Background
Cerebral microbleeds (CMBs) may have a differential impact on clinical outcome in stroke patients with atrial fibrillation (AF) treated with different types of oral anticoagulation (OAC).
...Methods
Observational single-center study on AF-stroke-patients treated with OAC. Magnetic-resonance-imaging was performed to assess CMBs. Outcome measures consisted of recurrent ischemic stroke (IS), intracranial hemorrhage (ICH), death, and their combined analysis. Functional disability was assessed by mRS. Using adjusted logistic regression and Cox proportional-hazards models, we assessed the association of the presence of CMBs and OAC type (vitamin K antagonists VKAs vs. direct oral anticoagulants DOACs) with clinical outcome.
Results
Of 310 AF-stroke patients treated with OAC DOACs:
n
= 234 (75%); VKAs:
n
= 76 (25%), CMBs were present in 86 (28%) patients; of these, 66 (77%) received DOACs. In both groups, CMBs were associated with an increased risk for the composite outcome: VKAs: HR 3.654 1.614; 8.277;
p
= 0.002; DOACs: HR 2.230 1.233; 4.034;
p
= 0.008. Patients with CMBs had ~50% higher absolute rates of the composite outcome compared to the overall cohort, with a comparable ratio between treatment groups VKAs 13/20(65%) vs. DOACs 19/66(29%);
p
< 0.01. The VKA-group had a 2-fold higher IS VKAs:4 (20%) vs. DOACs:6 (9%);
p
= 0.35 and a 10-fold higher ICH rate VKAs: 3 (15%) vs. DOACs: 1 (1.5%);
p
= 0.038. No significant interaction was observed between type of OAC and presence of CMBs. DOAC-patients showed a significantly better functional outcome (OR 0.40 0.17; 0.94;
p
= 0.04).
Conclusions
In AF-stroke patients treated with OAC, the presence of CMBs was associated with an unfavorable composite outcome for both VKAs and DOACs, with a higher risk for recurrent IS than for ICH. Strokes were numerically higher under VKAs and increased in the presence of CMBs.
Clinical trial registration
http://www.clinicaltrials.gov
, Unique identifier: NCT03826927.
Standard operating procedures (SOP) incorporating plasma levels of rivaroxaban might be helpful in selecting patients with acute ischemic stroke taking rivaroxaban suitable for IVthrombolysis (IVT) ...or endovascular treatment (EVT).
This was a single-center explorative analysis using data from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (clinicaltrials.gov:NCT02353585) including acute stroke patients taking rivaroxaban (September 2012 to November 2016). The SOP included recommendation, consideration, and avoidance of IVT if rivaroxaban plasma levels were <20 ng/mL, 20‒100 ng/mL, and >100 ng/mL, respectively, measured with a calibrated anti-factor Xa assay. Patients with intracranial artery occlusion were recommended IVT+EVT or EVT alone if plasma levels were ≤100 ng/mL or >100 ng/mL, respectively. We evaluated the frequency of IVT/EVT, door-to-needle-time (DNT), and symptomatic intracranial or major extracranial hemorrhage.
Among 114 acute stroke patients taking rivaroxaban, 68 were otherwise eligible for IVT/EVT of whom 63 had plasma levels measured (median age 81 years, median baseline National Institutes of Health Stroke Scale 6). Median rivaroxaban plasma level was 96 ng/mL (inter quartile range IQR 18‒259 ng/mL) and time since last intake 11 hours (IQR 4.5‒18.5 hours). Twenty-two patients (35%) received IVT/EVT (IVT n=15, IVT+EVT n=3, EVT n=4) based on SOP. Median DNT was 37 (IQR 30‒60) minutes. None of the 31 patients with plasma levels >100 ng/mL received IVT. Among 14 patients with plasma levels ≤100 ng/mL, the main reason to withhold IVT was minor stroke (n=10). No symptomatic intracranial or major extracranial bleeding occurred after treatment.
Determination of rivaroxaban plasma levels enabled IVT or EVT in one-third of patients taking rivaroxaban who would otherwise be ineligible for acute treatment. The absence of major bleeding in our pilot series justifies future studies of this approach.
Mannan-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are two key components of the lectin-pathway of complement-activation. Information on the potential role of lectin-pathway ...components in carcinogenesis versus immune surveillance of cancer is scarce. This study aimed to determine if serum concentrations of MBL and MASP-2 differ between children with cancer and healthy age-matched controls.
In this retrospective multicentre study, MBL and MASP-2 were measured by commercially available ELISA in frozen remnants of serum taken at diagnosis in paediatric patients with cancer. For six diagnostic groups, these concentrations were compared with serum concentrations of age-matched healthy controls using exact Wilcoxon signed-rank tests.
MBL and MASP-2 were measured in serum of 372 patients. MBL was significantly higher in patients with solid tumours vs. controls (median, 2,799 vs. 1,917 μg/L; P = 0.008), and MASP-2 was significantly higher in patients with acute lymphoblastic leukaemia (406 vs. 317 μg/L; P = 0.009), Non-Hodgkin lymphoma (361 vs. 293 μg/L; P = 0.037) and CNS tumors (463 vs. 296 μg/L; P = 0.002).
These results may indicate a role of MBL and MASP-2 in the initiation or progression of specific paediatric cancers, while other mechanisms remain possible as well. Larger, disease-specific studies are warranted for confirmation and for elucidation of the underlying mechanisms.
Patients with brain death have by definition irreversible and complete loss of brainstem reflexes. Before a definite diagnosis of brain death can be confirmed, all potential confounders must be ...thoroughly excluded. Baclofen intoxication is a rare cause of brain death mimic characterised by transient deep coma and absence of brainstem reflexes and might be mistaken with brain death. We report the case of a female patient in her 70s who ingested baclofen with suicidal intent and was admitted with a deep coma and loss of all brainstem reflexes and a spontaneous burst-suppression pattern in the electroencephalography which resolved over 10 hours. After a state mimicking brain death for 6 hours, the patient experienced complete recovery. Severe baclofen intoxication can mimic brain death clinically and is associated with temporary pathological electroencephalographic findings. Awareness of this toxidrome is crucial, as appropriate management can lead to full recovery.
Differentiation of syncope from seizure is challenging and has therapeutic implications. Cardioinhibitory reflex syncope typically affects young patients where permanent pacing should be avoided ...whenever possible. Cardioneuroablation may obviate the need for a pacemaker in well-selected patients.
A previously healthy 24-year-old woman was referred to the emergency department after recurrent episodes of transient loss of consciousness (TLOC). The electrocardiogram (ECG) and the echocardiogram were normal. An electroencephalogram (EEG) showed intermittent, generalized pathological activity. During EEG under photostimulation, the patient developed a short-term TLOC followed by brachial myocloni, while the concurrent ECG registered a progressive bradycardia, which turned into a complete atrioventricular block and sinus arrest with asystole for 14 s. Immediately after, the patient regained consciousness without sequelae. The episode was interpreted as cardioinhibitory convulsive syncope. However, due to the pathological EEG findings, an underlying epilepsy with ictal asystole could not be fully excluded. Therefore, an antiseizure therapy was also started. After discussing the consequences of pacemaker implantation, the patient agreed to undergo a cardioneuroablation and after 72 h without complications, she was discharged home. At 10 months, the patient autonomously discontinued the antiepileptics. The follow-up EEG displayed unspecific activities without clinical correlations. An implantable loop recorder didn't show any relevant bradyarrhythmia. At 1-year follow-up, the patient remained asymptomatic and without syncopal episodes.
Reflex syncope must be considered in the differential diagnosis of seizures. The cardioneuroablation obviated the need for a pacemaker and allowed for the withdrawal of anticonvulsants, originally started on the premise of seizure.
To investigate the frequency of induced EEG burst suppression pattern during continuous IV anesthesia (IVAD) and associated outcomes in adult patients treated for refractory status epilepticus (RSE).
...Patients with RSE treated with anesthetics at a Swiss academic care center from 2011 to 2019 were included. Clinical data and semiquantitative EEG analyses were assessed. Burst suppression was categorized as incomplete burst suppression (with ≥20% and <50% suppression proportion) or complete burst suppression (with ≥50% suppression proportion). The frequency of induced burst suppression and association of burst suppression with outcomes (persistent seizure termination, in-hospital survival, and return to premorbid neurologic function) were the endpoints.
We identified 147 patients with RSE treated with IVAD. Among 102 patients without cerebral anoxia, incomplete burst suppression was achieved in 14 (14%) with a median of 23 hours (interquartile range IQR 1-29) and complete burst suppression was achieved in 21 (21%) with a median of 51 hours (IQR 16-104). Age, Charlson comorbidity index, RSE with motor symptoms, the Status Epilepticus Severity Score and arterial hypotension requiring vasopressors were identified as potential confounders in univariable comparisons between patients with and without any burst suppression. Multivariable analyses revealed no associations between any burst suppression and the predefined endpoints. However, among 45 patients with cerebral anoxia, induced burst suppression was associated with persistent seizure termination (72% without vs 29% with burst suppression,
= 0.004) and survival (50% vs 14%
= 0.005).
In adult patients with RSE treated with IVAD, burst suppression with ≥50% suppression proportion was achieved in every fifth patient and not associated with persistent seizure termination, in-hospital survival, or return to premorbid neurologic function.
To test the accuracy of an equation in adult patients with status epilepticus that calculates the free concentration of serum valproic acid (fVPA) from the total concentration of serum valproic acid ...(tVPA) and serum albumin.
All adult patients with status epilepticus who were treated at a Swiss academic medical center between 2005 and 2018 with concurrent measurements of tVPA, fVPA, and serum albumin were included. fVPA was categorized as subtherapeutic, therapeutic (5-10 mg/L), or supratherapeutic. Agreement was defined as the proportion of measured and calculated fVPA falling within the same category.
Of 676 patients with status epilepticus, 104 had 506 measurements, with a median of 3 (interquartile range IQR 1.5-6.5) per patient. The median tVPA was 43.5 mg/L (27.4-63.6), with measured fVPA 9.1 mg/L (4.5-14.7) and calculated fVPA 10.1 mg/L (7.0-13.0), respectively. The median deviation of calculated from measured fVPA was -0.8 mg/L (-3.2 to 2.5) with 336 measurements >1 mg/L. While the association between measured and calculated fVPA was linear (regression coefficient 1.1, 95% confidence interval 0.9-1.2,
< 0.0001), the agreement on effective drug levels did not match in 39.8% of measurements regardless of serum albumin levels, with calculated fVPA overestimating measured fVPA in 30.4%. tVPA and serum albumin independently influenced the accuracy of the calculated fVPA in the multivariable model.
Calculated fVPA is inaccurate when using the proposed equation in adult patients with status epilepticus, calling for drug monitoring based on measured fVPA in this context.
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