Hagen B. Huttner

Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH).To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption.Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption.Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment.Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome.Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of ≥1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs ≥160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%).Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies.clinicaltrials.gov Identifier: NCT01829581.

Intracerebral hemorrhage (ICH) is the most serious and potentially fatal complication of oral anticoagulant therapy (OAT). Still, there are no universally accepted treatment regimens for patients with OAT-ICH, and randomized controlled trials do not exist. The aim of the present study was to compare the acute treatment strategies of OAT-associated ICH using vitamin K (VAK), fresh frozen plasma (FFP), and prothrombin complex concentrates (PCCs) with regard to hematoma growth and outcome.In this retrospective study, a total of 55 treated patients were analyzed. Three groups were compared by reviewing the clinical, laboratory, and neuroradiological parameters: (1) patients who received PCCs alone or in combination with FFP or VAK (n=31), (2) patients treated with FFP alone or in combination with VAK (n=18), and (3) patients who received VAK as a monotherapy (n=6). The end points of early hematoma growth and outcome after 12 months were analyzed including multivariate analysis.Hematoma growth within 24 hours occurred in 27% of patients. Incidence and extent of hematoma growth were significantly lower in patients receiving PCCs (19%/44%) compared with FFP (33%/54%) and VAK (50%/59%). However, this effect was no longer seen between PCC- and FFP-treated patients if international normalized ratio (INR) was completely reversed within 2 hours after admission. The overall outcome was poor (modified Rankin scale 4 to 6 in 77%). Predictors for hematoma growth were an increased INR after 2 hours, whereas administration of PCCs was significantly protective in multivariate analyses. Predictors for a poor outcome were age, baseline hematoma volume, and occurrence of hematoma growth.Overall, PCC was associated with a reduced incidence and extent of hematoma growth compared with FFP and VAK. This effect seems to be related to a more rapid INR reversal. Randomized controlled trials are needed to identify the most effective acute treatment regimen for lasting INR reversal because increased levels of INR were predisposing for hematoma enlargement.

Background and Purpose: This study aims to assess the number of patients with acute ischemic cerebrovascular events seeking in-patient medical emergency care since the implementation of social distancing measures in the coronavirus disease 2019 (COVID-19) pandemic. Methods: In this retrospective multicenter study, data on the number of hospital admissions due to acute ischemic stroke or transient ischemic attack and numbers of reperfusion therapies performed in weeks 1 to 15 of 2020 and 2019 were collected in 4 German academic stroke centers. Poisson regression was used to test for a change in admission rates before and after the implementation of extensive social distancing measures in week 12 of 2020. The analysis of anonymized regional mobility data allowed for correlations between changes in public mobility as measured by the number and length of trips taken and hospital admission for stroke/transient ischemic attack. Results: Only little variation of admission rates was observed before and after week 11 in 2019 and between the weeks 1 and 11 of 2019 and 2020. However, reflecting the impact of the COVID-19 pandemic, a significant decrease in the number of admissions for transient ischemic attack was observed (−85%, −46%, −42%) in 3 of 4 centers, while in 2 of 4 centers, stroke admission rates decreased significantly by 40% and 46% after week 12 in 2020. A relevant effect on reperfusion therapies was found for 1 center only (thrombolysis, −60%; thrombectomy, −61%). Positive correlations between number of ischemic events and mobility measures in the corresponding cities were identified for 3 of 4 centers. Conclusions: These data demonstrate and quantify decreasing hospital admissions due to ischemic cerebrovascular events and suggest that this may be a consequence of social distancing measures, in particular because hospital resources for acute stroke care were not limited during this period. Hence, raising public awareness is necessary to avoid serious healthcare and economic consequences of undiagnosed and untreated strokes and transient ischemic attacks.

After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome.To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage.The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours.A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage.Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage.Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, -0.12; 95% CI, -0.23 to -0.01; P = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%]; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, -0.11; 95% CI, -0.22 to 0; P = .04).In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage.ClinicalTrials.gov Identifier: NCT01258257.

Thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) is approved for use within 3 h after stroke onset. Thus only a small percentage of patients can benefit. Meta-analyses and more recent studies suggest a benefit for a subset of patients beyond 3 h. We assessed the safety and efficacy of an MRI-based selection protocol for stroke treatment within and beyond 3 h compared with standard CT-based treatment.We assessed clinical outcome and incidence of symptomatic intracerebral haemorrhage (ICH) in 400 consecutive patients treated with intravenous rtPA. Patients eligible for thrombolysis within 3 h were selected by CT or MRI and beyond 3 h only by MRI. 18 patients were excluded from analysis because of violation of that algorithm. The remaining 382 patients were divided into three groups: CT-based treatment within 3 h (n=209); MRI-based treatment within 3 h (n=103); and MRI-based treatment beyond 3 h (n=70).Patients in group 3 (MRI > 3 h) had a similar 90 day outcome to those in the other two groups (48% were independent in the CT < or = 3 h group, 51% in the MRI < or = 3 h group, and 56% in group 3), but without an increased risk for symptomatic ICH (9%, 1%, 6%) or mortality (21%, 13%, 11%). MRI-selected patients overall had a significantly lower risk than CT-selected patients for symptomatic ICH (3% vs 9%; p=0.013) and mortality (12% vs 21%; p=0.021). Time to treatment did not affect outcomes in univariate and multivariate analyses.Our data suggest that beyond 3 h and maybe even within 3 h, patient selection is more important than time to treatment for a good outcome. Furthermore, MRI-based thrombolysis, irrespective of the time window, shows an improved safety profile while being at least as effective as standard CT-based treatment within 3 h.

The ABC/2 formula is a reliable estimation technique of intracerebral hematoma volume. However, oral anticoagulant therapy (OAT)-related intracerebral hemorrhage (ICH) compared with primary ICH is based on a different pathophysiological mechanism, and various shapes of hematomas are more likely to occur. Our objective was to validate the ABC/2 technique based on analyses of the hematoma shapes in OAT-related ICH.We reviewed the computed tomography scans of 83 patients with OAT-associated intraparenchymal ICH. Location was divided into deep, lobar, cerebellar, and brain stem hemorrhage. Shape of the ICH was divided into (A) round-to-ellipsoid, (B) irregular with frayed margins, and (C) multinodular to separated. The ABC/2 technique was compared with computer-assisted planimetric analyses with regard to hematoma site and shape.The mean hematoma volume was 40.83+/-3.9 cm3 (ABC/2) versus 36.6+/-3.5 cm3 (planimetric analysis). Bland-Altman plots suggested equivalence of both estimation techniques, especially for smaller ICH volumes. The most frequent location was a deep hemorrhage (54%), followed by lobar (21%), cerebellar (14%) and brain stem hemorrhage (11%). The most common shape was round-to-ellipsoid (44%), followed by irregular ICH (31%) and separated and multinodular shapes (25%). In the latter, ABC/2 formula significantly overestimated volume by +32.1% (round shapes by +6.7%; irregular shapes by +14.9%; P ANOVA <0.01). Variation of the denominator toward ABC/3 in cases of irregularly and separately shaped hematomas revealed more a precise volume estimation with a deviation of -10.3% in irregular and +5.6% in separately shaped hematomas.In patients with OAT-related ICH, >50% of bleedings are irregularly shaped. In these cases, hematoma volume is significantly overestimated by the ABC/2 formula. Modification of the denominator to 3 (ie, ABC/3) measured ICH volume more accurately in these patients potentially facilitating treatment decisions.

<h2>Summary</h2> 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.

The objective of the present study was the development and validation of the method for determining AMB-FUBINACA and its metabolite - AMB-FUBINACA O-desmethyl acid – in blood samples, followed by verification of the method in toxicological judicial and forensic medicine practice employing the example of post-aggression suicide. Most likely in consequence of development of adverse effects resulting in psychotic symptoms, a male being under the influence of the synthetic cannabinoid AMB-FUBINACA and the new synthetic opioid U-47700, mortally wounded his female partner and subsequently committed suicide. Identification and determination of the afore-mentioned xenobiotics in blood samples collected from the male and female victims were performed employing high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The analytes were isolated from blood samples using the solid phase extraction (SPE) method. The blood samples collected from the male and female demonstrated respectively 110 and 196 ng/mL of AMB-FUBINACA O-desmethyl acid metabolite, 1935 and 357 ng/mL of U-47700, 250 and 200 ng/mL of N-desmethyl-U-47700, as well as 410 and 200 ng/mL of N,N-didesmethyl-U-47700. The concentration values of new psychoactive substances (NPS’s) in blood samples originating from the male and female were within the ranges encountered in cases of poisoning, including these resulting in death. Nevertheless, the evident signs of exsanguination proof that the woman was alive when she sustained lethal injuries. The presented cases illustrate the difficult to be anticipated effect exerted on the users by NPS’s.

Background and Purpose— Patients with acute cerebrovascular events are susceptible to serious cardiac arrhythmias, but data on the time course and the determinants of their onset are scarce. Methods— The prospective Stroke-Arrhythmia-Monitoring-Database (SAMBA) assessed cardiac arrhythmias with need for urgent evaluation and treatment in 501 acute neurovascular patients during the first 72 hours after admission to a monitored stroke unit. Arrhythmias were systematically detected by structured processing of telemetric data. Time of arrhythmia onset and predisposing factors were investigated. Results— Significant cardiac arrhythmias occurred in 25.1% of all patients. Incidence was highest during the first 24 hours after admission. Serious arrhythmic tachycardia (ventricular or supraventricular &gt;130 beats/min) was more frequent than bradycardic arrhythmia (sinus-node dysfunction, bradyarrhythmia, or atrioventricular block °II and °III). Arrhythmias were independently associated with higher age and severer neurological deficits as measured by the National Institutes of Health Stroke Scale on admission. Conclusions— The risk for significant cardiac arrhythmia after an acute cerebrovascular event is highest during the first 24 hours of care and declines with time during the first 3 days. Along with established vascular risk factors, the National Institutes of Health Stroke Scale may be considered for a stratified allocation of monitoring capabilities. Clinical Trial Registration— URL: www.clinicaltrials.gov . Unique identifier: NCT01177748.

Objective Oral anticoagulation treatment (OAT) resumption is a therapeutic dilemma in intracerebral hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought to determine whether OAT resumption after ICH is associated with long‐term outcome, accounting for ICH location (ie, lobar vs nonlobar). Methods We meta‐analyzed individual patient data from: (1) the multicenter RETRACE study (n = 542), (2) a U.S.‐based single‐center ICH study (n = 261), and (3) the Ethnic/Racial Variations of Intracerebral Hemorrhage study (n = 209). We determined whether, within 1 year from ICH, OAT resumption was associated with: (1) mortality, (2) favorable functional outcome (modified Rankin Scale = 0–3), and (3) stroke incidence. We separately analyzed nonlobar and lobar ICH cases using propensity score matching and Cox regression models. Results We included 1,012 OAT‐related ICH survivors (633 nonlobar and 379 lobar). Among nonlobar ICH survivors, 178/633 (28%) resumed OAT, whereas 86/379 (23%) lobar ICH survivors did. In multivariate analyses, OAT resumption after nonlobar ICH was associated with decreased mortality (hazard ratio [HR] = 0.25, 95% confidence interval [CI] = 0.14–0.44, p &lt; 0.0001) and improved functional outcome (HR = 4.22, 95% CI = 2.57–6.94, p &lt; 0.0001). OAT resumption after lobar ICH was also associated with decreased mortality (HR = 0.29, 95% CI = 0.17–0.45, p &lt; 0.0001) and favorable functional outcome (HR = 4.08, 95% CI = 2.48–6.72, p &lt; 0.0001). Furthermore, OAT resumption was associated with decreased all‐cause stroke incidence in both lobar and nonlobar ICH (both p &lt; 0.01). Interpretation These results suggest novel evidence of an association between OAT resumption and outcome following ICH, regardless of hematoma location. These findings support conducting randomized trials to explore risks and benefits of OAT resumption after ICH. Ann Neurol 2017;82:755–765

Objective To investigate parameters associated with hematoma enlargement in non–vitamin K antagonist oral anticoagulant (NOAC)‐related intracerebral hemorrhage (ICH). Methods This retrospective cohort study includes individual patient data for 190 patients with NOAC‐associated ICH over a 5‐year period (2011–2015) at 19 departments of neurology across Germany. Primary outcome was the association of prothrombin complex concentrate (PCC) administration with hematoma enlargement. Subanalyses were calculated for blood pressure management and its association with the primary outcome. Secondary outcomes include associations with in‐hospital mortality and functional outcome at 3 months assessed using the modified Rankin Scale. Results The study population for analysis of primary and secondary outcomes consisted of 146 NOAC‐ICH patients with available follow‐up imaging. Hematoma enlargement occurred in 49/146 (33.6%) patients with NOAC‐related ICH. Parameters associated with hematoma enlargement were blood pressure ≥ 160mmHg within 4 hours and—in the case of factor Xa inhibitor ICH—anti‐Xa levels on admission. PCC administration prior to follow‐up imaging was not significantly associated with a reduced rate of hematoma enlargement either in overall NOAC‐related ICH or in patients with factor Xa inhibitor intake (NOAC: risk ratio [RR] = 1.150, 95% confidence interval [CI] = 0.632–2.090; factor Xa inhibitor: RR = 1.057, 95% CI = 0.565–1.977), regardless of PCC dosage given or time interval until imaging or treatment. Systolic blood pressure levels &lt; 160mmHg within 4 hours after admission were significantly associated with a reduction in the proportion of patients with hematoma enlargement (RR = 0.598, 95% CI = 0.365–0.978). PCC administration had no effect on mortality and functional outcome either at discharge or at 3 months. Interpretation In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC‐related ICH. Our findings support the need of further investigations exploring new hemostatic reversal strategies for patients with factor Xa inhibitor–related ICH. Ann Neurol 2018;83:186–196

The purpose of this study was to analyze the effect of intraventricular fibrinolysis (IVF) compared with external ventricular drainage alone on mortality and functional outcome in the management of intraventricular hemorrhage secondary to spontaneous supratentorial intracerebral hemorrhage.The authors conducted a systematic review and performed a meta-analysis. They reviewed the PubMed, Cochrane Library, and Liliacs databases. In addition, they conducted a manual review of article bibliographies.Using a prespecified search strategy, 4 randomized and 8 observational studies were included in a meta-analysis. These studies involved a total of 316 patients with intraventricular hemorrhage at baseline, of whom 167 had IVF (52.8%). Pooled odds ratios of the impact of IVF on patient mortality, functional outcomes, and complications were calculated. The overall mortality risk decreased from 46.7% in the external ventricular drainage alone group to 22.7% in the external ventricular drainage+IVF group, corresponding to an overall pooled Peto OR of 0.32 (95% CI, 0.19 to 0.52). This result was highly significant with urokinase, not with recombinant tissue-type plasminogen activator. IVF was also associated with an increase in good functional outcome. There was no difference between the 2 groups in terms of shunt dependence and complications.The combination of IVF and external ventricular drainage in the management of severe intraventricular hemorrhage secondary to small intracerebral hemorrhage in young patients was associated with better survival and functional outcome results. Urokinase and recombinant tissue-type plasminogen activator could not have the same therapeutic effects. Well-designed randomized trials with special considerations to the fibrinolytic agents are needed.

The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established.To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH.Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015).Surgical hematoma evacuation vs conservative treatment.The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH.Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% [P = .003]; ARD, -34.7% [-38.8% to -30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02).Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.

To determine demographic characteristics, clinical features, treatment regimens, and outcome of myasthenic crisis (MC) requiring mechanical ventilation (MV).Analysis of patients who presented with MC between 2006 and 2015 in a German multicenter retrospective study.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.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.

&lt;b&gt;&lt;i&gt;Background and Purpose:&lt;/i&gt;&lt;/b&gt; Stroke-associated immunosuppression and inflammation are increasingly recognized as factors that trigger infections and thus, potentially influence the outcome after stroke. Several studies demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes in patients with ischemic stroke. However, little is known about the impact of NLR on short-term mortality in intracerebral hemorrhage (ICH). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This observational study included 855 consecutive ICH-patients. Patient demographics, clinical, laboratory, and in-hospital measures as well as neuroradiological data were retrieved from institutional databases. Functional 3-months-outcome was assessed and categorized as favorable (modified Rankin Scale [mRS] 0-3) and unfavorable (mRS 4-6). We (i) studied the natural course of NLR in ICH, (ii) analyzed parameters associated with NLR on admission (NLROA), and (iii) evaluated the clinical impact of NLR on mortality and functional outcome. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The median NLROA of the entire cohort was 4.66 and it remained stable during the entire hospital stay. Patients with NLR ≥4.66 showed significant associations with poorer neurological status (National Institute of Health Stroke Scale [NIHSS] 18 [9-32] vs. 10 [4-21]; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), larger hematoma volume on admission (17.6 [6.9-47.7] vs. 10.6 [3.8-31.7] mL; &lt;i&gt;p&lt;/i&gt; = 0.001), and more frequently unfavorable outcome (mRS 4-6 at 3 months: 317/427 [74.2%] vs. 275/428 [64.3%]; &lt;i&gt;p&lt;/i&gt; = 0.002). Patients with an NLR under the 25th percentile (NLR &lt;2.606) - compared to patients with NLR &gt;2.606 - presented with a better clinical status (NIHSS 12 [5-21] vs. 15 [6-28]; &lt;i&gt;p&lt;/i&gt; = 0.005), lower hematoma volumes on admission (10.6 [3.6-30.1] vs. 15.1 [5.7-42.3] mL; &lt;i&gt;p&lt;/i&gt; = 0.004) and showed a better functional outcome (3 months mRS 0-3: 82/214 [38.3%] vs. 185/641 [28.9%]; &lt;i&gt;p&lt;/i&gt; = 0.009). Patients associated with high NLR (≥8.508 = above 75th-percentile) showed the worst neurological status on admission (NIHSS 21 [12-32] vs. 12 [5-23]; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), larger hematoma volumes (21.0 [8.6-48.8] vs. 12.2 [4.1-34.9] mL; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and higher proportions of unfavorable functional outcome at 3 months (mRS 4-6: 173/214 vs. 418/641; &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Further, NLR was linked to more frequently occurring infectious complications (pneumonia 107/214 vs. 240/641; &lt;i&gt;p&lt;/i&gt; = 0.001, sepsis: 78/214 vs. 116/641; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and increased c-reactive-protein levels on admission (&lt;i&gt;p&lt;/i&gt; &lt; 0.001; &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.064). Adjusting for the above-mentioned baseline confounders, multivariable logistic analyses revealed independent associations of NLROA with in-hospital mortality (OR 0.967, 95% CI 0.939-0.997; &lt;i&gt;p&lt;/i&gt; = 0.029). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; NLR represents an independent parameter associated with increased mortality in ICH patients. Stroke physicians should focus intensely on patients with increased NLR, as these patients appear to represent a population at risk for infectious complications and increased short-mortality. Whether these patients with elevated NLR may benefit from a close monitoring and specially designed therapies should be investigated in future studies.

Intracerebral hemorrhage (ICH) accounts for up to 15% of all strokes and is characterized by high rates of mortality and morbidity. The post-ICH brain injury can be distinguished in 1) primary, which are caused by disruption and mechanical deformation of brain tissue due to hematoma growth and 2) secondary, which are induced by microglia activation, mitochondrial dysfunction, neurotransmitter and inflammatory mediator release. Although these events typically lead to necrosis, the occurrence of programmed cell death has also been reported after ICH.We reviewed recent publications describing advance in pre- and clinic ICH research.At present, treatment of ICH patients is based on oral anticoagulant reversal, management of blood pressure and other medical complications. Several pre-clinical studies showed promising results and demonstrated that anti-oxidative and anti-inflammatory treatments reduced neuronal cell death, however, to date, all of these attempts have failed in randomized controlled clinical trials. Yet, the time frame of administration may be crucial in translation from animal to clinical studies. Furthermore, the latest pre-clinical research points toward the existence of other, apoptosisunrelated forms kinds of programmed cell death.Our review summarizes current knowledge of pathways leading to programmed cell death after ICH in addition to data from clinical trials. Some of the pre-clinical results have not yet demonstrated clinical confirmation, however they significantly contribute to our understanding of post-ICH pathology and can contribute to development of new therapeutic approaches, decreasing mortality and improving ICH patients' quality of life.

As common prognostication models in intracerebral hemorrhage (ICH) are developed variably including patients with early (<24 hours) care limitations (ECL), we investigated its interaction with prognostication in maximally treated patients and sought to provide a new unbiased severity assessment tool.This observational cohort study analyzed consecutive ICH patients (n = 583) from a prospective registry over 5 years. We characterized the influence of ECL on overall outcome by propensity score matching and on conventional prognostication using receiver operating characteristic analyses. We established the max-ICH score based on independent predictors of 12-month functional outcome in maximally treated patients and compared it to existing models.Prevalence of ECL was 19.2% (n = 112/583) and all of these patients died. Yet propensity score matching displayed that 50.7% (n = 35/69) theoretically could have survived, with 18.8% (n = 13/69) possibly reaching favorable outcome (modified Rankin Scale score 0-3). Conventional prognostication seemed to be confounded by ECL, documented by a decreased predictive validity (area under the curve [AUC] 0.67, confidence interval [CI] 0.61-0.73 vs AUC 0.80, CI 0.76-0.83; p < 0.01), overestimating poor outcome (mortality by 44.8%, unfavorable outcome by 10.1%) in maximally treated patients. In these patients, the novel max-ICH score (0-10) integrates strength-adjusted predictors, i.e., NIH Stroke Scale score, age, intraventricular hemorrhage, anticoagulation, and ICH volume (lobar and nonlobar), demonstrating improved predictive accuracy for functional outcome (12 months: AUC 0.81, CI 0.77-0.85; p < 0.01). The max-ICH score may more accurately delineate potentials of aggressive care, showing favorable outcome in 45.4% (n = 214/471) and a long-term mortality rate of only 30.1% (n = 142/471).Care limitations significantly influenced the validity of common prognostication models resulting in overestimation of poor outcome. The max-ICH score demonstrated increased predictive validity with minimized confounding by care limitations, making it a useful tool for severity assessment in ICH patients.

Stroke-associated immunosuppression and inflammation are increasingly recognized as factors triggering infections and thus potentially influencing outcome after stroke. Several studies have demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes for patients with ischemic stroke or intracerebral hemorrhage. Thus far, in patients with subarachnoid hemorrhage the association between NLR and outcome is insufficiently established. The authors sought to investigate the association between NLR on admission and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH).This observational study included all consecutive aSAH patients admitted to a German tertiary center over a 5-year period (2008-2012). Data regarding patient demographics and clinical, laboratory, and in-hospital measures, as well as neuroradiological data, were retrieved from institutional databases. Functional outcome was assessed at 3 and 12 months using the modified Rankin Scale (mRS) score and categorized into favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Patients' radiological and laboratory characteristics were compared between aSAH patients with favorable and those with unfavorable outcome at 3 months. In addition, multivariate analysis was conducted to investigate parameters independently associated with favorable outcome. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the best cutoff for NLR to discriminate between favorable and unfavorable outcome in these patients. To account for imbalances in baseline characteristics, propensity score matching was carried out to assess the influence of NLR on outcome measures.Overall, 319 patients with aSAH were included. Patients with unfavorable outcome at 3 months were older, had worse clinical status on admission (Glasgow Coma Scale score and Hunt and Hess grade), greater amount of subarachnoidal and intraventricular hemorrhage (modified Fisher Scale grade and Graeb score), and higher rates of infectious complications (pneumonia and sepsis). A significantly higher NLR on admission was observed in patients with unfavorable outcome according to mRS score (median [IQR] NLR 5.8 [3.0-10.0] for mRS score 0-2 vs NLR 8.3 [4.5-12.6] for mRS score 3-6; p < 0.001). After adjustments, NLR on admission remained a significant predictor for unfavorable outcome in SAH patients (OR [95% CI] 1.014 [1.001-1.027]; p = 0.028). In ROC analysis, an NLR of 7.05 was identified as the best cutoff value to discriminate between favorable and unfavorable outcome (area under the curve = 0.614, p < 0.001, Youden's index = 0.211; mRS score 3-6: 94/153 [61.4%] for NLR ≥ 7.05 vs 67/166 [40.4%] for NLR < 7.05; p < 0.001). Subanalysis of patients with NLR levels ≥ 7.05 vs < 7.05, performed using 2 propensity score-matched cohorts (n = 133 patients in each group), revealed an increased proportion of patients with unfavorable functional outcome at 3 months in patients with NLR ≥ 7.05 (mRS score 3-6 at 3 months: NLR ≥ 7.05 82/133 [61.7%] vs NLR < 7.05 62/133 [46.6%]; p = 0.014), yet without differences in mortality at 3 months (NLR ≥ 7.05 37/133 [27.8%] vs NLR < 7.05 27/133 [20.3%]; p = 0.131).Among aSAH patients, NLR represents an independent parameter associated with unfavorable functional outcome. Whether the impact of NLR on functional outcome is related to preexisting comorbidities or represents independent causal relationships in the context of stroke-associated immunosuppression should be investigated in future studies.

To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up.A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method.Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27-0.74, p = 0.002) and no-ATM (RR = 0.47, 95% CI 0.29-0.77, p = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA: RR = 1.34, 95% CI 0.79-2.30, p = 0.28; VKA vs no-ATM: RR = 0.93, 95% CI 0.45-1.90, p = 0.84).In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.

<h3>Objective</h3> To evaluate the association of perihemorrhagic edema (PHE) evolution and peak edema extent with day 90 functional outcome in patients with intracerebral hemorrhage (ICH) and identify pathophysiologic factors influencing edema evolution. <h3>Methods</h3> This retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. ICH and PHE volumes were studied using a validated semiautomatic volumetric algorithm. Multivariable logistic regression and propensity score matching (PSM) accounting for age, ICH volume, and location were used for assessing measures associated with functional outcome and PHE evolution. Clinical outcome on day 90 was assessed using the modified Rankin Scale (0–3 = favorable, 4–6 = poor). <h3>Results</h3> 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). Besides established factors for functional outcome, i.e., ICH volume and location, age, intraventricular hemorrhage, and NIH Stroke Scale score on admission, multivariable logistic regression revealed peak PHE volume (odds ratio [OR] 0.984 [95% confidence interval (CI) 0.973–0.994]) as an independent predictor of day 90 outcome. Peak PHE volume was independently associated with initial PHE increase up to day 3 (OR 1.060 [95% CI 1.018–1.103]) and neutrophil to lymphocyte ratio on day 6 (OR 1.236 [95% CI 1.034–1.477; PSM cohort, n = 124]). Initial PHE increase (PSM cohort, n = 224) was independently related to hematoma expansion (OR 3.647 [95% CI 1.533–8.679]) and fever burden on days 2–3 (OR 1.456 [95% CI 1.103–1.920]). <h3>Conclusion</h3> Our findings suggest that peak PHE volume represents an independent predictor of functional outcome after ICH. Inflammatory processes and hematoma expansion seem to be involved in PHE evolution and may represent important treatment targets.

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.

To assess intensive care unit (ICU) complications, their management, and prognostic factors associated with outcomes in a cohort of patients with autoimmune encephalitis (AE).This study was an observational multicenter registry of consecutively included patients diagnosed with AE requiring Neuro-ICU treatment between 2004 and 2016 from 18 tertiary hospitals. Logistic regression models explored the influence of complications, their management, and diagnostic findings on the dichotomized (0-3 vs 4-6) modified Rankin Scale score at hospital discharge.Of 120 patients with AE (median age 43 years [interquartile range 24-62]; 70 females), 101 developed disorders of consciousness, 54 autonomic disturbances, 42 status epilepticus, and 39 severe sepsis. Sixty-eight patients were mechanically ventilated, 85 patients had detectable neuronal autoantibodies, and 35 patients were seronegative. Worse neurologic outcome at hospital discharge was associated with necessity of mechanical ventilation (sex- and age-adjusted OR 6.28; 95% CI, 2.71-15.61) tracheostomy (adjusted OR 6.26; 95% CI, 2.68-15.73), tumor (adjusted OR 3.73; 95% CI, 1.35-11.57), sepsis (adjusted OR 4.54; 95% CI, 1.99-10.43), or autonomic dysfunction (adjusted OR 2.91; 95% CI, 1.24-7.3). No significant association was observed with autoantibody type, inflammatory changes in CSF, or pathologic MRI.In patients with AE, mechanical ventilation, sepsis, and autonomic dysregulation appear to indicate longer or incomplete convalescence. Classic ICU complications better serve as prognostic markers than the individual subtype of AE. Increased awareness and effective management of these AE-related complications are warranted, and further prospective studies are needed to confirm our findings and to develop specific strategies for outcome improvement.

It is unestablished whether andexanet alfa, compared with guideline-based usual care including prothrombin complex concentrates, is associated with reduced hematoma expansion (HE) and mortality in patients with factor-Xa inhibitor-related intracerebral hemorrhage (ICH). We compared the occurrence of HE and clinical outcomes in patients treated either with andexanet alfa or with usual care during the acute phase of factor-Xa inhibitor-related ICH.Data were extracted from the multicenter, prospective, single-arm ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) and a multicenter observational cohort study, RETRACE-II (German-Wide Multicenter Analysis of Oral Anticoagulant-Associated Intracerebral Hemorrhage - Part Two). HE was based on computed tomography scans performed within 36 hours from baseline imaging. Inverse probability of treatment weighting was performed to adjust for baseline comorbidities and ICH severity. Patients presenting with atraumatic ICH while receiving apixaban or rivaroxaban within 18 hours of admission were included. Patients with secondary ICH or not fulfilling the inclusion criteria for the ANNEXA-4 trial were excluded. We compared ANNEXA-4 patients, who received andexanet alfa for hemostatic treatment, with RETRACE-II patients who were treated with usual care, primarily administration of prothrombin complex concentrates. Primary outcome was rate of HE defined as relative increase of ≥35%. Secondary outcomes comprised mean absolute change in hematoma volume, as well as in-hospital mortality and functional outcome.Overall, 182 patients with factor-Xa inhibitor-related ICH (85 receiving andexanet alfa versus 97 receiving usual care) were selected for analysis. There were no relevant differences regarding demographic or clinical characteristics between both groups. HE occurred in 11 of 80 (14%) andexanet alfa patients compared with 21 of 67 (36%) usual care patients (adjusted relative risk, 0.40 [95% CI, 0.20-0.78]; P=0.005), with a reduction in mean overall hematoma volume change of 7 mL. There were no statistically significant differences among in-hospital mortality or functional outcomes. Sensitivity analysis including only usual care patients receiving prothrombin complex concentrates demonstrated consistent results.As compared with usual care, andexanet alfa was associated with a lower rate of HE in atraumatic factor-Xa inhibitor-related ICH, however, without translating into significantly improved clinical outcomes. A comparative trial is needed to confirm the benefit on limiting HE and to explore clinical outcomes across patient subgroups and by time to treatment. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT02329327 and NCT03093233.

While intravenous recombinant tissue plasminogen activator (rt-PA) has been approved for acute stroke therapy within 3 hours, the optimum management of basilar artery occlusion (BAO) is still a matter of debate. We compared intraarterial thrombolysis with the combined bridging approach of intravenous abciximab and intraarterial thrombolysis with rt-PA (bridging therapy) in an observational, longitudinal, monocenter study.Between 1998 and 2006, information for 106 patients with acute BAO were prospectively entered into a local database. Patients eligible for treatment received either intraarterial thrombolysis with rt-PA alone (intraarterial thrombolysis) or were treated with intravenous abciximab and intraarterial rt-PA (bridging therapy). Outcome parameters were recanalization of the basilar artery according to Trial in Myocardial Infarction criteria, survival, and reduction of severe disability and death at 3 months. Logistic regression was used to identify independent predictors for recanalization, survival, and clinical outcome.Of a total of 106 patients with confirmed BAO, 87 patients underwent subsequent angiography. Among those, 75 patients were identified who received the full treatment protocol. Patients in the bridging group had a better recanalization rate (83.7% vs 62.5%; P=0.03), a higher survival rate (58.1% vs 25%; P=0.01), and a better chance for an outcome with no or only mild to moderate disability (modified Rankin Scale score, 0-3; 34.9% vs 12.5%; P=0.02). Symptomatic intracerebral hemorrhage rates were comparable in both groups (14% in the bridging group vs 18.8%; P=0.41). Independent predictors for recanalization were age (OR, 0.95; 95% CI, 0.91-0.99), atrial fibrillation (OR, 6.53; 95% CI, 1.14-37.49), and bridging therapy (OR, 3.37; 95% CI, 1.02 to 11.18). Independent prognostic factors for outcome were Glasgow coma scale score at presentation (OR, 1.24; 95% CI, 1.03-1.45) and the combination of bridging therapy with successful recanalization (OR, 3.744; 95% CI, 1.04-13.43).Bridging therapy for acute BAO with intravenous abciximab and intraarterial rt-PA appears to be safe and yields higher recanalization and improved survival rates, as well as an overall improved chance for a better outcome.

Surgical management of space-occupying cerebellar infarction is still controversial. Data on long-term outcome are lacking. The objective of this study was (1) to evaluate outcome after at least 3 years poststroke in patients with space-occupying cerebellar infarction treated by ventriculostomy/extraventricular drainage (EVD) or suboccipital decompressive craniectomy (SDC), or both, and (2) to determine predicting factors for outcome.In this retrospective single-center study 56 consecutive patients with acute space-occupying cerebellar infarction treated surgically between 1996 and 2005 were included. Baseline data included clinical findings, Glasgow Coma Scale on admission and before surgery, NIHSS on admission, mass effects on neuroimaging, and surgical treatment strategies. Modified Rankin Scale, NIHSS, and Scale for the Assessment and Rating of Ataxia were used to assess outcome.39.3% of patients had died, 51.8% had a mRS < or =3, 35.7% had a mRS < or =2, 28.6% had a mRS < or =1. There were no significant differences in survival between treatment groups. In multivariate analysis age and mRS score at discharge were the most evident independent predictors for outcome.So far this is the largest study on long-term outcome after space-occupying cerebellar infarction. The value of different treatment strategies and prognostic factors for patient selection remain unclear and should be evaluated in larger prospective case-series or registries. To investigate the issue of preventive SDC randomized trials are needed.

Thrombolytic therapy is frequently withheld in patients with minor stroke symptoms. However, recent studies demonstrate that a substantial proportion of these patients dies or remains permanently disabled because of underestimation of symptom severity at baseline or secondary deterioration. We aimed to assess the safety and outcome of thrombolysis therapy in patients with minor but disabling stroke symptoms.32 patients presenting with mild symptoms were treated with intravenous recombinant tissue-type plasminogen activator between April 2006 and April 2008. Data were extracted from a prospectively collected database. Baseline demographic data, and clinical, laboratory and imaging findings were analyzed. Outcome was assessed using the modified Rankin Scale (mRS) score at 3 months and was dichotomized into favorable (mRS 0-1) versus unfavorable (mRS 2-6).In the majority of patients, the left hemisphere was affected, with aphasia representing the most common symptom leading to treatment decision. The frequency of perfusion lesion (46%) and vessel occlusion (35%) at baseline was high but had no effect on the outcome at 3 months in our series of treated patients. Outcome was favorable in 94% of patients, and 47% recovered without any persisting symptom. Only one asymptomatic and no symptomatic hemorrhage was observed.Our data support current guidelines and international licenses which give no lower National Institutes of Health Stroke Scale (NIHSS) limit for intravenous thrombolysis (IVT). Considering the accumulating evidence that the natural course in patients with mild symptoms is not as favorable as often assumed and taking the low risk of bleeding in those patients into account, patients with mild but disabling symptoms should be treated with IVT regardless of their baseline NIHSS score.

Both intraventricular fibrinolysis (IVF) and lumbar drainage (LD) may reduce the need for exchange of external ventricular drainage (EVD) and shunt surgery in patients with intracerebral hemorrhage and severe intraventricular hemorrhage. We investigated the feasibility and safety of IVF followed by early LD for the treatment of posthemorrhagic hydrocephalus.This prospective study included patients with spontaneous ganglionic intracerebral hemorrhage and severe intraventricular hemorrhage with acute obstructive posthemorrhagic hydrocephalus who received an EVD (n=32). The treatment algorithm started with IVF (4 mg recombinant tissue plasminogen activator every 12 hours) until clearance of the third and fourth ventricles from blood. Thereupon, EVD was clamped and if clamping was unsuccessful, communicating posthemorrhagic hydrocephalus was assumed and LD placed. EVD was removed if there was neither an increase of intracranial pressure nor ventricle enlargement on CT. A ventriculoperitoneal shunt was indicated if "LD weaning" was unsuccessful for >10 days. Outcome was assessed at 90 and 180 days using the modified Rankin Scale.IVF resulted in fast clearance of the third and fourth ventricles (73+/-50 hours). However, early EVD removal was only possible in 4 patients. The remaining 28 patients developed communicating posthemorrhagic hydrocephalus. In all of these patients, early LD was capable to replace EVD. EVD exchange was not necessary and EVD duration was 105+/-59 hours. Only one patient required a ventriculoperitoneal shunt. At 180 days, 20 (62.5%) patients had a good (modified Rankin Scale 0 to 3) outcome and 5 (15.6%) patients had died. One patient had asymptomatic ventricular rebleeding.In patients with secondary intraventricular hemorrhage and posthemorrhagic hydrocephalus, the combined treatment approach of IVF and early LD is safe and feasible, avoids EVD exchange, and may markedly reduce the need for shunt surgery.

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.

Delayed cerebral infarction (DCI) has a significant impact on mortality and morbidity of patients with subarachnoid hemorrhage (SAH). The aim of this study was to define quantitative EEG (qEEG) parameters for the early and reliable prediction of DCI and compare the validity and time course of qEEG to standard procedures. 12 consecutive unselected SAH patients (8 female, mean age 52 years, Hunt-and-Hess grade I–IV) were prospectively examined. Continuous six channel EEG monitoring was started within 48 h after admission (mean duration 5.2 days; range: 2–12 days). All raw and unselected EEG signal underwent automated artifact rejection, Short Time Fast Fourier Transformation and a detrending procedure in order to analyze regional spectral power changes in different frequency bands. According to clinical standards, transcranial Doppler sonography (TCD) was performed at least on alternate days and repeat cerebral computer tomography (CCT) as needed. 6 patients (50%) developed vasospasm/DCI. Decrease of ⩾40% in power persisting over ⩾5 h in the alpha band and ⩾6 h in the theta band marked the optimal cut-off to detect DCI (sensitivity 89%, specificity 77% for alpha). EEG changes preceded detection of vasospasm/DCI in standard procedures by 2.3 days. Changes in the beta and delta band as well as in the alpha/delta ratio demonstrated lower correlation with imminent DCI. Focal reduction in alpha power may represent a valid, observer independent, non-invasive and continuous marker for vasospasm/DCI in SAH patients. qEEG indicates imminent ischemia earlier than established diagnostic tools, such as TCD.

Background Intravenous thrombolysis for acute stroke is more efficient the earlier the treatment is initiated. In-hospital delays account for a significant proportion of avoidable time loss before treatment is initiated. Paradoxically, studies have reported longer door-to-needle times the earlier the patients arrive (‘three-hour effect’). Hypothesis We hypothesized that a standardized thrombolysis procedure carried out in a specialized neurological emergency room can minimize in-hospital delays and erase the ‘three-hour effect’. Methods Onset-to-door and door-to-needle times of 246 consecutive thrombolysis patients were analyzed. A standardized protocol designed to minimize in-hospital delays was tested using a resident-based stroke team within a neurological emergency room. Correlation of onset-to-door and door-to-needle times was measured as well as differences in treatment times for daytime versus night hours and weekend vs. weekday. Outcome, rate of symptomatic intracranial hemorrhage and mortality were compared with the results of SITS-MOST. Results Median door-to-needle time was 25 min compared with a mean of 68 min in SITS-MOST. door-to-needle time did not correlate with onset-to-door time (Pearson's r=−0·097; P=0·13) and patients arriving within 90 min from symptom onset showed comparable door-to-needle times with patients arriving within 90–180 min. Neither treatment on weekends nor during night hours led to significant in-hospital treatment delays. Outcome and safety parameters were comparable with those observed in SITS-MOST. Conclusions By applying a standardized and diligently monitored thrombolysis protocol, carried out by a specialized stroke team within a neurological emergency room, in-hospital delays can be minimized. This allows improvement of door-to-needle times irrespective of the time to arrival and treatment during off-hours.

Hyponatremia is the most frequent electrolyte disturbance in critical care. Across various disciplines, hyponatremia is associated with increased mortality and longer hospital stay, yet in intracerebral hemorrhage (ICH) no data are available. This the first study that investigated the prevalence and clinical associations of hyponatremia in patients with ICH.This observational study included all consecutive spontaneous ICH patients (n=464) admitted during a 5-year period to the Department of Neurology. Patient characteristics, in-hospital measures, mortality, and functional outcome (90 days and 1 year) were analyzed to determine the effects of hyponatremia (Na<135 mEq/L). Multivariable regression analyses were calculated for factors associated with hyponatremia and predictors of in-hospital mortality.The prevalence of hyponatremia on hospital admission was 15.6% (n=66). Normonatremia was achieved and maintained in almost all hyponatremia patients<48 hours. In-hospital mortality was roughly doubled in hyponatremia compared with nonhyponatremia patients (40.9%; n=27 versus 21.1%; n=75), translating into a 2.5-fold increased odds ratio (P<0.001). Multivariable analyses identified hyponatremia as an independent predictor of in-hospital mortality (odds ratio, 2.2; 95% confidence interval, 1.05-4.62; P=0.037). Within 90 days after ICH, hyponatremia patients surviving hospital stay were also at greater risk of death (odds ratio, 4.8; 95% confidence interval, 2.1-10.6; P<0.001); thereafter, mortality rates were similar.Hyponatremia was identified as an independent predictor of in-hospital mortality with a fairly high prevalence in spontaneous ICH patients. The presence of hyponatremia at hospital admission is related to an increased short-term mortality in patients surviving acute care, possibly reflecting a preexisting condition that is linked to worse outcome due to greater comorbidity. Correction of hyponatremia does not seem to compensate its influence on mortality, which strongly warrants future research.

Objective Intraventricular hemorrhage (IVH) is a negative prognostic factor in intracerebral hemorrhage (ICH) and is associated with permanent shunt dependency in a substantial proportion of patients post‐ICH. IVH treatment by intraventricular fibrinolysis (IVF) was recently linked to reduced mortality rates in the CLEAR III study and IVF represents a safe and effective strategy to hasten clot resolution that may reduce shunt rates. Additionally, promising results from observational studies reported reductions in shunt dependency for a combined treatment approach of IVF plus lumbar drains (LDs). The present randomized, controlled trial investigated efficacy and safety of a combined strategy—IVF plus LD versus IVF alone—on shunt dependency in patients with ICH and severe IVH. Methods This randomized, open‐label, parallel‐group study included patients aged 18 to 85 years, prehospital modified Rankin Scale ≤3, ICH volume &lt; 60ml, Glasgow Coma Scale of &lt;9, and severe IVH with tamponade of the third and fourth ventricles requiring placement of external ventricular drainage (EVD). Over a 3‐year recruitment period, patients were allocated to either standard treatment (control group receiving IVF consisting of 1mg of recombinant human tissue plasminogen activator every 8 hours until clot clearance of third and fourth ventricles) or a combined treatment approach of IVF and—upon clot clearance of third and fourth ventricles—subsequent placement of an LD for drainage of cerebrospinal fluid (CSF; intervention group). The primary endpoint consisted of permanent shunt placement indicated after a total of three unsuccessful EVD clamping attempts or need for CSF drainage longer than 14 days in both groups. Secondary endpoints included IVF‐ and LD‐related safety, such as bleeding or infections, and functional outcome at 90 and 180 days. Conducted endpoint analyses used individual patient data meta‐analyses. The study was registered at clinicaltrials.gov (NCT01041950). Results The trial was stopped upon predefined interim analysis after 30 patients because of significant efficacy of tested intervention. The primary endpoint was analyzed without dropouts and was reached in 43% (7 of 16) of the control group versus 0% (0 of 14) of the intervention group ( p = 0.007). Meta‐analyses were based on overall 97 patients, 45 patients receiving IVF plus LD versus 42 with IVF only. Meta‐analyses on shunt dependency showed an absolute risk reduction of 24% for the intervention (LD, 2.2% [1 of 45] vs no‐LD, 26.2% [11 of 42]; odds ratio [OR] = 0.062; confidence interval [CI], 0.011–0.361; p = 0.002). Secondary endpoints did not show significant differences for CSF infections (OR = 0.869;CI, 0.445–1.695; p = 0.680) and functional outcome at 90 days (OR = 0.478; CI, 0.190–1.201; p = 0.116), yet bleeding complications were significantly reduced in favor of the intervention (OR = 0.401; CI, 0.302–0.532; p &lt; 0.001). Interpretation The present trial and individual patient data meta‐analyses provide evidence that, in patients with severe IVH, as compared to IVF alone, a combined approach of IVF plus LD treatment is feasible and safe and significantly reduces rates of permanent shunt dependency for aresorptive hydrocephalus post‐ICH. ANN NEUROL 2017;81:93–103

In light of an aging population with increased cardiovascular comorbidity, the use of oral anticoagulation (OAC) is steadily expanding. A variety of pharmacological alternatives to vitamin K antagonists (VKA) have emerged over recent years (direct oral anticoagulants, DOAC, i.e., dabigatran, rivaroxaban, apixaban, and edoxaban) which show a reduced risk for the occurrence of intracerebral hemorrhage (ICH). Yet, in the event of ICH under OAC (OAC-ICH), hematoma characteristics are similarly severe and clinical outcomes likewise substantially limited in both patients with VKA- and DOAC-ICH, which is why optimal acute hemostatic treatment in all OAC-ICH needs to be guaranteed. Currently, International Guidelines for the hemostatic management of patients with OAC-ICH are updated as several relevant large-sized observational studies and recent trials have established treatment approaches for both VKA- and DOAC-ICH. While the management of VKA-ICH is mainly based on the immediate reversal of elevated levels of international normalized ratio using prothrombin complex concentrates, hemostatic management of DOAC-associated ICH is challenging requiring specific antidotes, notably idarucizumab and andexanet alfa. This review will provide an overview of the latest studies and trials on hemostatic reversal agents and timing and summarizes the effects on hemorrhage progression and clinical outcomes in patients with OAC-ICH.

Background and Purpose— EG-1962 is a sustained release formulation of nimodipine administered via external ventricular drain in patients with aneurysmal subarachnoid hemorrhage. A randomized, open-label, phase 1/2a, dose-escalation study provided impetus for this study to evaluate efficacy and safety of a single intraventricular 600 mg dose of EG-1962 to patients with aneurysmal subarachnoid hemorrhage, compared with standard of care oral nimodipine. Methods— Subjects were World Federation of Neurological Surgeons grades 2–4, modified Fisher grades 2–4 and had an external ventricular drain inserted as part of standard of care. The primary end point was the proportion of subjects with favorable outcome at day 90 after aneurysmal subarachnoid hemorrhage (extended Glasgow outcome scale 6–8). The proportion of subjects with favorable outcome at day 90 on the Montreal cognitive assessment, as well as the incidence of delayed cerebral ischemia and infarction, use of rescue therapy and safety were evaluated. Results— The study was halted by the independent data monitoring board after planned interim analysis of 210 subjects (289 randomized) with day 90 outcome found the study was unlikely to achieve its primary end point. After day 90 follow-up of all subjects, the proportion with favorable outcome on the extended Glasgow outcome scale was 45% (65/144) in the EG-1962 and 42% (62/145) in the placebo group (risk ratio, 1.01 [95% CI, 0.83–1.22], P =0.95). Consistent with its mechanism of action, EG-1962 significantly reduced vasospasm (50% [69/138] EG-1962 versus 63% [91/144], P =0.025) and hypotension (7% [9/138] versus 10% [14/144]). Analysis of prespecified subject strata suggested potential efficacy in World Federation of Neurological Surgeons 3–4 subjects (46% [32/69] EG-1962 versus 32% [24/75] placebo, odds ratio, 1.22 [95% CI, 0.94–1.58], P =0.13). No safety concerns were identified that halted the study or that preclude further development. Conclusions— There was no significant increase in favorable outcome for EG-1962 compared with standard of care in the overall study population. The safety profile was acceptable. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02790632.

Abstract Background Approximately half of patients with spontaneous intracerebral hemorrhage (ICH) die within 1 year. Prognostication in this context is of great importance, to guide goals of care discussions, clinical decision-making, and risk stratification. However, available prognostic scores are hardly used in clinical practice. The purpose of this review article is to identify existing outcome prediction scores for spontaneous intracerebral hemorrhage (ICH) discuss their shortcomings, and to suggest how to create and validate more useful scores. Main text Through a literature review this article identifies existing ICH outcome prediction models. Using the Essen-ICH-score as an example, we demonstrate a complete score validation including discrimination, calibration and net benefit calculations. Score performance is illustrated in the Erlangen UKER-ICH-cohort (NCT03183167). We identified 19 prediction scores, half of which used mortality as endpoint, the remainder used disability, typically the dichotomized modified Rankin score assessed at variable time points after the index ICH. Complete score validation by our criteria was only available for the max-ICH score. Our validation of the Essen-ICH-score regarding prediction of unfavorable outcome showed good discrimination (area under the curve 0.87), fair calibration (calibration intercept 1.0, slope 0.84), and an overall net benefit of using the score as a decision tool. We discuss methodological pitfalls of prediction scores, e.g. the withdrawal of care (WOC) bias, physiological predictor variables that are often neglected by authors of clinical scores, and incomplete score validation. Future scores need to integrate new predictor variables, patient-reported outcome measures, and reduce the WOC bias. Validation needs to be standardized and thorough. Lastly, we discuss the integration of current ICH scoring systems in clinical practice with the awareness of their shortcomings. Conclusion Presently available prognostic scores for ICH do not fulfill essential quality standards. Novel prognostic scores need to be developed to inform the design of research studies and improve clinical care in patients with ICH.

Several automated computed tomography perfusion software applications have been developed to provide support in the definition of ischemic core and penumbra in acute ischemic stroke. However, the degree of interchangeability between software packages is not yet clear. Our study aimed to evaluate 2 commonly used automated perfusion software applications (Syngo.via and RAPID) for the indication of ischemic core with respect to the follow-up infarct volume (FIV) after successful recanalization and with consideration of the clinical impact.Retrospectively, 154 patients with large vessel occlusion of the middle cerebral artery or the internal carotid artery, who underwent endovascular therapy with a consequent Thrombolysis in Cerebral Infarction 3 result within 2 hours after computed tomography perfusion, were included. Computed tomography perfusion core volumes were assessed with both software applications with different thresholds for relative cerebral blood flow (rCBF). The results were compared with the FIV on computed tomography within 24 to 36 hours after recanalization. Bland-Altman was applied to display the levels of agreement and to evaluate systematic differences.Highest correlation between ischemic core volume and FIV without significant differences was found at a threshold of rCBF<38% for the RAPID software (r=0.89, P<0.001) and rCBF<25% for the Syngo software (r=0.87, P<0.001). Bland-Altman analysis revealed best agreement in these settings. In the vendor default settings (rCBF<30% for RAPID and rCBF<20% for Syngo) correlation between ischemic core volume and FIV was also high (RAPID: r=0.88, Syngo: r=0.86, P<0.001), but mean differences were significant (P<0.001). The risk of critical overestimation of the FIV was higher with rCBF<38% (RAPID) and rCBF<25% (Syngo) than in the default settings.By adjusting the rCBF thresholds, comparable results with reliable information on the FIV after complete recanalization can be obtained both with the RAPID and Syngo software. Keeping the software specific default settings means being more inclusive in patient selection, but forgo the highest possible accuracy in the estimation of the FIV.

The objective was to analyze the feasibility of a lumbar drainage (LD) for a communicating malresorptive hydrocephalus in patients with supratentorial hemorrhage (intracerebral hemorrhage) accompanied by severe ventricular involvement (intraventricular hemorrhage) who required an external ventricular drain (EVD).In this retrospective study, 16 patients received an EVD and concurrent LD and were compared with 39 historical patients treated with EVD alone. The duration of required EVD and need for permanent ventriculoperitoneal-shunt were analyzed.LD was inserted after 12 (4 to 18) days. In LD-treated patients, the LD was capable to replace repeated EVD exchanges, resulting in a shorter EVD-duration (12 versus 16 days) compared with patients treated with EVD alone. The overall duration of extracorporal cerebrospinal fluid drainage was longer (16 days EVD versus 21 days EVD+LD) and the frequency of ventriculoperitoneal-shunt lower (18.75% versus 33%; P<0.03) in LD-treated patients.Our data suggest that LD is safe and feasible for treatment of nonpersistent communicating hydrocephalus after intracerebral hemorrhage. After adequate treatment of the occlusive hydrocephalus using an EVD in the acute phase, LD discloses an alternative for further extracorporal cerebrospinal fluid drainage.

Aims We analyzed early diffusion-weighted magnetic resonance imaging of patients with acute basilar artery occlusion by applying different lesion scoring systems and determined their predictive value for favorable outcome. Methods Between 1998 and 2010, patients with confirmed basilar artery occlusion were entered in a local database. magnetic resonance imaging angiography was performed for diagnosis of basilar artery occlusion and/or during initiated recanalization therapy. We analyzed the patients’ clinical and radiological baseline data, recanalization, and favorable outcome modified Rankin Scale 0–2 after three-months. Diffusion weighted imaging findings were categorized into lesions in vascular territories as well as by two previously published scores for ischemic damage in the posterior circulation, the Renard score and posterior circulation Acute Stroke Prognosis Early computed tomography Score. Results Fifty patients with basilar artery occlusion received an early MRI, and in 30 of those, a follow-up MRI was performed. Median time to baseline MRI was 5·5 h (one-hour to 24 h). Median baseline Renard score and posterior circulation Acute Stroke Prognosis Early CT Score were 2·75 (0–10) and 7 (0–10), respectively. Of the patients, 82% received an acute recanalization therapy and in 78% of those, the basilar artery recanalized. Median time to therapy was five-hours (1·25–20 h). 24% of all patients had a favorable outcome (mRS 0–2). Patients with a favorable outcome had a lower Renard score and higher pcASPECTS, a lower rate of complete basilar artery occlusion, a higher Glasgow coma scale on admission, and a higher rate of successful recanalization (all P &lt; 0·05). After logistic regression, the only independent predictor for favorable outcome was a posterior circulation Acute Stroke Prognosis Early CT Score of 8 or more points (odds ratio 3·9, 95% confidence interval 1·4–11·7, P &lt; 0·05). Conclusion In patients with acute basilar artery occlusion, posterior circulation Acute Stroke Prognosis Early CT Score of 8 or more points on early diffusion weighted imaging is an independent predictor for favorable outcome.

There are only limited data on the long-term outcome of patients receiving specialized neurocritical care. In this study we analyzed survival, long-term mortality and functional outcome after neurocritical care and determined predictors for good functional outcome.We retrospectively investigated 796 consecutive patients admitted to a non-surgical neurologic intensive care unit over a period of two years (2006 and 2007). Demographic and clinical parameters were analyzed. Depending on the diagnosis, we grouped patients according to their diseases (cerebral ischemia, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), meningitis/encephalitis, epilepsy, Guillain-Barré syndrome (GBS) and myasthenia gravis (MG), neurodegenerative diseases and encephalopathy, cerebral neoplasm and intoxication). Clinical parameters, mortality and functional outcome of all treated patients were analyzed. Functional outcome (using the modified Rankin Scale, mRS) one year after discharge was assessed by a mailed questionnaire or telephone interview. Outcome was dichotomized into good (mRS ≤ 2) and poor (mRS ≥ 3). Logistic regression analyses were calculated to determine independent predictors for good functional outcome.Overall in-hospital mortality amounted to 22.5% of all patients, and a good long-term functional outcome was achieved in 28.4%. The parameters age, length of ventilation (LOV), admission diagnosis of ICH, GBS/MG, and inoperable cerebral neoplasm as well as Therapeutic Intervention Scoring System (TISS)-28 on Day 1 were independently associated with functional outcome after one year.This investigation revealed that age, LOV and TISS-28 on Day 1 were strongly predictive for the outcome. The diagnoses of hemorrhagic stroke and cerebral neoplasm leading to neurocritical care predispose for functional dependence or death, whereas patients with GBS and MG are more likely to recover after neurocritical care.

<h3>Background and objective:</h3> Intraventricular hemorrhage often leads to obstructive hydrocephalus, necessitating placement of extraventricular drainage to prevent increasing intracranial pressure and subsequent herniation. For clamping and removal of the drainage, repeated CT scans are required to rule out recurrent hydrocephalus. We performed a prospective observational study on the use of transcranial duplex sonography to monitor changes in width of the lateral ventricles during clamping as an alternative to CT. <h3>Methods:</h3> Patients with hydrocephalus after intracranial or subarachnoid hemorrhage were monitored by transcranial duplex sonography (TDS). Serial examinations were carried out before and directly after placement of extraventricular or lumbar drainage as well as every 12 hours until 48 hours after removal of all drainages. Clinicians were blinded for all ultrasound results. Receiver operating characteristic analysis and calculation of the positive and negative predictive values was used to identify the optimal cutoff point in increased ventricle width that best predicted reopening of the drainage by the clinician. <h3>Results:</h3> Ninety-two attempts to clamp either lumbar or extraventricular drainage were monitored in 37 patients during a 1-year period. A cutoff value for increase of ventricular width of 5.5 mm yielded high sensitivity (100%) and specificity (83%) in combination with a 100% negative predictive value for reopening of the drainage. <h3>Conclusions:</h3> TDS can be used to monitor ventricular width in experienced neurologic intensive care units. Because of its noninvasive character and suitability for bedside use, it offers a valuable alternative to repeated CT scans.

To date only two studies have evaluated anemia status in acute intracerebral hemorrhage (ICH) reporting that on admission anemia (OAA) was associated with larger hematoma volume, and lower hemoglobin levels during hospital stay, which related to poorer outcome. The question remains whether anemia influences outcome through related volume-effects or itself has an independent impact? This single-center investigation included 435 consecutive patients with spontaneous ICH admitted to the Department of Neurology over five years. Functional short- and long-term outcome (3 months and 1 year) were analyzed for anemia status. Multivariate logistic and graphical regression analyses were calculated for associations of anemia and to determine independent effects on functional outcome. It was decided to perform a separate analysis for patients with ICH-volume <30cm3 (minor-volume-ICH). Overall short-term-outcome was worse in anemic patients (mRS[4-6] OAA = 93.3% vs. non-OAA = 61.2%, P < 0.01), and there was a further shift towards an increased long-term mortality (P = 0.02). The probability of unfavorable long-term-outcome (mRS[4-6]) in OAA was elevated 7-fold (OR:7.5; P < 0.01). Receiver operating characteristics curve (ROC) analysis revealed a positive but poor association of ICH-volume and anemia (AUC = 0.67) suggesting volume-undriven outcome-effects of anemia (AUC = 0.75). Multivariate regression analyses revealed that anemia, besides established parameters, has the strongest relation to unfavorable outcome (OR:3.0; P < 0.01). This is even more pronounced in minor-volume-ICH (OR:5.6; P < 0.01). Anemia seems to be a previously unrecognized significant predictor of unfavorable functional outcome with independent effects beyond its association with larger hemorrhage volumes. The recognition of anemia and its treatment may possibly influence outcome after ICH and as such prospective interventional studies are warranted.

Intracerebral hemorrhage (ICH) is one of the most detrimental sub-types of stroke and accounts for 10–15 % of all strokes Qureshi et al. (Lancet 373(9675):1632–1644, 2009). ICH has an incidence of 10–30 cases per 100,000 people/year which is increasing and expected to double by the year 2050 Qureshi et al. (N Engl J Med 344 (19):1450–1460, 2001). Mortality rates still remain poor (30–50 %) and functional dependency after ICH is high (~75 %) van Asch et al. (Lancet Neurol 9 (2):167–176, 2010). Up to now, all randomized controlled trials investigating treatment approaches in ICH have failed to document improvements on clinical endpoints Mayer et al. (N Engl J Med 358 (20):2127–2137, 2008); Brouwers and Goldstein (Neurotherapeutics 9 (1):87–98, 2012). Only a specialized treatment of severely injured patients at dedicated neuro intensive care units [NICU] has been shown to be beneficial Qureshi et al. (Lancet 373(9675):1632–1644, 2009); Suarez et al. (Crit Care Med 32 (11):2311–2317, 2004). Currently, ongoing trials are investigating aggressive blood pressure lowering, hemostatic therapies, different operative strategies, intraventricular thrombolysis as well as neuroprotective approaches, and brain edema therapies. This review will summarize advanced treatment strategies and novel approaches which are currently under investigation.

Background and Purpose— This study determined the influence of concomitant antiplatelet therapy (APT) on hematoma characteristics and outcome in primary spontaneous intracerebral hemorrhage (ICH), vitamin K antagonist (VKA)- and non–VKA oral anticoagulant-associated ICH. Methods— Data of retrospective cohort studies and a prospective single-center study were pooled. Functional outcome, mortality, and radiological characteristics were defined as primary and secondary outcomes. Propensity score matching and logistic regression analyses were performed to determine the association between single or dual APT and hematoma volume. Results— A total of 3580 patients with ICH were screened, of whom 3545 with information on APT were analyzed. Three hundred forty-six (32.4%) patients in primary spontaneous ICH, 260 (11.4%) in VKA-ICH, and 30 (16.0%) in non–VKA oral anticoagulant-associated ICH were on APT, and these patients had more severe comorbidities. After propensity score matching VKA-ICH patients on APT presented with less favorable functional outcome (modified Rankin Scale score, 0–3; APT, 48/202 [23.8%] versus no APT, 187/587 [31.9%]; P =0.030) and higher mortality (APT, 103/202 [51.0%] versus no APT, 237/587 [40.4%]; P =0.009), whereas no significant differences were present in primary spontaneous ICH and non–VKA oral anticoagulant-associated ICH. In VKA-ICH, hematoma volume was significantly larger in patients with APT (21.9 [7.4–61.4] versus 15.7 [5.7–44.5] mL; P =0.005). Multivariable regression analysis revealed an association of APT and larger ICH volumes (odds ratio, 1.80 [1.20–2.70]; P =0.005), which was more pronounced in dual APT and supratherapeutically anticoagulated patients. Conclusions— APT does not affect ICH characteristics and outcome in primary spontaneous ICH patients; however, it is associated with larger ICH volume and worse functional outcome in VKA-ICH, presumably by additive antihemostatic effects. Combination of anticoagulation and APT should, therefore, be diligently evaluated and restricted to the shortest possible time frame.

Background and Purpose- Perihemorrhagic edema (PHE) is associated with poor outcome after intracerebral hemorrhage (ICH). Infiltration of immune cells is considered a major contributor of PHE. Recent studies suggest that immunomodulation via S1PR (sphingosine-1-phosphate receptor) modulators improve outcome in ICH. Siponimod, a selective modulator of sphingosine 1-phosphate receptors type 1 and type 5, demonstrated an excellent safety profile in a large study of patients with multiple sclerosis. Here, we investigated the impact of siponimod treatment on perihemorrhagic edema, neurological deficits, and survival in a mouse model of ICH. Methods- ICH was induced by intracranial injection of 0.075 U of bacterial collagenase in 123 mice. Mice were randomly assigned to different treatment groups: vehicle, siponimod given as a single dosage 30 minutes after the operation or given 3× for 3 consecutive days starting 30 minutes after operation. The primary outcome of our study was evolution of PHE measured by magnetic resonance-imaging on T2-maps 72 hours after ICH, secondary outcomes included evolution of PHE 24 hours after ICH, survival and neurological deficits, as well as effects on circulating blood cells and body weight. Results- Siponimod significantly reduced PHE measured by magnetic resonance imaging (P=0.021) as well as wet-dry method (P=0.04) 72 hours after ICH. Evaluation of PHE 24 hours after ICH showed a tendency toward attenuated brain edema in the low-dosage group (P=0.08). Multiple treatments with siponimod significantly improved neurological deficits measured by Garcia Score (P=0.03). Survival at day 10 was improved in mice treated with multiple dosages of siponimod (P=0.037). Mice treated with siponimod showed a reduced weight loss after ICH (P=0.036). Conclusions- Siponimod (BAF-312) attenuated PHE after ICH, increased survival, and reduced ICH-induced sensorimotor deficits in our experimental ICH-model. Findings encourage further investigation of inflammatory modulators as well as the translation of BAF-312 to a human study of ICH patients.

In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic.In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated.Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001).This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis.

Background: Stroke stimulates reactive astrogliosis, aquaporin 4 (AQP4) depolarization and neuroinflammation. Preconditioned extracellular vesicles (EVs) from microglia exposed to hypoxia, in turn, reduce poststroke brain injury. Nevertheless, the underlying mechanisms of such effects are elusive, especially with regards to inflammation, AQP4 polarization, and cerebrospinal fluid (CSF) flow. Methods: Primary microglia and astrocytes were exposed to oxygen-glucose deprivation (OGD) injury. For analyzing the role of AQP4 expression patterns under hypoxic conditions, a co-culture model of astrocytes and microglia was established. Further studies applied a stroke model, where some mice also received an intracisternal tracer infusion of rhodamine B. As such, these in vivo studies involved the analysis of AQP4 polarization, CSF flow, astrogliosis, and neuroinflammation as well as ischemia-induced brain injury. Results: Preconditioned EVs decreased periinfarct AQP4 depolarization, brain edema, astrogliosis, and inflammation in stroke mice. Likewise, EVs promoted postischemic CSF flow and cerebral blood perfusion, and neurological recovery. Under in vitro conditions, hypoxia stimulated M2 microglia polarization, whereas EVs augmented M2 microglia polarization and repressed M1 microglia polarization even further. In line with this, astrocytes displayed upregulated AQP4 clustering and proinflammatory cytokine levels when exposed to OGD, which was reversed by preconditioned EVs. Reduced AQP4 depolarization due to EVs, however, was not a consequence of unspecific inflammatory regulation, since LPS-induced inflammation in co-culture models of astrocytes and microglia did not result in altered AQP4 expression patterns in astrocytes. Conclusions: These findings show that hypoxic microglia may participate in protecting against stroke-induced brain damage by regulating poststroke inflammation, astrogliosis, AQP4 depolarization, and CSF flow due to EV release.

Over the recent years, fibrinolytic agents have been tested for intraventricular clot fibrinolysis (IVF). Compared with patients who did not receive IVF, administration of rt-PA induces rapid resorption of intraventricular blood and normalization of cerebrospinal fluid (CSF) circulation resulting in a reduced 30-day mortality and beneficial short-term outcome after 3 months. Our objective was to analyze possible influences of IVF on the long-term outcome after 12 months. Based on a prospective data base, patients with ganglionic supratentorial hematoma with additional intraventricular hemorrhage and occlusive hydrocephalus (n = 135) were isolated. Twenty-seven patients received IVF. To design a case-control study, we carefully matched 22 controls without IVF with regard to hematoma volume, Graeb score, Glasgow Coma Scale on admission and age (five patients remained unmatchable). We determined clinical and imaging parameters by reviewing the medical records and CT scans of all included patients. Outcome after 12 months was evaluated using the modified Rankin scale (mRS). One multivariate regression analysis was performed to determine predisposing factors for outcome. IVF significantly reduced Graeb score during treatment (eight on admission, three after IVF, one prior to discharge in the treated group versus 8/6/2 in patients without IVF). In patients with IVF requirement, a second external ventricular drainage (EVD) and a ventriculoperitoneal (VP) shunt were reduced (P = 0.08) and the incidence of a lumbar drainage was significantly higher (P < 0.01), whilst the overall time of extra-corporal CSF drainage was comparable. EVD associated complications were equal in both groups. Overall long-term outcome was poor but no significant differences were found between patients with and without IVF (mRS 4-6: 12/22 (54%) in patients with and 13/22 (59%) in patients without IVF; P = 0.81). The five excluded patients with IVF were similar to the 22 included ones with respect to imaging findings and outcome. The multivariate analysis revealed age and baseline hematoma volume, but not IVF to significantly impact the outcome. In accordance with previous studies, IVF hastened clot lysis and reduced the need for repeated EVD exchanges and permanent shunting. However, despite these advantages, IVF did not influence long-term outcome after 12 months. The results of the prospective randomized trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) need to be awaited.

Background Up to 25% of all acute ischaemic strokes occur during sleep. Because of the unclear time window, patients with stroke on awakening are usually not considered for acute therapy and excluded from most acute treatment trials. Aim To evaluate the feasibility of magnetic resonance imaging-based intravenous thrombolysis in patients with stroke on awakening in a routine clinical setting. Methods Forty-five patients with stroke on awakening clinically qualifying for intravenous thrombolysis and presenting within 6 h after symptom recognition were admitted to our institution between October 2006 and May 2008. Following an institutional protocol, patients received magnetic resonance imaging as a first-line imaging modality and were offered mismatch-based thrombolysis whenever possible. Baseline demographic data, clinical, laboratory and imaging findings were analysed. Outcome was assessed using the modified Rankin Scale score at 3 months. Results Magnetic resonance imaging screening was feasible in 43/45 patients (96%). After screening, 10 patients (22%) were treated with intravenous thrombolysis. There were no differences between treated and untreated patients regarding cardiovascular risk factors, stroke aetiology, previous prophylactic treatment and symptom recognition to door time or door to imaging time. Outcome was comparable in both groups despite a trend towards more severe strokes in the intravenous thrombolysis group. Only one asymptomatic and no symptomatic haemorrhage were observed. Conclusion Our data demonstrate that magnetic resonance imaging-based thrombolysis is feasible and possibly safe in patients with stroke on awakening (SOA). Randomised clinical trials for patients with stroke on awakening are needed to further test the safety and efficacy of intravenous thrombolysis in this patient group. The results of our study may help to initiate and design such studies.

Because of the narrow therapeutic range for thrombolysis in stroke, accurate weight-based dosing is essential for efficacy and safety. Stroke patients are frequently incapable to communicate their correct body weight (BW). Thus, dosing is often based on BW estimation, which may lead to dosing errors. The aim of our study was to evaluate availability of BW information, accuracy of estimations, and final dosing of Alteplase (tissue plasminogen activator [tPA]) in a routine clinical setting.A total of 109 consecutive intravenous thrombolysis patients were prospectively included in the study. Recruitment concluded with 100 complete data sets. Before therapy, BW was estimated independently by 2 physicians, 2 emergency nurses, and a neuroradiological technical assistant. Patients were weighed, and anthropometric measurements for BW approximation were taken. Dosing errors were assessed. Clinical outcome was evaluated at 90 days.Of 109 patients, 55 (50.5%) were unable to provide information on their BW. Of those, 11 (20%) were accompanied by relatives able to give BW information. For all patients, estimation errors rates ranged from 20.8% (patient's own estimation) up to 38.2% (treating physician) and 42.2% (emergency nurse). Finally, 29 patients received an Alteplase dosage diverging >10% from the optimal dose. Twelve were under- and 17 overdosed. Underdosage was an independent predictor for worse outcome in multivariate analysis.Our study shows that reliable BW data are missing for a majority of intravenous thrombolysis patients. Measuring BW before administering Alteplase remains challenging. Given dosing errors in one-third of patients and the observed impact on outcome, standardized weighing before thrombolysis should be considered. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006434.

Several contraindications for intravenous thrombolysis are not based on controlled trials. Specialized stroke centers often apply less restrictive criteria. The aim of our study was to analyze how many patients at our institution receive off-label thrombolysis. In addition, clinical outcome and safety data were compared to those from patients treated on-label, and the influence of different definitions of 'minor stroke' were examined.Consecutive thrombolysis patients treated between January 2006 and January 2010 were included. Patients treated off-label were compared to patients given on-label therapy according to the European license. Since no specified definition for 'minor neurological deficit' exists in the license, two distinct definitions were considered off-label, i.e. National Institutes of Health Stroke Scale score (NIHSSS) <1 (definition 1) and NIHSSS ≤4 (definition 2).Of a total of 422 patients, 232 (55%) were treated off-label. The most prevalent off-label criteria (OLCs) were the following: age >80 years (n = 113), minor stroke (definition 1, n = 3; definition 2, n = 84), elevated blood pressure necessitating aggressive treatment (n = 75), time window >3 h (n = 71) and major surgery or trauma within the preceding 3 months (n = 20). In group comparisons, off-label patients had an overall worse outcome using definition 1 for minor stroke, while there was no difference when definition 2 was applied. In multivariate analysis, off-label therapy (definition 1) in general and age >80 years were independent predictors of poor outcome. None of the contraindications were associated with an increased bleeding risk.Off-label therapy is frequently applied at our center and is not associated with higher complication rates. Overall outcome of off-label treatment largely depends on the definition used for minor stroke. Besides age >80 years, a known poor prognostic factor, no other specific OLC was associated with poor outcome. Our data suggest that the criteria in the European license may be too restrictive.

Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF).Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals.Median effective telemetry monitoring time was 75.5 hours (interquartile range 64-86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring.Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

Therapeutic hypothermia (TH) is an established treatment after cardiac arrest and growing evidence supports its use as neuroprotective treatment in stroke. Only few and heterogeneous studies exist on the effect of hypothermia in subarachnoid hemorrhage (SAH). A novel approach of early and prolonged TH and its influence on key complications in poor-grade SAH, vasospasm and delayed cerebral ischemia (DCI) was evaluated.This observational matched controlled study included 36 poor-grade (Hunt and Hess Scale >3 and World Federation of Neurosurgical Societies Scale >3) SAH patients. Twelve patients received early TH (<48 h after ictus), mild (35°C), prolonged (7 ± 1 days) and were matched to 24 patients from the prospective SAH database. Vasospasm was diagnosed by angiography, macrovascular spasm serially evaluated by Doppler sonography and DCI was defined as new infarction on follow-up CT. Functional outcome was assessed at 6 months by modified Rankin Scale (mRS) and categorized as favorable (mRS score 0-2) versus unfavorable (mRS score 3-6) outcome.Angiographic vasospasm was present in 71.0% of patients. TH neither influenced occurrence nor duration, but the degree of macrovascular spasm as well as peak spastic velocities were significantly reduced (p < 0.05). Frequency of DCI was 87.5% in non-TH vs. 50% in TH-treated patients, translating into a relative risk reduction of 43% and preventive risk ratio of 0.33 (95% CI 0.14-0.77, p = 0.036). Favorable functional outcome was twice as frequent in TH-treated patients 66.7 vs. 33.3% of non-TH (p = 0.06).Early and prolonged TH was associated with a reduced degree of macrovascular spasm and significantly decreased occurrence of DCI, possibly ameliorating functional outcome. TH may represent a promising neuroprotective therapy possibly targeting multiple pathways of DCI development, notably macrovascular spasm, which strongly warrants further evaluation of its clinical impact.

Background and Purpose— Intracerebral hemorrhage (ICH) causes high morbidity and mortality. Recently, perihemorrhagic edema (PHE) has been suggested as an important prognostic factor. Therapeutic hypothermia may be a promising therapeutic option to treat PHE. However, no data exist about the optimal timing and duration of therapeutic hypothermia in ICH. We examined the impact of therapeutic hypothermia timing and duration on PHE evolution. Methods— In this retrospective, single-center, case–control study, we identified patients with ICH treated with mild endovascular hypothermia (target temperature 35°C) from our institutional database. Patients were grouped according to hypothermia initiation (early: days 1–2 and late: days 4–5 after admission) and hypothermia duration (short: 4–8 days and long: 9–15 days). Patients with ICH matched for ICH volume, age, ICH localization, and intraventricular hemorrhage were identified as controls. Relative PHE, temperature, and intracranial pressure course were analyzed. Clinical outcome on day 90 was assessed using the modified Rankin scale (0–3=favorable and 4–6=poor). Results— Thirty-three patients with ICH treated with hypothermia and 37 control patients were included. Early hypothermia initiation led to relative PHE decrease between admission and day 3, whereas median relative PHE increased in control patients (−0.05 [interquartile range, −0.4 to 0.07] and 0.07 [interquartile range, −0.07 to 0.26], respectively; P =0.007) and patients with late hypothermia initiation (0.22 [interquartile range 0.12–0.27]; P =0.037). After day 3, relative PHE increased in all groups without difference. Outcome was not different between patients treated with hypothermia and controls. Conclusions— Early hypothermia initiation after ICH onset seems to have an important impact on PHE evolution, whereas our data suggest only limited impact later than day 3 after onset.

Direct oral anticoagulants (DOACs) are increasingly used for secondary prevention of cardioembolic stroke. While DOACs are associated with a long-term reduced risk of intracranial hemorrhage compared to vitamin K antagonists, pivotal trials avoided the very early period after stroke and few data exist on early initiation of DOAC therapy post stroke.We retrospectively analyzed data from our prospective database of all consecutive transient ischemic attack (TIA) or ischemic stroke patients with atrial fibrillation treated with DOACs during hospital stay. As per our institutional treatment algorithm for patients with cardioembolic ischemia DOACs are started immediately in TIA and minor stroke (group 1), within days 3-5 in patients with infarcts affecting one third or less of the middle cerebral artery, the anterior cerebral artery, or the posterior cerebral artery territories (group 2) as well as in infratentorial stroke (group 3) and after 1-2 weeks in patients with large infarcts (>⅓MCA territory, group 4). We investigated baseline characteristics, time to initiation of DOAC therapy after symptom onset, and hemorrhagic complications.In 243 included patients, administration of DOAC was initiated 40.5 hours (interquartile range [IQR] 23.0-65.5) after stroke onset in group 1 (n = 41) and after 76.7 hours (IQR 48.0-134.0), 108.4 hours (IQR 67.3-176.4), and 161.8 hours (IQR 153.9-593.8) in groups 2-4 (n = 170, 28, and 4), respectively. Two cases of asymptomatic intracranial hemorrhage (.8%) and 1 case of symptomatic intracranial hemorrhage (.4%) were observed, both in group 2.No severe safety issues were observed in early initiation of DOACs for secondary prevention after acute stroke in our in-patient cohort.

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.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.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.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.

Background and Purpose— Stroke-associated immunosuppression is an increasingly recognized factor triggering infections and thus potentially influencing outcome after stroke. Specifically, lymphocytopenia after intracerebral hemorrhage (ICH) has only been addressed in small-sized retrospective studies of mixed intracranial bleedings. This cohort study investigated the natural course of lymphocytopenia, parameters associated with lymphocytopenia on admission (LOA) and during stay, and evaluated the clinical impact of lymphocytopenia in solely ICH patients. Methods— This observational study included 855 consecutive patients with ICH. Patient demographics, clinical and neuroradiological data as well as laboratory and in-hospital measures were retrieved from institutional prospective databases. Functional 3-month outcome was assessed by mailed questionnaires. Lymphocytopenia was defined as &lt;1.0 (10 9 /L) and was correlated with patient’s characteristics and outcome. Results— Prevalence of LOA was 27.3%. Patients with LOA showed significant associations with poorer neurological status (18 [10–32] versus 13 [5–24]; P &lt;0.001), larger hematoma volume (18.5 [6.2–46.2] versus 12.8 [4.4–37.8]; P =0.006), and unfavorable outcome (74.7% versus 63.3%; P =0.0018). Natural course of lymphocyte count during hospital stay revealed a lymphocyte nadir of 1.1 (0.80–1.53 [10 9 /L]) at day 5. Focusing on patients with day-5-lymphocytopenia, compared with patients with LOA, revealed increased rates of infections (63 [71.6] versus 113 [48.5]; P &lt;0.001) and poorer functional outcome at 3 months (76 [86.4] versus 175 [75.1); P =0.029). Adjusting for baseline confounders, multivariable logistic and receiver operating characteristics analyses documented independent associations of day-5-lymphocytopenia with unfavorable outcome (day-5-lymphocytopenia: odds ratio, 2.017 [95% confidence interval, 1.029–3.955], P =0.041; LOA: odds ratio, 1.391 [0.795–2.432], P =0.248; receiver operating characteristics: day-5-lymphocytopenia: area under the curve=0.673, P &lt;0.0001, Youden’s index=0.290; LOA: area under the curve=0.513, P =0.676, Youden’s index=0.084), whereas receiver operating characteristics analyses revealed no association of age or hematoma volume with day-5-lymphocytopenia (age: area under the curve=0.540, P =0.198, Youden’s index=0.106; volume: area under the curve=0.550, P =0.0898, Youden’s index=0.1224). Conclusions— Lymphocytopenia is frequently present in patients with ICH and may represent an independent parameter associated with unfavorable functional outcome. Developing lymphocytopenia affected outcome even stronger than LOA, a finding that may open up new therapeutic avenues in specific subsets of patients with ICH.

<h3>Objective</h3> To determine the influence of intracerebral hemorrhage (ICH) location and volume and hematoma surface on perihemorrhagic edema evolution. <h3>Methods</h3> Patients with ICH of the prospective Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage (UKER-ICH) cohort study (NCT03183167) between 2010 and 2013 were analyzed. Hematoma and edema volume during hospital stay were volumetrically assessed, and time course of edema evolution and peak edema correlated to hematoma volume, location, and surface to verify the strength of the parameters on edema evolution. <h3>Results</h3> Overall, 300 patients with supratentorial ICH were analyzed. Peak edema showed a high correlation with hematoma surface (<i>R</i>² = 0.864, <i>p</i> &lt; 0.001) rather than with hematoma volumes, regardless of hematoma location. Smaller hematomas with a higher ratio of hematoma surface to volume showed exponentially higher relative edema (<i>R</i>² = 0.755, <i>p</i> &lt; 0.001). Multivariable logistic regression analysis revealed a cutoff ICH volume of 30 mL, beyond which an increase of total mass lesion volume (combined volume of hematoma and edema) was not associated with worse functional outcome. Specifically, peak edema was associated with worse functional outcome in ICH &lt;30 mL (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.68–4.12, <i>p</i> &lt; 0.001), contrary to ICH ≥30 mL (OR 1.20, 95% CI 0.88–1.63, <i>p</i> = 0.247). There were no significant differences between patients with lobar and those with deep ICH after adjustment for hematoma volumes. <h3>Conclusions</h3> Peak perihemorrhagic edema, although influencing mortality, is not associated with worse functional outcomes in ICH volumes &gt;30 mL. Although hematoma volume correlates with peak edema extent, hematoma surface is the major parameter for edema evolution. The effect of edema on functional outcome is therefore more pronounced in smaller and irregularly shaped hematomas, and these patients may particularly benefit from edema-modifying therapies.

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; While the short-term clinical outcome of patients with subarachnoid hemorrhage (SAH) is well described, there are limited data on long-term complications and their impact on social reintegration. This study aimed to assess the frequency of complications post-SAH and to investigate whether these complications attribute to functional and self-reported outcomes as well as the ability to return to work in these patients. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This retrospective single-center study included patients with atraumatic SAH over a 5-year period at a tertiary care center. Patients received a clinical follow-up for 12 months. In addition to demographics, imaging data, and parameters of acute treatment, the rate and extent of long-term complications after SAH were recorded. The functional outcome was assessed using the modified Rankin Scale (mRS; favorable outcome defined as mRS = 0–2). Further outcomes comprised self-reported subjective health measured by the EQ-5D and return to work for SAH patients with appropriate age. Multivariable analyses including in-hospital parameters and long-term complications were conducted to identify parameters independently associated with outcomes in SAH survivors. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; This study cohort consisted of 505 SAH patients of whom 405 survived the follow-up period of 12 months (i.e., mortality rate of 19.8%). Outcome data were available in 359/405 (88.6%) patients surviving SAH. At 12 months, a favorable functional outcome was achieved in 287/359 (79.9%) and 145/251 (57.8%) SAH patients returned to work. The rates of post-acute complications were headache (32.3%), chronic hydrocephalus requiring permanent ventriculoperitoneal shunting (VP shunt 25.4%) and epileptic seizures (9.5%). Despite patient’s and clinical characteristics, both presence of epilepsy and need for VP shunt were independently and negatively associated with a favorable functional outcome (epilepsy: adjusted odds ratio [aOR] (95% confidence interval [95% CI]): 0.125 [0.050–0.315]; VP shunt: 0.279 [0.132–0.588]; both &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001) as well as with return to work (aOR [95% CI]: epilepsy 0.195 [0.065–0.584], &lt;i&gt;p&lt;/i&gt; = 0.003; VP shunt 0.412 [0.188–0.903], &lt;i&gt;p&lt;/i&gt; = 0.027). Multivariable analyses revealed presence of headache, VP shunt, or epilepsy to be significantly related to subjective health impairment (aOR [95% CI]: headache 0.248 [0.143–0.430]; epilepsy 0.223 [0.085–0.585]; VP shunt 0.434 [0.231–0.816]; all &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.01). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Long-term complications occur frequently after SAH and are associated with an impairment of functional and social outcomes. Further studies are warranted to investigate if treatment strategies specifically targeting these complications, including preventive aspects, may improve the outcomes after SAH.

The impact of statins on hematoma characteristics, perihemorrhagic edema (PHE), cardiovascular events, seizures, and functional recovery in patients with intracerebral hemorrhage (ICH) is insufficiently studied.Patients with ICH of the prospective UKER-ICH (Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage) study (URL: https://www.clinicaltrials.gov; Unique identifier: NCT03183167) were analyzed by multivariable regression modeling and propensity score matching, and PHE volumes were volumetrically assessed. Outcomes comprised hematoma characteristics, the impact of continuation, discontinuation, and initiation of statins on peak PHE extent, and the influence of statin treatment on the occurrence of seizures, cardiovascular adverse events, and functional recovery after ICH.A total of 1275 patients with ICH with information on statin treatment were analyzed. Statin treatment on hospital admission (21.7%) was associated with higher rates of lobar versus nonlobar ICH (odds ratio, 1.57 [1.03-2.40]; P=0.038). Initiation of statins after ICH was associated with increased peak PHE (β=0.12, SE=0.06, P=0.008), whereas continuation versus discontinuation of prior statin treatment was not significantly associated with edema formation (P>0.10). There were no significant differences in the incidence of remote symptomatic seizures according to statin exposure during follow-up (statins: 11.5% versus no statins: 7.8%, subdistribution hazard ratio: 1.15 [0.80-1.66]; P=0.512). Patients on statins revealed less cardiovascular adverse events and more frequently functional recovery after 12 months (functional recovery: 57.7% versus 45.0%, odds ratio 1.67 [1.09-2.56]; P=0.019).Among statin users, lobar ICH occurs more frequently as compared with nonstatin users. While continuation of prior statin treatment appears to be safe regarding PHE formation, the initiation of statins during the first days after ICH may increase PHE extent. However, statins should be initiated thereafter (eg, at hospital discharge) to prevent cardiovascular events and potentially improve functional recovery.

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.

Background: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. Methods: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0–6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). Results: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4–14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39–2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35–0.64), without increased adverse events, absolute difference, 1.0% (95% CI, −2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6–21.8) to achieve the primary outcome. Conclusions: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window &lt;48 hours, specifying a target population for future trials.

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.

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.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.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]).Since our cognitive training showed beneficial effects, it could be a promising method to prevent POCD.

&lt;i&gt;Background:&lt;/i&gt; 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. &lt;i&gt;Methods:&lt;/i&gt; 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. &lt;i&gt;Results:&lt;/i&gt; 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. &lt;i&gt;Conclusions:&lt;/i&gt; 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.

&lt;i&gt;Background:&lt;/i&gt; Venous thromboembolism (VTE) is a common complication after stroke. Application of low molecular weight heparins (LMWH) has been proven to be beneficial for the prevention of VTE in ischemic stroke patients. However, there is no consensus whether and how to administer LMWH for prevention of thrombotic complications after acute spontaneous intracerebral hemorrhage (sICH), the main concern being possible hematoma growth. The objective of this study was to assess the safety of early subcutaneous LMWH in patients with sICH with respect to hemorrhage enlargement. &lt;i&gt;Methods:&lt;/i&gt; A total of 97 patients with sICH were analyzed. LMWH (either enoxaparin-natrium or dalteparin-natrium) were initiated within 36 h after admission in all patients without clinical evidence of hemorrhage enlargement or an absence of evidence of hematoma growth on CT. Hematoma growth (significant when &gt;33%, moderate when &gt;20%) was assessed on follow-up CT between days 5 and 11. &lt;i&gt;Results:&lt;/i&gt; None of the patients showed a significant hemorrhage growth. Between days 2 and 10, 2 patients experienced a moderate hematoma enlargement of 22.4 and 20.9%. None of the included patients developed a fatal lung embolism. &lt;i&gt;Conclusions:&lt;/i&gt; Early application of subcutaneous LMWH for prevention of venous thromboembolism seems to be safe, and probably does not increase the risk of hematoma growth in patients with sICH.

The goal in this study was to compare flat-panel detector (FD) CT with multislice (MS) CT in the visualization of intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), intraventricular hemorrhage, and external ventricular drains (EVDs) to evaluate the diagnostic quality and limitations of the new FD CT imaging modality.Neuroimages obtained in 65 patients, including 24 with EVDs, were reviewed by 2 independent, experienced clinicians. Lesions in all patients were investigated with FD CT and MS CT. The numbers of slices positive for ICH and SAH were counted, and for ICH the diameter and area of the lesion was measured. The positioning of drains was assessed. The presence of ventricular blood was noted. Statistical analysis was performed by calculating the Pearson correlation coefficient (r) to evaluate the level of inter- and intraobserver agreement, and linear regression analysis was done to visualize the results of the numbers of ICH- and SAH-positive slices.The authors found high interobserver agreement regarding the number of slices with evidence of ICH (r = 0.89 for MS CT, r = 0.78 for FD CT) and SAH (r = 0.88 for MS CT, r = 0.9 for FD CT). Thin layers of blood in the ventricles were not detected on FD CT in 36.4% of cases. Six of 7 perimesencephalic SAHs were not seen on FD CT scans. The EVDs could be assessed with both modalities in 83.3% of cases, but the position of the drain could not be determined with FD CT in 16.7% (4 of 24 cases).In some respects, FD CT is of limited use for the visualization of intracranial hemorrhage. However, despite limited contrast resolution, ICH and EVDs can be reliably demonstrated. Perimesencephalic SAH and thin layers of blood in the occipital horns may not be detected using FD CT. Further evaluation and improvement of the image quality is necessary before FD CT will provide identical quality in comparison with MS CT.

Background and Purpose— It is unknown whether blood pressure (BP) reduction influences secondary brain injury in spontaneous intracerebral hemorrhage (ICH). We tested the hypothesis that intensive BP reduction is associated with decreased perihematomal edema expansion rate (PHER) in deep ICH. Methods— We performed an exploratory analysis of the ATACH-2 randomized trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2). Patients with deep, supratentorial ICH were included. PHER was calculated as the difference in perihematomal edema volume between baseline and 24-hour computed tomography scans divided by hours between scans. We used regression analyses to determine whether intensive BP reduction was associated with PHER and if PHER was associated with poor outcome (3-month modified Rankin Scale score 4–6). We then used interaction analyses to test whether specific deep location (basal ganglia versus thalamus) modified these associations. Results— Among 1000 patients enrolled in ATACH-2, 870 (87%) had supratentorial, deep ICH. Of these, 780 (90%) had neuroimaging data (336 thalamic and 444 basal ganglia hemorrhages). Baseline characteristics of the treatment groups remained balanced ( P &gt;0.2). Intensive BP reduction was associated with a decrease in PHER in univariable (β= −0.15; 95% CI, −0.26 to −0.05; P =0.007) and multivariable (β=−0.12; 95% CI, −0.21 to −0.02; P =0.03) analyses. PHER was not independently associated with outcome in all deep ICH (odds ratio, 1.14; 95% CI, 0.93–1.41; P =0.20), but this association was modified by the specific deep location involved (multivariable interaction P =0.02); in adjusted analyses, PHER was associated with poor outcome in basal ganglia (odds ratio, 1.42; 1.05–1.97; P =0.03) but not thalamic (odds ratio, 1.02; 95% CI, 0.74–1.40; P =0.89) ICH. Conclusions— Intensive BP reduction was associated with decreased 24-hour PHER in deep ICH. PHER was not independently associated with outcome in all deep ICH but was associated with poor outcome in basal ganglia ICH. PHER may be a clinically relevant end point for clinical trials in basal ganglia ICH.

Given an ageing population the incidence of both patients suffering from intracerebral hemorrhage (ICH) and those requiring oral anticoagulation will increase. Up to now there are no results from randomized trials available whether or not, and when, ICH survivors should resume OAC. This review summarizes the most important observational studies, and initiated ongoing trials, to help guiding physicians in daily routine decision making.Several large observational studies and meta-analyses verified that OAC resumption was associated with a significant reduction of thromboembolic complications and mortality without leading to increased rates of recurrent ICH. OAC resumption seemed further associated with improved functional recovery and favorable long-term outcome. Given the general bleeding risk reduction in patients using Non-vitamin K antagonist oral anticoagulants (NOAC) compared to Vitamin-K-antagonist (VKA), NOAC use should also be preferred after ICH, although specific comparative studies are pending. Patients with lobar ICH need special attention as these patients showed increased ICH recurrence rates, why decision making should include extended diagnostic work-up evaluating cerebral microbleed burden, cortical subarachnoid hemorrhage and superficial siderosis. Further, patients with mechanical heart valves need specific consideration as restarting VKA may be unsafe until two weeks, whereas optimal balancing of hemorrhagic with thromboembolic complications may allow earlier re-initiation one week after ICH. In patients with atrial fibrillation, resumption generally should take place between 4 and 8 weeks after ICH depending on a patient's individual risk profile. Left atrial appendage occlusion (LAAO) might represent an alternative strategy in high-risk patients. Ongoing clinical trials will clarify whether OAC resumption versus LAAO versus no antithrombotic therapy may represent the best possible secondary stroke prevention in ICH survivors with atrial fibrillation.According to observational data OAC resumption after ICH seems beneficial and safe. Ongoing clinical trials will create evidence regarding treatment effects of pharmaceutical resumption and interventional alternatives. Yet, individual decision making weighing the patient's individual thromboembolic versus hemorrhagic risks remains essential.

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 &lt; 0.01; MGH: 0.85 [0.81–0.89] vs 0.78 [0.74–0.82], p &lt; 0.01), and for the entire cohort (AUROC, German cohort: 0.84 [0.82–0.86] vs 0.80 [0.77–0.82], p &lt; 0.01; MGH: 0.83 [0.81–0.85] vs 0.77 [0.75–0.79], p &lt; 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

<h3>Importance</h3> Intracerebral hemorrhage (ICH) contributes significantly to the global burden of disease. <h3>Objective</h3> To examine the association of ICH and secondary injury with disability-adjusted life-years (DALYs) for the individual patient. <h3>Design, Setting, and Participants</h3> This cohort study was conducted using data from the Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage study. Consecutive patients admitted to a single tertiary care center from January 1, 2006, to December 31, 2015, were included. The sample comprised patients with oral anticoagulation–associated ICH (OAC-ICH) or primary spontaneous ICH (non-OAC-ICH). Statistical analysis was conducted from October 1 to December 31, 2020. <h3>Exposures</h3> ICH occurrence and secondary injury. <h3>Main Outcomes and Measures</h3> DALYs, years of life lost (YLL), and years lived with disability (YLD) were analyzed by hematoma location, ICH volume, and secondary injury (ie, hematoma expansion [HE], intraventricular hemorrhage [IVH], and perihemorrhagic edema [PHE]). <h3>Results</h3> Among 1322 patients with ICH, 615 (46.5%) were women and the mean (SD) age at hospital admission was 71 (13) years; ICH was associated with a mean (SD) of 9.46 (8.08) DALYs, 5.72 (8.29) YLL, and 3.74 (5.95) YLD. There were statistically significant differences in mean (SD) DALYs by extent of hematoma volume (&lt; 10 mL ICH: 7.05 [6.79] DALYs; 10-30 mL ICH: 9.91 [8.35] DALYs; &gt;30 mL ICH: 12.42 [8.47] DALYs;<i>P</i> &lt; .001) and ICH location (deep location: 10.60 [8.35] DALYs; lobar location: 8.18 [7.63] DALYs; cerebellum: 8.14 [6.80] DALYs; brainstem: 12.63 [9.21] DALYs;<i>P</i> &lt; .001). Regarding population-level disease burden of secondary injuries after ICH, there was a statistically significant difference in mean (SD) by injury type, with 0.94 (3.19) DALYs for HE, 2.45 (4.16) DALYs for IVH, and 1.96 (2.66) DALYs for PHE (<i>P</i> &lt; .001) among the entire ICH cohort. Regarding individual-level exposure to secondary injuries after ICH, there were a mean (SD) 7.14 (6.62) DALYs for HE, 4.58 (4.75) DALYs for IVH, and 3.35 (3.28) DALYs for PHE among patients with ICH affected by secondary injuries. <h3>Conclusions and Relevance</h3> These findings suggest that there is a high burden of disability associated with ICH and secondary injuries, and the findings may guide public health strategies. The study findings further suggest that IVH and PHE may be relevant for the overall outcome of patients with ICH, that DALYs may represent a viable outcome parameter for studies to evaluate treatment outcomes in ICH research, and that IVH and PHE may represent potential treatment targets.

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).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.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.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.

To the best of our knowledge, we here report the first case of a panic attack based on Spice consumption in a 21-year-old male patient with attention deficit hyperactivity disorder (ADHD). The condition had been treated over several years with methylphenidate, but which had been taken irregularly. Within minutes after a third-ever consumption of Spice, the patient developed both blurred vision and an unsteady gait as well as an acute onset of an agonal state with the fear of ignorance of his friends. This panic attack was accompanied by a vegetative hyperirritability that lasted for more than two hours. After admission to the emergency department, acute cardiac disease was ruled out and the patient was transferred to our Department of Psychiatry where fixation became necessary. After intravenous application of 2 mg lorazepam and isotonic fluid substitution, the patient recovered over night. In light of the previously presumed association of panic attacks and consumption of cannabinoids, we here discuss the potential de-masking of panic attacks after Spice consumption (as a synthetic cannabinoid) by ADHD-based imbalances of the dopaminergic and norepiphrenic receptor profiles.

&lt;i&gt;Background:&lt;/i&gt; Approximately 5–10% of all acute ischemic strokes (AIS) occur in the territory of the posterior cerebral artery (PCA). Little is known about intravenous thrombolysis (IVT) in this infarct subgroup in terms of outcome and intracerebral hemorrhage rates. The aim of our study was to evaluate differences between supratentorial PCA infarcts and anterior circulation infarcts regarding baseline characteristics, stroke severity, outcome, safety and clinical findings, which would implicate a change in the existing thrombolysis practice in patients with PCA stroke. &lt;i&gt;Methods:&lt;/i&gt; All patients with AIS in the supratentorial PCA territory receiving IVT between 01/2006 and 01/2010 were selected from the Erlangen Thrombolysis Database (group 1, n = 21). They were compared to all IVT patients with strokes in other supratentorial vascular territories over the same period of time (group 2, n = 398). Baseline demographic data, as well as clinical and laboratory findings were analyzed. The outcome was assessed using the modified Rankin Scale at 3 months. &lt;i&gt;Results:&lt;/i&gt; Only serum glucose levels at baseline (110.5 ± 36.1 vs. 127.2 ± 48.2 mg/dl; p = 0.036) and the baseline National Institutes of Health Stroke Scale score (median 6.5 vs. 9; p = 0.016) were significantly lower in group 1 compared to group 2. Favorable clinical outcome (57.1 vs. 48.6%; p = 0.445) and intracerebral hemorrhage rates (4.8 vs. 4%; p = 1.000) were comparable in both groups. &lt;i&gt;Conclusions:&lt;/i&gt; No substantial differences were found between supratentorial PCA and anterior circulation infarcts. Our data on safety and efficacy support the present common thrombolysis practice in supratentorial PCA infarct patients, though an indication for IVT should rather be based on the existence of functionally disabling deficit than merely on the National Institutes of Health Stroke Scale.

The aim of the current study was to investigate the dose-dependent efficacy of intraventricular fibrinolysis (IVF) in patients with severe intraventricular hemorrhage (IVH).Patients with intracerebral hemorrhage, severe IVH, and obstructive hydrocephalus with the need for external ventricular drainage were treated with IVF through external ventricular drainage. The time course of IVH resolution and the safety profile were compared between patients treated with high-dose IVF (4 mg alteplase every 12 hours, maximum 20 mg; n=32) and low-dose IVF (1 mg alteplase every 8 hours, maximum 12 mg; n=22). CT scans on Days 1 to 4, 7 ± 1 and 10 ± 1 after admission, were analyzed volumetrically. Outcome was assessed after 3 months.The overall effect of IVF dosage was not significantly different between the 2 groups (F=1.3, P=0.25). The course of IVH volume in the third and fourth ventricles was similar with high- and low-dose IVF. High-dose IVF resulted in lower total IVH volumes on Days 7 (4.4 ± 4.2 mL versus 8.8 ± 8.1 mL; P=0.01) and 10 (1.4 ± 2.8 mL versus 4.9 ± 65.8 mL; P=0.005). Total clot half-life was 78 ± 43 hours in the low-dose and 56 ± 25 hours in the high-dose group (P=0.02). One asymptomatic ventricular bleeding, 2 cases of ventriculitis, and 1 death due to pulmonary embolism occurred in the high-dose group. There was no difference in outcome at 3 months.Low-dose IVF (3 mg alteplase/day) has a similar effect on IVH clearance from the third and fourth ventricles and a similar safety profile when compared with high-dose IVF (8 mg alteplase/day).

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.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.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 Zn(2+)-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.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.

PurposeSeveral scoring tools have been developed for the prognostication of outcome after status epilepticus (SE). In this study, we compared the performances of STESS (Status Epilepticus Severity Score), mSTESS (modified STESS), EMSE-EAL (Epidemiology-based Mortality Score in Status Epilepticus- Etiology, Age, Level of Consciousness) and END-IT (Encephalitis-NCSE-Diazepam resistance-Image abnormalities-Tracheal intubation) in predicting in-hospital mortality after SE.MethodData collected retrospectively from a cohort of 287 patients with SE were used to calculate STESS, mSTESS, EMSE-EAL, and END-IT scores. The differences between the scores’ performances were determined by means of area under the ROC curve (AUC) comparisons and McNemar testing.ResultsThe in-hospital mortality rate was 11.8%. The AUC of STESS (0.628; 95% confidence interval (CI), 0.529–0.727) was similar to that of mSTESS (0.620; 95% CI, 0.510–0.731), EMSE-EAL (0.556; 95% CI, 0.446–0.665), and END-IT (0.659; 95% CI, 0.550–0.768; p > .05 for each comparison) in predicting in-hospital mortality. STESS with a cutoff of 3 was found to have lowest specificity and number of correctly classified episodes. EMSE-EAL with a cutoff at 40 had highest specificity and showed a trend towards more correctly classified episodes while sensitivity tended to be low. END-IT with a cutoff of 3 had the most balanced sensitivity-specificity ratio.ConclusionsEMSE-EAL is as easy to calculate as STESS and tended towards higher diagnostic accuracy. Adding information on premorbid functional status to STESS did not enhance outcome prediction. END-IT was not superior to other scores in prediction of in-hospital mortality despite including information of diagnostic work-up and response to initial treatment.

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.

To investigate whether the systemic inflammatory response syndrome (SIRS) without infection as surrogate of a systemic immune response is associated with poor long-term functional outcome in patients with spontaneous intracerebral hemorrhage (ICH).We analyzed consecutive patients with spontaneous ICH from our prospective cohort study (2018-2015). SIRS was defined according to standard criteria: i.e., 2 or more of the following parameters during hospitalization: body temperature <36°C or >38°C, respiratory rate >20 per minute, heart rate >90 per minute, or white blood cell count <4,000/μL or >12,000/μL in the absence of infection. The primary outcome consisted of the modified Rankin Scale (mRS) at 3 and 12 months investigated by adjusted ordinal shift analyses. Bias and confounding were addressed by propensity score matching and multivariable regression models.Of 780 patients with ICH, 21.8% (n = 170) developed SIRS during hospitalization. Patients with SIRS showed more severe ICH compared with those without; i.e., larger ICH volumes (18.3 cm3, interquartile range [IQR 4.6-47.2 cm3] vs 7.4 cm3, IQR [2.4-18.6 cm3]; p < 0.01), increased intraventricular hemorrhage (57.6%, n = 98/170 vs 24.8%, n = 79/319; p < 0.01), and poorer neurologic admission status (NIH Stroke Scale score 16, IQR [7-30] vs 6, IQR [3-12]; p < 0.01). ICH severity-adjusted analyses revealed an independent association of SIRS with poorer functional outcome after 3 (OR 1.80, 95% CI [1.08-3.00]; p = 0.025) and 12 months (OR 1.76, 95% CI [1.04-2.96]; p = 0.034). Increased ICH volumes on follow-up imaging (OR 1.38, 95% CI [1.01-1.89]; p = 0.05) and previous liver dysfunction (OR 3.01, 95% CI [1.03-10.19]; p = 0.04) were associated with SIRS.In patients with ICH, we identified SIRS to be predictive of poorer long-term functional outcome over the entire range of mRS estimates. Clinically relevant associations with SIRS were documented for previous liver dysfunction and hematoma enlargement.

&lt;b&gt;&lt;i&gt;Background and Objective:&lt;/i&gt;&lt;/b&gt; Intraventricular hemorrhage (IVH) is a verified independent prognostic parameter in patients with intracerebral hemorrhage (ICH). However, the impact of the extent of IVH on clinical outcomes is unestablished. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We analyzed 1,112 consecutive primary ICH patients of the UKER-ICH cohort (NCT03183167) and hypothesized that there is no difference in outcome between patients without IVH and patients with minor IVH not leading to obstructive hydrocephalus. Propensity score matching and multivariable analyses were performed to account for imbalances in baseline characteristics. Primary outcome was defined as functional outcome 3 months after ICH ­assessed using the modified Rankin Scale (mRS) dichotomized into favorable (mRS = 0–3) and unfavorable outcome (mRS = 4–6). Secondary outcomes included mortality at 3 months and a Graeb score-based threshold analysis for association of the extent of IVH with unfavorable clinical outcome. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Among the 461 out of 1,112 (41.5%) ICH patients with IVH, 191 out of 461 (41.4%) showed IVH without obstructive hydrocephalus and no requirement of external ventricular drain (EVD) placement. After adjusting for baseline imbalances we found no difference in functional outcome at 3 months between patients without IVH (No-IVH) and patients with IVH not requiring EVD (IVH-w/o-EVD): mRS 0–3: No-IVH 64/161 (39.8%) vs. IVH-w/o-EVD 53/170 (31.2%); &lt;i&gt;p&lt;/i&gt; = 0.103. However, there was a trend toward a higher mortality in IVH-w/o-EVD patients (mRS 6: No IVH 40/161 [24.8%] vs. IVH-w/o-EVD 57/170 [33.5%]; &lt;i&gt;p&lt;/i&gt; = 0.083). Multivariable analysis revealed that a Graeb score &amp;#x3e;2 was independently associated with unfavorable outcome (mRS 4–6: OR 3.16 [1.54–6.48]; &lt;i&gt;p&lt;/i&gt; = 0.002), and higher mortality (mRS 6: OR 2.57 [1.40–4.74]; &lt;i&gt;p&lt;/i&gt; = 0.002) in IVH patients. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Small amounts of intraventricular blood (Graeb score ≤2) not leading to obstructive hydrocephalus are not associated with unfavorable outcome or death after ICH. Thus, IVH per se should not be considered a binary variable in outcome prediction for ICH patients.

Abstract This expert opinion paper on cardiac imaging after acute ischemic stroke or transient ischemic attack (TIA) includes a statement of the “Heart and Brain” consortium of the German Cardiac Society and the German Stroke Society. The Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork (AFNET) endorsed this paper. Cardiac imaging is a key component of etiological work-up after stroke. Enhanced echocardiographic tools, constantly improving cardiac computer tomography (CT) as well as cardiac magnetic resonance imaging (MRI) offer comprehensive non- or less-invasive cardiac evaluation at the expense of increased costs and/or radiation exposure. Certain imaging findings usually lead to a change in medical secondary stroke prevention or may influence medical treatment. However, there is no proof from a randomized controlled trial (RCT) that the choice of the imaging method influences the prognosis of stroke patients. Summarizing present knowledge, the German Heart and Brain consortium proposes an interdisciplinary, staged standard diagnostic scheme for the detection of risk factors of cardio-embolic stroke. This expert opinion paper aims to give practical advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on expert opinion, reported case series, and clinical experience.

In patients with perimesencephalic subarachnoid hemorrhage (pSAH) DSA is recommended to exclude aneurysms to due false negative findings in CT-angiography. However, whether a second DSA is indicated during the clinical course to exclude--in addition to aneurysms--fistulas, too, is still under debate. We aimed to evaluate the benefit of repeated DSA in patients with pSAH.The source of data was a prospective database set up at the neurological, neurosurgical and neuroradiological departments in our institution. A total of 69 patients with pSAH were enrolled and analyzed by reviewing the medical records and neuroradiological findings.68 patients presented with Hunt & Hess Grade I-II and one patient with Hunt & Hess Grade III. Median in-hospital stay was 8 days (3-22). In 2 patients mild vasospasm were diagnosed. DSA was performed in all patients at least once. DSA was repeated in 38 patients (55%) after a median of 7 (3-21) days. None of the repeated DSA did show any additional distinctive features with respect to the first DSA.In our opinion the procedure of repeating DSA in patients with pSAH is likely to become obsolete. One DSA should be performed prior to discharge--and subsequent to possible vasospasm--to exclude hemorrhage caused by aneurysms of the posterior circulation mimicking a perimesencephalic SAH pattern.

Object Only limited data exist addressing the long-term outcome of patients with ganglionic hemorrhage complicated by intraventricular hemorrhage (IVH) and hydrocephalus that requires an external ventricular drain (EVD). The aim of this study was to compare the long-term outcome of patients with pure ganglionic hemorrhage and those requiring an EVD due to additional IVH and hydrocephalus. Methods For this study, 116 patients with supratentorial ganglionic hemorrhage and occlusive hydrocephalus were screened. To avoid any bias the authors excluded all patients with nonprimary intracerebral hemorrhage as well as those who received no treatment. Forty patients with IVH and subsequent hydrocephalus were examined, and 40 more patients with pure ganglionic hematomas were matched with regard to age, sex, Glasgow Coma Scale score, need for mechanical ventilation, and, in particular, hematoma volume. Outcome analysis was performed using the Barthel Index and the modified Rankin Scale (mRS). The mean hematoma volume was 25.3 ± 15.2 ml. The overall long-term outcome was unfavorable (mRS Score 4–6) in 59% of all patients. Good outcome (mRS score &lt; 4) was observed in 25 (62.5%) of 40 patients with hematoma volumes less than 25 ml, compared with eight (20%) of 40 who had hematoma volumes greater than 25 ml (p &lt; 0.05, chi-square test). The need for an EVD was not associated with a worse long-term outcome in patients with comparable hematoma volumes. In contrast, the duration of treatment in the intensive care unit was longer for patients with EVDs than for those who had pure ganglionic hematomas (16 [range 5–29] days compared with 8 [range 2–19] days; p &lt; 0.05, Mann–Whitney U-test), regardless of hematoma volume. Conclusions The long-term outcome of treated patients with supratentorial ganglionic hemorrhage with ventricular involvement and occlusive hydrocephalus is comparable to that of patients with similar hematoma volumes but no IVH.

To describe a 71-year-old woman who developed clinical and neuroradiological features of posterior reversible leukoencephalopathy syndrome with a compromised blood-brain barrier after 5 days of intravenous linezolid therapy for an infected hip prosthesis.Case report.Academic research.Posterior reversible leukoencephalopathy syndrome was documented using serial cranial magnetic resonance imaging, and the blood-brain barrier disturbance was demonstrated by contrast enhancement of a lesion and by cerebrospinal fluid analysis.Other causes of posterior reversible leukoencephalopathy syndrome, such as renal failure, severe hypertension, inflammatory syndromes, and infectious diseases of the central nervous system, were excluded during hospitalization. After discontinuation of linezolid therapy, the patient's condition improved rapidly.To our knowledge, this is the first report of likely linezolid-induced posterior reversible leukoencephalopathy syndrome with an altered blood-brain barrier after short-term intravenous therapy.

<h3>Background:</h3> Intraventricular fibrinolysis (IVF) through bilateral external ventricular drains (EVD) may provide better access of the thrombolytic agent to the intraventricular clot, potentially influencing clot clearance and outcome. <h3>Methods:</h3> Patients with spontaneous ganglionic intracerebral haemorrhage (ICH)&lt;40 cm³ and intraventricular haemorrhage (IVH) with acute hydrocephalus have been treated with IVF. The decision for placement of one or two EVDs has been left to the discretion of the treating physician. CT volumetry, the effects on cerebrospinal fluid (CSF) circulation and outcome at 3 months have been analysed for patients with one (group I, n = 13) or two EVDs (group II, n = 14). <h3>Results:</h3> No difference was found in clot resolution between the two groups (clot half life 2.1 (SD 1.2) vs 2.4 (1.3) days). A separate analysis of the third and fourth ventricle clearance was similar (1.6 (0.6) versus 1.8 (0.8) days), indicating no difference in reconstitution of CSF circulation. A trend towards a longer EVD duration and higher infection rate was found in the bilateral EVD group. No difference was found in outcome at 3 months. <h3>Conclusions:</h3> Our results do not support the use of bilateral EVDs for IVF in patients with severe IVH.

&lt;i&gt;Background:&lt;/i&gt; Recombinant tissue plasminogen activator (rt-PA) is the only approved specific therapy for acute ischemic stroke. This study analyzes demographic and clinical characteristics of patients with early complete neurological recovery after thrombolysis. &lt;i&gt;Methods:&lt;/i&gt; Data of 320 consecutive patients treated with rt-PA within 3 h of stroke onset at our facility between April 2006 and March 2009 were extracted from our prospective institutional stroke and thrombolysis database. Baseline demographic parameters, risk factors, clinical characteristics as well as neuroradiologic findings of patients with complete recovery 24 h after treatment and at hospital discharge were analyzed. Outcome was evaluated using the modified Rankin Scale at 90 days. &lt;i&gt;Results:&lt;/i&gt; Thirty patients (9.4%) were asymptomatic 24 h after thrombolysis and 70 (22%) at hospital discharge. Patients with complete recovery were younger, more often male, had milder stroke symptoms, less often cardioembolic strokes, fewer bleeding complications and more often normal follow-up imaging. In addition, in-hospital time was shorter and these patients retained a better functional outcome at 90 days. Only 1 patient who had completely recovered at hospital discharge died during the follow-up time. In multivariate regression analysis, only the National Institute of Health Stroke Score (NIHSS) on admission was predictive for complete recovery at both examined time points. &lt;i&gt;Conclusion:&lt;/i&gt; Rapid complete recovery can be achieved in up to a fifth of acute stroke patients treated with thrombolysis. These patients are younger and have milder strokes, less often with cardioembolic origin. Better outcome and lower mortality are sustained at 3 months.

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.

Intraventricular haemorrhage (IVH) is an independent predictor of poor outcome in spontaneous intracerebral haemorrhage (ICH). Larger IVH volume and increasing number of affected ventricles have been associated with worse prognosis, however, little is known about the prognostic value of blood volume in the different parts of the ventricular system. Therefore, the correlation of IVH volume in the third, fourth and lateral ventricles with outcome in patients with ICH and severe IVH, treated with intraventricular fibrinolysis (IVF), was investigated.Patients with ICH <40 ml, severe IVH and acute hydrocephalus were treated with IVF. The course of IVH volume for each ventricle was measured by CT based volumetry. Outcome at 90 days was assessed by a telephone follow-up survey and correlated with initial IVH volume.50 patients aged 62.5±10.3 years with spontaneous ICH (12.5±10.8 ml) and severe IVH (33.5±25 ml) were included. Clearance of the third and fourth ventricle from blood occurred after 3±1.9&emsp14;days. Initial IVH volume in the third ventricle (3.8±3.3 ml) was predictive for poor outcome (OR 2.6 per ml, p=0.02). Correlation between larger IVH volume in the fourth ventricle and poor outcome showed a trend towards significance (p=0.07). Total IVH volume and lateral ventricle IVH volume were not correlated with outcome.Despite rapid clot removal, initial IVH volume in the third ventricle was a strong and independent negative predictor. This is possibly explained by irreversible damage of brainstem structures by the initial mass effect of IVH.