Publications by authors named "Gerrit Alexander Schubert"

47 Publications

Non-invasive Assessment of Neurovascular Coupling After Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Trial Using Retinal Vessel Analysis.

Front Neurol 2021 14;12:690183. Epub 2021 Jun 14.

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

Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus. Static and dynamic RVA were performed using a Retinal Vessel Analyzer (IMEDOS Systems GmbH, Jena) in 70 aSAH patients during the early (d), critical (d), late (d) phase, and at follow-up (f/u > 6 weeks) after the ictus. For comparison, an age-matched cohort of 42 healthy subjects was also included in the study. Vessel diameters were quantified in terms of the central retinal arterial and venous equivalent (CRAE, CRVE) and the retinal arterio-venous-ratio (AVR). Vessel responses to flicker light excitation (FLE) were quantified by recording the maximum arterial and venous dilation (MAD, MVD), the time to 30% and 100% of maximum dilation (tMAD, tMVD; tMAD, tMVD, resp.), and the arterial and venous area under the curve (AUC, AUC) during the FLE. For subgroup analyses, patients were stratified according to the development of DCI and clinical outcomes after 12 months. Vessel diameter (CRAE, CRVE) was significantly smaller in aSAH patients and showed little change throughout the whole observation period ( < 0.0001 vs. control for all time periods examined). In addition, aSAH patients exhibited impaired arterial but not venous responses to FLE, as reflected in a significantly lower MAD [2.2 (1.0-3.2)% vs. 3.6 (2.6-5.6)% in control subjects, = 0.0016] and AUC [21.5 (9.4-35.8)%s vs. 51.4 (32.5-69.7)%s in control subjects, = 0.0001] on d. However, gradual recovery was observed during the first 3 weeks, with close to normal levels at follow-up, when MAD and AUC amounted to 3.0 [2.0-5.0]% ( = 0.141 vs. control, = 0.0321 vs. d) and 44.5 [23.2-61.1]%s ( = 0.138 . control, < 0.01 vs. d & d). Finally, patients with clinical deterioration (DCI) showed opposite changes in the kinetics of arterial responses during early and late phase, as reflected in a significantly lower tMAD on d [4.0 (3.0-6.8) s vs. 7.0 (5.0-8.0) s in patients without DCI, = 0.022) and a significantly higher tMAD on d (24.0 (21.0-29.3) s . 18.0 (14.0-21.0) s in patients without DCI, = 0.017]. Our findings confirm and extend previous observations that aSAH results in sustained impairments of NVC in the retina. DCI may be associated with characteristic changes in the kinetics of retinal arterial responses. However, further studies will be required to determine their clinical implications and to assess if they can be used to identify patients at risk of developing DCI. ClinicalTrials.gov Identifier: NCT04094155.
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http://dx.doi.org/10.3389/fneur.2021.690183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236540PMC
June 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 Jun 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
June 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

Levosimendan as a therapeutic strategy to prevent neuroinflammation after aneurysmal subarachnoid hemorrhage?

J Neurointerv Surg 2021 May 26. Epub 2021 May 26.

Neurosurgery, Goethe University Hospital, Frankfurt am Main, Germany.

Background: Poor patient outcomes after aneurysmal subarachnoid hemorrhage (SAH) occur due to a multifactorial process, mainly involving cerebral inflammation (CI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia, followed by neurodegeneration. CI is mainly triggered by enhanced synthesis of serotonin (5-HT), prostaglandin F2alpha (PGF2a), and cytokines such as interleukins. Levosimendan (LV), a calcium-channel sensitizer, has already displayed anti-inflammatory effects in patients with severe heart failure. Therefore, we wanted to elucidate its potential anti-inflammatory role on the cerebral vasculature after SAH.

Methods: Experimental SAH was induced by using an experimental double-hemorrhage model. Sprague Dawley rats were harvested on day 3 and day 5 after the ictus. The basilar artery was used for isometric investigations of the muscular media tone. Vessel segments were either preincubated with LV or without, with precontraction performed with 5-HT or PGF2a followed by application of acetylcholine (ACh) or LV.

Results: After preincubation with LV 10 M and 5-HT precontraction, ACh triggered a strong vasorelaxation in sham segments (LV 10 M, E 65%; LV 10 M, E 48%; no LV, E 53%). Interestingly, SAH D3 (LV 10, E 76%) and D5 (LV 10, E 79%) segments showed greater vasorelaxation compared with sham. An LV series after PGF2a precontraction showed significantly enhanced relaxation in the sham (P=0.004) and SAH groups (P=0.0008) compared with solvent control vessels.

Conclusions: LV application after SAH seems to beneficially influence DCVS by antagonizing 5-HT- and PGF2a-triggered vasoconstriction. Considering this spasmolytic effect, LV might have a role in the treatment of SAH, additionally in selected patients suffering takotsubo cardiomyopathy.
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http://dx.doi.org/10.1136/neurintsurg-2021-017504DOI Listing
May 2021

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

World Neurosurg 2021 Jul 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

Retinal Vessel Responses to Flicker Stimulation Are Impaired in Ca 2.3-Deficient Mice-An Evaluation Using Retinal Vessel Analysis (RVA).

Front Neurol 2021 13;12:659890. Epub 2021 Apr 13.

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

Metabolic demand increases with neuronal activity and adequate energy supply is ensured by neurovascular coupling (NVC). Impairments of NVC have been reported in the context of several diseases and may correlate with disease severity and outcome. Voltage-gated Ca-channels (VGCCs) are involved in the regulation of vasomotor tone. In the present study, we compared arterial and venous responses to flicker stimulation in Ca2.3-competent (Ca2.3) and -deficient (Ca2.3) mice using retinal vessel analysis. The mice were anesthetized and the pupil of one eye was dilated by application of a mydriaticum. An adapted prototype of retinal vessel analyzer was used to perform dynamic retinal vessel analysis. Arterial and venous responses were quantified in terms of the area under the curve (AUC/AUC) during flicker application, mean maximum dilation (mMD/mMD) and time to maximum dilation (tMD/tMD) during the flicker, dilation at flicker cessation (DFC/DFC), mean maximum constriction (mMC/mMC), time to maximum constriction (tMC/tMC) after the flicker and reactive magnitude (RM/RM). A total of 33 retinal scans were conducted in 22 Ca2.3 and 11 Ca2.3 mice. Ca2.3 mice were characterized by attenuated and partially reversed arterial and venous responses, as reflected in significantly lower AUC ( = 0.031) and AUC ( = 0.047), a trend toward reduced DFC ( = 0.100), DFC ( = 0.100), mMD ( = 0.075), and RM ( = 0.090) and a trend toward increased tMD ( = 0.096). To our knowledge, this is the first study using a novel, non-invasive analysis technique to document impairment of retinal vessel responses in VGCC-deficient mice. We propose that Ca2.3 channels could be involved in NVC and may contribute to the impairment of vasomotor responses under pathophysiological conditions.
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http://dx.doi.org/10.3389/fneur.2021.659890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076560PMC
April 2021

Cortical volume reductions as a sign of secondary cerebral and cerebellar impairment in patients with degenerative cervical myelopathy.

Neuroimage Clin 2021 13;30:102624. Epub 2021 Mar 13.

Department of Neurosurgery, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany. Electronic address:

This study investigated supra- and infratentorial structural gray and white matter (GM, WM) alterations in patients with degenerative cervical myelopathy (DCM) as an indicator of secondary harm due to chronic cervical cord compression and micro trauma. With MRI-based anatomical assessment and subsequent voxel-based morphometry analyses, pre- and postoperative volume alterations in the primary motor cortex (MI), the primary somatosensory cortex (SI), the supplementary motor area (SMA), and the cerebellum were analyzed in 43 DCM patients and 20 controls. We assessed disease-related symptom severity by the modified Japanese Orthopaedic Association scale (mJOA). The study also explored symptom severity-based brain volume alterations as well as their association with clinical status. Patients had lower mJOA scores (p = .000) and lower GM volume than controls in SI (p = .016) and cerebellar regions (p = .001). Symptom severity-based subgroup analyses revealed volume reductions in almost all investigated GM ROIs (MI: p = .001; CB: p = .040; SMA: p = .007) in patients with severe clinical symptoms as well as atrophy already present in patients with moderate symptom severity. Clinical symptoms in DCM were associated with cortical and cerebellar volume reduction. GM volume alterations may serve as an indicator of both disease severity and ongoing disease progression in DCM, and should be considered in further patient care and treatment monitoring.
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http://dx.doi.org/10.1016/j.nicl.2021.102624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025145PMC
July 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

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

Neurocrit Care 2021 Aug 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

Risk of postprocedural intracerebral hemorrhage in patients with ruptured cerebral aneurysms after treatment with antiplatelet agents.

J Neurol Sci 2021 01 4;420:117219. Epub 2020 Nov 4.

Department of Neurosurgery, RWTH Aachen University, Germany.

Objective: Endovascular treatment of ruptured cerebral aneurysms frequently requires antiplatelet medication to prevent thromboembolism. This might raise concern regarding the risk of postprocedural hemorrhage (pH), e.g. from placement of intracranial probes. We explored the risk of PH associated with standard antiplatelet therapy (sAP: acetylsalicylic acid, and/or clopidogrel) in the context of aneurysmal subarachnoid hemorrhage (aSAH).

Methods: We retrospectively reviewed a total of 146 consecutive cases with cerebral aneurysms treated between 1/2011-12/2015, and distinguished between minor (0.5 cm) - 4 cm) or major (> 4 cm) PH occurring within four weeks after intervention. A separate analysis included hemorrhages related to placement of intracranial probes and drainages in the subgroup of 99 cases with such surgical interventions (pPH). Clinical outcome was assessed via Glasgow Outcome Scale (GOS) twelve months after aSAH.

Results: A total of 49 cases (33.6%) in the overall sample sustained PH, there were 19 cases of pPH. Multifactorial analyses yielded sAP as an independent predictor for minor, but not major PH (p < 0.001 vs. p = 0.829), with comparable results for pPH (p = 0.001 vs. p = 0.184). sAP did not influence the clinical outcome in either group.

Conclusions: sAP was associated with a higher rate of minor PH and, more specifically, of minor pPH. However, it was neither accompanied by the occurrence of major hemorrhages nor by unfavorable clinical outcome. Future prospective studies should confirm these observations and hemorrhage risks associated with extended anticoagulation regimes after complex interventions and intra-arterial vasospasm therapy should be explored in order to facilitate interdisciplinary decision-making in aSAH.
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http://dx.doi.org/10.1016/j.jns.2020.117219DOI Listing
January 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

Surgical nuances and placement of subgaleal drains for supratentorial procedures-a prospective analysis of efficacy and outcome in 150 craniotomies.

Acta Neurochir (Wien) 2020 04 15;162(4):729-736. Epub 2020 Jan 15.

Department of Neurosurgery, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.

Background: For supratentorial craniotomy, surgical access, and closure technique, including placement of subgaleal drains, may vary considerably. The influence of surgical nuances on postoperative complications such as cerebrospinal fluid leakage or impaired wound healing overall remains largely unclear. With this study, we are reporting our experiences and the impact of our clinical routines on outcome in a prospectively collected data set.

Method: We prospectively observed 150 consecutive patients undergoing supratentorial craniotomy and recorded technical variables (type/length of incision, size of craniotomy, technique of dural and skin closure, type of dressing, and placement of subgaleal drains). Outcome variables (subgaleal hematoma/CSF collection, periorbital edema, impairment of wound healing, infection, and need for operative revision) were recorded at time of discharge and at late follow-up.

Results: Early subgaleal fluid collection was observed in 36.7% (2.8% at the late follow-up), and impaired wound healing was recorded in 3.3% of all cases, with an overall need for operative revision of 6.7%. Neither usage of dural sealants, lack of watertight dural closure, and presence of subgaleal drains, nor type of skin closure or dressing influenced outcome. Curved incisions, larger craniotomy, and tumor size, however, were associated with an increase in early CSF or hematoma collection (p < 0.0001, p = 0.001, p < 0.01 resp.), and larger craniotomy size was associated with longer persistence of subgaleal fluid collections (p < 0.05).

Conclusions: Based on our setting, individual surgical nuances such as the type of dural closure and the use of subgaleal drains resulted in a comparable complication rate and outcome. Subgaleal fluid collections were frequently observed after supratentorial procedures, irrespective of the closing technique employed, and resolve spontaneously in the majority of cases without significant sequelae. Our results are limited due to the observational nature in our single-center study and need to be validated by supportive prospective randomized design.
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http://dx.doi.org/10.1007/s00701-019-04196-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066100PMC
April 2020

Findings and Prognostic Value of Contrast-Enhanced Early Magnetic Resonance Imaging After Coil Embolization of Cerebral Aneurysms.

World Neurosurg 2020 Mar 6;135:e382-e385. Epub 2019 Dec 6.

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

Background: Recent studies imply an association between aneurysm wall enhancement (AWE) on contrast-enhanced magnetic resonance imaging and aneurysm rupture. We investigated the prevalence and clinical significance of AWE and enhancement within the aneurysm (inner enhancement [IE]) in coiled aneurysms.

Methods: We assessed the frequency of AWE and IE after coil embolization on postinterventional magnetic resonance imaging (<6 weeks) in 30 consecutive patients with 33 aneurysms and elucidated the association between enhancement and subsequent aneurysm recurrence or hemorrhage.

Results: AWE and IE occurred in 97% and 36% of cases, respectively. There was no rehemorrhage, and there was no significant association between subsequent reperfusion and AWE (P = 0.200) or IE (P = 0.148) during a median follow-up period of 19 months. The greatest share of IE (8 of 12 aneurysms) was found in incompletely coiled aneurysms with small remnants (P = 0.001).

Conclusions: AWE after coil embolization cannot be used for recurrence risk stratification owing to its high prevalence. IE is likely to represent contrast inflow in the coiled aneurysm.
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http://dx.doi.org/10.1016/j.wneu.2019.11.173DOI Listing
March 2020

Unique Angioarchitecture of Sacral Dural Arteriovenous Fistula.

World Neurosurg 2020 Jan 21;133:25-28. Epub 2019 Sep 21.

Department of Neurosurgery, Justus-Liebig-University, Giessen, Germany.

Background: Spinal dural arteriovenous fistulas (DAVFs) in the sacral region are extremely rare. The location and complex angioarchitecture of these lesions make both identification and treatment challenging, even in experienced hands. We report on a sacral DAVF with a unique angioarchitecture and discuss its specific anatomy.

Case Description: A 76-year-old male presented with progressive distal paraparesis and spinal ataxia. Three lumbar decompression surgeries were performed between 2016 and 2018 elsewhere on the basis of suspected degenerative lumbar syndrome. On admission to our center, the patient was wheelchair dependent due to extensive spinal ataxia associated with bilateral foot paresis and hypoesthesia. Spinal contrast-enhanced time-resolved magnetic resonance angiography and digital subtraction angiography were performed after admission to our center. Contrast-enhanced magnetic resonance angiography examinations suggested a sacral DAVF. Subsequent digital subtraction angiography demonstrated a spinal DAVF on the left side at the S2 vertebral level supplied via an arterial epidural branch from the right L4 segmental artery. The fistula was treated via surgical interruption of the proximal part of the radicular drainage vein.

Conclusions: Sacral DAVFs present serious diagnostic difficulties and require a profound understanding of possible fistula-supplying arteries of the sacral region. Microsurgical interruption of the often ventrally located drainage vein presents an efficient treatment modality and could provide an immediate confirmation of fistula occlusion using indocyanine green videoangiography.
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http://dx.doi.org/10.1016/j.wneu.2019.09.078DOI Listing
January 2020

Acute changes of pro-inflammatory markers and corticosterone in experimental subarachnoid haemorrhage: A prerequisite for severity assessment.

PLoS One 2019 30;14(7):e0220467. Epub 2019 Jul 30.

Translational Neurosurgery and Neurobiology, University Hospital Aachen, RWTH Aachen, Aachen, Germany.

Many details of the pathophysiology of subarachnoid haemorrhage (SAH) still remain unknown, making animal experiments an indispensable tool for assessment of diagnostics and therapy. For animal protection and project authorization, one needs objective measures to evaluate the severity and burden in each model. Corticosterone is described as a sensitive stress parameter reflecting the acute burden, and inflammatory markers can be used for assessment of the extent of the brain lesion. However, the brain lesion itself may activate the hypothalamic-pituitary-adrenal-axis early after SAH, as shown for ischemic stroke, probably interfering with early inflammatory processes, thus complicating the assessment of severity and burden on the basis of corticosterone and inflammation. To assess the suitability of these markers in SAH, we evaluated the courses of corticosterone, IL-6 and TNF-α up to 6h in an acute model simulating SAH in continuously anaesthetized rats, lacking the pain and stress induced impact on these parameters. Animals were randomly allocated to sham or SAH. SAH was induced by cisterna magna blood-injection, and intracranial pressure and cerebral blood flow were measured under continuous isoflurane/fentanyl anaesthesia. Withdrawn at predetermined time points, blood was analysed by commercial ELISA kits. After 6h the brain was removed for western blot analysis of IL-6 and TNF-α. Serum corticosterone levels were low with no significant difference between sham and SAH. No activation of the HPA-axis was detectable, rendering corticosterone a potentially useful parameter for stress assessment in future chronic studies. Blood IL-6 and TNF-α increased in both groups over time, with IL-6 increasing significantly more in SAH compared to sham towards the end of the observation period. In the basal cortex, IL-6 and TNF-α increased only in SAH. The pro-inflammatory response seems to start locally in the brain, reflected by an increase in peripheral blood. An additional surgery-induced systemic inflammatory response should be considered.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220467PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667150PMC
March 2020

Modulation of Ca2.3 channels by unconjugated bilirubin (UCB) - Candidate mechanism for UCB-induced neuromodulation and neurotoxicity.

Mol Cell Neurosci 2019 04 12;96:35-46. Epub 2019 Mar 12.

Institute for Neurophysiology, University of Cologne, Germany. Electronic address:

Elevated levels of unbound unconjugated bilirubin (UCB) can lead to bilirubin encephalopathy and kernicterus. In spite of a large number of studies demonstrating UCB-induced changes in central neurotransmission, it is still unclear whether these effects involve alterations in the function of specific ion channels. To assess how different UCB concentrations and UCB:albumin (U/A) molar ratios affect neuronal R-type voltage-gated Ca channels, we evaluated their effects on whole-cell currents through recombinant Ca2.3 + β channel complexes and ex-vivo electroretinograms (ERGs) from wildtype and Ca2.3-deficient mice. Our findings show that modestly elevated levels of unbound UCB (U/A = 0.5) produce subtle but significant changes in the voltage-dependence of activation and prepulse inactivation, resulting in a stimulation of currents activated by weak depolarization and inhibition at potentials on the plateau of the activation curve. Saturation of the albumin binding capacity (U/A = 1) produced additional suppression that became significant when albumin was omitted completely and might involve a complete loss of channel function. Acutely administered UCB (U/A = 0.5) has recently been shown to affect transsynaptic signaling in the isolated vertebrate retina. The present report reveals that sustained exposure of the murine retina to UCB significantly suppresses also late responses of the inner retina (b-wave) from wildtype compared to Ca2.3-deficient mice. In addition, recovery during washout was significantly more complete and faster in retinae lacking Ca2.3 channels. Together, these findings show that UCB affects cloned and native Ca2.3 channels at clinically relevant U/A molar ratios and indicate that supersaturation of albumin is not required for modulation but associated with a loss of channel functional that could contribute to chronic neuronal dysfunction.
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http://dx.doi.org/10.1016/j.mcn.2019.03.003DOI Listing
April 2019

Endovascular Rescue Treatment for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Is Safe and Effective.

Front Neurol 2019 21;10:136. Epub 2019 Feb 21.

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

The implementation of rescue efforts for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage remains largely empirical for a lack of supporting evidence, while the associated risk profile is also unclear. The present study evaluates the safety and efficacy of endovascular rescue treatment (ERT, continuous intraarterial nimodipine; IAN, transcutaneous balloon angioplasty, TBA). In this prospective observational study, we assessed periprocedural complications and side effects in context of ERT. We evaluated neurological status, multimodal neuromonitoring (pO, lactate/pyruvate ratio, transcranial doppler), and cranial imaging (CTP, DSA). All parameters were included into multivariate analysis to determine predictors for the need of retreatment. We included 33 consecutive patients with 54 ERT (IAN = 35; TBA = 13; TBA + IAN = 6). We recorded no serious complications and initial improvement in all parameters (neurostatus 72.3% of patients; pO 15.0 ± 11.7 to 25.8 ± 15.5 mmHg, < 0.0001; lactate/pyruvate ratio 46.3 ± 27.5 to 31.0 ± 9.7, <0.05; transcranial doppler 139.0 ± 46.3 to 98.9 ± 29.6 cm/s, < 0.05; CTP 81.6% of patients; DSA 93.1% of patients). Retreatment ( = 16, 48.5%) was independently associated with preinterventional pO < 5 mmHg ( <0.01) and early (<72 h) discontinuation of IAN treatment ( = 0.08). DCI related cerebral infarction was noted in = 8 patients (24.2%). At 3 months after discharge, favorable outcome was noted for = 11 (35.5%) patients. Provided a detailed decision tree, timely ERT can provide a relatively safe and effective treatment option in those highly-selected patients undergoing multimodality monitoring where conservative treatment options are exhausted. Continuous treatment in particular may be suitable to surpass sustained DCI and was associated with a low rate of DCI related infarction and comparably high percentage of good outcome.
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http://dx.doi.org/10.3389/fneur.2019.00136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398410PMC
February 2019

Non-invasive evaluation of neurovascular coupling in the murine retina by dynamic retinal vessel analysis.

PLoS One 2018 4;13(10):e0204689. Epub 2018 Oct 4.

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

Background: Impairment of neurovascular coupling (NVC) was recently reported in the context of subarachnoid hemorrhage and may correlate with disease severity and outcome. However, previous techniques to evaluate NVC required invasive procedures. Retinal vessels may represent an alternative option for non-invasive assessment of NVC.

Methods: A prototype of an adapted retinal vessel analyzer was used to assess retinal vessel diameter in mice. Dynamic vessel analysis (DVA) included an application of monochromatic flicker light impulses in predefined frequencies for evaluating NVC. All retinae were harvested after DVA and electroretinograms were performed.

Results: A total of 104 retinal scans were conducted in 21 male mice (90 scans). Quantitative arterial recordings were feasible only in a minority of animals, showing an emphasized reaction to flicker light impulses (8 mice; 14 scans). A characteristic venous response to flicker light, however, could observed in the majority of animals. Repeated measurements resulted in a significant decrease of baseline venous diameter (7 mice; 7 scans, p < 0.05). Ex-vivo electroretinograms, performed after in-vivo DVA, demonstrated a significant reduction of transretinal signaling in animals with repeated DVA (n = 6, p < 0.001).

Conclusions: To the best of our knowledge, this is the first non-invasive study assessing murine retinal vessel response to flicker light with characteristic changes in NVC. The imaging system can be used for basic research and enables the investigation of retinal vessel dimension and function in control mice and genetically modified animals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204689PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171857PMC
March 2019

Anticoagulation Therapy After Surgical Treatment of Spinal Dural Arteriovenous Fistula. Effectiveness and Long-Term Outcome Analysis.

World Neurosurg 2018 Jun 14;114:e698-e705. Epub 2018 Mar 14.

Department of Diagnostic and Interventional Neuroradiology, RWTH Aachen University Hospital, Aachen, Germany.

Objective: Effectiveness and safety of anticoagulation therapy (AC) after treatment of spinal dural arteriovenous fistula (sdAVF) are still inadequately discussed in the literature and are addressed in this study.

Methods: We retrospectively analyzed our medical database for patients with sdAVF treated in our institution between 2006 and 2016. Neurologic status at time of admission, discharge, and last follow-up was assessed via Aminoff-Logue disability score. Patient cohorts were dichotomized as group A (postoperative therapeutic heparinization) and group B (routine thromboembolic prophylaxis with low-dose heparin).

Results: Fifty-three patients were included in this analysis. In group A (n = 11), no acute deterioration was reported. In group B (n = 42), 4 patients developed acute postoperative deterioration; therapeutic AC was initiated in all 4 patients resulting in complete neurologic recovery within the inpatient stay. However, the incidence of postoperative deterioration did not reach statistical significance between treatment groups (P = 0.57). Data of 40 patients were available for long-term analysis (mean, 53.4 ± 36 months). Neurologic status did not differ significantly between both groups at time of admission (P = 0.093), discharge (P = 0.723), and last follow-up (P = 0.222).

Conclusions: Acute postoperative deterioration in patients with sdAVF is a clinically relevant complication and was present in 7.5% of patients in our series. Although routine therapeutic AC did not decrease the rate of acute deterioration significantly, our findings imply that therapeutic AC in cases of acute postoperative deterioration might be a safe and efficient treatment option.
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http://dx.doi.org/10.1016/j.wneu.2018.03.061DOI Listing
June 2018

Unconjugated bilirubin modulates neuronal signaling only in wild-type mice, but not after ablation of the R-type/Ca 2.3 voltage-gated calcium channel.

CNS Neurosci Ther 2018 03 23;24(3):222-230. Epub 2017 Dec 23.

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

Introduction: The relationship between blood metabolites and hemoglobin degradation products (BMHDPs) formed in the cerebrospinal fluid and the development of vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been the focus of several previous studies, but their molecular and cellular targets remain to be elucidated.

Methods: Because BMHDP-induced changes in Ca 2.3 channel function are thought to contribute to DCI after aSAH, we studied their modulation by unconjugated bilirubin (UCB) in an organotypical neuronal network from wild-type (WT) and Ca 2.3-deficient animals (KO). Murine retinae were isolated from WT and KO and superfused with nutrient solution. Electroretinograms were recorded before, during, and after superfusion with UCB. Transretinal signaling was analyzed as b-wave, implicit time, and area under the curve (AUC).

Results: Superfusion of UCB significantly attenuated the b-wave amplitude in the isolated retina from wild-type mice by 14.9% (P < 0.05), followed by gradual partial recovery (P = 0.09). Correspondingly, AUC decreased significantly with superfusion of UCB (P < 0.05). During washout, the b-wave amplitude returned to baseline (P = 0.2839). The effects of UCB were absent in Ca 2.3-deficient mice, lacking the expression of Ca 2.3 as proofed on the biochemical level.

Conclusions: Ex vivo neuronal recording in the murine retina is able to detect transient impairment of transretinal signaling by UCB in WT, but not in KO. This new model may be useful to further clarify the role of calcium channels in neuronal signal alteration in the presence of BHMDPs.
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http://dx.doi.org/10.1111/cns.12791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489700PMC
March 2018

Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes.

Transl Stroke Res 2018 06 8;9(3):284-293. Epub 2017 Nov 8.

Department of Neurosurgery, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.

Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5-14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels-central retinal arteriolar and venular equivalent-was significantly reduced in the acute phase (p < 0.001) with gradual improvement in group B (p < 0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p < 0.001) and reduced area under the curve (p < 0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p < 0.05). Venous NVC was significantly delayed after SAH compared to group C (A p < 0.001; B p < 0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.
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http://dx.doi.org/10.1007/s12975-017-0585-8DOI Listing
June 2018

Electroretinographic Assessment of Inner Retinal Signaling in the Isolated and Superfused Murine Retina.

Curr Eye Res 2017 11 25;42(11):1518-1526. Epub 2017 Aug 25.

a Institute for Neurophysiology, University of Cologne , Cologne , Germany.

Purpose: Longer-lasting electroretinographic recordings of the isolated murine retina were initially achieved by modification of a phosphate-buffered nutrient solution originally developed for the bovine retina. During experiments with a more sensitive mouse retina, apparent model-specific limitations were addressed and improvements were analyzed for their contribution to an optimized full electroretinogram (ERG).

Material And Methods: Retinas were isolated from dark-adapted mice, transferred to a recording chamber and superfused with different solutions. Scotopic and photopic ERGs were recorded with white flashes every 3 minutes. The phosphate buffer (Sickel-medium) originally used was replaced by a carbonate-based system (Ames-medium), the pH of which was adjusted to 7.7-7.8. Moreover, addition of 0.1 mM BaCl was investigated to reduce b-wave contamination by the slow PIII component typically present in the murine ERG.

Results: B-wave amplitudes were increased by the pH-shift (pH 7.4 to pH 7.7) from 22.9 ± 1.9 µV to 37.5 ± 2.5 µV. Improved b-wave responses were also achieved by adding small amounts of Ba (100 µM), which selectively suppressed slow PIII components, thereby unmasking more of the true b-wave amplitude (100.0% with vs. 22.2 ± 10.7% without Ba). Ames medium lacking amino acids and vitamins was unable to maintain retinal signaling, as evident in a reversible decrease of the b-wave to 31.8 ± 3.9% of its amplitude in complete Ames medium.

Conclusions: Our findings provide optimized conditions for ex vivo ERGs from the murine retina and suggest that careful application of Ba supports reliable isolation of b-wave responses in mice. Under our recording conditions, murine retinas show reproducible ERGs for up to six hours.
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http://dx.doi.org/10.1080/02713683.2017.1339807DOI Listing
November 2017

Systemic and Cerebral Concentration of Nimodipine During Established and Experimental Vasospasm Treatment.

World Neurosurg 2017 Jun 23;102:459-465. Epub 2017 Mar 23.

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

Background: Oral nimodipine is an established prophylactic agent for cerebral vasospasm after subarachnoid hemorrhage (SAH). In highly selected cases, intra-arterial (IA) or intravenous (IV) application of nimodipine may be considered; however, the optimum dosage and modality of application remain a matter of debate. The purpose of this investigation is analysis of nimodipine concentration in serum, cerebrospinal fluid, and cerebral microdialysate in the context of currently effective dose and route of application (oral, IA, IV).

Methods: We prospectively collected 156 samples from 37 patients treated for aneurysmal SAH from May 2014 to July 2015. Treatment groups were stratified according to modality of application and low-dose or high-dose treatment. At time of sampling, current dose and modality of application effectively sustained cerebral perfusion as documented by common diagnostics. Samples were analyzed for nimodipine concentration via high-performance liquid chromatography and tandem mass spectrometry.

Results: In most cases (94.3%), nimodipine remained below the limit of quantification (0.5 ng/mL) within the brain (microdialysis, cerebrospinal fluid), even during targeted, local application (IA nimodipine). The median serum concentration for all treatment groups was 17.3 ng/mL. Modality of application (oral, IA, IV) was not associated with significant differences in serum concentrations (P = 0.712), even after stratification for dosage (P = 0.371), implying a comparable systemic distribution, if not efficacy.

Conclusions: Nimodipine does not accumulate sufficiently within the target organ for treatment monitoring. Comparable systemic concentrations can be observed irrespective of application modality and dosing. Future studies will clarify the role of efficacy-driven treatment algorithms, in which lowest dose and least invasive mode of application still effective should be identified.
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http://dx.doi.org/10.1016/j.wneu.2017.03.062DOI Listing
June 2017

Endovascular Rescue Therapies for Refractory Vasospasm After Subarachnoid Hemorrhage: A Prospective Evaluation Study Using Multimodal, Continuous Event Neuromonitoring.

Neurosurgery 2017 Jun;80(6):942-949

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

Background: Critical hypoperfusion and metabolic derangement are frequently encountered with refractory vasospasm. Endovascular rescue therapies (ERT) have proven beneficial in selected cases. However, angioplasty (AP) and intraarterial lysis (IAL) are measures of last resort and prospective, quantitative results regarding the efficacy (cerebral oxygenation, metabolism) are largely lacking.

Objective: To evaluate the efficacy of ERTs for medically refractory vasospasm using multimodal, continuous event neuromonitoring.

Methods: To detect cerebral compromise in a timely fashion, sedated patients with aneurysmal subarachnoid hemorrhage received continuous neuromonitoring (p ti O 2 measurement, intraparenchymal microdialysis). ERT (AP and/or IAL) was considered in cases of clinically relevant vasospasm refractory to conservative treatment measures. Oxygen saturation and cerebral and systemic metabolism before and after events of ERT was recorded.

Results: We prospectively included 13 consecutive patients and recorded a total of 25 ERT events: AP (n = 10), IAL (n = 11), or both (AP + IAL, n = 4). Average cerebral p ti O 2 was 10 ± 11 torr before and 49 ± 22 torr after ERT ( P < .001), with a lactate-pyruvate ratio decreasing from 146.6 ± 119.0 to 27.9 ± 10.7 after ERT ( P < .001). Comparable improvement was observed for each type of intervention (AP, IAL, or both). No significant alterations in systemic metabolism could be detected after ERT.

Conclusion: Multimodal event neuromonitoring is able to quantify treatment efficacy in subarachnoid hemorrhage-related vasospasm. In our small cohort of highly selected cases, ERT was associated with improvement in cerebral oxygenation and metabolism with reasonable outcome. Event neuromonitoring may facilitate individual and timely optimization of treatment modality according to the individual clinical course.
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http://dx.doi.org/10.1093/neuros/nyw132DOI Listing
June 2017

Twist Drill Procedure for Chronic Subdural Hematoma Evacuation: An Analysis of Predictors for Treatment Success.

World Neurosurg 2017 Apr 19;100:480-486. Epub 2017 Jan 19.

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

Background: Twist drill craniostomy (TDC) is a minimally invasive and cost-effective technique to treat chronic subdural hematomas (CSDHs). Predictors for treatment success such as imaging characteristics, hematoma volume, and drainage volume are not established; thus, they are purpose of this analysis.

Material And Methods: We retrospectively evaluated all data of patients with CSDH undergoing TDC in our institution between January 2010 and December 2013. We analyzed imaging characteristics (extension and composition), volumetrically calculated pre- and postoperative hematoma volumes, measured drainage volume, and clinical course. Primary treatment success was defined as sufficient if definitive treatment was achieved via a single TDC (TDC-1) and insufficient if more than one TDC was needed. The need for open surgical evacuation was defined as treatment failure.

Results: Data of 233 patients undergoing 387 TDCs were available for our study. A total of 67% of TDCs treated CSDHs effectively, whereas the remainder required further open surgical evacuation. Via use of the median-split-method, we found that sufficient treatment was achieved more frequently in smaller hematomas (P < 0.05). Treatment effectiveness was neither correlated with hematoma image characteristics (presence of membranes: P = 0.11, extent of chronification: P = 0.55) nor with the respective drainage volume (P = 0.95). Residual hematoma volume was consistently greater than expected by drainage calculation (P < 0.05).

Conclusions: TDC is an effective treatment option for CSDH. Sufficient treatment with single TDC was more common in smaller hematomas with an associated smaller residual hematoma. Failure of brain re-expansion after TDC may increase the treatment failure rates. In these cases, an open surgical evacuation might accelerate treatment and clinical recovery.
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http://dx.doi.org/10.1016/j.wneu.2017.01.037DOI Listing
April 2017

About the importance of the acute phase of subarachnoid hemorrhage and the chances for successful translation.

J Neurol Sci 2016 11 20;370:310-311. Epub 2016 Sep 20.

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

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http://dx.doi.org/10.1016/j.jns.2016.09.031DOI Listing
November 2016

Retinal Vessel Analysis (RVA) in the Context of Subarachnoid Hemorrhage - A Proof of Concept Study.

PLoS One 2016 7;11(7):e0158781. Epub 2016 Jul 7.

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

Background: Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH.

Methods: In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2-14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling.

Results: Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion.

Conclusion: RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158781PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936715PMC
July 2017

Volume perfusion CT imaging of cerebral vasospasm: diagnostic performance of different perfusion maps.

Neuroradiology 2016 Aug 18;58(8):787-92. Epub 2016 May 18.

Department of Diagnostic and Interventional Neuroradiology, RWTH Aachen University, Aachen, Germany.

Introduction: In this study, we aimed to evaluate the diagnostic performance of different volume perfusion CT (VPCT) maps regarding the detection of cerebral vasospasm compared to angiographic findings.

Methods: Forty-one datasets of 26 patients (57.5 ± 10.8 years, 18 F) with subarachnoid hemorrhage and suspected cerebral vasospasm, who underwent VPCT and angiography within 6 h, were included. Two neuroradiologists independently evaluated the presence and severity of vasospasm on perfusion maps on a 3-point Likert scale (0-no vasospasm, 1-vasospasm affecting <50 %, 2-vasospasm affecting >50 % of vascular territory). A third neuroradiologist independently assessed angiography for the presence and severity of vasospasm on a 3-point Likert scale (0-no vasospasm, 1-vasospasm affecting < 50 %, 2-vasospasm affecting > 50 % of vessel diameter). Perfusion maps of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to drain (TTD) were evaluated regarding diagnostic accuracy for cerebral vasospasm with angiography as reference standard. Correlation analysis of vasospasm severity on perfusion maps and angiographic images was performed. Furthermore, inter-reader agreement was assessed regarding findings on perfusion maps.

Results: Diagnostic accuracy for TTD and MTT was significantly higher than for all other perfusion maps (TTD, AUC = 0.832; MTT, AUC = 0.791; p < 0.001). TTD revealed higher sensitivity than MTT (p = 0.007). The severity of vasospasm on TTD maps showed significantly higher correlation levels with angiography than all other perfusion maps (p ≤ 0.048). Inter-reader agreement was (almost) perfect for all perfusion maps (kappa ≥ 0.927).

Conclusion: The results of this study indicate that TTD maps have the highest sensitivity for the detection of cerebral vasospasm and highest correlation with angiography regarding the severity of vasospasm.
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http://dx.doi.org/10.1007/s00234-016-1695-9DOI Listing
August 2016
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