A retrospective cohort study of all patients with MCA territory ischemic strokes who were admitted to the Royal Melbourne Hospital (RMH) between 1 January 2009 and 31 December 2009 (226 patients included). The main outcome measures were ASPECTS on admission for each patient and the development of malignant MCA infarction. Results: One-hundred-and-eight patients out of 226 (48%) developed malignant MCA infarction. Good (>0.8) inter-rater agreement between observers scoring ASPECTS was observed using weighted kappa, intra-class correlation coefficient and Lin's concordance coefficients. Using receiver operating characteristic (ROC) curve analysis, we validated that ASPECTS 7 was the optimal cut-off score to determine progression to malignant infarction, providing 50% sensitivity and 86% specificity. One hundred and fifty six patients had ASPECTS >7 (69%) and 70 patients had ASPECTS ≤7 (31%). Patients with ASPECTS ≤7 were significantly younger than those with ASPECTS >7, with the median age of each group being 72.5 and 78 respectively (p = 0.02); otherwise the groups were well-matched. With ASPECTS ≤7, 54 out of 70 patients (77%) developed malignant MCA infarction, compared with 54 out of 156 patients (35%) with ASPECTS >7 (age-adjusted OR = 0.12, 95% CI: 0.06, 0.25; p < 0.0001). If ASPECTS ≤7 is a positive result, then the positive predictive value is 77% and the negative predictive value is 65%. The median ASPECTS for developing malignant MCA infarction was 7.5 (IQR: 5 to 10), while the median ASPECTS for not developing MCA infarction was 10 (IQR: 8 to 10), resulting in a significant age-adjusted median difference of 2 (95% CI: 0.8, 3.2; p < 0.0001). We also found that coma on admission is associated with the development of malignant MCA infarction (OR = 22.63, 95% CI: 1.3, 393.7; p = 0.0323) and that a history of hypertension is not associated with the development of malignant MCA infarction (OR = 0.9707, 95% CI: 0.54, 1.75; p = 0.9213). Conclusions: ASPECTS ≤7 on initial brain CT in a patient with MCA infarction is associated with the development of malignant MCA infarction. We recommend close monitoring of, and early consideration of decompressive hemicraniectomy for, acute stroke patients with ASPECTS ≤7. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 09/2014; 38(1):39-45. DOI:10.1159/000363619 · 3.70 Impact Factor
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    ABSTRACT: BackgroundA key treatment for acute ischaemic stroke is thrombolysis (rtPA). However, treatment is not devoid of side effects and patients are carefully selected. AVERT (A Very Early Rehabilitation Trial), a large, ongoing international phase III trial, tests whether starting out of bed activity within 24 hours of stroke onset improves outcome. Patients treated with rtPA can be recruited if the physician allows (447 included to date). This study aimed to identify factors that might influence the inclusion of rtPA treated patients in AVERT.Methods Data from all patients thrombolysed at Austin Health, Australia, between September 2007 and December 2011 were retrospectively extracted from medical records. Factors of interest included: demographic and stroke characteristics, 24 hour clinical response to rtPA treatment, cerebral imaging and process factors (day and time of admission).Results211 patients received rtPA at Austin Health and 50 (24%) were recruited to AVERT (AVERT). Of the 161 patients not recruited, 105 (65%) were eligible, and could potentially have been included (pot-AVERT). There were no significant differences in demographics, Oxfordshire classification or stroke severity (NIHSS) on admission between groups. Size and localization of stroke on imaging and symptomatic intracerebral heamorrhage rate did not differ. Patients included in AVERT showed less change in NIHSS 24 hours post rtPA (median change = 1, IQR (¿1,4)) than those in the pot-AVERT group (median change = 3, IQR (0,6)) by the median difference of 2 points (95%CI:0.3; p = 0.03). A higher proportion of rtPA treated AVERT patients were admitted on weekdays (p = 0.04).Conclusion Excluding a possible clinical instability, no significant clinical differences were identified between thrombolysed patients included in AVERT and those who were not. Over 500 AVERT patients will be treated with rtPA at trial end. These results suggest we may be able to generalize findings to other rtPA treated patients beyond the trial population.
    BMC Neurology 08/2014; 14(1):163. DOI:10.1186/s12883-014-0163-6 · 2.49 Impact Factor
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    ABSTRACT: Background: Early neurological recovery after intravenous thrombolysis (IVT) is associated with favorable outcome after acute ischemic stroke. Leukoaraiosis, a marker of chronic ischemia, is a possible negative predictive factor of early recovery. However, its negative attenuating effects remain inadequately studied, leading to uncertainty in the prediction of outcomes after IVT. We aim to determine the influence of leukoaraiosis on early neurologic recovery. Methods: We included consecutive acute ischemic stroke patients who received IVT between 2007 and 2011. The following data were included: demographics, vascular risk factors, stroke type, National Institutes of Health Stroke Scale (NIHSS) at onset, and at 24 hours after IVT. Baseline computed tomography (CT) brain scans were analyzed. Two blinded assessors rated the CT scans using the van Swieten scale for leukoaraiosis. Median regression was used to assess the relationship between leukoaraiosis and neurologic recovery. Results: We included 158 patients. The median (interquartile range [IQR]) age was 77 (68-84) and 71 (45%) were female. The median (IQR) NIHSS was 13 (7-18.75) at baseline and 7.5 (2-16) at 24 hours. After taking into account variables independently associated with leukoaraiosis, median regression analysis failed to demonstrate the association between the presence of leukoaraiosis and early neurologic recovery (NIHSS relative one) after IVT, for either of the 3 prespecified dichotomization-based definitions of leukoaraiosis. Conclusions: In our sample, there was no evidence of the association between the degree of leukoaraiosis and early neurological recovery after IVT.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 08/2014; 23(9). DOI:10.1016/j.jstrokecerebrovasdis.2014.05.012 · 1.99 Impact Factor
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    ABSTRACT: Intra-arterial (IA) therapy for stroke is an increasingly utilised management approach for acute ischaemic stroke. We aimed to correlate radiological characteristics and recanalisation success with radiological and functional outcomes at 90 days in patients treated with IA therapy. This was a single centre, retrospective study investigating the correlation between pre-procedural Computed Tomography-Angiogram Source Image (CTA-SI) Alberta Stroke Program Early Computed Tomography Score (ASPECTS), recanalisation success, and functional outcome at 90 days in patients with an acute ischaemic stroke from 2007–2012. Outcome measures were pre-procedural non-contrast computed tomography (NCCT), CTA-SI, and post-procedural NCCT ASPECTS that were obtained and analysed by three blinded reviewers, recanalisation success (Thrombolysis in Cerebral Infarction [TICI] 2b–3) and favourable clinical outcome (90 day modified Rankin scale [mRS] score ⩽ 2). Forty-four patients satisfied the inclusion criteria. The mean age was 64.2 years (standard deviation: 14.9; median: 66.5; interquartile range [IQR]: 54.5–76.5). The median National Institutes of Health Stroke Scale score was 17 (IQR: 13.5–20). Twenty-one (47.7%) patients achieved a mRS score ⩽ 2. The 90 day mortality rate was 25.0% (n = 11). Of the patients who achieved TICI 2b–3, 65.5% (19/29) achieved mRS ⩽ 2. There was a statistically significant association between recanalisation success (TICI ⩾ 2b) and favourable neurological outcome at 90 days (odds ratio [OR] 25.22, 95% confidence interval [CI]: 2.86–222.37, p < 0.005). Patients with high pre-procedural CTA-SI ASPECTS are significantly more likely to have high post-procedural NCCT score (OR 23.36, 95% CI: 3.26–166.92, p = 0.002). Recanalisation success was strongly associated with good clinical outcome, unaffected by known predictive factors, which included age and stroke severity. This association was unattenuated by CTA-SI ASPECTS.
    Journal of Clinical Neuroscience 08/2014; 21(8). DOI:10.1016/j.jocn.2013.11.020 · 1.32 Impact Factor
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    ABSTRACT: Background and Purpose: Developing improved methods for analysis of the modified Rankin Scale (mRS) remains a critical issue for the stroke research community. A recently proposed permutation-based approach is assumption-free and easily interpretable but computationally intensive and does not provide confidence intervals to quantify the precision of the effect size estimate. We aimed to develop a method to over-come these limitations. Methods: We propose a procedure using generalized odds ratios to estimate the odds that a patient who received the investigational treatment will have a better outcome than a patient receiving standard treatment. This approach was vali-dated against the permutation method using hypothetical clinical trial scenarios of neuroprotective effect, early recanali-zation effect, late recanalization effect, and random benefit. Results: The generalized odds ratio approach had strong agreement with the permutation approach provided sample size was >15 patients per treatment arm. Simulation estab-lished that the confidence intervals generated were accurate. Ignoring patient pairs with tied mRS scores overestimates the treatment effect compared with splitting tied mRS scores. Conclusions: In addition to all the advantages of the recently proposed permutation-based approach, our method generates confidence intervals without the need for intensive computa-tional power. The resulting generalized odds ratios are particu-larly suitable for inclusion in meta-analyses and have a simple and intuitive connection with the number-needed-to-treat measure.
    International Journal of Stroke 07/2014; 9(8). DOI:10.1111/ijs.12364 · 4.03 Impact Factor
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    ABSTRACT: Objective Thyroid-peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TGAb) are frequently measured to investigate thyroid dysfunction in pregnancy. Despite the recognized fall of these autoantibodies in pregnancy, there is limited guidance on the timing of such testing. We assessed optimal test timing of TPOAb/TGAb for detection of Hashimoto's thyroiditis and postpartum thyroid dysfunction (PPTD).DesignProspective longitudinal study with recruitment in Trimester-1.PatientsHealthy women ≤13weeks gestation from Mercy Hospital for Women, a tertiary obstetric hospital in Melbourne.MeasurementsSerum TPOAb, TGAb, TSH and fT4 were measured at Trimester-1(T1), Trimester-2(T2), Trimester-3(T3), and postpartum(PP) in each participant. Postpartum thyroid dysfunction (PPTD) was defined if TSH deviated from the assay's non-pregnant reference interval. Longitudinal random-effect logistic regression was used to investigate the association between time and positive/negative thyroid autoantibody status.ResultsSamples from 140 women at T1(12.0:10.3-13.0) (median:IQR weeks gestation); 95 at T2(24.3:23.0-25.9), 79 at T3(35.9:34.8-36.7) and 83 at PP(12.4:10.8-14.6 weeks postpartum) were attained. At T1, 13(9%) and 15(11%) women had positive TPOAb and TGAb, respectively. The odds of having a positive TPOAb was 96% lower at T2(OR=0.04 (95%CI:0.02-0.8;p=0.03)) and 97% lower at T3(OR=0.03(95%CI:0.001-0.6;p=0.02)) than at T1. Similarly, the odds of having a positive TGAb was 99.4% lower (OR=0.006(95%CI:0-0.3;p=0.01)) at T2, and 99.5% lower (OR=0.005(95%CI:0-0.4;p=0.02)) at T3 than at T1. The ROC analysis diagnostic ORs for a positive TPOAb and/or TGAb to predict PPTD were 7.8(95%CI:2.2-27.6), 1.2(95%CI:0-8.9), 2.0(95%CI:0-16.8), and 12.2(95%CI:3.3-44.9) at T1, T2, T3 and postpartum, respectively.ConclusionsA significant proportion of pregnant women lose their thyroid autoantibody positivity after T1. The gestation dependent loss of TPOAb/TGAb positivity and reduction in diagnostic accuracy for predicting PPTD limits the value of testing at T2 and T3.This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 07/2014; 82(4). DOI:10.1111/cen.12571 · 3.35 Impact Factor
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    ABSTRACT: In acute stroke management, time efficiency in the continuum of patient management is critical. We aimed to determine if implementation of system improvements at our institution translated to reduced picture-to-puncture (P2P) times over a 6-year period.
    Journal of Neurointerventional Surgery 06/2014; DOI:10.1136/neurintsurg-2014-011177 · 2.50 Impact Factor
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    ABSTRACT: Background: Clinical deterioration in the acute stage of ischemic stroke powerfully predicts outcome and may serve as a marker for urgent intervention. However, accurate monitoring of acute stroke patients is hampered by the lack of validated continuous monitoring devices. We sought to assess the use of wireless accelerometry in this setting, hypothesizing that stroke patients would have a greater difference in movement between upper limbs than controls and that the magnitude of correlation between upper limb movements would be negatively associated with the National Institutes of Health Stroke Scale (NIHSS) score. Methods: In this pilot study, 20 patients with acute ischemic stroke and unilateral upper limb weakness and 10 controls were recruited from a comprehensive stroke centre. All subjects were fitted with two 3-axis accelerometers and underwent 24 h of continuous accelerometry recording of upper limb movements and repeat NIHSS assessments. The intra-class correlation coefficient (ICC), assessing the similarity (or otherwise) of spontaneous movements in each arm was calculated. The association between NIHSS (total and motor subset scores) and the magnitude of ICC was estimated by Spearman's rank correlation, receiver-operating characteristic curve analysis was performed and the optimal diagnostic threshold value of ICC was calculated. Results: The magnitude of the ICC was significantly associated with the baseline NIHSS score (p = 0.02) and non-significantly associated with the baseline NIHSS motor score (p = 0.08). At the optimal diagnostic threshold of ICC magnitude = 0.7, wireless accelerometry distinguished patients from controls with a sensitivity of 0.95, a specificity of 0.6 and a diagnostic odds ratio of 28.5. Conclusions: The wireless accelerometry system successfully detects a motor deficit in the setting of acute ischemic stroke, accurately differentiating patients from controls, and correlates well with the baseline NIHSS score. Its use is feasible in the acute stroke setting. Overall, it shows promise as a diagnostic tool to continuously monitor acute stroke patients but requires validation in a larger trial. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 06/2014; 37(5):336-341. DOI:10.1159/000360808 · 3.70 Impact Factor
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    ABSTRACT: Background and PurposeIn acute ischemic stroke perfusion/diffusion-weighted image, mismatch using magnetic resonance imaging approximates the ischemic penumbra. For early time windows, mismatch salvage improves clinical outcomes, but uncertainty exists at later time epochs. We hypothesized that (a) mismatch may exist up to 48 h; (b) the proportion of mismatch salvage is time independent; and (c) when salvaged, it improves clinical outcomes. Methods Magnetic resonance imaging was performed within 48 h of ischemic stroke. Perfusion-weighted image was defined by relative Tmax two-second delay. Perfusion/diffusion-weighted image mismatch was the perfusion-weighted image not overlapped by the diffusion-weighted image when coregistered. Infarct volume and disability (modified Rankin Score) were assessed at three-months. Mismatch salvage was the region not overlapped by final infarction. Favorable outcome was defined as modified Rankin Score 0–1. ResultsSixty-six patients were studied [mean age 69·9 years (standard deviation 13·1), initial median National Institute of Health Stroke Scale 9·0 (interquartile range 6·0, 18·3)]. There was no relationship between time of stroke onset and the proportion of mismatch salvaged (P = 0·73). Age (adjusted odds ratio = 0·92, 95% confidence interval 0·86–0·98, P = 0·01), initial National Institute of Health Stroke Scale (adjusted odds ratio = 0·80, 95% confidence interval 0·70–0·92, P < 0·01), mismatch volume (adjusted odds ratio = 0·98, 95% confidence interval 0·968–0·1, P = 0·05), and percentage of mismatch salvage (adjusted odds ratio = 1·04, 95% confidence interval 0·99–1·07, P = 0·05) were independently associated with favorable outcome. Conclusion Using coregistered perfusion/diffusion-weighted image criteria, mismatch persists up to 48 h post stroke. For the whole group, the proportion of mismatch salvage remains independent of time and, although the effect is small, its salvage is independently associated with improved clinical outcomes at three-months. Larger sample sizes are needed to determine the time limit for mismatch salvage.
    International Journal of Stroke 04/2014; DOI:10.1111/ijs.12203 · 4.03 Impact Factor
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    ABSTRACT: To determine symptoms, signs, and etiology of brain attacks in children presenting to the emergency department (ED) as a first step for developing a pediatric brain attack pathway. Prospective observational study of children aged 1 month to 18 years with brain attacks (defined as apparently abrupt-onset focal brain dysfunction) and ongoing symptoms or signs on arrival to the ED. Exclusion criteria included epilepsy, hydrocephalus, head trauma, and isolated headache. Etiology was determined after review of clinical data, neuroimaging, and other investigations. A random-effects meta-analysis of similar adult studies was compared with the current study. There were 287 children (46% male) with 301 presentations over 17 months. Thirty-five percent arrived by ambulance. Median symptom duration before arrival was 6 hours (interquartile range 2-28 hours). Median time from triage to medical assessment was 22 minutes (interquartile range 6-55 minutes). Common symptoms included headache (56%), vomiting (36%), focal weakness (35%), numbness (24%), visual disturbance (23%), seizures (21%), and altered consciousness (21%). Common signs included focal weakness (31%), numbness (13%), ataxia (10%), or speech disturbance (8%). Neuroimaging included CT imaging (30%), which was abnormal in 27%, and MRI (31%), which was abnormal in 62%. The most common diagnoses included migraine (28%), seizures (15%), Bell palsy (10%), stroke (7%), and conversion disorders (6%). Relative proportions of conditions in children significantly differed from adults for stroke, migraine, seizures, and conversion disorders. Brain attack etiologies differ from adults, with stroke being the fourth most common diagnosis. These findings will inform development of ED clinical pathways for pediatric brain attacks.
    Neurology 03/2014; 82(16). DOI:10.1212/WNL.0000000000000343 · 8.30 Impact Factor
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    ABSTRACT: Background. Sedentary behaviour is associated with health risks, independent of physical activity. This study aimed to investigate patterns of sedentary behaviour and physical activity among stroke survivors in rehabilitation hospitals. Methods. Stroke survivors admitted to four Swedish hospital-based rehabilitation units were recruited ≥7 days since stroke onset and their activity was measured using behavioural mapping. Sedentary behaviour was defined as lying down or sitting supported. Results. 104 patients were observed (53% men). Participants spent an average of 74% (standard deviation, SD 21%) of the observed day in sedentary activities. Continuous sedentary bouts of ≥1 hour represented 44% (SD 32%) of the observed day. A higher proportion (30%, SD 7%) of participants were physically active between 9:00 AM and 12:30 PM, compared to the rest of the observed day (23%, SD 6%, P < 0.0005). Patients had higher odds of being physically active in the hall (odds ratio, OR 1.7, P = 0.001) than in the therapy area. Conclusions. The time stroke survivors spend in stroke rehabilitation units may not be used in the most efficient way to promote maximal recovery. Interventions to promote reduced sedentary time could help improve outcome and these should be tested in clinical trials.
    03/2014; 2014:591897. DOI:10.1155/2014/591897
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    ABSTRACT: Stroke thrombolysis is highly time-critical, but data on long-term effects of small reductions in treatment delays have not been available. Our objective was to quantify patient lifetime benefits gained from faster treatment. Observational prospective data of consecutive stroke patients treated with intravenous thrombolysis in Australian and Finnish centers (1998-2011; n=2258) provided distributions of age, sex, stroke severity, onset-to-treatment times, and 3-month modified Rankin Scale in daily clinical practice. Treatment effects derived from a pooled analysis of thrombolysis trials were used to model the shift in 3-month modified Rankin Scale distributions with reducing treatment delays, from which we derived the expected lifetime and level of long-term disability with faster treatment. Each minute of onset-to-treatment time saved granted on average 1.8 days of extra healthy life (95% prediction interval, 0.9-2.7). Benefit was observed in all groups: each minute provided 0.6 day in old severe (age, 80 years; National Institutes of Health Stroke Scale [NIHSS] score, 20) patients, 0.9 day in old mild (age, 80 years; NIHSS score, 4) patients, 2.7 days in young mild (age, 50 years; NIHSS score, 4) patients, and 3.5 days in young severe (age, 50 years; NIHSS score, 20) patients. Women gained slightly more than men over their longer lifetimes. In the whole cohort, each 15 minute decrease in treatment delay provided an average equivalent of 1 month of additional disability-free life. Realistically achievable small reductions in stroke thrombolysis delays would result in significant and robust average health benefits over patients' lifetimes. The awareness of concrete importance of speed could promote practice change.
    Stroke 03/2014; 45(4). DOI:10.1161/STROKEAHA.113.002910 · 6.02 Impact Factor

Publication Stats

883 Citations
407.59 Total Impact Points

Institutions

  • 2011–2015
    • The Florey Institute of Neuroscience and Mental Health
      • Stroke Division
      Melbourne, Victoria, Australia
  • 2008–2014
    • University of Melbourne
      • Department of Mathematics and Statistics
      Melbourne, Victoria, Australia
  • 2013
    • La Trobe University
      • Department of Occupational Therapy
      Melbourne, Victoria, Australia
    • Victoria University Melbourne
      Melbourne, Victoria, Australia
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 2012
    • Neuroscience Research Australia
      Sydney, New South Wales, Australia
    • National Neuroscience Institute
      • Department of Neurology
      Singapore, Singapore
  • 2010
    • National Stroke Foundation
      Melbourne, Victoria, Australia
  • 1998–2008
    • Monash University (Australia)
      • School of Computer Science & Software Engineering
      Melbourne, Victoria, Australia
  • 2005–2006
    • University of Vic
      Vic, Catalonia, Spain