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Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

Background and Purpose: The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack. Methods: We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score. Results: We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60–3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59–1.62) in those without SVD ( P =0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01–3.53]; P =0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04–1.70]; P =0.023). Conclusions: In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02513316.

Although hypertension is known to cause brain damage and cognitive impairment, epidemiological studies suggest that lower blood pressure (BP) in patients with established cerebrovascular disease is associated with more rapid cognitive decline. We investigated the relationship between 24-h ambulatory blood pressure (ABP) measurements, cerebrovascular disease load and cognitive performance in patients with hypertensive cerebrovascular disease.Eighty-eight patients (mean age 65+9 years) with hypertensive cerebrovascular disease on MRI were recruited. BP was controlled optimally. ABP monitoring, quantitative MRI analysis of white matter lesion (WML) volume and executive cognitive function tests were performed. The relationships between ABP variables, WML volume and executive test performance were examined using regression analyses to adjust for age, sex, vascular risk profile and premorbid intelligence.Patients had a mean daytime ABP of 96+10 mmHg and mean night-time ABP of 88+11 mmHg (P = 0.001). Median WML volume was 8464 mm3. There were no significant associations between ABP variables and supratentorial WML volumes. Infratentorial WML volume correlated negatively with night-time mean BP (r = -0.6, P = 0.002) and positively with nocturnal dipping (r = 0.6, P = 0.002). Higher night-time mean BP was an independent predictor of reduced infratentorial WML volume (R2: 0.460, P = 0.008).Infratentorial WML volume correlated with impairments of phonemic verbal fluency (r = 0.5, P0.001) and choice reaction time (r = 0.7, P0.005).Physiological falls in nocturnal BP may be associated with increased infratentorial WML volume and cognitive dysfunction in optimally controlled hypertensive patients with cerebrovascular disease.

The importance of lowering blood pressure (BP) in hypertensive subjects is well-known and recent studies suggest that lowering of BP in patients who may already be in the normotensive range further reduces the risk of vascular events, particularly stroke. Epidemiological data have also shown that lower BP and antihypertensive treatment may be associated with cognitive impairment once cerebrovascular disease is established. However, the relationship between hypertension and cerebrovascular disease is more complex than suggested by epidemiological or intervention studies. Cerebral imaging studies have shown that cerebral blood flow (CBF) is reduced in areas of small-vessel disease (SVD) and the degree of hypoperfusion correlates with disease severity. Furthermore, impaired neuropsychological performance has been found to correlate with cerebral hypoperfusion in patients with established SVD. These findings raise questions surrounding the desirability of lowering of BP beyond a certain level in such patients. It is conceivable that indiscriminate BP reduction may compromise cerebral perfusion and function in these patients, increasing the risk of cognitive decline and cerebrovascular disease progression. Randomized clinical trials addressing the relationship between antihypertensive treatment and vascular cognitive impairment are lacking. Further studies are therefore needed to assess the cognitive consequences of BP reduction in people with established cerebrovascular disease. This will help to direct appropriate protective strategies and treatments in a vulnerable group of people, many of whom have hypertension and cerebrovascular disease at the same time.

Introduction: Initial randomised controlled trials (RCTs) showed endovascular treatment of acute ischaemic stroke (AIS) to improve recanalization and functional outcome but recent RCTs have failed to show clinical benefit. Methods: MEDLINE, EMBASE and Cochrane databases were searched for RCTs of endovascular treatment for AIS. Additional RCTs were identified from bibliographies of retrieved articles. Data was extracted on patient characteristics, study intervention, 90-day functional outcome and mortality, 24-hour symptomatic intracerebral haemorrhage (sICH), and post-procedural recanalization. Studies were reviewed independently by 2 trained readers and RCTs of differing methodology were evaluated separately to maintain homogeneity. Results: 12 RCTs were identified with 1910 subjects (mean(SD) age 65(3); 58% male; median(IQR) baseline NIHSS 17(3)) and mean(SD) time for endovascular intervention 4.9(2.9) hours. In 4 RCTs (n=350) comparing intra-arterial thrombolysis (IAT) with no thrombolysis, patients treated with IAT had significantly improved 90-day modified Rankin scale (mRS) Conclusions: IAT for AIS improves recanalization, functional outcome and mortality compared with placebo but not compared with or in addition to IVT. For patients receiving endovascular intervention, stent-retriever devices provide better outcome data than clot-retrieval devices.

Background: City-wide re-organisation of stroke care in London, incorporating 8 hyperacute stroke units (HASUs), has improved thrombolysis rates and survival cost-effectively. Continued staffing of HASUs requires stroke-specialist training to develop competencies for managing neurological emergencies. Simulation training provides an education platform for health care professionals to become immersed in realistic scenarios where outcome is dependent upon technical and non-technical skills. Methods: A standardised, curriculum-mapped, high-fidelity, simulation-training programme was developed on 4 HASUs for city-wide staff to attend. Learning outcomes included technical (acute stroke assessment/management) and non-technical skills (including time management/decision-making/teamwork). A mixed-methods evaluation approach was used to evaluate data from participants before, during, and after training. Results: Over a 2 year period, 152 HASU staff (70 medical; 82 nursing) participated. Quantitative analysis showed a pre/post-course increase in candidates’ ability to manage emergency stroke situations (t=6.6, p Conclusion: Simulation training may be effective in helping achieve HASU-specific learning outcomes and may be delivered in a standardised manner across multiple sites.

Case reportA 42-year-old male security guard was admitted to the Emergency Department having been found unconscious 15 min after starting work without any symptoms. He lived with his mother, who provided a collateral history of his having no previous medical history, family history, recent travel ex