National Stroke Research Institute

Melbourne, Australia

National Stroke Research Institute

Melbourne, Australia
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Hommel M.,Joseph Fourier University | Carey L.,National Stroke Research Institute | Jaillard A.,Grenoble University Hospital Center
International Journal of Stroke | Year: 2015

Background: Poststroke depression and cognitive dysfunction are common and are independent predictors of poor recovery. Aims: We assessed whether and how depression and cognition were correlated in the subacute period after stroke. Method: We prospectively recruited 207 nondemented patients (Mini Mental State Examination≥23) presenting with a first-ever ischemic stroke (127 males), mean age of 48.5 years (16.4 standard deviation), median 12 days after infarction, as assessed on magnetic resonance imaging. We administered a comprehensive neuropsychological battery involving cognitive domains including instrumental functions, memory, executive functions, and working memory. Depression was quantified with the Beck Depression Inventory. Results: Depression (Beck Depression Inventory>9) was identified in 30.4% of the patients (95% confidence interval 24.2-37.2%). Median Beck Depression Inventory was 6. Median Mini Mental State Examination was 30. Cognitive dysfunctioning in at least one neuropsychological test was present in 89% (95% confidence interval 84-93%). Each point increase of Beck Depression Inventory was associated with an odd of 1.1 (95% confidence interval 1.04-1.19) of changing to a worse category of cognition. Stroke location was not correlated with depression. All cognitive domains were significantly correlated with depression. In multivariate analysis, the executive functions (P=0.001) and the working memory (P=0.009) were the best predictors of depression when adjusted for demographic and stroke characteristics. Conclusions: The rates of depression and cognitive impairment were in the range of previous stroke studies. Our study suggested a strong relation between depression and cognition characterized by executive functions and working memory dysfunctioning. © 2013 World Stroke Organization.


Pascoe M.C.,Swinburne University of Technology | Crewther S.G.,La Trobe University | Carey L.M.,National Stroke Research Institute | Crewther D.P.,Swinburne University of Technology
International Journal of Stroke | Year: 2011

Ischaemic stroke often precedes the appearance of clinical depression. Poststroke depression in turn influences the prognostic outcome. In the interest of advancing our understanding of the biological mechanisms underlying the development of poststroke depression, this systematic review explores the immunological processes driving the development of inflammation-related cell death in mood-related brain regions. Particular attention has been paid to cytokine-driven intrinsic apoptosis factors, including intracellular calcium, glutamate excitotoxicity and free radicals that appear in the brain following ischaemic damage and whose presence significantly increases the likelihood of clinically defined depression. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.4.2-1 | Award Amount: 14.96M | Year: 2012

The consortium led by UKER and EuroHYP, the European Stroke Research Network for Hypothermia, proposes a large, multicentre clinical trial which will assess mild hypothermia as a novel treatment for ischemic stroke. Stroke is the second cause of death world-wide and the second cause of lost disability-adjusted life years in high-income countries. Stroke incidence rises exponentially with age, so its social and economic burden will grow with the ageing of the European population. Current treatment options for the 80 to 85% of all strokes due to cerebral ischaemia - around. 900,000 events in Europe every year, or one every 40 seconds - are extremely limited. Systematic review of experimental studies suggests that hypothermia is the most promising intervention identified to date. Therapeutic cooling is effective in reducing ischaemic brain injury following cardiac arrest, and hypothermia is therefore considered by experts the most promising treatment for patients with acute ischaemic stroke, next to reperfusion strategies. The EuroHYP-1 trial is a pan-European, open, randomised, phase III clinical trial which will assess the benefit or harm of therapeutic cooling in 1500 awake adult patients with acute ischaemic stroke. In addition to efficacy and safety, the economic impact of therapeutic hypothermia will be assessed, along with several sub-studies involving imaging, ultrasound, and biomarker methods. The investigators involved in the EuroHYP-1 consortium are leading European experts in statistical design and analysis, therapeutic hypothermia, imaging, health economics, ultrasound, biomarkers, and trial execution (implementation and monitoring). Moreover in addition to these academic experts the consortium also involves European patient and family advocacy groups and small and medium-size enterprises, and the joint endeavours of this extended team will ensure the successful enrolment of patients at eighty hospitals across 25 countries in Europe.


Cadilhac D.A.,National Stroke Research Institute | Cadilhac D.A.,University of Melbourne | Hoffmann S.,National Stroke Foundation | Kilkenny M.,National Stroke Research Institute | And 5 more authors.
Stroke | Year: 2011

Background And Purpose- The benefits of chronic disease self-management programs for stroke survivors are uncertain because individuals with severe impairments have been excluded from previous research. We undertook a phase II randomized controlled trial to determine whether a self-management program designed for survivors (SSMP; 8 weeks) was safe and feasible compared to standard care (control) or a generic self-management program (generic; 6 weeks). Methods- Stroke survivors were recruited from 7 South Australian hospitals via a letter or indirectly (eg, newspapers). Eligible participants were randomized at a 1:1:1 ratio of 50 per group. Primary outcomes were recruitment, participation, and participant safety. Secondary outcomes were positive and active engagement in life using the Health Education Impact Questionnaire and characteristics of quality of life and mood at 6 months from program completion. Results- Of 315 people screened, 149 were eligible and 143 were randomized (48 SSMP, 47 generic, 48 control); mean age was 69 years (SD, 11) and 59% were female. Demographic features were similar between groups and 41% had severe cognitive impairment; 57% accessed the interventions, with 52% SSMP and 38% generic completing >50% of sessions (P=0.18). Thirty-two participants reported adverse events (7 control, 12 generic, 13 SSMP; P=0.3; 34% severe); however, none was attributable to the interventions. Potential benefits for improved mood were found. Conclusions- SSMP was safe and feasible. Benefits of the stroke-specific program over the generic program included greater participation and completion rates. An efficacy trial is warranted given the forecast growth in the stroke population and improved survival trends. © 2011 American Heart Association, Inc.


Langhorne P.,University of Glasgow | Stott D.,University of Glasgow | Knight A.,Royal Infirmary | Bernhardt J.,National Stroke Research Institute | And 2 more authors.
Cerebrovascular Diseases | Year: 2010

Background: Stroke patients are more likely to make a good recovery if they receive care in a well-organised stroke unit. However, there are uncertainties about how best to provide such care. We studied 2 key aspects of early stroke unit care: early active mobilisation (EM) and automated monitoring (AM) for physiological complications such as hypoxia. Methods: This was an observer-blinded, factorial (2 × 2) pilot randomised controlled trial recruiting stroke patients within 36 h of symptom onset. The patients were randomised to 1 of 4 nurse-led treatment protocols: (a) standard stroke unit care, (b) EM, (c) AM or (d) combined EM and AM. The primary outcome was the Rankin score at 3 months. We also report the data on feasibility and safety. Results: We randomised 32 patients (mean age = 65 years; mean baseline modified NIH score = 6). On unadjusted comparisons, the EM patients were significantly (p < 0.05) more likely to mobilise very early (within 1 h of randomisation) and to achieve walking by day 5 and were less likely to develop complications of immobility. The AM group was significantly (p < 0.05) more likely to have pre-defined physiological complication events detected. All these associations remained, but were less statistically significant, after correcting for age, baseline NIH score and co-interventions. There were no significant safety concerns. Discussion: We have demonstrated the feasibility of implementing EM and AM for physiological complications in a randomised controlled trial. Larger trials are warranted to determine whether these interventions have clinical benefits. Copyright © 2010 S. Karger AG, Basel.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: HEALTH.2013.4.1-4 | Award Amount: 557.48K | Year: 2013

Millions of Europeans still suffer the consequences of neurological disease, but the number of new drugs coming to market continues to fall. Reasons for the failure of stroke drug efficacy to translate from animals to clinical trials is probably best studied, but the problem is widespread. The economic and social costs of translational failure are substantial; a new approach to translational medicine is required. We propose the development of a capacity for multi-centre animal studies to address issues of limited validity; poor generalisability; and inadequate sample size. This will include central randomisation, outcome adjudication, and monitoring of laboratory practice; planned heterogeneity between sites to increase generalisability; and the capacity quickly to deliver large studies. Our data will be more reliable, reducing the need for further animal studies; and because clinical trials will be founded on better evidence the risk to participants will be lower. This idea has been broadly welcomed, and the next stage is to establish a framework within which this may be achieved. Our objective is to engage with all partners to build consensus around the feasibility, structure, composition and operation of multi-centre consortia. Issues include the role of industry and regulators; whether the capacity to deliver such studies exists; the statistical analysis to be used; and ethical, legal and governance issues. This consensus will be achieved through a series of themed meetings involving the applicants and others; the development of a detailed plan for such a consortium; and the validation of that plan with a specially constituted Scientific Advisory Board. We will then seek funding for the delivery of multi-centre animal studies based on this plan to allow its delivery. The applicants bring together substantial relevant expertise. This is a high-risk project, but the potential research, economic and health gains both in Europe and beyond are huge.


Carey L.,Florey Neuroscience Institutes | Carey L.,La Trobe University | Carey L.,National Stroke Research Institute | Macdonell R.,University of Melbourne | And 3 more authors.
Neurorehabilitation and Neural Repair | Year: 2011

Background. Sensory loss is common after stroke, with negative impact on exploration of the immediate environment, hand function, and return to daily activities. Objective. To compare the effectiveness of a perceptual-learning based sensory discrimination program versus non-specific exposure to sensory stimuli via passive movements and grasping of common objects. Methods. The authors conducted a randomized parallel-group controlled trial, with blinding of subjects, clinical assessors, and data analysts. Fifty subjects with impaired texture discrimination, limb position sense, and/or tactile object recognition (>6 weeks, median 48 weeks poststroke) were randomized to receive somatosensory discrimination training (n = 25) or repeated exposure to sensory stimuli (n = 25) in 60-minute sessions for a total of 10 hours. The primary outcome was change in a composite standardized somatosensory deficit (SSD) index following intervention. Follow-up was at 6 weeks and 6 months posttraining. Results. Between-group comparisons revealed a significantly greater improvement in sensory capacity following sensory discrimination training, t(47) = 2.75, P = .004, 1-tailed; mean between-group change = 11.1 SSD; confidence interval 3.0 to 19.2. Improvements were maintained at 6 weeks and 6 months. Conclusion. Sensory discrimination training can achieve significant improvements in functional sensory discrimination capacity after stroke. The clinically oriented training achieved transfer of training effects to novel stimuli. Our findings provide support for introducing SENSe discrimination training in rehabilitation of sensory deficits after stroke. © The Author(s) 2011.


Cumming T.B.,National Stroke Research Institute | Bernhardt J.,National Stroke Research Institute | Linden T.,Gothenburg University
Stroke | Year: 2011

Background and Purpose-Cognitive function is often ignored in stroke research trials. The brief Montreal Cognitive Assessment (MoCA) may be sensitive to stroke-related cognitive deficits. Methods-We evaluated the feasibility of administering the MoCA at 3 months in a large stroke trial (A Very Early Rehabilitation Trial [AVERT]). Results-Data (blinded to intervention group) are presented for 294 patients with mean age of 70.6 years (SD, 12.8); 220 (75%) completed the MoCA, 54 (18%) had missing data, and 20 (7%) had died. Of those surviving to 3 months, the MoCA was completed by 87% with mild stroke, 79% with moderate stroke, and 67% with severe stroke on admission. Mean MoCA score was 21.1 (SD 7.5) out of 30; only 78 of 220 (35%) patients attained the "normal" cutoff (26). Conclusions-The MoCA is a feasible global cognitive screening tool in stroke trials. © 2011 American Heart Association. All rights reserved.


Cumming T.B.,National Stroke Research Institute | Churilov L.,National Stroke Research Institute | Skoog I.,Gothenburg University | Blomstrand C.,Gothenburg University | Linden T.,Gothenburg University
Acta Psychiatrica Scandinavica | Year: 2010

Objective: It remains unclear whether mood depressive disorders after stroke have a distinct phenomenology. We evaluated the symptom profile of poststroke depression (PSD) and assessed whether somatic symptoms were reported disproportionately by stroke patients. Method: The sample was 149 stroke patients at 18 months poststroke and 745 age- and sex-matched general population controls. A comprehensive psychiatric interview was undertaken and depression was diagnosed according to DSM-III-R criteria. Results: Depressed controls reported more 'inability to feel' (P = 0.002) and 'disturbed sleep' (P = 0.008) than depressed stroke patients. Factor analysis of the 10 depressive symptoms identified two main factors, which appeared to represent somatic and psychological symptoms. There was no difference in scores on these two factors between stroke patients and controls. Conclusion: Phenomenology of depression at 18 months poststroke is broadly similar but not the same as that described by controls. Somatic symptoms of depression were not over-reported by stroke patients. © 2010 John Wiley & Sons A/S.


Randall M.,The Royal Childrens Hospital | Imms C.,La Trobe University | Carey L.,National Stroke Research Institute
Developmental Medicine and Child Neurology | Year: 2012

Aim This paper reports the second phase of a study to extend the Melbourne Assessment for use with children with neurological impairment aged 2 to 4years. The aim was to establish if (1) children's scores on the Modified Melbourne Assessment (MMA) and the Quality of Upper Extremity Skills Test (QUEST) showed a moderate to high, positive relation, (2) children had comparable behaviours for task and time demands on both tools, and (3) scores on the MMA could discriminate between children with mild, moderate, and severe levels of upper limb impairment. Method An observational study of 30 children (19 males, 11 females) with neurological impairment aged 2 to 4years. Twenty-four children had spasticity (20 with a unilateral and four with a bilateral impairment) and two children presented with athetosis, two with ataxia, and two with hypotonia. Results A high, positive relation was found between children's scores on the MMA and the QUEST (ρ=0.90; p=0.001). The clinical use of the MMA was comparable to the QUEST. MMA scores were able to discriminate between children's levels of upper limb impairment as determined by clinicians' ratings (F 2,27=67.76, p=0.001). Interpretation These findings suggest the MMA can be clinically useful for children as young as 2.5years and has the advantage of being valid for use with older children. Scores from the tool can also provide therapists with a quantitative means of consistently reporting level of upper limb impairment. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

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