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Objective: Current literature debates the role of newly developed three-dimensional (3D) Exoscopes in the daily routine of neurosurgical practice. So far, only a small number of cadaver lab studies or case reports have examined the novel Aesculap Aeos Three-Dimensional Robotic Digital Microscope. This study aims to evaluate the grade of satisfaction and intraoperative handling of this novel system in neurosurgery. Methods: Nineteen neurosurgical procedures (12 cranial, 6 spinal and 1 peripheral nerve) performed over 9 weeks using the Aeos were analyzed. Ten neurosurgeons of varying levels of training were included after undergoing device instruction and training. Following every surgery, a questionnaire consisting of 43 items concerning intraoperative handling was completed. The questionnaires were analyzed using descriptive statistics. Results: No intraoperative complications occurred. Surgical satisfaction was ranked high (78.95%). In total, 84.21% evaluated surgical ergonomics as satisfactory, while 78.95% of the surgeons would like to use this system frequently. Image quality, independent working zoom function and depth of field were perceived as suboptimal by several neurosurgeons. Conclusion: The use of Aeos is feasible and safe in microsurgical procedures, and surgical satisfaction was ranked high among most neurosurgeons in our study. The system might offer advanced ergonomic conditions in comparison to conventional ocular-based microscopes.
Anti-inflammatory response of Vitamin D on extracranial vessels after subarachnoid hemorrhage
(2023)
Oral e-Poster Presentations - Booth 1: Vascular A (Aneurysms), September 25, 2023, 1:00 PM - 2:30 PM
Background: Vitamin D has been promoted to vascular regeneration in non-cerebral arteries because of its anti-inflammatory properties. Systematic inflammatory reaction as a multifactorial complication after subarachnoid hemorrhage (SAH), correlated with higher mortality and poor outcome, is the result of a multifactorial mechanism with vasoactive inflammation on extracranial vessels. We therefore hypothesized that vitamin D attenuates the systemic vascular inflammatory reaction.
Methods: We investigated the effect of vitamin D pretreatment (100 ng/kg/d; 5 days) in a blood injection SAH model in adult male C57BL6 mice. Vasomotor function (via wire myograph) of carotid and femoral artery and neurological deficits were measured. Different inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM), were also tested.
Results: A significantly enhanced vasorelaxation was identified in Vitamin D pretreated mice (SAH-VitD versus SAH-control: p<0,001; n=10). Missing a relevant difference in vasocontraction of carotid and femoral artery comparing SAH mice with and without vitamin D treatment, there was a significantly higher endothelial related vasorelaxing effect in treated SAH mice (p<0,01, n=5). Neurological deficits in vitamin D pre-treated SAH mice were significantly decreased (p<0,05; n=10). All tested inflammatory factors were down-regulated in vitamin D pre-treated mice (SAH-VitD versus SAH-control: p<0,0001; n=10).
Conclusions: Extracranial vascular Inflammation after SAH, as one of the influencing components in the follow-up after SAH onset, was significantly attenuated by Vitamin D pretreatment. Furthermore, anti-inflammatory effect of vitamin D resulted in a decrease of extracranial vasoconstriction and neurological deficits. Further research should be focused on vitamin D to optimize therapeutic strategies for SAH patients in critical care units.
Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de).
Humanized mouse models have become increasingly valuable tools to study human hematopoiesis and infectious diseases. However, human T cell differentiation remains inefficient. We generated mice expressing human interleukin (IL-7), a critical growth and survival factor for T cells, under the control of murine IL-7 regulatory elements. After transfer of human cord blood-derived hematopoietic stem and progenitor cells, transgenic mice on the NSGW41 background, termed NSGW41hIL7, showed elevated and prolonged human cellularity in the thymus while maintaining physiological ratios of thymocyte subsets. As a consequence, numbers of functional human T cells in the periphery were increased without evidence for pathological lymphoproliferation or aberrant expansion of effector or memory-like T cells. We conclude that the novel NSGW41hIL7 strain represents an optimized mouse model for humanization to better understand human T cell differentiation in vivo and to generate a human immune system with a better approximation of human lymphocyte ratios.
umanized mouse models have become increasingly valuable tools to study human hematopoiesis and infectious diseases. However, human T-cell differentiation remains inefficient. We generated mice expressing human interleukin-7 (IL-7), a critical growth and survival factor for T cells, under the control of murine IL-7 regulatory elements. After transfer of human cord blood-derived hematopoietic stem and progenitor cells, transgenic mice on the NSGW41 background, termed NSGW41hIL7, showed elevated and prolonged human cellularity in the thymus while maintaining physiological ratios of thymocyte subsets. As a consequence, numbers of functional human T cells in the periphery were increased without evidence for pathological lymphoproliferation or aberrant expansion of effector or memory-like T cells. We conclude that the novel NSGW41hIL7 strain represents an optimized mouse model for humanization to better understand human T-cell differentiation in vivo and to generate a human immune system with a better approximation of human lymphocyte ratios.
Background: Previous studies reported decreased volumes of acute stroke admissions during the COVID-19 pandemic. We aimed to examine whether aneurysmal subarachnoid hemorrhage (aSAH) volumes demonstrated similar declines in our department. Furthermore, the impact of the pandemic on disease progression should be analyzed.
Methods: We conducted a retrospective study in the neurosurgical department of the university hospital Frankfurt including patients with the diagnosis of aSAH during the first year of the COVID pandemic. One year cumulative volume for aSAH hospitalization procedures was compared to the year before (03/2020 – 02/2021 vs. 03/2019 – 02/2020) and the last 5 pre-COVID-pandemic years (2015-2020). All relevant patient characteristics concerning family history, disease history, clinical condition at admission, active/past COVID-infection, treatment management, complications, and outcome were analyzed.
Results: Compared to the 84 hospital admissions during the pre-pandemic years, the number of aSAH hospitalizations (n = 56) declined during the pandemic without reaching significance. No significant difference in the analyzed patient characteristics including clinical condition at onset, treatment, complications, and outcome, between 56 patients with aSAH admitted during the COVID pandemic and the treated patients in the last 5 years in the pre-COVID period were found. In our multivariable analysis, we detected young age (p < 0.05; OR 4.2) and no existence of early hydrocephalus (p < 0.05; OR 0.13) as important factors for a favorable outcome (mRS ≤ 0–2) after aSAH during the COVID pandemic. A past COVID-infection was detected in young patients suffering from aSAH (Age < 50years, p < 0.05; OR 10.5) with an increased rate of cerebral vasospasm after aSAH onset (p < 0.05; OR 26). Nevertheless, past COVID-infection did not reach significance as a high-risk factor for unfavorable outcomes.
Conclusion: There was a relative decrease in the number of patients with aSAH during the COVID-19 pandemic. Despite the extremely different conditions of hospitalization, there was no impairing significant effect on the treatment and outcome of admitted patients with aSAH. A past COVID infection seemed to be an irrelevant limiting factor concerning favorable outcomes.
Background: During the COVID-19 pandemic, decreased volumes of acute stroke admissions were reported. We aimed to examine whether subarachnoid hemorrhage (SAH) volumes demonstrated similar declines in our department. Furthermore, the impact of pandemic on disease progression should be analyzed.
Methods: We conducted a retrospective study in neurosurgical department of university hospital Frankfurt including patients with the diagnosis of aneurysmal SAH during the first year of COVID-pandemic. One year cumulative volume for SAH hospitalization procedures were compared to the one-year period before (03/2020–02/2021 versus 03/2019–02/2020) and the last 5 pre-COVID-pandemic years (2015-2020). All relevant patient characteristics concerning family history, disease history, clinical condition at admission, active/past COVID-infection, treatment management, complications and outcome were analyzed.
Results: There was a decline in SAH hospitalizations, with 84 admissions in the year immediately before and 56 admissions during the pandemic, without reaching a significance. No significant difference in analyzed patient characteristics including clinical condition at onset, treatment, complications and outcome, between 56 SAH patients admitted during COVID pandemic and treated patients in the last 5 years in pre-COVID period were found. Using a multivariable analysis, we detected young age (p<0.05;OR4,2) and no existence of early hydrocephalus (p<0.05;OR0,13) as important factors for a favorable outcome (mRS≤0-2) after aSAH during the COVID-pandemic. A past COVID-infection was detected in young patients suffering from aSAH (Age< 50years, p<0.05;OR10,5) with increased rate of cerebral vasospasm after SAH onset (p<0.05;OR26). Nevertheless, past COVID-infection did not reach a significance as a high risk factor for unfavorable outcome.
Conclusion: There was a relative decrease in the volume of SAH during the COVID-19 pandemic. Despite of extremely different conditions of hospitalization, there was no impairing significant effect on treatment and outcome of admitted SAH patients. A past COVID-infection seemed not to be a relevant limiting factor concerning favorable outcome.
Background: Following elective craniotomy patients routinely receive monitoring on ICU. However, the benefit of ICU monitoring in these patients is discussed controversially. Due to the current COVID-19 pandemic, there are further limitations of ICU capacities. This study aimed to compare this strategy with a standardized management of post-craniotomy patients on ICU.
Methods: Two postoperative strategies were compared in a matched-pair analysis: The first cohort included patients treated between May-August 2021 according to the “No ICU – unless” concept (NIU group), where patients were managed on the normal ward postoperatively. The second cohort contained patients routinely admitted to the ICU between February-April 2021 (control group). Outcome parameters contained complications, length of stay, duration to first postoperative mobilization, number of unplanned imaging, number/type of ICU interventions and pre- and postoperative mRS. Patient characteristics were analyzed using electronic medical records.
Results: The NIU group consisted of 96 patients, the control group of 75 patients. Complication rates were comparable in both cohorts (16% in NIU vs. 17% in control; p=0.123). Groups did not differ significantly in the number of imaging (10% in NIU vs. 13% in control; p=0.67), in the type of interventions on ICU (antihypertensive therapy 5% (NIU) vs. 6% (control); p=0.825) or in the time to first postoperative mobilization (average 1.1± 1.6 days vs. 0.9± 1.2 days; p=0.402). Length of hospital stay was shorter in the NIU group without reaching statistical significance (average 5.8 vs. 6.8 days; p=0.481). There was no significant change in the distribution of preoperative (p=0.960) and postoperative (p=0.425) mRS scores.
Conclusion: Postoperative ICU management does not reduce postoperative complications and has no effect on the surgical outcome of elective craniotomies. The majority of postoperative complications are detected after a 24-hour observation period. This approach may represent a potential strategy to prevent overutilization of ICU capacities while maintaining sufficient postoperative care for neurosurgical patients.
Propranolol as a potentially novel treatment of arteriovenous malformations: from bench to bedside
(2022)
Background: Propranolol is a non-selective blocker of the β-adrenergic receptor and has been used for treatment of proliferative infantile hemangiomas. The vasoconstrictive and antiangiogenic effects of propranolol led us to explore its potential application for the treatment of AVMs.
Methods: AVM tissue was cultured after surgical resection in the presence of 100μM propranolol or solvent DMSO. After incubation for 72 hours, tissue was harvested for testing. The expression levels of SDF1α, CXCR4, VEGF and HIF-1 was measured by rt-PCR. Furthermore, data of patients in 2 vascular centres harboring AVM was retrospectively interrogated for a time period of 20 years. The database included information about hemorrhage, AVM size and antihypertensive medication. Descriptive analyses were performed, focusing on the risk of hemorrhage, size of the lesion at presentation and clinical follow-up in patients on β-blocker medication versus those who were not.
Results: Among 483 patients, 73 (15%) were under β-blocker-treatment. 48% AVMs presented with hemorrhage at diagnosis. Patients under β-blocker-treatment had a lower risk of hemorrhage at the time of diagnosis in a univariate analysis (p<0,0001;OR13). Patients under β-blocker-treatment showed a significant higher chance for a lower Spetzler-Martin-grade ≤III (p<0,0001;OR6,5) and a lower risk for the presence of an associated aneurysm (p<0,0001;OR3,6).
Multivariate analysis including Spetzler-Martin-Grading, young age ≤50, presence of associated aneurysm and β-blocker-treatment showed reduced risk for hemorrhage under β-blocker-treatment (p<0,01,OR0,2).
The expression of CXCR4 was suppressed by propranolol most likely through the HIF-1-pathways. The gene-expression of vasculogenesis factors was decreased in with propranolol incubated AVMs.
Conclusion: β-Blocker medication seems to be associated with a decreased risk of AVM-related hemorrhage and AVM-size at presentation or during follow-up. Propranolol inhibits SDF1α-induced vasculogenesis by suppressing the expression of CXCR4 most likely through the HIF-1-pathways. Therefore, SDF1α/CXCR4 axis plays an important role in the vasculogenesis and migration of inflammatory cells in AVM lesions.
The midbrain DA system comprising dopamine (DA) neurons of the substantia nigra (SN) and the ventral tegmental area (VTA) is involved in various brain functions, including voluntary movement and the encoding and prediction of behaviorally relevant stimuli. In Parkinsonʼs disease (PD), a progressive degeneration of particularly vulnerable SN DA neurons causes a progressive DA depletion of striatal projection sites. As a consequence, motor symptoms such as tremor, hypokinesia and rigidity appear once about 50 % to 70 % of SN DA neurons have been lost. Under physiological conditions, SN DA neurons can encode behaviorally salient events and coordinated movements through tonic and phasic activity and correlated striatal DA release. Burst-activity mediates a phasic, supralinear rise of striatal DA levels and allows to activate coordinated movements via modulation of corticostriatal signals.
In the present dissertation project, pathophysiological adaptations of surviving SN DA neurons after a partial degeneration of the nigrostiatal system have been studied using a 6-hydroxydopamine mouse model of PD. Combining in vivo retrograde tracing techniques with in vitro whole-cell patch-clamp recordings, multifluorescent immunolabeling and confocal microscopy allowed an unambiguous correlation of electrophysiological phenotypes, anatomical positions and neurochemical phenotypes of recorded neurons on a single-cell level. In vitro, neuronal activity of SN DA neurons is characterized by spontaneous, slow pacemaker activity of 1 to 10 Hz and a high degree of spike-timing precision. In vitro current-clamp recordings of surviving SN DA neurons using acute brain slice preparations after a partial, PD-like degeneration of the nigrostriatal DA system showed a significant perturbation of spontaneous pacemaker activity, mirrored by a decreased spike-timing precision compared to controls. Selective pharmacology and whole-cell voltage-clamp recordings served to identify calciumactivated SK channels as molecular effectors of a perturbated pacemaker activity of surviving SN DA neurons. SK channels and have been shown to critically contribute to the spike-timing precision of SN DA neurons. Consistently, in vitro current-clamp recordings after pharmacological blockade of SK channels in vitro caused a significant decrease of spike-timing precision, occluding previously observed differences between surviving SN DA neurons and controls.In addition to in vitro patch-clamp recordings, extracellular single-unit recordings in anaesthetized animals in vivo served to study surviving SN DA neurons embedded in an intact neuronal network after a partial, PD-like degeneration of the nigrostriatal DA system. Combining in vivo single-unit recordings, juxtacellular neurobiotin labeling and multifluorescent immunohistochemistry allowed to directly correlate electrophysiological and neurochemical phenotypes as well as anatomical positions on a single-cell level. In vivo, surviving SN DA neurons showed a significant decrease of spike-timing precision as reflected by an increased irregularity and an augmented burst activity compared to controls.
The present dissertation project provided a unique combination of a neurotoxicological PD mouse model, retrograde tracing techniques and in vitro as well as in vivo electrophysiologiy, allowing to unambiguously correlate electrophysiological adaptations, projection-specific anatomical positions and neurochemical phenotypes of SN DA neurons after a partial degeneration of the nigrostriatal system. Surviving SN DA neurons exhibited a significant deficit of SK channel activity after a partial degeneration of the nigrostriatal DA system. In consequence of a diminished SK channel activity observed in vitro, surviving SN DA neurons exhibited and enhanced burst activity in vivo, providing a plausible mechanism to compensate a striatal DA depletion.