Absent leptomeningeal collateralization is associated with greatest benefit from mechanical thrombectomy in the 6-24 hour time window.

INTRODUCTION: The impact of leptomeningeal collateralization on the efficacy of mechanical thrombectomy (MT) in patients with anterior circulation large vessel occlusion (aLVO) presenting in the 6-24 h time window remains poorly elucidated. PATIENTS AND METHODS: Retrospective multicenter study of aLVO patients presenting between 6 and 24 h after stroke onset who received MT plus Best Medical Treatment (BMT) or BMT alone. Leptomeningeal collateralization was assessed using single-phase computed tomography angiography (grade 0: no filling; grade 1: filling ⩽50%; grade 2: filling >50% but <100%; grade 3: filling 100% of the occluded territory). Inverse probability of treatment weighted ordinal regression was performed to assess the association between treatment and shift of the modified Rankin Scale (mRS) score toward lower categories at 3 months. We used interaction analysis to explore differential treatment effects on functional outcomes (probabilities for each mRS subcategory at 3 months) at different collateral grades. RESULTS: Among 363 included patients, 62% received MT + BMT. Better collateralization was associated with better functional outcomes at 3 months in the BMT alone group (collateral grade 1 vs 0: acOR 5.06, 95% CI 2.33-10.99). MT + BMT was associated with higher odds of favorable functional outcome at 3 months (acOR 1.70, 95% CI 1.11-2.62) which was consistent after adjustment for collateral status (acOR 1.54, 95% CI 1.01-2.35). Regarding treatment effect modification, patients with absent collateralization had higher probabilities for a mRS of 0-4 and a lower mortality at 3 months for the MT + BMT group. DISCUSSION AND CONCLUSION: In the 6-to-24-h time window, aLVO patients with absent leptomeningeal collateralization benefit most from MT + BMT, indicating potential advantages for this group despite their poorer baseline prognosis.

CADMUS: A Novel MRI-Based Classification of Spontaneous Intracerebral Hemorrhage Associated With Cerebral Small Vessel Disease

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. METHODS: We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. RESULTS: The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. DISCUSSION: CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.

BACKGROUND: Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS: We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS: Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS: In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.

Mechanical Thrombectomy Versus Best Medical Treatment in the Late Time Window in Non-DEFUSE-Non-DAWN Patients: A Multicenter Cohort Study.

BACKGROUND: We assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion presenting in the late time window not fulfilling the DEFUSE-3 (Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging trial) and DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct trial) inclusion criteria. METHODS: Cohort study of adults with anterior circulation large vessel occlusion admitted between 6 and 24 hours after last-seen-well at 5 participating Swiss stroke centers between 2014 and 2021. Mismatch was assessed by computer tomography or magnetic resonance imaging perfusion with automated software (RAPID or OLEA). We excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone by inverse probability of treatment weighting using the propensity score. The primary efficacy end point was a favorable functional outcome at 90 days, defined as a modified Rankin Scale score shift toward lower categories. The primary safety end point was symptomatic intracranial hemorrhage within 7 days of stroke onset; the secondary was all-cause mortality within 90 days. RESULTS: Among 278 patients with anterior circulation large vessel occlusion presenting in the late time window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the inverse probability of treatment weighting analysis, patients in the MT group had higher odds of favorable outcomes compared with the best medical treatment alone group (modified Rankin Scale shift: acOR, 1.46 [1.02-2.10]; P=0.04) and lower odds of all-cause mortality within 90 days (aOR, 0.59 [0.37-0.93]; P=0.02). There were no significant differences in symptomatic intracranial hemorrhage (MT versus best medical treatment alone: 5% versus 2%, P=0.63). CONCLUSIONS: Two out of 3 patients with anterior circulation large vessel occlusion presenting in the late time window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of symptomatic intracranial hemorrhage. These findings support the enrollment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.

Mechanical thrombectomy for large vessel occlusion between 6 and 24 h: outcome comparison of DEFUSE-3/DAWN eligible versus non-eligible patients.

BACKGROUND: The DEFUSE-3 and DAWN trials showed that mechanical thrombectomy (MT) improves the outcome of selected patients with anterior circulation large vessel occlusions (LVO) up to 24 h after stroke onset. However, it is unknown whether only those patients fulfilling the trial inclusion criteria benefit, or whether benefit is seen in a broader range of patients presenting between 6 and 24 h. AIMS: We determined whether fulfilling the DEFUSE-3 and DAWN selection criteria affects outcomes in MT patients in clinical practice. METHODS: We reviewed adult patients with LVO treated with MT between 6 and 24 h after stroke onset at five Swiss stroke centers between 2014 and 2021. We compared two groups: (1) patients who satisfied neither DEFUSE-3 nor DAWN criteria (NDND) and (2) those who satisfied DEFUSE-3 or DAWN criteria (DOD). We used logistic regression to examine the impact of trial eligibility on two safety outcomes (symptomatic intracranial hemorrhage [sICH] and all-cause mortality at 3 months) and two efficacy outcomes (modified Rankin Score [mRS] shift toward lower categories and mRS of 0-2 at 3 months). RESULTS: Of 174 patients who received MT, 102 (59%) belonged to the NDND group. Rates of sICH were similar between the NDND group and the DOD group (3% vs. 4%, p = 1.00). Multivariable regression revealed no differences in 3-month all-cause mortality (aOR 2.07, 95% CI 0.64-6.84, p = 0.23) or functional outcomes (mRS shift: acOR 0.81, 95% CI 0.37-1.79, p = 0.60; mRS 0-2: aOR 0.91, 95% CI 0.31-2.57, p = 0.85). CONCLUSION: Among adult patients with LVO treated with MT between 6 and 24 h, safety and efficacy outcomes were similar between DEFUSE-3/DAWN eligible and ineligible patients. Our data provide a compelling rationale for randomized trials with broader inclusion criteria for MT.

A forgotten disease: Pelvic congestion syndrome as a cause of chronic lower abdominal pain.

OBJECTIVES: Pelvic congestion syndrome is defined as chronic pelvic pain due to incompetent (dilated and refluxing) pelvic veins. The aim of this study was to investigate the prevalence of this condition by examining the prevalence of dilated ovarian and para-uterine veins in pre- and postmenopausal female patients, irrespective of their symptoms. We subsequently investigated how many women with dilated veins suffered from chronic pelvic pain. Additionally, we attempted to define diagnostic criteria that may allow for early identification of affected patients. METHODS: We reassessed 2384 abdomino-pelvic computed tomography scans performed on women at our institution. The maximal diameters of the ovarian and para-uterine veins were measured. Patients with a pathological process in the abdomen or pelvis affecting the veins were excluded. We considered ovarian vein dilation to be 6 mm or more in the axial plane. For patients that met these criteria, we performed a retrospective chart review to evaluate the clinical presentation and/or symptoms of these patients. RESULTS: Dilated pelvic veins were present in 293/2384 (12%) patients, 118/559 premenopausal (21%) and 175/1825 postmenopausal (10%). Chronic pelvic pain of unclear etiology had been documented prior to the CT in 54/293 (18%) women with dilated veins-2% of the whole study collective (54/2384); 8% of all premenopausal (44/559) and 0.5% of all postmenopausal (10/1825). It was often accompanied by urological symptoms such as hematuria, dysuria, and urinary frequency, in the absence of infection (p<0.05). We identified a strong correlation between the presence of dilated ovarian veins and chronic pelvic pain in premenopausal parous patients with hematuria. CONCLUSIONS: Pelvic congestion syndrome appears to be an underdiagnosed and undertreated disease. In our study, 8% of all premenopausal women had documented chronic pelvic pain of unclear etiology and dilated ovarian and pelvic veins on cross-sectional imaging studies. The features we identified in this study as most relevant should enable a faster identification of patients who could benefit from a specific treatment regimen for this condition.