Dural Arteriovenous Fistulae After Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE: This analysis examined the frequency of dural arteriovenous fistulae (dAVF) after cerebral venous thrombosis (CVT) in patients included in a randomized controlled trial comparing dabigatran etexilate with dose-adjusted warfarin (RE-SPECT CVT [A Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate With Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis]), who had systematic follow-up magnetic resonance (MR) imaging. METHODS: RE-SPECT CVT was a Phase 3, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded end point adjudication. We allocated patients with acute CVT to dabigatran 150 mg twice daily or dose-adjusted warfarin, for 24 weeks and obtained a standardized MR protocol including time-of-flight MR angiography, 3-dimensional phase-contrast venography, and 3-dimensional contrast-enhanced MR venography at the end of the treatment period. A blinded adjudication committee assessed the presence of dAVF in a predefined substudy of the trial. RESULTS: We analyzed development of dAVF in 112 of 120 randomized patients; 57 allocated to dabigatran and 55 to warfarin. For 3 (2.7%) of these 112 patients, quality of follow-up imaging was insufficient to evaluate dAVF. A dAVF (Borden I) was found in 1 patient (0.9%) allocated to warfarin; however, this dAVF was already present at baseline. The patient did not present with hemorrhage at baseline or during the trial and was asymptomatic at follow-up. CONCLUSIONS: Despite systematic imaging, we found no new dAVF 6 months after CVT. Routine follow-up cerebral MR angiography aiming to detect new dAVF 6 months after CVT has a very low yield. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02913326.

d-Cycloserine enhanced extinction of cocaine-induced conditioned place preference is attenuated in serotonin transporter knockout rats.

d-Cycloserine (DCS), a partial NMDA receptor agonist, has been proposed as a cognitive enhancer to facilitate the extinction of drug-related memories. However, it is unknown whether there are individual differences in the efficacy of DCS. Here, we set out to investigate the influence of serotonin transporter (5-HTT) genotype on DCS treatment outcome and the underlying neural mechanism. To that end, we first determined the mRNA levels of several NMDA receptor subunits and observed a reduction in NR1/NR2C receptors in the ventromedial prefrontal cortex and nucleus accumbens of 5-HTT-/- compared with 5-HTT+/+ rats. Based on this finding, we hypothesized a lower sensitivity to DCS in the 5-HTT-/- rats. To test this, rats were trained in a cocaine-induced conditioned place preference (CPP) paradigm. A significant extinction of CPP was observed in 5-HTT+/+ rats receiving 1 mg/kg i.v. DCS, while a similar effect was found in the 5-HTT-/- rats only after 5 mg/kg. Following CPP, we tested if DCS were able to reduce FosB/∆FosB protein expression, a molecular switch for cocaine-seeking behaviour. We observed an overall lower number of FosB/∆FosB positive cells in 5-HTT-/- ventromedial prefrontal cortex and amygdala and an overall effect of DCS treatment on the number of positive cells in the nucleus accumbens. In conclusion, in this study, we show that the dosing of DCS to facilitate the extinction of cocaine-seeking behaviour is, at least partially, determined by 5-HTT genotype.

Achieving a door-to-needle time of 25 minutes in thrombolysis for acute ischemic stroke: a quality improvement project.

BACKGROUND: Providing intravenous thrombolysis with short door-to-needle time is the result of a complex process that requires specific work standards. To expedite care for acute ischemic stroke patients, close collaboration between all participating health care professionals is required. The aim of this project was to reduce in-hospital treatment delay for acute ischemic stroke patients through the introduction of a standard operating procedure and by creating higher and sustained awareness of the importance of intravenous thrombolysis. METHODS: This study was set up as a before-versus-after study, divided into a preintervention period, an immediate postintervention period, and a late postintervention period. During the study, a standard operating procedure was implemented that defined the targeted standard of care to be provided to all acute stroke patients. Involved health care professionals received regular feedback to create greater awareness of the importance of this time-driven protocol. RESULTS: The median door-to-needle time decreased significantly, from 60 minutes in the preintervention period to 30 minutes in the immediate postintervention period (P < .001), and compared with the immediate postintervention period it decreased significantly further, to 25 minutes, in the late postintervention period (P < .001). The proportion of patients with a door-to-needle time <30 minutes and <20 minutes increased significantly across the 3 study periods (P < .001). CONCLUSIONS: The door-to-needle time for acute ischemic stroke patients can be reduced through the introduction of a standard operating procedure and by creating higher and sustained awareness of the importance of intravenous thrombolysis among health care professionals involved.

Pre- and Interhospital Workflow Times for Patients With Large Vessel Occlusion Stroke Transferred for Endovasvular Thrombectomy.

Background: Patients with large vessel occlusion (LVO) stroke are often initially admitted to a primary stroke center (PSC) and subsequently transferred to a comprehensive stroke center (CSC) for endovascular thrombectomy (EVT). This interhospital transfer delays initiation of EVT. To identify potential workflow improvements, we analyzed pre- and interhospital time metrics for patients with LVO stroke who were transferred from a PSC for EVT. Methods: We used data from the regional emergency medical services and our EVT registry. We included patients with LVO stroke who were transferred from three nearby PSCs for EVT (2014-2021). The time interval between first alarm and arrival at the CSC (call-to-CSC time) and other time metrics were calculated. We analyzed associations between various clinical and workflow-related factors and call-to-CSC time, using multivariable linear regression. Results: We included 198 patients with LVO stroke. Mean age was 70 years (±14.9), median baseline NIHSS was 14 (IQR: 9-18), 136/198 (69%) were treated with intravenous thrombolysis, and 135/198 (68%) underwent EVT. Median call-to-CSC time was 162 min (IQR: 137-190). In 133/155 (86%) cases, the ambulance for transfer to the CSC was dispatched with the highest level of urgency. This was associated with shorter call-to-CSC time (adjusted ß [95% CI]: -27.6 min [-51.2 to -3.9]). No clinical characteristics were associated with call-to-CSC time. Conclusion: In patients transferred from a PSC for EVT, median call-to-CSC time was over 2.5 h. The highest level of urgency for dispatch of ambulances for EVT transfers should be used, as this clearly decreases time to treatment.

The association between computed tomography angiography timing and workflow times in patients with acute ischemic stroke.

BACKGROUND: In most hospitals, computed tomography angiography (CTA) is nowadays routinely performed in patients with acute ischemic stroke. However, it is unclear whether CTA is best performed before or after start of intravenous thrombolysis (IVT), since acquisition of CTA before IVT may prolong door-to-needle times, while acquisition after IVT may prolong door-to-groin times in patients undergoing endovascular treatment. METHODS: We performed a before-versus-after study (CTA following IVT, period I and CTA prior to IVT, period II), consisting of two periods of one year each. This study is based on a prospective registry of consecutive patients treated with IVT in two collaborating high-volume stroke centers; one primary stroke center and one comprehensive stroke center. The primary outcome was door-to-needle times. Secondary outcomes included door-to-groin times. Quantile regression analyses were performed to evaluate the association between timing of CTA and workflow times, adjusted for prognostic factors. RESULTS: A total of 519 patients received IVT during the study period (246 in period I, 273 in period II). In the adjusted analysis, we found a nonsignificant 1.13 min median difference in door-to-needle times (95% confidence interval: 1.03-3.29). Door-to-groin times was significantly shorter in period II in both unadjusted and adjusted analysis with the latter showing a 19.16 min median difference (95% confidence interval: 3.08-35.24). CONCLUSIONS: CTA acquisition prior to start of IVT did not adversely affect door-to-needle times. However, a significantly shorter door-to-groin times was observed in endovascular treatment eligible patients. Performing CTA prior to start of IVT seems the preferred strategy.