Publications by authors named "Michael Veldeman"

21 Publications

  • Page 1 of 1

Letter: The Retroauricular Incision as an Effective and Safe Alternative Incision for Decompressive Hemicraniectomy.

Oper Neurosurg (Hagerstown) 2021 Sep 8. Epub 2021 Sep 8.

Department of Neurosurgery RWTH Aachen University Hospital Aachen, Germany.

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http://dx.doi.org/10.1093/ons/opab321DOI Listing
September 2021

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

Clin Neurol Neurosurg 2021 Sep 6;208:106870. Epub 2021 Aug 6.

Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany. Electronic address:

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 (d) and in five pre-defined time intervals during the early (d), critical (d, d, d) and late (d) 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 (d) and progressed to the late phase (d), during which almost 80% of the patients reached daytime melatonin levels above 5 pg/ml. In addition, subgroup analyses revealed higher melatonin levels on d 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.
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http://dx.doi.org/10.1016/j.clineuro.2021.106870DOI Listing
September 2021

Invasive Multimodal Neuromonitoring in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.

Stroke 2021 Jul 26:STROKEAHA121034633. Epub 2021 Jul 26.

Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany (M.A., W.A., M.W., A.H., H.C., G.A.S.).

Background And Purpose: Aneurysmal subarachnoid hemorrhage is a devastating disease leaving surviving patients often severely disabled. Delayed cerebral ischemia (DCI) has been identified as one of the main contributors to poor clinical outcome after subarachnoid hemorrhage. The objective of this review is to summarize existing clinical evidence assessing the diagnostic value of invasive neuromonitoring (INM) in detecting DCI and provide an update of evidence since the 2014 consensus statement on multimodality monitoring in neurocritical care.

Methods: Three invasive monitoring techniques were targeted in the data collection process: brain tissue oxygen tension (pO), cerebral microdialysis, and electrocorticography. Prospective and retrospective studies as well as case series (≥10 patients) were included as long as monitoring was used to detect DCI or guide DCI treatment.

Results: Forty-seven studies reporting INM in the context of DCI were included (pO: N=21; cerebral microdialysis: N=22; electrocorticography: N=4). Changes in brain oxygen tension are associated with angiographic vasospasm or reduction in regional cerebral blood flow. Metabolic monitoring with trend analysis of the lactate to pyruvate ratio using cerebral microdialysis, identifies patients at risk for DCI. Clusters of cortical spreading depolarizations are associated with clinical neurological worsening and cerebral infarction in selected patients receiving electrocorticography monitoring.

Conclusions: Data supports the use of INM for the detection of DCI in selected patients. Generalizability to all subarachnoid hemorrhage patients is limited by design bias of available studies and lack of randomized trials. Continuous data recording with trend analysis and the combination of INM modalities can provide tailored treatment support in patients at high risk for DCI. Future trials should test interventions triggered by INM in relation to cerebral infarctions.
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http://dx.doi.org/10.1161/STROKEAHA.121.034633DOI Listing
July 2021

Levels of bioactive adrenomedullin in plasma and cerebrospinal fluid in relation to delayed cerebral ischemia in patients after aneurysmal subarachnoid hemorrhage: A prospective observational study.

J Neurol Sci 2021 08 5;427:117533. Epub 2021 Jun 5.

Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany. Electronic address:

Objectives: Adrenomedullin (ADM) has been identified as a promising biomarker of mortality and outcome in sepsis, heart failure and after major surgery. A recently developed assay specific for bioactive adrenomedullin (bio-ADM) has not yet been assessed in aneurysmal subarachnoid hemorrhage (aSAH). The objective of this prospective trial was to assess the time course of bio-ADM after aSAH in relation to the development of delayed cerebral ischemia (DCI) and its association with clinical outcome.

Methods: Bio-ADM levels in plasma and cerebrospinal fluid (CSF) were measured during five predefined epochs, for up to 21 days in 30 aSAH patients: early, (day 0 to day 3); acute, (day 4 to day 8); early critical, (day 9 to day 12); late critical, (day 13 to day 15), and late (day 16 to day 21). DCI was diagnosed clinically or based on multimodal monitoring and imaging, and the occurrence of DCI-related cerebral infarction, and outcome after 12 months (extended Glasgow outcome scale), was noted.

Results: Higher median bio-ADM levels in plasma during the acute phase were predictive of long-term unfavorable outcome (AUC = 0.97; 95% CI 0.91 to 1.00; p < 0.001). Early critical bio-ADM levels during DCI were lower in CSF and confirmed DCI occurrence (AUC = 0.80; 95% CI 0.59 to 1.00; p = 0.044).

Conclusion: The dynamics of bio-ADM levels in CSF present a fairly different course compared to plasma with observed higher bio-ADM concentrations in patients spared from DCI and/or developing favorable outcome.
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http://dx.doi.org/10.1016/j.jns.2021.117533DOI Listing
August 2021

Ocular Trauma with Ophthalmic Artery Injury as a Rare Cause of Subarachnoid Hemorrhage: a Case Report and Review of the Literature.

J Neurol Surg A Cent Eur Neurosurg 2021 Jun 7. Epub 2021 Jun 7.

Department of Neurosurgery, Universitätsklinikum Aachen, RWTH Aachen University, Aachen, Germany.

Background And Importance:  Traumatic avulsion of the ophthalmic artery is a rare cause of subarachnoid hemorrhage (SAH). In this case, a relative minor fall with isolated ocular trauma caused bulbar dislocation and rupture of the ophthalmic artery in its intracranial segment resulting in subarachnoid bleeding.

Clinical Presentation:  In a female patient in her 70s, a direct penetrating trauma to the orbit by a door handle resulted in basal SAH with blood dispersion into both Sylvian fissures. Cerebral angiography revealed a blunt-ending stump at the origin of the ophthalmic artery. To provide protection against further bleeding, a flow diverter stent was placed in the internal carotid artery to cover the origin of the ophthalmic artery. After a longer intensive care stay complicated by pneumonia and respiratory insufficiency, the patient made a full recovery. Of all four reported cases (including ours), delayed cerebral ischemia was seen in one patient and hydrocephalus in two patients. These potential complications necessitate close observation and fitting treatment similar to aneurysmal SAH.

Conclusion:  Due to similar physiologic aspects, this type of bleed mimics many aspects of aneurysmal SAH. In this case, we observed no hydrocephalus or the development of delayed cerebral ischemia. This represents, however, the first reported case treated by placement of a flow diverter stent to prevent rebleeding and pseudoaneurysm formation.
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http://dx.doi.org/10.1055/s-0041-1725956DOI Listing
June 2021

Urea-Creatinine Ratio (UCR) After Aneurysmal Subarachnoid Hemorrhage: Association of Protein Catabolism with Complication Rate and Outcome.

World Neurosurg 2021 07 18;151:e961-e971. Epub 2021 May 18.

Department of Neurosurgery, RWTH Aachen University, Aachen, Germany.

Objective: The urea-creatinine ratio (UCR) has been proposed as potential biomarker for critical illness-associated catabolism. Its role in the context of aneurysmal subarachnoid hemorrhage (aSAH) remains to be elucidated, which was the aim of the present study.

Methods: We enrolled 66 patients with aSAH with normal renal function and 36 patients undergoing elective cardiac surgery as a control group for the effects of surgery. In patients with aSAH, the predictive or diagnostic value of early (day 0-2) and critical (day 5-7) UCRs was assessed with regard to delayed cerebral ischemia (DCI), DCI-related infarction, and clinical outcome after 12 months.

Results: Preoperatively, UCR was similar both groups. Within 2 days postoperatively, UCRs increased significantly in patients in the elective cardiac surgery group (P < 0.001) but decreased back to baseline on day 5-7 (P = 0.245), whereas UCRs in patients with aSAH increased to significantly greater levels on day 5-7 (P = 0.028). Greater early or critical UCRs were associated with poor clinical outcomes (P = 0.015) or DCI (P = 0.011), DCI-related infarction (P = 0.006), and poor clinical outcomes (P < 0.001) respectively. In multivariate analysis, there was an independent association between greater early UCRs and poor clinical outcomes (P = 0.026).

Conclusions: In this exploratory study of UCR in the context of aSAH, greater early values were predictive for a poor clinical outcome after 12 months, whereas greater critical values were associated with DCI, DCI-related infarctions, and poor clinical outcomes. The clinical implications as well as the pathophysiologic relevance of protein catabolism should be explored further in the context of aSAH.
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http://dx.doi.org/10.1016/j.wneu.2021.05.025DOI Listing
July 2021

Body mass index and leptin levels in serum and cerebrospinal fluid in relation to delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage.

Neurosurg Rev 2021 Apr 17. Epub 2021 Apr 17.

Department of Neurosurgery, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.

Aneurysmal subarachnoid hemorrhage (SAH) is associated with a high mortality rate and may leave surviving patients severely disabled. After the initial hemorrhage, clinical outcome is further compromised by the occurrence of delayed cerebral ischemia (DCI). Overweight and obesity have previously been associated with protective effects in the post-bleeding phase. The aim of this study was to assess the effects of a patient's body mass index (BMI) and leptin levels on the occurrence of DCI, DCI-related cerebral infarction, and clinical outcome. In total, 263 SAH patients were included of which leptin levels were assessed in 24 cases. BMI was recorded along disease severity documented by the Hunt and Hess and modified Fisher scales. The occurrence of clinical or functional DCI (neuromonitoring, CT Perfusion) was assessed. Long-term clinical outcome was documented after 12 months (extended Glasgow outcome scale). A total of 136 (51.7%) patients developed DCI of which 72 (27.4%) developed DCI-related cerebral infarctions. No association between BMI and DCI occurrence (P = .410) or better clinical outcome (P = .643) was identified. Early leptin concentration in serum (P = .258) and CSF (P = .159) showed no predictive value in identifying patients at risk of unfavorable outcomes. However, a significant increase of leptin levels in CSF occurred from 326.0 pg/ml IQR 171.9 prior to DCI development to 579.2 pg/ml IQR 211.9 during ongoing DCI (P = .049). In our data, no association between obesity and clinical outcome was detected. After DCI development, leptin levels in CSF increased either by an upsurge of active transport or disruption of the blood-CSF barrier. This trial has been registered at ClinicalTrials.gov (NCT02142166) as part of a larger-scale prospective data collection. BioSAB: https://clinicaltrials.gov/ct2/show/NCT02142166.
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http://dx.doi.org/10.1007/s10143-021-01541-1DOI Listing
April 2021

How I do it-the posterior question mark incision for decompressive hemicraniectomy.

Acta Neurochir (Wien) 2021 05 31;163(5):1447-1450. Epub 2021 Mar 31.

Department of Neurosurgery, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.

Background: Decompressive hemicraniectomy (DHC) is a lifesaving procedure which every neurosurgeon should master early on. As indications for the procedure are growing, the number of patients eventually requiring skull reconstruction via cranioplasty also increases. The posterior question mark incision is a straightforward alternative to the classic trauma-flap and can easily be adopted. Some particularities exist one should consider beforehand and are discussed here in detail.

Methods: Surgical steps, aids, and pitfalls are comprehensively discussed to prepare surgeons who wish to gain experience with this type of incision.

Conclusion: Due to the lower complication rate after cranioplasty, the posterior question mark incision has superseded the traditional pre-auricular starting anterior question mark incisions, in our department for the performance of decompressive hemicraniectomies.
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http://dx.doi.org/10.1007/s00701-021-04812-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053663PMC
May 2021

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

J Neurol Surg A Cent Eur Neurosurg 2021 Feb 14. Epub 2021 Feb 14.

Department of Neurosurgery, RWTH Aachen University, Aachen, Germany.

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.
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http://dx.doi.org/10.1055/s-0040-1721000DOI Listing
February 2021

Circulatory dipeptidyl peptidase 3 (cDPP3) is a potential biomarker for early detection of secondary brain injury after aneurysmal subarachnoid hemorrhage.

J Neurol Sci 2021 Mar 30;422:117333. Epub 2021 Jan 30.

Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany. Electronic address:

Introduction: Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) that can culminate in secondary brain damage. Although it remains one of the main preventable causes of aSAH-related morbidity, there is still a lack of prognostic criteria for identification of patients at risk of developing DCI. Because elevated circulatory levels of the enzyme dipeptidyl peptidase 3 (cDPP3) were recently identified as a potential biomarker for outcome prediction in critically ill patients, we evaluated the time-course of changes in cDPP3 levels after aSAH.

Materials And Methods: cDPP3 levels were quantified in serum obtained from 96 confirmed aSAH patients during the early (EP: d), critical (CP: d, d, d) and late (LP: d) phase after aSAH onset. Associations between cDPP3 levels and demographic or clinical parameters were evaluated. The relations between cDPP3 levels and DCI, DCI-related infarctions and long-term clinical outcomes were examined by receiver operating characteristics (ROC) curve analysis and multivariate logistic regression.

Results: Significantly higher cDPP3 levels during CP (d, d, d) were observed in patients with poor clinical (p < 0.001 to p = 0.033) or radiological (p = 0.012 to p = 0.039) status on admission, DCI (p < 0.001 to p = 0.001), DCI-related infarctions (p = 0.002 to p = 0.007), and poorer long-term outcome (p = 0.007 to p = 0.019). ROC curve analysis indicated that higher cDPP3 levels on d are predictive for a poor clinical outcome (area under the curve = 0.677, p = 0.007). In multivariate analysis, there was an independent association between cDPP3 levels on d and development of DCI-related infarctions (p = 0.038).

Conclusion: Our results provide first evidence that cDPP3 could serve as a promising biomarker for early diagnosis of DCI-related infarctions in poor grade aSAH patients.
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http://dx.doi.org/10.1016/j.jns.2021.117333DOI Listing
March 2021

Risk profile of decompressive hemicraniectomy for malignant stroke after revascularization treatment.

J Neurol Sci 2021 01 16;420:117275. Epub 2020 Dec 16.

Department of Neurosurgery, RWTH Aachen University, Aachen, Germany. Electronic address:

Objective: Revascularization by pharmacological and/or endovascular treatment is an effective therapy for acute ischemic stroke caused by artery occlusion. In the context of malignant middle cerebral artery infarction (MMI), decompressive hemicraniectomy (DHC) can be life-saving. However, its effectiveness and safety after revascularization have not been thoroughly assessed. This retrospective study aimed to determine the risk profile of pre-surgical revascularization treatment (RT) for subsequent DHC.

Methods: A total of 152 consecutive patients treated by DHC after MMI were identified between 2012 and 2015. After elimination of cases with previous stroke and cases pre-treated with antiplatelets or anticoagulants (increased postoperative bleeding), twenty-four out of fifty patients (n = 24/50, 48%) received pre-surgical revascularization treatment by intravenous thrombolysis (TL), mechanical thrombectomy (MT) or a combination of both. Demographic data was compared alongside perioperative, postoperative complications (intra-/extracerebral hemorrhage, revision surgery due to hemorrhage or infection, and overall mortality) and economic parameters.

Results: Comparing patients with and without prior RT, there was no statistically significant difference in duration of surgery (RT: 83 [57-116] min vs. no-RT: 96 [69-119] min, p = 0.308), intraoperative blood loss (RT: 300 [225-375] ml vs. no-RT: 300 [250-400] ml, p = 0.763), intraoperative transfusion requirement (RT: 12.5% vs. no-RT: 26.9%, p = 0.294), or need for volume substitution (RT: 1300 [1200-1400] ml vs. no-RT: 1200 [1100-1400] ml, p = 0.359). The rate of postoperative complications was also comparable in both groups, including intra-/extracerebral hemorrhage, revision due to hemorrhage or infections, and mortality (p = 0.814, p = 0.520, p = 0.697, and p = 0.769). Health economic parameters were not affected (ventilation time: RT: 309 [12-527] hrs. vs. no-RT: 444 [171-605] hrs., p = 0.120, length of stay: RT: 23 [13-32] days vs. no-RT: 28 [19-41], p = 0.156, and stay costs: RT: 27768 [13044-60,248] € vs. no-RT: 35422 [21225-49,585] €, p = 0.312).

Conclusion: DHC for patients with MMI who previously received revascularization therapy appears to be safe and not associated with a higher complication rate or increased health economic burden.
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http://dx.doi.org/10.1016/j.jns.2020.117275DOI Listing
January 2021

Treatment of Delayed Cerebral Ischemia in Good-Grade Subarachnoid Hemorrhage: Any Role for Invasive Neuromonitoring?

Neurocrit Care 2021 08 10;35(1):172-183. Epub 2020 Dec 10.

Department of Neurosurgery, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.

Background: Good-grade aneurysmal subarachnoid hemorrhage (Hunt and Hess 1-2) is generally associated with a favorable prognosis. Nonetheless, patients may still experience secondary deterioration due to delayed cerebral ischemia (DCI), contributing to poor outcome. In those patients, neurological assessment is challenging and invasive neuromonitoring (INM) may help guide DCI treatment.

Methods: An observational analysis of 135 good-grade SAH patients referred to a single tertiary care center between 2010 and 2018 was performed. In total, 54 good-grade SAH patients with secondary deterioration evading further neurological assessment, were prospectively enrolled for this analysis. The cohort was separated into two groups: before and after introduction of INM in 2014 (pre-INM: n = 28; post-INM: n = 26). INM included either parenchymal oxygen saturation measurement (pO), cerebral microdialysis or both. Episodes of DCI (pO < 10 mmHg or lactate/pyruvate > 40) were treated via induced hypertension or in refractory cases by endovascular means. The primary outcome was defined as the extended Glasgow outcome scale after 12 months. In addition, we recorded the amount of imaging studies performed and the occurrence of silent and overall DCI-related infarction.

Results: Secondary deterioration, impeding neurological assessment, occurred in 54 (40.0%) of all good-grade SAH patients. In those patients, a comparable rate of favorable outcome at 12 months was observed before and after the introduction of INM (pre-INM 14 (50.0%) vs. post-INM 16, (61.6%); p = 0.253). A significant increase in good recovery (pre-INM 6 (50.0%) vs. post-INM 14, (61.6%); p = 0.014) was observed alongside a reduction in the incidence of silent infarctions (pre-INM 8 (28.6%) vs. post-INM 2 (7.7%); p = 0.048) and of overall DCI-related infarction (pre-INM 12 (42.8%) vs. post-INM 4 (23.1%); p = 0.027). The number of CT investigations performed during the DCI time frame decreased from 9.8 ± 5.2 scans in the pre-INM group to 6.1 ± 4.0 (p = 0.003) in the post-INM group.

Conclusions: A considerable number of patients with good-grade SAH experiences secondary deterioration rendering them neurologically not assessable. In our cohort, the introduction of INM to guide DCI treatment in patients with secondary deterioration increased the rate of good recovery after 12 months. Additionally, a significant reduction of CT scans and infarction load was recorded, which may have an underestimated impact on quality of life and more subtle neuropsychological deficits common after SAH.
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http://dx.doi.org/10.1007/s12028-020-01169-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285339PMC
August 2021

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

Dis Model Mech 2020 12 29;13(12). Epub 2020 Dec 29.

Department of Neurosurgery, University Hospital Aachen, RWTH Aachen University, D-52047 Aachen, Germany

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.
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http://dx.doi.org/10.1242/dmm.044651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790196PMC
December 2020

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

Med Gas Res 2020 Jul-Sep;10(3):103-109

Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany.

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).
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http://dx.doi.org/10.4103/2045-9912.296039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086619PMC
July 2021

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

J Neurosurg 2020 Sep 4:1-9. Epub 2020 Sep 4.

Departments of1Neurosurgery and.

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).
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http://dx.doi.org/10.3171/2020.5.JNS201337DOI Listing
September 2020

Invasive neuromonitoring with an extended definition of delayed cerebral ischemia is associated with improved outcome after poor-grade subarachnoid hemorrhage.

J Neurosurg 2020 May 15;134(5):1527-1534. Epub 2020 May 15.

Departments of1Neurosurgery.

Objective: The current definition of delayed cerebral ischemia (DCI) is based on clinical characteristics precluding its use in patients with poor-grade subarachnoid hemorrhage (SAH). Additional concepts to evaluate the unconscious patient are required. Invasive neuromonitoring (INM) may allow timely detection of metabolic and oxygenation crises before irreversible damage has occurred.

Methods: The authors present a cohort analysis of all consecutive SAH patients referred to a single tertiary care center between 2010 and 2018. The cohort (n = 190) was split into two groups: one before (n = 96) and one after (n = 94) the introduction of INM in 2014. A total of 55 poor-grade SAH patients were prospectively monitored using parenchymal oxygen saturation measurement and cerebral microdialysis. The primary outcome was the Glasgow Outcome Scale-Extended (GOSE) score after 12 months.

Results: With neuromonitoring, the first DCI event was detected earlier (mean 2.2 days, p = 0.002). The overall rate of DCI-related infarctions decreased significantly (from 44.8% to 22.3%; p = 0.001) after the introduction of invasive monitoring. After 12 months, a higher rate of favorable outcome was observed in the post-INM group, compared to the pre-INM group (53.8% vs 39.8%), with a significant difference in the GOSE score distribution (OR 4.86, 95% CI -1.17 to -0.07, p = 0.028).

Conclusions: In this cohort analysis of poor-grade SAH patients, the introduction of INM and the extension of the classic DCI definition toward a functional dimension resulted in an earlier detection and treatment of DCI events. This led to an overall decrease in DCI-related infarctions and an improvement in outcome.
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http://dx.doi.org/10.3171/2020.3.JNS20375DOI Listing
May 2020

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

J Neurosurg 2020 Apr 24;134(3):1262-1270. Epub 2020 Apr 24.

1Department of Neurosurgery, RWTH Aachen University Hospital, Aachen; and.

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.
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http://dx.doi.org/10.3171/2020.2.JNS193335DOI Listing
April 2020

Post-stroke treatment with argon attenuated brain injury, reduced brain inflammation and enhanced M2 microglia/macrophage polarization: a randomized controlled animal study.

Crit Care 2019 Jun 3;23(1):198. Epub 2019 Jun 3.

Department of Anesthesiology, Medical Faculty RWTH Aachen University, Aachen, Germany.

Background: In recent years, argon has been shown to exert neuroprotective effects in an array of models. However, the mechanisms by which argon exerts its neuroprotective characteristics remain unclear. Accumulating evidence imply that argon may exert neuroprotective effects via modulating the activation and polarization of microglia/macrophages after ischemic stroke. In the present study, we analyzed the underlying neuroprotective effects of delayed argon application until 7 days after reperfusion and explored the potential mechanisms.

Methods: Twenty-one male Wistar rats underwent transient middle cerebral artery occlusion or sham surgery randomly for 2 h using the endoluminal thread model. Three hours after transient middle cerebral artery occlusion induction and 1 h after reperfusion, animals received either 50% vol Argon/50% vol O or 50% vol N/50% vol O for 1 h. The primary outcome was the 6-point neuroscore from 24 h to d7 after reperfusion. Histological analyses including infarct volume, survival of neurons (NeuN) at the ischemic boundary zone, white matter integrity (Luxol Fast Blue), microglia/macrophage activation (Iba1), and polarization (Iba1/Arginase1 double staining) on d7 were conducted as well. Sample size calculation was performed using nQuery Advisor + nTerim 4.0. Independent t test, one-way ANOVA and repeated measures ANOVA were performed, respectively, for statistical analysis (SPSS 23.0).

Results: The 6-point neuroscore from 24 h to d7 after reperfusion showed that tMCAO Ar group displayed significantly improved neurological performance compared to tMCAO N group (p = 0.026). The relative numbers of NeuN-positive cells in the ROIs of tMCAO Ar group significantly increased compared to tMCAO N group (p = 0.010 for cortex and p = 0.011 for subcortex). Argon significantly suppressed the microglia/macrophage activation as revealed by Iba1 staining (p = 0.0076) and promoted the M2 microglia/macrophage polarization as revealed by Iba1/Arginase 1 double staining (p = 0.000095).

Conclusions: Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion significantly alleviated neurological deficit within the first week and preserved the neurons at the ischemic boundary zone 7 days after stroke. Moreover, argon reduced the excessive microglia/macrophage activation and promoted the switch of microglia/macrophage polarization towards the anti-inflammatory M2 phenotype. Studies making efforts to further elucidate the protective mechanisms and to benefit the translational application are of great value.
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http://dx.doi.org/10.1186/s13054-019-2493-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547472PMC
June 2019

Time Courses of Inflammatory Markers after Aneurysmal Subarachnoid Hemorrhage and Their Possible Relevance for Future Studies.

Front Neurol 2017 22;8:694. Epub 2017 Dec 22.

Department of Anesthesiology, University Hospital RWTH Aachen, Aachen, Germany.

Object: Aneurysmal subarachnoid hemorrhage triggers an intense inflammatory response, which is suspected to increase the risk for secondary complications such as delayed cerebral ischemia (DCI). However, to date, the monitoring of the inflammatory response to detect secondary complications such as DCI has not become part of the clinical routine diagnostic. Here, we aim to illustrate the time courses of inflammatory parameters after aneurysmal subarachnoid hemorrhage (aSAH) and discuss the problems of inflammatory parameters as biomarkers but also their possible relevance for deeper understanding of the pathophysiology after aSAH and sophisticated planning of future studies.

Materials And Methods: In this prospective cohort study, 109 patients with aSAH were initially included,  = 28 patients had to be excluded. Serum and-if possible-cerebral spinal fluid samples ( = 48) were retrieved at days 1, 4, 7, 10, and 14 after aSAH. Samples were analyzed for leukocyte count and C-reactive protein (CRP) (serum samples only) as well as matrix metallopeptidase 9 (MMP9), intercellular adhesion molecule 1 (ICAM1), and leukemia inhibitory factor (LIF) [both serum and cerebrospinal fluid (CSF) samples]. Time courses of the inflammatory parameters were displayed and related to the occurrence of DCI.

Results: We illustrate the time courses of leukocyte count, CRP, MMP9, ICAM1, and LIF in patients' serum samples from the first until the 14th day after aSAH. Time courses of MMP9, ICAM1, and LIF in CSF samples are demonstrated. Furthermore, no significant difference was shown relating the time courses to the occurrence of DCI.

Conclusion: We estimate that the wide range of the measured values hampers their interpretation and usage as a biomarker. However, understanding the inflammatory response after aSAH and generating a multicenter database may facilitate further studies: realistic sample size calculations on the basis of a multicenter database will increase the quality and clinical relevance of the acquired results.
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http://dx.doi.org/10.3389/fneur.2017.00694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744005PMC
December 2017

Xenon Reduces Neuronal Hippocampal Damage and Alters the Pattern of Microglial Activation after Experimental Subarachnoid Hemorrhage: A Randomized Controlled Animal Trial.

Front Neurol 2017 27;8:511. Epub 2017 Sep 27.

Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany.

Objective: The neuroprotective properties of the noble gas xenon have already been demonstrated using a variety of injury models. Here, we examine for the first time xenon's possible effect in attenuating early brain injury (EBI) and its influence on posthemorrhagic microglial neuroinflammation in an rat model of subarachnoid hemorrhage (SAH).

Methods: Sprague-Dawley rats ( = 22) were randomly assigned to receive either Sham surgery ( = 9; divided into two groups) or SAH induction endovascular perforation ( = 13, divided into two groups). Of those randomized for SAH, 7 animals were postoperatively ventilated with 50 vol% oxygen/50 vol% xenon for 1 h and 6 received 50 vol% oxygen/50 vol% nitrogen (control). The animals were sacrificed 24 h after SAH. Of each animal, a cerebral coronal section (-3.60 mm from bregma) was selected for assessment of histological damage 24 h after SAH. A 5-point neurohistopathological severity score was applied to assess neuronal cell damage in H&E and NeuN stained sections in a total of four predefined anatomical regions of interest. Microglial activation was evaluated by a software-assisted cell count of Iba-1 stained slices in three cortical regions of interest.

Results: A diffuse cellular damage was apparent in all regions of the ipsilateral hippocampus 24 h after SAH. Xenon-treated animals presented with a milder damage after SAH. This effect was found to be particularly pronounced in the medial regions of the hippocampus, CA3 ( = 0.040), and dentate gyrus (DG  = 0.040). However, for the CA1 and CA2 regions, there were no statistical differences in neuronal damage according to our histological scoring. A cell count of activated microglia was lower in the cortex of xenon-treated animals. This difference was especially apparent in the left piriform cortex ( = 0.017).

Conclusion: In animals treated with 50 vol% xenon (for 1 h) after SAH, a less pronounced neuronal damage was observed for the ipsilateral hippocampal regions CA3 and DG, when compared to the control group. In xenon-treated animals, a lower microglial cell count was observed suggesting an immunomodulatory effect generated by xenon. As for now, these results cannot be generalized as only some hippocampal regions are affected. Future studies should assess the time and localization dependency of xenon's beneficial properties after SAH.
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http://dx.doi.org/10.3389/fneur.2017.00511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623683PMC
September 2017

Anaesthesia Management for Awake Craniotomy: Systematic Review and Meta-Analysis.

PLoS One 2016 26;11(5):e0156448. Epub 2016 May 26.

Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany.

Background: Awake craniotomy (AC) renders an expanded role in functional neurosurgery. Yet, evidence for optimal anaesthesia management remains limited. We aimed to summarise the latest clinical evidence of AC anaesthesia management and explore the relationship of AC failures on the used anaesthesia techniques.

Methods: Two authors performed independently a systematic search of English articles in PubMed and EMBASE database 1/2007-12/2015. Search included randomised controlled trials (RCTs), observational trials, and case reports (n>4 cases), which reported anaesthetic approach for AC and at least one of our pre-specified outcomes: intraoperative seizures, hypoxia, arterial hypertension, nausea and vomiting, neurological dysfunction, conversion into general anaesthesia and failure of AC. Random effects meta-analysis was used to estimate event rates for four outcomes. Relationship with anaesthesia technique was explored using logistic meta-regression, calculating the odds ratios (OR) and 95% confidence intervals [95%CI].

Results: We have included forty-seven studies. Eighteen reported asleep-awake-asleep technique (SAS), twenty-seven monitored anaesthesia care (MAC), one reported both and one used the awake-awake-awake technique (AAA). Proportions of AC failures, intraoperative seizures, new neurological dysfunction and conversion into general anaesthesia (GA) were 2% [95%CI:1-3], 8% [95%CI:6-11], 17% [95%CI:12-23] and 2% [95%CI:2-3], respectively. Meta-regression of SAS and MAC technique did not reveal any relevant differences between outcomes explained by the technique, except for conversion into GA. Estimated OR comparing SAS to MAC for AC failures was 0.98 [95%CI:0.36-2.69], 1.01 [95%CI:0.52-1.88] for seizures, 1.66 [95%CI:1.35-3.70] for new neurological dysfunction and 2.17 [95%CI:1.22-3.85] for conversion into GA. The latter result has to be interpreted cautiously. It is based on one retrospective high-risk of bias study and significance was abolished in a sensitivity analysis of only prospectively conducted studies.

Conclusion: SAS and MAC techniques were feasible and safe, whereas data for AAA technique are limited. Large RCTs are required to prove superiority of one anaesthetic regime for AC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156448PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882028PMC
July 2017
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