A scoring tool to predict mortality and dependency after cerebral venous thrombosis.

BACKGROUND AND PURPOSE: A prognostic score was developed to predict dependency and death after cerebral venous thrombosis (CVT) to identify patients for targeted therapy in future clinical trials. METHODS: Data from the International CVT Consortium were used. Patients with pre-existent functional dependency were excluded. Logistic regression was used to predict poor outcome (modified Rankin Scale score 3-6) at 6 months and Cox regression to predict 30-day and 1-year all-cause mortality. Potential predictors derived from previous studies were selected with backward stepwise selection. Coefficients were shrunk using ridge regression to adjust for optimism in internal validation. RESULTS: Of 1454 patients with CVT, the cumulative number of deaths was 44 (3%) and 70 (5%) for 30 days and 1 year, respectively. Of 1126 patients evaluated regarding functional outcome, 137 (12%) were dependent or dead at 6 months. From the retained predictors for both models, the SI2 NCAL2 C score was derived utilizing the following components: absence of female-sex-specific risk factor, intracerebral hemorrhage, infection of the central nervous system, neurological focal deficits, coma, age, lower level of hemoglobin (g/l), higher level of glucose (mmol/l) at admission, and cancer. C-statistics were 0.80 (95% confidence interval [CI] 0.75-0.84), 0.84 (95% CI 0.80-0.88) and 0.84 (95% CI 0.80-0.88) for the poor outcome, 30-day and 1-year mortality model, respectively. Calibration plots indicated a good model fit between predicted and observed values. The SI2 NCAL2 C score calculator is freely available at www.cerebralvenousthrombosis.com. CONCLUSIONS: The SI2 NCAL2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted.

Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial.

Importance: Patients with cerebral venous thrombosis (CVT) are at risk of recurrent venous thrombotic events (VTEs). Non-vitamin K oral anticoagulants have not been evaluated in randomized controlled trials in CVT. Objective: To compare the efficacy and safety of dabigatran etexilate with those of dose-adjusted warfarin in preventing recurrent VTEs in patients who have experienced a CVT. Design, Setting, and Participants: RE-SPECT CVT is an exploratory, prospective, randomized (1:1), parallel-group, open-label, multicenter clinical trial with blinded end-point adjudication (PROBE design). It was performed from December 21, 2016, to June 22, 2018, with a follow-up of 25 weeks, at 51 tertiary sites in 9 countries (France, Germany, India, Italy, the Netherlands, Poland, Portugal, Russia, and Spain). Adult consecutive patients with acute CVT, who were stable after 5 to 15 days of treatment with parenteral heparin, were screened for eligibility. Patients with CVT associated with central nervous system infection or major trauma were excluded, but those with intracranial hemorrhage from index CVT were allowed to participate. After exclusions, 120 patients were randomized. Data were analyzed following the intention-to-treat approach. Interventions: Dabigatran, 150 mg twice daily, or dose-adjusted warfarin for a treatment period of 24 weeks. Main Outcomes and Measures: Primary outcome was a composite of patients with a new VTE (recurrent CVT, deep vein thrombosis of any limb, pulmonary embolism, and splanchnic vein thrombosis) or major bleeding during the study period. Secondary outcomes were cerebral venous recanalization and clinically relevant non-major bleeding events. Results: In total, 120 patients with CVT were randomized to the 2 treatment groups (60 to dabigatran and 60 to dose-adjusted warfarin). Of the randomized patients, the mean (SD) age was 45.2 (13.8) years, and 66 (55.0%) were women. The mean (SD) duration of exposure was 22.3 (6.16) weeks for the dabigatran group and 23.0 (5.20) weeks for the warfarin group. No recurrent VTEs were observed. One (1.7%; 95% CI, 0.0-8.9) major bleeding event (intestinal) was recorded in the dabigatran group, and 2 (3.3%; 95% CI, 0.4-11.5) (intracranial) in the warfarin group. One additional patient (1.7; 95% CI, 0.0-8.9) in the warfarin group experienced a clinically relevant non-major bleeding event. Recanalization occurred in 33 patients in the dabigatran group (60.0%; 95% CI, 45.9-73.0) and in 35 patients in the warfarin group (67.3%; 95% CI, 52.9-79.7). Conclusions and Relevance: This trial found that patients who had CVT anticoagulated with either dabigatran or warfarin had low risk of recurrent VTEs, and the risk of bleeding was similar with both medications, suggesting that both dabigatran and warfarin may be safe and effective for preventing recurrent VTEs in patients with CVT. Trial Registration: ClinicalTrials.gov identifier: NCT02913326.

Recommendations on telestroke in Europe.

Lack of stroke specialists determines that many European rural areas remain underserved. Use of telemedicine in stroke care has shown to be safe, increase use of evidence-based therapy and enable coverage of large areas of low population density. The aim of this article is to summarise the following recommendations of the Telestroke Committee of the European Stroke Organisation on the setup of telestroke networks in Europe: Hospitals participating in telestroke networks should be chosen according to criteria that include population density, transportation distance, geographic specifics and in-hospital infrastructure and professional resources. Three hospital categories are identified to be part of a hub-and-spoke network: (1) the Telemedicine Stroke Centre (an European Stroke Organisation stroke centre or equivalent with specific infrastructure and setup for network and telemedicine support), (2) the telemedicine-assisted stroke Unit (equivalent to an European Stroke Organisation stroke unit but without 24 h onsite stroke expertise) and (3) the telemedicine-assisted stroke ready hospital (only covering hyperacute treatment in the emergency department and transferring all patients for further treatment).

A Comparison of Remote and Bedside Assessment of the National Institute of Health Stroke Scale in Acute Stroke Patients.

INTRODUCTION: Telestroke videoconference for conducting the National Institute of Health Stroke Scale (NIHSS) is recommended when the facility of a direct bedside evaluation by a stroke specialist is not immediately available for hyperacute stroke assessment. However, some NIHSS-telestroke studies inherit systematic bias due to the subjective nature of NIHSS administration. We aimed to evaluate NIHSS telestroke assessment, while implementing measures to minimize subjectivity bias. PATIENTS AND METHODS: Ninety stroke patients within 48 h of onset were assessed by 6 stroke neurologists grouped in 15 pairs. Each pair of physicians assessed 6 patients. Patients were allocated through block randomization to a physician pair and order of bedside or remote assessment. Every patient was assessed once at the bedside and once remotely. Remote examination was performed by a neurologist through high-quality videoconferencing (HQ-VTC), assisted by a nurse at the patient's bedside. Kappa coefficients and the number of patients with a cumulative difference of ≤3 NIHSS points were calculated to compare bedside and remote measures. RESULTS: Cumulative difference of ≤3 NIHSS points was observed in 85.6% (95% CI 76.6-92.1%) cases. Therefore, every fifth remote examination may have been inaccurate. Quadratically weighted kappa for total NIHSS score was 0.91 (95% CI 0.87-0.95). Minimal agreements were for commands (k = 0.46), facial palsy (k = 0.43), and ataxia (k = 0.27). Remote assessments were longer than bedside: 8 min (interquartile range, IQR 7-9) vs. 6 (IQR 5-8), p < 0.001. CONCLUSIONS: NIHSS-telestroke assessment using HQ-VTC in the acute stroke settings is closely matched with NIHSS-bedside assessment but it's credibility for clinical use needs further evaluation.

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis.

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of-trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-to-treatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5-15), randomised 11 days (interquartile range IQR 4-238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p = 0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p = 0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p = 0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis.

Granulocyte-colony-stimulating Factor for Acute Ischemic Stroke: A Randomized Controlled Trial (STEMTHER).

Granulocyte-colony-stimulating factor (G-CSF) functions both as a neuroprotectant and a stimulator of autologous bone marrow stem cell release. Therefore, administration of G-CSF should improve the outcome of stroke. Here, we examine the safety of using G-CSF to treat acute ischemic stroke using a randomized controlled trial involving 20 adult patients presenting with ischemia in the carotid region within 48 h of onset. The experimental group (n = 10) received subcutaneous G-CSF injections (10 mg kg(-1) day(-1)) in addition to conventional therapy for 5 days. The primary outcome was motor function as measured by the modified Rankin Scale 180 days post-stroke. Safety was evaluated according to the frequency of hemorrhagic transformation of infarctions and serious adverse events. Only six patients in the experimental group completed full course of treatment, while four patients (three in the control and one in the experimental group) were lost to follow-up. We found the experimental and control groups did not differ significantly in either neurological impairment or degree of disability/dependence at 180 days post-stroke. We conclude that while adding G-CSF (10 mg kg(-1) day(-1)) to acute ischemic stroke therapy for 5 days is safe, its efficacy remains unproven.