Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review.

BACKGROUND: Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The lack of standardized experimental setups and outcome assessments, particularly regarding secondary vasospastic/ischemic events, may be partly responsible for the translational failure. The study aims to delineate the procedural characteristics and assessment modalities of secondary vasospastic and ischemic events, serving as surrogates for clinically relevant delayed cerebral ischemia, in recent rat and murine subarachnoid hemorrhage models. METHODS AND RESULTS: We conducted a systematic review of rat and murine in vivo subarachnoid hemorrhage studies (published: 2016-2020) using delayed cerebral ischemia/vasospasm as outcome parameters. Our analysis included 102 eligible studies. In murine studies (n=30), the endovascular perforation model was predominantly used, while rat studies primarily employed intracisternal blood injection to mimic subarachnoid hemorrhage. Particularly, the injection models exhibited considerable variation in injection volume, rate, and cerebrospinal fluid withdrawal. Peri-interventional monitoring was generally inadequately reported across all models, with body temperature and blood pressure being the most frequently documented parameters (62% and 34%, respectively). Vasospastic events were mainly assessed through microscopy of large cerebral arteries. In 90% of the rat and 86% of the murine studies, only male animals were used. CONCLUSIONS: Our study underscores the substantial heterogeneity in procedural characteristics and outcome assessments of experimental subarachnoid hemorrhage research. To address these challenges, drafting guidelines for standardization and ensuring rigorous control of methodological and experimental quality by funders and journals are essential. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022337279.

Intra-arterial nimodipine for the treatment of refractory delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is one of the main contributors to poor clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). Endovascular spasmolysis with intra-arterial nimodipine (IAN) may resolve angiographic vasospasm, but its effect on infarct prevention and clinical outcome is still unclear. We report the effect of IAN on infarction rates and functional outcome in a consecutive series of SAH patients. METHODS: To assess the effectiveness of IAN, we collected functional outcome data of all SAH patients referred to a single tertiary center since its availability (2011-2020). IAN was primarily reserved as a last tier option for DCI refractory to induced hypertension (iHTN). Functional outcome was assessed after 12 months according to the Glasgow Outcome Scale (GOS, favorable outcome = GOS4-5). RESULTS: Out of 376 consecutive SAH patients, 186 (49.5%) developed DCI. Thereof, a total of 96 (25.5%) patients remained unresponsive to iHTN and received IAN. DCI-related infarction was observed in 44 (45.8%) of IAN-treated patients with a median infarct volume of 111.6 mL (Q1: 51.6 to Q3: 245.7). Clinical outcome was available for 84 IAN-treated patients. Of those, a total of 40 (47.6%) patients reached a favorable outcome after 1 year. Interventional complications were observed in 9 (9.4%) of the IAN-treated patients. CONCLUSION: Intra-arterial spasmolysis using nimodipine infusion was associated with low treatment specific complications. Despite presenting a subgroup of severely affected SAH patients, almost half of IAN-treated patients were able to lead an independent life after 1 year of follow-up. TRIAL REGISTRATION NUMBER: German Clinical Trial Register DRKS00030505.

The Hibiscus Model: A Feasible Cadaveric Model Using Continuous Arterial Circulation for Intracranial Bypass Training and Its Validation.

OBJECTIVE: The frequency of intracranial bypass procedures has declined. Thus it is difficult for neurosurgeons to develop the necessary skills for this complex procedure. We present a perfusion-based cadaveric model to provide a realistic training experience with high anatomic and physiological fidelity, as well as instantaneous assessment of bypass patency. Validation was assessed by evaluating the educational impact and skill improvement of the participants. METHODS: Fourteen participants attended a hands-on revascularization course with 7 cadaveric models connected to a continuous arterial circulation system pumping a red-colored solution through the entire cranial vasculature, mimicking blood circulation. The ability to perform a vascular anastomosis was evaluated initially. Further, a questionnaire on prior experience was provided. At the end of the 36-hour course, the ability to perform an intracranial bypass was reexamined and the participants completed a self-assessment questionnaire. RESULTS: Initially, only 3 attendees were able to perform an end-to-end anastomosis within the time limit, and only 2 of these anastomoses showed adequate patency. After having accomplished the course, all participants were able to complete a patent end-to-end anastomosis within the time limit, thus demonstrating a significant improvement. Further, both overall educational gain and surgical skills were regarded as remarkable (n = 11 and n = 9). CONCLUSIONS: Simulation-based education is considered an important aspect of medical and surgical development. The presented model is a feasible and accessible alternative to the prior models used for cerebral bypass training. This training may serve as a helpful and widely available tool to improve neurosurgeons' development irrespective of financial resources.

Procedural and Methodological Quality in Preclinical Stroke Research-A Cohort Analysis of the Rat MCAO Model Comparing Periods Before and After the Publication of STAIR/ARRIVE.

The translation of preclinical stroke research into successful human clinical trials remains a challenging task. The first Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for preclinical research and several other guidelines were published to address these challenges. Most guidelines recommend the use of physiological monitoring to detect the occurrence of undesired pathologies such as subarachnoid hemorrhage and to limit the variability of the infarct volume and-therefore-homogenize the experimental result for complete reporting particularly with respect to transparency and methodological rigor. From the years 2009 and 2019, 100 published articles each using a rat stroke model were analyzed to quantify parameters related to anesthesia, physiological monitoring, stroke model type, ischemia verification, and overall study quality over time. No significant difference in the frequency of cerebral blood flow (CBF) measurements over time (28/34% for 2009/2019) was found. Notably, significantly fewer studies reported temperature, blood pressure, and blood gas monitoring data in 2019 compared to 2009. On the other hand, an increase in general study quality parameters (e.g., randomization, reporting of approval) was seen. In conclusion, the frequency of periinterventional monitoring has decreased over time. Some general methodological quality aspects, however, partially have increased. CBF measurement-the gold standard for ischemia verification-was applied rarely. Despite the growing recognition of current guidelines such as STAIR and ARRIVE (both widely approved in 2019) reporting, methods and procedures mostly do not follow these guidelines. These deficits may contribute to the translational failure of preclinical stroke research in search for neuroprotective therapies.

Clinical Outcome and Prognostic Factors of Patients with Perimesencephalic and Nonperimesencephalic Subarachnoid Hemorrhage.

OBJECTIVE: To demonstrate the clinical outcome of patients with nonperimesencephalic subarachnoid hemorrhage (npSAH) compared with patients with aneurysmal SAH (aSAH) and perimesencephalic SAH (pSAH) and to evaluate predictive value of various clinical and radiological findings in patients with npSAH. METHODS: We retrospectively identified patients with SAH who presented at our institution between 2009 and 2018. We analyzed demographic and clinical data and outcomes. Multivariable analysis was performed for outcome parameters. RESULTS: Of 608 patients with confirmed SAH, 78% had aSAH, and 22% had nonaneurysmal SAH. Nonaneurysmal SAH was perimesencephalic in 30% of cases and nonperimesencephalic in 70%. Initial clinical status (Hunt and Hess score) was significantly worse in patients with aSAH compared with patients with nonaneurysmal SAH. Complications such as delayed cerebral ischemia occurred significantly more often in patients with aSAH. Patients with pSAH had a more favorable clinical course than patients with aSAH or npSAH. There was no significant difference in 30-day mortality between aSAH (29%) and npSAH (28%) patients (P = 0.835). Hunt and Hess score emerged as a strong predictor of unfavorable outcome in both aSAH and npSAH in multivariable regression. CONCLUSIONS: Patients with npSAH had a similar clinical outcome as patients with aSAH, although there were significantly fewer clinical complications in patients with npSAH. Patients with pSAH demonstrated an overall good clinical course. Our multivariable analysis showed that initial Hunt and Hess score was an important predictor for clinical outcome in aSAH as well as npSAH.

Chronic Subdural Hematoma.

BACKGROUND: Chronic subdural hematoma (cSDH) is typically a disease that affects the elderly. Neurosurgical evacuation is generally indicated for hematomas that are wider than the thickness of the skull. The available guidelines do not address the common clinical issue of the proper management of antithrombotic drugs that the patient has been taking up to the time of diagnosis of the cSDH. Whether antithrombotic treatment should be stopped or continued depends on whether the concern about spontaneous or postoperative intracranial bleeding, and a presumably higher rate of progression or recurrence, with continued medication outweighs the concern about a possibly higher rate of thrombotic complications if it is stopped. METHODS: In this article, we review publications from January 2015 to October 2020 addressing the issue of the management of antithrombotics in patients with cSDH that were retrieved by a selective search in the Pubmed and EMBASE databases, and we present the findings of a cohort study of 395 patients who underwent surgery for cSDH consecutively between October 2014 and December 2019. RESULTS: The findings published in the literature are difficult to summarize concisely because of the heterogeneity of study designs. Among the seven studies in which a group of patients on antithrombotics was compared with a control group, four revealed significant differences with respect to the risk of thromboembolic complications depending on previous antithrombotic use and the duration of discontinuation, while three others did not. In our own cohort, discontinuation of antithrombotics (including both plasmatic and antiplatelet drugs) was associated with thrombotic complications in 9.1% of patients. CONCLUSION: These findings imply that the management of antithrombotics should be dealt with critically on an individual basis. In patients with cSDH who are at elevated risk, an early restart of antithrombotic treatment or even an operation under continued antithrombotic therapy should be considered.

Post-stroke treatment with argon preserved neurons and attenuated microglia/macrophage activation long-termly in a rat model of transient middle cerebral artery occlusion (tMCAO).

In a previous study from our group, argon has shown to significantly attenuate brain injury, reduce brain inflammation and enhance M2 microglia/macrophage polarization until 7 days after ischemic stroke. However, the long-term effects of argon have not been reported thus far. In the present study, we analyzed the underlying neuroprotective effects and potential mechanisms of argon, up to 30 days after ischemic stroke. Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion demonstrated long-term neuroprotective effect by preserving the neurons at the ischemic boundary zone 30 days after stroke. Furthermore, the excessive microglia/macrophage activation in rat brain was reduced by argon treatment 30 days after ischemic insult. However, long-lasting neurological improvement was not detectable. More sensorimotor functional measures, age- and disease-related models, as well as further histological and molecular biological analyses will be needed to extend the understanding of argon's neuroprotective effects and mechanism of action after ischemic stroke.

Coarctation of the Aorta as a Rare Indirect Cause of Aneurysmal Subarachnoid Hemorrhage in the Adolescent: A Case Report and Review of the Literature.

Aneurysmal subarachnoid hemorrhage (SAH) is rare in teenagers. We present the case of a 19-year-old woman with an aneurysmal SAH and four anterior circulation aneurysms. Due to the urgency of operative treatment, no initial conventional cerebral angiography was performed. The CT angiography depicted the aortic arch incompletely. The coarctation was discovered on day 5 after ictus in a cerebral angiography for vasospasm surveillance. We believe that in young SAH patients without an explainable predilection for aneurysm formation, imaging of the aortic arch during the initial CT angiography, not to miss a coarctation of the aorta, is highly recommended.

Elevated concentrations of macrophage migration inhibitory factor in serum and cerebral microdialysate are associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Objective: Inflammation is increasingly recognized to be involved in the pathophysiology of aneurysmal subarachnoid hemorrhage (aSAH) and may increase the susceptibility to delayed cerebral ischemia (DCI). Macrophage migration inhibitory factor (MIF) has been shown to be elevated in serum and cerebrospinal fluid (CSF) after aSAH. Here, we determined MIF levels in serum, CSF and cerebral microdialysate (MD) at different time-points after aSAH and evaluated their clinical implications. Methods: MIF levels were measured in serum, CSF and MD obtained from 30 aSAH patients during early (EPd1-4), critical (CPd5-15) and late (LPd16-21) phase after hemorrhage. For subgroup analyses, patients were stratified based on demographic and clinical data. Results: MIF levels in serum increased during CPd5-15 and decreased again during LPd16-21, while CSF levels showed little changes over time. MD levels peaked during EPd1-4, decreased during CPd5-15 and increased again during LPd16-21. Subgroup analyses revealed significantly higher serum levels in patients with aneurysms located in the anterior vs. posterior circulation during CPd5-15 (17.3 [15.1-21.1] vs. 10.0 [8.4-11.5] ng/ml, p = 0.009) and in patients with DCI vs. no DCI during CPd5-15 (17.9 [15.1-22.7] vs. 11.9 [8.9-15.9] ng/ml, p = 0.026) and LPd16-21 (17.4 [11.7-27.9] vs. 11.3 [9.2-12.2] ng/ml, p = 0.021). In addition, MIF levels in MD during CPd5-15 were significantly higher in patients with DCI vs. no DCI (3.6 [1.8-10.7] vs. 0.2 [0.1-0.7] ng/ml, p = 0.026), while CSF levels during the whole observation period were similar in all subgroups. Conclusion: Our findings in a small cohort of aSAH patients provide preliminary data on systemic, global cerebral and local cerebral MIF levels after aSAH and their clinical implications. Clinical trial registration: ClinicalTrials.gov, identifier: NCT02142166.

A Retrospective Analysis of Randomized Controlled Trials on Traumatic Brain Injury: Evaluation of CONSORT Item Adherence.

Traumatic brain injury (TBI) contributes to death and disability, resulting in an enormous individual and socio-economic challenges. Despite huge efforts, there are still controversies on treatment strategies and early outcome estimation. We evaluate current randomized controlled trials (RCTs) on TBI according to their fulfillment of the CONSORT (Consolidated Statement of Reporting Trials) statement's criteria as a marker of transparency and the quality of study planning and realization. A PubMed search for RCTs on TBI (January 2014-December 2019) was carried out. After screening of the abstracts (n = 1.926), the suitable full text manuscripts (n = 72) were assessed for the fulfillment of the CONSORT criteria. The mean ratio of consort statement fulfillment was 59% (±13%), 31% of the included studies (n = 22) complied with less than 50% of the CONSORT criteria. Citation frequency was moderately related to ratio of CONSORT item fulfillment (r = 0.4877; p < 0.0001) and citation frequency per year (r = 0.5249; p < 0.0001). The ratio of CONSORT criteria fulfillment was associated with the impact factor of the publishing journal (r = 0.6428; p < 0.0001). Essential data for study interpretation, such as sample size determination (item 7a), participant flow (item 13a) as well as losses and exclusions (item 13b), were only reported in 53%, 60% and 63%, respectively. Reporting and methodological aspects in RCTs on TBI still may be improved. Thus, the interpretation of study results may be hampered due to methodological weaknesses.

Changes in endogenous daytime melatonin levels after aneurysmal subarachnoid hemorrhage - Preliminary findings from an observational cohort study.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH. MATERIALS AND METHODS: Daytime (from 11:00 am to 05:00 pm) melatonin levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from 30 patients on the day of aSAH onset (d0) and in five pre-defined time intervals during the early (d1-4), critical (d5-8, d9-12, d13-15) and late (d16-21) phase. Perioperative daytime melatonin levels determined in 30 patients who underwent elective open aortic surgery served as a control for the acute effects of surgical treatment on melatonin homeostasis. RESULTS: There was no difference between serum melatonin levels measured in the control patients and on the day of aSAH onset (p = 0.664). However, aSAH was associated with a sustained up-regulation that started during the critical phase (d9-12) and progressed to the late phase (d16-21), during which almost 80% of the patients reached daytime melatonin levels above 5 pg/ml. In addition, subgroup analyses revealed higher melatonin levels on d5-8 in patients with a poor clinical status on admission (p = 0.031), patients with anterior communicating artery aneurysms (p = 0.040) and patients without an external ventricular drain (p = 0.018), possibly pointing to a role of hypothalamic dysfunction. CONCLUSION: Our observations in a small cohort of patients provide first evidence for a delayed up-regulation of circulatory daytime melatonin levels after aSAH and a role of aneurysm location for higher levels during the critical phase. These findings are discussed in terms of previous results about stress-induced melatonin production and the role of hypothalamic and brainstem involvement for melatonin levels after aSAH.

Female Participation in Academic European Neurosurgery-A Cross-Sectional Analysis.

The study aims to provide data on authors' gender distribution with special attention on publications from Europe. Articles (October 2019-March 2020) published in three representative neurosurgical journals (Acta Neurochirurgica, Journal of Neurosurgery, Neurosurgery) were analyzed with regard to female participation. Out of 648 publications, 503 original articles were analyzed: 17.5% (n = 670) of the 3.821 authors were female, with 15.7% (n = 79) females as first and 9.5% (n = 48) as last authors. The lowest ratio of female first and last authors was seen in original articles published in the JNS (12.3%/7.7% vs. Neurosurgery 14.9%/10.6% and Acta 23.0/11.5%). Articles originated in Europe made up 29.8% (female author ratio 21.1% (n = 226)). Female first authorship was seen in 20.7% and last authorship in 10.7% (15.3% and 7.3% were affiliated to a neurosurgical department). The percentages of female authorship were lower if non-original articles (n = 145) were analyzed (11.7% first/4.8% last authorships). Female participation in editorial boards was 8.0%. Considering the percentages of European female neurosurgeons, the current data are proportional. However, the lack of female last authors, the discrepancy regarding non-original articles and the composition of the editorial boards indicate that there still is a structural underrepresentation and that females are limited in achieving powerful positions.

Noble gases and neuroprotection: summary of current evidence.

PURPOSE OF REVIEW: To summarize the current data on neuroprotection derived by noble gas treatment focusing on xenon and argon. RECENT FINDINGS: Both xenon and argon have demonstrated neuroprotective properties in an array of disease models. However, current data for argon after traumatic brain injury (TBI) is conflicting. Recent human data is only available for xenon showing some beneficial aspects (fewer adverse events) but no effect on outcomes, such as incidence of postoperative delirium. SUMMARY: Promising results are available for neuroprotection derived by noble gas treatment. Results for xenon are more consistent than those for argon. The mechanism of action of xenon (noncompetitive NMDA-receptor inhibition) is also better understood compared with that of argon. The evidence for argon's neuroprotective actions (particularly after TBI) remains uncertain.

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride.

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs-nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)-might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.

Argon treatment after experimental subarachnoid hemorrhage: evaluation of microglial activation and neuronal survival as a subanalysis of a randomized controlled animal trial.

Hereinafter, we evaluate argon's neuroprotective and immunomodulatory properties after experimental subarachnoid hemorrhage (SAH) examining various localizations (hippocampal and cortical regions) with respect to neuronal damage and microglial activation 6, 24 and 72 hours after SAH. One hour after SAH (endovascular perforation rat model) or sham surgery, a mixture of gas containing 50% argon (argon group) or 50% nitrogen (control group) was applied for 1 hour. At 6 hours after SAH, argon reduced neuronal damage in the hippocampal regions in the argon group compared to the control group (P < 0.034). Hippocampal microglial activation did not differ between the treatment groups over time. The basal cortical regions did not show a different lesion pattern, but microglial activation was significantly reduced in the argon group 72 hours after SAH (P = 0.034 vs. control group). Whereas callosal microglial activation was significantly reduced at 24 hours in the argon-treated group (P = 0.018). Argon treatment ameliorated only early hippocampal neuronal damage after SAH. Inhibition of microglial activation was seen in some areas later on. Thus, argon may influence the microglial inflammatory response and neuronal survival after SAH; however, due to low sample sizes the interpretation of our results is limited. The study protocol was approved by the Government Agency for Animal Use and Protection (Protocol number: TVA 10416G1; initially approved by the "Landesamt für Natur, Umwelt und Verbraucherschutz NRW," Recklinghausen, Germany, on April 28, 2009).

Predicting experimental success: a retrospective case-control study using the rat intraluminal thread model of stroke.

The poor translational success rate of preclinical stroke research may partly be due to inaccurate modelling of the disease. We provide data on transient middle cerebral artery occlusion (tMCAO) experiments, including detailed intraoperative monitoring to elaborate predictors indicating experimental success (ischemia without occurrence of confounding pathologies). The tMCAO monitoring data (bilateral cerebral blood flow, CBF; heart rate, HR; and mean arterial pressure, MAP) of 16 animals with an 'ideal' outcome (MCA-ischemia), and 48 animals with additional or other pathologies (subdural haematoma or subarachnoid haemorrhage), were checked for their prognostic performance (receiver operating characteristic curve and area under the curve, AUC). Animals showing a decrease in the contralateral CBF at the time of MCA occlusion suffered from unintended pathologies. Implementation of baseline MAP, in addition to baseline HR (AUC, 0.83, 95% c.i. 0.68 to 0.97), increased prognostic relevance (AUC, 0.89, 95% c.i. 0.79 to 0.98). Prediction performance improved when two additional predictors referring to differences in left and right CBF were considered (AUC, 1.00, 95% c.i. 1.0 to 1.0). Our data underline the importance of peri-interventional monitoring to verify a successful experimental performance in order to ensure a disease model as homogeneous as possible.

Procalcitonin in the context of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) initiates a deleterious cascade activating multiple inflammatory processes, which can contribute to delayed cerebral ischemia (DCI). Procalcitonin (PCT) is an established marker for sepsis treatment monitoring, and its time course in the context of DCI after aSAH remains unclear. The aim of this trial was to assess the predictive and confirmative value of PCT levels in the context of DCI. METHODS: All patients admitted to the authors' institution with aSAH between 2014 and 2018 were prospectively screened for eligibility. Daily PCT levels were recorded alongside relevant aSAH characteristics. The predictive and confirmative values of PCT levels were assessed using a receiver operating characteristic and area under the curve (AUC) analysis. The course of PCT levels around the DCI event was evaluated in an infection-free subgroup of patients. RESULTS: A total of 132 patients with aSAH were included. Early PCT levels (first 3 days post-aSAH) had a low predictive value for the development of DCI (AUC 0.661, standard error [SE] 0.050; p = 0.003) and unfavorable long-term outcome (i.e., Glasgow Outcome Scale-Extended scores 1-4; AUC 0.674, SE 0.054; p = 0.003). In a subgroup analysis of infection-free patients (n = 72), PCT levels were higher in patients developing DCI (p = 0.001) and DCI-related cerebral infarction (p = 0.002). PCT concentrations increased gradually after DCI and decreased with successful intervention. In refractory cases progressing to cerebral infarction, PCT levels showed a secondary increase. CONCLUSIONS: Early higher PCT levels were associated with the later development of DCI and unfavorable outcome. Analysis of PCT beyond the first couple of days after hemorrhage is hampered by nosocomial infections. In infection-free patients, however, PCT levels rise during DCI and an additional increase develops in patients developing cerebral infarction. Clinical trial registration no.: NCT02142166 (clinicaltrials.gov).

An altered posterior question-mark incision is associated with a reduced infection rate of cranioplasty after decompressive hemicraniectomy.

OBJECTIVE: Performing a cranioplasty (CP) after decompressive craniotomy is a straightforward neurosurgical procedure, but it remains associated with a high complication rate. Surgical site infection (SSI), aseptic bone resorption (aBR), and need for a secondary CP are the most common complications. This observational study aimed to identify modifiable risk factors to prevent CP failure. METHODS: A retrospective analysis was performed of all patients who underwent CP following decompressive hemicraniectomy (DHC) between 2010 and 2018 at a single institution. Predictors of SSI, aBR, and need for allograft CP were evaluated in a univariate analysis and multivariate logistic regression model. RESULTS: One hundred eighty-six patients treated with CP after DHC were included. The diagnoses leading to a DHC were as follows: stroke (83 patients, 44.6%), traumatic brain injury (55 patients, 29.6%), subarachnoid hemorrhage (33 patients, 17.7%), and intracerebral hemorrhage (15 patients, 8.1%). Post-CP SSI occurred in 25 patients (13.4%), whereas aBR occurred in 32 cases (17.2%). An altered posterior question-mark incision, ending behind the ear, was associated with a significantly lower infection rate and CP failure, compared to the classic question-mark incision (6.3% vs 18.4%; p = 0.021). The only significant predictor of aBR was patient age, in which those developing resorption were on average 16 years younger than those without aBR (p < 0.001). CONCLUSIONS: The primary goal of this retrospective cohort analysis was to identify adjustable risk factors to prevent post-CP complications. In this analysis, a posterior question-mark incision proved beneficial regarding infection and CP failure. The authors believe that these findings are caused by the better vascularized skin flap due to preservation of the superficial temporal artery and partial preservation of the occipital artery. In this trial, the posterior question-mark incision was identified as an easily and costless adaptable technique to reduce CP failure rates.

Randomized Controlled Trials on Intracerebral Hemorrhage: A Cross Sectional Retrospective Analysis of CONSORT Item Adherence.

Object: Intracranial hemorrhage (ICH) is the second most common cause of stroke but still there is little consolidated knowledge about the optimal treatment strategies (e.g., the benefit of surgical evacuation). We evaluated the current randomized controlled trials (RCTs) on primary ICH (01.2013-03.2017) according to their fulfillment of the CONSORT statement's criteria (published in 2010) -as a marker of transparency and quality of study planning and realization. Methods: A Pubmed and a Cochrane database (including clinicaltrials.gov) search was carried out (01.2014-3.2017, respectively 01.2013-12.2013). Abstracts were screened for inclusion. Eligible full text manuscripts were assessed for the implementation of the CONSORT criteria. Citation frequencies and impact factors of the journals were related to ratio of CONSORT criteria fulfillment. Further, the risk of bias according to the Risk of bias tool 2 (RoB 2) was assessed. Results: Overall 3097 abstracts were screened for inclusion; 39 studies were suitable for final analysis. A mean fulfillment ratio of 51% (±28%) was found. A high correlation between impact factor and adherence to CONSORT criteria was shown (r = 0.7664; p < 0.0001). Citation frequency per year was related to ratio of CONSORT item fulfillment (r = 0.6747; p < 0.0001) and to the impact factor of the publishing journal (r = 0.7310; p < 0.0001). Of note, the items 10 (randomization: implementation) and 21 (generalizability) showed particularly high rates of non-fulfillment (87 and 85%). The majority of studies (95%) complied with item 2b (specific objectives or hypotheses), but strikingly objectives were mostly described vaguely. Other essential criteria such as sample size determination, definition of outcome parameters, and participant flow were only fulfilled weakly (51, 54, and 39%). Conclusions: Over 20 years after its inception there is still weak adherence to the CONSORT statement. As a consequence, conclusions are hampered by inadequate planning and/or reporting. Particularly with respect to pathologies as ICH lacking clear, evidence-based guidelines adherence to the CONSORT statement might improve research quality in order to define valuable treatment strategies.