Introduction: DOACs are associated with an increased risk of hematoma expansion (HE) in spontaneous ICH, yet the critical DOAC plasma levels influencing this risk are unknown. Methods: A retrospective multicenter study on DOAC-associated ICH across 10 centers in Germany and Taiwan. Patients with emergent DOAC plasma levels upon admission were included. DOAC levels were categorized using proposed cut-offs and ROC analysis. HE was defined as a ≥35% increase in hematoma volume between admission and 48-hour CT scans, with symptomatic HE defined as a concurrent ≥4-point NIHSS increase. Multivariable regression analysis explored associations between DOAC cut-offs and HE, adjusting for baseline ICH volume, onset-to-imaging time, systolic blood pressure and reversal use. Results: In this preliminary analysis, 197 patients were included (57% male; median age 81 [75–84] years; median NIHSS 12 [IQR 7–19]). Most received FXa inhibitors (98%), four dabigatran (median DOAC level: 101.5 ng/mL [IQR 51–187.5]). Overall, HE within 48 hours occurred in 58 of 197 patients (29.4%) and symptomatic HE in 23 patients (11.7%). The frequency of symptomatic HE increased stepwise with higher DOAC levels: 9.2% below 100 ng/mL, 14.1% at ≥100 ng/mL, 16.4% at ≥150 ng/mL, 20.5% at ≥200 ng/mL, 23.8% at ≥250 ng/mL and 25.0% at ≥300 ng/mL. While unadjusted analysis indicated higher rates of symptomatic HE at ≥200 ng/mL (p=0.04), multivariable models did not reach statistical significance (aOR 2.0, 95%CI 0.7–5.8; p=0.21 at ≥200 ng/mL). A nonsignificant trend toward higher risk was observed at very high levels (aOR 3.0, 95%CI 0.8–10.7; p=0.09 at ≥300 ng/mL). Conclusions: The risk of symptomatic HE may increase with higher DOAC plasma levels in patients with DOAC-associated ICH, with a possible threshold effect at very high levels. These preliminary findings require further analysis of the full multicenter cohort to assess the predictive value of specific DOAC thresholds for clinical risk stratification.

A heart-transplant recipient developed fatal neurologic disease. High-throughput sequencing (HTS) identified Dobrava - Belgrade virus in central nervous system (CNS) and peripheral specimens. Genomic analyzes showed distinct viral populations across compartments, suggesting CNS tropism. This case highlights atypical infection presentations in immunosuppressed patients and underscores the diagnostic value of HTS.

Background Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome. Methods This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS. Results Both groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission ( p = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months ( p = 0.043). Conclusions Although the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.

Purpose: The Harlequin syndrome may occur in patients treated with venoarterial extracorporal membrane oxygenation (VA-ECMO), in whom blood from the left ventricle and the ECMO system supply different parts of the body with different paCO2-levels. The purpose of this study was to compare two variants of paCO2-analysis to account for the Harlequin syndrome during apnea testing (AT) in brain death (BD) determination. Materials and methods: Twenty-seven patients (median age 48 years, 26-76 years; male n = 19) with VA-ECMO treatment were included who underwent BD determination. In variant 1, simultaneous arterial blood gas (ABG) samples were drawn from the right and the left radial artery. In variant 2, simultaneous ABG samples were drawn from the right radial artery and the postoxygenator ECMO circuit. Differences in paCO2-levels were analysed for both variants. Results: At the start of AT, median paCO2-difference between right and left radial artery (variant 1) was 0.90 mmHg (95%-confidence intervall [CI]: 0.7-1.3 mmHg). Median paCO2-difference between right radial artery and postoxygenator ECMO circuit (variant 2) was 3.3 mmHg (95%-CI: 1.5-6.0 mmHg) and thereby significantly higher compared to variant 1 (p = 0.001). At the end of AT, paCO2-difference according to variant 1 remained unchanged with 1.1 mmHg (95%-CI: 0.9-1.8 mmHg). In contrast, paCO2-difference according to variant 2 increased to 9.9 mmHg (95%-CI: 3.5-19.2 mmHg; p = 0.002). Conclusions: Simultaneous paCO2-analysis from right and left distal arterial lines is the method of choice to reduce the risk of adverse effects (e.g. severe respiratory acidosis) while performing AT in VA-ECMO patients during BD determination.

BACKGROUND:Computed tomography angiography (CTA) has been investigated as a confirmatory study (CS) for the diagnosis of brain death (BD). International consensus regarding its use, study parameters, and evaluation criteria is lacking. In the German BD guideline, a CTA protocol was first introduced in 2015. METHODS:The authors obtained a comprehensive dataset of all BD examinations in adults from the German organ procurement organization to investigate implementation, results, and impact of CTA on BD determination during the first 4 years. RESULTS:In 5152 patients with clinically absent brain function, 1272 CTA were reported by 676 hospitals. Use of CTA increased from 17.2% of patients in the first year to 29.7% in the final year. CTA replaced other CS such as electroencephalography without increasing overall CS frequency. Technical failure was rare (0.9%); 89.3% of studies were positive. Negative results (9.8%) were more frequent with secondary brain injury, longer duration of the clinical BD syndrome, or unreliable clinical assessment. Median time to diagnosis was longer with CTA (2.6 h) versus other CS (1.6 h). CTA had no differential impact on the rate of confirmed BD and did not improve access of small hospitals to CS for BD determination. CONCLUSIONS:CTA expands the range of available CS for the diagnosis of BD in adults. Real-world evidence from a large cohort confirms usability of the German CTA protocol within the guideline-specified context.

BACKGROUND:Selective water uptake by neurons and glial cells and subsequent brain tissue oedema are key pathophysiological processes of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Although brain computed tomography (CT) is widely used to assess the severity of HIE, changes of brain radiodensity over time have not been investigated. These could be used to quantify regional brain net water uptake (NWU), a potential prognostic biomarker. METHODS:We conducted an observational prognostic accuracy study including a derivation (single center cardiac arrest registry) and a validation (international multicenter TTM2 trial) cohort. Early (<6 h) and follow-up (>24 h) head CTs of CA patients were used to determine regional NWU for grey and white matter regions after co-registration with a brain atlas. Neurological outcome was dichotomized as good versus poor using the Cerebral Performance Category Scale (CPC) in the derivation cohort and Modified Rankin Scale (mRS) in the validation cohort. RESULTS:We included 115 patients (81 derivation, 34 validation) with out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA). Regional brain water content remained unchanged in patients with good outcome. In patients with poor neurological outcome, we found considerable regional water uptake with the strongest effect in the basal ganglia. NWU >8% in the putamen and caudate nucleus predicted poor outcome with 100% specificity (95%-CI: 86-100%) and 43% (moderate) sensitivity (95%-CI: 31-56%). CONCLUSION:This pilot study indicates that NWU derived from serial head CTs is a promising novel biomarker for outcome prediction after CA. NWU >8% in basal ganglia grey matter regions predicted poor outcome while absence of NWU indicated good outcome. NWU and follow-up CTs should be investigated in larger, prospective trials with standardized CT acquisition protocols.

Im Zuge der Fünften Fortschreibung der Richtlinie der Bundesärztekammer zur Feststellung des irreversiblen Hirnfunktionsausfalls, gültig seit September 2022, wurden die Empfehlungen der Deutschen Gesellschaft für Klinische Neurophysiologie und Funktionelle Bildgebung (DGKN) zu den ergänzenden elektrophysiologischen und Doppler-sonografischen Untersuchungen aktualisiert. Die hier präsentierten Empfehlungen der DGKN beinhalten die Indikationen, Voraussetzungen und die Durchführung dieser Zusatzverfahren bei Kindern und Erwachsenen.

Along with the Fifth Update of the German Medical Association guideline for the determination of the irreversible loss of brain function (brain death/death by neurologic criteria), effective from September 2022, the recommendations of the German Society for Clinical Neurophysiology and Functional Imaging (DGKN) for the ancillary electrophysiological (electroencephalography, early auditory evoked potentials, somatosensory evoked potentials) and neurovascular (Doppler sonography, duplex sonography) tests were updated. In particular, for Doppler and duplex sonography age-related minimum levels of mean arterial blood pressure in children were specified, and the applicability of sonography in patients with extracorporeal membrane oxygenation (ECMO) depending on the ECMO mode was determined. For the electrophysiological methods unified specifications of electrode use and the inter-electrode difference of skin-electrode impedances were newly formulated.These herewith presented recommendations describe the indications, the limitations, the requirements and the execution of these ancillary tests in the diagnosis of irreversible loss of brain function in children and adults.

results when considering treatment to support breathing after severe stroke.

Zusammenfassung Hintergrund Seit Inkrafttreten der 4. Fortschreibung der Richtlinie der Bundesärztekammer gelten in Deutschland wesentliche neue Normierungen in der Diagnostik des irreversiblen Hirnfunktionsausfalls (IHA). Hierzu zählen die Qualifikationsanforderungen an die Untersucher, zugelassene Verfahren zur apparativen Zusatzdiagnostik und eine Präzisierung zur Abfolge der Prozessschritte. Fragestellung Untersuchung der Auswirkungen auf die Praxis der IHA-Feststellung. Methodik Deskriptive Auswertung der Dokumentation der Deutschen Stiftung Organtransplantation über IHA-Diagnostik im Vergleich der Zeiträume Juli 2011 bis Juni 2015 (3. Fortschreibung) und Juli 2015 bis Juni 2019 (4. Fortschreibung). Ergebnisse Die Zahl der erfassten Patienten sank von 6100 auf 5403. Die stärkste Abnahme betraf Krankenhäuser ohne Neurochirurgie. Kinder unter 14 Jahren waren nicht betroffen. Die klinische Diagnostik erfolgte ab Juli 2015 vermehrt im Bereitschaftsdienst durch externe neurologische Konsiliare. Zusatzdiagnostik erhielten nun 83,8 % der Patienten, zuvor 80,1 %. Die neu etablierte CTA wurde bei 23,2 % eingesetzt. Sie wies in 89,4 % den zerebralen Zirkulationsstillstand nach. Die Zeitdauer zwischen erstmaliger Feststellung der klinischen Ausfallzeichen und Feststellung des IHA stieg von 7,0 ± 12,7 h auf 8,2 ± 14,2 h. Der IHA wurde mit 95,3 % gegenüber 96,6 % geringfügig seltener festgestellt. Diskussion Die neuen Normierungen wurden richtlinienkonform umgesetzt. Der Bedarf an konsiliarischer Unterstützung durch Neurologen und Neurochirurgen sowie der Zeitbedarf für die IHA-Feststellung haben zugenommen. Negative Effekte auf die pädiatrische IHA-Diagnostik wurden nicht deutlich. Die CTA wird bei Erwachsenen als neues zusatzdiagnostisches Verfahren flächendeckend erfolgreich eingesetzt.

Abstract Background Acute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%. Methods Inclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey. Results Eleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%–16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8–69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0–9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate. Conclusions Even in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment.

Der unfreiwillige Fahrraddiebstahl -62-jährige Patientin mit fulminant verlaufender akuter Bewusstseinsstörung Anamnese Eine 62-jährige Patientin wurde mit dem Rettungswagen aufgrund einer qualitativen Bewusstseinsstörung und Fieber (39,5 °C) in unsere Klinik eingeliefert.Sie war zuvor verwirrt auf der Straße aufgefunden worden, als

In dieser Rubrik stellen wir Standard Operating Procedures (SOPs) für perioperativ und intensivmedizinisch relevante Prozesse vor. Die Form ist eher im Sinne einer Schablone zu verstehen als – durchaus subjektiv gefärbte – Anregung, eigene, auf lokale Gegebenheiten adaptierte stationsinterne SOPs zu entwerfen und zu implementieren.

Background and objectives 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. Methods 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. Results 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). Discussion 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.