Background and Purpose— In patients with ischemic stroke on therapy with vitamin K antagonists, stroke severity and clinical course are affected by the quality of anticoagulation at the time of stroke onset, but clinical data for patients using direct oral anticoagulants (DOACs) are limited. Methods— Data from our registry including all patients admitted with acute cerebral ischemia while taking oral anticoagulants for atrial fibrillation between November 2014 and October 2017 were investigated. The activity of vitamin K antagonists was assessed using the international normalized ratio on admission and categorized according to a threshold of 1.7. DOAC plasma levels were measured using the calibrated Xa-activity (apixaban, rivaroxaban, and edoxaban) or the Hemoclot-assay (dabigatran) and categorized into low (<50 ng/mL), intermediate (50–100 ng/mL), or high (>100 ng/mL). Primary objective was the association between anticoagulant activity and clinical and imaging characteristics. Results— Four hundred sixty patients were included (49% on vitamin K antagonists and 51% on DOAC). Patients on vitamin K antagonists with low international normalized ratio values had higher scores on the National Institutes of Health Stroke Scale and a higher risk of large vessel occlusion on admission. For patients on DOAC, plasma levels were available in 75.6% and found to be low in 49 (27.7%), intermediate in 41 (23.2%), and high in 87 patients (49.2%). Low plasma levels were associated with higher National Institutes of Health Stroke Scale scores on admission (low: 8 [interquartile range, 3–15] versus intermediate: 4 [1–11] versus high: 3 [0–8]; P <0.001) and higher risk of persisting neurological deficits or cerebral infarction on imaging (85.7% versus 75.6% versus 54.0%; P <0.001). Low DOAC plasma levels were an independent predictor of large vessel occlusion (odds ratio, 3.84 [95% CI, 1.80–8.20]; P =0.001). Conclusions— The activity of anticoagulation measured by specific DOAC plasma levels on admission is associated with stroke severity and presence of large vessel occlusion.

We assessed pain characteristics and sensory profiles of a large and extensively phenotyped cohort of patients with polyneuropathies (PNPs) and small fiber neuropathy (SFN) using quantitative sensory testing (QST). Our aim was to detect potentially discriminative QST profiles of patient subgroups determined by pain, etiology, or skin innervation. We prospectively recruited 350 patients with painful and painless PNPs and with SFN at 1 neuromuscular center. After neurological work-up, patients underwent QST at the dorsal foot and 5-mm skin punch biopsy at the lower leg and upper thigh for intraepidermal nerve fiber counts. A healthy control group of 273 volunteers was investigated accordingly. Pain was present in 50% of the patients with PNP with a median intensity of 6/10 on a numeric rating scale, and, by definition, in all patients with SFN, with a median intensity of 5/10 numeric rating scale. Axonal PNP was painful more often than demyelinating PNP (P < 0.01). Patients with PNP mostly had loss of function profiles, whereas most patients with SFN belonged to the gain of function (hyperalgesia) phenotype. In healthy controls, skin innervation positively correlated with sensory thresholds, whereas this correlation was lost in patients with PNP and SFN. Quantitative sensory testing did not distinguish between painful and painless neuropathies regarding small fiber function, but revealed higher mechanical pain (P < 0.01) and detection thresholds (P < 0.05) and lower mechanical pain sensitivity in the group of patients with painful neuropathies. Etiological neuropathy subgroups were not distinguished by QST.

ImportanceInternational guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC).ObjectiveTo determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion.Design, Setting, and ParticipantsThis international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021.ExposuresPrior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation.Main Outcomes and MeasuresThe main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses.ResultsOf 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion.Conclusions and RelevanceIn this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

ObjectiveTo investigate differences in procedure times, safety and efficacy outcomes comparing 2 different protocols to enable thrombolysis in the extended or unknown time window after stroke onset using either multimodal CT or MRI.MethodsPatients with ischemic stroke in the extended or unknown time window, who received IV-thrombolysis between January 2011 and May 2019 were identified from an institutional registry. Imaging based selection was done by multimodal CT or MRI according to institutional treatment algorithms.ResultsIV-thrombolysis was performed in 100 patients (54.3%) based on multimodal CT-imaging and in 84 patients (45.7%) based on MRI. Baseline clinical data including stroke severity and time from last seen normal to hospital admission were similar in CT- and MRI-patients. Door-to-needle times were shorter in patients with CT-based selection (median [IQR] 45 minutes [37–62] vs 75 minutes [59–90]; mean difference [95% CI] −28 minutes [−35 to −21]). No differences were detected regarding the incidence of symptomatic intracranial hemorrhage (2 [2.0%] vs 4 [4.8%]; aOR [95% CI]: 0.47 [0.08–2.83]) and favorable outcome at day 90: 25 (33.8%) vs 33 (42.9%); aOR 0.95 (0.45–2.02).ConclusionIV-thrombolysis in ischemic stroke in the unknown or extended time window appeared safe in CT and MRI selected patients while the use of CT-imaging led to faster door-to-needle times.Classification of evidenceThis study provides Class IV evidence that for patients with ischemic stroke in the extended or unknown time window, imaging-based selection for IV-thrombolysis by multimodal CT compared to MRI led to shorter door-to-needle times.