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Introduction: Neurocritical care patients with neurovascular disease often face poor long-term outcomes, highlighting the pivotal role of evidence-based interventions. Although International Guidelines emphasize managing basic physiological parameters like temperature, blood glucose, blood pressure, and oxygen levels, physician adherence to these targets remains uncertain. This study aimed to assess adherence to guideline-based treatment targets for basic physiological parameters in neurocritical care., Patients and Methods: This multicenter observational study was conducted across eight tertiary University Hospitals in Germany analyzed 474 patients requiring mechanical ventilation (between January 1st and December 31st, 2021). Adherence was defined as the rate of measurements within therapeutic ranges for systolic blood pressure (situation-adapted), mean blood pressure (MAP, 60-90 mmHg), glucose levels (80-180 mg/dl), body temperature (<37.5°C), partial arterial pressure of oxygen (PaO 2 ) 80-120 mmHg und partial arterial pressure of carbon dioxide (PaCO 2 ) 35-45 mmHg during the initial 96 h of hospitalization in 4 hour-intervals., Results: Overall, 70.7% of all measurements were within the predetermined therapeutic ranges including SBP (71.3%), temperature (68.3%), MAP (71.4%), PaO 2 (65.2%), PaCO 2 (75.0%) and blood glucose (80.7%)., Discussion and Conclusion: This multicenter study demonstrates adherence to guideline-based treatment targets, underscoring the high standards maintained by neurological intensive care units. Our study offers valuable insights into adherence to guideline-based treatment targets for neurocritical care patients in Germany. To improve patient care and optimize therapeutic strategies in neurovascular diseases, further research is needed to examine the impact of these adherence parameters on long-term outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intra-arterial nimodipine administration is a widely used rescue therapy for cerebral vasospasm. Although it is known that its effect sets in with delay, there is little evidence in current literature. Our aim was to prove that the maximal vasodilatory effect is underestimated in direct angiographic controls. We reviewed all cases of intra-arterial nimodipine treatment for subarachnoid hemorrhage-related cerebral vasospasm between January 2021 and December 2022. Inclusion criteria were availability of digital subtraction angiography runs before and after nimodipine administration and a delayed run for the most affected vessel at the end of the procedure to decide on further escalation of therapy. We evaluated nimodipine dose, timing of administration and vessel diameters. Delayed runs were performed in 32 cases (19 patients) with a mean delay of 37.6 (± 16.6) min after nimodipine administration and a mean total nimodipine dose of 4.7 (± 1.2) mg. Vessel dilation was more pronounced in delayed vs. immediate controls, with greater changes in spastic vessel segments (n = 31: 113.5 (± 78.5%) vs. 32.2% (± 27.9%), p < 0.0001) vs. non-spastic vessel segments (n = 32: 23.1% (± 13.5%) vs. 13.3% (± 10.7%), p < 0.0001). In conclusion intra-arterially administered nimodipine seems to exert a delayed vasodilatory effect, which should be considered before escalation of therapy., (© 2024. The Author(s).)

Purpose: Patients with glioblastoma are exposed to severe symptoms and organs failures (e.g., coma or acute respiratory failure), that may require intensive care unit (ICU) admission and invasive mechanical ventilation (IMV). However, only limited data are available concerning the prognosis of patients with glioblastoma receiving IMV. We sought to describe the reasons for ICU admission, and outcomes of patients with glioblastoma requiring IMV for unplanned critical complications., Methods: In this retrospective analysis, four certified interdisciplinary brain tumor centers performed a retrospective review of their electronic data systems. All patients with glioblastoma admitted to an in-house ICU and receiving IMV between January 2015 and December 2019 were included. Clinical and prognostic factors as well as relevant outcome parameters were evaluated by group comparisons and Kaplan Meier survival curves., Results: We identified 33 glioblastoma patients with a duration of IMV of 9.2 ± 9.4 days. Main reasons for ICU admission were infection (n = 12; 34.3%) including 3 cases of Pneumocystis jirovecii pneumonia, status epilepticus (31.4%) and elevated intracranial pressure (22.9%). In-hospital mortality reached 60.6%. Younger age, low number of IMV days, better Karnofsky Performance Status Scale before admission and elevated intracranial pressure as cause of ICU admission were associated with positive prognostic outcome., Conclusion: We conclude that less than 50% of patients with glioblastoma have a favorable short-term outcome when unplanned ICU treatment with IMV is required. Our data mandate a careful therapy guidance and frequent reassessment of goals during ICU stay., (© 2023. The Author(s).)

Purpose: Ureaplasma species are associated with urogenital infections, infertility and adverse pregnancy outcomes as well as neonatal infections. Involvement of the central nervous system in adults is extremely rare. We report an unusual case of a brain abscess secondary to otitis media with Ureaplasma parvum in a patient with granulomatosis with polyangiitis (GPA)., Methods: Imaging and laboratory findings, treatment decisions, and outcome of this case are explicated., Results: A young adult with GPA presented with progredient earache after ambulant diagnosis of otitis media. Despite different courses of broad-spectrum antibiotic therapy, she developed meningoencephalitis due to mastoiditis following temporal abscess formation. Mastoidectomy and neurosurgical abscess removal were performed. Standard cultures of cerebrospinal fluid, blood and intracranial abscess material, as well as polymerase chain reaction (PCR) for common bacterial and viral meningitis pathogens remained negative. Only eubacterial PCR of intracranial abscess material returned positive for Ureaplasma parvum. The patient finally improved under antibiotic therapy with moxifloxacin and doxycycline., Conclusion: Ureaplasma species are rare causative pathogens in immunocompromised patients. They should be considered in patients with humoral immunodeficiencies with culture-negative infections failing standard therapy. Eubacterial PCR should be performed in early states of infection in these patients for immediate diagnosis and initiation of appropriate treatment to prevent adverse outcomes., (© 2022. The Author(s).)

Objective: Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction. However, evidence shaping treatment decisions, particularly for treatment-refractory cases, is sparse. Both rituximab and eculizumab may be considered as therapeutic options for refractory MG after insufficient symptom control by standard immunosuppressive therapies., Methods: In this retrospective observational study, we included 57 rituximab-treated and 20 eculizumab-treated patients with MG to compare the efficacy of treatment agents in generalised, therapy-refractory anti-acetylcholine receptor antibody (anti-AChR-ab)-mediated MG with an observation period of 24 months. Change in the quantitative myasthenia gravis (QMG) score was defined as the primary outcome parameter. Differences between groups were determined in an optimal full propensity score matching model., Results: Both groups were comparable in terms of clinical and demographic characteristics. Eculizumab was associated with a better outcome compared with rituximab, as measured by the change of the QMG score at 12 and 24 months of treatment. Minimal manifestation of disease was more frequently achieved in eculizumab-treated patients than rituximab-treated patients at 12 and 24 months after baseline. However, the risk of myasthenic crisis (MC) was not ameliorated in either group., Interpretation: This retrospective, observational study provides the first real-world evidence supporting the use of eculizumab for the treatment of refractory, anti-AChR-ab positive MG. Nonetheless, the risk of MC remained high and prompts the need for intensified monitoring and further research effort aimed at this vulnerable patient cohort., Competing Interests: Competing interests: CN reports no conflicts of interest. CBS reports no conflicts of interest. FS received speaking honoraria from Biogen and Alexion. MP received speaker honoraria and travel/accommodation/meeting expenses from Novartis. LR-N reports no disclosures. NM reports no conflicts of interest. PM is on the Advisory Board of HealthNextGen and has equity interest in the company. His research is funded by the Bundesministerium für Bildung und Forschung (BMBF), the European Union, the Else Kröner-Fresenius Stiftung, the Volkswagen Stiftung and the Einstein Foundation Berlin. AG reports no conflicts of interest. HS reports no conflicts of interest. MS reports no conflicts of interest. BB received travel grants and/or training expenses from Bayer Vital GmbH, IpsenPharma GmbH, Norvartis, Biogen GmbH and Genzyme, as well as lecture fees from Ipsen Pharma GmbH, Alexion Pharma GmbH, Merck, Sanofi Genzyme and Roche. AT reports on conflicts of interest. TH received speaker honoraria and advisor honoraria from Alexion, Argenx, Biogen, Roche, Sanofi-Genzyme, Novartis and Hormosan. SS reports no conflicts of interest. SV reports no conflicts of interest. AM received speaker honoraria, consulting services and/or research support research from Alexion, argnx, GRIFOLS, Hormosan, Janssen, Octapharma, UCB and Vitaccess. He serves as chairman of the medical advisory board of the German Myasthenia Gravis Society. HW receives honoraria for acting as a member of Scientific Advisory Boards, Biogen, Evgen, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG and Sanofi-Aventis as well as speaker honoraria and travel support from Alexion, Biogen, Cognomed, F. Hoffmann-La Roche, Gemeinnützige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Genzyme, TEVA and WebMD Global. HW is acting as a paid consultant for AbbVie, Actelion, Biogen, IGES, Johnson & Johnson, Novartis, Roche, Sanofi-Aventis and the Swiss Multiple Sclerosis Society. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Else Kröner Fresenius Foundation, Fresenius Foundation, the European Union, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster and RE Children’s Foundation, Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme. SGM receives honoraria for lecturing, and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Bundesinstitut für Risikobewertung (BfR), Deutsche Forschungsgemeinschaft (DFG), Deutsche Multiple Sklerose Gesellschaft (DMSG), Else Kröner Fresenius Foundation, Gemeinsamer Bundesausschuss (G-BA), German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology and Alexion, Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, HERZ Burgdorf, Merck Serono, Novartis, ONO Pharma, Roche and Teva. HW receives honoraria for acting as a member of Scientific Advisory Boards, Biogen, Evgen, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG and Sanofi-Aventis as well as speaker honoraria and travel support from Alexion, Biogen, Cognomed, F. Hoffmann-La Roche, Gemeinnützige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Genzyme, TEVA and WebMD Global. TR reports grants from German Ministry of Education, Science, Research and Technology, grants and personal fees from Sanofi-Genzyme and Alexion; personal fees from Biogen, Roche and Teva; personal fees and non-financial support from Merck Serono, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Myasthenic crisis (MC) and disease exacerbation in myasthenia gravis (MG) are associated with significant lethality and continue to impose a high disease burden on affected patients. Therefore, we sought to determine potential predictors for MC and exacerbation as well as to identify factors affecting outcome., Methods: We examined a retrospective, observational cohort study of patients diagnosed with MG between 2000 and 2021 with a mean follow-up of 62.6 months after diagnosis from eight tertiary hospitals in Germany. A multivariate Cox regression model with follow-up duration as the time variable was used to determine independent risk factors for MC and disease exacerbation., Results: 815 patients diagnosed with MG according to national guidelines were included. Disease severity at diagnosis (quantitative MG score or Myasthenia Gravis Foundation of America class), the presence of thymoma and anti-muscle specific tyrosine kinase-antibodies were independent predictors of MC or disease exacerbation. Patients with minimal manifestation status 12 months after diagnosis had a lower risk of MC and disease exacerbation than those without. The timespan between diagnosis and the start of immunosuppressive therapy did not affect risk. Patients with a worse outcome of MC were older, had higher MGFA class before MC and at admission, and had lower vital capacity before and at admission. The number of comorbidities, requirement for intubation, prolonged mechanical ventilation, and MC triggered by infection were associated with worse outcome. No differences between outcomes were observed comparing treatments with IVIG (intravenous immunoglobulin) vs. plasma exchange vs. IVIG together with plasma exchange., Conclusions: MC and disease exacerbations inflict a substantial burden of disease on MG patients. Disease severity at diagnosis and antibody status predicted the occurrence of MC and disease exacerbation. Intensified monitoring with emphasis on the prevention of infectious complications could be of value to prevent uncontrolled disease in MG patients., (© 2022. The Author(s).)

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

Importance: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established., Objective: To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH., Design, Setting, and Participants: 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)., Exposure: Surgical hematoma evacuation vs conservative treatment., Main Outcomes and Measures: 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., Results: 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)., Conclusions and Relevance: 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.

Introduction: The overall prevalence of myasthenic crisis is quite low at 30/1 million inhabitants because myasthenia gravis is a rare disease per se. But it should be noted that 15-20% of patients with myasthenia gravis experience at least one crisis in their lives. Most often, the crisis occurs within the first 2 years of the disease or is even the first manifestation of a yet undiagnosed myasthenia gravis in up to 20%.Median duration of MC is about 2 weeks (median 12-14 days of ventilation) under sufficient treatment, but prolonged courses are not uncommon and often due to comorbidities and complications, so that about 20% are still mechanically ventilated after 1 month.The lifetime risk of recurrence of a crisis is approx. 30%. Data on mortality differ between about 2-5% to even more than 16%. Lethal outcomes are almost never caused by the crisis itself, but because comorbidities or complications eventually become limiting., Definition: Myasthenic crisis (MC) is the life-threatening maximal manifestation of myasthenia gravis (MG) necessitating mechanical ventilation, supportive feeding and (neuro-)intensive care. Weakness may develop within minutes to days and encompass flaccid tetraparesis with immobility, severe dyspnea, respiratory insufficiency and aspiration. Globus events may be life threatening due to rapidly exhausting coughing and swallowing., First Steps Immediate Measures: ● Check and secure vital functions., Comments: ● not applicable., Conclusion: The main symptom of (imminent) myasthenic crisis is the rapidly progressive weakness of the respiratory and bulbar muscles, which lead to a decompensation with aspiration and respiratory insufficiency. Clinical examination and clinical history should lead early to the diagnosis of MG with (impending) crisis. The detection of red flags and the dynamic deterioration of symptoms entail admission to the intensive care unit. Due to bulbar symptoms with aspiration and/or respiratory insufficency, early intubation to secure the airway is essential. Therapy includes symptomatic treatment with pyridostigmine or neostigmine and acute causal treatment by immunoadsorption/plasmapheresis or alternatively with immunoglobulins. If used early, intubation may still be prevented and clinical improvement can be achieved within a few days. At the same time, immunosuppression with corticosteroids and azathioprine should be initiated or optimized. For escalation rituximab is an option. The early diagnosis and consequent treatment of infections and other complications such as delirium influence the further course., Competing Interests: Competing interestsH. Stetefeld declares that he has no competing interests. M. Schroeter has received speaking fees from Alexion, Biogen, Genzyme/Sanofi, Grifols, Miltenyi Biotec, Novartis., (© The Author(s) 2019.)

Objective: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH., Methods: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC., Results: IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC., Conclusions: Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention., Competing Interests: Competing interests: JBK reports grants from Covidien (Medtronic), personal fees from Bayer, Pfizer and Sanofi. ME reports grants and other from Bayer, other from Boehringer Ingelheim, BMS/Pfizer and Daiichi Sankyo during the conduct of the study; grants from DFG, BMBF, EU, Corona Foundation and Fondation Leducq, other from Amgen, GSK, Novartis, Sanofi and Covidien. KGH reports grants and personal fees from Bayer, personal fees from Daiichi Sankyo, BMS, Pfizer, Boehringer Ingelheim, Sanofi-Aventis and Edwards Lifesciences, non-financial support from Getemed, personal fees from EIP Pharma and Medtronic. JS reports personal fees from Bayer, Pfizer/BMS, Daiichi and Boehringer Ingelheim. PAR reports personal fees from Boehringer Ingelheim, Bayer, Daiichi Sankyo and Pfizer. JCP reports personal fees from Boehringer Ingelheim and Pfizer. TR reports personal fees from BMS Pfizer, Bayer Healthcare, Daiichi Sankyo and Boehringer Ingelheim. JV reports grants from Medtronic and Boston Scientific and fees from Medtronic, St Jude, Boston Scientific, UCB, Merz, Allergan, Teva, Novartis and AbbVie. WM reports personal fees from Boehringer Ingelheim and Bayer Pharma. PK reports personal fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo and Pfizer/Bristol-Myers Squibb. FE reports grants and personal fees from Boehringer Ingelheim, personal fees from Bayer Pharma, Pfizer Pharma, Bristol-Myers Squibb and Daiichi Sankyo. MN reports personal fees from Speaker’s fee Pfizer/BMS and Boehringer Ingelheim. PDS reports personal fees from Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi and Medtronic. JG reports personal fees from Pfizer. UJK reports other from Daiichi Sankyo and Bayer. GRF reports personal fees from Bayer and Boehringer. CD reports speaking fees from Bayer, UCB, Daiichi Sankyo and Pfizer. JM reports personal fees from Boehringer Ingelheim and Bayer Healthcare. HN reports personal fees from Boehringer Ingelheim and Daiichi. JR reports personal fees from Bayer, Boehringer, Pfizer and Bristol Myers Squibb. MS reports grants from Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), and the European Union (EU) and fees from Bristol-Myers Squibb, GlaxoSmithKline, Merz Pharmaceuticals, Novartis Pharma, Orion Pharma, Pharmacia, Roche, Sanofi, Teva Pharma and UCB Pharma. GR reports personal fees from Boehringer Ingelheim, Pfizer and Bayer, grants from Daiichi. HB reports personal fees from Honoraria for lectures from Bayer Vital, Boehringer Ingelheim, Bristol-Myers Squibb and Daiichi Sankyo. HS reports grants from Bayer Healthcare. FP reports personal fees from Pfizer/BMS, Bayer, Boehringer Ingelheim and Daiichi Sankyo. JCW reports personal fees from Boehringer Ingelheim Pharma GmbH & Co. KGH reports personal fees from Daiichi Sankyo Pharma. AG reports personal fees from Daiichi Sankyo, Bayer, Boehringer Ingelheim and Bristol-Myers Squibb/Pfizer. GFH reports participation in the Respect-ESUS trial. SS reports personal fees from Boehringer Ingelheim and grants from Daiichi. HBH reports personal fees from Boehringer Ingelheim, Daiichi Sankyo and Novartis, grants from Medtronic., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Correction to: Clin Neuroradiol 2017 https://doi.org/10.1007/s00062-017-0651-3 The original version of this article unfortunately contained a mistake. The presentation of Fig. 2 was incorrect. The corrected figure is given ….

Background: Mechanical thrombectomy (MT) of basilar artery occlusions (BAO) is a subject of debate. We investigated the clinical outcome of MT in BAO and predictors of a favorable outcome., Material and Methods: A total of 104 MTs of BAO (carried out between 2010 and 2016) were analyzed. Favorable outcome as a modified Rankin scale (mRS) ≤ 2 at 90 days was the primary endpoint. The influence of the following variables on outcome was investigated: number of detectable posterior communicating arteries (PcoAs), patency of basilar tip, completeness of BAO and posterior circulation Alberta Stroke Program early computed tomography score (PC-ASPECTS). Secondary endpoints were technical periprocedural parameters including symptomatic intracranial hemorrhage (sICH)., Results: The favorable clinical outcome at 90 days was 25% and mortality was 43%. The rate of successful reperfusion, i.e. modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was 82%. Presence of bilateral PcoAs (area under the curve, AUC: 0.81, odds ratio, OR: 4.2, 2.2-8.2; p < 0.0001), lower National Institute of Health Stroke Scale (NIHSS) on admission (AUC: 0.74, OR: 2.6, 1.3-5.2; p < 0.01), PC-ASPECTS ≥ 9 (AUC: 0.72, OR: 4.2, 1.5-11.9; p < 0.01), incomplete BAO (AUC: 0.66, OR: 2.6, 1.4-4.8; p < 0.001), and basilar tip patency (AUC: 0.66, OR: 2.5, 1.3-4.8; p < 0.01) were associated with a favorable outcome. Stepwise logistic regression analysis revealed that the strongest predictors of favorable outcome at 90 days were bilateral PcoAs, low NIHSS on admission, and incomplete BAO (AUC: 0.923, OR: 7.2, 3-17.3; p < 0.0001)., Conclusion: The use of MT for BAO is safe with high rates of successful reperfusion. Aside from baseline NIHSS and incomplete vessel occlusion, both known predictors of favorable outcome in anterior circulation events, we found that collateral flow based on the presence or absence of PcoAs had a decisive prognostic impact.

Aims: 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., Methods and Results: 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)., Conclusion: 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.

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 < 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., (© 2018 American Neurological Association.)

Background and Purpose: Cerebral large vessel occlusion (LVO) in acute ischemic stroke (AIS) may be complete (CLVO) or incomplete (ILVO). The influence of ILVO on clinical outcome after mechanical thrombectomy (MT) remains unclear. We investigated primarily the clinical outcome in patients with AIS due to ILVO or CLVO., Methods: Five hundred three consecutive AIS patients with LVO treated with stent-retriever or direct aspiration-based MT between 2010 and 2016 were analyzed. The primary endpoint was favorable clinical outcome (modified Rankin Scale ≤2) at 90 days; secondary endpoints were periprocedural parameters., Results: Forty-nine patients (11.3%) with a median National Institutes of Health Stroke Scale (NIHSS) of 11 presented with ILVO and the remainder presented with CLVO and median NIHSS of 15 (p < 0.001). The median groin puncture-to-reperfusion time was 30 vs. 67 min, respectively (p < 0.001). Successful reperfusion was reached in 47 out of 49 ILVO (95.9%) vs. 298 out of 381 CLVO (78.2%; p < 0.005) with less retrieval maneuvers (1.7 ± 2.2 vs. 3.0 ± 2.5; p < 0.001). The favorable outcome at 90 days was 81% in patients with ILVO vs. 29.1% in CLVO (p < 0.001); respective all-cause mortality rates were 6.4 vs. 28.5% (p < 0.001). Periprocedural complications (6.9%) occurred exclusively in CLVO patients (p < 0.05). ILVO was associated with favorable clinical outcome independent of age and NIHSS in multivariate logistic regression both in the anterior (OR 3.6; 95% CI 1.8-6.9; p < 0.001) and posterior circulation (OR 3.5; 95% CI 1.8-6.9; p < 0.001)., Conclusions: AIS due to ILVO is frequent and is associated with a nearly threefold higher chance of favorable clinical outcome at 90 days, independent of age and initial NIHSS compared to CLVO., (© 2017 S. Karger AG, Basel.)

Background: Haematoma expansion is a major cause of mortality in intracranial haemorrhage related to vitamin K antagonists (VKA-ICH). Normalisation of the international normalised ratio (INR) is recommended, but optimum haemostatic management is controversial. We assessed the safety and efficacy of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with VKA-ICH., Methods: We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2·0 were randomly assigned (1:1) by numbered sealed envelopes to 20 mL/kg of intravenous FFP or 30 IU/kg of intravenous four-factor PCC within 1 h after initial cerebral CT scan. The primary endpoint was the proportion of patients with INR 1·2 or lower within 3 h of treatment initiation. Masking of treatment was not possible, but the primary analysis was observer masked. Analyses were done using a treated-as-randomised approach. This trial is registered with EudraCT, number 2008-005653-37, and ClinicalTrials.gov, number NCT00928915., Findings: Between Aug 7, 2009, and Jan 9, 2015, 54 patients were randomly assigned (26 to FFP and 28 to PCC) and 50 received study drug (23 FFP and 27 PCC). The trial was terminated on Feb 6, 2015, after inclusion of 50 patients after a safety analysis because of safety concerns. Two (9%) of 23 patients in the FFP group versus 18 (67%) of 27 in the PCC group reached the primary endpoint (adjusted odds ratio 30·6, 95% CI 4·7-197·9; p=0·0003). 13 patients died: eight (35%) of 23 in the FFP group (five from haematoma expansion, all occurring within 48 h after symptom onset) and five (19%) of 27 in the PCC group (none from haematoma expansion), the first of which occurred on day 5 after start of treatment. Three thromboembolic events occurred within 3 days (one in the FFP group and two in the PCC group), and six after day 12 (one and five). 43 serious adverse events (20 in the FFP group and 23 in the PCC group) occurred in 26 patients. Six serious adverse events were judged to be FFP related (four cases of haematoma expansion, one anaphylactic reaction, and one ischaemic stroke) and two PCC related (ischaemic stroke and pulmonary embolism)., Interpretation: In patients with VKA-related intracranial hemorrhage, four-factor PCC might be superior to FFP with respect to normalising the INR, and faster INR normalisation seemed to be associated with smaller haematoma expansion. Although an effect of PCC on clinical outcomes remains to be shown, our data favour the use of PCC over FFP in intracranial haemorrhage related to VKA., Funding: Octapharma., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Bacterial meningitis is a life-threatening emergency that is still associated with high mortality and poor outcome., Objective: The purpose of this article is to provide a review of clinical presentation, diagnostic procedure, therapy, and prognosis in bacterial meningitis. Prognostic factors which could be influenced positively are identified and a focused procedure in the emergency setting and for the treatment of complications are provided., Material and Methods: This work is based on a literature search (PubMed, guidelines) and personal experience (standard operating procedures, SOP)., Results: Despite improved health care, bacterial meningitis is still associated with high mortality and poor neurological outcome, which has remained largely unaltered during recent decades. Diagnosis and, more importantly, effective therapy of bacterial meningitis are often delayed, having an immediate negative influence on clinical outcome. Neurological and nonneurological complications often necessitate intensive care and may occur rapidly or in the further course of the disease., Conclusion: Immediate initiation of effective therapy is crucial to positively influence mortality and neurological outcome. Antibiotics should be administered within 30 min after admission. To achieve this, a focused and well-organized procedure in the emergency setting is necessary. Because of intra- and extracranial complications, patients need to be treated on intensive care units including neurological expertise and interdisciplinary support.

Background and Purpose: Intravenous thrombolysis with rtPA is the standard of care for patients with acute ischemic stroke within 4.5 hours after symptom onset. However, a considerable number of patients are ineligible for IV thrombolysis due to various contraindications. Recent studies have proved the superiority of mechanical thrombectomy for patients with large-vessel occlusions in combination with IV rtPA compared with IV rtPA alone. We aimed to demonstrate the efficacy of mechanical thrombectomy for patients who are ineligible for IV rtPA., Materials and Methods: Patients from the stroke registries of 4 dedicated centers who were treated with mechanical thrombectomy from January 2010 to October 2014 were retrospectively evaluated. Inclusion criteria were the following: acute stroke due to proved large-artery occlusion, ineligibility for IV thrombolysis, and a timeframe of ≤4.5 hours between stroke and the start of mechanical thrombectomy. Recanalization success, periprocedural complications, clinical outcome, and hemorrhages were evaluated., Results: One hundred thirty endovascular recanalization procedures were identified. The locations were the following: proximal ICA in 17 (13.1%), terminus ICA in 25 (19.2%), M1 segment in 77 (59.2%), and M2 segment in 11 (8.5%). TICI 2b/3 results were achieved in 101 (77.7%), and an mRS score of 0-2 in 47 patients (37.9%). There was a significant correlation between TICI 2b/3 results and good clinical outcomes (87.2% versus 6.8%; P = .048). A good clinical result was most frequent when recanalization was achieved within 4.5 hours (37/74 = 50% versus 10/50 = 20.0%; P = .001). Symptomatic hemorrhage occurred in 13.1% of patients; mortality was 24.2%. Periprocedural complications were recorded in 10 patients (7.7%)., Conclusions: Mechanical thrombectomy can achieve good clinical outcomes in patients with acute large-artery occlusion ineligible for IV thrombolysis, in particular when recanalization is reached early., (© 2016 by American Journal of Neuroradiology.)

Background: There is growing evidence for the efficacy of mechanical thrombectomy in acute stroke patients with large-vessel occlusions in the anterior circulation. Although distal occlusions of the middle cerebral artery (MCA) can cause severe clinical symptoms, endovascular therapy is not considered here as the first choice. The aim of our study was to prove the efficacy and safety of mechanical thrombectomy for distal occlusion types in the anterior circulation (M2-segment)., Methods: Stentretriever-based thrombectomy was performed in 119 patients with acute MCA occlusions between October 2011 and April 2013: 104 (87.4%) were M1- and 15 (12.6%) M2-occlusions. These groups were compared with regard to recanalization success, periprocedural complications, hemorrhage, and modified Rankin Scale (mRS) at 90 days., Results: Thrombolysis in cerebral infarction 2b/3 reperfusion was more frequent in M2- than in M1-occlusions (93.3% versus 76.0%; P = .186). There was no significant difference in the mean National Institutes of Health Stroke Scale between the M1- and the M2-group both at admission and at discharge (16.18 ± 7.30 versus 13.73 ± 8.30, P = .235; 9.36 ± 8.60 versus 7.43 ± 9.84, P = .446). A good clinical outcome (mRS 0-2) at 3 months was more frequent in the M2-group (60% versus 43.3%; P = .273) and mortality was higher in the M1-group (21.2% versus 6.7%; P = .297). There were 3 periprocedural complications in the M1- and none in the M2-group., Conclusions: Endovascular treatment of M2-occlusions in severely affected patients is not associated with a higher procedural risk or postprocedural hemorrhage. Compared with M1-occlusions, there was a greater chance for a good angiographic and clinical result in our case series. Therefore, stentretriever-based thrombectomy should also be considered for patients with severe symptoms because of an acute M2-occlusion., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Importance: Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH)., Objective: To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption., Design, Setting, and Participants: 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., Exposures: Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment., Main Outcomes and Measures: 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., Results: 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%)., Conclusions and Relevance: 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., Trial Registration: clinicaltrials.gov Identifier: NCT01829581.