Intravenous thrombolysis in acute central retinal artery occlusion – A prospective interventional case series

<div><p>Background</p><p>No evidence-based therapy exists for non-arteritic central retinal artery occlusion (NA-CRAO). Retinal ischemic tolerance is low; irreversible damage occurs within four hours of experimental NA-CRAO. In previous randomized trials evaluating intra-arterial or intravenous thrombolysis (IVT) in NA-CRAO, only one patient was treated this early. In December 2013, the Departments of Neurology & Stroke and Ophthalmology at University Hospital Tuebingen, Germany, decided to treat patients using IVT within 4.5 hours of NA-CRAO, the therapeutic window established for ischemic stroke.</p><p>Materials and methods</p><p>Consecutive NA-CRAO patients with severe visual loss received IVT after exclusion of intracranial hemorrhage. Follow-up was conducted at day 5 (d5) and day 30 (d30). Visual outcomes were compared to the conservative standard treatment (CST) arm of the EAGLE-trial.</p><p>Results</p><p>Until August 2016, 20 patients received IVT within 4.5 hours after NA-CRAO with a median onset-to-treatment time of 210 minutes (IQR 120–240). Visual acuity improved from baseline mean logarithm of the minimum angle of resolution 2.46±0.33 (SD) (light perception) to 1.52±1.09 (Snellen equivalent: 6/200) at d5 (p = 0.002) and 1.60±1.08 (Snellen equivalent: 6/240) at d30. Compared to the EAGLE CST-arm, functional recovery to reading ability occurred more frequently after IVT: 6/20 (30%) versus 1/39 (3%) at d5 (p = 0.005) and at d30 5/20 (25%) versus 2/37 (5%) (p = 0.045). Two patients experienced serious adverse events (one angioedema and one bleeding from an abdominal aortic aneurysm) but recovered without sequelae.</p><p>Conclusions</p><p>IVT within 4.5 hours after symptom onset may represent an effective treatment of NA-CRAO. Randomized trials are warranted to evaluate efficacy and safety of early IVT in acute NA-CRAO.</p></div

Comparison of patients with and without elevated IgG index.

Comparison of patients with and without elevated IgG index.</p

Quotient of CSF and serum IgG as well as quotient of CSF and serum albumin for all OCB positive (red spots) and OCB negative (blue spots) patients.

Quotient of CSF and serum IgG as well as quotient of CSF and serum albumin for all OCB positive (red spots) and OCB negative (blue spots) patients.</p

Patients with intrathecal IgG synthesis and chronic inflammatory CNS disease.

Patients with intrathecal IgG synthesis and chronic inflammatory CNS disease.</p

Additional file 1: Table S1. of Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants

Patient characteristics in the study groups. Table S2. Baseline laboratory results of patients in the study groups. Table S3. Diagnostic accuracy of HemochronŽ Signature aPTT and ACT-LR POCT cards for dabigatran. (DOC 87 kb

Occurrence of intrathecal IgG synthesis in context of autoimmune disease.

Occurrence of intrathecal IgG synthesis in context of autoimmune disease.</p

Patient flow.

<p>BCVA = best corrected visual acuity, CRAO = central retinal artery occlusion, IVT = intravenous thrombolysis, INR = international normalized ratio, LogMAR = logarithm of the minimum angle of resolution.</p

Intravenous thrombolysis in acute central retinal artery occlusion – A prospective interventional case series - Fig 2

<p><b>Evolution of best corrected visual acuity over time (BCVA):</b> (A) mean BCVA of our intravenous thrombolysis (IVT) cohort (N = 20) and of the conservative standard treatment (CST) group of the EAGLE-trial [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198114#pone.0198114.ref007" target="_blank">7</a>]. (B) individual BCVA of our IVT-cohort and (C) of the EAGLE CST-arm. Functional blindness (LogMAR >1.3) and functional recovery (LogMAR ≤0.5) are indicated by a gray and blue background, respectively. LogMAR = logarithm of the minimum angle of resolution.</p

Categorical presentation of best corrected visual acuity.

<p>Categorical presentation of best corrected visual acuity (according to the current version of the WHO International Classification of Diseases [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198114#pone.0198114.ref014" target="_blank">14</a>]) at baseline and at day 30 of our intravenous thrombolysis cohort and of the conservative standard treatment group of the EAGLE-trial [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198114#pone.0198114.ref007" target="_blank">7</a>]. We defined favorable outcome as mild or no visual impairment (LogMAR ≤0.5, indicated in blue). Unfavorable outcome includes moderate or severe visual impairment (LogMAR >0.5 to ≤1.3) and functional blindness (LogMAR >1.3). LogMAR = logarithm of the minimum angle of resolution.</p

TRoponin of Unknown origin in STroke evaluated by multi-component cardiac Magnetic resonance Imaging - The TRUST-MI study

AimsIncreased high-sensitive cardiac troponin I (hs-cTnI) levels are common in patients with acute ischemic stroke. However, only a minority demonstrates culprit lesions on coronary angiography, suggesting other mechanisms, e.g., inflammation, as underlying cause of myocardial damage. Late Gadolinium Enhancement (LGE)-cardiac magnetic resonance (CMR) with mapping techniques [T1, T2, extracellular volume (ECV)] allow the detection of both focal and diffuse myocardial abnormalities. We investigated the prevalence of culprit lesions by coronary angiography and myocardial tissue abnormalities by a comprehensive CMR protocol in troponin-positive stroke patients.Methods and resultsPatients with troponin-positive acute ischemic stroke and no history of coronary artery disease were prospectively enrolled. Coronary angiography and CMR (LGE, T1 + T2 mapping, ECV) were performed within the first days of the acute stroke. Twenty-five troponin-positive patients (mean age 62 years, 44% females) were included. 2 patients (8%) had culprit lesions on coronary angiography and underwent percutaneous coronary intervention. 13 patients (52%) demonstrated LGE: (i) n = 4 ischemic, (ii) n = 4 non-ischemic, and (iii) n = 5 ischemic AND non-ischemic. In the 12 LGE-negative patients, mapping revealed diffuse myocardial damage in additional 9 (75%) patients, with a high prevalence of increased T2 values.ConclusionsOur data show a low prevalence of culprit lesions in troponin-positive stroke patients. However, > 50% of the patients demonstrated myocardial scars (ischemic + non-ischemic) by LGE-CMR. Mapping revealed additional myocardial abnormalities (mostly inflammatory) in the majority of LGE-negative patients. Therefore, a comprehensive CMR protocol gives important insights in the etiology of troponin which might have implications for the further work-up of troponin-positive stroke patients.</p