The effect of nitroglycerin treatment on cerebral ischaemia: A systematic review and meta-analysis of animal studies.

BACKGROUND: Nitroglycerin has been of considerable interest as a treatment for ischaemic stroke. Recent clinical trials with nitroglycerin transdermal patches during the acute phase of stroke failed to improve functional outcomes. Systematic review and meta-analysis of the effectiveness of nitroglycerin in preclinical models of ischaemic stroke has not previously been reported, despite several clinical trials. OBJECTIVE: To conduct a systematic review and meta-analysis of preclinical evidence regarding the effect of nitroglycerin on infarct volume in animal models of ischaemic stroke. SUMMARY OF REVIEW: The protocol was registered in PROSPERO (CRD42023432644). Our search identified 238 publications. Three publications met inclusion criteria (including 10 comparisons of infarct size). Study quality was modest (median 6 out of 9), with no evidence of publication bias. Nitroglycerin did not significantly reduce infarct volume (NMD point estimate 20.2 % reduction, 95 % CI -1.52-52.7 %, p = 0.068). Subgroup analysis suggested greater efficacy of nitroglycerin with direct intracarotid administration to the ischaemic territory at the time of reperfusion. CONCLUSIONS: A small number of studies (three) were included in this review. Overall, nitroglycerin did not reduce infarct volume in experimental stroke models. However, nitroglycerin may be of benefit when administered directly into the ischaemic territory. Given nitroglycerin's short half-life, we propose this route may minimise harmful reduction of cerebral perfusion pressure resulting from hypotension following systemic administration.

Role of cardiac computed tomography in hyperacute stroke assessment.

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.

Ultra-Long Transfers for Endovascular Thrombectomy-Mission Impossible?: The Australia-New Zealand Experience.

BACKGROUND: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0-2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. METHODS: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). RESULTS: There were 131 patients; the median age was 64 [53-74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12-22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1-3] versus 3 [1-6] in the patients selected with noncontrast CT+CT angiography, P=0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01-0.19]; P<0.01). CONCLUSIONS: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.

Blood pressure variability is associated with Infarct Growth in Acute Ischemic Stroke.

Introduction Evidence based blood pressure (BP) targets in acute ischemic 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-hours. Infarct growth and evidence of parenchymal haemorrhage were determined by follow-up magnetic resonance imaging at 24 hours. Functional outcome at 3-months was assessed using the modified Rankin Scale. Subgroup analysis was performed according to stroke etiology and treatment for the association between BP, infarct volume growth and risk of hemorrhagic 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. Blood pressure variability (BPV) was independently associated with increased infarct growth (multivariate coefficient 1.60, 95% CI 0.27-2.94, P=0.019) 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 hemorrhagic transformation (adjusted OR 1.26, 95% CI 1.01-1.57, P=0.045). Conclusions: 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.

Depression and a lack of socialization are associated with high levels of boredom during stroke rehabilitation: An exploratory study using a new conceptual framework.

This exploratory sub-study aimed to develop a framework to conceptualize boredom in stroke survivors during inpatient rehabilitation, establish the effect of an activity promotion intervention on boredom, and to investigate factors that are associated with boredom. A framework was developed and explored within a cluster non-randomised controlled trial. Self-reported boredom was measured in 160 stroke survivors 13 (±5) days after rehabilitation admission; 91 participants received usual-care (control) and 69 had access to a patient-driven model of activity promotion (intervention). Individuals with pre-existing dementia or unable to participate in standard rehabilitation were excluded. Hierarchical logistic regression analysis was used to identify demographic, health and activity measures associated with boredom. Results indicated 39% of participants were highly bored. There was no statistically significant difference in boredom levels between treatment groups (difference -11%, 95% CI -26% to 4%). The presence of depression (OR 6.17, 95% CI 2.57-14.79) and lower levels of socialization (OR 0.96, 95% CI 0.92-0.99) predicted high boredom levels. This comprehensive framework provides a foundation for understanding the many interacting factors associated with boredom. Results suggest managing depression and improving opportunities for socialization may support meaningful engagement in rehabilitation to optimize recovery following stroke.

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).

OBJECTIVES: To compare processes of care and clinical outcomes of community-based management of TIAs and minor strokes (TIAMS) between rural and metropolitan Australia. DESIGN: Inception cohort study between 2012 and 2016 with 12-month follow-up after index event (sub-study of INSIST). SETTING: Hunter and Manning valley regions of New South Wales, within the referral territory of the John Hunter Hospital Acute Neurovascular Clinic (JHHANC). PARTICIPANTS: Consecutive patients of 16 participating general practices, presenting with possible TIAMS to either primary or secondary care. MAIN OUTCOME MEASURES: Processes of care (referrals, key management processes, time-based metrics) and clinical outcomes. RESULTS: Of 613 participants with possible TIAMS who completed the baseline interview, 298 were adjudicated as having TIAMS (119 from rural, 179 from metropolitan). Mean age was 72.3 years (SD, 10.7) and 127 (43%) were women. Rural participants were more likely to be managed solely by a general practitioner (GP) than metropolitan participants (34% v 20%) and less likely to be referred to a JHHANC specialist (13% v 38%) or have brain magnetic resonance imaging (MRI) [24% v 51%]. Those rural participants who were referred, also waited longer (both p < 0.001). Recurrent stroke, myocardial infarction and death at 12 months were not significantly different between rural and metropolitan participants. CONCLUSIONS: Although TIAMS prognosis in rural settings where solely GP care is common is very good, the processes of care in such areas are inferior to metropolitan. This suggests there is further scope to support rural GPs to optimise care of TIAMS patients.

Diagnostic Utility of Computed Tomography Perfusion in the Telestroke Setting.

BACKGROUND: Definitive diagnosis of acute ischemic stroke is challenging, particularly in telestroke settings. Although the prognostic utility of CT perfusion (CTP) has been questioned, its diagnostic value remains under-appreciated, especially in cases without an easily visible intracranial occlusion. We assessed the diagnostic accuracy of routine CTP in the acute telestroke setting. METHODS: Acute and follow-up data collected prospectively from consecutive suspected patients with stroke assessed by a state-wide telestroke service between March 2020 and August 2021 at 12 sites in Australia were analyzed. All patients in the final analysis had been assessed with multimodal CT, including CTP, which was post-processed with automated volumetric software. Diagnostic sensitivity and specificity were calculated for multimodal CT and each individual component (noncontrast CT [NCCT], CT angiogram [CTA], and CTP). Final diagnosis determined by consensus review of follow-up imaging and clinical data was used as the reference standard. RESULTS: During the study period, complete multimodal CT examination was obtained in 831 patients, 457 of whom were diagnosed with stroke. Diagnostic sensitivity for ischemic stroke increased by 19.5 percentage points when CTP was included with NCCT and CTA compared with NCCT and CTA alone (73.1% positive with NCCT+CTA+CTP [95% CI, 68.8-77.1] versus 53.6% positive with NCCT+CTA alone [95% CI, 48.9-58.3], P<0.001). No difference was observed between specificities of NCCT+CTA and NCCT+CTA+CTP (98.7% [95% CI, 98.5-100] versus 98.7% [95% CI, 96.9-99.6], P=0.13). Multimodal CT, including CTP, demonstrated the highest negative predictive value (75.0% [95% CI, 72.1-77.7]). Patients with stroke not evident on CTP had small volume infarcts on follow-up (1.2 mL, interquartile range 0.5-2.7mL). CONCLUSIONS: Acquisition of CTP as part of a telestroke imaging protocol permits definitive diagnosis of cerebral ischemia in 1 in 5 patients with normal NCCT and CTA.

Evaluation of an online intervention for improving stroke survivors' health-related quality of life: A randomised controlled trial.

BACKGROUND: The aim of this trial was to evaluate the effectiveness of an online health behaviour change intervention-Prevent 2nd Stroke (P2S)-at improving health-related quality of life (HRQoL) amongst stroke survivors at 6 months of follow-up. METHODS AND FINDINGS: A prospective, blinded-endpoint randomised controlled trial, with stroke survivors as the unit of randomisation, was conducted between March 2018 and November 2019. Adult stroke survivors between 6 and 36 months post-stroke with capacity to use the intervention (determined by a score of ≥4 on the Modified Rankin Scale) and who had access and willingness to use the internet were recruited via mail-out invitations from 1 national and 1 regional stroke registry. Participants completed baseline (n = 399) and 6-month follow-up (n = 356; 89%) outcome assessments via computer-assisted telephone interviewing (CATI). At baseline the sample had an average age of 66 years (SD 12), and 65% were male. Randomisation occurred at the end of the baseline survey; CATI assessors and independent statisticians were blind to group allocation. The intervention group received remote access for a 12-week period to the online-only P2S program (n = 199; n = 28 lost at follow-up). The control group were emailed and posted a list of internet addresses of generic health websites (n = 200; n = 15 lost at follow-up). The primary outcome was HRQoL as measured by the EuroQol Visual Analogue Scale (EQ-VAS; self-rated global health); the outcome was assessed for differences between treatment groups at follow-up, adjusting for baseline measures. Secondary outcomes were HRQoL as measured by the EQ-5D (descriptive health state), diet quality, physical activity, alcohol consumption, smoking status, mood, physical functioning, and independent living. All outcomes included the variable 'stroke event (stroke/transient ischaemic attack/other)' as a covariate, and analysis was intention-to-treat. At 6 months, median EQ-VAS HRQoL score was significantly higher in the intervention group than the control group (85 vs 80, difference 5, 95% CI 0.79-9.21, p = 0.020). The results were robust to the assumption the data were missing at random; however, the results were not robust to the assumption that the difference in HRQoL between those with complete versus missing data was at least 3 points. Significantly higher proportions of people in the intervention group reported no problems with personal care (OR 2.17, 95% CI 1.05-4.48, p = 0.0359) and usual activities (OR 1.66, 95% CI 1.06-2.60, p = 0.0256) than in the control group. There were no significant differences between groups on all other secondary outcomes. The main limitation of the study is that the sample comprises mostly 'well' stroke survivors with limited to no disability. CONCLUSIONS: The P2S online healthy lifestyle program improved stroke survivors' self-reported global ratings of HRQoL (as measured by EQ-VAS) at 6-month follow-up. Online platforms represent a promising tool to engage and support some stroke survivors. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12617001205325.

Stroke survivors' perceptions of the factors that influence engagement in activity outside dedicated therapy sessions in a rehabilitation unit: A qualitative study.

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.

Transition in Incidence Rate of Hospitalised Stroke and Case Fatality Rate in the Hunter Region, Australia, 2001-2019: A Prospective Hospital-Based Study.

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.

Impact of an outpatient telestroke clinic on management of rural stroke patients.

OBJECTIVE: Report on feasibility, use and effects on investigations and treatment of a neurologist-supported stroke clinic in rural Australia. DESIGN: Data were collected prospectively for consecutive patients referred to atelehealth stroke clinic from November 2018 to August 2021. SETTINGS, PARTICIPANTS AND INTERVENTIONS: Patients attended the local hospital, with a rural stroke care coordinator, and were assessed by stroke neurologist over videoconference. MAIN OUTCOME MEASURES: The following feasibility outcomes on the first appointments were analysed: (1) utility (a) change in medication, (b) request of additional investigations, (c) enrolment/offering clinical trials or d) other; (2) acceptability (attendance rate); and (3) process of care (waiting time to first appointment, distance travelled). RESULTS: During the study period, 173 appointments were made; 125 (73.5%) were first appointments. The median age was 70 [63-79] years, and 69 patients were male. A diagnosis of stroke or transient ischemic attack was made by the neurologist in 106 patients. A change in diagnosis was made in 23 (18.4%) patients. Of the first appointments, 102 (81.6%) resulted in at least one intervention: medication was changed in 67 (53.6%) patients, additional investigations requested in 72 (57.6%), 15 patients (12%) were referred to a clinical trial, and other interventions were made in 23 patients. The overall attendance rate of booked appointments was high. The median waiting time and distance travelled (round-trip) for a first appointment were 38 [24-53] days and 60.8 [25.6-76.6] km respectively. CONCLUSION: The telestroke clinic was very well attended, and it led to high volume of interventions in rural stroke patients.

Role of Computed Tomography Perfusion in Identification of Acute Lacunar Stroke Syndromes.

BACKGROUND AND PURPOSE: Lacunar syndromes correlate with a lacunar stroke on imaging in 50% to 60% of cases. Computed tomography perfusion (CTP) is becoming the preferred imaging modality for acute stroke triage. We aimed to estimate the sensitivity, specificity, and predictive values for noncontrast computed tomography and CTP in lacunar syndromes, and for cortical, subcortical, and posterior fossa regions. METHODS: A retrospective analysis of confirmed ischemic stroke patients who underwent acute CTP and follow-up magnetic resonance imaging between 2010 and 2018 was performed. Brain noncontrast computed tomography and CTP were assessed independently by 2 stroke neurologists. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and area under the curve (AUC) for the detection of strokes in patients with lacunar syndromes using different CTP maps. RESULTS: We found 106 clinical lacunar syndromes, but on diffusion-weighted imaging, these consisted of 59 lacunar, 33 cortical, and 14 posterior fossa strokes. The discrimination of ischemia identification was very poor using noncontrast computed tomography in all 3 regions, but good for cortical (AUC, 0.82) and poor for subcortical and posterior regions (AUCs, 0.55 and 0.66) using automated core-penumbra maps. The addition of delay time and mean transient time maps substantially increased subcortical (AUC, 0.80) and slightly posterior stroke detection (AUC, 0.69). CONCLUSIONS: Analysis of mean transient time and delay time maps in combination with core-penumbra maps improves detection of subcortical and posterior strokes.

Stroke Patients With Faster Core Growth Have Greater Benefit From Endovascular Therapy.

BACKGROUND AND PURPOSE: This study aimed to explore whether the therapeutic benefit of endovascular thrombectomy (EVT) was mediated by core growth rate. METHODS: This retrospective cohort study identified acute ischemic stroke patients with large vessel occlusion and receiving reperfusion treatment, either EVT or intravenous thrombolysis (IVT), within 4.5 hours of stroke onset. Patients were divided into 2 groups: EVT versus IVT only patients (who had no access to EVT). Core growth rate was estimated by the acute core volume on perfusion computed tomography divided by the time from stroke onset to perfusion computed tomography. The primary clinical outcome was good outcome defined by 3-month modified Rankin Scale score of 0-2. Tissue outcome was the final infarction volume. RESULTS: A total of 806 patients were included, 429 in the EVT group (recanalization rate of 61.6%) and 377 in the IVT only group (recanalization rate of 44.7%). The treatment effect of EVT versus IVT only was mediated by core growth rate, showing a significant interaction between EVT treatment and core growth rate in predicting good clinical outcome (interaction odds ratio=1.03 [1.01-1.05], P=0.007) and final infarct volume (interaction odds ratio=-0.44 [-0.87 to -0.01], P=0.047). For patients with fast core growth of >25 mL/h, EVT treatment (compared with IVT only) increased the odds of good clinical outcome (adjusted odds ratio=3.62 [1.21-10.76], P=0.021) and resulted in smaller final infarction volume (37.5 versus 73.9 mL, P=0.012). For patients with slow core growth of <15 mL/h, there were no significant differences between the EVT and the IVT only group in either good clinical outcome (adjusted odds ratio=1.44 [0.97-2.14], P=0.070) or final infarction volume (22.6 versus 21.9 mL, P=0.551). CONCLUSIONS: Fast core growth was associated with greater benefit from EVT compared with IVT in the early <4.5-hour time window.

Permeability Measures Predict Hemorrhagic Transformation after Ischemic Stroke.

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 χ2 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.

Secondary Prevention of Stroke: Study Protocol for a Telehealth-Delivered Physical Activity and Diet Pilot Randomized Trial (ENAbLE-Pilot).

BACKGROUND: Increasing physical activity (PA) and improving diet quality are opportunities to improve secondary stroke prevention, but access to appropriate services is limited. Interventions co-designed with stroke survivors and delivered by telehealth are a potential solution. AIM: The aim of this study is to test the feasibility, safety, and potential efficacy of a 6-month, telehealth-delivered PA and/or dietary (DIET) intervention. METHODS: Pilot randomized trial. 80 adults with previous stroke who are living at home with Internet access and able to exercise will be randomized in a 2 × 2 factorial (4-arm) pilot randomized, open-label, blinded outcome assessment trial to receive PA, DIET, PA + DIET, or control interventions via telehealth. The PA intervention aims to support participants to meet the minimum recommended levels of PA (150 min/week moderate exercise), and the DIET intervention aims to support participants to follow the AusMed (Mediterranean-style) diet. The control group receives usual care plus education about PA and healthy eating. The co-primary outcomes are feasibility (proportion and characteristics of eligible participants enrolled and proportion of scheduled intervention sessions attended) and safety (adverse events) at 6 months. The secondary outcomes include recurrent stroke risk factors (blood pressure, physical activity levels, and diet quality), fatigue, mood, and quality of life. Outcomes are measured at 3, 6, and 12 months. CONCLUSION: This trial will produce evidence for the feasibility, safety, and potential effect of telehealth-delivered PA and DIET interventions for people with stroke. Results will inform development of an appropriately powered trial to test effectiveness to reduce major risk factors for recurrent stroke. TRIAL REGISTRATION: ACTRN12620000189921.

Physiotherapy using a free-standing robotic exoskeleton for patients with spinal cord injury: a feasibility study.

BACKGROUND: Evidence is emerging for the use of overground lower limb robotic exoskeletons in the rehabilitation of people with spinal cord injury (SCI), with suggested benefits for gait speed, bladder and bowel function, pain management and spasticity. To date, research has focused on devices that require the user to support themselves with a walking aid. This often precludes use by those with severe trunk, postural or upper limb deficits and places the user in a suboptimal, flexed standing position. Free-standing exoskeletons enable people with higher level injuries to exercise in an upright position. This study aimed to evaluate the feasibility of therapy with a free-standing exoskeleton for those with SCI, and to determine the potential health-related benefits of this intervention. METHODS: This 12-week intervention study with 12-week waitlist control and 12-week follow up, provided people with SCI scoring < 5 on the mobility section of the spinal cord independence measure (SCIM-III) twice weekly therapy in the REX (Rex Bionics, Auckland, NZ), a free-standing lower limb robotic exoskeleton. The primary outcome measure of interest was function, as measured on the SCIM-III. A battery of secondary outcomes was included. Participants also completed a survey on their perceptions of this treatment modality, to determine acceptability. RESULTS: Forty-one potential participants were screened for eligibility. Two females (one ASIA A, one ASIA C) and one male (ASIA B) completed all 24 intervention sessions, and the follow up assessment. One participant showed positive trends in function, fatigue, quality of life and mood during the intervention phase. Grip and quadriceps strength, and lower limb motor function improved in another. Two improved their percentage of lean body mass during the intervention phase. Remaining results were varied across patients, time points and outcomes. The intervention was highly acceptable to all participants. CONCLUSION: With three of 41 potential participants being eligible and completing this study, our results show that there are potential benefits of exercise in a free-standing exoskeleton for people with severe mobility impairment due to SCI, for a small subset of patients. Further research is warranted to determine those most likely to benefit, and the type of benefit depending on the patient characteristics. Trial registration The trial was registered prospectively on 20 April 2018 at www.anzctr.org.au/ (ACTRN12618000626268).

Computed Tomography Perfusion Identifies Patients With Stroke With Impaired Cardiac Function.

Background and Purpose- Low left ventricular ejection fraction (LVEF) leads to worse outcomes after stroke. We hypothesized that the arterial input function (AIF) variability on perfusion computed tomography, especially the time between scan onset and end of AIF (SO-EndAIF), would reflect reduction of cardiac output. Methods- Retrospective analysis of consecutive stroke patients, who underwent computed tomography between January 2013 and September 2018, was performed in 2 parts. (1) To determine the correlation between SO-EndAIF and LVEF, all patients with a transthoracic echocardiogram performed ±6 months from the time of stroke were included. LVEF was dichotomized as either normal (≥50%) or decreased (<50%). (2) AIF was compared with hypoperfusion volume, defined as delay time >3 seconds and with clinical outcome measured using 3-month modified Rankin Scale. Results- A total of 732 ischemic stroke patients underwent computed tomography, 231 with transthoracic echocardiogram were included in part (1), 393 with outcome data were included in part (2). In part (1), 193/231 (83.5%) had normal LVEF (median 61%) and 38/231 (16.5%) decreased LVEF (median 39%). The low-LVEF group had significantly prolonged SO-EndAIF compared with normal-LVEF group (mean of 39.7 versus 26 second; P<0.001), and larger hypoperfusion lesions (94.9 versus 37.6 mL; P<0.001). SO-EndAIF time was strongly associated with EF, with an area under the curve of 0.86. Twenty nine seconds was the best threshold to distinguish between normal and impaired EF (area under the curve, 0.77). In part (2), the SO-EndAIF ≥29 second group had larger hypoperfusion volumes (21.8 versus 89.7 mL; P<0.001) and infarct core (12.2 versus 2.3 mL; P<0.0001) and patients with SO-EndAIF ≥29 seconds had fewer excellent or good clinical outcomes (modified Rankin Scale score 0-1; 40% versus 22%; OR, 2.79; P<0.001, modified Rankin Scale score 0-2; 65% versus 35%; OR, 1.41; P=0.033). Conclusions- AIF width correlates with ejection fraction in acute ischemic stroke. A 29-second threshold from scan onset to end of AIF accurately predicts reduced LVEF and identifies patients more likely to have worse outcomes after stroke.

An online cross-sectional survey of the health risk behaviours among informal caregivers.

ISSUE ADDRESSED: Informal caregivers may experience unique barriers to engaging in healthy lifestyles, consequently increasing their risk of chronic disease. Among a convenience sample of informal caregivers, this study aimed to: (a) assess the self-reported health risk behaviours of low fruit and vegetable consumption, low physical activity, current smoking and hazardous alcohol consumption; (b) examine the demographic, caree condition and country of residence variables associated with each health risk behaviour; and (c) report the engagement in multiple health risk behaviours. METHODS: An online cross-sectional survey among caregivers in Australia, Canada, New Zealand, the United Kingdom and the United States was conducted. Self-reported health risk behaviours were assessed and compared to key Australian healthy living guidelines. Logistic regression modelling identified participant factors associated with each health risk behaviour. RESULTS: Overall, 384 caregivers were included in the analysis. Hazardous alcohol consumption was the only self-reported health risk behaviour which was much higher than in the general population (60.0%). Caregiver age (P = .018) and country of residence (P = .015) were associated with hazardous alcohol consumption. A majority of caregivers reported engaging in three health risk behaviours (55.0%). CONCLUSIONS: Caregivers are engaging in a range of health risk behaviours; however, rates of hazardous alcohol consumption among the sample were high. Health promotion interventions targeted to address alcohol consumption should consider caregiver age and country of residence. SO WHAT?: This study highlights the health risk behaviours caregivers engage in across a number of countries, and suggests that caregivers require further support to manage alcohol consumption in particular.

Predicting Modafinil-Treatment Response in Poststroke Fatigue Using Brain Morphometry and Functional Connectivity.

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. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: ACTRN12615000350527.

Single-phase CT angiography: collateral grade is independent of scan weighting.

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.