The prevalence of cardiovascular diseases requiring long-term oral anticoagulation (OAC) is increasing, notably the incidence and prevalence of atrial fibrillation.^1,2 The most significant complication of OAC is intracerebral hemorrhage (ICH).³ Based on OAC-induced coagulopathy, large hematoma volumes and increased rates of hematoma enlargement are characteristics of OAC-associated ICH (OAC-ICH) and contribute to an even higher mortality when compared with ischemic stroke or primary ICH.^4-7

Objective To determine demographic characteristics, clinical features, treatment regimens, and outcome of myasthenic crisis (MC) requiring mechanical ventilation (MV). Methods Analysis of patients who presented with MC between 2006 and 2015 in a German multicenter retrospective study. Results We identified 250 cases in 12 participating centers. Median age at crisis was 72 years. Median duration of MV was 12 days. Prolonged ventilation (>15 days) depended on age (p = 0.0001), late-onset myasthenia gravis (MG), a high Myasthenia Gravis Foundation of America Class before crisis (p = 0.0001 for IVb, odds ratio [OR] = infinite), number of comorbidities (>3 comorbidities: p = 0.002, OR 2.99), pneumonia (p = 0.0001, OR 3.13), and resuscitation (p = 0.0008, OR 9.15). MV at discharge from hospital was necessary in 20.5% of survivors. Patients with early-onset MG (p = 0.0001, OR 0.21), thymus hyperplasia (p = 0.002, OR 0), and successful noninvasive ventilation trial were more likely to be ventilated for less than 15 days. Noninvasive ventilation in 92 cases was sufficient in 38%, which was accompanied by a significantly shorter duration of ventilation (p = 0.001) and intensive care unit (ICU) stay (p = 0.01). IV immunoglobulins, plasma exchange, and immunoadsorption were more likely to be combined sequentially if the duration of MV and the stay in an ICU extended (p = 0.0503, OR 2.05). Patients who received plasma exchange or immunoadsorption as first-line therapy needed invasive ventilation significantly less often (p = 0.003). In-hospital mortality was 12%, which was significantly associated with the number of comorbidities (>3) and complications such as acute respiratory distress syndrome and resuscitation. Main cause of death was multiorgan failure, mostly due to sepsis. Conclusion Mortality and duration of MC remained comparable to previous reports despite higher age and a high disease burden in our study. Prevention and treatment of complications and specialized neurointensive care are the cornerstones in order to improve outcome.

Based on an age-adjusted incidence-rate for intracerebral hemorrhage (ICH) in high-income countries for the year 2010, it was estimated that cerebellar ICH affects approximately 35 000 patients annually within the European Union and the United States.^1-3 There have not been randomized trials of treatment interventions for patients with cerebellar ICH. Since 1984, surgical hematoma evacuation has been the preferred treatment approach, specifically in patients with larger hematomas and intraventricular involvement, given increased risk for brainstem compression and herniation.^4-8 However, evidence on the association between surgical hematoma evacuation and clinical outcomes after cerebellar ICH has been limited to small observational studies.^9,10 International guidelines including the American Heart Association/American Stroke Association guideline recommend surgical hematoma evacuation for cerebellar ICH with diameter greater than 3 cm to improve outcome; however, definite evidence to validate or refute this recommendation is currently not available.^4,9,10 As a result, there is no commonly accepted management strategy for cerebellar ICH and no general agreement regarding whether, when, and how these patients should undergo surgical intervention.^8,11 The purpose of this study was to assess the association of surgical hematoma evacuation with functional outcome and mortality in patients with cerebellar ICH.

Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH. We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67–35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33–21.37; P < 0.01). The hazard for the composite—balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10–5.70; P = 0.03). Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing—between least risks for thromboembolic and haemorrhagic complications—provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk.

Cerebrospinal fluid (CSF) is routinely used for diagnosing and monitoring neurological diseases. The CSF proteins used so far for diagnostic purposes (except for those associated with whole cells) are soluble. Here, we show that human CSF contains specific membrane particles that carry prominin-1/CD133, a neural stem cell marker implicated in brain tumors, notably glioblastoma. Differential and equilibrium centrifugation and detergent solubility analyses showed that these membrane particles were similar in physical properties and microdomain organization to small membrane vesicles previously shown to be released from neural stem cells in the mouse embryo. The levels of membrane particle-associated prominin-1/CD133 declined during childhood and remained constant thereafter, with a remarkably narrow range in healthy adults. Glioblastoma patients showed elevated levels of membrane particle-associated prominin-1/CD133, which decreased dramatically in the final stage of the disease. Hence, analysis of CSF for membrane particles carrying the somatic stem cell marker prominin-1/CD133 offers a novel approach for studying human central nervous system disease. Disclosure of potential conflicts of interest is found at the end of this article.