Brain death determination in patients with veno-arterial extracorporeal membrane oxygenation: A systematic study to address the Harlequin syndrome.

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.

Surgical Versus Dilational Tracheostomy in Patients with Severe Stroke: A SETPOINT2 Post hoc Analysis.

BACKGROUND: Tracheostomy in mechanically ventilated patients with severe stroke can be performed surgically or dilationally. Prospective data comparing both methods in patients with stroke are scarce. The randomized Stroke-Related Early Tracheostomy vs Prolonged Orotracheal Intubation in Neurocritical Care Trial2 (SETPOINT2) assigned 382 mechanically ventilated patients with stroke to early tracheostomy versus extubation or standard tracheostomy. Surgical tracheostomy (ST) was performed in 41 of 307 SETPOINT2 patients, and the majority received dilational tracheostomy (DT). We aimed to compare ST and DT in these patients with patients. METHODS: All SETPOINT2 patients with ST were compared with a control group of patients with stroke undergoing DT (1:2), selected by propensity score matching that included the factors stroke type, SETPOINT2 randomization group, Stroke Early Tracheostomy score, patient age, and premorbid functional status. Successful decannulation was the primary outcome, and secondary outcome parameters included functional outcome at 6 months and adverse events attributable to tracheostomy. Potential predictors of decannulation were evaluated by regression analysis. RESULTS: Baseline characteristics were comparable in the two groups of patients with stroke undergoing ST (n = 41) and matched patients with stroke undergoing DT (n = 82). Tracheostomy was performed significantly later in the ST group than in the DT group (median 9 [interquartile range {IQR} 5-12] vs. 9 [IQR 4-11] days after intubation, p = 0.025). Patients with ST were mechanically ventilated longer (median 19 [IQR 17-24] vs.14 [IQR 11-19] days, p = 0.008) and stayed in the intensive care unit longer (median 23 [IQR 16-27] vs. 17 [IQR 13-24] days, p = 0.047), compared with patients with DT. The intrahospital infection rate was significantly higher in the ST group compared to the DT group (14.6% vs. 1.2%, p = 0.002). At 6 months, decannulation rates (56% vs. 61%), functional outcomes, and mortality were not different. However, decannulation was performed later in the ST group compared to the DT group (median 81 [IQR 66-149] vs. 58 [IQR 32-77] days, p = 0.004). Higher baseline Stroke Early Tracheostomy score negatively predicted decannulation. CONCLUSIONS: In ventilated patients with severe stroke in need of tracheostomy, surgical and dilational methods are associated with comparable decannulation rate and functional outcome at 6 months. However, ST was associated with longer time to decannulation and higher rates of early infections, supporting the dilational approach to tracheostomy in ventilated patients with stroke.

Fit for Service: Preparing Residents for Neurointensive Care with Entrustable Professional Activities: A Delphi Study.

BACKGROUND: Although the relevance of neurointensive medicine and high-quality training of corresponding physicians is increasingly recognized, there is high heterogeneity in the nature, duration, and quality of neurointensive care curricula around the world. Thus, we aimed to identify, define, and establish validity evidence for entrustable professional activities (EPAs) for postgraduate training in neurointensive care to determine trainees' readiness for being on-call. METHODS: After defining EPAs through an iterative process by an expert group, we used a modified Delphi approach with a single-center development process followed by a national consensus and a single-center validation step. EPAs were evaluated by using the EQual rubric (Queen's EPA Quality Rubric). Interrater reliability was measured with Krippendorff's α. RESULTS: The expert group defined seven preliminary EPAs for neurointensive care. In two consecutive Delphi rounds, EPAs were adapted, and consensus was reached for level of entrustment and time of expiration. Ultimately, EPAs reached a high EQual score of 4.5 of 5 and above. Interrater reliability for the EQual scoring was 0.8. CONCLUSIONS: Using a multistep Delphi process, we defined and established validity evidence for seven EPAs for neurointensive medicine with a high degree of consensus to objectively describe readiness for on-call duty in neurointensive care. This operationalization of pivotal clinical tasks may help to better train clinical residents in neurointensive care across sites and health care systems and has the potential to serve as a blueprint for training in general intensive care medicine. It also represents a starting point for further research and development of medical curricula.

Outcomes After Decompressive Surgery for Severe Cerebral Venous Sinus Thrombosis Associated or Not Associated with Vaccine-Induced Immune Thrombosis with Thrombocytopenia: A Multicenter Cohort Study.

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.

COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke (COTTIS): a pilot study.

BACKGROUND: To evaluate the feasibility and safety of a fast initiation of cooling to a target temperature of 35°C by means of transnasal cooling in patients with anterior circulation large vessel occlusion (LVO) undergoing endovascular thrombectomy (EVT). METHODS: Patients with an LVO onset of <24 hour who had an indication for EVT were included in the study. Transnasal cooling (RhinoChill) was initiated immediately after the patient was intubated for EVT and continued until an oesophageal target temperature of 35°C was reached. Hypothermia was maintained with surface cooling for 6-hour postrecanalisation, followed by active rewarming (+0.2°C/hour). The primary outcome was defined as the time required to reach 35°C, while secondary outcomes comprised clinical, radiological and safety parameters. RESULTS: Twenty-two patients (median age, 77 years) were included in the study (14 received additional thrombolysis, 4 additional stenting of the proximal internal carotid artery). The median time intervals were 309 min for last-seen-normal-to-groin, 58 min for door-to-cooling-initiation, 65 min for door-to-groin and 123 min for door-to-recanalisation. The target temperature of 35°C was reached within 30 min (range 13-78 min), corresponding to a cooling rate of 2.6 °C/hour. On recanalisation, 86% of the patients had a body temperature of ≤35°C. The median National Institutes of Health Stroke Scale at admission was 15 and improved to 2 by day 7, and 68% of patients had a good outcome (modified Rankin Scale 0-2) at 3 months. Postprocedure complications included asymptomatic bradycardia (32%), pneumonia (18%) and asymptomatic haemorrhagic transformation (18%). CONCLUSION: The combined application of hypothermia and thrombectomy was found to be feasible in sedated and ventilated patents. Adverse events were comparable to those previously described for EVT in the absence of hypothermia. The effect of this procedure will next be evaluated in the randomised COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke-2 trial.

[Prospective investigation of extracranial duplex sonography for the detection of cerebral circulatory arrest in patients with irreversible loss of brain function]. / Prospektive Untersuchung der extrakraniellen Duplexsonographie zum Nachweis des zerebralen Perfusionsstillstands bei Patienten mit irreversiblem Hirnfunktionsausfall.

BACKGROUND: A broader distribution of bedside color-coded duplex sonography (CCD) for detection of cerebral circulatory arrest (CCA) would be important to improve its use in the diagnosis of irreversible loss of brain function (ILBF-Dx). QUESTION: Is extracranial compared to the commonly applied transcranial CCD of the brain-supplying vessels (ECCD vs. TCCD) equivalent for the detection of CCA in ILBF-Dx regarding specificity and sensitivity? MATERIAL AND METHODS: Study period January 2019-June 2022, screening of 136 and inclusion of 114 patients with severe brain lesions > 24 h after onset of fixed and dilated pupils, apnea and completed ILBF-Dx. Exclusion of patients without brainstem areflexia and guideline-conform applicability of CCD. Complementary ECCD (and TCCD, if other method used for irreversibility detection). RESULTS: Detection of ILBF (ILBF+) in 86.8% (99/114), no ILBF (ILBF-) in 13.2% (15/114). ECCD was fully feasible in all patients; findings matching CCA were found in 94/99 ILBF+ cases (ECCD+) and not in 5 patients (ECCD-). All 15 patients with ILBF- showed ECCD- findings. Thus, the specificity of ECCD was 1.0, and the sensitivity was 0.949. TCCD showed CCA in 56 patients (TCCD+), and ECCD+ was also found in all of them. An inconclusive result of TCCD in ILBF+ was found in 38 cases, with parallel ECCD+ in all of these patients. In 20 cases, TCCD did not show CCA (TCCD-), these also showed ECCD-. Of these patients 15 were ILBF- and 5 were ILBF+. DISCUSSION: TCCD was not completely feasible or inconclusive in one third of the cases, whereas ECCD was always feasible. ECCD showed high validity with respect to the detection of CCA. Therefore, the possibility of using ECCD alone to detect CCA in ILBF-Dx should be discussed.

Minimally-invasive bedside catheter haematoma aspiration followed by local thrombolysis in spontaneous supratentorial intracerebral haemorrhage: a retrospective single-center study.

Background and purpose: The role of surgery in the treatment of intracerebral haemorrhage (ICH) remains controversial. Whereas open surgery has failed to show any clinical benefit, recent studies have suggested that minimal invasive procedures can indeed be beneficial, especially when they are applied at an early time point. This retrospective study therefore evaluated the feasibility of a free-hand bedside catheter technique with subsequent local lysis for early haematoma evacuation in patients with spontaneous supratentorial ICH. Methods: Patients with spontaneous supratentorial haemorrhage of a volume of >30 mL who were treated with bedside catheter haematoma evacuation were identified from our institutional database. The entry point and evacuation trajectory of the catheter were based on a 3D-reconstructed CT scan. The catheter was inserted bedside into the core of the haematoma, and urokinase (5,000 IE) was administered every 6 h for a maximum of 4 days. Evolution of haematoma volume, perihaemorrhagic edema, midline-shift, adverse events and functional outcome were analyzed. Results: A total of 110 patients with a median initial haematoma volume of 60.6 mL were analyzed. Haematoma volume decreased to 46.1 mL immediately after catheter placement and initial aspiration (with a median time to treatment of 9 h after ictus), and to 21.0 mL at the end of urokinase treatment. Perihaemorrhagic edema decreased significantly from 45.0 mL to 38.9 mL and midline-shift from 6.0 mm to 2.0 mm. The median NIHSS score improved from 18 on admission to 10 at discharge, and the median mRS at discharge was 4; the latter was even lower in patients who reached a target volume ≤ 15 mL at the end of local lysis. The in-hospital mortality rate was 8.2%, and catheter/local lysis-associated complications occurred in 5.5% of patients. Conclusion: Bedside catheter aspiration with subsequent urokinase irrigation is a safe and feasible procedure for treating spontaneous supratentorial ICH, and can immediately reduce the mass effects of haemorrhage. Additional controlled studies that assess the long-term outcome and generalizability of our findings are therefore warranted. Clinical trial registration: [www.drks.de], identifier [DRKS00007908].

Exclusive color-coded duplex sonography of extracranial vessels reliably confirms brain death: A prospective study.

Background: Transcranial color-coded duplex sonography (TCCD) can be used as an ancillary test for determining irreversible loss of brain function (ILBF) when demonstration of cerebral circulatory arrest (CCA) is required. However, visualization of the intracranial vessels by TCCD is often difficult, or even impossible, in this patient cohort due to elevated intracranial pressure, an insufficient transtemporal bone window, or warped anatomical conditions. Since extracranial color-coded duplex sonography (ECCD) can be performed without restriction in the aforementioned situations, we investigated the feasibility of omitting TCCD altogether, such that the ILBF examination would be simplified, without compromising on its reliability. Methods: A total of 122 patients were prospectively examined by two experienced neurointensivists for the presence of ILBF from 01/2019-12/2021. Inclusion criteria were (i) the presence of a severe cerebral lesion on cranial CT or MRI, and (ii) brainstem areflexia. Upon standardized clinical examination, 9 patients were excluded due to incomplete brainstem areflexia, and a further 22 due to the presence of factors with a potentially confounding influence on apnea testing, EEG or sonography. A total of 91 patients were enrolled and underwent needle-EEG recording for >30 min (= gold standard), as well as ECCD and TCCD. The sonographer was blinded to the EEG result. Results: All patients whose ECCD result was consistent with ILBF had this diagnosis confirmed by EEG (n = 77; specificity: 1). Both ECCD and EEG were not consistent with ILBF in a further 12 patients. In the remaining two patients, ECCD detected reperfusion due to long-lasting cerebral hypoxia; however, ILBF was ultimately confirmed by EEG (sensitivity: 0.975). This yielded a positive predictive value (PPV) of one and a negative predictive value of 0.857 for the validity of ECCD in ILBF confirmation. TCCD was not possible/inconclusive in 31 patients (34%). Conclusions: The use of ECCD for the confirmation of ILBF is associated with high levels of specificity and a high positive predictive value when compared to needle-electrode EEG. This makes ECCD a potential alternative to the ancillary tests currently used in this setting, but confirmation in a multi-center trial is warranted. Trial registration: https://www.drks.de, DRKS00017803.

Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial.

BACKGROUND: The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only. METHODS: SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017. FINDINGS: 513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group. INTERPRETATION: CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. FUNDING: German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation: The SETPOINT2 Randomized Clinical Trial.

Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation. Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation. Design, Setting, and Participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10. Patients were randomized between July 28, 2015, and January 24, 2020, at 26 US and German neurocritical care centers. The final date of follow-up was August 9, 2020. Interventions: Patients were assigned to an early tracheostomy strategy (n = 188) or to a standard tracheostomy (control group) strategy (n = 194). Main Outcomes and Measures: The primary outcome was functional outcome at 6 months, based on the modified Rankin Scale score (range, 0 [best] to 6 [worst]) dichotomized to a score of 0 (no disability) to 4 (moderately severe disability) vs 5 (severe disability) or 6 (death). Results: Among 382 patients randomized (median age, 59 years; 49.8% women), 366 (95.8%) completed the trial with available follow-up data on the primary outcome (177 patients [94.1%] in the early group; 189 patients [97.4%] in the standard group). A tracheostomy (predominantly percutaneously) was performed in 95.2% of the early tracheostomy group in a median of 4 days after intubation (IQR, 3-4 days) and in 67% of the control group in a median of 11 days after intubation (IQR, 10-12 days). The proportion without severe disability (modified Rankin Scale score, 0-4) at 6 months was not significantly different in the early tracheostomy vs the control group (43.5% vs 47.1%; difference, -3.6% [95% CI, -14.3% to 7.2%]; adjusted odds ratio, 0.93 [95% CI, 0.60-1.42]; P = .73). Of the serious adverse events, 5.0% (6 of 121 reported events) in the early tracheostomy group vs 3.4% (4 of 118 reported events) were related to tracheostomy. Conclusions and Relevance: Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months. However, the wide confidence intervals around the effect estimate may include a clinically important difference, so a clinically relevant benefit or harm from a strategy of early tracheostomy cannot be excluded. Trial Registration: ClinicalTrials.gov Identifier: NCT02377167.

Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic.

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.

Ultrasound Perfusion Imaging for the Detection of Cerebral Hypoperfusion After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia increases mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Various techniques are applied to detect cerebral vasospasm and hypoperfusion. Contrast-enhanced ultrasound perfusion imaging (UPI) is able to detect cerebral hypoperfusion in acute ischemic stroke. This prospective study aimed to evaluate the use of UPI to enable detection of cerebral hypoperfusion after aSAH. METHODS: We prospectively enrolled patients with aSAH and performed UPI examinations every second day after aneurysm closure. Perfusion of the basal ganglia was outlined to normalize the perfusion records of the anterior and posterior middle cerebral artery territory. We applied various models to characterize longitudinal perfusion alterations in patients with delayed ischemic neurologic deficit (DIND) across the cohort and predict DIND by using a multilayer classification model. RESULTS: Between August 2013 and December 2015, we included 30 patients into this prospective study. The left-right difference of time to peak (TTP) values showed a significant increase at day 10-12. Patients with DIND demonstrated a significant, 4.86 times increase of the left-right TTP ratio compared with a mean fold change in patients without DIND of 0.9 times (p = 0.032). CONCLUSIONS: UPI is feasible to enable detection of cerebral tissue hypoperfusion after aSAH, and the left-right difference of TTP values is the most indicative result of this finding.

Basilar Artery Embolism Mimicking Transient Global Amnesia in a 61-Year-Old Female: A Case Report.

Transient global amnesia (TGA) is a self-limiting neurological condition that temporarily affects patients' ability to access and store memories. So far, its etiology is unknown; however, ischemic origin has been discussed in the past. We present the case of a 61-year-old female with clinical appearance of TGA. MRI and duplex scan revealed punctiform and patchy ischemic lesions in both temporal lobes and right vertebral artery dissection, suggesting basilar artery embolism as the underlying cause. Our case report shows that TGA can be a symptom of ischemic lesions in the hippocampus and patients with presentation of additional focal neurologic symptoms or atypical distribution or appearance of the diffusion-weighted image (multiple/patchy) lesions should get ischemic stroke diagnosis and treatment.

Temporal Expression Pattern of Hemoxygenase-1 Expression and Its Association with Vasospasm and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Red blood cell-induced cerebral inflammation and toxicity has been shown to be attenuated by induction of the heme-catalyzing enzyme, hemoxygenase-1 (HO-1), in animal models of subarachnoid hemorrhage (SAH). Although inflammatory mechanisms leading to secondary neuronal injury in SAH are becoming increasingly well understood, markers of cerebral inflammation have so far not been implemented in clinical prediction models of SAH. METHODS: In this biomarker observational study, HO-1 messenger ribonucleic acid (mRNA) expression levels were determined in cerebrospinal fluid (CSF) and blood of 66 patients with aneurysmal SAH on days 1, 7, and 14 after the SAH event. HO-1 mRNA expression was determined via real time polymerase chain reaction (PCR), and relative expression changes were quantified in comparison with expression levels in nonhemorrhagic control CSF. Subarachnoid blood burden, as well as presence of vasospasm and delayed cerebral ischemia (DCI), were recorded. Short and long-term clinical outcomes were assessed using the Modified Rankin Scale at discharge and 1 year after the SAH event. RESULTS: CSF HO-1 expression levels showed a significant increase over the 14-day observation period (p < 0.001, F = 22.53) and correlated with intracranial hematoma burden (ρ = 0.349, p = 0.025). In multivariate analyses, CSF HO-1 expression levels did not reach significance as independent predictors of outcome. Vasospasm on computed tomographic angiography was associated with lower CSF HO-1 expression levels on day 7 after SAH (n = 53, p = 0.010), whereas patients with DCI showed higher CSF HO-1 expression levels on day 14 after SAH (n = 21, p = 0.009). CONCLUSIONS: HO-1 expression in CSF in patients with SAH follows a distinct temporal induction pattern and is dependent on intracranial hematoma burden. CSF HO-1 expression was unable to predict functional outcome. Associations of early low HO-1 expression with vasospasm and late elevated HO-1 expression with DCI may point to detrimental effects of late HO-1 induction, warranting the need for further investigation in a larger study population.

Drip-and-Ship for Thrombectomy Treatment in Patients With Acute Ischemic Stroke Leads to Inferior Clinical Outcomes in a Stroke Network Covering Vast Rural Areas Compared to Direct Admission to a Comprehensive Stroke Center.

Introduction: Organizing regional stroke care considering thrombolysis as well as mechanical thrombectomy (MTE) remains challenging in light of a wide range of regional population distribution. To compare outcomes of patients in a stroke network covering vast rural areas in southwestern Germany who underwent MTE via direct admission to a single comprehensive stroke center [CSC; mothership (MS)] with those of patients transferred from primary stroke centers [PSCs; drip-and-ship (DS)], we undertook this analysis of consecutive stroke patients with MTE. Materials and Methods: Patients who underwent MTE at the CSC between January 2013 and December 2016 were included in the analysis. The primary outcome measure was 90-day functional independence [modified Rankin score (mRS) 0-2]. Secondary outcome measures included time from stroke onset to recanalization/end of MTE, angiographic outcomes, and mortality rates. Results: Three hundred and thirty-two consecutive patients were included (MS 222 and DS 110). Median age was 74 in both arms of the study, and there was no significant difference in baseline National Institutes of Health Stroke Scale scores (median MS 15 vs. 16 DS). Intravenous (IV) thrombolysis (IVT) rates differed significantly (55% MS vs. 70% DS, p = 0.008). Time from stroke onset to recanalization/end of MTE was 112 min shorter in the MS group (median 230 vs. 342 min, p < 0.001). Successful recanalization [thrombolysis in cerebral infarction (TICI) 2b-3] was achieved in 72% of patients in the MS group and 73% in the DS group. There was a significant difference in 90-day functional independence (37% MS vs. 24% DS, p = 0.017), whereas no significant differences were observed for mortality rates at 90 days (MS 22% vs. DS 17%, p = 0.306). Discussion: Our data suggest that patients who had an acute ischemic stroke admitted directly to a CSC may have better 90-day outcomes than those transferred secondarily for thrombectomy from a PSC.

Contralateral Stenosis and Echolucent Plaque Morphology are Associated with Elevated Stroke Risk in Patients Treated with Asymptomatic Carotid Artery Stenosis within a Controlled Clinical Trial (SPACE-2).

BACKGROUND: Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS. METHODS: The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed. RESULTS: Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50%ECST vs. 20%ECST; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70%ECST vs. 20%ECST; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS. CONCLUSION: In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.

Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model.

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model.Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes.Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups.Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial.

BACKGROUND: Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer's solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH. METHODS: This is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0-3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints. DISCUSSION: New approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer's solution. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645 . Registered on 8 May 2019.

Intracerebral Hemorrhage in COVID-19 Patients with Pulmonary Failure: A Propensity Score-Matched Registry Study.

BACKGROUND: Hypercoagulability in Coronavirus Disease 2019 (COVID-19) causes deep vein thrombosis and pulmonary embolism necessitating systemic anticoagulation. Case reports of intracerebral hemorrhages in ventilated COVID-19 patients warrant precaution. It is unclear, however, if COVID-19 patients with acute respiratory distress syndrome (ARDS) with or without veno-venous extracorporeal membrane oxygenation therapy (VV-ECMO) have more intracerebral hemorrhages (ICH) compared to other ARDS patients. METHODS: We conducted a retrospective observational single-center study enrolling all patients with ARDS from 01/2018 to 05/2020. PCR-positive SARS-CoV-2 patients with ARDS were allocated to the COVID-19 group. Propensity score matching was performed for age, VV-ECMO, and bleeding risk. RESULTS: A total of 163 patients with moderate or severe ARDS were identified, 47 (28.8%) in the COVID-19 group, and 116 (71.2%) in the non-COVID-19 group. In 63/163 cases (38.7%), VV-ECMO therapy was required. The ICU survival was 52.8%. COVID-19 patients were older, more often male, and exhibited a lower SOFA score, but the groups showed similar rates of VV-ECMO therapy. Treatments with antiplatelet agents (p = 0.043) and therapeutic anticoagulation (p = 0.028) were significantly more frequent in the COVID-19 patients. ICH was detected in 22 patients (13.5%) with no statistical difference between the groups (11.2 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.21). Propensity score matching confirmed similar rates of ICH in both groups (12.8 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.57), thus leveling out possible confounders. CONCLUSIONS: Intracerebral hemorrhage was detected in every tenth patient with ARDS. Despite statistically higher rates of antiplatelet therapy and therapeutic anticoagulation in COVID-19 patients, we found a similar rate of ICH in patients with ARDS due to COVID-19 compared to other causes of ARDS.