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Significant advances in the acute treatment of patients with intracerebral hemorrhage (ICH) have been achieved in recent years. While many randomized trials have provided neutral results, important findings have been generated for the design of follow-up studies. Furthermore, a number of observational studies have been published, which in turn provide the basis for further methodologically stronger investigations. The focus is on avoidance of early bleeding progression, which can be influenced by blood pressure management and hemostasis. Furthermore, ICH surgery may experience a renaissance through minimally invasive techniques. In addition, perihemorrhagic edema and its pharmacological modulation are becoming increasingly more important. Optimal treatment of ventricular involvement is continuing to develop dynamically. Finally, long-term antithrombotic treatment has been intensely studied in observational analyses and is currently being investigated in randomized trials. This article addresses these most relevant topics in acute and long-term treatment of ICH patients and provides an overview of current debates in these areas of treatment. [ABSTRACT FROM AUTHOR]

Background The most recent years have significantly expanded knowledge regarding risks and benefits of resuming oral anticoagulation (OAC) after intracerebral hemorrhage (ICH). No randomized data is yet available, though several large observational studies and meta-analyses have investigated the impact of resuming OAC on thromboembolic versus hemorrhagic complications in these high-risk patients after ICH. Aims The present review will summarize the most important studies conducted over the last years and will focus on relevant factors help guiding on decision-making on whether to start OAC after ICH. Summary of review Several important factors (demographic, co-morbidities, clinical characteristics) need to be considered before individual decision-making for or against OAC is employed. Existing observational data suggest that patients after ICH with indication for long-term oral anticoagulation benefit from OAC given significant reductions of thromboembolic events without significantly increasing bleeding complications. Studies even suggest that thereby also clinical outcomes may be improved. Prospective trials currently recruiting patients will clarify whether OAC after ICH – or left atrial appendage closure as a meaningful alternative – is of clinical net-benefit. Conclusions Large sized and well-executed investigations (moderate quality of evidence) are showing that OAC resumption after ICH decreases thromboembolic complications and long-term mortality without significantly increasing bleeding complications. Further, data suggest that resumption may be safer in non-lobar ICH compared to lobar ICH, but overall, thoughtful selection, strict blood pressure control, and precise communication are paramount before starting a patient on OAC after ICH. [ABSTRACT FROM AUTHOR]

Background and Purpose: Elevated intracranial pressure (ICP) as a result of intracerebral hemorrhage (ICH) and perihematomal edema often leads to tissue shift, which can be identified in cross-sectional imaging and presents a known predictor of functional outcome. Pulsatility indices (PIs) of the intracranial arteries as measured by transcranial Doppler sonography (TCD) may serve as surrogate parameters for ICP. This study aims to investigate whether PI correlates with ICP and midline shift and serves as a reliable predictor of functional outcome in patients with ICH. Methods: Within a 1-year period between April 2009 and April 2010, 136 patients with acute spontaneous, supratentorial ICH were admitted to our tertiary care hospital. One-hundred and twenty-four patients fulfilled the inclusion criteria and were eligible for analysis. TCD and transcranial duplex sonography were performed on admission and at least once more during hospital stay. Functional outcome was assessed 6 months after discharge. Correlation analyses, logistic regression analyses and receiver operating characteristic curves were calculated. Results: One-hundredand twenty-four patients were included in the analysis. Six-month mortality amounted to 39.5%. The ICH score and PIs of the middle cerebral artery were independent predictors of outcome 6 months after discharge. Conclusions: Early PI monitoring by TCD correlated with ICP and may be used to predict the outcome after 6 months. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM) is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathological conditions, there are few studies on secretory ASM limited only to cell models, plasma or serum. Methods: An optimized assay based on a fluorescent substrate was applied to measure the ASM activity in cerebrospinal fluid (CSF) collected from mice and from 42 patients who were classified as controls based on normal routine CSF values. Results: We have detected ASM activity in human CSF, established a sensitive quantitative assay and characterized the enzyme’s properties. The enzyme resembles plasmatic ASM including protein stability and Zn2+-dependence but the assays differ considerably in the optimal detergent concentration. Significantly increased activities in the CSF of ASM transgenic mice and undetectable levels in ASM knock-out mice prove that the measured ASM activity originates from the ASM-encoding gene SMPD1. CSF localized ASM activities were comparable to corresponding serum ASM levels at their respective optimal reaction conditions, but no correlation was observed. The large variance in ASM activity was independent of sex, age or analyzed routine CSF parameters. Conclusions: Human and mouse CSF contain detectable levels of secretory ASM, which are unrelated to serum ASM activities. Further investigations in humans and in animal models will help to elucidate the role of this enzyme in human disease and to assess its value as a potential biomarker for disease type, severity, progress or therapeutic success. [ABSTRACT FROM AUTHOR]

Background: Spontaneous intracerebral hemorrhage (ICH) and the evolution of subsequent perihemorrhagic edema lead to midline shift (MLS), which can be assessed by transcranial duplex sonography (TDS). In this observational study, we monitored MLS with TDS in patients with supratentorial ICH up to day 14 after the ictus, and then correlated MLS with the outcome 6 months after hospital discharge. Methods: Sixty-eight patients with spontaneous ICH (volume >20 cm3) were admitted during a 1-year period between April 2009 and April 2010. Sixty-one patients fulfilled the inclusion criteria and were eligible for analysis. TDS to measure MLS was performed upon admission and then subsequently, using serial examinations in 24-hour intervals up to day 14. Statistical tests were used to determine cut-off values for functional outcome and mortality after 6 months. Results: The median National Institutes of Health Stroke Scale (NIHSS) score upon admission was 21 and the mean hematoma volume was 52 cm3. NIHSS score, functional outcome, hematoma volume and MLS were correlated in the examined patient cohort. ICH score upon admission, hematoma volume and the extent of MLS on days 1-14 were predictive of functional outcome and death. Values of MLS showed two peaks, the first between day 2 and day 5 and the second between day 12 and day 14, indicating that edema progresses not only during the acute but also during the subacute phase. Depending on the time point, an MLS of 4.5-7.5 mm or greater indicated an impending failure of conservative therapy. An MLS of 12 mm or greater at any time indicated mortality with a sensitivity of 69%, a specificity of 100% and positive and negative predictive values of 100 and 74%, respectively. Conclusions: MLS seems to be a crucial factor for outcome after ICH. Apart from the hematoma volume itself, edema adds to the intracranial pressure. To monitor MLS in early patient management after ICH, TDS is a useful noninvasive bedside alternative, avoiding increased radiation exposure and repeated transportation of critically ill patients. Cut-off values may help to reliably predict functional outcome and treatment failure in patients undergoing maximal neurointensive therapy. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary: Purpose: Recent analyses provided evidence that human adult cerebrospinal fluid (CSF) in addition to soluble proteins also contains membrane particles that moreover carry the somatic stem cell marker CD133. The significance of CD133 as a potential marker of cellular proliferation, including neurogenesis, remains unresolved. As adult neurogenesis has been implicated to be induced by epileptic seizures this study investigated whether patients with partial epilepsy show a varying amount of membrane-associated CD133 in CSF as compared to healthy adults. Methods: CSF samples of 34 partial epilepsy patients were analyzed and compared to 61 healthy controls. Following sequential centrifugation up to 200,000g quantitative immunoblotting was performed using a mouse monoclonal antibody. Antigen-antibody complexes were detected using enhanced chemiluminescence, and visualized and quantified digitally. Results: The overall amount of membrane particle-associated CD133 was significantly increased in epilepsy patients compared to healthy controls (9.6±2.9ng of bound CD133 antibody versus 7.4±3.8ng; p <0.01). There were no differences according to etiology of epilepsy (cryptogenic, neoplasia, dysplasia, ammon''s horn sclerosis, and others). Dichotomization of the patients according to temporal versus extratemporal foci revealed a significant increase of membrane particle-associated CD133 in patients with temporal lobe epilepsy (10.88±3.3ng of bound CD133 antibody versus 8.35±3.48ng; p <0.05). Conclusion: The increased amount of membrane particle-associated CD133 in the CSF of patients with partial epilepsy contributes to the ongoing debate of the source of these particles potentially emerging from subventricular zone astrocytes serving as neural stem cells. As neurogenesis in adults is related to the hippocampus, the significance of the increase of membrane particle-associated CD133 especially in temporal lobe epilepsy needs further clinical correlation. [Copyright &y& Elsevier]

Background: Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH), but has rarely been reported after intracerebral hemorrhage (ICH) without subarachnoidal bleeding. The underlying pathophysiological mechanism is mainly mediated by circulating heme products within the cerebrospinal fluid, and thus patients with ICH and ventricular involvement (IVH) may also be in danger of developing VSP. The incidence and role of VSP in IVH, however, have not been systematically studied. Methods: We prospectively enrolled 115 patients with ICH with or without IVH into the study between April 2009 and April 2010. All patients received serial extracranial and transcranial Doppler sonography (TCD) at baseline, on days 3-5 and 7-9 to detect and monitor VSP. In addition, CT scans taken on admission, after 24 h and before discharge were evaluated for the occurrence of delayed cerebral ischemia. Results: Three out of 53 patients (5.7%) with IVH showed a significant elevation of flow velocities over the examined timeframe. One of these patients developed severe VSP resulting in secondary ischemic infarction. None of the ICH patients without IVH showed significantly elevated flow velocities or secondary infarction. Conclusions: Cerebral VSP with secondary infarction may occur in patients with spontaneous IVH, though far less frequently than in SAH; thus, systematic screening of all patients with IVH may not be warranted. However, serial TCD should be considered in patients with secondary clinical worsening or extensive IVH. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Intracerebral haemorrhage is the most devastating subtype of stroke. It affects approximately two million patients worldwide every year and is a major cause of morbidity and mortality. After decades of research, we still face the fact that there is no evidence-based treatment strategy for this disease. However, research has contributed to a better understanding of the pathophysiology of intracerebral haemorrhage and also to the identification of new treatment targets. Several novel aspects of treatment of spontaneous intracerebral haemorrhage are reviewed in the present article. [ABSTRACT FROM AUTHOR]

Background: There is little data on the association of peripheral arterial disease and stroke. We aimed to assess the prevalence of peripheral arterial disease in acute stroke and to identify the predisposing factors for peripheral arterial disease in a stroke cohort. Methods: We enrolled all consecutive patients who were admitted to our stroke- and neurocritical care units with the diagnosis of a transient ischaemic attack, ischaemic or haemorrhagic stroke over a period of 5 months. As controls, we analysed 50 nonvascular neurological patients who were matched to age. Upon admission, assessment of the ankle brachial index was performed in all patients. The only exclusion criteria was decompensated congestive heart failure. Results: Altogether, we compared 374 stroke patients (95 transient ischaemic attack, 231 ischaemic, and 48 haemorrhagic strokes) and 50 nonstroke controls. The prevalence of peripheral arterial disease in the control group was 14%. There was a trend towards a higher prevalence of peripheral arterial disease in stroke patients ( χ2-test: P=0·051; prevalence peripheral arterial disease in transient ischaemic attack: 16·8%, ischaemic stroke: 32%, and haemorrhagic stroke: 20·8%). A higher proportion of ischaemic stroke patients were peripheral arterial disease-positive, compared with transient ischaemic attack patients ( P=0·005) and controls ( P=0·011), respectively. Multivariate regression analyses identified the parameters age, arterial hypertension, current or former smokers and a history of cardiovascular events to be predisposing factors of peripheral arterial disease. Conclusion: This study represents the first systematic investigation of the prevalence of peripheral arterial disease in stroke. By now, it is clear that: • peripheral arterial disease is more commonly found in stroke than in nonstroke patients • ischaemic stroke patients show the highest prevalence of peripheral arterial disease, and • peripheral arterial disease in stroke is related to common vascular risk factors. [ABSTRACT FROM AUTHOR]

Summary: Space-occupying, malignant middle cerebral artery (MCA) infarctions are still one of the most devastating forms of ischaemic stroke, with a mortality of up to 80% in untreated patients. An early diagnosis is essential and depends on CT and MRI to aid the prediction of a malignant course. Several pharmacological strategies have been proposed but the efficacy of these approaches has not been supported by adequate evidence from clinical trials and, until recently, treatment of malignant MCA infarctions has been a major unmet need. Over the past 3 years, results from randomised controlled trials and their pooled analyses have provided evidence that an early hemicraniectomy leads to a substantial decrease in mortality at 6 and 12 months and is likely to improve functional outcome. Hemicraniectomy is now in routine use for the clinical management of malignant MCA infarction in patients younger than 60 years of age. However, there are still important questions about the individual indication for decompressive surgery, particularly with regard to the ideal timing of hemicraniectomy, a potential cut-off age for the procedure, the hemisphere affected, and ethical considerations about functional outcome in surviving patients. [Copyright &y& Elsevier]

In multiple sclerosis (MS) more than 95% of the patients have positive oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). Previous studies have reported differences between patients with and without OCB mainly with regard to clinical parameters such as age, gender, disease duration, and clinical severity. However, several MRI characteristics have also been hypothesized to be distinct, and a varying lesion load in OCB-negative and -positive patients is proposed. In this study, we aimed to evaluate whether Barkhof’s diagnostic MRI criteria are unequally frequently fulfilled in OCB-negative and -positive MS patients. We screened our database for all OCB-negative MS patients who had (1) been treated with the diagnosis of a clinical definite relapsing-remitting MS in our institution as well as (2) undergone CSF analysis and MR brain imaging during hospital stay between January 2004 and December 2007. Eleven OCB-negative patients were identified who fulfilled these criteria. In a second step, we carefully matched each of them to two OCB-positive controls according to age, gender, EDSS, and disease duration. The separate analysis of the several parameters of Barkhof’s criteria revealed a less frequent prevalence of infratentorial (3/11 vs. 18/22; P = 0.005) and a more frequent occurrence of juxtacortical lesions (10/11 vs. 10/22; P = 0.022) in OCB-negative as compared to OCB-positive patients. The overall fulfillment of the Barkhof criteria did not differ in OCB-negative and -positive patients (7/11 vs. 16/22; P = 0.696). Further analyses of MRI findings between OCB-negative and -positive MS patients might contribute to a better pathophysiological understanding of the genesis and evidence of OCB in the CSF of MS patients. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effects of age on differences in the clinical course and functional outcome of mechanically ventilated Guillain-Barré syndrome (GBS) patients. Methods: 32 consecutive patients with GBS in need of mechanical ventilation were divided into two groups: (1) 15 patients <65 years, and (2) 17 patients ≥65 years. Length of ventilation, therapy, incidence of bulbar involvement, dysautonomia, preceding infections, need for tracheostomy, mortality, and functional outcome at 1-year follow-up using the Hughes outcome scale were analyzed. Results: The groups were comparable regarding treatment, lesion type, incidence of bulbar involvement, dysautonomia, preceding infections and duration of ventilation. The majority of patients (75%) received combination therapy (intravenous immunoglobulin and plasma exchange). Tracheostomy was performed in 91% of patients. Mortality was higher in older patients (41 vs. 7%; p = 0.02) and overall outcome worse (p = 0.05). Interestingly, once surviving the early, most critical period, older patients functionally recovered as well as younger patients (80% good outcome vs. 86%; p = 0.71). Conclusions: Despite all the advances in intensive care, mortality in older, ventilated GBS patients is still substantial. However, once they have survived the early, most critical period, older patients may recover as well as younger patients. Special care should therefore be taken to prevent and, if present, to vigorously treat complications commonly associated with intensive care treatment of severe GBS in elderly patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In this study we analyzed whether demographic, clinical and neuroradiological parameters are associated with time to hospital admission in patients with spontaneous intracerebral hemorrhage (ICH). We a priori hypothesized that the earlier a patient was admitted to hospital, the worse the clinical status would be. Methods: Demographic, clinical and neuroradiological parameters of consecutive patients with spontaneous ICH directly admitted to 2 neurological university departments were subjected to correlation, trichotomization and logistic regression analyses for prediction of (i) early hospital admission, and (ii) favorable clinical presentation at admission [dichotomized Glasgow Coma Scale (GCS) score ≥9]. Results: We analyzed 157 patients with a median age of 66 (39–93) years. Patient trichotomization according to the GCS revealed a significant difference (p < 0.001) between all groups with regard to the time from symptom onset to hospital admission: patients with a GCS score of 3–5 were admitted after 105 (40–300) min (mean: 113 ± 53), those with a GCS score of 6–9 after 180 (45–420) min (mean: 184 ± 95) and those with a GCS score of 10–15 after 300 (60–1,560) min (mean: 324 ± 367). There were significant correlations between (i) hematoma volume and GCS (r = –0.632; p < 0.001); (ii) time to admission and GCS (r = 0.596; p < 0.001), and (iii) Graeb scores for intraventricular hemorrhage and hematoma volume (r = 0.348; p < 0.001). In the multivariate regression model for prediction of time until hospital admission, presence of intraventricular hemorrhage and the GCS score on admission were significant. In the multivariate regression model for prediction of a GCS score of ≥9 on admission, hematoma volume and time until hospital admission were significant parameters. Conclusions: Clinically more severely affected patients were admitted to hospital earlier. This highlights the importance of most rapid diagnosis of ICH. Efforts should be made to get less severely affected patients admitted earlier as they might be ideal candidates for emerging innovative treatments. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Glutamic acid decarboxylase (GAD) is the enzyme which catalyzes the production of gamma aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system (CNS). There is increasing evidence that severe GAD autoimmunity may be associated with refractory epilepsy. Immunomodulation and GABAergic drugs have been suggested as treatment options. We report here for the first time on a patient with sudden onset of refractory status epilepticus in the presence of strong intrathecal anti-GAD antibody synthesis who was successfully treated with cyclophosphamide, and give an overview of available data on epilepsy associated with GAD autoimmunity. [ABSTRACT FROM AUTHOR]

Background: Up to 30% of patients with supratentorial intracerebral hemorrhage (ICH) require mechanical ventilation during the course of treatment. For these patients, tracheostomy is necessary in cases of protracted weaning. As only limited data exist about predictors for a tracheostomy in patients with ICH, the aim of this study was to investigate the frequency of tracheostomy and clinical findings that increase the risk for a tracheostomy in patients with supratentorial hemorrhage. Methods: A total of 392 patients with supratentorial ICH were analyzed. The parameters age, gender, chronic obstructive pulmonary disease (COPD), Glasgow Coma Scale on admission, ganglionic or non-ganglionic localization, presence of ventricular hemorrhage, hydrocephalus, hematoma volume, and hematoma evacuation were in vestigated. The effects on the end-point tracheostomy were analyzed using multivariate regression analyses. Results: The overall need for tracheostomy was 9.9% (16.3% in patients with ganglionic hemorrhage versus 2.8% in patients with non-ganglionic hemorrhages). 31% of the ventilated patients required tracheostomy. The risk for tracheostomy was increased eightfold in patients who developed hydrocephalus. The presence of ventricular blood, in general, showed no significant impact on the need for tracheostomy, whereas hemorrhage extending into the third and fourth ventricles in conjunction with hydrocephalus increased the risk for tracheostomy. The hematoma volume correlated positively with the risk for tracheostomy. Conclusions: Our study demonstrates that approximately 10% of patients with ICH require tracheostomy during the course of their disease. Presence of COPD, hematoma volume, ganglionic location of the hematoma, and the development of hydrocephalus are predisposing factors for tracheostomy. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: MRI data of 100 healthy human brains were analyzed to establish a neuroanatomical map of the most frequently occurring ‘sulcal basins’ of the human frontal cortex. Sulcal basins are defined to be concavities in the white matter surface constituting/representing components of entire sulci. We determined their volume, depth, and interindividual variability. The sulcal basins were found to fall into two groups, on average, eight anterior basins in the prefrontal and premotor region and four posterior ones in the motor region of the frontal lobe. Compared to posterior basins, anterior basins are characterized by lower volume and depth. Furthermore, they showed greater interindividual variability in volume, depth, and occurrence. Our results indicate the existence of a mechanism for cortical folding which shows a greater flexibility in the phylogenetically younger, anterior prefrontal areas. [Copyright &y& Elsevier]

Background: Our objective was to test the association between hematoma volume and long-term (> 72 h) edema extension distance (EED) evolution and the association between peak EED and early EED increase with functional outcome at 3 months in patients with intracerebral hemorrhage (ICH). Methods: This retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. EED, an edema measure defined as the distance between the hematoma border and the outer edema border, was calculated by using absolute hematoma and edema volumes. We used multivariable logistic regression accounting for age, ICH volume, and location and receiver operating characteristic analysis for assessing measures associated with functional outcome and EED evolution. Functional outcome after 3 months was assessed by using the modified Rankin Scale (0–3 = favorable, 4–6 = unfavorable). To identify properties associated with peak EED multivariable linear and logistic regression analyses were conducted. Results: A total of 292 patients were included. Median age was 70 years (interquartile range [IQR] 62–78), median ICH volume on admission 17.7 mL (IQR 7.9–40.2), median peak perihemorrhagic edema (PHE) volume was 37.5 mL (IQR 19.1–60.6), median peak EED was 0.67 cm (IQR 0.51–0.84) with an early EED increase up to 72 h (EED72–0) of 0.06 cm (− 0.02 to 0.15). Peak EED was found to be independent of ICH volume (R2 = 0.001, p = 0.6). In multivariable analyses, peak EED (odds ratio 0.224, 95% confidence interval [CI] [0.071–0.705]) and peak PHE volume (odds ratio 0.984 [95% CI 0.973–0.994]) were inversely associated with favorable functional outcome at 3 months. Receiver operating characteristic analysis identified a peak PHE volume of 26.8 mL (area under the curve 0.695 [95% CI 0.632–0.759]; p ≤ 0.001) and a peak EED of 0.58 cm (area under the curve 0.608 [95% CI 0.540–0.676]; p = 0.002) as best predictive values for outcome discrimination. Conclusions: Compared with absolute peak PHE volume, peak EED represents a promising edema measure in patients with ICH that is largely hematoma volume-independent and nevertheless associated with functional outcome. [ABSTRACT FROM AUTHOR]

Using ferric chloride (FeCl3) to induce experimental superior sagittal sinus (SSS) thrombosis might interfere with magnetic resonance imaging (MRI)-assisted visualization and evaluation of the thrombus, the brain parenchyma, and the quality of the occlusion. The aim of this study was to investigate whether aluminum chloride (AlCl3)-induced thrombosis of the SSS has comparable properties to those of FeCl3 without causing artifacts in MRI. SSS thrombosis was induced in 14 male Wistar rats by exposure of the SSS and subsequent topical application of a filter paper strip soaked in AlCl3 (n = 7) or FeCl3 (n = 7) over a period of 15 min. The animals with AlCl3-induced SSS thrombosis showed a constant and complete occlusion with in histological analysis large thrombi. Blood flow measurements indicated a significant reduction on the first and seventh postoperative day compared to preoperative measurements. MRI enabled visualization and subsequent evaluation of the thrombus and the surrounding parenchyma. In comparison, FeCl3-induced SSS thrombosis could not be evaluated by MRI due to artifacts caused by the paramagnetic properties and increased susceptibility of FeCl3. The occluded sinus and the surrounding area appeared hypointense. The quality of SSS occlusion by AlCl3 was comparable to that of FeCl3. AlCl3 therefore represents a significant alternative substance in experimental SSS thrombosis ideally suited for studies using MRI. [ABSTRACT FROM AUTHOR]

It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived 14C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival. [ABSTRACT FROM AUTHOR]

Introduction: Although automated pupillometry is increasingly used in critical care settings, predictive value of automatically assessed pupillary parameters during different intracranial pressure (ICP) levels and possible clinical implications are unestablished. Methods: This retrospective cohort study at the neurocritical care unit of the University of Erlangen-Nuremberg (2016–2018) included 23 nontraumatic supratentorial (intracerebral hemorrhage) ICH patients without signs of abnormal pupillary function by manual assessment, i.e., absent light reflex. We assessed ICP levels by an external ventricular drain simultaneously with parameters of pupillary reactivity [i.e., maximum and minimum apertures, light reflex latency (Lat), constriction and redilation velocities (CV, DV), and percentage change of apertures (per-change)] using a portable pupillometer (NeurOptics®). Computed tomography (CT) scans were analyzed to determine lesion location, size, intraventricular hemorrhage, hydrocephalus, midline shift, and compression or absence of the basal cisterns. We performed receiver operating characteristics analysis to investigate associations of ICP levels with pupillary parameters and to determine best cutoff values for prediction of ICP elevation. After dichotomization of assessments according to ICP values (normal: < 20 mmHg, elevated: ≥ 20 mmHg), prognostic performance of the determined cutoff parameters of pupillary function versus of CT-imaging findings was analyzed by calculating sensitivity, specificity, positive and negative predictive values (logistic regression, corresponding ORs with 95% CIs). Results: In 23 patients (11 women, median age 59.0 (51.0–69.0) years), 1,934 assessments were available for analysis. A total of 74 ICP elevations ≥ 20 mmHg occurred in seven patients. Best discriminative thresholds for ICP elevation were: CV < 0.8 mm/s (AUC 0.740), per-change < 10% (AUC 0.743), DV < 0.2 mm/s (AUC 0.703), and Lat > 0.3 s (AUC 0.616). Positive predictive value of all four parameters to indicate ICP elevation ranged between 7.2 and 8.3% only and was similarly low for CT abnormalities (9.1%). We found high negative predictive values of pupillary parameters [CV: 99.2% (95% CI 98.3–99.6), per-change: 98.7% (95% CI 97.8–99.2), DV: 98.0% (95% CI 97.0–98.7), Lat: 97.0% (95% CI 96.0–97.7)], and CT abnormalities [99.7% (95% CI 99.2–99.9)], providing evidence that both techniques adequately identified ICH patients without ICP elevation. Conclusions: Our data suggest an association between noninvasively detected changes in pupillary reactivity and ICP levels in sedated ICH patients. Although automated pupillometry and neuroimaging seem not sufficient to noninvasively indicate ICP elevation, both techniques, however, adequately identified ICH patients without ICP elevation. This finding may facilitate routine management by saving invasive ICP monitoring or repeated CT controls in patients with specific automated pupillometry readings. [ABSTRACT FROM AUTHOR]

Myasthenic crisis (MC) requiring mechanical ventilation is a serious complication of myasthenia gravis (MG). Here we analyze the frequency and risk factors of weaning- and extubation failure as well as its impact on the clinical course in a large cohort. We performed a retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015. Weaning failure (WF) was defined as negative spontaneous breathing trial, primary tracheostomy, or extubation failure (EF) (reintubation or death). WF occurred in 138 episodes (64.2%). Older Age (p = 0.039), multiple comorbidities (≥ 3) (p = 0.007, OR = 4.04), late-onset MG (p = 0.004, OR = 2.84), complications like atelectasis (p = 0.008, OR = 3.40), pneumonia (p < 0.0001, OR = 3.45), cardio-pulmonary resuscitation (p = 0.005, OR = 5.00) and sepsis (p = 0.02, OR = 2.57) were associated with WF. WF occurred often in patients treated with intravenous immungloblins (IVIG) (p = 0.002, OR = 2.53), whereas WF was less often under first-line therapy with plasma exchange or immunoadsorption (p = 0.07, OR = 0.57). EF was observed in 58 of 135 episodes (43.0%) after first extubation attempt and was related with prolonged mechanical ventilation, intensive care unit stay and hospital stay (p ≤ 0.0001 for all). Extubation success was most likely in a time window for extubation between day 7 and 12 after intubation (p = 0.06, OR = 2.12). We conclude that WF and EF occur very often in MC and are associated with poor outcome. Older age, multiple comorbidities and development of cardiac and pulmonary complications are associated with a higher risk of WF and EF. Our data suggest that WF occurs less frequently under first-line plasma exchange/immunoadsorption compared with first-line use of IVIG. [ABSTRACT FROM AUTHOR]

Background: Lipid droplets (LD), lipid-storing organelles containing neutral lipids like glycerolipids and cholesterol, are increasingly accepted as hallmarks of inflammation. The nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA with over 200 nucleotides, exerts an indispensable impact on regulating both LD agglomeration and autophagy in multiple neurological disorders. However, knowledge as to how NEAT1 modulates the formation of LD and associated signaling pathways is limited. Methods: In this study, primary microglia were isolated from newborn mice and exposed to oxygen-glucose-deprivation/reoxygenation (OGD/R). To further explore NEAT1-dependent mechanisms, an antisense oligonucleotide (ASO) was adopted to silence NEAT1 under in vitro conditions. Studying NEAT1-dependent interactions with regard to autophagy and LD agglomeration under hypoxic conditions, the inhibitor and activator of autophagy 3-methyladenine (3-MA) and rapamycin (RAPA) were used, respectively. In a preclinical stroke model, mice received intraventricular injections of ASO NEAT1 or control vectors in order to yield NEAT1 knockdown. Analysis of readout parameters included qRT-PCR, immunofluorescence, western blot assays, and behavioral tests. Results: Microglia exposed to OGD/R displayed a temporal pattern of NEAT1 expression, peaking at four hours of hypoxia followed by six hours of reoxygenation. After effectively silencing NEAT1, LD formation and autophagy-related proteins were significantly repressed in hypoxic microglia. Stimulating autophagy in ASO NEAT1 microglia under OGD/R conditions by means of RAPA reversed the downregulation of LD agglomeration and perilipin 2 (PLIN2) expression. On the contrary, application of 3-MA promoted repression of both LD agglomeration and expression of the LD-associated protein PLIN2. Under in vivo conditions, NEAT1 was significantly increased in mice at 24 h post-stroke. Knockdown of NEAT1 significantly alleviated LD agglomeration and inhibited autophagy, resulting in improved cerebral perfusion, reduced brain injury and increased neurological recovery. Conclusion: NEAT1 is a key player of LD agglomeration and autophagy stimulation, and NEAT1 knockdown provides a promising therapeutic value against stroke. [ABSTRACT FROM AUTHOR]

Hypoxia triggers reactive microglial inflammation and lipid droplet (LD) accumulation under stroke conditions, although the mutual interactions between these two processes are insufficiently understood. Hence, the involvement of transforming growth factor (TGF)-β1 in inflammation and LD accumulation in cultured microglia exposed to hypoxia were analyzed herein. Primary microglia were exposed to oxygen-glucose deprivation (OGD) injury and lipopolysaccharide (LPS) stimulation. For analyzing the role of TGF-β1 patterns under such conditions, a TGF-β1 siRNA and an exogenous recombinant TGF-β1 protein were employed. Further studies applied Triacsin C, an inhibitor of LD formation, in order to directly assess the impact of LD formation on the modulation of inflammation. To assess mutual microglia-to-neuron interactions, a co-culture model of these cells was established. Upon OGD exposure, microglial TGF-β1 levels were significantly increased, whereas LPS stimulation yielded decreased levels. Elevating TGF-β1 expression proved highly effective in suppressing inflammation and reducing LD accumulation in microglia exposed to LPS. Conversely, inhibition of TGF-β1 led to the promotion of microglial cell inflammation and an increase in LD accumulation in microglia exposed to OGD. Employing the LD formation inhibitor Triacsin C, in turn, polarized microglia towards an anti-inflammatory phenotype. Such modulation of both microglial TGF-β1 and LD levels significantly affected the resistance of co-cultured neurons. This study provides novel insights by demonstrating that TGF-β1 plays a protective role against microglia-mediated neuroinflammation through the suppression of LD accumulation. These findings offer a fresh perspective on stroke treatment, suggesting the potential of targeting this pathway for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Spontaneous intracerebral hemorrhage (ICH) is a frequent cerebrovascular disorder and still associated with high mortality and poor clinical outcomes. The purpose of this review was to update a 15-year-old former meta-analysis on randomized clinical trials (RCTs) addressing the question of whether ICH patients treated with dexamethasone have better outcomes than controls. Methods: The electronic databases PubMed, SCOPUS, and Cochrane as well as web platforms on current clinical trials were searched for the years 1970–2020 without constriction on language. Data were extracted and outcomes were pooled for conventional and cumulative meta-analysis using a commercial software program (www.Meta-Analysis.com). Results: Finally, 7 RCTs were identified and analyzed including 248 participants in the dexamethasone groups and 242 in the control groups. Five studies showed a high risk of bias. The overall relative risk (RR) for death was 1.32 (95% confidence interval [CI] 0.99–1.76; p = 0.06) and did not differ significantly between the 2 groups. After exclusion of studies with high risk of bias, the RR for death was 1.37 (95% CI 0.54–3.42; p = 0.51). The RR for poor outcome did not differ significantly between the 2 groups analyzed for all included studies (RR = 0.69; 95% CI 0.47–1; p = 0.05) and after exclusion of studies with high risk of bias (RR = 0.7; 95% CI 0.45–1.08; p = 0.11). The RR for complications did not differ significantly including all studies (RR = 1.29; 95% CI 0.77–2.17; p = 0.34) and after exclusion of studies with high risk of bias (RR = 1.27; 95% CI 0.18–8.89; p = 0.81). The cumulative statistics delivered no other results; however, it pointed out fewer complications over time in the dexamethasone group. Conclusion: Clear evidence of a beneficial or negative effect of dexamethasone is still lacking. Modern RCTs or observational studies with propensity design are necessary to evaluate the efficacy and safety of treatment with dexamethasone in patients with ICH. [ABSTRACT FROM AUTHOR]

Brain injured patients often need deep sedation to prevent or treat increased intracranial pressure. The mainly used IV sedatives have side effects and/or high context-sensitive half-lives, limiting their use. Inhalative sedatives have comparatively minor side effects and a brief context-sensitive half-life. Despite the theoretical advantages, evidence in this patient group is lacking. A Germany-wide survey with 21 questions was conducted to find out how widespread the use of inhaled sedation is. An invitation for the survey was sent to 226 leaders of intensive care units (ICU) treating patients with brain injury as listed by the German Society for Neurointensive Care. Eighty-nine participants answered the questionnaire, but not all items were responded to, which resulted in different absolute counts. Most of them (88%) were university or high-level hospital ICU leaders and (67%) were leaders of specialized neuro-ICUs. Of these, 53/81 (65%) use inhalative sedation, and of the remaining 28, 17 reported interest in using this kind of sedation. Isoflurane is used by 43/53 (81%), sevoflurane by 15/53 (28%), and desflurane by 2. Hypotension and mydriasis are the most common reported side effects (25%). The presented survey showed that inhalative sedatives were used in a significant number of intensive care units in Germany to treat severely brain-injured patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "CSF-air-exchange for pharmacorefractory status epilepticus," that was published in the online edition of the "Journal of Neurology" on April 11, 2006.

Aim: The aim of this study was to re‐evaluate risk factors for post‐ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH. Background and purpose: Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain. Methods: We retrospectively included patients with spontaneous ICH treated in our hospital in 2006–2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni‐ and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation. Results: Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow‐up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1–132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14–2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33–2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20–2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08–0.84]; p = 0.025). Conclusions: Post‐ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies postulate a high prognostic value of the Alberta Stroke Programme Early CT Score (ASPECTS) applied on non-contrast whole-brain flat-detector CT (FDCT) after successful endovascular treatment (EVT). The aim of this study was the evaluation of long-term patient outcome after endovascular treatment using postinterventional FDCT. Methods: Using a local database (Stroke Research Consortium in Northern Bavaria, STAMINA), 517 patients with successful endovascular treatment (modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2B) due to acute ischaemic stroke (AIS) and large vessel occlusion (LVO) of the anterior circulation were recruited retrospectively. In all cases, non-contrast FDCT after EVT was analysed with special focus at ASPECTS. These results were correlated with the functional outcome in long-term (modified Rankin Scale (mRS) shift from pre-stroke to 90 days after discharge). Results: A significant difference in FDCT-ASPECTS compared to the subgroup of favourable vs. unfavourable outcome (Δ mRS) (median ASPECTS 10 (10–9) vs. median ASPECTS 9 (10–7); p = 0,001) could be demonstrated. Multivariable regression analysis revealed FDCT-ASPECTS (OR 0.234, 95% CI − 0.102–0.008, p = 0.022) along with the NHISS at admission (OR 0.169, 95% CI 0.003–0.018, p = 0.008) as independent factors for a favourable outcome. Cut-off point for a favourable outcome (Δ mRS) was identified at an ASPECTS ≥ 8 (sensitivity 90.6%, specificity 35%). Conclusion: For patients with LVO and successful EVT, FDCT-ASPECTS was found to be highly reliable in predicting long-term outcome. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Following cardiac surgery, postoperative cognitive decline (POCD) is a common complication that can impair the quality of life and increase mortality. The aim of this study was to investigate whether early postoperative cognitive training can decrease POCD after cardiac surgery. METHODS The study was a multi-centred, two-arm, randomized (1:1 ratio), controlled trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation. Recruitment took place at the Department of Cardiac Surgery of the Kerckhoff-Clinic in Bad Nauheim (Germany) and the University-Hospital in Giessen (Germany). The patients were randomized to either a paper-and-pencil-based cognitive training group or a standard rehabilitation care control group. The cognitive training started 1 week after surgery and lasted about 3 weeks until discharge from rehabilitation. To detect POCD, neuropsychological functions were assessed prior to surgery, upon discharge from rehabilitation (primary outcome), and 3 months after discharge (secondary outcome). Data were primarily analysed in a per-protocol fashion. RESULTS The frequency of POCD at discharge from rehabilitation (training group, n  = 37; control group, n  = 44) was 50% in the control group and 19% in the training group (χ2[1] = 8.45, P  = 0.004; odds ratio = 4.29, 95% confidence interval [1.56–11.80]). Three months after the cognitive training (training group, n  = 33; control group, n  = 34), POCD frequency was 29% in the control group and 6% in the training group (χ2[1] = 6.21, P  = 0.013; odds ratio = 6.46, 95% confidence interval [1.29–32.28]). CONCLUSIONS Since our cognitive training showed beneficial effects, it could be a promising method to prevent POCD. [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and aim: To assess associations between clinical severity and possible dysfunction of autonomic cardiovascular modulation within the acute phase after spontaneous subarachnoid hemorrhage (SAH). Methods: In this prospective observational study, in 51 patients with spontaneous SAH, Hunt-and-Hess scores (H&H) were assessed and cardiovascular autonomic modulation was monitored within 24 h after SAH-onset. From 5 min time-series of R–R-intervals (RRI) and blood-pressure (BP) recordings, we calculated autonomic parameters including time-domain [RRI-coefficient-of-variation (RRI-CV) and square-root-of-the-mean-squared-differences-of-successive-RRIs (RMSSD)] and frequency-domain parameters [low- and high-frequency-powers of RRI- and BP-modulation (RRI-LF-, RRI-HF-, SBP-LF-powers) and RRI-total-powers]. Data were compared to those of 20 healthy volunteers. Results: RRI- and BP-values did not differ between groups. Yet, parameters of sympathetic (RRI-LF-powers 141.0 (18.9–402.4) ms2 vs 442.3 (246.8–921.2) ms2, p = 0.001) and total autonomic modulation (RRI-CV 2.4 (1.2–3.7) ms2 vs 3.7 (3.1–5.3) ms2, p = 0.001) were significantly lower in patients than in controls. Subgroup analyses (patients with H&H < 3 vs H&H ≥ 3) and Spearman-rank-correlations revealed increasing loss of sympathetic (RRI-LF-powers 338.6 (179.7–710.4) ms2 vs 72.1 (10.1–175.9) ms2, p = 0.001, rho = − 0.524) and total autonomic modulation (RRI-CV 3.5 (2.3–5.4) ms2 vs 1.6 (1.0–2.8) ms2, p < 0.001, rho = − 0.519) with higher H&H-scores. Multiple-logistic-regression underlined the significant influence of H&H-scores on sympathetic (RRI-LF-powers, p = 0.033) and total autonomic modulation (RRI-CV, p = 0.040) compared to possible confounders (e.g., age, intubation). Conclusion: Within the acute phase, spontaneous SAH induces a decrease in sympathetic and total autonomic cardiovascular modulation. Higher H&H-scores were associated with increasing autonomic dysfunction and may therefore augment the risk of cardiovascular complications and poor clinical outcome. [ABSTRACT FROM AUTHOR]

Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Seronegative patients represent around 10–15% of MG, but data on outcome of seronegative MCs are lacking. We performed a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody-positive MG (AChR-MG) or seronegative MG between 2006 and 2015 in a retrospective German multicenter study. We identified 15 seronegative MG patients with 17 MCs and 142 AChR-MG with 159 MCs. Seronegative MCs were younger (54.3 ± 14.5 vs 66.5 ± 16.3 years; p = 0.0037), had a higher rate of thymus hyperplasia (29.4% vs 3.1%; p = 0.0009), and were more likely to be female (58.8% vs 37.7%; p = 0.12) compared to AChR-MCs. Time between diagnosis of MG and MC was significantly longer in seronegative patients (8.2 ± 7.6 vs 3.1 ± 4.4 years; p < 0.0001). We found no differences in duration of mechanical ventilation (16.2 ± 15.8 vs 16.5 ± 15.9 days; p = 0.94) and length of stay at intensive care unit (17.6 ± 15.2 vs 17.8 ± 15.4 days; p = 0.96), or in-hospital mortality (11.8% vs. 10.1%; p = 0.69). We conclude that MC in seronegative MG affects younger patients after a longer period of disease, but that crisis treatment efficacy and outcome do not differ compared to AChR-MCs. [ABSTRACT FROM AUTHOR]

Neurocritical patients suffer from a substantial risk of extubation failure. The aim of this prospective study was to analyze if quantitative EEG (qEEG) monitoring is able to predict successful extubation in these patients. We analyzed EEG-monitoring for at least six hours before extubation in patients receiving mechanical ventilation (MV) on our neurological intensive care unit (NICU) between November 2017 and May 2019. Patients were divided in 2 groups: patients with successful extubation (SE) versus patients with complications after MV withdrawal (failed extubation; FE), including reintubation, need for non-invasive ventilation (NIV) or death. Bipolar six channel EEG was applied. Unselected raw EEG signal underwent automated artefact rejection and Short Time Fast Fourier Transformation. The following relative proportions of global EEG spectrum were analyzed: relative beta (RB), alpha (RA), theta (RT), delta (RD) as well as the alpha delta ratio (ADR). Coefficient of variation (CV) was calculated as a measure of fluctuations in the different power bands. Mann–Whitney U test and logistic regression were applied to analyze group differences. 52 patients were included (26 male, mean age 65 ± 17 years, diagnosis: 40% seizures/status epilepticus, 37% ischemia, 13% intracranial hemorrhage, 10% others). Successful extubation was possible in 40 patients (77%), reintubation was necessary in 6 patients (12%), 5 patients (10%) required NIV, one patient died. In contrast to FE patients, SE patients showed more stable EEG power values (lower CV) considering all EEG channels (RB: p < 0.0005; RA: p = 0.045; RT: p = 0.045) with RB as an independent predictor of weaning success in logistic regression (p = 0.004). The proportion of the EEG frequency bands (RB, RA RT, RD) of the entire EEG power spectrum was not significantly different between SE and FE patients. Higher fluctuations in qEEG frequency bands, reflecting greater fluctuation in alertness, during the hours before cessation of MV were associated with a higher rate of complications after extubation in this cohort. The stability of qEEG power values may represent a non-invasive, examiner-independent parameter to facilitate weaning assessment in neurocritical patients. [ABSTRACT FROM AUTHOR]

The human amygdala is involved in processing of memory, decision-making, and emotional responses. Previous studies suggested that the amygdala may represent a neurogenic niche in mammals. By combining two distinct methodological approaches, lipofuscin quantification and 14C-based retrospective birth dating of neurons, along with mathematical modelling, we here explored whether postnatal neurogenesis exists in the human amygdala. We investigated post-mortem samples of twelve neurologically healthy subjects. The average rate of lipofuscin-negative neurons was 3.4%, representing a substantial proportion of cells substantially younger than the individual. Mass spectrometry analysis of genomic 14C-concentrations in amygdala neurons compared with atmospheric 14C-levels provided evidence for postnatal neuronal exchange. Mathematical modelling identified a best-fitting scenario comprising of a quiescent and a renewing neuronal population with an overall renewal rate of >2.7% per year. In conclusion, we provide evidence for postnatal neurogenesis in the human amygdala with cell turnover rates comparable to the hippocampus. Lipofuscin labeling and 14 C retrospective birth-dating of neurons, along with mathematical modelling, here suggest continued postnatal neurogenesis in the human amygdala, rather than protracted maturation of developmentally generated neurons. [ABSTRACT FROM AUTHOR]

Oropharyngeal sensitivity plays a vital role in the initiation of the swallowing reflex and is thought to decline as part of the aging-process. Taste and smell functions appear to decline with age as well. The aim of our study was to generate data of oral sensitivity in healthy participants for future studies and to analyse age-related changes and their interdependence by measuring oral sensitivity, taste, and smell function. The experiment involved 30 participants younger than and 30 participants older than 60. Sensitivity threshold as a surrogate of oral sensitivity was measured at the anterior faucial pillar by electrical stimulation using commercially available pudendal electrode mounted on a gloved finger. Smell and taste were evaluated using commercially available test kits. Mean sensitivity was lower in young participants compared to older participants (1.9 ± 0.59 mA vs. 2.42 ± 1.03 mA; p = 0.021). Young participants also performed better in smell (Score 11.13 ± 0.86 vs 9.3 ± 1.93; p < 0.001) and taste examinations (Score 11.83 ± 1.86 vs 8.53 ± 3.18; p < 0.001). ANCOVA revealed a statistical association between sensitivity and smell (p = 0.08) that was moderated by age (p = 0.044). Electrical threshold testing at the anterior faucial pillar is a simple, safe, and accurate diagnostic measure of oral sensitivity. We detected a decline of oral sensitivity, taste, and smell in older adults. Trial registration: Clinicaltrials.gov, NCT03240965. Registered 7th August 2017—https://clinicaltrials.gov/ct2/show/NCT03240965. [ABSTRACT FROM AUTHOR]

Background: Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk factors correlating with a tracheostomy, as well as the impact of an early tracheostomy on ventilation time and ICU length of stay (LOS) in MC. Methods: Retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015 to assess demographic/diagnostic data, rates and timing of tracheostomy and outcome. Results: In 107 out of 215 MC (49.8%), a tracheostomy was performed. Patients without tracheostomy were more likely to have an early-onset myasthenia gravis (27 [25.2%] vs 12 [11.5%], p = 0.01). Patients receiving a tracheostomy, however, were more frequently suffering from multiple comorbidities (20 [18.7%] vs 9 [8.3%], p = 0.03) and also the ventilation time (34.4 days ± 27.7 versus 7.9 ± 7.8, p < 0.0001) and ICU-LOS (34.8 days ± 25.5 versus 12.1 ± 8.0, p < 0.0001) was significantly longer than in non-tracheostomized patients. Demographics and characteristics of the course of the disease up to the crisis were not significantly different between patients with an early (within 10 days) compared to a late tracheostomy. However, an early tracheostomy correlated with a shorter duration of MV at ICU (26.2 days ± 18.1 versus 42.0 ± 33.1, p = 0.006), and ICU-LOS (26.2 days ± 14.6 versus 42.3 ± 33.0, p = 0.003). Conclusion: Half of the ventilated patients with MC required a tracheostomy. Poorer health condition before the crisis and late-onset MG were associated with a tracheostomy. An early tracheostomy (≤ day 10), however, was associated with a shorter duration of MV and ICU-LOS by 2 weeks. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the association between seizure termination and side effects of isoflurane for the treatment of refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) in neurointensive care units (neuro-ICUs). Methods: This was a multicenter retrospective study of patients with RSE/SRSE treated with isoflurane for status epilepticus termination admitted to the neuro-ICUs of nine German university centers during 2011–2018. Results: We identified 45 patients who received isoflurane for the treatment of RSE/SRSE. During isoflurane treatment, electroencephalograms showed no epileptiform discharges in 33 of 41 (80%) patients, and burst suppression pattern was achieved in 29 of 41 patients (71%). RSE/SRSE was finally terminated after treatment with isoflurane in 23 of 45 patients (51%) for the entire group and in 13 of 45 patients (29%) without additional therapy. Lengths of stay in the hospital and in the neuro-ICU were significantly extended in cases of ongoing status epilepticus under isoflurane treatment (p = 0.01 for length of stay in the hospital, p = 0.049 for length in the neuro-ICU). During isoflurane treatment, side effects were reported in 40 of 45 patients (89%) and mainly included hypotension (n = 40, 89%) and/or infection (n = 20, 44%). Whether side effects occurred did not affect the outcome at discharge. Of 22 patients with follow-up magnetic resonance imaging, 2 patients (9%) showed progressive magnetic resonance imaging alterations that were considered to be potentially associated with RSE/SRSE itself or with isoflurane therapy. Conclusions: Isoflurane was associated with a good effect in stopping RSE/SRSE. Nevertheless, establishing remission remained difficult. Side effects were common but without effect on the outcome at discharge. [ABSTRACT FROM AUTHOR]

Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Muscle-specific kinase-antibodies (MuSK-ABs) are detected in ~ 6% of MG, but data on outcome of MuSK-MCs are still lacking. We made a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody positive MG (AchR-MG) or MuSK-MG between 2006 and 2015 in a retrospective German multicenter study. We identified 19 MuSK-AB associated MCs in 15 patients and 161 MCs in 144 patients with AchR-ABs only. In contrast to patients with AchR-AB, MuSK-AB patients were more often female (p = 0.05, OR = 2.74) and classified as Myasthenia Gravis Foundation of America-class IV before crisis (p = 0.04, OR = 3.25). MuSK-AB patients suffer more often from multiple chronic disease (p = 0.016, OR = 4.87) and were treated more invasively in terms of plasma exchanging therapies (not significant). The number of days of mechanical ventilation (MV) (43.0 ± 53.1 vs. 17.4 ± 18; p < 0.0001), days on an intensive care unit (ICU) (45.3 ± 49.5 vs. 21.2 ± 19.7; p < 0.0001), and hospital-length of stay (LOS) (55.9 ± 47.6 vs. 28.8 ± 20.9 days; p < 0.0001) were significantly increased in MuSK-MC. Remarkable is that these changes were mainly due to patients with MusK-ABs only, whereas patients' outcome with both antibodies was similar to AchR-MCs. Furthermore, our data showed a shortened duration of MV after treatment with plasma exchanging therapies compared to treatment with intravenous immunoglobulin in MuSK-MCs. We conclude that MuSK-AB-status is associated with a longer need of MV, ICU-LOS, and hospital-LOS in MC, and therefore recommend early initiation of a disease-specific therapy. [ABSTRACT FROM AUTHOR]

Background: For outcome assessment in patients surviving subarachnoid hemorrhage (SAH), the modified Rankin scale (mRS) represents the mostly established outcome tool, whereas other dimensions of outcome such as mood disorders and impairments in social life remain unattended so far. Objective: The aim of our study was to correlate 12-month functional and subjective health outcomes in SAH survivors. Methods: All SAH patients treated over a 5-year period received outcome assessment at 12 months, including functional scores (mRS and Barthel Index [BI]), subjective health measurement (EQ-5D), and whether they returned to work. Analyses – including utility-weighted mRS – were conducted to detect associations and correlations among different outcome measures, especially in patients achieving good functional outcome (i.e., mRS 0-2) at 12 months. Results: Of 351 SAH survivors, 287 (81.2%) achieved favorable functional outcome at 12 months. Contrary to the BI, the EQ-5D visual analog scale (VAS) showed a strong association with different mRS grades, accentuated in patients with favorable functional outcome. Despite favorable functional outcome, patients reported a high rate of impairments in activities (24.0%), pain (33.4%), and anxiety/depression (42.5%). Further, multivariable analysis revealed (i) impairments in activities (odds ratio [OR] [95% confidence interval {CI}]: 0.872 [0.817–0.930]), (ii) presence of depression or anxiety (OR [95% CI]: 0.836 [0.760–0.920]), and (iii) return to work (OR [95% CI]: 1.102 [0.1.013–1.198]) to be independently associated with self-reported subjective health. Conclusion: Established stroke scores mainly focusing on functional outcomes do poorly reflect the high rate of subjective impairments reported in SAH survivors, specifically in those achieving good functional outcome. Further studies are needed to investigate whether psychoeducational approaches aiming at improving coping mechanisms and perceived self-efficacy may result in higher subjective health in these patients. [ABSTRACT FROM AUTHOR]

Background Intracerebral hemorrhage accounts for up to 15% of all strokes and is frequently associated with poor functional outcome and high mortality. So far, there is no clear evidence for a specific therapy, apart from general stroke unit or neurointensive care and management of secondary complications. Promising experimental and pilot clinical data support the use of therapeutic hypothermia after intracerebral hemorrhage. Aims The study aims to determine if therapeutic hypothermia improves survival rates and reduces cerebral lesion volume after large intracerebral hemorrhage compared with conventional treatment. Material and methods The Cooling in IntraCerebral Hemorrhage trial is a prospective, multicenter, interventional, randomized, parallel, two-arm (1 : 1) phase II trial with blinded end-point adjudication. Enrolment: 50 patients (age: 18 to 65 years) with large (25 to 64 ml on cranial computertomography), primary intracerebral hemorrhage of the basal ganglia or thalamus within 6 to 18 h after symptom onset are randomly allocated to therapeutic hypothermia for eight-days or conventional temperature management. In the therapeutic hypothermia group, a target temperature of 35·0° C is achieved by endovascular catheters and followed by slow controlled rewarming. Data analysis is based on the intent-to-treat population. The primary outcome measure of the study is the development in total lesion volume on cranial computertomography (intracerebral hemorrhage plus perihemorrhagic edema on day 8 ± 0·5 and day 11 ± 0·5 after intracerebral hemorrhage) and the mortality after 30 days. Secondary end-points are the in-hospital mortality, mortality, and functional outcome (modified Rankin Scale and Barthel-Index) after 90 and 180 days. Safety measures include any adverse events associated with therapeutic hypothermia. Discussion In the face of a lack of evidence-based therapies for patients with large intracerebral hemorrhage, new promising approaches are desperately needed, but need evaluation in randomized controlled trials. Conclusion The results of Cooling in IntraCerebral Hemorrhage trial are believed to directly influence future therapy of large intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Background: We investigated the feasibility and accuracy of intracranial pressure (ICP)-measurement by lumbar drainage (LD) catheter in patients with post-hemorrhagic communicating hydrocephalus (PHCH). Methods: Patients with subarachnoid hemorrhage (SAH, n = 21) or spontaneous ganglionic hemorrhage (ICH, n = 22) with ventricular involvement and the need for external ventricular drainage (EVD) due to acute hydrocephalus were included. When EVD weaning was not feasible due to persistent hydrocephalus, an additional LD was placed, after which EVD was clamped off. During this overlap period, patients underwent simultaneous pressure recording via EVD ('EVD-ICP') and LD ('LD-ICP'). Testing included manual compression of the jugular veins and body-posture changes from supine to 30° position. After EVD removal, we evaluated sensitivity and specificity of ICP-rise >20 mmHg during continuous monitoring via LD for the detection of persistent PHCH using additional evaluation with computed tomography (CT). Results: A total of 1,806 measurements were performed in 43 patients. 'LD-ICP' was strongly correlated to 'EVD-ICP', with determination coefficients R for the baseline measurements and each of the maneuvers ranging from 0.95-0.99, and slopes ranging 0.96-1.01. Sensitivity of 'LD-ICP' >20 mmHg for detection of persistent PHCH as compared to CT was 81% and specificity was 100%. Two patients with severe SAH developed reversible signs of herniation after gradually increasing differences between 'LD-ICP' and 'EVD-ICP' indicated a cranio-spinal pressure gradient, likely due to cerebrospinal fluid overdrainage via LD. Conclusion: ICP measured via LD highly and reliably correlated to ICP measured via EVD in patients with PHCH. [ABSTRACT FROM AUTHOR]

More than ten years after its approval intravenous thrombolysis with rtPA still is the only approved therapy for acute ischemic stroke. In this review we aim to give an up-to-date overview of acute stroke imaging within and outside of approved indications for thrombolysis. We discuss the potential applications of modern CT techniques such as CT angiography and perfusion CT as well as stroke MRI for the selection-based treatment of acute ischemic stroke. Recent publications regarding diagnostic strength as well as new randomized trials and larger prospective but open studies are reviewed and discussed. Finally we present a suggestion for the selection of patients for thrombolysis within and beyond the 3-hour time window in the form of an institutional algorithm prioritizing according to present evidence and pathophysiological reasoning. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Data regarding the influence of concomitant parenchymatous hematoma (PH) on long-term outcomes in patients with atraumatic subarachnoid hemorrhage (SAH) are scarce. Further, it is not established if these patients benefit from surgical intervention. Aim: The aim of this study was to determine the influence of concomitant PH in SAH patients on functional long-term outcome, and whether these patients may benefit from surgical hematoma evacuation. Methods: Over a 5-year period, all consecutive patients with SAH treated at the Departments of Neurology, Neuroradiology, and Neurosurgery, at the University Hospital Erlangen (Germany) were recorded. In addition to the clinical and imaging characteristics of SAH, we documented the presence, location, and volume of PH as well as treatment parameters. Outcome assessment at 12 months included functional outcome (modified Rankin scale (mRS), favorable = 0–2), health-related quality of life, and long-term complications. For outcome analysis, a propensity score matching (ratio 1:1, caliper 0.1) was performed to compare SAH patients with and without PH. Sub-analyses were performed regarding PH treatment (surgical evacuation vs. conservative). Results: A total of 494 patients with atraumatic SAH were available. Eighty-five (17.2%) had PH on initial imaging. SAH patients with PH had a worse clinical condition on admission and had a greater extent of subarachnoid/intraventricular hemorrhage. Median PH volume was 11.0 ml (5.4–31.8) with largest volumes observed in patients with ruptured middle cerebral artery (MCA)-aneurysm (31.7 ml (16.3–43.2)). After propensity-score matching (PSM), patients with PH had worse functional outcomes at 12 months (modified Rankin scale (mRS) 0–2: PH 31.8% vs. ØPH57.7% p < 0.001), and a lower rate of self-reported health compared to patients without PH (EQ-5D VAS: PH 50(30–70) vs. ØPH 80(65–95); p < 0.001). In PH patients, surgical evacuation was associated with a higher rate of favorable outcome at 12 months compared to those treated conservatively (surgery 14/28 (50.0%) vs. conservative 14/57 (24.6%); adjusted odds-ratio (OR; 95%CI): 1.34 (1.08–1.66); p = 0.001), irrespective of aneurysm location. Subgroup-analysis revealed positive associations of surgical hematoma evacuation with outcome in subgroups with larger PH volumes (>10 ml; OR (95%CI): 1.39 (1.09–1.79)), frontal PH location (OR 1.59 (1.14–2.23)), and early surgery (within 600 min after onset; OR 1.42 (1.03–1.94)). Conclusions: Concomitant PH occurs frequently in patients with SAH and is associated with functional impairment after 1 year. Surgical evacuation of PH may improve outcomes in these patients, irrespective of aneurysm-location. [ABSTRACT FROM AUTHOR]

• Extent of alpha power decrease in qEEG moderately correlates with severity of vasospasm in transcranial ultrasound. • qEEG is able to differentiate between patients with and without development of cerebral infarction after subarachnoid haemorrhage. • Total duration of alpha power decrease in qEEG is an easy, non-invasive marker to survey treatment of delayed cerebral ischemia. In subarachnoid hemorrhage (SAH), transcranial Doppler/color-coded-duplex sonography (TCD/TCCS) is used to detect delayed cerebral ischemia (DCI). In previous studies, quantitative electroencephalography (qEEG) also predicted imminent DCI. This study aimed to compare and analyse the ability of qEEG and TCD/TCCS to early identify patients who will develop later manifest cerebral infarction. We analysed cohorts of two previous qEEG studies. Continuous six-channel-EEG with artefact rejection and a detrending procedure was applied. Alpha power decline of ≥ 40% for ≥ 5 hours compared to a 6-hour-baseline was defined as significant EEG event. Median reduction and duration of alpha power decrease in each channel was determined. Vasospasm was diagnosed by TCD/TCCS, identifying the maximum frequency and days of vasospasm in each territory. 34 patients were included (17 male, mean age 56 ± 11 years, Hunt and Hess grade: I–V, cerebral infarction: 9). Maximum frequencies in TCD/TCCS and alpha power reduction in qEEG were correlated (r = 0.43; p = 0.015). Patients with and without infarction significantly differed in qEEG parameters (maximum alpha power decrease: 78% vs 64%, p = 0.019; summed hours of alpha power decline: 236 hours vs 39 hours, p = 0.006) but showed no significant differences in TCD/TCCS parameters. There was a moderate correlation of TCD/TCCS frequencies and qEEG alpha power reduction but only qEEG differentiated between patients with and without cerebral infarction. qEEG represents a non-invasive, continuous tool to identify patients at risk of cerebral infarction. [ABSTRACT FROM AUTHOR]

In community-acquired bacterial meningitis (CABM) intracranial vascular alterations are devastating complications which are triggered by neuroinflammation and result in worse clinical outcome. The Neutrophil-to-Lymphocyte ratio (NLR) represents a reliable parameter of the inflammatory response. In this study we analyzed the association between NLR and elevated cerebral blood flow velocity (CBFv) in CABM-patients. This study included all (CABM)-patients admitted to a German tertiary center between 2006 and 2016. Patients' demographics, in-hospital measures, neuroradiological data and clinical outcome were retrieved from institutional databases. CBFv was assessed by transcranial doppler (TCD). Patients', radiological and laboratory characteristics were compared between patients with/without elevated CBFv. Multivariate-analysis investigated parameters independently associated with elevated CBFv. Receiver operating characteristic(ROC-)curve analysis was undertaken to identify the best cut-off for NLR to discriminate between increased CBFv. 108 patients with CABM were identified. 27.8% (30/108) showed elevated CBFv. Patients with elevated CBFv and normal CBFv, respectively had a worse clinical status on admission (Glasgow Coma Scale: 12 [9–14] vs. 14 [11–15]; p = 0.005) and required more often intensive care (30/30 [100.0%] vs. 63/78 [80.8%]; p = 0.01).The causative pathogen was S. pneumoniae in 70%. Patients with elevated CBFv developed more often cerebrovascular complications with delayed cerebral ischemia (DCI) within hospital stay (p = 0.031). A significantly higher admission-NLR was observed in patients with elevated CBFv (median [IQR]: elevated CBFv:24.0 [20.4–30.2] vs. normal CBFv:13.5 [8.4–19.5]; p < 0.001). Multivariate analysis, revealed NLR to be significantly associated with increased CBFv (Odds ratio [95%CI] 1.042 [1.003–1.084]; p = 0.036). ROC-analysis identified a NLR of 20.9 as best cut-off value to discriminate between elevated CBFv (AUC = 0.713, p < 0.0001, Youden's Index = 0.441;elevated CBFv: NLR ≥ 20.9 19/30[63.5%] vs. normal CBFv: NLR > 20.9 15/78[19.2%]; p < 0.001). Intracranial vascular complications are common among CABM-patients and are a risk factor for unfavorable outcome at discharge. Elevated NLR is independently associated with high CBFv and may be useful in predicting patients' prognosis. [ABSTRACT FROM AUTHOR]

The role of neuroinflammation in the pathophysiology of seizures is increasingly recognized, and the evaluation of potential biochemical markers of inflammatory processes in seizures and status epilepticus (SE), such as C‐reactive protein (CRP), has gained attention. The present study assessed the first CRP level obtained in an SE episode regarding its value for SE outcome prediction. Among 362 admissions for SE during the study period, 231 episodes satisfied the inclusion criteria. Higher initial CRP concentrations were independently associated with in‐hospital mortality and poor functional outcome at discharge in logistic regression models adjusting for SE severity, severity of SE etiology, and development of treatment refractoriness. Therefore, initial CRP levels may add to the prediction of SE prognosis. The pathomechanisms through which CRP is linked with the prognosis of SE, however, remain to be established. [ABSTRACT FROM AUTHOR]

Objective: Outcome prognostication unbiased by early care limitations (ECL) is essential for guiding treatment in patients presenting with intracerebral hemorrhage (ICH). The aim of this study was to determine whether the max‐ICH (maximally treated ICH) Score provides improved and clinically useful prognostic estimation of functional long‐term outcomes after ICH. Methods: This multicenter validation study compared the prognostication of the max‐ICH Score versus the ICH Score regarding diagnostic accuracy (discrimination and calibration) and clinical utility using decision curve analysis. We performed a joint investigation of individual participant data of consecutive spontaneous ICH patients (n = 4,677) from 2 retrospective German‐wide studies (RETRACE I + II; anticoagulation‐associated ICH only) conducted at 22 participating centers, one German prospective single‐center study (UKER‐ICH; nonanticoagulation‐associated ICH only), and 1 US‐based prospective longitudinal single‐center study (MGH; both anticoagulation‐ and nonanticoagulation‐associated ICH), treated between January 2006 and December 2015. Results: Of 4,677 included ICH patients, 1,017 (21.7%) were affected by ECL (German cohort: 15.6% [440 of 2,377]; MGH: 31.0% [577 of 1,283]). Validation of long‐term functional outcome prognostication by the max‐ICH Score provided good and superior discrimination in patients without ECL compared with the ICH Score (area under the receiver operating curve [AUROC], German cohort: 0.81 [0.78–0.83] vs 0.74 [0.72–0.77], p < 0.01; MGH: 0.85 [0.81–0.89] vs 0.78 [0.74–0.82], p < 0.01), and for the entire cohort (AUROC, German cohort: 0.84 [0.82–0.86] vs 0.80 [0.77–0.82], p < 0.01; MGH: 0.83 [0.81–0.85] vs 0.77 [0.75–0.79], p < 0.01). Both scores showed no evidence of poor calibration. The clinical utility investigated by decision curve analysis showed, at high threshold probabilities (0.8, aiming to avoid false‐positive poor outcome attribution), that the max‐ICH Score provided a clinical net benefit compared with the ICH Score (14.1 vs 2.1 net predicted poor outcomes per 100 patients). Interpretation: The max‐ICH Score provides valid and improved prognostication of functional outcome after ICH. The associated clinical net benefit in minimizing false poor outcome attribution might potentially prevent unwarranted care limitations in patients with ICH. ANN NEUROL 2021;89:474–484 [ABSTRACT FROM AUTHOR]

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor protein predominantly expressed in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and microglial phagocytosis. Recent studies have found that TREM2 is highly expressed in activated microglia after ischemic stroke. However, the role of TREM2 in the pathologic response after stroke remains unclear. Herein, TREM2-deficient microglia exhibit an impaired phagocytosis rate and cholesteryl ester (CE) accumulation, leading to lipid droplet formation and upregulation of Perilipin-2 (PLIN2) expression after hypoxia. Knockdown of TREM2 results in increased lipid synthesis (PLIN2, SOAT1) and decreased cholesterol clearance and lipid hydrolysis (LIPA, ApoE, ABCA1, NECH1, and NPC2), further impacting microglial phenotypes. In these lipid droplet-rich microglia, the TGF-β1/Smad2/3 signaling pathway is downregulated, driving microglia towards a pro-inflammatory phenotype. Meanwhile, in a neuron-microglia co-culture system under hypoxic conditions, we found that microglia lost their protective effect against neuronal injury and apoptosis when TREM2 was knocked down. Under in vivo conditions, TREM2 knockdown mice express lower TGF-β1 expression levels and a lower number of anti-inflammatory M2 phenotype microglia, resulting in increased cerebral infarct size, exacerbated neuronal apoptosis, and aggravated neuronal impairment. Our work suggests that TREM2 attenuates stroke-induced neuroinflammation by modulating the TGF-β1/Smad2/3 signaling pathway. TREM2 may play a direct role in the regulation of inflammation and also exert an influence on the post-ischemic inflammation and the stroke pathology progression via regulation of lipid metabolism processes. Thus, underscoring the therapeutic potential of TREM2 agonists in ischemic stroke and making TREM2 an attractive new clinical target for the treatment of ischemic stroke and other inflammation-related diseases. [Display omitted] • TREM2 regulates multiple microglial functions including lipid metabolism, inflammation, and microglial phagocytosis. • TREM2-deficient microglia exhibit an impaired phagocytosis rate and lipid droplet accumulation. • TREM2 knockdown leads lower TGF-β1 levels and less anti-inflammatory M2 phenotype microglia. • TREM2-deficient microglia display a lower neuroprotective potential. • TREM2 regulates post-ischemic inflammation in both a direct and an indirect way by modulating lipid metabolism. [ABSTRACT FROM AUTHOR]

Aims: This study determined the influence of age on bleeding characteristics and clinical outcomes in primary spontaneous (non-OAC), vitamin K antagonist-related (VKA-) and non-vitamin K antagonist oral anticoagulant-related (NOAC-) ICH. Methods: Pooled individual patient data of multicenter cohort studies were analyzed by logistic regression modelling and propensity-score-matching (PSM) to explore the influence of advanced age on clinical outcomes among non-OAC-, VKA-, and NOAC-ICH. Primary outcome measure was functional outcome at three months assessed by the modified Rankin Scale, dichotomized into favorable (mRS = 0–3) and unfavorable (mRS = 4–6) functional outcome. Secondary outcome measures included mortality, hematoma characteristics, and frequency of invasive interventions. Results: In VKA-ICH 33.5% (670/2001), in NOAC-ICH 44.2% (69/156) and in non-OAC-ICH 25.2% (254/1009) of the patients were ≥80 years. After adjustment for treatment interventions and relevant parameters, elderly ICH patients comprised worse functional outcome at three months (adjusted odds ratio (aOR) in VKA-ICH: 1.49 (1.21–1.84); p < 0.001; NOAC-ICH: 2.01 (0.95–4.26); p = 0.069; non-OAC-ICH: 3.54 (2.50–5.03); p < 0.001). Anticoagulation was significantly associated with worse functional outcome below the age of 70 years, (aOR: 2.38 (1.78–3.16); p < 0.001), but not in patients of ≥70 years (aOR: 1.21 (0.89–1.65); p = 0.217). The differences in initial ICH volume and extent of ICH enlargement between OAC-ICH and non-OAC-ICH gradually decreased with increasing patient age. Conclusions: As compared to elderly ICH-patients, in patients <70 years OAC-ICH showed worse clinical outcomes compared to non-OAC-ICH because of larger baseline ICH-volumes and extent of hematoma enlargement. Treatment strategies aiming at neutralizing altered coagulation should be aware of these findings. [ABSTRACT FROM AUTHOR]