Ferdinand Oliver Bohmann

Background: The timing of ischemic stroke and intracerebral hemorrhage (ICH) onsets follow distinct daily patterns, but it remains unclear whether these patterns influence ICH outcomes. Methods: Consecutive data were obtained from the prospective stroke inpatient quality assurance registry of Hesse, Germany from 2015 to 2023. Patients with ICH were grouped according to the time of symptom onset: morning (5:00 AM to 10:59 AM), midday (11:00 AM to 4:59 PM), evening (5:00 PM to 10:59 PM), and night (11:00 PM to 4:59 AM). The primary outcome was global disability at discharge, analyzed using ordinal logistic regression. Secondary outcomes included mortality and complications during hospitalization. To account for potential confounding, the analysis incorporated both inverse probability weighting (IPW) and propensity score matching (PSM) based on baseline characteristics. Results: After exclusions, 5665 patients underwent final analysis. Peak ICH incidences occurred around 8:30 AM and 5:00 PM with a minimum at approximately midnight. Patients experiencing ICH during the evening and particularly at night had higher discharge disability, compared to those with symptom onset in the morning or midday. Unadjusted analyses found daily variations in mortality and in‐hospital complications that were no longer significant after adjustment by PSM or IPW. Conclusion: Our study confirms the daily pattern previously observed in ICH onset, with peak onset during daytime. Functional outcomes were worse in evening and night onset ICH patients. These findings underscore the potential for chronobiologically informed prevention and treatment strategies and the need for further research into time‐dependent pathophysiology and care delivery.

Introduction: In acute ischemic stroke, the time of day has been shown to influence the progression of the ischemic core, ultimately impacting patient outcomes. For intracerebral hemorrhage (ICH), data on such an impact on ICH severity are conflicting. Our aim was to identify possible associations between the timing of ICH onset and radiographic and clinical characteristics. Methods: We conducted a retrospective monocentric study on 381 adult patients with spontaneous ICH who were treated between 2010 and 2024. Patients were categorized by time of symptom onset (morning: 5:00 AM−10:59 AM, midday: 11:00 AM−4:59 PM, evening: 5:00 PM−22:59 PM and night: 23:00 PM−4:59 AM). Primary outcome was ICH volume at the first imaging scan. Secondary outcomes included edema volume, mortality, the presenting syndrome severity and Modified Rankin Scale (mRS) at discharge. Results: Intracerebral hemorrhage (ICH) onset exhibited a distinct distribution, with peaks around noon and afternoon (~4 PM), and the lowest frequency during nighttime. ICH and edema volumes, mortality, initial clinical severity, and functional outcomes did not differ significantly between onset-time groups. Independent predictors of mortality included age (OR 1.04, 95% CI 1.01–1.07, p = 0.03), pre-mRS score (OR 1.37, 95% CI 1.04–1.81, p = 0.03), and NIHSS at admission (OR 1.05, 95% CI 1.02–1.09, p = 0.002). Unfavorable outcomes (higher mRS at discharge) were associated with pre-mRS (OR 1.33, 95% CI 1.19–1.48, p < 0.001), NIHSS (OR 1.06, 95% CI 1.04–1.07, p < 0.001), hypertension (OR 1.49, 95% CI 1.06–2.10, p = 0.02), and atrial fibrillation (OR 1.43, 95% CI 1.05–1.94, p = 0.02). Conclusion: In our cohort, ICH onset times peaked during the daytime, however initial ICH and perifocal edema volumes did not differ according to the time of day. Among patients with witnessed and precisely documented ICH onset, early survival and short-term functional outcomes in patients treated at a university hospital with 24-h neurosurgical availability appear to be more strongly influenced by individual patient characteristics such as age and pre-existing conditions than by the timing of symptom onset.

Objective: With the introduction of andexanet alfa, a specific antidote is now available to address life-threatening bleeding associated with factor Xa inhibitors. In this study, we explore its use in an experimental model of traumatic brain injury (TBI), mimicking a closed head trauma under rivaroxaban-induced anticoagulation. Methods: Male C57BL6 mice were fed with rivaroxaban (10 mg/kg body weight). Subsequently, TBI was induced by controlled cortical impact (CCI) and andexanet alfa or placebo were administered as intravenous bolus injections. Edema and hemorrhage volume was quantified by magnetic resonance imaging (MRI) 24 h and 7 days after CCI. Functional outcome was assessed at day 1, 3, and 7 thereafter. Results: Andexanet alfa led to reduced hemorrhage volume 24 h and 7 days after CCI as compared with control group without reversal of anticoagulation (2.9 ± 1.4 µl vs. 5.2 ± 3.3 µl, p = 0.02; 3.4 µl ± 1.5 µl vs. 5.5 µl ± 2.4 µl, p = 0.04). Along with the smaller hematoma sizes in the MRI, edema volume was significantly lower in mice treated with andexanet alfa 24 h and 7 days after CCI (−6.3% of contralateral hemisphere, p = 0.0002; and −7.1% of contralateral hemisphere, p = 0.006). While functional outcomes did not differ at 24 h following TBI, andexanet alfa improved neurological deficits after 7 days. Conclusions: Our experimental data suggests that the use of andexanet alfa improves functional outcomes by reduction of factor Xa inhibitor–associated hematoma expansion in the subacute phase following TBI.

Introduction: Antiplatelet and anticoagulant therapies complicate the management and outcomes of traumatic brain injury (TBI) patients. This study evaluates clinical profiles and short-term outcomes focusing on prior antihemostatic therapy and tranexamic acid (TXA) use.Patients and methods: We analyzed TBI patients admitted to University Hospital Frankfurt (2018–2021), assessing demographics, injury characteristics, clinical course, and short-term outcomes. The primary endpoint was hemorrhage progression; secondary endpoints included the modified Rankin Scale (mRS) at discharge, mortality and thromboembolic complications. Regression models identified predictors of functional outcome and mortality.Results: Among 218 patients (median age 70 years, 35% female, median GCS at admission 7), 44% had prior antiplatelet or anticoagulation therapy. These patients were older, had higher pre-injury mRS scores, and more often sustained TBIs from falls. While hemorrhage progression was similar, they had worse mRS scores (p = 0.02) and higher mortality (p = 0.002). Coagulopathy (OR 1.11, CI 1.07–1.16, p < 0.001), injury severity (OR 2.25, CI 1.51–3.41, p < 0.001), and bleeding progression (OR 2.23, CI 1.48–3.41, p < 0.001) predicted poor functional outcomes. TXA was more often given to younger, severely injured patients but did not impact outcome.Conclusion: This study underscores the need for tailored therapeutic approaches to improve survival and functional recovery in patients with pre-injury antiplatelet and anticoagulant therapies.

Beim akuten ischämischen Schlaganfall handelt es sich um ein unmittelbar lebensbedrohliches und zeitkritisches Krankheitsbild. Der Verschluss der A. basilaris stellt aufgrund seiner hohen Mortalität und seines schlechten klinischen Outcomes sowie seiner variablen Symptomatik einen Sonderfall in Bezug auf Diagnostik, Therapie und Prognoseabschätzung dar. Article published online: 04 June 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Background and Objectives Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). Methods We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1–6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1–4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4–5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6–0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31–1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82–2.97], 5,656/195,539) of all stroke hospitalizations. Discussion There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. Trial Registration Information This study is registered under NCT04934020.

(Background): Effective prevention strategies and acute therapies have been established and distributed in recent years to reduce the global burden of stroke. However, beyond randomized clinical trials, limited data exist on the real-world impact of these measures. Our goal was to analyze whether the stroke-associated disability in the population decreased over time based on a state-wide stroke registry analysis. (Methods): Consecutive data from a state-wide inpatient stroke registry covering the entire federal state of Hesse, Germany, were obtained. The clinical data of 141,287 patients with ischemic stroke (ICD-10: I63) admitted between 2010 and 2019 were included. The primary outcome was the odds ratio for a change of modified Ranking Scale (mRS) at discharge over time, estimated by ordinary logistic regression and adjusted for age and sex. The secondary outcome was the odds ratio for a lower National Institutes of Health Stroke Scale (NIHSS) score at hospital admission. (Results): The absolute number of severely disabled (mRS 4–5) stroke patients at discharge decreased over time (2010: 3223 (equivalent to 53/100,000 population); 2019: 2429 [39/100,000 population]). The odds at hospital admission for a higher mRS at discharge decreased significantly by 3.7% per year (OR 0.963 (95% CI 0.960–0.966), p < 0.001). The absolute number of severely affected stroke patients (NIHSS > 15) at admission declined over time (2010: 1589 [26/100,000]; 2019: 1185 [19/100,000]; p < 0.001). The odds for a higher NIHSS score at admission to hospital decreased by 3.8% per year (OR 0.962 (95% CI 0.959–0.965), p < 0.001). Trends were most prominent for patients aged 80 years and older and for patients with atrial fibrillation but absent in patients <60 years. (Conclusions): Stroke-associated disability in the population steadily decreased between 2010 and 2019. The improved prevention of severe strokes in elderly patients may be a major driver of this observation.

(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.