Introduction: Measures of cerebral small vessel disease (cSVD), such as white matter hyperintensities (WMH) and cerebral microbleeds (CMB), are associated with an unfavorable clinical course in ...stroke patients on oral anticoagulation (OAC) for atrial fibrillation (AF). Here, we investigated whether similar findings can be observed for global cortical atrophy (GCA). Methods: Registry-based prospective observational study of 320 patients treated with OAC following AF stroke. Patients underwent magnetic resonance imaging (MRI) allowing assessment of GCA. Using the simplified visual Pasquier scale, the severity of GCA was categorized as follows: 0: no atrophy, 1: mild atrophy; 2: moderate atrophy, and 3: severe atrophy. Using adjusted logistic and Cox regression analysis, we investigated the association of GCA using a composite outcome measure, comprising: (i) recurrent acute ischemic stroke (IS); (ii) intracranial hemorrhage (ICH); and (iii) death. Results: In our time to event analysis after adjusting for potential confounders (i.e., WMH, CMB, age, sex, diabetes, arterial hypertension, coronary heart disease, hyperlipidemia, and antiplatelet use), GCA was associated with an increased risk for the composite outcome in all three degrees of atrophy (grade 1: aHR 3.95, 95% CI 1.34–11.63, p = 0.013; grade 2: aHR 3.89, 95% CI 1.23–12.30, p = 0.021; grade 3: aHR 4.16, 95% CI 1.17–14.84, p = 0.028). Conclusion: GCA was associated with our composite outcome also after adjusting for other cSVD markers (i.e., CMB, WMH) and age, indicating that GCA may potentially serve as a prognostic marker for stroke patients with atrial fibrillation on oral anticoagulation.
Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on ...the daily help of others at hospital discharge are scarce.
Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry from Basel, Switzerland, we compared the occurrence of the primary outcome—the composite of recurrent ischemic stroke, major bleeding, and all-cause death—among consecutive patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders.
We analyzed 801 patients (median age 80 years, 46% female), of whom 391 (49%) were dependent at discharge and 680 (85%) received DOACs. Over a total follow-up of 1216 patient-years, DOAC- compared to VKA-treated patients had a lower hazard for the composite outcome (hazard ratio HR, 0.58 95% CI, 0.42–0.81), as did independent compared to dependent patients (HR, 0.54 95% CI, 0.40–0.71). There was no evidence that the effect of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome differed between dependent (HRdependent, 0.68 95% CI, 0.45–1.01) and independent patients (HRindependent, 0.44 95% CI, 0.26–0.75) in the simple model (Pinteraction=0.212). Adjusted (HRdependent, 0.74 95% CI, 0.49–1.11 and HRindependent, 0.51 95% CI, 0.30–0.87; Pinteraction=0.284) and weighted models (HRdependent, 0.79 95% CI, 0.48–1.31 and HRindependent, 0.46 95% CI, 0.26–0.81; Pinteraction=0.163) yielded concordant results. Secondary analyses focusing on the individual components of the composite outcome were consistent to the primary analyses.
The benefits of DOACs in patients with atrial fibrillation with a recent stroke were maintained among patients who were dependent on the help of others at discharge.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03826927.
Doublecortin (DCX) is a microtubule‐associated protein widely used as an indicator of neurogenesis in immunohistochemical analyses of the postmortem adult brain. A recent study reported that DCX can ...be quantified in the cerebrospinal fluid (CSF) from healthy rats between postnatal day 0 (P0) and P30. However, it is currently unclear whether the concentration of DCX in the CSF (CSF‐DCX) may represent a measure of endogenous neurogenesis. To address this question, this study examined the impact of a neonatal hypoxic‐ischemic (HI) brain injury, known to induce neurogenesis, on CSF‐DCX. HI was elicited at P7 in Sprague–Dawley rat neonates, and CSF was collected serially from the cisterna magna at P5 and P10, or at P10 and P15. A sandwich immunoassay was used to measure CSF‐DCX. Brains from P10 neonates were analyzed immunohistochemically for neurogenesis and cell death markers. Mean CSF‐DCX was significantly higher in HI‐ than in sham‐exposed animals, at both P10 and P15. In the HI group at P10, CSF‐DCX and stroke severity correlated positively. DCX immunoreactivity was increased in the ipsilateral neurogenic niches from the P10 HI brains in comparison with that of shams. The number of proliferative DCX‐positive cells was higher in the ipsilateral hippocampal subgranular zone (SGZ) than in the HI contralateral or sham SGZ. Thus, neonatal HI brain injury disrupts the developmental time‐course of DCX levels in the CSF. Our data suggest that the increased concentration of DCX in the CSF after neonatal HI is the result of both cellular injury and increased neurogenesis.
The main goal of this report was to examine whether the concentration of the protein doublecortin (DCX) in the CSF (CSF‐DCX) reflects endogenous neurogenesis in the brain. Using a rat model of neonatal hypoxia‐ischemia (HI), we found that CSF‐DCX was a measure of both stroke severity and HI‐induced neurogenesis. ** = P < 0.01, *** = P < 0.0001.
Current guidelines advocate to treat refractory status epilepticus (RSE) with continuously administered anesthetics to induce an artificial coma if first- and second-line antiseizure drugs have ...failed to stop seizure activity. A common surrogate for monitoring the depth of the artificial coma is the appearance of a burst-suppression pattern (BS) in the EEG. This review summarizes the current knowledge on the origin and neurophysiology of the BS phenomenon as well as the evidence from the literature for the presumed benefit of BS as therapy in adult patients with RSE.
Plasma levels of Rivaroxaban (RivLev) might be useful to guide therapeutic decisions in patients with acute stroke under Rivaroxaban. A prerequisite for the potential clinical usefulness is their ...rapid availability in emergency situations. Single-center explorative analysis from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (NOACISP, cinicaltrials.gov:NCT02353585). We included consecutive patients with acute ischemic or hemorrhagic stroke under Rivaroxaban (last intake <48 h) in which RivLev determined by an automated anti-factor Xa-based chromogenic assay (Hyphen-Biomed, France) are available. Primary endpoint was the turnaround time (TAT), defined as time from registration of the blood sample in the lab to first result published. Furthermore, we studied, whether TAT is influenced by (1) on- and off-hour-measurements and (2) early versus later patient arrival (cut-off: 270 min after symptom onset). Thirty-eight patients met the eligibility criteria (mean age 77 years, 44 % female). TAT was 34 min (IQR 29–65 min). TATs were similar for on- (n = 14; median 34 min; IQR 30–56 min) and off-hours-TATs (n = 24; median 35 min; IQR 29–75 min) as well as for early (n = 16; median 33 min; IQR 30–40 min) and late patient arrival (n = 22, median 34 min, IQR 28–58 min; all nonsignificant.). Taking into account RivLev in the decision process about the use of intravenous thrombolysis, three patients received intravenous thrombolysis on an individualized basis, none of them with bleeding complications. Emergency measurement of RivLev among patients with acute stroke is available within a median of 34 min and therefore feasible for ED use. Due to the rapid availability, further research to evaluate the role of RivLev in order to guide acute treatment decisions is warranted.
Background:
Data on the impact of competing stroke etiologies in stroke patients with atrial fibrillation (AF) are scarce.
Methods:
We used prospectively obtained data from an observational registry ...(Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-(NOACISP)-LONGTERM) of consecutive AF-stroke patients treated with oral anticoagulants. We compared the frequency of (i) the composite outcome of recurrent ischemic stroke (IS), intracerebral hemorrhage (ICH) or all-cause death as well as (ii) recurrent IS alone among AF-stroke patients with versus without competing stroke etiologies according to the TOAST classification. We performed cox proportional hazards regression modeling adjusted for potential confounders. Furthermore, the etiology of recurrent IS was assessed.
Results:
Among 907 patients (median age 81, 45.6% female), 184 patients (20.3%) had competing etiologies, while 723 (79.7%) had cardioembolism as the only plausible etiology. During 1587 patient-years of follow-up, patients with additional large-artery atherosclerosis had higher rates of the composite outcome (adjusted HR 95% CI 1.64 1.11, 2.40, p = 0.017) and recurrent IS (aHR 2.96 1.65, 5.35 , p < 0.001), compared to patients with cardioembolism as the only plausible etiology. Overall 71 patients had recurrent IS (7.8%) of whom 26.7% had a different etiology than the index IS with large-artery-atherosclerosis (19.7%) being the most common non-cardioembolic cause.
Conclusion:
In stroke patients with AF, causes other than cardioembolism as competing etiologies were common in index or recurrent IS. Concomitant presence of large-artery-atherosclerosis seems to indicate an increased risk for recurrences suggesting that stroke preventive means might be more effective if they also address competing stroke etiologies in AF-stroke patients.
Clinical Trial Registration:
NCT 03826927
Graphical abstract
Epithelial to mesenchymal transition (EMT) describes the process of epithelium transdifferentiating into mesenchyme. EMT is a fundamental process during embryonic development that also commonly ...occurs in glioblastoma, the most frequent malignant brain tumor. EMT has also been observed in multiple carcinomas outside the brain including breast cancer, lung cancer, colon cancer, gastric cancer. EMT is centrally linked to malignancy by promoting migration, invasion and metastasis formation. The mechanisms of EMT induction are not fully understood. Here we describe an in vitro system for standardized isolation of cortical neural stem cells (NSCs) and subsequent EMT-induction. This system provides the flexibility to use either single cells or explant culture. In this system, rat or mouse embryonic forebrain NSCs are cultured in a defined medium, devoid of serum and enzymes. The NSCs expressed Olig2 and Sox10, two transcription factors observed in oligodendrocyte precursor cells (OPCs). Using this system, interactions between FGF-, BMP- and TGFβ-signaling involving Zeb1, Zeb2, and Twist2 were observed where TGFβ-activation significantly enhanced cell migration, suggesting a synergistic BMP-/TGFβ-interaction. The results point to a network of FGF-, BMP- and TGFβ-signaling to be involved in EMT induction and maintenance. This model system is relevant to investigate EMT in vitro. It is cost-efficient and shows high reproducibility. It also allows for the comparison of different compounds with respect to their migration responses (quantitative distance measurement), and high-throughput screening of compounds to inhibit or enhance EMT (qualitative measurement). The model is therefore well suited to test drug libraries for substances affecting EMT.
Since the introduction of modern surgical techniques and monitoring tools for the treatment of severe traumatic brain injury (TBI) in Switzerland, standardized nationwide operative procedures are ...still lacking. This study aimed to assess surgical management and monitoring strategies in patients admitted throughout Switzerland with severe TBI.
Demographic, clinical, and radiologic data from a prospective national cohort study on severe brain-injured patients (Patient-relevant Endpoints after Brain Injury from Traumatic Accidents PEBITA) were collected during a 3-year period. This study evaluated patients admitted to 7 of the 11 trauma centers included in PEBITA. We retrospectively analyzed surgery-related computed tomography (CT) findings prior to and after treatment, intracranial pressure (ICP) monitoring, size and technical features of craniotomy, as well as surgical complications. ResULTS: This study included 353 of the 921 patients enrolled in PEBITA who underwent surgical treatment for severe TBI. At admission, acute subdural hematoma was the most frequent focal lesion diagnosed (n = 154 44%), followed by epidural hematoma (n = 96 27%) and intracerebral hematoma (n = 84 24%). A total of 198 patients (61%) presented with midline shift. Clinical deterioration in terms of Glasgow Coma Scale scores or intractable ICP values as an indication for surgical evacuation or decompression were documented in 20% and 6%, respectively. A total of 97 (27.5%) only received a catheter/probe for ICP monitoring. Surgical procedures to treat a focal lesion or decompress the cerebrum were performed in 256 patients (72.5%). Of the 290 surgical procedures (excluding ICP probe implantation), craniotomy (137 47.2%) or decompressive craniectomy (133 45.9%) were performed most frequently. The mean size of craniectomy in terms of maximal linear width on the CT axial slice was 8.4 ± 2.9 cm. Intraoperative ICP monitoring was reported in 61% of the interventions. Significant intraoperative brain swelling was documented in 50.6% of the procedures. Surgery-related complications occurred in 89 cases (32%).
This study highlights the lack of standardized and systematic documentation of technical aspects of surgical treatment of patients presenting with severe TBI in Switzerland. Technical strategies such as size of craniectomy and the use of perioperative ICP measurement were not documented in a standardized manner. A prospective systematic surgical documentation system might contribute to future formulation of recommendations for the surgical treatment of patients presenting with severe TBI in Switzerland.
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