2024 |
Postol N, Barton J, Wakely L, Bivard A, Spratt NJ, Marquez J, '"Are we there yet?" expectations and experiences with lower limb robotic exoskeletons: a qualitative evaluation of the therapist perspective.', Disabil Rehabil, 46 1023-1030 (2024) [C1]
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2024 |
Hasnain MG, Garcia-Esperon C, Tomari YK, Walker R, Saluja T, Rahman MM, et al., 'Bushfire-smoke trigger hospital admissions with cerebrovascular diseases: Evidence from 2019 20 bushfire in Australia', European Stroke Journal, [C1]
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2024 |
Tomari S, Chew BLA, Soans B, AI-Hadethi S, Ottavi T, Lillicrap T, et al., 'Role of cardiac computed tomography in hyperacute stroke assessment', Journal of Stroke and Cerebrovascular Diseases, 33 (2024) [C1]
Background: Incorporating cardiac CT with hyperacute stroke imaging may increase the yield for cardioembolic sources. It is not clarified whether stroke severity influences on rat... [more]
Background: Incorporating cardiac CT with hyperacute stroke imaging may increase the yield for cardioembolic sources. It is not clarified whether stroke severity influences on rates of intracardiac thrombus. We aimed to investigate a National Institutes of Health Stroke Scale (NIHSS) threshold below which acute cardiac CT was unnecessary. Methods: Consecutive patients with suspected stroke who underwent multimodal brain imaging and concurrent non-gated cardiac CT with delayed timing were prospectively recruited from 1st December 2020 to 30th November 2021. We performed receiver operating characteristics analysis of the NIHSS and intracardiac thrombus on hyperacute cardiac CT. Results: A total of 314 patients were assessed (median age 69 years, 61% male). Final diagnoses were ischemic stroke (n=205; 132 etiology-confirmed stroke, independent of cardiac CT and 73 cryptogenic), transient ischemic attack (TIA) (n=21) and stroke-mimic syndromes (n=88). The total yield of cardiac CT was 8 intracardiac thrombus and 1 dissection. Cardiac CT identified an intracardiac thrombus in 6 (4.5%) with etiology-confirmed stroke, 2 (2.7%) with cryptogenic stroke, and none in patients with TIA or stroke-mimic. All of those with intracardiac thrombus had NIHSS =4 and this was the threshold below which hyperacute cardiac CT was not justified (sensitivity 100%, specificity 38%, positive predictive value 4.0%, negative predictive value 100%). Conclusions: A cutoff NIHSS =4 may be useful to stratify patients for cardiac CT in the hyperacute stroke setting to optimize its diagnostic yield and reduce additional radiation exposure.
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2024 |
English C, Ramage ER, Attia J, Bernhardt J, Bonevski B, Burke M, et al., 'Secondary prevention of stroke. A telehealth-delivered physical activity and diet pilot randomized trial (ENAbLE-pilot).', Int J Stroke, 19 199-208 (2024) [C1]
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2023 |
Chew BLA, Garcia-Esperon C, Dunkerton S, Spratt NJ, 'Pilot experience using a portable electrocardiography device for atrial fibrillation detection in an outpatient stroke clinic', AUSTRALIAN JOURNAL OF RURAL HEALTH, 31 587-588 (2023)
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2023 |
Garcia-Esperon C, Ostman C, Walker FR, Chew BLA, Edwards S, Emery J, et al., 'The Hunter-8 Scale Prehospital Triage Workflow for Identification of Large Vessel Occlusion and Brain Haemorrhage', PREHOSPITAL EMERGENCY CARE, [C1]
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2023 |
Dunphy H, Garcia-Esperon C, Hong JB, Manoczki C, Wilson D, Chew BLA, et al., 'Endovascular thrombectomy for acute ischaemic stroke improves and maintains function in the very elderly: A multicentre propensity score matched analysis', EUROPEAN STROKE JOURNAL, 8 191-198 (2023) [C1]
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2023 |
Kenah K, Bernhardt J, Spratt NJ, Oldmeadow C, Janssen H, 'Depression and a lack of socialization are associated with high levels of boredom during stroke rehabilitation: An exploratory study using a new conceptual framework', NEUROPSYCHOLOGICAL REHABILITATION, 33 497-527 (2023) [C1]
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2023 |
Garcia-Esperon C, Bivard A, Johns H, Chen C, Churilov L, Lin L, Butcher K, 'Association of Endovascular Thrombectomy With Functional Outcome in Patients With Acute Stroke With a Large Ischemic Core', NEUROLOGY, 100 (2023)
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2023 |
Garcia-Esperon C, Wu TY, Carraro do Nascimento V, Yan B, Kurunawai C, Kleinig T, et al., 'Ultra-Long Transfers for Endovascular Thrombectomy-Mission Impossible?: The Australia-New Zealand Experience.', Stroke, 54 151-158 (2023) [C1]
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2023 |
Warren KE, Coupland KG, Hood RJ, Kang L, Walker FR, Spratt NJ, 'Movement of cerebrospinal fluid tracer into brain parenchyma and outflow to nasal mucosa is reduced at 24 h but not 2 weeks post-stroke in mice', Fluids and Barriers of the CNS, 20 (2023) [C1]
Background: Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24... [more]
Background: Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24¿h after experimental stroke and that this reduces blood flow to ischaemic tissue. CSF outflow resistance is increased at this time point. We hypothesised that reduced transit of CSF through brain parenchyma and reduced outflow of CSF via the cribriform plate at 24¿h after stroke may contribute to the previously identified post-stroke intracranial pressure elevation. Methods: Using a photothrombotic permanent occlusion model of stroke in C57BL/6 adult male mice, we examined the movement of an intracisternally infused 0.5% Texas Red dextran throughout the brain and measured tracer efflux into the nasal mucosa via the cribriform plate at 24¿h or two weeks after stroke. Brain tissue and nasal mucosa were collected ex vivo and imaged using fluorescent microscopy to determine the change in CSF tracer intensity in these tissues. Results: At 24¿h after stroke, we found that CSF tracer load was significantly reduced in brain tissue from stroke animals in both the ipsilateral and contralateral hemispheres when compared to sham. CSF tracer load was also reduced in the lateral region of the ipsilateral hemisphere when compared to the contralateral hemisphere in stroke brains. In addition, we identified an 81% reduction in CSF tracer load in the nasal mucosa in stroke animals compared to sham. These alterations to the movement of CSF-borne tracer were not present at two weeks after stroke. Conclusions: Our data indicates that influx of CSF into the brain tissue and efflux via the cribriform plate are reduced 24¿h after stroke. This may contribute to reported increases in intracranial pressure at 24¿h after stroke and thus worsen stroke outcomes.
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2023 |
Woods AG, Lillicrap T, Hood R, Fletcher JW, Ranhage V, Larsson E, et al., 'Blood Pressure Variability Is Associated with Infarct Growth in Acute Ischaemic Stroke', Cerebrovascular Diseases, (2023) [C1]
Introduction: Evidence-based blood pressure (BP) targets in acute ischaemic stroke are lacking. Previous observational studies have focused on single baseline BP and clinical outc... [more]
Introduction: Evidence-based blood pressure (BP) targets in acute ischaemic stroke are lacking. Previous observational studies have focused on single baseline BP and clinical outcomes, without consideration for dynamic changes. We aim to determine the association between BP parameters including variability, peak, nadir, median and mean during stroke and infarct growth (primary outcome), risk of haemorrhagic transformation, and functional outcome (secondary outcomes). Methods: Suspected stroke patients were prospectively recruited from a single comprehensive stroke centre. Multimodal computed tomography imaging was used to define infarct core. BP was recorded as per national stroke guidelines during the initial 24 h. Infarct growth and evidence of parenchymal haemorrhage were determined by follow-up magnetic resonance imaging at 24 h. Functional outcome at 3 months was assessed using the modified Rankin Scale. Subgroup analysis was performed according to stroke aetiology and treatment for the association between BP, infarct volume growth, and risk of haemorrhagic transformation. The association between BP parameters and outcomes were determined using regression modelling. Results: A total of 229 patients were included in this study. The median age was 67.4, 64.4% were male, and the baseline National Institutes of Health Stroke Scale was 8. BP variability (BPV) was independently associated with increased infarct growth (multivariate coefficient 1.60, 95% CI: 0.27¿2.94, p = 0.19) and an increased odds of parenchymal haemorrhage (adjusted OR 1.21, 95% CI: 1.02¿1.44, p = 0.028). The odds of a favourable outcome at 90 days were inversely associated with BPV on simple, but not adjusted logistic regression. On subgroup analysis, only in patients with large vessel occlusions, undergoing endovascular clot retrieval, was BPV associated with infarct growth (multivariate-adjusted coefficient 2.62, 95% CI: 0.53¿4.70, p = 0.014) and an increased odds of haemorrhagic transformation (adjusted OR 1.26, 95% CI: 1.01¿1.57, p = 0.045). Conclusion: An increase in BPV was associated with infarct expansion, increased risk of haemorrhagic transformation and was negatively associated with favourable functional outcomes at 3 months.
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2023 |
Kenah K, Tavener M, Bernhardt J, Spratt NJ, Janssen H, '"Wasting time": a qualitative study of stroke survivors' experiences of boredom in non-therapy time during inpatient rehabilitation.', Disability and rehabilitation, 1-9 (2023) [C1]
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2023 |
Hasnain MG, Garcia-Esperon C, Tomari YK, Walker R, Saluja T, Rahman MM, et al., 'Effect of short-term exposure to air pollution on daily cardio- and cerebrovascular hospitalisations in areas with a low level of air pollution', ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH, 30 102438-102445 (2023)
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2023 |
Bull NJ, Honan B, Spratt NJ, Quilty S, 'A method for rapid machine learning development for data mining with doctor-in-the-loop.', PLoS One, 18 e0284965 (2023) [C1]
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2023 |
Bivard A, Garcia-Esperon C, Churilov L, Spratt N, Russell M, Campbell BC, et al., 'Tenecteplase versus alteplase for stroke thrombolysis evaluation (TASTE): A multicentre, prospective, randomized, open-label, blinded-endpoint, controlled phase III non-inferiority trial protocol', INTERNATIONAL JOURNAL OF STROKE, 18 751-756 (2023)
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2023 |
Gyawali P, Lillicrap TP, Esperon CG, Bhattarai A, Bivard A, Spratt N, 'Whole Blood Viscosity and Cerebral Blood Flow in Acute Ischemic Stroke.', Semin Thromb Hemost, (2023) [C1]
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2023 |
Tomari S, Lillicrap T, Garcia-Esperon C, Kashida YT, Bivard A, Lin L, et al., 'Ischemic Lesion Growth in Patients with a Persistent Target Mismatch After Large Vessel Occlusion', Clinical Neuroradiology, 33 41-48 (2023) [C1]
Background: Failure to reperfuse a¿cerebral occlusion resulting in a¿persistent penumbral pattern has not been fully described. Methods: We retrospectively reviewed patients with ... [more]
Background: Failure to reperfuse a¿cerebral occlusion resulting in a¿persistent penumbral pattern has not been fully described. Methods: We retrospectively reviewed patients with anterior large vessel occlusion who did not receive reperfusion, and underwent repeated perfusion imaging, with baseline imaging <¿6¿h after onset and follow-up scans from 16¿168¿h. A¿persistent target mismatch (PTM) was defined as core volume of <¿100¿mL, mismatch ratio >¿1.2, and mismatch volume >¿10¿mL on follow-up imaging. Patients were divided into PTM or non-PTM groups. Ischemic core and penumbral volumes were compared between baseline and follow-up imaging between the two groups, and collateral flow status assessed using CT perfusion collateral index. Results: A total of 25 patients (14¿PTM and 11¿non-PTM) were enrolled in the study. Median core volumes increased slightly in the PTM group, from 22 to 36¿ml. There was a¿much greater increase in the non-PTM group, from 57 to 190¿ml. Penumbral volumes were stable in the PTM group from a¿median of 79¿ml at baseline to 88¿ml at follow-up, whereas penumbra was reduced in the non-PTM group, from 120 to 0¿ml. Collateral flow status was also better in the PTM group and the median collateral index was 33% compared with 44% in the non-PTM group (p¿= 0.043). Conclusion: Multiple patients were identified with limited core growth and large penumbra (persistent target mismatch) >¿16¿h after stroke onset, likely due to more favorable collateral flow.
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2023 |
Werdiger F, Parsons MW, Visser M, Levi C, Spratt N, Kleinig T, et al., 'Machine learning segmentation of core and penumbra from acute stroke CT perfusion data', Frontiers in Neurology, 14 (2023) [C1]
Introduction: Computed tomography perfusion (CTP) imaging is widely used in cases of suspected acute ischemic stroke to positively identify ischemia and assess suitability for tre... [more]
Introduction: Computed tomography perfusion (CTP) imaging is widely used in cases of suspected acute ischemic stroke to positively identify ischemia and assess suitability for treatment through identification of reversible and irreversible tissue injury. Traditionally, this has been done via setting single perfusion thresholds on two or four CTP parameter maps. We present an alternative model for the estimation of tissue fate using multiple perfusion measures simultaneously. Methods: We used machine learning (ML) models based on four different algorithms, combining four CTP measures (cerebral blood flow, cerebral blood volume, mean transit time and delay time) plus 3D-neighborhood (patch) analysis to predict the acute ischemic core and perfusion lesion volumes. The model was developed using 86 patient images, and then tested further on 22 images. Results: XGBoost was the highest-performing algorithm. With standard threshold-based core and penumbra measures as the reference, the model demonstrated moderate agreement in segmenting core and penumbra on test images. Dice similarity coefficients for core and penumbra were 0.38 ± 0.26 and 0.50 ± 0.21, respectively, demonstrating moderate agreement. Skull-related image artefacts contributed to lower accuracy. Discussion: Further development may enable us to move beyond the current overly simplistic core and penumbra definitions using single thresholds where a single error or artefact may lead to substantial error.
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2023 |
Karimi-Haghighi S, Pandamooz S, Jurek B, Fattahi S, Safari A, Azarpira N, et al., 'From Hair to the Brain: The Short-Term Therapeutic Potential of Human Hair Follicle-Derived Stem Cells and Their Conditioned Medium in a Rat Model of Stroke.', Mol Neurobiol, 60 2587-2601 (2023) [C1]
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2023 |
Maltby S, Garcia-Esperon C, Jackson K, Butcher K, Evans JW, O'Brien W, et al., 'TACTICS VR Stroke Telehealth Virtual Reality Training for Health Care Professionals Involved in Stroke Management at Telestroke Spoke Hospitals: Module Design and Implementation Study.', JMIR Serious Games, 11 e43416 (2023) [C1]
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2023 |
Hasnain MG, Garcia-Esperon C, Tomari YK, Walker R, Saluja T, Rahman MM, et al., 'Effect of short-term exposure to air pollution on daily cardio- and cerebrovascular hospitalisations in areas with a low level of air pollution.', Environ Sci Pollut Res Int, 30 102438-102445 (2023) [C1]
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2023 |
van de Munckhof A, Borhani-Haghighi A, Aaron S, Krzywicka K, van Kammen MS, Cordonnier C, et al., 'Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries', International Journal of Stroke, 18 1112-1120 (2023) [C1]
Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vacci... [more]
Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20¿37) versus 47 (IQR 32¿58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11¿40]) than in HICs (44/102 [43%, 95% CI 34¿53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.
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2023 |
Lin L, Zhang H, Liu F, Chen C, Chen C, Bivard A, et al., 'Bridging Thrombolysis Before Endovascular Therapy in Stroke Patients With Faster Core Growth.', Neurology, 100 e2083-e2092 (2023) [C1]
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2022 |
Alemseged F, Rocco A, Arba F, Schwabova JP, Wu T, Cavicchia L, et al., 'Posterior National Institutes of Health Stroke Scale Improves Prognostic Accuracy in Posterior Circulation Stroke', Stroke, 53 1247-1255 (2022) [C1]
Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) underestimates clinical severity in posterior circulation stroke and patients presenting with low NI... [more]
Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) underestimates clinical severity in posterior circulation stroke and patients presenting with low NIHSS may be considered ineligible for reperfusion therapies. This study aimed to develop a modified version of the NIHSS, the Posterior NIHSS (POST-NIHSS), to improve NIHSS prognostic accuracy for posterior circulation stroke patients with mild-moderate symptoms. Methods: Clinical data of consecutive posterior circulation stroke patients with mild-moderate symptoms (NIHSS <10), who were conservatively managed, were retrospectively analyzed from the Basilar Artery Treatment and Management registry. Clinical features were assessed within 24 hours of symptom onset; dysphagia was assessed by a speech therapist within 48 hours of symptom onset. Random forest classification algorithm and constrained optimization were used to develop the POST-NIHSS in the derivation cohort. The POST-NIHSS was then validated in a prospective cohort. Poor outcome was defined as modified Rankin Scale score =3 at 3 months. Results: We included 202 patients (mean [SD] age 63 [14] years, median NIHSS 3 [interquartile range, 1-5]) in the derivation cohort and 65 patients (mean [SD] age 63 [16] years, median NIHSS 2 [interquartile range, 1-4]) in the validation cohort. In the derivation cohort, age, NIHSS, abnormal cough, dysphagia and gait/truncal ataxia were ranked as the most important predictors of functional outcome. POST-NIHSS was calculated by adding 5 points for abnormal cough, 4 points for dysphagia, and 3 points for gait/truncal ataxia to the baseline NIHSS. In receiver operating characteristic analysis adjusted for age, POST-NIHSS area under receiver operating characteristic curve was 0.80 (95% CI, 0.73-0.87) versus NIHSS area under receiver operating characteristic curve, 0.73 (95% CI, 0.64-0.83), P=0.03. In the validation cohort, POST-NIHSS area under receiver operating characteristic curve was 0.82 (95% CI, 0.69-0.94) versus NIHSS area under receiver operating characteristic curve 0.73 (95% CI, 0.58-0.87), P=0.04. Conclusions: POST-NIHSS showed higher prognostic accuracy than NIHSS and may be useful to identify posterior circulation stroke patients with NIHSS <10 at higher risk of poor outcome.
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2022 |
Vasaghi Gharamaleki M, Habibagahi M, Hooshmandi E, Tabrizi R, Arsang-Jang S, Barzegar Z, et al., 'The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study', Journal of Stroke and Cerebrovascular Diseases, 31 (2022) [C1]
Objectives: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare th... [more]
Objectives: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). Materials and methods: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. Results: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients > 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score =3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P<0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. Conclusion: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended.
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2022 |
Gangadharan S, Tomari S, Levi CR, Weaver N, Holliday E, Bajorek B, et al., 'Rural versus metropolitan comparison of processes of care in the community-based management of TIA and minor stroke in Australia (an analysis from the INSIST study)', AUSTRALIAN JOURNAL OF RURAL HEALTH, (2022) [C1]
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2022 |
Guillaumier A, Spratt N, Pollack M, Baker A, Magin P, Turner A, et al., 'Evaluation of an online intervention for improving stroke survivors' health-related quality of life: A randomised controlled trial', PLOS MEDICINE, 19 (2022) [C1]
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2022 |
Hinwood M, Nyberg J, Leigh L, Gustavsson S, Attia J, Oldmeadow C, et al., 'Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries', BMJ Open, (2022)
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2022 |
Arora K, Gaekwad A, Evans J, O'Brien W, Ang T, Garcia-Esperon C, et al., 'Diagnostic Utility of Computed Tomography Perfusion in the Telestroke Setting', STROKE, 53 2917-2925 (2022) [C1]
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2022 |
Rostamihosseinkhani M, Hooshmandi E, Ostovan VR, Bazrafshan H, Bahrami Z, Borhani-Haghighi A, et al., 'True Mycotic Aneurysms: A Report of Three Patients with Internal Carotid Artery Aneurysm and Mucormycosis and Literature Review', Shiraz E Medical Journal, 23 (2022)
Introduction: Aneurysm formation of internal carotid arteries (ICA) in patients with mucormycosis is a scarce phenomenon. How-ever, the prevalence of rhino-cerebral mucormycosis h... [more]
Introduction: Aneurysm formation of internal carotid arteries (ICA) in patients with mucormycosis is a scarce phenomenon. How-ever, the prevalence of rhino-cerebral mucormycosis has been reported to increase after the Coronavirus disease 2019 (COVID-19) pandemic. Case Presentation: Three patients with stroke and subarachnoid hemorrhage presented due to ICA aneurysm after the involvement of adjacent paranasal sinuses (PNS) with mucormycosis. They had a history of diabetes and corticosteroid use. Also, one of them was treated with imatinib. Two out of the three patients were infected with SARS-CoV-2 before developing mucormycosis. Two patients had diagnostic angiography before endovascular intervention. One patient did not undergo any therapeutic intervention due to total artery occlusion, whereas the other patient experienced a successful parent artery occlusion by coiling and only survived this patient. Although all patients received antifungal treatment and surgical debridement, two of them died. Conclusions: In patients with rhino-cerebral mucormycosis, aneurysm evolution should be promptly and meticulously investigated by Magnetic Resonance Angiography (MRA) and Computed Tomography Angiography (CTA). As this type of aneurysm is very fast-growing, as soon as the involvement of the sphenoid sinus is detected, the possibility of ICA aneurysm formation should always be kept in mind. If the patient develops an aneurysm, prompt intensive antifungal therapy and therapeutic endovascular interven-tions such as stenting, coiling, or sacrificing should be considered as soon as possible to optimize outcomes.
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2022 |
Mitchell PJ, Yan B, Churilov L, Dowling RJ, Bush SJ, Bivard A, et al., 'Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial', The Lancet, 400 116-125 (2022) [C1]
Background: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusi... [more]
Background: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy). Methods: DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0¿2 or return to baseline at 90 days, with a non-inferiority margin of ¿0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants. Findings: Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference ¿0·051, two-sided 95% CI ¿0·160 to 0·059; per-protocol risk difference ¿0·062, two-sided 95% CI ¿0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22¿13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46¿1·84). Interpretation: We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment. Funding: Australian National Health and Medical Research Council and Stryker USA.
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2022 |
Janssen H, Bird M-L, Luker J, Sellar B, Berndt A, Ashby S, et al., 'Impairments, and physical design and culture of a rehabilitation unit influence stroke survivor activity: qualitative analysis of rehabilitation staff perceptions.', Disabil Rehabil, 44 8436-8441 (2022) [C1]
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2022 |
Arora K, Gaekwad A, Evans J, O'Brien W, Ang T, Garcia-Esperon C, et al., 'Diagnostic Utility of Computed Tomography Perfusion in the Telestroke Setting (vol 53, pg 2917, 2022)', STROKE, 53 E439-E439 (2022)
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2022 |
Janssen H, Bird ML, Luker J, McCluskey A, Blennerhassett J, Ada L, et al., 'Stroke survivors perceptions of the factors that influence engagement in activity outside dedicated therapy sessions in a rehabilitation unit: A qualitative study', Clinical Rehabilitation, 36 822-830 (2022) [C1]
Objective: To investigate stroke survivors¿ perceptions of factors influencing their engagement in activity outside of dedicated therapy sessions during inpatient rehabilitation. ... [more]
Objective: To investigate stroke survivors¿ perceptions of factors influencing their engagement in activity outside of dedicated therapy sessions during inpatient rehabilitation. Design: Qualitative study. Setting: Four metropolitan rehabilitation units in Australia. Participants: People undertaking inpatient rehabilitation after stroke. Methods: Semi-structured interviews conducted in person by a speech pathologist A stepped iterative process of inductive analysis was employed until data saturation was achieved with themes then applied against the three domains of the Theory of Planned Behaviour (perceived behavioural control, social norms and attitude). Results: Interviews of 33 stroke survivors (60% female, median age of 73 years) revealed five themes (i) uncertainty about how to navigate and what was available for use in the rehabilitation unit restricts activity and (ii) post-stroke mobility, fatigue and pre- and post-stroke communication impairments restrict activity (perceived behavioural control); (iii) unit set up, rules (perceived and actual) and staff expectations influence activity and (iv) visiting family and friends are strong facilitators of activity (social norms), and (v) personal preferences and mood influence level of activity (attitude). Conclusion: At the individual level, stroke survivors perceived that their ability to be active outside of dedicated therapy sessions was influenced by their impairments, including mood, and their attitude towards and preference for activity. At the ward level, stroke survivors perceived that their ability to be active was influenced by ward set-up, rules and staff expectations. Visitors were perceived to be important facilitators of activity outside of therapy sessions.
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Nova |
2022 |
Ostman C, Garcia-Esperon C, Lillicrap T, Alanati K, Chew BLA, Pedler J, et al., 'Comparison of two pre-hospital stroke scales to detect large vessel occlusion strokes in Australia: A prospective observational study', Australasian Journal of Paramedicine, 19 (2022) [C1]
Aims: Hunter-8 and ACT-FAST are two stroke scales used in Australia for the pre-hospital identification of large vessel occlusion (LVO) stroke, but they have not previously been c... [more]
Aims: Hunter-8 and ACT-FAST are two stroke scales used in Australia for the pre-hospital identification of large vessel occlusion (LVO) stroke, but they have not previously been compared. Moreover, their use in identifying distal arterial occlusions has not previously been assessed. We therefore aimed to describe the area under the receiver operating curve (AUC) of Hunter-8 versus ACT-FAST for the detection of LVO stroke. Methods: Both scales were performed on consecutive patients presenting with stroke-like symptoms within 24 hours of symptom onset presenting to the emergency department at a tertiary referral hospital between June 2018 and January 2019. The AUC of Hunter-8 and ACT-FAST was calculated for the detection of LVO using different definitions (classic LVO ¿ proximal segment of the middle cerebral artery (MCA-M1), terminal internal carotid artery (T-ICA) or tandem occlusions ¿ and extended LVO ¿ classic LVO plus proximal MCA-M2 and basilar occlusions). Results: Of 126 suspected stroke patients, there were 24 classic LVO and 34 extended LVO. For detection of classic LVO, Hunter-8 had an AUC of 0.79 and ACT-FAST had an AUC of 0.77. For extended LVO, the AUC was 0.71 and 0.70 respectively. The AUC for the subgroup of patients with MCA-M2 and basilar occlusions was 0.42 and 0.43 respectively. Conclusion: Both scales represent a significant opportunity to identify patients with proven potential benefit from thrombectomy (classic LVO), however M2 and basilar occlusions may be more challenging to identify with these scales.
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Nova |
2022 |
Garcia-Esperon C, Chew BLA, Minett F, Cheah J, Rutherford J, Wilsmore B, et al., 'Impact of an outpatient telestroke clinic on management of rural stroke patients', AUSTRALIAN JOURNAL OF RURAL HEALTH, 30 337-342 (2022) [C1]
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Nova |
2022 |
Garcia-Esperon C, Bivard A, Johns H, Chen C, Churilov L, Lin L, et al., 'Association of Endovascular Thrombectomy With Functional Outcome in Patients With Acute Stroke With a Large Ischemic Core.', Neurology, 99 e1345-e1355 (2022) [C1]
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Nova |
2022 |
Gyawali P, Lillicrap TP, Tomari S, Bivard A, Holliday E, Parsons M, et al., 'Whole blood viscosity is associated with baseline cerebral perfusion in acute ischemic stroke', Neurological Sciences, 43 2375-2381 (2022) [C1]
Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk... [more]
Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2¿h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke.
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Nova |
2022 |
Ryan A, Paul CL, Cox M, Whalen O, Bivard A, Attia J, et al., 'TACTICS-Trial of Advanced CT Imaging and Combined Education Support for Drip and Ship: evaluating the effectiveness of an 'implementation intervention' in providing better patient access to reperfusion therapies: protocol for a non-randomised controlled stepped wedge cluster trial in acute stroke', BMJ OPEN, 12 (2022)
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2022 |
Maltby S, Garcia-Esperon C, Jackson K, Butcher K, Evans JW, O'Brien W, et al., 'TACTICS VR Stroke Telehealth Virtual Reality Training for Health Care Professionals Involved in Stroke Management at Telestroke Spoke Hospitals: Module Design and Implementation Study (Preprint) (2022)
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2022 |
Kashida YT, Lillicrap T, Walker R, Holliday E, Hasnain MG, Tomari S, et al., 'Transition in Incidence Rate of Hospitalised Stroke and Case Fatality Rate in the Hunter Region, Australia, 2001-2019: A Prospective Hospital-Based Study: 19-year trend of stroke hospitalisation in Australia', Journal of Stroke and Cerebrovascular Diseases, 31 (2022) [C1]
Introduction: Continuous surveillance of stroke admissions has been conducted in the Hunter region, Australia, over the past two decades. We aimed to describe the trends in incide... [more]
Introduction: Continuous surveillance of stroke admissions has been conducted in the Hunter region, Australia, over the past two decades. We aimed to describe the trends in incidence rates of hospitalised stroke and case-fatality rates in this region, 2001-2019. Methods: From a hospital-based stroke registry, data for admitted adult stroke patients residing in the Hunter region were collected using ICD-10 codes for ischemic and haemorrhagic stroke. Negative binomial regression and logistic regression analysis were used to analyse trends for age-standardised and age-specific incidence rates of hospitalised stroke and 28-day case-fatality rates. Results: A total of 14,662 hospitalisations for stroke in 13,242 individuals were registered. The age-standardised incidence rate declined from 123 per 100,000 population in the 2001-2005 epoch to 96 in the 2016-2019 epoch (mean annual change -2.0%, incidence rate ratio (IRR) = 0.980 [95%CI: 0.976-0.984]). Age-specific analyses identified significant reduction in the group aged 75-84 (1039 per 100,000 population in 2001-2005 to 633 in 2016-2019, annual change -3.5%, IRR= 0.965 [95%CI: 0.960-0.970]). The 28-day case-fatality rates fluctuated over time (18.5% in 2001-2005, 20.8% in 2010-2015, and 17.8% in 2016-2019). Projected population aging suggests annual volume of patients with new stroke will increase by 77% by 2041 if incidence rates remain unchanged at the 2016-2019 level. Conclusion: Although age-standardised hospitalised stroke incidence rates have declined in the Hunter region, the health system will face an increase in stroke hospitalisations related to the aging population.
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Nova |
2022 |
Janssen H, Ada L, Middleton S, Pollack M, Nilsson M, Churilov L, et al., 'Altering the rehabilitation environment to improve stroke survivor activity: A Phase II trial', International Journal of Stroke, 17 299-307 (2022) [C1]
Background: Environmental enrichment involves organization of the environment and provision of equipment to facilitate engagement in physical, cognitive, and social activities. In... [more]
Background: Environmental enrichment involves organization of the environment and provision of equipment to facilitate engagement in physical, cognitive, and social activities. In animals with stroke, it promotes brain plasticity and recovery. Aims: To assess the feasibility and safety of a patient-driven model of environmental enrichment incorporating access to communal and individual environmental enrichment. Methods: A nonrandomized cluster trial with blinded measurement involving people with stroke (n = 193) in four rehabilitation units was carried out. Feasibility was operationalized as activity 10 days after admission to rehabilitation and availability of environmental enrichment. Safety was measured as falls and serious adverse events. Benefit was measured as clinical outcomes at three months, by an assessor blinded to group. Results: The experimental group (n = 91) spent 7% (95% CI -14 to 0) less time inactive, 9% (95% CI 0¿19) more time physically, and 6% (95% CI 2¿10) more time socially active than the control group (n = 102). Communal environmental enrichment was available 100% of the time, but individual environmental enrichment was rarely within reach (24%) or sight (39%). There were no between-group differences in serious adverse events or falls at discharge or three months or in clinical outcomes at three months. Conclusions: This patient-driven model of environmental enrichment was feasible and safe. However, the very modest increase in activity by people with stroke, and the lack of benefit in clinical outcomes three months after stroke do not provide justification for an efficacy trial.
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Nova |
2022 |
Yassi N, Zhao H, Churilov L, Campbell BC, Wu T, Ma H, et al., 'Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial', STROKE AND VASCULAR NEUROLOGY, 7 158-165 (2022)
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2022 |
Denham AMJ, Wynne O, Baker AL, Spratt NJ, Loh M, Turner A, et al., 'The long-term unmet needs of informal carers of stroke survivors at home: a systematic review of qualitative and quantitative studies', Disability and Rehabilitation, 44 1-12 (2022) [C1]
Aim: To synthesise research describing the long-term unmet needs of carers who are providing care to a stroke survivor at home who is at least 3¿months post-discharge. Methods: A ... [more]
Aim: To synthesise research describing the long-term unmet needs of carers who are providing care to a stroke survivor at home who is at least 3¿months post-discharge. Methods: A systematic review with a narrative synthesis of the English-language qualitative and quantitative studies identified from MEDLINE, CINAHL, PsycINFO, EMBASE, AMED, and Scopus was undertaken. Results: Five quantitative studies, seven qualitative studies, and one mixed-method study were included in the review. Five themes of unmet needs were identified from the synthesis: (1) Obtaining adequate information, (2) Taking care of oneself, (3) Service accessibility, (4) Emotional and psychological, and (5) Relationship. Commonly reported needs across the 13 final studies included the need for support from health care and/or service providers, help with self-care, and help with coping and managing emotions. Variables associated with unmet needs included the severity of the stroke that the stroke survivor experienced and the length of hospital stay. Conclusions: Evidence from this review suggests that carers are experiencing a range of long-term unmet needs, particularly in education and training, coping and managing their own emotions, and accessing much-needed services. Recommendations to support carers at home include continuing engagement, assessment, and support from health care providers and services to meet the needs of carers throughout the stroke recovery process.IMPLICATIONS FOR REHABILITATION Carers of stroke survivors experience complex long-term unmet needs around managing the recovery process of the stroke survivor when they have been discharged from hospital and returned home. Evidence suggests that continuing engagement and support from health care providers and services may assist carers in meeting their unmet needs. Healthcare professionals should provide help in accessing training and services. Support is required to help carers cope and to manage their emotions.
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Nova |
2021 |
Tomari S, Levi C, Lasserson D, Quain D, Valderas J, Dewey H, et al., 'One-year risk of stroke after transient ischemic attack or minor stroke in Hunter New England, Australia (INSIST study)', AUSTRALIAN JOURNAL OF PRIMARY HEALTH, 27 LII-LII (2021)
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2021 |
Garcia-Esperon C, Visser M, Churilov L, Miteff F, Bivard A, Lillicrap T, et al., 'Role of Computed Tomography Perfusion in Identification of Acute Lacunar Stroke Syndromes', STROKE, 52 339-343 (2021) [C1]
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Nova |
2021 |
Lin L, Zhang H, Chen C, Bivard A, Butcher K, Garcia-Esperon C, et al., 'Stroke Patients With Faster Core Growth Have Greater Benefit From Endovascular Therapy', STROKE, 52 3998-4006 (2021) [C1]
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Nova |
2021 |
Kashida YT, Garcia-Esperon C, Lillicrap T, Miteff F, Garcia-Bermejo P, Gangadharan S, et al., 'The Need for Structured Strategies to Improve Stroke Care in a Rural Telestroke Network in Northern New South Wales, Australia: An Observational Study', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Hood RJ, Maltby S, Keynes A, Kluge MG, Nalivaiko E, Ryan A, et al., 'Development and Pilot Implementation of TACTICS VR: A Virtual Reality-Based Stroke Management Workflow Training Application and Training Framework', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Gao L, Bivard A, Parsons M, Spratt NJ, Levi C, Butcher K, et al., 'Real-World Cost-Effectiveness of Late Time Window Thrombectomy for Patients With Ischemic Stroke', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Postol N, Spratt NJ, Bivard A, Marquez J, 'Physiotherapy using a free-standing robotic exoskeleton for patients with spinal cord injury: a feasibility study', JOURNAL OF NEUROENGINEERING AND REHABILITATION, 18 (2021) [C1]
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Nova |
2021 |
Postol N, Grissell J, McHugh C, Bivard A, Spratt NJ, Marquez J, 'Effects of therapy with a free-standing robotic exoskeleton on motor function and other health indicators in people with severe mobility impairment due to chronic stroke: A quasi-controlled study.', Journal of Rehabilitation and Assistive Technologies Engineering, 8 1-13 (2021) [C1]
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Nova |
2021 |
Lin L, Yang J, Chen C, Tian H, Bivard A, Spratt NJ, et al., 'Association of Collateral Status and Ischemic Core Growth in Patients With Acute Ischemic Stroke', NEUROLOGY, 96 E161-E170 (2021) [C1]
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Nova |
2021 |
Omileke D, Pepperall D, Bothwell SW, Mackovski N, Azarpeykan S, Beard DJ, et al., 'Ultra-Short Duration Hypothermia Prevents Intracranial Pressure Elevation Following Ischaemic Stroke in Rats', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Garcia-Esperon C, Raposo N, Seners P, Spratt N, Parsons M, Olivot JM, 'Role of neuroimaging before reperfusion therapy. Part 1 IV thrombolysis Review', Revue Neurologique, 177 908-918 (2021) [C1]
This review paper summarises the yield of the different imaging modalities in the evaluation of patients for IV thrombolysis. Non-contrast CT and CTA or brain MRI combined with MR... [more]
This review paper summarises the yield of the different imaging modalities in the evaluation of patients for IV thrombolysis. Non-contrast CT and CTA or brain MRI combined with MRA are the recommended sequences for the evaluation of patients within the 4.5 hours time window. Multimodal MRI (DWI/PWI), and more recently, CT perfusion, offer reliable surrogate of salvageable penumbra, the target mismatch, which is now currently used as selection criteria for revascularisation treatment in an extended time window. Those sequences may also help the physician for the management of other limited cases when the diagnosis of acute ischemic stroke is difficult. Another approach the DWI/FLAIR mismatch has been proposed to identify among wake-up stroke patients those who have been experiencing an acute ischemic stroke evolving from less than 4.5 hrs. Other biomarkers, such as the clot imaging on MRI and CT, help to predict the recanalisation rate after IVT, while the impact of the presence microbleeds on MRI remains to be determined.
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Nova |
2021 |
Tomari S, Levi CR, Holliday E, Lasserson D, Valderas JM, Dewey HM, et al., 'One-Year Risk of Stroke After Transient Ischemic Attack or Minor Stroke in Hunter New England, Australia (INSIST Study)', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
English C, Attia JR, Bernhardt J, Bonevski B, Burke M, Galloway M, et al., 'Secondary Prevention of Stroke: Study Protocol for a Telehealth-Delivered Physical Activity and Diet Pilot Randomized Trial (ENAbLE-Pilot)', CEREBROVASCULAR DISEASES, 50 605-611 (2021)
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2021 |
Omileke D, Azarpeykan S, Bothwell SW, Pepperall D, Beard DJ, Coupland K, et al., 'Short-duration hypothermia completed prior to reperfusion prevents intracranial pressure elevation following ischaemic stroke in rats', SCIENTIFIC REPORTS, 11 (2021) [C1]
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Nova |
2021 |
Chen C, Parsons MW, Levi CR, Spratt NJ, Lin L, Kleinig T, et al., 'What Is the Optimal Target Mismatch Criteria for Acute Ischemic Stroke?', Frontiers in Neurology, 11 (2021) [C1]
We aimed to compare Perfusion Imaging Mismatch (PIM) and Clinical Core Mismatch (CCM) criteria in ischemic stroke patients to identify the effect of these criteria on selected pat... [more]
We aimed to compare Perfusion Imaging Mismatch (PIM) and Clinical Core Mismatch (CCM) criteria in ischemic stroke patients to identify the effect of these criteria on selected patient population characteristics and clinical outcomes. Patients from the INternational Stroke Perfusion Imaging REgistry (INSPIRE) who received reperfusion therapy, had pre-treatment multimodal CT, 24-h imaging, and 3 month outcomes were analyzed. Patients were divided into 3 cohorts: endovascular thrombectomy (EVT), intravenous thrombolysis alone with large vessel occlusion (IVT-LVO), and intravenous thrombolysis alone without LVO (IVT-nonLVO). Patients were classified using 6 separate mismatch criteria: PIM-using 3 different measures to define the perfusion deficit (Delay Time, Tmax, or Mean Transit Time); or CCM-mismatch between age-adjusted National Institutes of Health Stroke Scale and CT Perfusion core, defined as relative cerebral blood flow <30% within the perfusion deficit defined in three ways (as above). We assessed the eligibility rate for each mismatch criterion and its ability to identify patients likely to respond to treatment. There were 994 patients eligible for this study. PIM with delay time (PIM-DT) had the highest inclusion rate for both EVT (82.7%) and IVT-LVO (79.5%) cohorts. In PIM positive patients who received EVT, recanalization was strongly associated with achieving an excellent outcome at 90-days (e.g., PIM-DT: mRS 0-1, adjusted OR 4.27, P = 0.005), whereas there was no such association between reperfusion and an excellent outcome with any of the CCM criteria (all p > 0.05). Notably, in IVT-LVO cohort, 58.2% of the PIM-DT positive patients achieved an excellent outcome compared with 31.0% in non-mismatch patients following successful recanalization (P = 0.006). Conclusion: PIM-DT was the optimal mismatch criterion in large vessel occlusion patients, combining a high eligibility rate with better clinical response to reperfusion. No mismatch criterion was useful to identify patients who are most likely response to reperfusion in non-large vessel occlusion patients.
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Nova |
2021 |
Bothwell SW, Omileke D, Hood RJ, Pepperall D-G, Azarpeykan S, Patabendige A, Spratt NJ, 'Altered Cerebrospinal Fluid Clearance and Increased Intracranial Pressure in Rats 18 h After Experimental Cortical Ischaemia', FRONTIERS IN MOLECULAR NEUROSCIENCE, 14 (2021) [C1]
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Nova |
2021 |
Bivard A, Levi C, Lin L, Cheng X, Aviv R, Spratt NJ, et al., 'Assessing the Relative Value of CT Perfusion Compared to Non-contrast CT and CT Angiography in Prognosticating Reperfusion-Eligible Acute Ischemic Stroke Patients', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Bothwell SW, Omileke D, Patabendige A, Spratt NJ, 'CSF Secretion Is Not Altered by NKCC1 Nor TRPV4 Antagonism in Healthy Rats', BRAIN SCIENCES, 11 (2021) [C1]
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Nova |
2021 |
Omileke D, Bothwell SW, Pepperall D, Beard DJ, Coupland K, Patabendige A, Spratt NJ, 'Decreased Intracranial Pressure Elevation and Cerebrospinal Fluid Outflow Resistance: A Potential Mechanism of Hypothermia Cerebroprotection Following Experimental Stroke', Brain Sciences, 11 (2021) [C1]
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Nova |
2021 |
Haslam RL, Bezzina A, Herbert J, Spratt N, Rollo ME, Collins CE, 'Can Ketogenic Diet Therapy Improve Migraine Frequency, Severity and Duration?', HEALTHCARE, 9 (2021) [C1]
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Nova |
2021 |
Tran L, Lin L, Spratt N, Bivard A, Chew BLA, Evans JW, et al., 'Telestroke Assessment With Perfusion CT Improves the Diagnostic Accuracy of Stroke vs. Mimic', FRONTIERS IN NEUROLOGY, 12 (2021) [C1]
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Nova |
2021 |
Omileke D, Bothwell S, Beard D, MacKovski N, Azarpeykan S, Coupland K, et al., 'Short-duration hypothermia induction in rats using
models for studies examining clinical relevance and
mechanisms', Journal of Visualized Experiments, 169 (2021) [C1]
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Nova |
2020 |
Lin L, Chen C, Tian H, Bivard A, Spratt N, Levi CR, Parsons MW, 'Perfusion Computed Tomography Accurately Quantifies Collateral Flow After Acute Ischemic Stroke', STROKE, 51 1006-1009 (2020) [C1]
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Nova |
2020 |
Ostman C, Garcia-Esperon C, Lillicrap T, Tomari S, Holliday E, Levi C, et al., 'Multimodal Computed Tomography Increases the Detection of Posterior Fossa Strokes Compared to Brain Non-contrast Computed Tomography', FRONTIERS IN NEUROLOGY, 11 (2020) [C1]
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Nova |
2020 |
Lillicrap T, Pinheiro A, Miteff F, Garcia-Bermejo P, Gangadharan S, Wellings T, et al., 'No Evidence of the "Weekend Effect" in the Northern New South Wales Telestroke Network', FRONTIERS IN NEUROLOGY, 11 (2020) [C1]
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Nova |
2020 |
Denham AMJ, Baker AL, Spratt NJ, Wynne O, Hunt SA, Bonevski B, Kumar R, 'YouTube as a resource for evaluating the unmet needs of caregivers of stroke survivors', Health Informatics Journal, 26 1599-1616 (2020) [C1]
Content produced by caregivers of stroke survivors on the online video-sharing platform YouTube may be a good source of knowledge regarding caregivers¿ unmet needs. We aimed to ex... [more]
Content produced by caregivers of stroke survivors on the online video-sharing platform YouTube may be a good source of knowledge regarding caregivers¿ unmet needs. We aimed to examine the content, quantity and quality of YouTube videos that target and discuss the needs and concerns of caregivers of stroke survivors. YouTube was systematically searched using six search strings, and the first 20 videos retrieved from each search were screened against the inclusion criteria. A pre-determined coding schedule was used to report the rate of unmet needs in each video. Twenty-six videos were included in the analysis. In total, 291 unmet needs were reported by caregivers of stroke survivors, an average of 11.2 unmet needs per video. The most common unmet needs domain was ¿Impact of Caregiving on Daily Activities¿ (44%). Most videos were developed in the United States (61.5%) and featured spouses of stroke survivors (65.47%). Content produced by caregivers of stroke survivors on YouTube may be used as a tool for caregivers to provide and receive support through online communication. YouTube videos offer insight into the unmet needs of caregivers of stroke survivors and may be used as an additional resource for stroke services to support caregivers.
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Nova |
2020 |
Yang J, Wu Y, Gao X, Bivard A, Levi CR, Parsons MW, Lin L, 'Intraarterial Versus Intravenous Tirofiban as an Adjunct to Endovascular Thrombectomy for Acute Ischemic Stroke', STROKE, 51 2925-2933 (2020) [C1]
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Nova |
2020 |
Denham AMJ, Wynne O, Baker AL, Spratt NJ, Turner A, Magin P, et al., 'An online cross-sectional survey of the health risk behaviours among informal caregivers', Health Promotion Journal of Australia, 31 423-435 (2020) [C1]
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Nova |
2020 |
Gangadharan S, Lillicrap T, Miteff F, Garcia-Bermejo P, Wellings T, O'Brien B, et al., 'Air vs. Road Decision for Endovascular Clot Retrieval in a Rural Telestroke Network', Frontiers in Neurology, 11 1-6 (2020) [C1]
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Nova |
2020 |
Bajorek B, Gao L, Lillicrap T, Bivard A, Garcia-Esperon C, Parsons M, et al., 'Exploring the Economic Benefits of Modafinil for Post-Stroke Fatigue in Australia: A Cost-Effectiveness Evaluation', Journal of Stroke and Cerebrovascular Diseases, 29 (2020) [C1]
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Nova |
2020 |
Gao L, Tan E, Moodie M, Parsons M, Spratt NJ, Levi C, et al., 'Reduced Impact of Endovascular Thrombectomy on Disability in Real-World Practice, Relative to Randomized Controlled Trial Evidence in Australia', FRONTIERS IN NEUROLOGY, 11 (2020) [C1]
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Nova |
2020 |
Bothwell SW, Omileke D, Pepperall D-G, Patabendige A, Spratt N, 'Spinal cerebrospinal fluid flow is increased in rats with elevated intracranial pressure 18 hours after cortical ischaemic stroke (2020)
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2020 |
Denham AMJ, Wynne O, Baker AL, Spratt NJ, Turner A, Magin P, et al., 'An online survey of informal caregivers' unmet needs and associated factors', PLOS ONE, 15 (2020) [C1]
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Nova |
2020 |
Thomalla G, Boutitie F, Ma H, Koga M, Ringleb P, Schwamm LH, et al., 'Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data', The Lancet, 396 1574-1584 (2020) [C1]
Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe ... [more]
Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0¿1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0¿2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4¿6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10¿2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05¿1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06¿2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4¿6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52¿1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03¿4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22¿25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None.
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Nova |
2020 |
Whitehead N, Williams T, Brienesse S, Ferreira D, Murray N, Inder K, et al., 'Contemporary trends in stroke complicating cardiac catheterisation', Internal Medicine Journal, 50 859-865 (2020) [C1]
Background: Stroke remains an important complication of diagnostic cardiac catheterisation and percutaneous coronary intervention and is associated with high rates of in-hospital ... [more]
Background: Stroke remains an important complication of diagnostic cardiac catheterisation and percutaneous coronary intervention and is associated with high rates of in-hospital mortality. Aims: To evaluate the incidence of stroke over a 10-year period and assess the long-term influence of stroke following cardiac catheterisation and PCI on functional outcomes, based on modified Rankin score and mortality. Methods: The study was performed using a case¿control design in a single tertiary referral centre. Patients were identified by correlating those patients undergoing cardiac catheterisation between October 2006 and December 2016 with patients who underwent neuroimaging within 7 days to identify possible cases of suspected stroke or transient ischaemic attack. Results: A total of 21 510 patients underwent cardiac catheterisation during the study period. Sixty (0.28%) patients experienced stroke or transient ischaemic attack. Compared to control patients, those who did experience cerebral ischaemic events were older (70.5 vs 64 years; P < 0.001), with higher rates of atrial fibrillation, hypertension and diabetes mellitus. Stroke complicating cardiac catheterisation was associated with an increased risk of readmission, with a significantly higher hazard of readmission for stroke noted. Despite minimal functional impairment based on modified Rankin score, stroke was associated with a significant risk of early and cumulative mortality. Stroke incidence remained stable over the study period despite changes in procedural practice. Conclusions: The incidence and functional severity of stroke remains low despite evolving procedural practice with a stable incidence over time despite changes in procedural practice; however, post-procedural stroke confirms an increased mortality hazard.
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Nova |
2020 |
Postol N, Lamond S, Galloway M, Palazzi K, Bivard A, Spratt NJ, Marquez J, 'The Metabolic Cost of Exercising with a Robotic Exoskeleton: A Comparison of Healthy and Neurologically Impaired People', IEEE Transactions on Neural Systems and Rehabilitation Engineering, 28 3031-3039 (2020) [C1]
While neuro-recovery is maximized through active engagement, it has been suggested that the use of robotic exoskeletons in neuro-rehabilitation provides passive therapy. Using oxy... [more]
While neuro-recovery is maximized through active engagement, it has been suggested that the use of robotic exoskeletons in neuro-rehabilitation provides passive therapy. Using oxygen consumption (VO2) as an indicator of energy expenditure, we investigated the metabolic requirements of completing exercises in a free-standing robotic exoskeleton, with 20 healthy and 12 neurologically impaired participants (six with stroke, and six with multiple sclerosis (MS)). Neurological participants were evaluated pre- and post- 12 weeks of twice weekly robotic therapy. Healthy participants were evaluated in, and out of, the exoskeleton. Both groups increased their VO2 level from baseline during exoskeleton-assisted exercise (Healthy: mean change in VO2 = 2.10 ± 1.61 ml/kg/min, p =< 0.001; Neurological: 1.38 ± 1.22, p = 0.002), with a lower predicted mean in the neurological sample (-1.08, 95%CI -2.02, -0.14, p = 0.02). Healthy participants exercised harder out of the exoskeleton than in it (difference in VO2 = 3.50, 95%CI 2.62, 4.38, p =< 0.001). There was no difference in neurological participants' predicted mean VO2 pre- and post- 12 weeks of robotic therapy 0.45, 95%CI -0.20, 1.11, p = 0.15), although subgroup analysis revealed a greater change after 12 weeks of robotic therapy in those with stroke (MS: -0.06, 95%CI -0.78, 0.66, p = 0.85; stroke: 1.00, 95%CI 0.3, 1.69, p = 0.01; difference = 1.06, p = 0.04). Exercise in a free-standing robotic exoskeleton is not passive in healthy or neurologically impaired people, and those with stroke may derive more benefit than those with MS.
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Nova |
2020 |
Bivard A, Kleinig T, Churilov L, Levi C, Lin L, Cheng X, et al., 'Permeability Measures Predict Hemorrhagic Transformation after Ischemic Stroke', Annals of Neurology, 88 466-476 (2020) [C1]
Objective: We sought to examine the diagnostic utility of existing predictors of any hemorrhagic transformation (HT) and compare them with new perfusion imaging permeability measu... [more]
Objective: We sought to examine the diagnostic utility of existing predictors of any hemorrhagic transformation (HT) and compare them with new perfusion imaging permeability measures in ischemic stroke patients receiving alteplase only. Methods: A pixel-based analysis of pretreatment CT perfusion (CTP) was undertaken to define the optimal CTP permeability thresholds to predict the likelihood of HT. We then compared previously proposed predictors of HT using regression analyses and receiver operating characteristic curve analysis to produce an area under the curve (AUC). We compared AUCs using ¿2 analysis. Results: From 5 centers, 1,407 patients were included in this study; of these, 282 had HT. The cohort was split into a derivation cohort (1,025, 70% patients) and a validation cohort (382 patients or 30%). The extraction fraction (E) permeability map at a threshold of 30% relative to contralateral had the highest AUC at predicting any HT (derivation AUC 0.85, 95% confidence interval [CI], 0.79¿0.91; validation AUC 0.84, 95% CI 0.77¿0.91). The AUC improved when permeability was assessed within the acute perfusion lesion for the E maps at a threshold of 30% (derivation AUC 0.91, 95% CI 0.86¿0.95; validation AUC 0.89, 95% CI 0.86¿0.95). Previously proposed associations with HT and parenchymal hematoma showed lower AUC values than the permeability measure. Interpretation: In this large multicenter study, we have validated a highly accurate measure of HT prediction. This measure might be useful in clinical practice to predict hemorrhagic transformation in ischemic stroke patients before receiving alteplase alone. ANN NEUROL 2020;88:466¿476.
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Nova |
2020 |
Meretoja A, Yassi N, Wu TY, Churilov L, Sibolt G, Jeng JS, et al., 'Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial', The Lancet Neurology, 19 980-987 (2020) [C1]
Background: Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decrease... [more]
Background: Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decreases haemorrhage in conditions such as acute trauma and menorrhoea. We aimed to assess whether tranexamic acid reduces intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage. Methods: We did a prospective, double-blind, randomised, placebo-controlled, investigator-led, phase 2 trial at 13 stroke centres in Australia, Finland, and Taiwan. Patients were eligible if they were aged 18 years or older, had an acute intracerebral haemorrhage fulfilling clinical criteria (eg, Glasgow Coma Scale score of >7, intracerebral haemorrhage volume <70 mL, no identified or suspected secondary cause of intracerebral haemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 h, and no use of anticoagulation), had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 h of symptom onset and within 1 h of CT angiography. Patients were randomly assigned (1:1) to receive either 1 g of intravenous tranexamic acid over 10 min followed by 1 g over 8 h or matching placebo, started within 4·5 h of symptom onset. Randomisation was done using a centralised web-based procedure with randomly permuted blocks of varying size. All patients, investigators, and staff involved in patient management were masked to treatment. The primary outcome was intracerebral haemorrhage growth (>33% relative or >6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636). Findings: Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57¿79) and median intracerebral haemorrhage volume was 14·6 mL (7·9¿32·7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32¿1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication. Interpretation: Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified. Funding: National Health and Medical Research Council, Royal Melbourne Hospital Foundation.
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Nova |
2020 |
Lillicrap T, Keragala CB, Draxler DF, Chan J, Ho H, Harman S, et al., 'Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples', FRONTIERS IN NEUROLOGY, 11 (2020)
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2020 |
Tomari S, Magin P, Lasserson D, Quain D, Valderas JM, Dewey HM, et al., 'The Characteristics of Patients With Possible Transient Ischemic Attack and Minor Stroke in the Hunter and Manning Valley Regions, Australia (the INSIST Study)', FRONTIERS IN NEUROLOGY, 11 (2020) [C1]
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Nova |
2020 |
Garcia-Esperon C, Soderhjelm Dinkelspiel F, Miteff F, Gangadharan S, Wellings T, O´Brien B, et al., 'Implementation of multimodal computed tomography in a telestroke network: Five-year experience', CNS Neuroscience and Therapeutics, 26 367-373 (2020) [C1]
Aims: Penumbral selection is best-evidence practice for thrombectomy in the 6-24¿hour window. Moreover, it helps to identify the best responders to thrombolysis. Multimodal comput... [more]
Aims: Penumbral selection is best-evidence practice for thrombectomy in the 6-24¿hour window. Moreover, it helps to identify the best responders to thrombolysis. Multimodal computed tomography (mCT) at the primary centre¿including noncontrast CT, CT perfusion, and CT angiography¿may enhance reperfusion therapy decision-making. We developed a network with five spoke primary stroke sites and assessed safety, feasibility, and influence of mCT in rural hospitals on decision-making for thrombolysis. Methods: Consecutive patients assessed via telemedicine from April 2013 to June 2018. Clinical outcomes were measured, and decision-making compared using theoretical models for reperfusion therapy applied without mCT guidance. Symptomatic intracranial hemorrhage (sICH) was assessed according to Safe Implementation of Treatments in Stroke Thrombolysis Registry criteria. Results: A total of 334 patients were assessed, 240 received mCT, 58 were thrombolysed (24.2%). The mean age of thrombolysed patients was 70¿years, median baseline National Institutes of Health Stroke Scale was 10 (IQR 7-18) and 23 (39.7%) had a large vessel occlusion. 1.7% had sICH and 3.5% parenchymal hematoma. Three months poststroke, 55% were independent, compared with 70% in the non-thrombolysed group. Conclusion: Implementation of CTP in rural centers was feasible and led to high thrombolysis rates with low rates of sICH.
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Nova |
2020 |
Garcia-Esperon C, Spratt NJ, Gangadharan S, Miteff F, Bivard A, Lillicrap T, et al., 'Computed Tomography Perfusion Identifies Patients With Stroke With Impaired Cardiac Function', STROKE, 51 498-503 (2020) [C1]
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Nova |
2019 |
Levi CR, Lasserson D, Quain D, Valderas J, Dewey HM, Barber PA, et al., 'The International comparison of Systems of care and patient outcomes In minor Stroke and Tia (InSIST) study: A community-based cohort study', INTERNATIONAL JOURNAL OF STROKE, 14 186-190 (2019)
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2019 |
Tian H, Parsons MW, Levi CR, Lin L, Aviv RI, Spratt NJ, et al., 'Influence of occlusion site and baseline ischemic core on outcome in patients with ischemic stroke', Neurology, 92 E2626-E2643 (2019) [C1]
Objective: We assessed patient clinical outcomes based on occlusion location, focusing on distal occlusions to understand if occlusion location was an independent predictor of out... [more]
Objective: We assessed patient clinical outcomes based on occlusion location, focusing on distal occlusions to understand if occlusion location was an independent predictor of outcome, and tested the relationship between occlusion location and baseline ischemic core, a known predictor of modified Rankin Scale (mRS) score at 90 days. Methods: We analyzed a prospectively collected cohort of thrombolysis-eligible ischemic stroke patients from the International Stroke Perfusion Imaging Registry who underwent multimodal CT pretreatment. For the primary analysis, logistic regression was used to predict the effect of occlusion location and ischemic core on the likelihood of excellent (mRS 0-1) and favorable (mRS 0-2) 90-day outcomes. Results: This study included 945 patients. The rates of excellent and favorable outcome in patients with distal occlusion (M2, M3 segment of middle cerebral artery, anterior cerebral artery, and posterior cerebral artery) were higher than M1 occlusions (mRS 0%-1%, 55% vs 37%; mRS 0%-2%, 73% vs 50%, p < 0.001). Vessel occlusion location was not a strong predictor of outcomes compared to baseline ischemic core (area under the curve, mRS 0-1, 0.64 vs 0.83; mRS 0-2, 0.70 vs 0.86, p < 0.001). There was no interaction between occlusion location and ischemic core (interaction coefficient 1.00, p = 0.798). Conclusions: Ischemic stroke patients with a distal occlusion have higher rate of excellent and favorable outcome than patients with an M1 occlusion. The baseline ischemic core was shown to be a more powerful predictor of functional outcome than the occlusion location, but the relationship between ischemic core and outcome does not different by occlusion locations.
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Nova |
2019 |
Patabendige A, MacKovski N, Pepperall D, Hood R, Spratt N, 'A26 Cerebrospinal fluid outflow resistance is increased following small-moderate ischaemic stroke (vol 16, 16, 2019)', FLUIDS AND BARRIERS OF THE CNS, 16 (2019)
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2019 |
Bisson DA, Mahmoudian D, Shatil AS, Waggass G, Zhang L, Levi C, et al., 'Single-phase CT angiography: collateral grade is independent of scan weighting', Neuroradiology, 61 19-28 (2019) [C1]
Purpose: Collateral grading may vary on single-phase CTA (sCTA) depending on whether the CTA is arterial (A), arteriovenous (AV), or venous (V) weighted. We studied the impact of ... [more]
Purpose: Collateral grading may vary on single-phase CTA (sCTA) depending on whether the CTA is arterial (A), arteriovenous (AV), or venous (V) weighted. We studied the impact of sCTA weighting on collateral grading using the Tan, MAAS, and Menon methods, and their ability to predict infarct and clinical outcome hypothesizing that AV-weighted sCTA should better predict these outcomes. Methods: Multicenter retrospective analysis of 212 patients undergoing baseline CTP/sCTA. sCTA weighting was determined by comparing ICA to torcula AV ratios with those from concomitant CTP time-density curves at peak arterial or venous contrast attenuation. A generalized linear mixed model investigated the predictive value for infarct volume or 90-day mRS of the three collateral scores stratified by sCTA weighting and adjusting for age, sex, clot burden score (CBS), and NIHSS. Bayesian information criterion (BIC) differences were calculated between the null and fitted models. Results: Mean age, baseline median NIHSS, ASPECTS, and onset to treatment time were 69.89 ± 14.45, 13 (6¿18), 10 (8¿10), and 128 (66¿181) minutes. sCTA scans were AV-weighted in 137/212 (65%) and A-weighted in 73 (34%). No association was demonstrated between sCTA weighting, hospital site, and sCTA technique. All collateral scores were related to infarct volume irrespective of sCTA weighting, with greatest fit with the regional leptomeningeal score (BIC 18.29, p = 0.0001). No association was shown between sCTA weighting, collateral grade, and clinical outcome. Conclusion: sCTA weighting did not significantly impact collateral grade using three common collateral scores or their ability to predict final infarct.
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Nova |
2019 |
Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, et al., 'Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke', The New England journal of medicine, 380 1795-1803 (2019) [C1]
BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggeste... [more]
BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P¿=¿0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P¿=¿0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).
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Nova |
2019 |
Alemseged F, Van der Hoeven E, Di Giuliano F, Shah D, Sallustio F, Arba F, et al., 'Response to Late-Window Endovascular Revascularization Is Associated With Collateral Status in Basilar Artery Occlusion', STROKE, 50 1415-1422 (2019)
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2019 |
Dunn A, Marsden DL, Barker D, van Vliet P, Spratt NJ, Callister R, 'Evaluation of three measures of cardiorespiratory fitness in independently ambulant stroke survivors', Physiotherapy Theory and Practice, 35 622-632 (2019) [C1]
Measuring cardiorespiratory fitness (CRF) in the stroke population is challenging. Currently, the recommended method is a graded exercise test (GXT) on an ergometer such as a trea... [more]
Measuring cardiorespiratory fitness (CRF) in the stroke population is challenging. Currently, the recommended method is a graded exercise test (GXT) on an ergometer such as a treadmill or cycle, which may not always be possible. We investigated whether walking tests such as the six-minute walk test (6MWT) and the shuttle walk test (SWT) may be appropriate indicators of CRF in the stroke population. Twenty-three independently ambulant stroke survivors (11 men, age 61.5¿±¿18.4¿years) within one-year post stroke performed the 6MWT, SWT, and cycle GXT, during which peak oxygen consumption (VO2peak) and heart rate (HRpeak) were recorded. There were no differences (p¿>¿0.05) in mean VO2peak among the three tests (min-max: 17.08¿18.09¿mL¿kg-1¿min-1). For individuals, small discrepancies in VO2peak between the 6MWT and other tests were greater with higher fitness levels. HRpeak was significantly (p¿=¿0.005) lower during the 6MWT. Correlations between VO2peak and performance measures within each test were high (6MWT VO2peak and distance: r¿=¿0.78, SWT VO2peak and shuttles: r¿=¿0.73, cycle GXT VO2peak and workload: r¿=¿0.77) suggesting the performance measures may be clinically useful as proxy measures of CRF. Common comorbidities, such as lower-limb joint pain and poor balance, and participant¿s fastest walking speed, should inform the choice of CRF test.
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Nova |
2019 |
Visser MM, Goodin P, Parsons MW, Lillicrap T, Spratt NJ, Levi CR, Bivard A, 'Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue', SCIENTIFIC REPORTS, 9 (2019) [C1]
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Nova |
2019 |
Denham AMJ, Wynne O, Baker AL, Spratt NJ, Turner A, Magin P, et al., '"This is our life now. Our new normal": A qualitative study of the unmet needs of carers of stroke survivors', PLOS ONE, 14 (2019) [C1]
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Nova |
2019 |
Campbell BC, van Zwam WH, Goyal M, 'Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data (vol 17, pg 47, 2018)', LANCET NEUROLOGY, 18 E2-E2 (2019)
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2019 |
Mackie P, Crowfoot G, Janssen H, Dunstan DW, Bernhardt J, Walker FR, et al., 'Breaking up sitting time after stroke - How much less sitting is needed to improve blood pressure after stroke (BUST-BP-Dose): Protocol for a dose-finding study', CONTEMPORARY CLINICAL TRIALS COMMUNICATIONS, 13 (2019)
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2019 |
Diener H-C, Sacco RL, Easton JD, Granger CB, Bernstein RA, Uchiyama S, et al., 'Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source', NEW ENGLAND JOURNAL OF MEDICINE, 380 1906-1917 (2019)
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2019 |
Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, et al., 'Extending thrombolysis to 4·5 9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data', The Lancet, 394 139-147 (2019) [C1]
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 salv... [more]
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.
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Nova |
2019 |
Visser MM, Yassi N, Campbell BCV, Desmond PM, Davis SM, Spratt N, et al., 'White Matter Degeneration after Ischemic Stroke: A Longitudinal Diffusion Tensor Imaging Study', Journal of Neuroimaging, 29 111-118 (2019) [C1]
BACKGROUND AND PURPOSE: Degeneration of gray matter and subcortical structures after ischemic stroke has been well described. However, little is known about white matter degenerat... [more]
BACKGROUND AND PURPOSE: Degeneration of gray matter and subcortical structures after ischemic stroke has been well described. However, little is known about white matter degeneration after stroke. It is unclear whether white matter degeneration occurs throughout the whole brain, or whether patterns of degeneration occur more in specific brain areas. METHODS: We prospectively collected National Institutes of Health Stroke Scale (NIHSS) scores and diffusion tensor imaging (DTI) in patients with acute ischemic stroke within the first week after onset (baseline), and at 1 and 3 months. DTI was processed to produce maps of fractional anisotropy, apparent diffusion coefficients, and axial and radial diffusivity. DTI parameters in specified regions-of-interest corresponding to items on the NIHSS were calculated and changes over time were assessed using linear mixed-effect modeling. RESULTS: Seventeen patients were included in the study. Mean age (SD) was 71 (11.7) years, and median (IQR) baseline NIHSS 9 (5-13.3). Changes over time were observed in both visual cortices, contralesional primary motor cortex, premotor cortex, and superior temporal gyrus (P <.05). Changes in the ipsilesional motor cortex and inferior parietal lobule were only seen in patients with scores on the respective NIHSS-items (P <.05). No significant changes in global white matter diffusivity parameters were identified (P >.05). CONCLUSION: White matter changes after stroke may be localized rather than a global phenomenon.
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Nova |
2019 |
Campbell BCV, Majoie CBLM, Albers GW, Menon BK, Yassi N, Sharma G, et al., 'Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data', LANCET NEUROLOGY, 18 46-55 (2019) [C1]
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2019 |
Guillaumier A, McCrabb S, Spratt NJ, Pollack M, Baker AL, Magin P, et al., 'An online intervention for improving stroke survivors' health-related quality of life: study protocol for a randomised controlled trial', TRIALS, 20 (2019)
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2019 |
Denham AMJ, Guillaumier A, McCrabb S, Turner A, Baker AL, Spratt NJ, et al., 'Development of an online secondary prevention programme for stroke survivors: Prevent 2nd Stroke', BMJ Innovations, 5 35-42 (2019) [C1]
Background Stroke events often result in long-term negative health outcomes. People who experience a first stroke event are 30%-40% more likely to experience a second stroke event... [more]
Background Stroke events often result in long-term negative health outcomes. People who experience a first stroke event are 30%-40% more likely to experience a second stroke event within 5 years. An online secondary prevention programme for stroke survivors may help stroke survivors improve their health risk behaviours and lower their risk of a second stroke. Objectives This paper describes the development and early iteration testing of the usability and acceptability of an online secondary prevention programme for stroke survivors (Prevent 2nd Stroke, P2S). P2S aims to address six modifiable health risk behaviours of stroke: blood pressure, physical activity, nutrition, depression and anxiety, smoking, and alcohol consumption. Methods P2S was developed as an eight-module online secondary prevention programme for stroke survivors. Modelled on the DoTTI (Design and development, Testing early iterations, Testing for effectiveness, Integration and implementation) framework for the development of online programmes, the following stages were followed during programme development: (1) content development and design; and (2) testing early iteration. The programme was pilot-tested with 15 stroke survivors who assessed P2S on usability and acceptability. Results In stage 1, experts provided input for the content development of P2S. In stage 2, 15 stroke survivors were recruited for usability testing of P2S. They reported high ratings of usability and acceptability of P2S. P2S was generally regarded as easy to use' and relevant to stroke survivors'. Participants also largely agreed that it was appropriate to offer lifestyle advice to stroke survivors through the internet. Conclusions The study found that an online secondary prevention programme was acceptable and easily usable by stroke survivors. The next step is to conduct a randomised controlled trial to assess the effectiveness of the programme regarding behaviour change and determine the cost-effectiveness of the intervention.
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Nova |
2019 |
Egorova N, Gottlieb E, Khlif MS, Spratt NJ, Brodtmann A, 'Choroid plexus volume after stroke', International Journal of Stroke, 14 923-930 (2019) [C1]
Background: Cerebrospinal fluid circulation is crucial for the functioning of the brain. Aging and brain pathologies such as Alzheimer¿s disease have been associated with a change... [more]
Background: Cerebrospinal fluid circulation is crucial for the functioning of the brain. Aging and brain pathologies such as Alzheimer¿s disease have been associated with a change in the morphology of the ventricles and the choroid plexus. Despite the evidence from animal models that the cerebrospinal fluid system plays an important role in neuroinflammation and the restoration of the brain after ischemic brain injury, little is known about changes to the choroid plexus after stroke in humans. Aims: Our goal was to characterize structural choroid plexus changes poststroke. Methods: We used an automatic segmentation tool to estimate the volumes of choroid plexus and lateral ventricles in stroke and control participants at three time points (at baseline, 3 and 12 months) over the first year after stroke. We assessed group differences cross-sectionally at each time point and longitudinally. For stroke participants, we specifically differentiated between ipsi- and contra-lesional volumes. Statistical analyses were conducted for each region separately and included covariates such as age, sex, total intracranial volume, and years of education. Results: We observed significantly larger choroid plexus volumes in stroke participants compared to controls in both cross-sectional and longitudinal analyses. Choroid plexus volumes did not exhibit any change over the first year after stroke, with no difference between ipsi- and contra-lesional volumes. This was in contrast to the volume of lateral ventricles that we found to enlarge over time in all participants, with more accelerated expansion in stroke survivors ipsi-lesionally. Conclusions: Our results suggest that chronic stages of stroke are characterized by larger choroid plexus volumes, but the enlargement likely takes place prior to or very early after the stroke incident.
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Nova |
2019 |
Visser MM, Maréchal B, Goodin P, Lillicrap TP, Garcia-Esperon C, Spratt NJ, et al., 'Predicting modafinil-treatment response in poststroke fatigue using brain morphometry and functional connectivity', Stroke, 50 602-609 (2019) [C1]
Background and Purpose - Poststroke fatigue affects a large proportion of stroke survivors and is associated with a poor quality of life. In a recent trial, modafinil was shown to... [more]
Background and Purpose - Poststroke fatigue affects a large proportion of stroke survivors and is associated with a poor quality of life. In a recent trial, modafinil was shown to be an effective agent in reducing poststroke fatigue; however, not all patients reported a significant decrease in fatigue with therapy. We sought to investigate clinical and radiological predictors of fatigue reduction with modafinil therapy in a stroke survivor cohort. Methods - Twenty-six participants with severe fatigue (multidimensional fatigue inventory-20 =60) underwent magnetic resonance imaging at baseline and during the last week of a 6-week treatment period of 200 mg modafinil taken daily. Resting-state functional magnetic resonance imaging and high-resolution structural imaging data were obtained, and functional connectivity and regional brain volumes within the fronto-striato-thalamic network were obtained. Linear regression analysis was used to identify predictors of modafinil-induced fatigue reduction. Results - Multiple regression analysis showed that baseline multidimensional fatigue inventory-20 score (ß=0.576, P=0.006) and functional connectivity between the dorsolateral prefrontal cortex and the caudate nucleus (ß=-0.424, P=0.008) were significant predictors of modafinil-associated decreases in poststroke fatigue (adjusted r2=0.52, area under the receiver operator characteristic curve=0.939). Conclusions - Fronto-striato-thalamic functional connectivity predicted modafinil response for poststroke fatigue. Fatigue in other neurological disease has been attributed to altered function of the fronto-striato-thalamic network and may indicate that poststroke fatigue has a similar mechanism to other neurological injury related fatigue. Self-reported fatigue in patients with normal fronto-striato-thalamic functional connectivity may have a different mechanism and require alternate therapeutic approaches.
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Nova |
2019 |
Postol N, Marquez J, Spartalis S, Bivard A, Spratt NJ, 'Do powered over-ground lower limb robotic exoskeletons affect outcomes in the rehabilitation of people with acquired brain injury?', Disability and Rehabilitation: Assistive Technology, 14 764-775 (2019) [C1]
Purpose: To assess the effects of lower limb robotic exoskeletons on outcomes in the rehabilitation of people with acquired brain injury. Materials and methods: A systematic revie... [more]
Purpose: To assess the effects of lower limb robotic exoskeletons on outcomes in the rehabilitation of people with acquired brain injury. Materials and methods: A systematic review of seven electronic databases was conducted. The primary outcome of interest was neuromuscular function. Secondary outcomes included quality of life, mood, acceptability and safety. Studies were assessed for methodological quality and recommendations were made using the GRADE system. Results: Of 2469 identified studies, 13 (n = 322) were included in the review. Five contained data suitable for meta-analysis. When the data were pooled, there were no differences between exoskeleton and control for 6-Minute Walk Test, Timed Up and Go or 10-Meter Walk Test. Berg Balance Scale outcomes were significantly better in controls (MD = 2.74, CI = 1.12¿4.36, p = 0.0009). There were no severe adverse events but drop-outs were 11.5% (n = 37). No studies reported the effect of robotic therapy on quality of life or mood. Methodological quality was on average fair (15.6/27 on Downs and Black Scale). Conclusions: Only small numbers of people with acquired brain injury had data suitable for analysis. The available data suggests no more benefit for gait or balance with robotic therapy than conventional therapy. However, some important outcomes have not been studied and further well-conducted research is needed to determine whether such devices offer benefit over conventional therapy, in particular subgroups of those with acquired brain injury.Implications for Rehabilitation There is adequate evidence to recommend that powered over-ground lower limb robotic exoskeletons should not be used clinically in those with ABI, and that use should be restricted to research. Further research (controlled trials) with dependent ambulators is recommended. Research of other outcomes such as acceptability, spasticity, sitting posture, cardiorespiratory and psychological function, should be considered.
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Nova |
2019 |
Hong L, Cheng X, Lin L, Bivard A, Ling Y, Butcher K, et al., 'The blood pressure paradox in acute ischemic stroke.', Ann Neurol, 85 331-339 (2019) [C1]
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Nova |
2019 |
English C, Patterson A, MacDonald-Wicks L, Attia J, Callister R, Hillier S, et al., 'ENAbLE: Secondary prevention of stroke. A physical activity and diet trial protocol', International Journal of Stroke, 14 12-12 (2019)
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2019 |
Chen C, Parsons MW, Levi CR, Spratt NJ, Miteff F, Lin L, et al., 'Exploring the relationship between ischemic core volume and clinical outcomes after thrombectomy or thrombolysis', Neurology, 93 E283-E292 (2019) [C1]
ObjectiveTo assess whether complete reperfusion after IV thrombolysis (IVT-R) would result in similar clinical outcomes compared to complete reperfusion after endovascular thrombe... [more]
ObjectiveTo assess whether complete reperfusion after IV thrombolysis (IVT-R) would result in similar clinical outcomes compared to complete reperfusion after endovascular thrombectomy (EVT-R) in patients with a large vessel occlusion (LVO).MethodsEVT-R patients were matched by age, clinical severity, occlusion location, and baseline perfusion lesion volume to IVT-R patients from the International Stroke Perfusion Imaging Registry (INSPIRE). Only patients with complete reperfusion on follow-up imaging were included. The excellent clinical outcome rates at day 90 on the modified Rankin Scale (mRS) were compared between EVT-R vs IVT-R patients within quintiles of increasing baseline ischemic core and penumbral volumes.ResultsFrom INSPIRE, there were 141 EVT-R patients and 141 matched controls (IVT-R) who met the eligibility criteria. In patients with a baseline core <30 mL, EVT-R resulted in a lower odds of achieving an excellent outcome at day 90 compared to IVT-R (day 90 mRS 0-1 odds ratio 0.01, p < 0.001). The group with a baseline core <30 mL contained mostly patients with distal M1 or M2 occlusions, and good collaterals (p = 0.01). In patients with a baseline ischemic core volume >30 mL (internal carotid artery and mostly proximal M1 occlusions), EVT-R increased the odds of patients achieving an excellent clinical outcome (day 90 mRS 0-1 odds ratio 1.61, p < 0.001) and there was increased symptomatic intracranial hemorrhage in the IVT-R group with core >30 mL (20% vs 3% in EVT-R, p = 0.008).ConclusionFrom this observational cohort, LVO patients with larger baseline ischemic cores and proximal LVO, with poorer collaterals, clearly benefited from EVT-R compared to IVT-R alone. However, for distal LVO patients, with smaller ischemic cores and better collaterals, EVT-R was associated with a lower odds of favorable outcome compared to IVT-R alone.
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Nova |
2019 |
Wong R, Al-Omary M, Baker D, Spratt N, Boyle A, Baker N, et al., 'Cognitive dysfunction is associated with abnormal responses in cerebral blood flow in patients with single ventricular physiology: Novel insights from transcranial Doppler ultrasound', Congenital Heart Disease, 14 638-644 (2019) [C1]
Objectives: Improvements in the management of complex congenital heart disease, including those with single ventricle physiology, have resulted in increased survival. As this popu... [more]
Objectives: Improvements in the management of complex congenital heart disease, including those with single ventricle physiology, have resulted in increased survival. As this population ages, the recognition of cognitive impairment is increasingly important. At present, little is known about the potential mechanisms of cognitive dysfunction. In this cross-sectional study, we aimed to characterize the nature of abnormalities in cerebral blood flow and the relationship to cognitive deficits in adults with single ventricular physiology. Patients: Ten adults with single ventricular physiology (age 18-40¿years) and 12 age- and gender-matched controls underwent transcranial Doppler ultrasound and accompanying cognitive assessment. Outcome Measures: Patients underwent neuropsychological testing that assessed differing cognitive domains, with subjective cognitive decline determined from a 24-question survey. Transcranial Doppler ultrasound was used to assess baseline cerebral blood flow as well as change in cerebral blood flow velocities from baseline and during cognitive testing. Age, ethnicity, individual, and parental education levels were considered in the multivariate analyses. Results: On assessment of cognitive function, the patient group performed more poorly across each of the measured domains. The control group had a significantly greater increase in cerebral blood flow in response to cognitive stimuli compared to the patient cohort; these differences in response to cognitive stimuli were seen to a similar extent across each of the measured cognitive domains. Conclusion: Adults with Fontan physiology are underperforming in assessments of executive function with associated abnormalities in cerebral perfusion potentially contributing to cognitive deficits.
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Nova |
2019 |
Chen C, Bivard A, Lin L, Levi CR, Spratt NJ, Parsons MW, 'Thresholds for infarction vary between gray matter and white matter in acute ischemic stroke: A CT perfusion study', Journal of Cerebral Blood Flow and Metabolism, 39 536-546 (2019) [C1]
We aimed to investigate optimal perfusion thresholds defining ischemic core and penumbra for hemispheric-cortical gray matter (GM) and subcortical white matter (WM). A total of 65... [more]
We aimed to investigate optimal perfusion thresholds defining ischemic core and penumbra for hemispheric-cortical gray matter (GM) and subcortical white matter (WM). A total of 65 sub-6 h ischemic stroke patients were assessed, who underwent acute computed tomography perfusion (CTP) and acute magnetic resonance imaging. CTP maps were generated by both standard singular value deconvolution (sSVD) and SVD with delay and dispersion correction (ddSVD). Analyses were undertaken to calculate sensitivity, specificity, and area under the curve (AUC) for each CTP threshold for core and penumbra in GM and WM. With sSVD, the core was best defined in GM by cerebral blood flow (CBF) < 30% (AUC: 0.73) and in WM by CBF < 20% (AUC: 0.67). With ddSVD, GM core was best defined by CBF < 35% (AUC: 0.75) and in WM by CBF < 25% (AUC: 0.68). A combined GM/WM threshold overestimated core compared to diffusion-weighted imaging, CBF < 25% from sSVD (1.88 ml, P = 0.007) and CBF < 30% from ddSVD (1.27 ml, P = 0.011). The perfusion lesion was best defined by T max > 5 s (AUC: 0.80) in GM and T max > 7 s (AUC: 0.75) in WM. With sSVD, a delay time (DT) > 3 s from ddSVD was the optimal for both GM (AUC: 0.78) and WM (AUC: 0.75). Using tissue-specific thresholds for GM/WM provides more accurate estimation of acute ischemic core.
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Nova |
2018 |
Bivard A, Spratt N, Miteff F, Levi C, Parsons MW, 'Tissue Is More Important than Time in Stroke Patients Being Assessed for Thrombolysis', Frontiers in Neurology, 9 1-7 (2018) [C1]
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Nova |
2018 |
Roman LS, Menon BK, Blasco J, Hernandez-Perez M, Davalos A, Majoie CBLM, et al., 'Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data', LANCET NEUROLOGY, 17 895-904 (2018)
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2018 |
Lillicrap T, Garcia-Esperon C, Walker FR, Ong LK, Nilsson M, Spratt N, et al., 'Growth Hormone Deficiency Is Frequent After Recent Stroke', FRONTIERS IN NEUROLOGY, 9 (2018) [C1]
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Nova |
2018 |
Kenah K, Bernhardt J, Cumming T, Spratt N, Luker J, Janssen H, 'Boredom in patients with acquired brain injuries during inpatient rehabilitation: a scoping review', Disability and Rehabilitation, 40 2713-2722 (2018) [C1]
Purpose: Boredom may impede engagement in inpatient rehabilitation following an acquired brain injury. This review aimed to: (1) describe the experience and (2) quantify the incid... [more]
Purpose: Boredom may impede engagement in inpatient rehabilitation following an acquired brain injury. This review aimed to: (1) describe the experience and (2) quantify the incidence of boredom; (3) identify measurement tools used to quantify boredom; (4) summarize factors contributing to boredom, and (5) outline evidence-based interventions shown to reduce boredom during inpatient rehabilitation. Methods: Two researchers independently screened publications retrieved from electronic database searches. Publications presenting patient, carer or staff data relating to boredom in inpatients with acquired brain injuries were included. Results: Two thousand four hundred and ninety-nine references were retrieved, 88 full texts were reviewed, with 24 studies included. The majority of studies reported qualitative data indicating boredom to be a common experience of patients with acquired brain injuries (n = 14 studies +1 review). The incidence of boredom post acquired brain injury is unknown. Personal and organizational factors and the physical environment may contribute to boredom (n = 11 studies +2 reviews). Qualitative work (n = 9 studies) indicates that use of the creative-arts or exposure to environmental enrichment may help alleviate boredom in patients with acquired brain injuries during inpatient rehabilitation. Conclusion: Further mixed-methods research is required to establish the incidence of and contributing factors to boredom in patients with acquired brain injuries undergoing rehabilitation. Understanding this will help inform future research aimed at improving patient engagement in inpatient rehabilitation.Implications for rehabilitation Boredom is commonly reported by hospitalised patients with ABI to negatively affect their rehabilitation yet the scope of the problem has not been measured. Boredom is a complex phenomenon, likely influenced by a number of personal and environmental factors that are not fully understood in this population. Through a better understanding of boredom, interventions may be developed to improve patient engagement in inpatient rehabilitation programs.
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Nova |
2018 |
Denham AMJ, Baker AL, Spratt NJ, Wynne O, Hunt S, Sharma-Kumar R, Bonevski B, 'The unmet needs of caregivers of stroke survivors: A review of the content of YouTube videos (Preprint)', JMIR Rehabilitation and Assistive Technologies,
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2018 |
English C, Janssen H, Crowfoot G, Bourne J, Callister R, Dunn A, et al., 'Frequent, short bouts of light-intensity exercises while standing decreases systolic blood pressure: Breaking Up Sitting Time after Stroke (BUST-Stroke) trial', International Journal of Stroke, 13 932-940 (2018) [C1]
Background: Stroke survivors sit for long periods each day. Uninterrupted sitting is associated with increased risk of cardiovascular disease. Breaking up uninterrupted sitting wi... [more]
Background: Stroke survivors sit for long periods each day. Uninterrupted sitting is associated with increased risk of cardiovascular disease. Breaking up uninterrupted sitting with frequent, short bouts of light-intensity physical activity has an immediate positive effect on blood pressure and plasma clotting factors in healthy, overweight, and type 2 diabetic populations. Aim: We examined the effect of frequent, short bouts of light-intensity physical activity on blood pressure and plasma fibrinogen in stroke survivors. Methods: Prespecified secondary analyses from a three-armed randomized, within-participant, crossover trial. Participants were 19 stroke survivors (nine female, aged 68 years old, 90% able to walk independently). The experimental conditions were sitting for 8 h uninterrupted, sitting with 3 min bouts of light-intensity exercise while standing every 30 min, or sitting with 3 min of walking every 30 min. Blood pressure was measured every 30 min over 8 h and plasma fibrinogen at the beginning, middle, and end of each day. Intention-to-treat analyses were performed using linear mixed models including fixed effects for condition, period, and order, and a random intercept for participant to account for repeated measures and missing data. Results: Sitting with 3 min bouts of light-intensity exercise while standing every 30 min decreased systolic blood pressure by 3.5 mmHg (95% CI 1.7¿5.4) compared with sitting for 8 h uninterrupted. For participants not taking antihypertensive medications, sitting with 3 min of walking every 30 min decreased systolic blood pressure by 5.0 mmHg (95% CI -7.9 to 2.0) and sitting with 3 min bouts light-intensity exercise while standing every 30 min decreased systolic blood pressure by 4.2 mmHg (95% CI -7.2 to -1.3) compared with sitting for 8 h uninterrupted. There was no effect of condition on diastolic blood pressure (p = 0.45) or plasma fibrinogen levels (p = 0.91). Conclusion: Frequent, short bouts of light-intensity physical activity decreases systolic blood pressure in stroke survivors. However, before translation into clinical practice, the optimal duration and timing of physical activity bouts needs to be determined. Clinical trial registration: Australian and New Zealand Clinical Trials Registry http://www.anzctr.org.au ANZTR12615001189516.
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Nova |
2018 |
English C, Janssen H, Crowfoot G, Callister R, Dunn A, Mackie P, et al., 'Breaking up sitting time after stroke (BUST-stroke)', International Journal of Stroke, 13 921-931 (2018) [C1]
Objectives: People with stroke sit for long periods each day, which may compromise blood glucose control and increase risk of recurrent stroke. Studies in other populations have f... [more]
Objectives: People with stroke sit for long periods each day, which may compromise blood glucose control and increase risk of recurrent stroke. Studies in other populations have found regular activity breaks have a significant immediate (within-day) positive effect on glucose metabolism. We examined the effects of breaking up uninterrupted sitting with frequent, short bouts of light-intensity physical activity in people with stroke on post-prandial plasma glucose and insulin. Methods: Randomized within-participant crossover trial. We included people between 3 months and 10 years post-stroke, ambulant with minimal assistance and not taking diabetic medication other than metformin. The three experimental conditions (completed in random order) were: sitting for 8 h uninterrupted, sitting with 3 min bouts of light-intensity exercise while standing every 30 min, or sitting with 3 min of walking every 30 min. Meals were standardized and bloods were collected half- to one-hourly via an intravenous cannula. Results: A total of 19 participants (9 female, mean [SD] age 68.2 [10.2]) completed the trial. The majority (n = 12, 63%) had mild stroke symptoms (National Institutes of Stroke Scale score 0¿13). There was no significant effect of experimental condition on glucose (mean [SD] positive incremental area [+iAUC] mmol·L·h-1 under the curve during sitting 42.3 [29.5], standing 47.4 [23.1], walking 44.6 [26.5], p = 0.563) or insulin (mean + iAUC pmol·L·h-1 sitting 14,161 [7,560], standing 14,043 [8,312], walking 14,008 [8,269], p = 0.987). Conclusion: Frequent, short bouts of light-intensity physical activity did not have a significant effect on post-prandial plasma glucose and insulin in this sample of people with stroke. Further studies are needed to identify strategies that improve inactivity-related glucose metabolism after stroke.
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Nova |
2018 |
Campbell BCV, van Zwam WH, Goyal M, Menon BK, Dippel DWJ, Demchuk AM, et al., 'Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data', LANCET NEUROLOGY, 17 47-53 (2018) [C1]
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2018 |
Lin L, Bivard A, Kleinig T, Spratt NJ, Levi CR, Yang Q, Parsons MW, 'Correction for Delay and Dispersion Results in More Accurate Cerebral Blood Flow Ischemic Core Measurement in Acute Stroke', STROKE, 49 924-+ (2018) [C1]
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Nova |
2018 |
Denham AMJ, Baker AL, Spratt N, Guillaumier A, Wynne O, Turner A, et al., 'The unmet needs of informal carers of stroke survivors: a protocol for a systematic review of quantitative and qualitative studies', BMJ OPEN, 8 (2018)
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2018 |
Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, et al., 'Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA', NEW ENGLAND JOURNAL OF MEDICINE, 379 215-225 (2018) [C1]
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2018 |
Tan KN, Hood R, Warren K, Pepperall D, Carrasco-Pozo C, Manzanero S, et al., 'Heptanoate is neuroprotective in vitro but triheptanoin post-treatment did not protect against middle cerebral artery occlusion in rats', Neuroscience Letters, 683 207-214 (2018) [C1]
Triheptanoin, the medium-chain triglyceride of heptanoate, has been shown to be anticonvulsant and neuroprotective in several neurological disorders. In the gastrointestinal tract... [more]
Triheptanoin, the medium-chain triglyceride of heptanoate, has been shown to be anticonvulsant and neuroprotective in several neurological disorders. In the gastrointestinal tract, triheptanoin is cleaved to heptanoate, which is then taken up by the blood and most tissues, including liver, heart and brain. Here we evaluated the neuroprotective effects of heptanoate and its effects on mitochondrial oxygen consumption in vitro. We also investigated the neuroprotective effects of triheptanoin compared to long-chain triglycerides when administered after stroke onset in rats. Heptanoate pre-treatment protected cultured neurons against cell death induced by oxygen glucose deprivation and N-methyl-D-aspartate. Incubation of cultured astrocytes with heptanoate for 2 h increased mitochondrial proton leak and also enhanced basal respiration and ATP turnover, suggesting that heptanoate protects against oxidative stress and is used as fuel. However, continuous 72 h infusion of triheptanoin initiated 1 h after middle cerebral artery occlusion in rats did not alter stroke volume at 3 days or neurological deficit at 1 and 3 days relative to long-chain triglyceride control treatment.
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Nova |
2018 |
Tian H, Parsons MW, Levi CR, Cheng X, Aviv R, Spratt NJ, et al., 'Intravenous Thrombolysis May Not Improve Clinical Outcome of Acute Ischemic Stroke Patients Without a Baseline Vessel Occlusion', FRONTIERS IN NEUROLOGY, 9 (2018) [C1]
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Nova |
2017 |
Demuth HU, Dijkhuizen RM, Farr TD, Gelderblom M, Horsburgh K, Iadecola C, et al., 'Recent progress in translational research on neurovascular and neurodegenerative disorders', Restorative Neurology and Neuroscience, 35 87-103 (2017) [C1]
The already established and widely used intravenous application of recombinant tissue plasminogen activator as a re-opening strategy for acute vessel occlusion in ischemic stroke ... [more]
The already established and widely used intravenous application of recombinant tissue plasminogen activator as a re-opening strategy for acute vessel occlusion in ischemic stroke was recently added by mechanical thrombectomy, representing a fundamental progress in evidence-based medicine to improve the patient's outcome. This has been paralleled by a swift increase in our understanding of pathomechanisms underlying many neurovascular diseases and most prevalent forms of dementia. Taken together, these current advances offer the potential to overcome almost two decades of marginally successful translational research on stroke and dementia, thereby spurring the entire field of translational neuroscience. Moreover, they may also pave the way for the renaissance of classical neuroprotective paradigms. This review reports and summarizes some of the most interesting and promising recent achievements in neurovascular and dementia research. It highlights sessions from the 9th International Symposium on Neuroprotection and Neurorepair that have been discussed from April 19th to 22nd in Leipzig, Germany. To acknowledge the emerging culture of interdisciplinary collaboration and research, special emphasis is given on translational stories ranging from fundamental research on neurode- and -regeneration to late stage translational or early stage clinical investigations.
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Nova |
2017 |
Rostas JAP, Spratt NJ, Dickson PW, Skelding KA, 'The role of Ca
Studies in multiple experimental systems show that Ca2+-calmodulin stimulated protein kinase II (CaMKII) is a major mediator of ischaemia-induced cell death and suggest that CaMKI... [more]
Studies in multiple experimental systems show that Ca2+-calmodulin stimulated protein kinase II (CaMKII) is a major mediator of ischaemia-induced cell death and suggest that CaMKII would be a good target for neuroprotective therapies in acute treatment of stroke. However, as CaMKII regulates many cellular processes in many tissues any clinical treatment involving the inhibition of CaMKII would need to be able to specifically target the functions of ischaemia-activated CaMKII. In this review we summarise new developments in our understanding of the molecular mechanisms involved in ischaemia-induced CaMKII-mediated cell death that have identified ways in which such specificity of CaMKII inhibition after stroke could be achieved. We also review the mechanisms and phases of tissue damage in ischaemic stroke to identify where and when CaMKII-mediated mechanisms may be involved.
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Nova |
2017 |
Rostas JAP, Hoffman A, Murtha LA, Pepperall D, McLeod DD, Dickson PW, et al., 'Ischaemia- and excitotoxicity-induced CaMKII-Mediated neuronal cell death: The relative roles of CaMKII autophosphorylation at T286 and T253', Neurochemistry International, 104 6-10 (2017) [C1]
Ischaemia/excitotoxicity produces persistent activation of CaMKII (Ca2+-calmodulin stimulated protein kinase II) that initiates cell death. This study investigated the involvement... [more]
Ischaemia/excitotoxicity produces persistent activation of CaMKII (Ca2+-calmodulin stimulated protein kinase II) that initiates cell death. This study investigated the involvement of CaMKII phosphorylation at T286 and T253 in producing this persistent activation. In T286A-aCaMKII transgenic mice that lack the ability to phosphorylate aCaMKII at T286, transient occlusion of the middle cerebral artery for 90¿min resulted in no significant difference in infarct size compared to normal littermate controls. Overexpression of the phospho-mimic mutant T286D-aCaMKII in differentiated neuroblastoma cell lines did not enhance excitotoxicity-induced cell death compared to overexpression of wild type aCaMKII. By contrast, overexpression of the phospho-mimic mutant T253D-aCaMKII significantly enhanced excitotoxicity-induced cell death whereas overexpression of the phospho-null mutant T253V-aCaMKII produced no enhancement. These results indicate that T286 phosphorylation does not play a significant role in ischaemia/excitotoxicity induced CaMKII-mediated cell death and suggest that T253 phosphorylation is required to produce the persistent activation of CaMKII involved in ischaemia/excitotoxicity induced cell death.
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Nova |
2017 |
Demeestere J, Sewell C, Rudd J, Ang T, Jordan L, Wills J, et al., 'The establishment of a telestroke service using multimodal CT imaging decision assistance: Turning on the fog lights ', Journal of Clinical Neuroscience, 37 1-5 (2017) [C1]
Telestroke services have been shown to increase stroke therapy access in rural areas. The implementation of advanced CT imaging for patient assessment may improve patient selectio... [more]
Telestroke services have been shown to increase stroke therapy access in rural areas. The implementation of advanced CT imaging for patient assessment may improve patient selection and detection of stroke mimics in conjunction with telestroke. We implemented a telestroke service supported by multimodal CT imaging in a rural hospital in Australia. Over 21¿months we conducted an evaluation of service activation, thrombolysis rates and use of multimodal imaging to assess the feasibility of the service. Rates of symptomatic intracranial haemorrhage and 90-day modified Rankin Score were used as safety outcomes. Fifty-eight patients were assessed using telestroke, of which 41 were regarded to be acute ischemic strokes and 17 to be stroke mimics on clinical grounds. Of the 41 acute stroke patients, 22 patients were deemed eligible for thrombolysis. Using multimodal CT imaging, 8 more patients were excluded from treatment because of lack of treatment target. Multimodal imaging failed to be obtained in one patient. For the 14 treated patients, median door-imaging time was 38¿min. Median door-treatment time was 91¿min. A 90-day mRS ¿2 was achieved in 40% of treated patients. We conclude that a telestroke service using advanced CT imaging for therapy decision assistance can be successfully implemented in regional Australia and can be used to guide acute stroke treatment decision-making and improve access to thrombolytic therapy. Efficiency and safety is comparable to established telestroke services.
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Nova |
2017 |
Liebeskind DS, Woolf GW, Shuaib A, 'Collaterals 2016: Translating the collaterome around the globe', INTERNATIONAL JOURNAL OF STROKE, 12 338-342 (2017)
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2017 |
Bivard A, Huang X, Levi CR, Spratt N, Campbell BCV, Cheripelli BK, et al., 'Tenecteplase in ischemic stroke offers improved recanalization', Neurology, 89 62-67 (2017) [C1]
Objective: To test whether patients with complete vessel occlusion show greater recanalization at 24 hours and have improved clinical outcomes at 24 hours and 90 days when treated... [more]
Objective: To test whether patients with complete vessel occlusion show greater recanalization at 24 hours and have improved clinical outcomes at 24 hours and 90 days when treated with tenecteplase compared to alteplase. Methods: Pooled clinical and imaging data from 2 phase 2 randomized trials comparing tenecteplase with alteplase allowed CT angiography (CTA) scans to be assessed centrally for occlusion status at baseline and at 24 hours post thrombolysis using the modified thrombolysis in cerebral infarction (TICI) scale. Twenty-four-hour poststroke NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores were also compared between treatment groups using linear regression to generate odds ratios (ORs). Results: From 146 pooled patients, 69 had a TICI 0/1 occlusion overall at baseline. Tenecteplase-treated patients with a complete vessel occlusion had greater complete recanalization rates at 24 hours (71% for tenecteplase vs 43% for alteplase, p < 0.001). Patients with a TICI 0/1 occlusion who were treated with tenecteplase also showed greater early clinical improvement (median NIHSS change with tenecteplase was 9, interquartile range [IQR] 6, alteplase 1, IQR 1, p = 0.001) and higher rates of favorable 90-day outcomes (mRS 0-1 of tenecteplase compared with alteplase, OR 4.82, 95% confidence interval 1.02-7.84, p = 0.05). Conclusions: Tenecteplase may offer greater recanalization efficacy compared to alteplase, possibly exaggerated in patients with complete vessel occlusions on baseline CTA.
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Nova |
2017 |
Dunn A, Marsden DL, Barker D, Van Vliet P, Spratt NJ, Callister R, 'Cardiorespiratory fitness and walking endurance improvements after 12 months of an individualised home and community-based exercise programme for people after stroke.', Brain injury, 31 1617-1624 (2017) [C1]
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Nova |
2017 |
Wong R, Ahmad W, Davies A, Spratt N, Boyle A, Levi C, et al., 'Assessment of cerebral blood flow in adult patients with aortic coarctation', Cardiology in the Young, 27 1606-1613 (2017) [C1]
Background Survival into adult life in patients with aortic coarctation is typical following surgical and catheter-based techniques to relieve obstruction. Late sequelae are recog... [more]
Background Survival into adult life in patients with aortic coarctation is typical following surgical and catheter-based techniques to relieve obstruction. Late sequelae are recognised, including stroke, hypertension, and intracerebral aneurysm formation, with the underlying mechanisms being unclear. We hypothesised that patients with a history of aortic coarctation may have abnormalities of cerebral blood flow compared with controls. Methods Patients with a history of aortic coarctation underwent assessment of cerebral vascular function. Vascular responsiveness of intracranial vessels to hypercapnia and degree of cerebral artery stiffness using Doppler-derived pulsatility indices were used. Response to photic stimuli was used to assess neurovascular coupling, which reflects endothelial function in response to neuronal activation. Patient results were compared with age- and sex-matched controls. Results A total of 13 adult patients (males=10; 77%) along with 13 controls underwent evaluation. The mean age was 36.1±3.7 years in the patient group. Patients with a background of aortic coarctation were noted to have increased pulse pressure on blood pressure assessment at baseline with increased intracranial artery stiffness compared with controls. Patients with a history of aortic coarctation had less reactive cerebral vasculature to hypercapnic stimuli and impaired neurovascular coupling compared with controls. Results Adult patients with aortic coarctation had increased intracranial artery stiffness compared with controls, in addition to cerebral vasculature showing less responsiveness to hypercapnic and photic stimuli. Further studies are required to assess the aetiology and consequences of these documented abnormalities in cerebral blood flow in terms of stroke risk, cerebral aneurysm formation, and cognitive dysfunction.
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Nova |
2017 |
Bivard A, Levi C, Lin L, Cheng X, Aviv R, Spratt NJ, et al., 'Validating a Predictive Model of Acute Advanced Imaging Biomarkers in Ischemic Stroke', Stroke, 48 645-650 (2017) [C1]
Background and Purpose - Advanced imaging to identify tissue pathophysiology may provide more accurate prognostication than the clinical measures used currently in stroke. This st... [more]
Background and Purpose - Advanced imaging to identify tissue pathophysiology may provide more accurate prognostication than the clinical measures used currently in stroke. This study aimed to derive and validate a predictive model for functional outcome based on acute clinical and advanced imaging measures. Methods - A database of prospectively collected sub-4.5 hour patients with ischemic stroke being assessed for thrombolysis from 5 centers who had computed tomographic perfusion and computed tomographic angiography before a treatment decision was assessed. Individual variable cut points were derived from a classification and regression tree analysis. The optimal cut points for each assessment variable were then used in a backward logic regression to predict modified Rankin scale (MRS) score of 0 to 1 and 5 to 6. The variables remaining in the models were then assessed using a receiver operating characteristic curve analysis. Results - Overall, 1519 patients were included in the study, 635 in the derivation cohort and 884 in the validation cohort. The model was highly accurate at predicting MRS score of 0 to 1 in all patients considered for thrombolysis therapy (area under the curve [AUC] 0.91), those who were treated (AUC 0.88) and those with recanalization (AUC 0.89). Next, the model was highly accurate at predicting MRS score of 5 to 6 in all patients considered for thrombolysis therapy (AUC 0.91), those who were treated (0.89) and those with recanalization (AUC 0.91). The odds ratio of thrombolysed patients who met the model criteria achieving MRS score of 0 to 1 was 17.89 (4.59-36.35, P<0.001) and for MRS score of 5 to 6 was 8.23 (2.57-26.97, P<0.001). Conclusions - This study has derived and validated a highly accurate model at predicting patient outcome after ischemic stroke.
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Nova |
2017 |
Bhaskar S, Stanwell P, Bivard A, Spratt N, Walker R, Kitsos GH, et al., 'The influence of initial stroke severity on the likelihood of unfavourable clinical outcome and death at 90 days following acute ischemic stroke: A tertiary hospital stroke register study', Neurology India, 65 1252-1259 (2017) [C1]
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Nova |
2017 |
Demeestere J, Garcia-Esperon C, Lin L, Bivard A, Ang T, Smoll NR, et al., 'Validation of the National Institutes of Health Stroke Scale-8 to Detect Large Vessel Occlusion in Ischemic Stroke', Journal of Stroke and Cerebrovascular Diseases, 26 1419-1426 (2017) [C1]
Background Patients with acute ischemic stroke and large vessel occlusion (LVO) may benefit from prehospital identification and transfer to a center offering endovascular therapy.... [more]
Background Patients with acute ischemic stroke and large vessel occlusion (LVO) may benefit from prehospital identification and transfer to a center offering endovascular therapy. Aims We aimed to assess the accuracy of an existing 8-item stroke scale (National Institutes of Health Stroke Scale-8 [NIHSS-8]) for identification of patients with acute stroke with LVO. Methods We retrospectively calculated NIHSS-8 scores in a population of consecutive patients with presumed acute stroke assessed by emergency medical services (EMS). LVO was identified on admission computed tomography angiography. Accuracy to identify LVO was calculated using receiver operating characteristics analysis. We used weighted Cohen's kappa statistics to assess inter-rater reliability for the NIHSS-8 score between the EMS and the hospital stroke team on a prospectively evaluated subgroup. Results Of the 551 included patients, 381 had a confirmed ischemic stroke and 136 patients had an LVO. NIHSS scores were significantly higher in patients with LVO (median 18; interquartile range 14-22). The NIHSS-8 score reliably predicted the presence of LVO (area under the receiver operating characteristic curve.82). The optimum NIHSS-8 cutoff of 8 or more had a sensitivity of.81, specificity of.75, and Youden index of.56 for prediction of LVO. The EMS and the stroke team reached substantial agreement (¿ =.69). Conclusions Accuracy of the NIHSS-8 to identify LVO in a population of patients with suspected acute stroke is comparable to existing prehospital stroke scales. The scale can be performed by EMS with reasonable reliability. Further validation in the field is needed to assess accuracy of the scale to identify patients with LVO eligible for endovascular treatment in a prehospital setting.
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Nova |
2017 |
Janssen H, Dunstan DW, Bernhardt J, Walker FR, Patterson A, Callister R, et al., 'Breaking up sitting time after stroke (BUST-Stroke)', INTERNATIONAL JOURNAL OF STROKE, 12 425-429 (2017)
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2017 |
Dunn A, Marsden DL, Van Vliet P, Spratt NJ, Callister R, 'Independently ambulant, community-dwelling stroke survivors have reduced cardiorespiratory fitness, mobility and knee strength compared to an age- and gendermatched cohort', Topics in Stroke Rehabilitation, 24 163-169 (2017) [C1]
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Nova |
2017 |
Marsden DL, Dunn A, Callister R, McElduff P, Levi CR, Spratt NJ, 'Interval circuit training for cardiorespiratory fitness is feasible for people after stroke', International Journal of Therapy and Rehabilitation, 24 190-202 (2017) [C1]
Aims: To determine if community-dwelling stroke survivors can achieve exercise intensities sufficient to improve cardiorespiratory fitness during a single session of circuit train... [more]
Aims: To determine if community-dwelling stroke survivors can achieve exercise intensities sufficient to improve cardiorespiratory fitness during a single session of circuit training using an interval training approach. Methods: Thirteen independently ambulant participants within 1 year of stroke were included in this observational study (females=54%; median age=65.6 years; interquartile range=23.9). Exercise intensities were assessed throughout an individually tailored circuit of up to seven 5-minute workstations from a selection of nine functional (e.g. walking, stairs, balance) and three ergometer (upright cycle, rower, treadmill) workstations. The interval durations ranged from 5¿60 seconds. Oxygen consumption (VO2) was recorded continuously using a portable metabolic system. The average VO2 during each 30-second epoch was determined. VO2=10.5 mL/kg/min was categorised as =moderate intensity. Findings: Participants exercised at VO2=10.5 mL/kg/min for the majority of the time on the workstations [functional: 369/472 epochs (78%), ergometer: 170/204 epochs (83%)]. Most (69%) participants exercised for =30 minutes. No serious adverse events occurred. Conclusions: Applying interval training principles to a circuit of functional and ergometer workstations enabled ambulant participants to exercise at an intensity and for a duration that can improve cardiorespiratory fitness. The training approach appears feasible, safe and a promising way to incorporate both cardiorespiratory fitness and functional training into post-stroke management.
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Nova |
2016 |
Kawano H, Levi C, Inatomi Y, Pagram H, Kerr E, Bivard A, et al., 'International benchmarking for acute thrombolytic therapy implementation in Australia and Japan', Journal of Clinical Neuroscience, 29 87-91 (2016) [C1]
Although a wide range of strategies have been established to improve intravenous tissue plasminogen activator (IV-tPA) treatment rates, international benchmarking has not been reg... [more]
Although a wide range of strategies have been established to improve intravenous tissue plasminogen activator (IV-tPA) treatment rates, international benchmarking has not been regularly used as a systems improvement tool. We compared acute stroke codes (ASC) between two hospitals in Australia and Japan to study the activation process and potentially improve the implementation of thrombolysis. Consecutive patients who were admitted to each hospital via ASC were prospectively collected. We compared IV-tPA rates, factors contributing to exclusion from IV-tPA, and pre- and in-hospital process of care. IV-tPA treatment rates were significantly higher in the Australian hospital than in the Japanese (41% versus 25% of acute ischaemic stroke patients, p = 0.0016). In both hospitals, reasons for exclusion from IV-tPA treatment were intracerebral haemorrhage, mild symptoms, and stroke mimic. Patients with baseline National Institutes of Health Stroke Scale score =5 were more likely to be excluded from IV-tPA in the Japanese hospital. Of patients treated with IV-tPA, the door-to-needle time (median, 63 versus 54 minutes, p = 0.0355) and imaging-to-needle time (34 versus 27 minutes, p = 0.0220) were longer in the Australian hospital. Through international benchmarking using cohorts captured under ASC, significant differences were noted in rates of IV-tPA treatment and workflow speed. This variation highlights opportunity to improve and areas to focus targeted practice improvement strategies.
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Nova |
2016 |
Bivard A, Cheng X, Lin LT, Levi C, Spratt N, Kleinig T, et al., 'Global White Matter Hypoperfusion on CT Predicts Larger Infarcts and Hemorrhagic Transformation after Acute Ischemia', CNS Neuroscience and Therapeutics, 22 238-243 (2016) [C1]
Introduction: Presence of white matter hyperintensity (WMH) on MRI is a marker of cerebral small vessel disease and is associated with increased small vessel stroke and increased ... [more]
Introduction: Presence of white matter hyperintensity (WMH) on MRI is a marker of cerebral small vessel disease and is associated with increased small vessel stroke and increased risk of hemorrhagic transformation (HT) after thrombolysis. Aim: We sought to determine whether white matter hypoperfusion (WMHP) on perfusion CT (CTP) was related to WMH, and if WMHP predisposed to acute lacunar stroke subtype and HT after thrombolysis. Methods: Acute ischemic stroke patients within 12 h of symptom onset at 2 centers were prospectively recruited between 2011 and 2013 for the International Stroke Perfusion Imaging Registry. Participants routinely underwent baseline CT imaging, including CTP, and follow-up imaging with MRI at 24 h. Results: Of 229 ischemic stroke patients, 108 were Caucasians and 121 Chinese. In the contralateral white matter, patients with acute lacunar stroke had lower cerebral blood flow (CBF) and cerebral blood volume (CBV), compared to those with other stroke subtypes (P = 0.041). There were 46 patients with HT, and WMHP was associated with increased risk of HT (R 2 = 0.417, P = 0.002). Compared to previously reported predictors of HT, WMHP performed better than infarct core volume (R 2 = 0.341, P = 0.034), very low CBV volume (R 2 = 0.249, P = 0.026), and severely delayed perfusion (Tmax>14 second R 2 = 0.372, P = 0.011). Patients with WMHP also had larger acute infarcts and increased infarct growth compared to those without WMHP (mean 28 mL vs. 13 mL P < 0.001). Conclusion: White matter hypoperfusion remote to the acutely ischemic region on CTP is a marker of small vessel disease and was associated with increased HT, larger acute infarct cores, and greater infarct growth.
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Nova |
2016 |
Schleicher N, Tomkins AJ, Kampschulte M, Hyvelin JM, Botteron C, Juenemann M, et al., 'Sonothrombolysis with BR38 microbubbles improves microvascular patency in a rat model of stroke', PLoS ONE, 11 (2016) [C1]
Background: Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical... [more]
Background: Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model. Methods: We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography. Results: Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p<0.05), but was not significantly different from the contralateral hemisphere in all microbubble-treated groups (p>0.1). Conclusions: Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory.
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Nova |
2016 |
Beard DJ, Murtha LA, McLeod DD, Spratt NJ, 'Intracranial Pressure and Collateral Blood Flow', Stroke, 47 1695-1700 (2016) [C1]
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Nova |
2016 |
Marsden DL, Dunn A, Callister R, McElduff P, Levi CR, Spratt NJ, 'A Home- and Community-Based Physical Activity Program Can Improve the Cardiorespiratory Fitness and Walking Capacity of Stroke Survivors', Journal of Stroke and Cerebrovascular Diseases, 25 2386-2398 (2016) [C1]
Background The cardiorespiratory fitness of stroke survivors is low. Center-based exercise programs that include an aerobic component have been shown to improve poststroke cardior... [more]
Background The cardiorespiratory fitness of stroke survivors is low. Center-based exercise programs that include an aerobic component have been shown to improve poststroke cardiorespiratory fitness. This pilot study aims to determine the feasibility, safety, and preliminary efficacy of an individually tailored home- and community-based exercise program to improve cardiorespiratory fitness and walking capacity in stroke survivors. Methods Independently ambulant, community-dwelling stroke survivors were recruited. The control (n¿=¿10) and intervention (n¿=¿10) groups both received usual care. In addition the intervention group undertook a 12-week, individually tailored, home- and community-based exercise program, including once-weekly telephone or e-mail support. Assessments were conducted at baseline and at 12 weeks. Feasibility was determined by retention and program participation, and safety by adverse events. Efficacy measures included change in cardiorespiratory fitness (peak oxygen consumption [VO2peak]) and distance walked during the Six-Minute Walk Test (6MWT). Analysis of covariance was used for data analysis. Results All participants completed the study with no adverse events. All intervention participants reported undertaking their prescribed program. VO2peak improved more in the intervention group (1.17¿±¿.29¿L/min to 1.35¿±¿.33¿L/min) than the control group (1.24¿±¿.23¿L/min to 1.24¿±¿.33¿L/min, between-group difference¿=¿.18¿L/min, 95% confidence interval [CI]:.01-.36). Distance walked improved more in the intervention group (427¿±¿123¿m to 494¿±¿67m) compared to the control group (456¿±¿101m to 470¿±¿106m, between-group difference¿=¿45¿m, 95% CI:.3-90). Conclusions Our individually tailored approach with once-weekly telephone or e-mail support was feasible and effective in selected stroke survivors. The 16% greater improvement in VO2peak during the 6MWT achieved in the intervention versus control group is comparable to improvements attained in supervised, center-based programs.
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Nova |
2016 |
Zheng D, Sato S, Arima H, Heeley E, Delcourt C, Cao Y, et al., 'Estimated GFR and the Effect of Intensive Blood Pressure Lowering after Acute Intracerebral Hemorrhage', American Journal of Kidney Diseases, 68 94-102 (2016) [C1]
Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielde... [more]
Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP < 140 mm Hg) or contemporaneous guideline-based (target SBP < 180 mm Hg) BP management. Setting & Participants: 2,823 patients from 144 clinical hospitals in 21 countries. Predictors Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60 mL/min/1.73 m2, respectively). Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitations: Generalizability issues arising from a clinical trial population. Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs.
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Nova |
2016 |
Beard DJ, Logan CL, McLeod DD, Hood RJ, Pepperall D, Murtha LA, Spratt NJ, 'Ischemic penumbra as a trigger for intracranial pressure rise - A potential cause for collateral failure and infarct progression?', J Cereb Blood Flow Metab, 36 917-927 (2016) [C1]
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Nova |
2016 |
Schumacher TL, Burrows TL, Rollo ME, Spratt NJ, Callister R, Collins CE, 'Effectiveness of a Brief Dietetic Intervention for Hyperlipidaemic Adults Using Individually-Tailored Dietary Feedback', HEALTHCARE, 4 (2016) [C1]
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Nova |
2016 |
Murtha LA, Beard DJ, Bourke JT, Pepperall D, McLeod DD, Spratt NJ, 'Intracranial Pressure Elevation 24 h after Ischemic Stroke in Aged Rats Is Prevented by Early, Short Hypothermia Treatment.', Front Aging Neurosci, 8 124 (2016) [C1]
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Nova |
2016 |
Tomkins AJ, Hood RJ, Pepperall D, Null CL, Levi CR, Spratt NJ, 'Thrombolytic Recanalization of Carotid Arteries Is Highly Dependent on Degree of Stenosis, Despite Sonothrombolysis.', J Am Heart Assoc, 5 (2016) [C1]
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Nova |
2016 |
Anderson CS, Robinson T, Lindley RI, Arima H, Lavados PM, Lee TH, et al., 'Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke', New England Journal of Medicine, 374 2313-2323 (2016) [C1]
BACKGROUND: Thrombolytic therapy for acute ischemic stroke with a lower-than-standard dose of intravenous alteplase may improve recovery along with a reduced risk of intracerebral... [more]
BACKGROUND: Thrombolytic therapy for acute ischemic stroke with a lower-than-standard dose of intravenous alteplase may improve recovery along with a reduced risk of intracerebral hemorrhage. METHODS: Using a 2-by-2 quasi-factorial open-label design, we randomly assigned 3310 patients who were eligible for thrombolytic therapy (median age, 67 years; 63% Asian) to low-dose intravenous alteplase (0.6 mg per kilogram of body weight) or the standard dose (0.9 mg per kilogram); patients underwent randomization within 4.5 hours after the onset of stroke. The primary objective was to determine whether the low dose would be noninferior to the standard dose with respect to the primary outcome of death or disability at 90 days, which was defined by scores of 2 to 6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Secondary objectives were to determine whether the low dose would be superior to the standard dose with respect to centrally adjudicated symptomatic intracerebral hemorrhage and whether the low dose would be noninferior in an ordinal analysis of modified Rankin scale scores (testing for an improvement in the distribution of scores). The trial included 935 patients who were also randomly assigned to intensive or guideline-recommended blood-pressure control. RESULTS: The primary outcome occurred in 855 of 1607 participants (53.2%) in the low-dose group and in 817 of 1599 participants (51.1%) in the standard-dose group (odds ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; the upper boundary exceeded the noninferiority margin of 1.14; P=0.51 for noninferiority). Low-dose alteplase was noninferior in the ordinal analysis of modified Rankin scale scores (unadjusted common odds ratio, 1.00; 95% CI, 0.89 to 1.13; P=0.04 for noninferiority). Major symptomatic intracerebral hemorrhage occurred in 1.0% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group (P=0.01); fatal events occurred within 7 days in 0.5% and 1.5%, respectively (P=0.01). Mortality at 90 days did not differ significantly between the two groups (8.5% and 10.3%, respectively; P=0.07). CONCLUSIONS: This trial involving predominantly Asian patients with acute ischemic stroke did not show the noninferiority of low-dose alteplase to standard-dose alteplase with respect to death and disability at 90 days. There were significantly fewer symptomatic intracerebral hemorrhages with low-dose alteplase.
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Nova |
2016 |
Kawano H, Bivard A, Lin L, Spratt NJ, Miteff F, Parsons MW, Levi CR, 'Relationship between Collateral Status, Contrast Transit, and Contrast Density in Acute Ischemic Stroke', Stroke, 47 742-749 (2016) [C1]
Background and Purpose-Collateral circulation is recognized to influence the life expectancy of the ischemic penumbra in acute ischemic stroke. The best method to quantify collate... [more]
Background and Purpose-Collateral circulation is recognized to influence the life expectancy of the ischemic penumbra in acute ischemic stroke. The best method to quantify collateral status on acute imaging is uncertain. We aimed to determine the relationship between visual collateral status, quantitative collateral assessments, baseline computed tomographic perfusion measures, and tissue outcomes on follow-up imaging. Methods-Sixty-six consecutive patients with acute ischemic stroke clinically eligible for recanalization therapy and with M1 or M2 middle cerebral artery occlusion were evaluated. We compared the visual collateral scoring with measures of contrast peak time delay and contrast peak density. We also compared these measures for their ability to predict perfusion lesion and infarct core volumes, final infarct, and infarct growth. Results-Shorter contrast peak time delay (P=0.041) and higher contrast peak density (P=0.002) were associated with good collateral status. Shorter contrast peak time delay correlated with higher contrast peak density (ß=-4.413; P=0.037). In logistic regression analysis after adjustment for age, sex, onset-computed tomographic time, and occlusion site, higher contrast peak density was independently associated with good collateral status (P=0.009). Multiple regression analysis showed that higher contrast peak density was an independent predictor of smaller perfusion lesion volume (P=0.029), smaller ischemic core volume (P=0.044), smaller follow-up infarct volume (P=0.005), and smaller infarct growth volume (P=0.010). Conclusions-Visual collateral status, contrast peak density, and contrast peak time delay were inter-related, and good collateral status was strongly associated with contrast peak density. Contrast peak density in collateral vessel may be an important factor in tissue fate in acute ischemic stroke.
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Nova |
2016 |
Schumacher TL, Burrows TL, Thompson DI, Callister R, Spratt NJ, Collins CE, 'The Role of Family in a Dietary Risk Reduction Intervention for Cardiovascular Disease.', Healthcare (Basel), 4 (2016) [C1]
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Nova |
2016 |
Bivard A, Yassi N, Krishnamurthy V, Lin L, Levi C, Spratt NJ, et al., 'A comprehensive analysis of metabolic changes in the salvaged penumbra', Neuroradiology, 58 409-415 (2016) [C1]
Introduction: We aimed to assess metabolite profiles in peri-infarct tissue with magnetic resonance spectroscopy (MRS) and correlate these with early and late clinical recovery. M... [more]
Introduction: We aimed to assess metabolite profiles in peri-infarct tissue with magnetic resonance spectroscopy (MRS) and correlate these with early and late clinical recovery. Methods: One hundred ten anterior circulation ischemic stroke patients presenting to hospital within 4.5¿h of symptom onset and treated with intravenous thrombolysis were studied. Patients underwent computer tomography perfusion (CTP) scanning and subsequently 3-T magnetic resonance imaging (MRI) 24¿h after stroke onset, including single-voxel, short-echo-time (30¿ms) MRS, and diffusion- and perfusion-weighted imaging (DWI and PWI). MRS voxels were placed in the peri-infarct region in reperfused penumbral tissue. A control voxel was placed in the contralateral homologous area. Results: The concentrations of total creatine (5.39 vs 5.85¿mM, p = 0.044) and N-acetylaspartic acid (NAA, 6.34 vs 7.13¿mM ± 1.57, p < 0.001) were reduced in peri-infarct tissue compared to the matching contralateral region. Baseline National Institutes of Health Stroke Score was correlated with glutamate concentration in the reperfused penumbra at 24¿h (r2 = 0.167, p = 0.017). Higher total creatine was associated with better neurological outcome at 24¿h (r2 = 0.242, p = 0.004). Lower peri-infarct glutamate was a stronger predictor of worse 3-month clinical outcome (area under the curve (AUC) 0.89, p < 0.001) than DWI volume (AUC = 0.79, p < 0.001). Conclusion: Decreased glutamate, creatine, and NAA concentrations are associated with poor neurological outcome at 24¿h and greater disability at 3¿months. The significant metabolic variation in salvaged tissue may potentially explain some of the variability seen in stroke recovery despite apparently successful reperfusion.
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Nova |
2015 |
Murtha LA, McLeod DD, Pepperall D, McCann SK, Beard DJ, Tomkins AJ, et al., 'Intracranial pressure elevation after ischemic stroke in rats: Cerebral edema is not the only cause, and short-duration mild hypothermia is a highly effective preventive therapy', Journal of Cerebral Blood Flow and Metabolism, 35 592-600 (2015) [C1]
In both the human and animal literature, it has largely been assumed that edema is the primary cause of intracranial pressure (ICP) elevation after stroke and that more edema equa... [more]
In both the human and animal literature, it has largely been assumed that edema is the primary cause of intracranial pressure (ICP) elevation after stroke and that more edema equates to higher ICP. We recently demonstrated a dramatic ICP elevation 24 hours after small ischemic strokes in rats, with minimal edema. This ICP elevation was completely prevented by short-duration moderate hypothermia soon after stroke. Here, our aims were to determine the importance of edema in ICP elevation after stroke and whether mild hypothermia could prevent the ICP rise. Experimental stroke was performed in rats. ICP was monitored and short-duration mild (35 °C) or moderate (32.5 °C) hypothermia, or normothermia (37 °C) was induced after stroke onset. Edema was measured in three studies, using wet-dry weight calculations, T 2-weighted magnetic resonance imaging, or histology. ICP increased 24 hours after stroke onset in all normothermic animals. Short-duration mild or moderate hypothermia prevented this rise. No correlation was seen between ¿ICP and edema or infarct volumes. Calculated rates of edema growth were orders of magnitude less than normal cerebrospinal fluid production rates. These data challenge current concepts and suggest that factors other than cerebral edema are the primary cause of the ICP elevation 24 hours after stroke onset.
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Nova |
2015 |
Campbell BCV, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, et al., 'Endovascular therapy for ischemic stroke with perfusion-imaging selection', New England Journal of Medicine, 372 1009-1018 (2015) [C1]
Background: Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently de... [more]
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.)
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Nova |
2015 |
Beard DJ, Mcleod DD, Logan CL, Murtha LA, Imtiaz MS, Van Helden DF, Spratt NJ, 'Intracranial pressure elevation reduces flow through collateral vessels and the penetrating arterioles they supply. A possible explanation for 'collateral failure' and infarct expansion after ischemic stroke', Journal of Cerebral Blood Flow and Metabolism, 35 861-872 (2015) [C1]
Recent human imaging studies indicate that reduced blood flow through pial collateral vessels ('collateral failure') is associated with late infarct expansion despite st... [more]
Recent human imaging studies indicate that reduced blood flow through pial collateral vessels ('collateral failure') is associated with late infarct expansion despite stable arterial occlusion. The cause for 'collateral failure' is unknown. We recently showed that intracranial pressure (ICP) rises dramatically but transiently 24 hours after even minor experimental stroke. We hypothesized that ICP elevation would reduce collateral blood flow. First, we investigated the regulation of flow through collateral vessels and the penetrating arterioles arising from them during stroke reperfusion. Wistar rats were subjected to intraluminal middle cerebral artery (MCA) occlusion (MCAo). Individual pial collateral and associated penetrating arteriole blood flow was quantified using fluorescent microspheres. Baseline bidirectional flow changed to MCA-directed flow and increased by >450% immediately after MCAo. Collateral diameter changed minimally. Second, we determined the effect of ICP elevation on collateral and watershed penetrating arteriole flow. Intracranial pressure was artificially raised in stepwise increments during MCAo. The ICP increase was strongly correlated with collateral and penetrating arteriole flow reductions. Changes in collateral flow post-stroke appear to be primarily driven by the pressure drop across the collateral vessel, not vessel diameter. The ICP elevation reduces cerebral perfusion pressure and collateral flow, and is the possible explanation for 'collateral failure' in stroke-in-progression.
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Nova |
2015 |
Dunn A, Marsden DL, Nugent E, Van Vliet P, Spratt NJ, Attia J, Callister R, 'Protocol variations and six-minute walk test performance in stroke survivors: A systematic review with meta-analysis', Stroke Research and Treatment, 2015 1-28 (2015) [C1]
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Nova |
2015 |
White JH, Bartley E, Janssen H, Jordan LA, Spratt N, 'Exploring stroke survivor experience of participation in an enriched environment: A qualitative study', Disability and Rehabilitation, 37 593-600 (2015) [C1]
Background: Data highlight the importance of undertaking intense and frequent repetition of activities within stroke rehabilitation to maximise recovery. An enriched environment (... [more]
Background: Data highlight the importance of undertaking intense and frequent repetition of activities within stroke rehabilitation to maximise recovery. An enriched environment (EE) provides a medium in which these activities can be performed and enhanced recovery achieved. An EE has been shown to promote neuroplasticity in animal models of stroke, facilitating enhanced recovery of motor and cognitive function. However, the benefit of enriching the environment of stroke survivors remains unknown. Aim: To qualitatively explore stroke survivors' experience of implementation of exposure to an EE within a typical stroke rehabilitation setting, in order to identify facilitators and barriers to participation. Methods: Semi-structured interviews with 10 stroke survivors (7 females and 3 males, mean age of 70.5 years) exposed to an EE for a 2-week period following exposure to routine rehabilitation within a stroke rehabilitation ward. An inductive thematic approach was utilised to collect and analyse data. Results: Qualitative themes emerged concerning the environmental enrichment paradigm including: (1) "It got me moving"-perceived benefits of participation in an EE; (2) "You can be bored or you can be busy."-Attenuating factors influencing participation in an EE; (3) "I don't like to make the staff busier"-limitations to use of the EE. Conclusions: This study provides preliminary support for the implementation of an EE within a typical stroke rehabilitation setting from a patient perspective. Reported benefits included (1) increased motor, cognitive and sensory stimulation, (2) increased social interaction, (3) alleviation of degree of boredom and (4) increased feelings of personal control. However, participants also identified a number of barriers affecting implementation of the EE. We have previously published findings on perceptions of nursing staff working with stroke survivors in this enriched rehabilitation environment who identified that patients benefited from having better access to physical, cognitive and social activities. Together, results contribute to valuable evidence for future implementation of an EE in stroke rehabilitation settings.Implications for RehabilitationStroke survivor access to an enriched environment (EE):Results identified that participation in both individual and communal forms of environment enrichment within the stroke rehabilitation ward resulted in increased access to activities providing increased opportunities for enhanced motor, cognitive and sensory stimulation.Increased access to and participation in activities of the environmental enrichment (individual and communal) interrupted the ongoing cycle of boredom and inactivity experienced by many participants.This study provides preliminary support for the implementation of an EE within a typical stroke rehabilitation setting from a patient perspective.
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Nova |
2015 |
Schumacher TL, Burrows TL, Thompson DI, Spratt NJ, Callister R, Collins CE, 'Feasibility of Recruiting Families into a Heart Disease Prevention Program Based on Dietary Patterns.', Nutrients, 7 7042-7057 (2015) [C1]
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Nova |
2015 |
Jones KA, Zouikr I, Patience M, Clarkson AN, Isgaard J, Johnson SJ, et al., 'Chronic stress exacerbates neuronal loss associated with secondary neurodegeneration and suppresses microglial-like cells following focal motor cortex ischemia in the mouse', Brain, Behavior, and Immunity, 48 57-67 (2015) [C1]
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2015 |
Bivard A, Levi C, Krishnamurthy V, McElduff P, Miteff F, Spratt NJ, et al., 'Perfusion computed tomography to assist decision making for stroke thrombolysis', Brain, 138 1919-1931 (2015) [C1]
The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aim... [more]
The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aimed to measure the outcomes for patients treated with intravenous recombinant tissue plasminogen activator (rtPA) at a comprehensive stroke care facility where perfusion computed tomography was routinely used for thrombolysis eligibility decision assistance. Our overall hypothesis was that patients with 'target' mismatch on perfusion computed tomography would have improved outcomes with rtPA. This was a prospective cohort study of consecutive ischaemic stroke patients who fulfilled standard clinical/non-contrast computed tomography eligibility criteria for treatment with intravenous rtPA, but for whom perfusion computed tomography was used to guide the final treatment decision. The 'real-time' perfusion computed tomography assessments were qualitative; a large perfusion computed tomography ischaemic core, or lack of significant perfusion lesion-core mismatch were considered relative exclusion criteria for thrombolysis. Specific volumetric perfusion computed tomography criteria were not used for the treatment decision. The primary analysis compared 3-month modified Rankin Scale in treated versus untreated patients after 'off-line' (post-treatment) quantitative volumetric perfusion computed tomography eligibility assessment based on presence or absence of 'target' perfusion lesion-core mismatch (mismatch ratio >1.8 and volume >15 ml, core <70 ml). In a second analysis, we compared outcomes of the perfusion computed tomography-selected rtPA-treated patients to an Australian historical cohort of non-contrast computed tomography-selected rtPA-treated patients. Of 635 patients with acute ischaemic stroke eligible for rtPA by standard criteria, thrombolysis was given to 366 patients, with 269 excluded based on visual real-time perfusion computed tomography assessment. After off-line quantitative perfusion computed tomography classification: 253 treated patients and 83 untreated patients had 'target' mismatch, 56 treated and 31 untreated patients had a large ischaemic core, and 57 treated and 155 untreated patients had no target mismatch. In the primary analysis, only in the target mismatch subgroup did rtPA-treated patients have significantly better outcomes (odds ratio for 3-month, modified Rankin Scale 0-2 = 13.8, P < 0.001). With respect to the perfusion computed tomography selected rtPA-treated patients (n = 366) versus the clinical/non-contrast computed tomography selected rtPA-treated patients (n = 396), the perfusion computed tomography selected group had higher adjusted odds of excellent outcome (modified Rankin Scale 0-1 odds ratio 1.59, P = 0.009) and lower mortality (odds ratio 0.56, P = 0.021). Although based on observational data sets, our analyses provide support for the hypothesis that perfusion computed tomography improves the identification of patients likely to respond to thrombolysis, and also those in whom natural history may be difficult to modify with treatment.
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2015 |
Mcleod DD, Parsons MW, Hood R, Hiles B, Allen J, Mccann SK, et al., 'Perfusion computed tomography thresholds defining ischemic penumbra and infarct core: Studies in a rat stroke model', International Journal of Stroke, 10 553-559 (2015) [C1]
Background: Perfusion computed tomography is becoming more widely used as a clinical imaging tool to predict potentially salvageable tissue (ischemic penumbra) after ischemic stro... [more]
Background: Perfusion computed tomography is becoming more widely used as a clinical imaging tool to predict potentially salvageable tissue (ischemic penumbra) after ischemic stroke and guide reperfusion therapies. Aims: The study aims to determine whether there are important changes in perfusion computed tomography thresholds defining ischemic penumbra and infarct core over time following stroke. Methods: Permanent middle cerebral artery occlusion was performed in adult outbred Wistar rats (n=6) and serial perfusion computed tomography scans were taken every 30 mins for 2h. To define infarction thresholds at 1h and 2h post-stroke, separate groups of rats underwent 1h (n=6) and 2h (n=6) of middle cerebral artery occlusion followed by reperfusion. Infarct volumes were defined by histology at 24h. Co-registration with perfusion computed tomography maps (cerebral blood flow, cerebral blood volume, and mean transit time) permitted pixel-based analysis of thresholds defining infarction, using receiver operating characteristic curves. Results: Relative cerebral blood flow was the perfusion computed tomography parameter that most accurately predicted penumbra (area under the curve=0·698) and also infarct core (area under the curve=0·750). A relative cerebral blood flow threshold of <75% of mean contralateral cerebral blood flow most accurately predicted penumbral tissue at 0·5h (area under the curve=0·660), 1h (area under the curve=0·659), 1·5h (area under the curve=0·636), and 2h (area under the curve=0·664) after stroke onset. A relative cerebral blood flow threshold of <55% of mean contralateral most accurately predicted infarct core at 1h (area under the curve=0·765) and at 2h (area under the curve=0·689) after middle cerebral artery occlusion. Conclusions: The data provide perfusion computed tomography defined relative cerebral blood flow thresholds for infarct core and ischemic penumbra within the first two hours after experimental stroke in rats. These thresholds were shown to be stable to define the volume of infarct core and penumbra within this time window.
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2015 |
Tomkins AJ, Schleicher N, Murtha L, Kaps M, Levi CR, Nedelmann M, Spratt NJ, 'Platelet rich clots are resistant to lysis by thrombolytic therapy in a rat model of embolic stroke', Experimental and Translational Stroke Medicine, 7 (2015) [C1]
Background: Early recanalization of occluded vessels in stroke is closely associated with improved clinical outcome. Microbubble-enhanced sonothrombolysis is a promising therapy t... [more]
Background: Early recanalization of occluded vessels in stroke is closely associated with improved clinical outcome. Microbubble-enhanced sonothrombolysis is a promising therapy to improve recanalization rates and reduce the time to recanalization. Testing any thrombolytic therapy requires a model of thromboembolic stroke, but to date these models have been highly variable with regards to clot stability. Here, we developed a model of thromboembolic stroke in rats with site-specific delivery of platelet-rich clots (PRC) to the main stem of the middle cerebral artery (MCA). This model was used in a subsequent study to test microbubble-enhanced sonothrombolysis. Methods: In Study 1 we investigated spontaneous recanalization rates of PRC in vivo over 4 hours and measured infarct volumes at 24 hours. In Study 2 we investigated tPA-mediated thrombolysis and microbubble-enhanced sonothrombolysis in this model. Results: Study 1 demonstrated stable occlusion out to 4 hours in 5 of 7 rats. Two rats spontaneously recanalized at 40 and 70 minutes post-embolism. Infarct volumes were not significantly different in recanalized rats, 43.93 ± 15.44% of the ischemic hemisphere, compared to 48.93 ± 3.9% in non-recanalized animals (p = 0.7). In Study 2, recanalization was not observed in any of the groups post-treatment. Conclusions: Site specific delivery of platelet rich clots to the MCA origin resulted in high rates of MCA occlusion, low rates of spontaneous clot lysis and large infarction. These platelet rich clots were highly resistant to tPA with or without microbubble-enhanced sonothrombolysis. This resistance of platelet rich clots to enhanced thrombolysis may explain recanalization failures clinically and should be an impetus to better clot-type identification and alternative recanalization methods.
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2015 |
Tomkins AJ, Hood RJ, Levi CR, Spratt NJ, 'Tissue Plasminogen Activator for preclinical stroke research: Neither "rat" nor "human" dose mimics clinical recanalization in a carotid occlusion model', SCIENTIFIC REPORTS, 5 (2015) [C1]
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Nova |
2014 |
Meretoja A, Churilov L, Campbell BCV, Aviv RI, Yassi N, Barras C, et al., 'The Spot sign and Tranexamic acid On Preventing ICH growth - AUStralasia Trial (STOP-AUST): Protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial', International Journal of Stroke, 9 519-524 (2014) [C3]
Rationale: No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is... [more]
Rationale: No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. Aim: The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation 'spot sign' will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4·5-hours of stroke onset compared with placebo. Design: The Spot sign and Tranexamic acid On Preventing ICH growth - AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume <70ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1g 10-min bolus followed by 1g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. Study outcomes: The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. Discussion: This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636. © 2013 World Stroke Organization.
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2014 |
Bivard A, Krishnamurthy V, Stanwell P, Levi C, Spratt NJ, Davis S, Parsons M, 'Arterial Spin Labeling Versus Bolus-Tracking Perfusion in Hyperacute Stroke', Stroke, 45 127-133 (2014) [C1]
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2014 |
Janssen H, Ada L, Bernhardt J, McElduff P, Pollack M, Nilsson M, Spratt N, 'Physical, cognitive and social activity levels of stroke patients undergoing rehabilitation within a mixed rehabilitation unit', Clinical Rehabilitation, 28 91-101 (2014) [C1]
Objective: To determine physical, cognitive and social activity levels of stroke patients undergoing rehabilitation, and whether these changed over time. Design: Observational stu... [more]
Objective: To determine physical, cognitive and social activity levels of stroke patients undergoing rehabilitation, and whether these changed over time. Design: Observational study using behavioural mapping techniques to record patient activity over 12 hours on one weekday and one weekend day at baseline (week 1) and again two weeks later (week 2). Setting: A 20-bed mixed rehabilitation unit. Subjects: Fourteen stroke patients. Interventions: None. Main measures: Percentage of day spent in any activity or physical, cognitive and social activities. Level of independence using the Functional Independence Measure (FIM) and mood using the Patient Health Questionniare-9 (PHQ-9). Results: The stroke patients performed any activity for 49%, social activity for 32%, physical activity for 23% and cognitive activity for 4% of the day. Two weeks later, physical activity levels had increased by 4% (95% confidence interval (CI) 1 to 8), but levels of any activity or social and cognitive activities had not changed significantly. There was a significant: (i) positive correlation between change in physical activity and change in FIM score (r = 0.80), and (ii) negative correlation between change in social activity and change in PHQ-9 score (r = -0.72). The majority of activity was performed by the bedside (37%), and most physical (47%) and cognitive (54%) activities performed when alone. Patients undertook 5% (95% CI 2 to 9) less physical activity on the weekends compared with the weekdays. Conclusions: Levels of physical, cognitive and social activity of stroke patients were low and remained so even though level of independence and mood improved. These findings suggest the need to explore strategies to stimulate activity within rehabilitation environments. © The Author(s) 2013.
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2014 |
Bivard A, Krishnamurthy V, Stanwell P, Yassi N, Spratt NJ, Nilsson M, et al., 'Spectroscopy of reperfused tissue after stroke reveals heightened metabolism in patients with good clinical outcomes', JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 34 1944-1950 (2014) [C1]
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Nova |
2014 |
Chen G, Arima H, Wu G, Heeley E, Delcourt C, Zhang P, et al., 'Subarachnoid Extension of Intracerebral Hemorrhage and 90-Day Outcomes in INTERACT2', STROKE, 45 258-260 (2014)
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2014 |
Janssen H, Ada L, Bernhardt J, McElduff P, Pollack M, Nilsson M, Spratt NJ, 'An enriched environment increases activity in stroke patients undergoing rehabilitation in a mixed rehabilitation unit: a pilot non-randomized controlled trial', DISABILITY AND REHABILITATION, 36 255-262 (2014) [C1]
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Nova |
2014 |
Beard DJ, McLeod DD, Murtha LA, Spratt NJ, 'Elevation of intracranial pressure reduces leptomeningeal collateral and watershed blood flow during experimental stroke', CEREBROVASCULAR DISEASES, 37 65-65 (2014)
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2014 |
Bivard A, Krishnamurthy V, Levi C, McElduff P, Miteff F, Spratt N, et al., 'Stroke thrombolysis: Tissue is more important than time.', CEREBROVASCULAR DISEASES, 37 154-154 (2014)
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2014 |
Murtha LA, McLeod DD, Beard DJ, Pepperall DG, Spratt NJ, 'Short duration mild hypothermia prevents delayed intracranial pressure rise following experimental ischaemic stroke', CEREBROVASCULAR DISEASES, 37 340-340 (2014)
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2014 |
Bivard A, Krishnamurthy V, Levi C, McElduff P, Miteff F, Spratt N, et al., 'Does the presence of CTP mismatch predict better outcomes in thrombolysis-treated patients?', CEREBROVASCULAR DISEASES, 37 344-344 (2014)
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2014 |
Bivard A, Levi C, Krishnamurthy V, McElduff P, Miteff F, Spratt N, et al., 'Better stroke outcomes despite worse baseline stroke severity - the value of a combined clinical and advanced CT selection approach to thrombolysis.', CEREBROVASCULAR DISEASES, 37 701-701 (2014)
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2014 |
Egan KJ, Janssen H, Sena ES, Longley L, Speare S, Howells DW, et al., 'Exercise reduces infarct volume and facilitates neurobehavioral recovery: Results from a systematic review and meta-analysis of exercise in experimental models of focal ischemia', Neurorehabilitation and Neural Repair, 28 800-812 (2014) [C1]
Background. Regular exercise reduces the risk of a first-ever stroke and is associated with smaller infarcts. Although evidence has suggested that therapeutic exercise following s... [more]
Background. Regular exercise reduces the risk of a first-ever stroke and is associated with smaller infarcts. Although evidence has suggested that therapeutic exercise following stroke is beneficial, we do not yet know whether exercise reduces stroke severity and improves functional recovery. The mechanisms underlying any benefit remain unclear.
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Nova |
2014 |
Spratt NJ, Tomkins AJ, Pepperall D, McLeod DD, Calford MB, 'Allopregnanolone and its precursor progesterone do not reduce injury after experimental stroke in hypertensive rats - role of postoperative temperature regulation?', PLoS One, 9 e107752 (2014) [C1]
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Nova |
2014 |
Murtha LA, Mcleod DD, Mccann SK, Pepperall D, Chung S, Levi CR, et al., 'Short-duration hypothermia after ischemic stroke prevents delayed intracranial pressure rise', International Journal of Stroke, 9 553-559 (2014) [C1]
Background: Intracranial pressure elevation, peaking three to seven post-stroke is well recognized following large strokes. Data following small-moderate stroke are limited. Thera... [more]
Background: Intracranial pressure elevation, peaking three to seven post-stroke is well recognized following large strokes. Data following small-moderate stroke are limited. Therapeutic hypothermia improves outcome after cardiac arrest, is strongly neuroprotective in experimental stroke, and is under clinical trial in stroke. Hypothermia lowers elevated intracranial pressure; however, rebound intracranial pressure elevation and neurological deterioration may occur during rewarming. Hypotheses: (1) Intracranial pressure increases 24h after moderate and small strokes. (2) Short-duration hypothermia-rewarming, instituted before intracranial pressure elevation, prevents this 24h intracranial pressure elevation. Methods: Long-Evans rats with two hour middle cerebral artery occlusion or outbred Wistar rats with three hour middle cerebral artery occlusion had intracranial pressure measured at baseline and 24h. Wistars were randomized to 2·5h hypothermia (32·5°C) or normothermia, commencing 1h after stroke. Results: In Long-Evans rats (n=5), intracranial pressure increased from 10·9±4·6mmHg at baseline to 32·4±11·4mmHg at 24h, infarct volume was 84·3±15·9mm3. In normothermic Wistars (n=10), intracranial pressure increased from 6·7±2·3mmHg to 31·6±9·3mmHg, infarct volume was 31·3±18·4mm3. In hypothermia-treated Wistars (n=10), 24h intracranial pressure did not increase (7·0±2·8mmHg, P<0·001 vs. normothermia), and infarct volume was smaller (15·4±11·8mm3, P<0·05). Conclusions: We saw major intracranial pressure elevation 24h after stroke in two rat strains, even after small strokes. Short-duration hypothermia prevented the intracranial pressure rise, an effect sustained for at least 18h after rewarming. The findings have potentially important implications for design of future clinical trials. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.
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2014 |
White JH, Alborough K, Janssen H, Spratt N, Jordan L, Pollack M, 'Exploring staff experience of an "enriched environment" within stroke rehabilitation: a qualitative sub-study.', Disabil Rehabil, 36 1783-1789 (2014) [C1]
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Nova |
2014 |
Murtha LA, Yang Q, Parsons MW, Levi CR, Beard DJ, Spratt NJ, McLeod DD, 'Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats', Fluids and Barriers of the CNS, 11 (2014) [C1]
Background: Many aspects of CSF dynamics are poorly understood due to the difficulties involved in quantification and visualization. In particular, there is debate surrounding the... [more]
Background: Many aspects of CSF dynamics are poorly understood due to the difficulties involved in quantification and visualization. In particular, there is debate surrounding the route of CSF drainage. Our aim was to quantify CSF flow, volume, and drainage route dynamics in vivo in young and aged spontaneously hypertensive rats (SHR) using a novel contrast-enhanced computed tomography (CT) method.Methods: ICP was recorded in young (2-5 months) and aged (16 months) SHR. Contrast was administered into the lateral ventricles bilaterally and sequential CT imaging was used to visualize the entire intracranial CSF system and CSF drainage routes. A customized contrast decay software module was used to quantify CSF flow at multiple locations.Results: ICP was significantly higher in aged rats than in young rats (11.52 ± 2.36 mmHg, versus 7.04 ± 2.89 mmHg, p = 0.03). Contrast was observed throughout the entire intracranial CSF system and was seen to enter the spinal canal and cross the cribriform plate into the olfactory mucosa within 9.1 ± 6.1 and 22.2 ± 7.1 minutes, respectively. No contrast was observed adjacent to the sagittal sinus. There were no significant differences between young and aged rats in either contrast distribution times or CSF flow rates. Mean flow rates (combined young and aged) were 3.0 ± 1.5 µL/min at the cerebral aqueduct; 3.5 ± 1.4 µL/min at the 3rd ventric= and 2.8 ± 0.9 µL/min at the 4th ventricle. Intracranial CSF volumes (and as percentage total brain volume) were 204 ± 97 µL (8.8 ± 4.3%) in the young and 275 ± 35 µL (10.8 ± 1.9%) in the aged animals (NS).Conclusions: We have demonstrated a contrast-enhanced CT technique for measuring and visualising CSF dynamics in vivo. These results indicate substantial drainage of CSF via spinal and olfactory routes, but there was little evidence of drainage via sagittal sinus arachnoid granulations in either young or aged animals. The data suggests that spinal and olfactory routes are the primary routes of CSF drainage and that sagittal sinus arachnoid granulations play a minor role, even in aged rats with higher ICP. © 2014 Murtha et al.; licensee BioMed Central Ltd.
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2013 |
Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, et al., 'Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage', NEW ENGLAND JOURNAL OF MEDICINE, 368 2355-2365 (2013) [C1]
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2013 |
Bivard A, Levi C, Spratt N, Parsons M, 'Perfusion CT in Acute Stroke: A Comprehensive Analysis of Infarct and Penumbra', RADIOLOGY, 267 543-550 (2013) [C1]
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Nova |
2013 |
Menon BK, O'Brien B, Bivard A, Spratt NJ, Demchuk AM, Miteff F, et al., 'Assessment of leptomeningeal collaterals using dynamic CT angiography in patients with acute ischemic stroke', Journal of Cerebral Blood Flow and Metabolism, 33 365-371 (2013) [C1]
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Nova |
2013 |
Janssen H, Speare S, Spratt NJ, Sena ES, Ada L, Hannan AJ, et al., 'Exploring the Efficacy of Constraint in Animal Models of Stroke: Meta-analysis and Systematic Review of the Current Evidence', NEUROREHABILITATION AND NEURAL REPAIR, 27 3-12 (2013) [C1]
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Nova |
2013 |
Marsden DL, Dunn A, Callister R, Levi CR, Spratt NJ, 'Characteristics of Exercise Training Interventions to Improve Cardiorespiratory Fitness After Stroke: A Systematic Review With Meta-analysis', NEUROREHABILITATION AND NEURAL REPAIR, 27 775-788 (2013) [C1]
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Nova |
2013 |
Zareie H, Quain DA, Parsons M, Inder KJ, McElduff P, Miteff F, et al., 'The influence of anterior cerebral artery flow diversion measured by transcranial Doppler on acute infarct volume and clinical outcome in anterior circulation stroke', INTERNATIONAL JOURNAL OF STROKE, 8 228-234 (2013) [C1]
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2013 |
Magin P, Lasserson D, Parsons M, Spratt N, Evans M, Russell M, et al., 'Referral and triage of patients with transient ischemic attacks to an acute access clinic: Risk stratification in an Australian setting', International Journal of Stroke, 8 81-89 (2013) [C1]
Background: Transient ischemic attacks and minor stroke entail considerable risk of completed stroke but this risk is reduced by prompt assessment and treatment. Risk can be strat... [more]
Background: Transient ischemic attacks and minor stroke entail considerable risk of completed stroke but this risk is reduced by prompt assessment and treatment. Risk can be stratified according to the ABCD2 prediction score. Current guidelines suggest specialist assessment and treatment within 24h for high-risk event (ABCD2 score 4-7) and seven-days for low-risk event (ABCD2 score =3). Aims: The study aims to establish paths to care and outcomes for patients referred by general practitioners and emergency departments to an Australian acute access transient ischemic attack service. Methods: This is a prospective audit. Primary outcomes were time from event to referral, from referral to clinic appointment, and from event to appointment. ABCD2 score was calculated for each event. Time from event was modeled using Cox proportional hazards regression. Results: There were 231 clinic attendees (general practitioner: 127; emergency department: 104). Mean time from event to referral was 9·2 days (SD 23·7, median 2), from referral to being seen in the clinic was 13·6 days (SD 19·0, median 7), and from event to being seen in the clinic was 17·2 days (SD 27·1, median 10). Of low-risk patients, 38·5% were seen within seven-days of event. Of high-risk patients, 36·7% were seen within one-day. ABCD2 score was not a significant predictor of any time interval from event to clinic attendance. There were no completed strokes prior to clinic attendance. Conclusions: Times from event to clinic assessment were in excess of current recommendations and risk stratification was suboptimal, though short-term outcomes were good. Improvements in referral mechanisms may enhance risk-stratification and triage. © 2013 World Stroke Organization.
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2013 |
McLeod DD, Beard DJ, Parsons MW, Levi CR, Calford MB, Spratt NJ, 'Inadvertent Occlusion of the Anterior Choroidal Artery Explains Infarct Variability in the Middle Cerebral Artery Thread Occlusion Stroke Model', PLOS ONE, 8 (2013) [C1]
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2012 |
Murtha L, McLeod D, Spratt N, 'Epidural intracranial pressure measurement in rats using a fiber-optic pressure transducer.', Journal of visualized experiments : JoVE, (2012) [C1]
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Nova |
2012 |
Rostas JA, Skelding KA, Fluechter L, Dickson PW, Spratt NJ, 'CaMKII is Differentially Regulated in Striatum and Cortex', JOURNAL OF NEUROCHEMISTRY, 123 63-63 (2012) [E3]
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2012 |
Parsons MW, Spratt NJ, Bivard A, Campbell B, Chung K, Miteff F, et al., 'A randomized trial of tenecteplase versus alteplase for acute ischemic stroke', New England Journal of Medicine, 366 1099-1107 (2012) [C1]
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2012 |
Skelding KA, Spratt NJ, Fluechter L, Dickson PW, Rostas JA, 'alpha CaMKII is differentially regulated in brain regions that exhibit differing sensitivities to ischemia and excitotoxicity', Journal of Cerebral Blood Flow and Metabolism, 32 2181-2192 (2012) [C1]
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2012 |
The IST-3 Collaborative Group, 'The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial', Lancet, 379 2352-2363 (2012) [C1]
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2012 |
Janssen H, Ada L, Karayanidis F, Drysdale K, McElduff P, Pollack MR, et al., 'Translating the use of an enriched environment poststroke from bench to bedside: study design and protocol used to test the feasibility of environmental enrichment on stroke patients in rehabilitation', International Journal of Stroke, 7 521-526 (2012) [C3]
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2011 |
Bivard A, Spratt NJ, Levi CR, Parsons MW, 'Acute stroke thrombolysis: Time to dispense with the clock and move to tissue-based decision making?', Expert Review of Cardiovascular Therapy, 9 451-461 (2011) [C1]
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Nova |
2011 |
McLeod DD, Parsons MW, Levi CR, Beautement S, Buxton D, Roworth B, Spratt NJ, 'Establishing a rodent stroke perfusion computed tomography model', International Journal of Stroke, 6 284-289 (2011) [C1]
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Nova |
2011 |
Bivard A, Spratt NJ, Levi CR, Parsons MW, 'Perfusion computer tomography: Imaging and clinical validation in acute ischaemic stroke', Brain, 134 3408-3416 (2011) [C1]
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Nova |
2011 |
Spratt NJ, Donnan GA, McLeod DD, Howells DW, ''Salvaged' stroke ischaemic penumbra shows significant injury: Studies with the hypoxia tracer FMISO', Journal of Cerebral Blood Flow and Metabolism, 31 934-943 (2011) [C1]
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2011 |
Parsons MW, Bivard A, McElduff P, Spratt NJ, Levi CR, 'Defining the extent of irreversible brain ischemia using perfusion computed tomography', Cerebrovascular Diseases, 31 238-245 (2011) [C1]
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Nova |
2010 |
Janssen H, Bernhardt J, Collier JM, Sena ES, McElduff P, Attia JR, et al., 'An enriched environment improves sensorimotor function post-ischemic stroke', Neurorehabilitation and Neural Repair, 24 802-813 (2010) [C1]
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Nova |
2010 |
Garnett AR, Marsden DL, Parsons MW, Quain DA, Spratt NJ, Loudfoot AR, et al., 'The rural Prehospital Acute Stroke Triage (PAST) trial protocol: A controlled trial for rapid facilitated transport of rural acute stroke patients to a regional stroke centre', International Journal of Stroke, 5 506-513 (2010) [C1]
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2010 |
Rewell SSJ, Fernandez JA, Cox SF, Spratt NJ, Hogan L, Aleksoska E, et al., 'Inducing stroke in aged, hypertensive, diabetic rats', JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 30 729-733 (2010) [C1]
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2010 |
The VITATOPS Trial Study Group, 'B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial', Lancet Neurology, 9 855-865 (2010)
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2010 |
Marsden DL, Spratt NJ, Walker R, Barker DJ, Attia JR, Pollack MR, et al., 'Trends in stroke attack rates and case fatality in the Hunter Region, Australia 1996-2008', Cerebrovascular Diseases, 30 500-507 (2010) [C1]
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Nova |
2010 |
Abed H, Barlow MA, Wellings TP, Spratt NJ, Collins N, 'Cardiogenic shock complicating subarachnoid haemorrhage diagnosed as Tako Tsubo Cardiomyopathy: A cautionary tale', Heart Lung and Circulation, 19 476-479 (2010) [C3]
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2009 |
Levi CR, Bateman GA, Spratt NJ, McElduff P, Parsons MW, Miteff F, 'The independent predictive utility of computed tomography angiographic collateral status in acute ischaemic stroke', Brain, 132 2231-2238 (2009) [C1]
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Nova |
2009 |
Spratt NJ, Donnan GA, Howells DW, 'Characterisation of the timing of binding of the hypoxia tracer FMISO after stroke', Brain Research, 1288 135-142 (2009) [C1]
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2009 |
Levi C, Parsons M, Spratt N, Evans M, Royan A, 'Predicting Outcome in hyper-acute stroke: validation of a prognostic model in the Thir', Journal of Neurology, Neurosurgery and Psychiatry, 79 397-400 (2009) [C3] |
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2009 |
Parsons MW, Miteff F, Bateman GA, Spratt NJ, Loiselle A, Attia JR, Levi CR, 'Acute ischemic stroke imaging-guided tenecteplase treatment in an extended time window', Neurology, 72 915-921 (2009) [C1]
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Nova |
2008 |
Scope Collaborations SCAOPE, Ist, Levi C, Parsons M, Spratt N, Evans M, Royan A, 'Predicting outcome in hyper-acute stroke: validation of a prognostic model in the Third International Stroke Trial (IST3)', Journal of Neurology Neurosurgery and Psychiatry, 79 397-400 (2008) [C1]
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2008 |
Quain DA, Parsons MW, Loudfoot AR, Spratt NJ, Evans MK, Russell ML, et al., 'Improving access to acute stroke therapies: A controlled trial of organised pre-hospital and emergency care', Medical Journal of Australia, 189 429-433 (2008) [C1]
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Nova |
2006 |
Spratt N, Ackerman U, Tochon-Danguy HJ, Donnan GA, Howells DW, 'Characterization of fluoromisonidazole binding in stroke', Stroke, 37 1862-1867 (2006) [C1]
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2006 |
Spratt N, Fernandez J, Chen M, Rewell S, Cox S, Van Raay L, et al., 'Modification of the method of thread manufacture improves stroke induction rate and reduces mortality after thread-occlusion of the middle cerebral artery in young or aged rats', Journal of Neuroscience Methods, 155 285-290 (2006) [C1]
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2006 |
Falzon CL, Ackermann U, Spratt N, Tochon-Danguy HJ, White J, Howells D, Scott AM, 'F-18 labelled N, N-bis-haloethylamino-phenylsulfoxides - a new class of compounds for the imaging of hypoxic tissue', Journal of Labelled Compounds and Radiopharmaceuticals, 49 1089-1103 (2006) [C1]
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2004 |
Saita K, Chen M, Spratt NJ, Porritt MJ, Liberatore GT, Read SJ, et al., 'Imaging the Ischemic Penumbra with F-Fluoromisonidazole in a Rat Model of Ischemic Stroke', Stroke: a journal of cerebral circulation, 35 975-980 (2004) [C1]
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2003 |
Wang Y, Levi CR, Attia JR, D'Este CA, Spratt N, Fisher JD, 'Seasonal Variation in Stroke in the Hunter Region, Australia: A 5-Year Hospital-Based Study, 1995-2000', Stroke: a journal of cerebral circulation, 34 1144-1150 (2003) [C1]
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2003 |
Spratt N, Wang Y, Levi CR, Ng K, Evans M, Fisher JD, 'A prospective study of predictors of prolonged hospital stay and disability after stroke', Journal of Clinical Neuroscience, 10 665-669 (2003) [C1]
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