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BackgroundTo investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require, we characterized the reality of care for patients presenting with neuro-emergencies during the first phase of the COVID-19 pandemic.MethodsIn this observational, longitudinal cohort study, all neurosurgical admissions that presented to our department between February 1 and April 15 during the COVID-19 pandemic and during the same time period in 2019 were identified and categorized according to the presence of a neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with aneurysmal subarachnoid hemorrhage (aSAH) and chronic subdural hematoma (cSDH) was investigated representatively for severe vascular and semi-urgent traumatic conditions that present with a wide variety of symptoms.ResultsDuring the pandemic, the percentage of neuro-emergencies among all neurosurgical admissions remained similar but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p = 0.009). The total number of neuro-emergencies was significantly reduced (*p = 0.0007) across all types of disease, particularly in vascular (*p = 0.036) but also in spinal (*p = 0.007) and hydrocephalus (*p = 0.048) emergencies. Patients with spinal emergencies presented 48 h later (*p = 0.001) despite comparable symptom severity. For aSAH, the number of cases, aSAH grade, aneurysm localization, and treatment modality did not change but strikingly, elderly patients with cSDH presented less frequently, with more severe symptoms (*p = 0.046), and were less likely to reach favorable outcome (*p = 0.003) at discharge compared with previous years.ConclusionsDespite pandemic-related restrictive measures and reallocation of resources, patients with neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite of fighting COVID-19.

Neuronal cytotoxic edema is the morphological correlate of the near-complete neuronal battery breakdown called spreading depolarization, or conversely, spreading depolarization is the electrophysiological correlate of the initial, still reversible phase of neuronal cytotoxic edema. Cytotoxic edema and spreading depolarization are thus different modalities of the same process, which represents a metastable universal reference state in the gray matter of the brain close to Gibbs-Donnan equilibrium. Different but merging sections of the spreading-depolarization continuum from short duration waves to intermediate duration waves to terminal waves occur in a plethora of clinical conditions, including migraine aura, ischemic stroke, traumatic brain injury, aneurysmal subarachnoid hemorrhage and delayed cerebral ischemia, spontaneous intracerebral hemorrhage, subdural hematoma, development of brain death, and the dying process during circulatory arrest. Thus, spreading depolarization represents a prime and simultaneously the most neglected pathophysiological process in acute neurology. Aristides Leão postulated as early as the 1940s that the pathophysiological process in neurons underlying migraine aura is of the same nature as the pathophysiological process in neurons that occurs in response to cerebral circulatory arrest, because he assumed that spreading depolarization occurs in both conditions. With this in mind, it is not surprising that patients with migraine with aura have about a twofold increased risk of stroke, as some spreading depolarizations leading to the patient percept of migraine aura could be caused by cerebral ischemia. However, it is in the nature of spreading depolarization that it can have different etiologies and not all spreading depolarizations arise because of ischemia. Spreading depolarization is observed as a negative direct current (DC) shift and associated with different changes in spontaneous brain activity in the alternating current (AC) band of the electrocorticogram. These are non-spreading depression and spreading activity depression and epileptiform activity. The same spreading depolarization wave may be associated with different activity changes in adjacent brain regions. Here, we review the basal mechanism underlying spreading depolarization and the associated activity changes. Using original recordings in animals and patients, we illustrate that the associated changes in spontaneous activity are by no means trivial, but pose unsolved mechanistic puzzles and require proper scientific analysis.

It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we tested whether SDs and DCI are abolished when vasospasm is reduced or abolished by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal intracranial vessels. The SDs were recorded using a subdural electrode strip. Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs were recorded in 10 of 13 patients (77%). Digital subtraction angiography revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate vasospasm in the remaining. Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.

Currently, there is no adequate technique for intraoperative monitoring of cerebral blood flow (CBF). To evaluate laser speckle imaging (LSI) for assessment of relative CBF, LSI was performed in 30 patients who underwent direct surgical revascularization for treatment of arteriosclerotic cerebrovascular disease (ACVD), Moyamoya disease (MMD), or giant aneurysms, and in 8 control patients who underwent intracranial surgery for reasons other than hemodynamic compromise. The applicability and sensitivity of LSI was investigated through baseline perfusion and CO2 reactivity testing. The dynamics of LSI were assessed during bypass test occlusion and flow initiation procedures. Laser speckle imaging permitted robust (pseudo-) quantitative assessment of relative microcirculatory flow and standard bypass grafting resulted in significantly higher postoperative baseline perfusion values in ACVD and MMD. The applicability and sensitivity of LSI was shown by a significantly reduced CO2 reactivity in ACVD (9.6 ± 9%) and MMD (8.5 ± 8%) compared with control (31.2 ± 5%; P < 0.0001). In high- and intermediate-flow bypass patients, LSI was characterized by a dynamic real-time response to acute perfusion changes and ultimately confirmed a sufficient flow substitution through the bypass graft. Thus, LSI can be used for sensitive and continuous, non-invasive real-time visualization and measurement of relative cortical CBF in excellent spatial-temporal resolution.

Management of malignant hemispheric stroke (MHS) after cardiothoracic surgery (CTS) remains difficult as decision-making needs to consider severe cardiovascular comorbidities and complex coagulation management. The results of previous randomized controlled trials on decompressive surgery for MHS cannot be generally translated to this patient population and the expected outcome might be substantially worse. Here, we analyzed mortality and functional outcome in patients undergoing decompressive hemicraniectomy (DC) for MHS following CTS and assessed the impact of perioperative coagulation management on postoperative hemorrhagic and cardiovascular complications. All patients that underwent DC for MHS resulting as a complication of CTS between June 2012 and November 2021 were included in this observational cohort study. Outcome was determined according to the modified Rankin Scale (mRS) score at 1 and 3–6 months. Clinical and demographic data, anticoagulation management and postoperative hemorrhagic and thromboembolic complications were assessed. In order to evaluate a predictive association between clinical and radiological parameters and the outcome, we used a multivariate logistic regression analysis. Twenty-nine patients undergoing DC for MHS after CTS with a female-to-male ratio of 1:1.9 and a median age of 60 (IQR 49–64) years were identified out of 123 patients undergoing DC for MHS. Twenty-four patients (83%) received pre- or intraoperative substitution. At 30 days, the in-hospital mortality rate and neurological outcome corresponded to 31% and a median mRS of 5 (5–6), which remained stable at 3–6 months [Mortality: 42%, median mRS: 5 (4–6)]. Postoperatively, 15/29 patients (52%) experienced new hemorrhagic lesions and Bayesian logistic regression predicting mortality (mRS = 6) after imputing missing data demonstrated a significantly increased risk for mortality with longer aPPT (OR = 13.94, p = .038) and new or progressive hemorrhagic lesions after DC (OR = 3.03, p = .19). Notably, all but one hemorrhagic lesion occurred before discontinued anticoagulation and/or platelet inhibition was re-initiated. Despite perioperative discontinuation of anticoagulation and/or platelet inhibition, no coagulation-associated cardiovascular complications were noted. In conclusion, Cardiothoracic surgery patients suffering MHS will likely experience severe neurological disability after DC, which should remain a central aspect during counselling and decision-making. The complex coagulation situation after CTS, however, should not per se rule out the option of performing life-saving surgical decompression.

Radiolucent carbon-fiber reinforced PEEK (CFRP) implants have helped improve oncological follow-up and radiation therapy. Here, we investigated the performance of 3D intraoperative imaging and navigation systems for instrumentation and precision assessment of CFRP pedicle screws across the thoraco-lumbar spine. Thirty-three patients with spinal tumors underwent navigated CFRP instrumentation with intraoperative CT (iCT), robotic cone-beam CT (rCBCT) or cone-beam CT (CBCT) imaging. Two different navigation systems were used for iCT-/rCBCT- and CBCT-based navigation. Demographic, clinical and outcome data was assessed. Four blinded observers rated image quality, assessability and accuracy of CFRP pedicle screws. Inter-observer reliability was determined with Fleiss` Kappa analysis. Between 2018 and 2021, 243 CFRP screws were implanted (iCT:93, rCBCT: 99, CBCT: 51), of which 13 were non-assessable (iCT: 1, rCBCT: 9, CBCT: 3; *p = 0.0475; iCT vs. rCBCT). Navigation accuracy was highest using iCT (74%), followed by rCBCT (69%) and CBCT (49%) (*p = 0.0064; iCT vs. CBCT and rCBCT vs. CBCT). All observers rated iCT image quality higher than rCBCT/CBCT image quality (*p < 0.01) but relevant pedicle breaches were reliably identified with substantial agreement between all observers regardless of the imaging modality. Navigation accuracy for CFRP pedicle screws was considerably lower than expected from reports on titanium implants and CT may be best for reliable assessment of CFRP materials.

Spreading depolarizations (SDs) are characterized by near-complete breakdown of the transmembrane ion gradients, neuronal oedema and activity loss (=depression). The SD extreme in ischemic tissue, termed 'terminal SD,' shows prolonged depolarization, in addition to a slow baseline variation called 'negative ultraslow potential' (NUP). The NUP is the largest bioelectrical signal ever recorded from the human brain and is thought to reflect the progressive recruitment of neurons into death in the wake of SD. However, it is unclear whether the NUP is a field potential or results from contaminating sensitivities of platinum electrodes. In contrast to Ag/AgCl-based electrodes in animals, platinum/iridium electrodes are the gold standard for intracranial direct current (DC) recordings in humans. Here, we investigated the full continuum including short-lasting SDs under normoxia, long-lasting SDs under systemic hypoxia, and terminal SD under severe global ischemia using platinum/iridium electrodes in rats to better understand their recording characteristics. Sensitivities for detecting SDs or NUPs were 100% for both electrode types. Nonetheless, the platinum/iridium-recorded NUP was 10 times smaller in rats than humans. The SD continuum was then further investigated by comparing subdural platinum/iridium and epidural titanium peg electrodes in patients. In seven patients with either aneurysmal subarachnoid hemorrhage or malignant hemispheric stroke, two epidural peg electrodes were placed 10 mm from a subdural strip. We found that 31/67 SDs (46%) on the subdural strip were also detected epidurally. SDs that had longer negative DC shifts and spread more widely across the subdural strip were more likely to be observed in epidural recordings. One patient displayed an SD-initiated NUP while undergoing brain death despite continued circulatory function. The NUP's amplitude was -150 mV subdurally and -67 mV epidurally. This suggests that the human NUP is a bioelectrical field potential rather than an artifact of electrode sensitivity to other factors, since the dura separates the epidural from the subdural compartment and the epidural microenvironment was unlikely changed, given that ventilation, arterial pressure and peripheral oxygen saturation remained constant during the NUP. Our data provide further evidence for the clinical value of invasive electrocorticographic monitoring, highlighting important possibilities as well as limitations of less invasive recording techniques.

Background External ventricular drainage (EVD)-associated ventriculitis is a serious complication in neurocritical care. Diagnostic uncertainty and heterogeneous infection prevention and control (IPC) practices may contribute to variable ventriculitis rates and potentially avoidable antibiotic exposure. We evaluated the impact of implementing an interdisciplinary standard operating procedure (SOP) on ventriculitis incidence and antimicrobial stewardship (ABS)-related outcomes. Methods We conducted a retrospective single-centre pre–post study in one intensive care unit (ICU) at Charité–Universitätsmedizin Berlin (2019–2023). Adult patients with EVDs were assigned to a pre-SOP cohort (Group 1) or a post-SOP cohort (Group 2). The SOP comprised standardized IPC protocols, an algorithm-based diagnostic workup and evidence-based anti-infective strategies. The primary endpoint was study-defined EVD-associated ventriculitis, adjudicated retrospectively using uniform criteria. Secondary endpoints included empirical antibiotic initiation, duration of therapy, antibiotic consumption, ICU length of stay (LOS), mortality, and SOP adherence. Cerebrospinal fluid (CSF) parameters and clinical signs were summarized descriptively. Results A total of 166 patients were included (pre-SOP, Group 1: n  = 50; post-SOP, Group 2: n  = 116). The study-defined ventriculitis rate decreased from 22% [95% CI 0.13–0.35] to 9.5% [95% CI 0.05–0.16] with an unadjusted OR 0.37 [95% CI 0.13–1.04]; p  = 0.053, attenuated with an adjusted OR of 0.50 [95% CI 0.19–1.35]; p  = 0.169. Incidence density declined from 21.1 to 12.0 per 1000 EVD days. Empirical antibiotic use fell from 28.0% [95% CI 17.5–41.7] to 12.9% [95% CI 8.0–20.2], corresponding to an unadjusted OR of 0.38 [95% CI 0.17–0.87] and median therapy duration decreased from 16 [95% CI 13.5–18.5] to 10 days [95% CI 6.5–13.5]. ICU LOS shortened by 4 days, while ICU mortality remained unchanged (26% vs. 27%). Conclusion An interdisciplinary SOP was associated with reduced empirical antibiotic exposure and shorter treatment duration without affecting ICU mortality. The SOP appeared to improve diagnostic consistency and standardization of the workup rather than diagnostic test performance. Trial registration The study is registered in the German Clinical Trial Register (DRKS ID: 00036075) in February 2025.

Study Design Retrospective Cohort Study Objective To evaluate the accuracy of intraoperatively measured computed tomography (CT) Hounsfield unit (HU) values by comparison with preoperative CT HU values and to compare the radiation exposure between preoperative and intraoperative CT scans. Methods HU values of lumbar vertebrae were measured and compared between preoperative and intraoperative CT scans in patients undergoing lumbar interbody fusion. In patient group one, Canon CT scanners were used preoperatively and the AIRO CT scanner was used intraoperatively. In patient group two, Canon CT scanners were used preoperatively and the O-arm Cone Beam CT (CBCT) scanner was used intraoperatively. In a subgroup analysis of patient group one, radiation by means of CT Dose Index (CTDI) was compared between Canon and AIRO CT scanners. Results In the first patient group, a total of 250 vertebrae were analysed in 74 patients showing a strong Pearson correlation of >.94 between pre- and intraoperative HU values. Bland-Altman analysis indicated consistency and equivalence with a bias of 3.9 and 95% limits of agreement from −27.17 to 34.97 when comparing all pre- and intraoperative HU values of L1–5. In the second patient group, a total of 27 vertebrae were analysed in 10 patients showing weak Pearson correlation and Bland-Altman analysis indicated no equivalence. CTDI did not differ between Canon and AIRO CT scanners. Conclusion Correct and reliable CT HU measurement as mandatory key factor for the intraoperative assessment of bone quality and robotic-assisted surgery is feasible with intraoperative AIRO CT imaging without increase of radiation exposure.

Surgical flow augmentation for treatment of cerebral hemodynamic impairment remains controversial. Here, we investigated the benefit of endothelial progenitor cell (EPC) treatment in a rat model of chronic cerebral hypoperfusion. At repeated time points after 3-vessel occlusion (3-VO), animals were treated with 1 × 10 6 Dil-labeled (a) ex vivo-expanded embryonic-EPC (e-EPC), (b) cyclic AMP-differentiated embryonic-endothelial progenitor-derived cells (e-EPDC as biologic control) or, (c) saline. The cerebrovascular reserve capacity (CVRC) was assessed immediately before and on days 7 and 21 after 3-VO. Structural effects were assessed by latex perfusion, immunohistochemistry, and intravital fluorescence video microscopy on day 21. Three-vessel occlusion resulted in a significant impairment of the CVRC with better functional recovery after treatment with e-EPC (16.4 ± 8%) compared with e-EPDC (3.7 ± 8%) or saline (6.4 ± 9%) by day 21 (P<0.05), which was paralleled by a significant increase in the vessel diameters of the anterior Circle of Willis, a significantly higher number of leptomeningeal anastomoses and higher parenchymal capillary density in e-EPC-treated animals. Interestingly, despite in vivo interaction of e-EPC with the cerebral endothelium, e-EPC incorporation into the cerebral vasculature was not observed. Our results suggest that EPC may serve as a novel therapeutic agent in clinical trials for nonsurgical treatment of chronic cerebral hemodynamic impairment.