Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention to promote upper limb recovery after stroke. We aimed to identify differences in the efficacy of rTMS treatment on ...upper limb function depending on the onset time post-stroke.
We searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs from their inception to February 2018. RCTs on the effects of rTMS on upper limb function in adult patients with stroke were included. Study quality and risk of bias were assessed independently by two authors. Meta-analyses were performed for outcomes on individual upper limb outcome measures (function or activity) and for function and activity measures jointly, categorized by timing of treatment initiation. Timing of treatment initiation post-stroke was categorized as follows: acute to early subacute (<1 month), early subacute (1-3 months), late subacute (3-6 months), and chronic (>6 months).
We included 38 studies involving 1,074 stroke patients. Subgroup analysis demonstrated benefit of rTMS applied within the first month post-stroke MD = 9.31; 95% confidence interval (6.27-12.34);
< 0.0001, but not in the early subacute phase (1-3 months post-stroke) MD = 1.14; 95% confidence interval (-5.32 to 7.59),
= 0.73) or chronic phase (>6 months post-stroke) MD = 1.79; 95% confidence interval (-2.00 to 5.59;
= 0.35), when assessed with a function test Fugl-Meyer Arm test (FMA). There were no studies within the late subacute phase (3-6 months post-stroke) that used the FMA. Tests at the level of function revealed improved upper limb function after rTMS SMD = 0.43; 95% confidence interval (0.02-0.75);
= 0.0001, but tests at the level of activity did not, independent of rTMS onset post-stroke SMD = 0.17; 95% confidence interval (-0.09 to 0.44);
= 0.19. Heterogeneities in the results of the individual studies included in the main analyses were large, as suggested by funnel plot asymmetry.
Based on the FMA, rTMS seems more beneficial only when started in the first month post-stroke. Tests at the level of function are likely more sensitive to detect beneficial rTMS effects on upper limb function than tests at the level of activity. However, heterogeneities in treatment designs and outcomes are high. Future rTMS trials should include the FMA and work toward a core set of outcome measures.
Summary Background Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions ...affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. Methods Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com , number ISRCTN 25337470. Findings 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17–6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10–8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40–3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38–5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29–6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45–27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7. Interpretation The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. Funding Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.
Summary Background High body temperature in the first 12–24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess ...whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing body temperature and preventing fever. Methods In a multicentre, randomised, double-blind, placebo-controlled trial, patients with ischaemic stroke or intracerebral haemorrhage and body temperature between 36°C and 39°C were randomly assigned treatment with paracetamol (6 g daily) or placebo within 12 h from symptom onset. Treatment allocation was based on a computer-generated list of random numbers with varying block size. The primary outcome was improvement beyond expectation on the modified Rankin scale at 3 months, according to the sliding dichotomy approach. This trial is registered, number ISRCTN74418480. Findings Between March, 2003, and May, 2008, 1400 patients were randomly allocated treatment. 260 (37%) of 697 patients receiving paracetamol and 232 (33%) of 703 receiving placebo improved beyond expectation (adjusted odds ratio OR 1·20, 95% CI 0·96–1·50). In a post-hoc analysis of patients with baseline body temperature 37–39°C, treatment with paracetamol was associated with improved outcome (1·43, 1·02–1·97). There were 55 serious adverse events in the paracetamol group (8%) and 70 in the placebo group (10%). Interpretation These results do not support routine use of high-dose paracetamol in patients with acute stroke. Paracetamol might have a beneficial effect on functional outcome in patients admitted with a body temperature 37–39°C, but this post-hoc finding needs further study. Funding Netherlands Heart Foundation.
Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which ...anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24-7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.
Background and Purpose- Intravenous administration of heparin during endovascular treatment for ischemic stroke may improve outcomes. However, risks and benefits of this adjunctive therapy remain ...uncertain. We aimed to evaluate periprocedural intravenous heparin use in Dutch stroke intervention centers and to assess its efficacy and safety. Methods- Patients registered between March 2014 and June 2016 in the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke), including all patients treated with endovascular treatment in the Netherlands, were analyzed. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. Secondary outcomes were successful recanalization (extended Thrombolysis in Cerebral Infarction ≥2B), symptomatic intracranial hemorrhage, and mortality at 90 days. We used multilevel regression analysis to evaluate the association of periprocedural intravenous heparin on outcomes, adjusted for center effects and prognostic factors. To account for possible unobserved confounding by indication, we analyzed the effect of center preference to administer intravenous heparin, defined as percentage of patients treated with intravenous heparin in a center, on functional outcome. Results- One thousand four hundred eighty-eight patients from 16 centers were analyzed, of whom 398 (27%) received intravenous heparin (median dose 5000 international units). There was substantial between-center variability in the proportion of patients treated with intravenous heparin (range, 0%-94%). There was no significant difference in functional outcome between patients treated with intravenous heparin and those without (adjusted common odds ratio, 1.17; 95% CI, 0.87-1.56), successful recanalization (adjusted odds ratio, 1.24; 95% CI, 0.89-1.71), symptomatic intracranial hemorrhage (adjusted odds ratio, 1.13; 95% CI, 0.65-1.99), or mortality (adjusted odds ratio, 0.95; 95% CI, 0.66-1.38). Analysis at center level showed that functional outcomes were better in centers with higher percentages of heparin administration (adjusted common odds ratio, 1.07 per 10% more heparin, 95% CI, 1.01-1.13). Conclusions- Substantial between-center variability exists in periprocedural intravenous heparin use during endovascular treatment, but the treatment is safe. Centers using heparin more often had better outcomes. A randomized trial is needed to further study these effects.
Recombinant human tissue plasminogen activator (rh-tPA) is an important thrombolytic agent for treatment of acute ischemic stroke. It requires fibrin binding for plasminogen activation. In contrast, ...Microlyse, a novel thrombolytic agent, requires von Willebrand factor (VWF) binding for plasminogen activation. We compared rh-tPA with Microlyse, administered 20 minutes after inducing thrombosis, in 2 randomized blinded acute ischemic stroke mouse models. Thrombosis was induced in the middle cerebral artery with different experimental triggers. Where thrombin infusion generates fibrin-rich thrombi, topical FeCl3 application generates platelet-rich thrombi. In the fibrin-rich model, both rh-tPA and Microlyse increased cortical reperfusion (determined by laser speckle imaging) 10 minutes after therapy administration (35.8 ± 17.1%; P = .001 39.3 ± 13.1%; P < .0001; 15.6 ± 7.5%, respectively, vs vehicle). In addition, both thrombolytic agents reduced cerebral lesion volume (determined by magnetic resonance imaging) after 24 hours (18.9 ± 11.2 mm3; P = .033; 16.1 ± 13.9 mm3; P = .018; 26.6 ± 5.6 mm3, respectively, vs vehicle). In the platelet-rich model, neither rh-tPA nor Microlyse increased cortical reperfusion 10 minutes after therapy (7.6 ± 8.8%; P = .216; 16.3 ± 13.9%; P = .151; 10.1 ± 7.9%, respectively, vs vehicle). However, Microlyse, but not rh-tPA, decreased cerebral lesion volumes (13.9 ± 11.4 mm3; P < .001; 23.6 ± 11.1 mm3; P = .188; 30.3 ± 10.9 mm3, respectively, vs vehicle). These findings support broad applicability of Microlyse in ischemic stroke, irrespective of the thrombus composition.
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