MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset.

BACKGROUND: Under current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase. METHODS: In a multicenter trial, we randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. We excluded patients for whom thrombectomy was planned. The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days. A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo (shift analysis). RESULTS: The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients. Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02). The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 to 2.23; P=0.003). There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P=0.07). The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P=0.15). CONCLUSIONS: In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days. (Funded by the European Union Seventh Framework Program; WAKE-UP ClinicalTrials.gov number, NCT01525290; and EudraCT number, 2011-005906-32 .).

Significance of arterial spin labeling perfusion and susceptibility weighted imaging changes in patients with transient ischemic attack: a prospective cohort study.

BACKGROUND: In a prospective cohort of patients with transient ischemic attack (TIA), we investigated usefulness and feasibility of arterial spin labeling (ASL) perfusion and susceptibility weighted imaging (SWI) alone and in combination with standard diffusion weighted (DWI) imaging in subacute diagnostic work-up. We investigated rates of ASL and SWI changes and their potential correlation to lasting infarction 8 weeks after ictus. METHODS: Patients with TIA underwent 3T-MRI including DWI, ASL and SWI within 72 h of symptom onset. We defined lasting infarction as presence of 8-week MRI T2-fluid attenuated inversion recovery (FLAIR) hyperintensity or atrophy in the area of initial DWI-lesion. RESULTS: We included 116 patients. Diffusion and perfusion together identified more patients with ischemia than either alone (59% vs. 40%, p < 0.0001). The presence of both diffusion and perfusion lesions had the highest rate of 8-week gliosis scars, 65% (p < 0.0001). In white matter, DWI-restriction was the determinant factor for scar development. However, in cortical gray matter half of lesions with perfusion deficit left a scar, while lesions without perfusion change rarely resulted in scars (56% versus 21%, p = 0.03). SWI lesions were rare (6%) and a subset of perfusion lesions. SWI-lesions with DWI-lesions were all located in cortical gray matter and showed high scar rate. CONCLUSIONS: ASL perfusion increased ischemia detection in patients with TIA, and was most useful in conjunction with DWI. ASL was fast, robust and useful in a subacute clinical diagnostic setting. SWI had few positive findings and did not add information. TRIAL REGISTRATION: http://www.clinicaltrials.gov . Unique Identifier NCT01531946 , prospectively registered February 9, 2012.

Sex-Differences in Oral Anticoagulant-Related Intracerebral Hemorrhage.

Introduction and Aim: Data remain limited on sex-differences in patients with oral anticoagulant (OAC)-related intracerebral hemorrhage (ICH). We aim to explore similarities and differences in risk factors, acute presentation, treatments, and outcome in men and women admitted with OAC-related ICH. Method: This study was a retrospective observational study based on 401 consecutive patients with OAC-related ICH admitted within 24 h of symptom onset. The study was registered on osf.io. We performed logarithmic regression and cox-regression adjusting for age, hematoma volume, Charlson Comorbidity Index (CCI), and pre-stroke modified Ranking Scale (mRS). Gender and age were excluded from CHA2DS2-VASc and CCI was not adjusted for age. Results: A total of 226 men and 175 women were identified. More men were pre-treated with vitamin K-antagonists (73.5% men vs. 60.6% women) and more women with non-vitamin K-antagonist oral anticoagulants (26.5% men vs. 39.4% women), p = 0.009. Women were older (mean age 81.9 vs. 76.9 years, p < 0.001). CHA2DS2-VASc and CCI were similar in men and women.Hematoma volumes (22.1 ml in men and 19.1 ml in women) and National Institute of Health Stroke Scale (NIHSS) scores (13 vs. 13) were not statistically different, while median Glasgow Coma Scale (GCS) was lower in women, (14 [8;15] vs. 14 [10;15] p = 0.003).Women's probability of receiving reversal agents was significantly lower (adjusted odds ratio [aOR] = 0.52, p = 0.007) but not for surgical clot removal (aOR = 0.56, p = 0.25). Women had higher odds of receiving do-not-resuscitate (DNR) orders within a week (aOR = 1.67, p = 0.04). There were no sex-differences in neurological deterioration (aOR = 1.48, p = 0.10), ability to walk at 3 months (aOR = 0.69, p = 0.21) or 1-year mortality (adjusted hazard ratio = 1.18, p = 0.27). Conclusion: Significant sex-differences were observed in age, risk factors, access to treatment, and DNRs while no significant differences were observed in comorbidity burden, stroke severity, or hematoma volume. Outcomes, such as adjusted mortality, ability to walk, and neurological deterioration, were comparable. This study supports the presence of sex-differences in risk factors and care but not in presentation and outcomes.

Corrigendum: Sex-differences in oral anticoagulant-related intracerebral hemorrhage.

[This corrects the article DOI: 10.3389/fneur.2022.832903.].

Trends in incidence of oral anticoagulant-related intracerebral hemorrhage and sales of oral anticoagulants in Capital Region of Denmark 2010-2017.

INTRODUCTION: Non-vitamin K-antagonist oral anticoagulants (NOAC) have become first choice oral anticoagulant (OAC) with decreasing use of vitamin K antagonists (VKA), partly due to lower risk of intracerebral hemorrhage (ICH). Aim: to identify trends in sale of OACs and relate them to trends in OAC-related ICH (OAC-ICH). PATIENTS AND METHODS: Study was based on the population in the Capital Region of Denmark (1.8 million inhabitants). We identified all patients admitted with a non-traumatic OAC-ICH in 2010-2017 and ascertained diagnosis and drug use through medical charts. We used information available in the public domain on sale of defined daily doses (DDD) of OAC in the Capital Region of Denmark. RESULTS: 453 patients with OAC-ICH out of a total of 2877 ICH-events were identified. From 2010 to 2017 sale of NOAC rose from 0.1 to 11.8 DDD/1000 inhabitants/day (p < 0.001); while VKA sale decreased from 7.6 to 5.2 DDD/1000 inhabitants/day (p < 0.001). The total number of ICH events was stable between 2010 and 2017, but the proportion of OAC-ICH events increased from 13% in 2010 to 22% in 2017 (p < 0.001). The proportion of ICH events related to NOAC had a significant increasing trend (p < 0.001), whereas a decreasing trend was observed for VKA (p = 0.04). DISCUSSION: In Denmark, the population on OACs has increased; resulting from increased use of NOACs. Parallel to this development, the proportion of OAC-ICH overall has increased based on an increasing trend in NOAC-related ICH. CONCLUSION: Our findings document a need for further research on prevention and treatment of this complication.

[Limb-shaking transient ischaemic attack].

Limb-shaking transient ischaemic attack (LS-TIA) is a symptom of cerebral haemodynamic failure caused by large vessel disease. LS-TIA often remains unrecognised though associated with a poor prognosis. The patient presents with irregular hemiform jerks caused by ischaemia. Imaging demonstrating reduced perfusion or/and flow is essential for the diagnosis, and treatment is aimed at reducing development in atherosclerosis and improving perfusion. As described in this review, management is focused optimising secondary prevention, and in selected cases surgical interventions are considered. Evidence remains weak, especially as to surgical interventions.

Small cortical grey matter lesions show no persistent infarction in transient ischaemic attack? A prospective cohort study.

OBJECTIVES: To find determining factors for persistent infarction signs in patients with transient ischaemic attack (TIA), herein initial diffusion lesion size, visibility on apparent diffusion coefficient (ADC) or fluid-attenuated inversion recovery (FLAIR) and location. DESIGN: Prospective cohort study of patients with clinical TIA receiving 3T-MRI within 72 hours of symptom onset and at 8-week follow-up. SETTING: Clinical workflow in a single tertiary stroke centre between February 2012 and June 2014. PARTICIPANTS: 199 candidate patients were recruited, 64 patients were excluded due to non-TIA discharge diagnosis or no 8-week MRI. 122 patients completed the study. PRIMARY OUTCOME MEASURES: The primary outcome was visible persistent infarction defined as 8-week FLAIR hyperintensity or atrophy corresponding to the initial diffusion-weighted imaging (DWI) lesion. RESULTS: 50 patients showed 84 initial DWI lesions. 29 (35%) DWI lesions did not result in infarction signs on 8-week FLAIR. 26 (90%, P<0.0001) reversing lesions were located in the cortical grey matter (cGM). cGM location (vs any other location) strongly predicted no 8-week infarction sign development (OR 0.02, 95% CI 0.001 to 0.17) or partial lesion area decrease (>30% of initial DWI-area, OR 14.10, 95% CI 3.61 to 54.72), adjusted for FLAIR-visibility, DWI-area, ADC-confirmation and time to scan (TTS) from symptom onset to baseline MRI. Acute FLAIR-visibility was a strong associated factor for persistent infarction signs (OR 33.06, 95% CI 2.94 to 1432.34). For cGM lesions area size was sole associated factor for persistent infarction signs with a 0.31 cm2 (area under the curve (AUC), 0.97) threshold. In eight (16%) DWI-positive patients, all lesions reversed fully. CONCLUSIONS: 16% of DWI-positive patients and one-third of acute DWI lesions caused no persistent infarction signs, especially small cGM lesions were not followed by development of persistent infarction signs. Late MRI after TIA is likely to be less useful in the clinical setting, and it is dubious if the absence of old vascular lesions can be taken as evidence of no prior ischaemic attacks. TRIAL REGISTRATION NUMBER: NCT01531946; Results.

Comparison of 3- and 20-Gradient Direction Diffusion-Weighted Imaging in a Clinical Subacute Cohort of Patients with Transient Ischemic Attack: Application of Standard Vendor Protocols for Lesion Detection and Final Infarct Size Projection.

OBJECTIVE: Diffusion tensor imaging may aid brain ischemia assessment but is more time consuming than conventional diffusion-weighted imaging (DWI). We compared 3-gradient direction DWI (3DWI) and 20-gradient direction DWI (20DWI) standard vendor protocols in a hospital-based prospective cohort of patients with transient ischemic attack (TIA) for lesion detection, lesion brightness, predictability of persisting infarction, and final infarct size. METHODS: We performed 3T-magnetic resonance imaging including diffusion and T2-fluid attenuated inversion recovery (FLAIR) within 72 h and 8 weeks after ictus. Qualitative lesion brightness was assessed by visual inspection. We measured lesion area and brightness with manual regions of interest and compared with homologous normal tissue. RESULTS: 117 patients with clinical TIA showed 78 DWI lesions. 2 lesions showed only on 3DWI. No lesions were uniquely 20DWI positive. 3DWI was visually brightest for 34 lesions. 12 lesions were brightest on 20DWI. The median 3DWI lesion area was larger for lesions equally bright, or brightest on 20DWI [median (IQR) 39 (18-95) versus 18 (10-34) mm2, P = 0.007]. 3DWI showed highest measured relative lesion signal intensity [median (IQR) 0.77 (0.48-1.17) versus 0.58 (0.34-0.81), P = 0.0006]. 3DWI relative lesion signal intensity was not correlated to absolute signal intensity, but 20DWI performed less well for low-contrast lesions. 3DWI lesion size was an independent predictor of persistent infarction. 3-gradient direction apparent diffusion coefficient areas were closest to 8-week FLAIR infarct size. CONCLUSION: 3DWI detected more lesions and had higher relative lesion SI than 20DWI. 20DWI appeared blurred and did not add information. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique Identifier NCT01531946.