European Stroke Journal

To describe the association between factors routinely available in hyperacute care of spontaneous intracerebral haemorrhage (ICH) patients and functional outcome.

We searched Medline, Embase and CINAHL in February 2020 for original studies reporting associations between markers available within six hours of arrival in hospital and modified Rankin Scale (mRS) at least 6 weeks post-ICH. A random-effects meta-analysis was performed where three or more studies were included.

Thirty studies were included describing 40 markers. Ten markers underwent meta-analysis and age (OR = 1.06; 95%CI = 1.05 to 1.06; p < 0.001), pre-morbid dependence (mRS, OR = 1.73; 95%CI = 1.52 to 1.96; p < 0.001), level of consciousness (Glasgow Coma Scale, OR = 0.82; 95%CI = 0.76 to 0.88; p < 0.001), stroke severity (National Institutes of Health Stroke Scale, OR=1.19; 95%CI = 1.13 to 1.25; p < 0.001), haematoma volume (OR = 1.12; 95%CI=1.07 to 1.16; p < 0.001), intraventricular haemorrhage (OR = 2.05; 95%CI = 1.68 to 2.51; p < 0.001) and deep (vs. lobar) location (OR = 2.64; 95%CI = 1.65 to 4.24; p < 0.001) were predictive of outcome but systolic blood pressure, CT hypodensities and infratentorial location were not. Of the remaining markers, sex, medical history (diabetes, hypertension, prior stroke), prior statin, prior antiplatelet, admission blood results (glucose, cholesterol, estimated glomerular filtration rate) and other imaging features (midline shift, spot sign, sedimentation level, irregular haematoma shape, ultraearly haematoma growth, Graeb score and onset to CT time) were associated with outcome.

Multiple demographic, pre-morbid, clinical, imaging and laboratory factors should all be considered when prognosticating in hyperacute ICH. Incorporating these in to accurate and precise models will help to ensure appropriate levels of care for individual patients.

Trials of tranexamic acid (TXA) in acute intracerebral hemorrhage (ICH) have focused on the imaging outcomes of intraparenchymal hematoma growth. However, intraventricular hemorrhage (IVH) growth is also strongly associated with outcome after ICH. Revised definitions of hematoma expansion incorporating IVH growth have been proposed.

We sought to evaluate the effect of TXA on IVH growth.

We analyzed data from the STOP-AUST trial, a prospective randomized trial comparing TXA to placebo in ICH patients presenting ≤ 4.5 h from symptom onset with a CT-angiography spot sign. New IVH development at follow-up, any interval IVH growth, and IVH growth ≥ 1 mL were compared between the treatment groups using logistic regression. The treatment effect of TXA against placebo using conventional (> 6 mL or 33%), and revised definitions of hematoma expansion (> 6 mL or 33% or IVH expansion ≥ 1 mL, > 6 mL or 33%, or any IVH expansion, and > 6 mL or 33% or new IVH development) were also assessed. Treatment effects were adjusted for baseline ICH volume.

The analysis population consisted of 99 patients (50 placebo, 49 TXA). New IVH development at follow-up was observed in 6/49 (12%) who received TXA and 13/50 (26%) who received placebo (aOR: 0.38 [95% CI: 0.13–1.13]). Any interval IVH growth was observed in 12/49 (25%) who received TXA versus 26/50 (32%) receiving placebo (aOR: 0.69 [95% CI: 0.28–1.66]). IVH growth ≥ 1 mL did not differ between the two groups. Using revised definitions of hematoma expansion, no significant difference in treatment effect was observed between TXA and placebo.

IVH may be attenuated by TXA following ICH; however, studies with larger cohorts are required to investigate this further.

http://www.clinicaltrials.gov; Unique identifier: NCT01702636.

Data on oral anticoagulant-related (OAC) intracerebral hemorrhage (ICH) incidence are scarce. Most studies on incidence time trends were performed before the introduction of Direct Oral Anticoagulants (DOACs). Between 2008 and 2018, the number of OAC-users in the Netherlands increased by 63%, with the number of DOAC-users almost equaling that of Vitamin K Antagonists (VKA)-users. We aimed to determine the recent total and OAC-related ICH incidence and assess changes over the last decade, including the effect of DOAC introduction.

All adult non-traumatic ICH patients presenting in any of three hospitals in the enclosed region of South-Limburg, the Netherlands, were retrospectively included, during two 3-year time periods: 2007–2009 and 2017–2019. OAC-related ICH was defined as ICH in patients using VKAs or DOACs. We calculated the incidence rate ratio (IRR) between the two study periods.

In the 2007–2009 period, we registered 652 ICHs of whom 168 (25.8%) were OAC-related (all VKA). In the 2017–2019 period, we registered 522 ICHs, 121 (23.2%) were OAC-related (70 VKA and 51 DOAC). In 2007–2009, the annual incidence of total ICH and OAC-related ICH was 40.9 and 10.5 per 100,000 person-years, respectively, which decreased to 32.4 and 7.5 per 100,000 person-years in 2017–2019. The IRR for total ICH and OAC-related ICH was 0.67 (95%-CI: 0.60–0.75) and 0.58 (0.46–0.73), respectively.

Both total ICH and OAC-related ICH incidence decreased over the past decade in South-Limburg, the Netherlands, despite the aging population and increasing number of OAC-users. The introduction of DOACs, and possibly an improved cardiovascular risk management and change in OAC prescription pattern, could explain these findings.

To guide policy when planning thrombolysis (IVT) and thrombectomy (MT) services for acute stroke in England, focussing on the choice between ‘mothership’ (direct conveyance to an MT centre) and ‘drip-and-ship’ (secondary transfer) provision and the impact of bypassing local acute stroke centres.

Outcome-based modelling study.

107 acute stroke centres in England, 24 of which provide IVT and MT (IVT/MT centres) and 83 provide only IVT (IVT-only units).

242,874 emergency admissions with acute stroke over 3 years (2015–2017).

Reperfusion delivered by drip-and-ship, mothership or ‘hybrid’ models; impact of additional travel time to directly access an IVT/MT centre by bypassing a more local IVT-only unit; effect of pre-hospital selection for large artery occlusion (LAO).

Population benefit from reperfusion, time to IVT and MT, admission numbers to IVT-only units and IVT/MT centres.

Without pre-hospital selection for LAO, 94% of the population of England live in areas where the greatest clinical benefit, assuming unknown patient status, accrues from direct conveyance to an IVT/MT centre. However, this policy produces unsustainable admission numbers at these centres, with 78 out of 83 IVT-only units receiving fewer than 300 admissions per year (compared to 3 with drip-and-ship). Implementing a maximum permitted additional travel time to bypass an IVT-only unit, using a pre-hospital test for LAO, and selecting patients based on stroke onset time, all help to mitigate the destabilising effect but there is still some significant disruption to admission numbers, and improved selection of patients suitable for MT selectively reduces the number of patients who would receive IVT at IVT-only centres, challenging the sustainability of IVT expertise in IVT-only centres.

Implementation of reperfusion for acute stroke based solely on achieving the maximum population benefit potentially leads to destabilisation of the emergency stroke care system. Careful planning is required to create a sustainable system, and modelling may be used to help planners maximise benefit from reperfusion while creating a sustainable emergency stroke care system.

Outcomes after mechanical thrombectomy (MT) in young stroke patients remain elusive due to small patient cohorts. We sought to determine outcomes after MT in stroke patients between ages 18 and 64 years and compare with outcomes in older patients in a large national stroke cohort.

We used the Swedish National Stroke Registry and the Swedish National Endovascular Thrombectomy Registry to identify all patients treated with MT for anterior circulation occlusions. We examined outcome measures in terms of functional independence at 90 days (modified Rankin Scale score of 0–2), symptomatic intracerebral hemorrhage (sICH), and mortality at 90 days with multivariable logistic regression analysis.

Of 2143 patients, 565 were between 18 and 64 years (26.4%) and 1179 (55.0%) were males. Analysis showed that patient aged 18–64 achieved higher rate of functional independence at 90 days (46.2% vs 28.4%, p < .001), had less often sICH (5.5% vs 6.8%, p = .008), and lower 90-day mortality rate (6.9% vs 17.7%, p < .001). Increasing age was associated with a lesser probability of functional independence at 90 days (adjusted odds ratio (aOR), 0.94; [95% confidence intervals (CIs) 0.93–0.95]), higher odds of mortality at 90 days (aOR, 1.05; [95% CIs 1.03–1.06]), and of sICH (aOR 1.03; [95% CIs 1.01–1.05]).

Patients aged 18–64 years demonstrated better outcome after thrombectomy regarding functional independence, sICH, and mortality at 90 days when compared to older ages.

Vascular anatomy might affect endovascular treatment success in acute ischemic stroke patients with large vessel occlusion. We investigated the prognostic value of extracranial vascular characteristics on procedural time and revascularization success in patients with large vessel occlusion in the anterior cerebral circulation.

We included 828 patients endovascularly treated within 6.5 hours of symptom onset from the Dutch MR CLEAN-Registry. We evaluated aortic arch configuration, stenosis and tortuosity of supra-aortic arteries, and internal carotid arteries (ICAs) on pre-intervention CTA. We constructed logistic prediction models for outcome variables procedural duration (≥60 minutes) and non-successful revascularization (extended thrombolysis in cerebral infarction (eTICI) of 0–2A) using baseline characteristics and assessed the effect of extracranial vascular characteristics on model performance.

Cervical ICA tortuosity and stenosis ≥99% improved prediction of long procedural duration compared with baseline characteristics from area under the curve of 0.61 (95% CI: 0.57–0.65) to 0.66 (95% CI: 0.62–0.70) (P < 0.001). Cervical ICA tortuosity was significantly associated with non-successful recanalization. Prediction of non-successful revascularization did not improve after including aortic arch elongation, acute take-off angle, aortic variant, origin stenosis of supra-aortic arteries, and cervical ICA tortuosity, with an area under the curve of 0.63 (95% CI: 0.59–0.67) compared with 0.59 (95% CI: 0.55–0.63) (P = 0.11).

Extracranial vascular characteristics have additional prognostic value for procedural duration, but not for revascularization success, compared with baseline characteristics. Performance of both prediction models is limited in patients treated for large vessel occlusion.

Studies of differences in very long-term outcomes between people with lacunar/small vessel disease (SVD) versus other types of ischaemic stroke report mixed findings, with limited data on myocardial infarction (MI). We investigated whether long-term mortality, recurrent stroke and MI risks differ in people with versus without lacunar/SVD ischaemic stroke.

We included first-ever strokes from a hospital-based stroke cohort study recruited in 2002–2005. We compared risks of death, recurrent stroke and MI during follow-up among lacunar/SVD versus other ischaemic stroke subtypes using Cox regression, adjusting for confounding factors.

We included 812 participants, 283 with lacunar/SVD ischaemic stroke and 529 with other stroke. During a median of 9.2 years (interquartile range 3.1–11.8), there were 519 deaths, 181 recurrent strokes and 79 MIs. Lacunar/SVD stroke was associated with lower mortality (adjusted HR 0.79, 95% CI 0.65 to 0.95), largely due to markedly lower all-cause mortality in the first year. From one year onwards this difference attenuated, with all-cause mortality only slightly and not statistically significantly lower in the lacunar/SVD group (0.86, 95% CI 0.70 to 1.05). There was no clear difference in risk of recurrent stroke (HR 0.84, 95% CI 0.61–1.15) or MI (HR 0.83, 95% CI 0.52–1.34).

Long-term risks of all-cause mortality, recurrent stroke and MI are similar, or only slightly lower, in patients with lacunar/SVD as compared to other ischaemic stroke. Patients and physicians should be as vigilant in optimising short- and long-term secondary prevention of vascular events in lacunar/SVD as for other stroke types.

Early neurological deterioration is encountered in up to a third of patients with isolated pontine infarcts. A limited number of clinical and imaging features have been suggested as predictors of neurological progression in this setting. In this study, we assessed whether quantitative apparent diffusion coefficient (ADC) measurements within the ischemic pontine region could be used as a radiomic feature to forecast clinical deterioration.

We calculated the mean ADC value of ischemic voxels within the ischemic region and normalized them to the contralateral non-ischemic tissue (relative ADC, rADC) in patients with isolated pontine infarcts. This imaging signature was then compared among patients with neurological progression (n = 21) and a propensity matched cohort of non-progressors (n = 42), together with other clinical and imaging features in bivariate and multivariate statistical models.

The rADC_mean was significantly lower among patients with progression (p = 0.008). Female gender and extension of the ischemic lesion to the ventral pontine surface were other features significantly associated with progression. The association between rADC_mean and progression persisted in multivariate models with an odds ratio of 13.7 (95% CI 2.6–72.8; p = 0.002) for progression among patients with rADC_mean ≤ 0.67 in their ischemic tissue. The probability for worsening was 80% among patients who had an ischemic lesion extending to the ventral pontine surface with a mean rADC ≤ 0.67.

The mean rADC value within the ischemic lesion is closely related with early neurological deterioration in patients with isolated pontine infarcts.

Tenecteplase has higher fibrin specificity with a longer half-life and the potential to achieve higher rates of recanalization than alteplase. A critical limitation of tenecteplase is no commercial use in Japan and no experience with its administration to Japanese patients.

Tenecteplase is superior to alteplase in achieving recanalization on the initial angiogram when administered ≤4.5-hour of stroke onset in patients planned for mechanical thrombectomy (MT) in Japan where alteplase at the unique dose of 0.6mg/kg is officially used.

The Tenecteplase versus alteplase For LArge Vessel Occlusion Recanalization (T-FLAVOR) trial is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, masked-endpoint, superiority study. Eligibility criteria include acute ischemic stroke with pre-stroke modified Rankin Scale score ≤3 and large vessel occlusion (internal carotid artery, middle cerebral artery, or basilar artery) eligible for intravenous thrombolysis ≤4.5-hour and MT ≤6-hour of stroke onset. After completing the safety confirmation phase involving three patients who received non-masked tenecteplase (0.25 mg/kg), 220 patients will be randomized to two groups (1:1), intravenous alteplase (0.6mg/kg, n = 110) or tenecteplase (0.25mg/kg, n = 110), prior to MT.

In the safety confirmation phase, the primary outcome is symptomatic intracranial hemorrhage (sICH) ≤24-36-hour. In the randomized, comparative phase, the primary efficacy outcome is substantial angiographic reperfusion (mTICI grade 2b/2c/3) or absence of retrievable thrombus on the initial angiogram. The primary safety outcome is sICH ≤24-36-hour and 90-day mortality.

T-FLAVOR may help determine if tenecteplase should be recommended as a routine clinical strategy before MT for Japanese stroke patients.

jRCTs051210055

Balance and gait impairments are the most common motor deficits due to stroke, limiting the patients' daily life activities and participation in society. Studies investigating effect of task-specific training using biomechanical balance and gait variables (i.e. kinetic and kinematic parameters) as well as posturography after stroke are scarce.

The primary aim of this study is to assess the efficacy and long-term outcome of task-specific training based on motor relearning program (MRP) on balance, mobility and performance of activities of daily living among post-stroke patients.

In this two-armed randomised controlled clinical trial, a total of 66 sub-acute stroke patients who meet the trial criteria will be recruited. The patients will randomly receive task-specific training based on MRP or a conventional physical therapy program (CPT). Twenty-four physiotherapy sessions will be conducted, divided into three training sessions per week, 1 h per session, for 8 weeks, followed by an analysis of changes in patient’s balance, gait and performance of activates of daily living at three time periods; baseline, post-intervention and follow-up after 3-months, using clinical outcome measures and instrumental analysis of balance and gait.

The results of this study can guide to better understanding and provide an objective clinical basis for the use of task-specific training in stroke rehabilitation. Also, it intends to help bridge the current knowledge gap in rehabilitation and training recommendations to provide a therapeutic plan in post-stroke rehabilitation.

ClinicalTrials.gov (NCT05076383). Registered on 13 October 2021 (Protocol version: v2.0).