Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial.

BACKGROUND: Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke. METHODS: We did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621. FINDINGS: Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores. INTERPRETATION: Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

Vestibular Implantation and the Feasibility of Fluoroscopy-Guided Electrode Insertion.

Recent research has shown promising results for the development of a clinically feasible vestibular implant in the near future. However, correct electrode placement remains a challenge. It was shown that fluoroscopy was able to visualize the semicircular canal ampullae and electrodes, and guide electrode insertion in real time. Ninety-four percent of the 18 electrodes were implanted correctly (<1.5 mm distance to target). The median distances were 0.60 mm, 0.85 mm, and 0.65 mm for the superior, lateral, and posterior semicircular canal, respectively. These findings suggest that fluoroscopy can significantly improve electrode placement during vestibular implantation.

Detection of tremor bursts by a running second order moment function and analysis using interburst histograms.

INTRODUCTION: Conventional linear signal processing techniques are not always suitable for the detection of tremor bursts in clinical practice due to inevitable noise from electromyographic (EMG) bursts. This study introduces (1) a non-linear analysis technique based on a running second order moment function (SOMF) and (2) auto- and cross-interburst interval histograms (IBIH) showing distributions of interburst interval EMG bursts of pathological tremors illustrating an application of the SOMF. MATERIALS AND METHODS: EMG recordings from extensors and flexors of two patients with Parkinson's disease with a rest tremor and from a healthy subject during sustained muscular contraction were preliminary analyzed in a pilot study. The SOMF was obtained by repeated second order moment calculations within a window of fixed width W (time scale parameter) plotted as a function of time. Minimum SOMF values indicate local "moments of inertia" of each EMG burst. Bursts were detected and located when minimum SOMF values were below level L (decision parameter). Optimal settings of parameters W and L were calculated empirically for pathological tremor EMGs. Auto- and cross-IBIHs were obtained from minimum SOMF values of detected bursts. RESULTS: Tremor frequency and phase relation between EMG bursts from auto- and cross-IBIHs agreed with those derived from spectral analysis. Burst detection by SOMF has a high sensitivity and selectivity even with noisy background. CONCLUSION: The SOMF is appropriate for detection of individual EMG bursts of pathological tremors. The technique is sensitive to non-stationary changes of tremor bursts regardless of their amplitude. IBIHs provide a measure of tremor frequency and phase difference between EMG bursts.