APL@voro-interactive visualization and analysis of cell membrane simulations.

SUMMARY: Molecular dynamics (MD) simulations of cell membranes allow for a better understanding of complex processes such as changing membrane dynamics, lipid rafts and the incorporation/passing of macromolecules into/through membranes. To explore and understand cell membrane compositions, dynamics and processes, visual analytics can help to interpret MD simulation data. APL@Voro is a software for the interactive visualization and analysis of cell membrane simulations. Here, we present the new APL@Voro, which has been continuously developed since its initial release in 2013. We discuss newly implemented algorithms, methodologies and features, such as the interactive comparison of related simulations and methods to assign lipids to either the upper or lower leaflet. AVAILABILITY AND IMPLEMENTATION: The current open-source version of APL@Voro can be downloaded from http://aplvoro.com.

Intraoperative radiotherapy after neurosurgical resection of brain metastases as institutional standard treatment- update of the oncological outcome form a single center cohort after 117 procedures.

PURPOSE: Stereotactic radiotherapy (SRT) is the predominant method for the irradiation of resection cavities after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50 kV x-rays is an alternative way to irradiate the resection cavity focally. We have already reported the outcome of our first 40 IORT patients treated until 2020. Since then, IORT has become the predominant cavity treatment in our center due to patients´ choice. METHODS: We retrospectively analyzed the outcomes of all patients who underwent resection of BM and IORT between 2013 and August 2023 at Augsburg University Medical Center (UKA). RESULTS: We identified 105 patients with 117 resected BM treated with 50 kV x-ray IORT. Median diameter of the resected metastases was 3.1 cm (range 1.3 - 7.0 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including three-monthly MRI of the brain. Mean FU was 14 months, with a median MRI FU for patients alive of nine months. Median overall survival (OS) of all treated patients was 18.2 months (estimated 1-year OS 57.7%). The observed local control (LC) rate of the resection cavity was 90.5% (estimated 1-year LC 84.2%). Distant brain control (DC) was 61.9% (estimated 1-year DC 47.9%). Only 16.2% of all patients needed WBI in the further course of disease. The observed radio necrosis rate was 2.6%. CONCLUSION: After 117 procedures IORT still appears to be a safe and appealing way to perform cavity RT after neurosurgical resection of BM with low toxicity and excellent LC.

Focal cavity radiotherapy after neurosurgical resection of brain metastases: sparing neurotoxicity without compromising locoregional control.

PURPOSE: Does focal cavity radiotherapy after resection of brain metastasis "spare" whole-brain radiotherapy, which is associated with toxicity for patients, through the complete course of their disease without compromising long-term local control of the brain? METHODS: We retrospectively analyzed outcomes of patients who underwent adjuvant focal cavity radiotherapy between 2014 and 2021 at our center. RESULTS: A total of 83 patients with 86 resected brain metastases were analyzed. 64% had singular, 36% two to four brain metastases. In cases with multiple metastases, omitted lesions were treated with radiosurgery. Median follow-up was 7.3 months (range 0-71.2 months), 1­year overall survival rate was 57.8% (95% CI 44.9-68.8%). Radiotherapy was administered with a median biologically effective dose (α/ß 10) surrounding the planning target volume of 48 Gy (range 23.4-60 Gy). Estimated 1­year local control rate was 82.7% (95% CI 67.7-91.2%), estimated 1­year distant brain control rate was 55.7% (95% CI 40.5-68.4%), estimated 1­year leptomeningeal disease rate was 16.0% (95% CI 7.3-32.9%). Eleven distant brain recurrences could be salvaged with radiosurgery. In the further course of disease, 14 patients (17%) developed disseminated metastatic disease in the brain. Estimated 1­year free of whole-brain radiotherapy rate was 72.3% (95% CI 57.1-82.9%). All applied treatments led to an estimated 1­year neuro-control rate of 79.1% (95% CI 65.0-88.0%), estimated 1­year radionecrosis rate was 23% (95% CI 12.4-40.5%). CONCLUSION: In our single-center study, focal cavity radiotherapy was associated with high local control. In three out of four patients, whole-brain radiotherapy could be avoided in the complete course of disease, using radiosurgery as salvage approach without compromising neuro-control.

Hydrocephalus, cerebral vasospasm, and delayed cerebral ischemia following non-aneurysmatic spontaneous subarachnoid hemorrhages: an underestimated problem.

Non-aneurysmal subarachnoid hemorrhage (NASAH) is rare and mostly benign. However, complications such as cerebral vasospasm (CV), delayed cerebral ischemia (DCI), or post-hemorrhagic hydrocephalus (HC) may worsen the prognosis. The aim of this study was to evaluate the rate of these complications comparing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH. Monocentric, retrospective analysis of patients diagnosed with NASAH from 01/2010 to 01/2021. Diagnosis was set only if vascular pathologies were excluded in at least one digital subtraction angiography, and NASAH was confirmed by cranial computed tomography (cCT) or lumbar puncture (LP). One hundred patients (62 female) with a mean age of 54.9 years (27-84) were identified. Seventy-three percent had a World Federation of Neurological Surgeons (WFNS) grading scale score I, while 9% were WFNS score IV or V at the time of admission. SAH was diagnosed by cCT in 86%, in 14% by lumbar puncture. Twenty-five percent necessitated short-term CSF diversion by extraventricular drainage or lumbar drainage, whereof 7 suffered from long-term HC treated with ventriculoperitoneal shunting (VPS). One patient without a short-term CSF drainage developed long-term HC. Ten percent developed CV, four of whom received intraarterial spasmolysis. Radiological DCI was diagnosed in 2%; none of these correlated with CV. Despite a mortality of 3% occurring solely in NPM SAH, the analyzed complication rate was comparable in both groups. We observed post-hemorrhagic complications in 35% of cases during the first 3 weeks after bleeding, predominantly in patients with NPM SAH. For this reason, close observation and cranial imaging within this time may be indicated not to overlook these complications.

Intraoperative radiotherapy with low-energy x-rays after neurosurgical resection of brain metastases-an Augsburg University Medical Center experience.

PURPOSE: External-beam radiotherapy (EBRT) is the predominant method for localized brain radiotherapy (LBRT) after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50-kV x­rays is an alternative way to focally irradiate the resection cavity after BM surgery, with the option of shortening the overall treatment time and limiting normal tissue irradiation. METHODS: We retrospectively analyzed the outcomes of all patients who underwent neurosurgical resection of BM and 50-kV x­ray IORT between 2013 and 2020 at Augsburg University Medical Center. RESULTS: We identified 40 patients with 44 resected BM treated with 50-kV x­ray IORT. Median diameter of the resected metastases was 2.8 cm (range 1.5-5.9 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including 3­monthly MRI of the brain. Mean FU was 14.4 months, with a median MRI FU for alive patients of 12.2 months. Median overall survival (OS) of all treated patients was 26.4 months (estimated 1­year OS 61.6%). The observed local control (LC) rate of the resection cavity was 88.6% (estimated 1­year LC 84.3%). Distant brain control (DC) was 47.5% (estimated 1­year DC 33.5%). Only 25% of all patients needed WBI in the further course of disease. The observed radionecrosis rate was 2.5%. CONCLUSION: IORT with 50-kV x­rays is a safe and appealing way to apply LBRT after neurosurgical resection of BM, with low toxicity and excellent LC. Close MRI FU is paramount to detect distant brain failure (DBF) early.

Surgical management of spinal metastases involving the cervicothoracic junction: results of a multicenter, European observational study.

OBJECTIVE: Surgical management of spinal metastases at the cervicothoracic junction (CTJ) is highly complex and relies on case-based decision-making. The aim of this multicentric study was to describe surgical procedures for metastases at the CTJ and provide guidance for clinical and surgical management. METHODS: Patients eligible for this study were those with metastases at the CTJ (C7-T2) who had been consecutively treated in 2005-2019 at 7 academic institutions across Europe. The Spine Instability Neoplastic Score, neurological function, clinical status, medical history, and surgical data for each patient were retrospectively assessed. Patients were divided into four surgical groups: 1) posterior decompression only, 2) posterior decompression and fusion, 3) anterior corpectomy and fusion, and 4) anterior corpectomy and 360° fusion. Endpoints were complications, surgical revision rate, and survival. RESULTS: Among the 238 patients eligible for inclusion this study, 37 were included in group 1 (15%), 127 in group 2 (53%), 18 in group 3 (8%), and 56 in group 4 (24%). Mechanical pain was the predominant symptom (79%, 189 patients). Surgical complications occurred in 16% (group 1), 20% (group 2), 11% (group 3), and 18% (group 4). Of these, hardware failure (HwF) occurred in 18% and led to surgical revision in 7 of 8 cases. The overall complication rate was 34%. In-hospital mortality was 5%. CONCLUSIONS: Posterior fusion and decompression was the most frequently used technique. Care should be taken to choose instrumentation techniques that offer the highest possible biomechanical load-bearing capacity to avoid HwF. Since the overall complication rate is high, the prevention of in-hospital complications seems crucial to reduce in-hospital mortality.

Inflammatory Pathways Regulated by Tumor Necrosis Receptor-Associated Factor 1 Protect From Metabolic Consequences in Diet-Induced Obesity.

RATIONALE: The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. OBJECTIVE: We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-α, IL (interleukin)-1ß, and TLRs (toll-like receptors). METHODS AND RESULTS: Mice deficient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1-/- mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance-an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic and proinflammatory cues were synergistically driven by ß3-adrenergic and inflammatory signaling and required the presence of both TRAF-1-deficient adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were upregulated. CONCLUSIONS: Enhancing TRAF-1-dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These findings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism.

Long-term Outcome and Adverse Events of Intrathecal Opioid Therapy for Nonmalignant Pain Syndrome.

OBJECTIVE: Intrathecal (IT) opioid pumps are one therapeutic cornerstone of refractory nonmalignant pain syndromes. The aim of this study was to evaluate the efficacy of and surgical and pharmacological complications of IT pumps beyond a time span of 10 years. METHODS: In this retrospective single-center cohort study, 27 patients (14 female, 13 male, age 64.0 ± 8.9 [median, 1 SD] years) were identified. Pain intensity using the numeric rating scale (NRS), pain and IT pump characteristics, and complications were analyzed. The German Pain Questionnaire was used to investigate the physical and mental health status. RESULTS: Overall time of IT therapy from first implantation to last follow-up was 20.4 ± 6.0 years. Time to implantation of the second pump (n = 18) was 10.0 ± 5.3 years, and between the second and third pump (n = 6) 6.5 ± 2.7 years; 2 patients received their fourth pump 6 years later. The NRS score was 9.0 ± 0.9 before implantation, 7.0 ± 1.8 1 year after implantation, and 4.0 ± 2.3 at the last follow-up. IT drug dose remained stable after 3 years. Opioid intoxications occurred in 3 patients (10%). One patient (3%) underwent revision surgery due to a catheter infection. Drug side effects occurred in 4 patients (14%). Our patient group had pain-related restrictions in physical activities with menial impact regarding mental and emotional stress. CONCLUSION: Even after a time span of over 15 years and several exchanges of pump systems, pain intensity was still reduced. After 3 years, IT drug dose remained unchanged with low side-effect and complication rates.

From Single Variants to Protein Cascades: MULTISCALE MODELING OF SINGLE NUCLEOTIDE VARIANT SETS IN GENETIC DISORDERS.

Understanding the role of genetics in disease has become a central part of medical research. Non-synonymous single nucleotide variants (nsSNVs) in coding regions of human genes frequently lead to pathological phenotypes. Beyond single variations, the individual combination of nsSNVs may add to pathogenic processes. We developed a multiscale pipeline to systematically analyze the existence of quantitative effects of multiple nsSNVs and gene combinations in single individuals on pathogenicity. Based on this pipeline, we detected in a data set of 842 nsSNVs discovered in 76 genes related to cardiomyopathies, associated nsSNV combinations in seven genes present in at least 70% of all 639 patient samples, but not in a control cohort of healthy humans. Structural analyses of these revealed primarily an influence on the protein stability. For amino acid substitutions located at the protein surface, we generally observed a proximity to putative binding pockets. To computationally analyze cumulative effects and their impact, pathogenicity methods are currently being developed. Our approach supports this process, as shown on the example of a cardiac phenotype but can be likewise applied to other diseases such as cancer.

Resection of cerebral gangliogliomas causing drug-resistant epilepsy: short- and long-term outcomes using intraoperative MRI and neuronavigation.

OBJECT Cerebral gangliogliomas (GGs) are highly associated with intractable epilepsy. Incomplete resection due to proximity to eloquent brain regions or misinterpretation of the resection amount is a strong negative predictor for local tumor recurrence and persisting seizures. A potential method for dealing with this obstacle could be the application of intraoperative high-field MRI (iopMRI) combined with neuronavigation. METHODS Sixty-nine patients (31 female, 38 male; median age 28.5 ± 15.4 years) suffering from cerebral GGs were included in this retrospective study. Five patients received surgery twice in the observation period. In 48 of the 69 patients, 1.5-T iopMRI combined with neuronavigational guidance was used. Lesions close to eloquent brain areas were resected with the implementation of preoperative diffusion tensor imaging tractography and blood oxygenation level-dependent functional MRI (15 patients). RESULTS Overall, complete resection was accomplished in 60 of 69 surgical procedures (87%). Two patients underwent biopsy only, and in 7 patients, subtotal resection was accomplished because of proximity to critical brain areas. Excluding the 2 biopsies, complete resection using neuronavigation/iopMRI was documented in 33 of 46 cases (72%) by intraoperative imaging. Remnant tumor mass was identified intraoperatively in 13 of 46 patients (28%). After intraoperative second-look surgery, the authors improved the total resection rate by 9 patients (up to 91% [42 of 46]). Of 21 patients undergoing conventional surgery, 14 (67%) had complete resection without the use of iopMRI. Regarding epilepsy outcome, 42 of 60 patients with seizures (70%) became completely seizure free (Engel Class IA) after a median follow-up time of 55.5 ± 36.2 months. Neurological deficits were found temporarily in 1 (1.4%) patient and permanently in 4 (5.8%) patients. CONCLUSIONS Using iopMRI combined with neuronavigation in cerebral GG surgery, the authors raised the rate of complete resection in this series by 19%. Given the fact that total resection is a strong predictor of long-term seizure control, this technique may contribute to improved seizure outcome and reduced neurological morbidity.

Analysis of signaling networks distributed over intracellular compartments based on protein-protein interactions.

BACKGROUND: Biological processes are usually distributed over various intracellular compartments. Proteins from diverse cellular compartments are often involved in similar signaling networks. However, the difference in the reaction rates between similar proteins among different compartments is usually quite high. We suggest that the estimation of frequency of intracompartmental as well as intercompartmental protein-protein interactions is an appropriate approach to predict the efficiency of a pathway. RESULTS: Using data from the databases STRING, ANDSystem, IntAct and UniProt, a PPI frequency matrix of intra/inter-compartmental interactions efficiencies was constructed. This matrix included 15 human-specific cellular compartments. An approach for estimating pathway efficiency using the matrix of intra/inter-compartmental PPI frequency, based on analysis of reactions efficiencies distribution was suggested. An investigation of KEGG pathway efficiencies was conducted using the developed method. The clusterization and the ranking of KEGG pathways based on their efficiency were performed. "Amino acid metabolism" and "Genetic information processing" revealed the highest efficiencies among other functional classes of KEGG pathways. "Nervous system" and "Signaling molecules interaction" contained the most inefficient pathways. Statistically significant differences were found between efficiencies of KEGG and randomly-generated pathways. Based on these observations, the validity of this approach was discussed. CONCLUSION: The estimation of efficiency of signaling networks is a complicated task because of the need for the data on the kinetic reactions. However, the proposed method does not require such data and can be used for preliminary analysis of different protein networks.

Whole Body Vibration Exercise Protocol versus a Standard Exercise Protocol after ACL Reconstruction: A Clinical Randomized Controlled Trial with Short Term Follow-Up.

The suitability and effectiveness of whole body vibration (WBV) exercise in rehabilitation after injury of the anterior cruciate ligament (ACL) was studied using a specially designed WBV protocol. We wanted to test the hypothesis if WBV leads to superior short term results regarding neuromuscular performance (strength and coordination) and would be less time consuming than a current standard muscle strengthening protocol. In this prospective randomized controlled clinical trial, forty patients who tore their ACL and underwent subsequent ligament reconstruction were enrolled. Patients were randomized to the whole body vibration (n=20) or standard rehabilitation exercise protocol (n=20). Both protocols started in the 2(nd) week after surgery. Isometric and isokinetic strength measurements, clinical assessment, Lysholm score, neuromuscular performance were conducted weeks 2, 5, 8 and 11 after surgery. Time spent for rehabilitation exercise was reduced to less than a half in the WBV group. There were no statistically significant differences in terms of clinical assessment, Lysholm score, isokinetic and isometric strength. The WBV group displayed significant better results in the stability test. In conclusion, preliminary data indicate that our whole body vibration muscle exercise protocol seems to be a good alternative to a standard exercise program in ACL-rehabilitation. Despite of its significant reduced time requirement it is at least equally effective compared to a standard rehabilitation protocol. Key pointsIn this prospective randomized controlled clinical trial, we tested the hypothesis if WBV leads to superior short term results regarding neuromuscular performance (strength and coordination) and would be less time consuming than a current standard muscle strengthening protocol in forty patients who underwent ACL reconstruction.Time spent for rehabilitation exercise was reduced to less than a half in the WBV group as compared to the standard exercise group. Both protocols showed no differences regarding clinical assessment, Lysholm score, isokinetic and isometric strength.Despite a more than 50% reduction in time spent for exercise sessions, the WBV group achieved significant better results in the stability test.In conclusion, the presented WBV program can be considered as a practical alternative to a standard exercise program during ACL-rehabilitation.

Early Intravenous Magnesium Sulfate and Its Impact on Cerebral Vasospasm as well as Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Retrospective Matched Case-Control Analysis.

BACKGROUND: Magnesium sulfate (MgSO4) is a potential neuroprotective agent for patients with aneurysmal subarachnoid hemorrhage (SAH). We analyzed the effect of early application of intraoperative intravenous MgSO4 and compared cerebral vasospasm (CV), delayed cerebral ischemia (DCI), and neurological outcome in 2 patient cohorts. METHODS: A retrospective matched-pair analysis from patients at a single center in Germany was performed without (group A) and with (group B) MgSO4 application <24 hours after diagnosis. Pairs were matched according to the known risk factors for DCI and CV (age, Fisher grade, smoking, severity of SAH). Incidence of CV and DCI and neurological outcome using the modified Rankin Scale score 3 and 12 months after SAH were recorded. RESULTS: The inclusion criteria were met by 196 patients. After risk stratification, 48 patients were included in the final analysis (age 54.2 ± 8.1 years; 30 women and 18 men) and were assigned to group A (n = 24) or group B (n = 24). CV occurred less frequently in group B (33%) than in group A (46%). Likewise, DCI was present in 13% in group B compared with 42% in group A. After 12 months, 22 patients in group B had a favorable functional outcome (modified Rankin Scale score 0-3) compared with 15 patients in group A. CONCLUSIONS: In this study, the incidence of CV and DCI was lower in patients receiving intravenous MgSO4 within 24 hours after aneurysmal SAH onset. Favorable functional outcome was more likely in the MgSO4 group after 12 months of follow-up.

Dural reconstruction with or without a bone graft of paranasal and anterior skullbase malignancies: Retrospective single-center analysis of 11 cases and review of literature.

Introduction: The reconstruction of frontobasal defects following oncologic resections of paranasal and anterior skull base (ASB) malignancies remains challenging. Ineffective reconstruction could lead to cerebrospinal fluid leak, meningitis, and tension pneumocephalus. Research question: Aim of this investigation was to analyse postoperative complication rates with or without bone graft for anterior skull base reconstruction. Material and methods: In this retrospective study, we included patients following resection of paranasal and/or anterior skull base malignancies between October 2013 and December 2022. Complications were analysed with regards to the type of skull base reconstruction. Results: Eleven patients were identified (2 female, 9 male, age (median, SD) 64 ± 14.1 years (range 38-81). There were nine cases of paranasal sinus and nasal cavity carcinomas and two cases of olfactory neuroblastomas. Overall survival was 22.5 ± 28 months (range: 5-78), progression free survival was 17.0 ± 20.3 months (range: 11-78). Bone skull base reconstruction using a split graft was performed in three cases. Postoperative complications requiring surgical intervention were seen in 33% (one tension pneumocephalus) of cases in the bone reconstruction group and 50% (three patients with cerebrospinal fluid leak, one infection) in the non-bone reconstruction group. Discussion and conclusion: The structural reinforcement of structural bone chip grafting might provide additional support of the ASB and prevent CSF leakage or encephalocele. Especially in large (>10 cm2) bone defects of advanced sinonasal malignancies extending into the middle cranial fossa, the full armamentarium of reconstruction possibilities should be considered.

APL@Voro: a Voronoi-based membrane analysis tool for GROMACS trajectories.

APL@Voro is a new program developed to aid in the analysis of GROMACS trajectories of lipid bilayer simulations. It can read a GROMACS trajectory file, a PDB coordinate file, and a GROMACS index file to create a two-dimensional geometric representation of a bilayer. Voronoi diagrams and Delaunay triangulations--generated for different selection models of lipids--support the analysis of the bilayer. The values calculated on the geometric structures can be visualized in a user-friendly interactive environment and, then, plotted and exported to different file types. APL@Voro supports complex bilayers with a mix of various lipids and proteins. For the calculation of the projected area per lipid, a modification of the well-known Voronoi approach is presented as well as the presentation of a new approach for including atoms into an existing triangulation. The application of the developed software is discussed for three example systems simulated with GROMACS. The program is written in C++, is open source, and is available free of charge.

Integration of functional neuronavigation and intraoperative MRI in surgery for drug-resistant extratemporal epilepsy close to eloquent brain areas.

OBJECT: The authors performed a retrospective study to assess the impact of functional neuronavigation and intraoperative MRI (iMRI) on surgery of extratemporal epileptogenic lesions on postsurgical morbidity and seizure control. METHODS: Twenty-five patients (14 females and 11 males) underwent extratemporal resections for drug-resistant epilepsy close to speech/motor brain areas or adjacent to white matter tracts. The mean age at surgery was 34 years (range 12-67 years). The preoperative mean disease duration was 13.2 years. To avoid awake craniotomy, cortical motor-sensory representation was mapped during preoperative evaluation in 14 patients and speech representation was mapped in 15 patients using functional MRI. In addition, visualization of the pyramidal tract was performed in 11 patients, of the arcuate fascicle in 7 patients, and of the visual tract in 6 patients using diffusion tensor imaging. The mean minimum distance of tailored resection between the eloquent brain areas was 5.6 mm. During surgery, blood oxygen level-dependent imaging and diffusion tensor imaging data were integrated into neuronavigation and displayed through the operating microscope. The postoperative mean follow-up was 44.2 months. RESULTS: In 20% of these patients, further intraoperative resection was performed because of intraoperatively documented residual lesions according to iMRI findings. At the end of resection, the final iMRI scans confirmed achievement of total resection of the putative epileptogenic lesion in all patients. Postoperatively, transient complications and permanent complications were observed in 20% and 12% of patients, respectively. Favorable postoperative seizure control (Engel Classes I and II) was achieved in 84% and seizure freedom in 72% of these consecutive surgical patients. CONCLUSIONS: By using functional neuronavigation and iMRI for treatment of epileptogenic brain lesions, the authors achieved a maximum extent of resection despite the lesions' proximity to eloquent brain cortex and fiber tracts in all cases. The authors' results underline possible benefits of this technique leading to a favorable seizure outcome with acceptable neurological deficit rates in difficult-to-treat extratemporal epilepsy.

Microcirculation Under an Elastic Bandage During Rest and Exercise - Preliminary Experience With the Laser-Doppler Spectrophotometry System O2C.

There is an abundace of studies on the influence of rest and exercise as well as external compression on cutaneous, subcutaneous and muscle tissue blood flow using different measurement techniques. As a novel approach, we simultaneously examined the influence of a custom- made elastic thigh bandage on cutaneous and subcutaneous venous blood oxygenation (SO2), postcapillary venous filling pressures (rHb) and blood flow (flow) using the non-invasive laser- Doppler spectrophotometry system "Oxygen-to-see(O2C)". Parameters were obtained in 20 healthy volunteers in 2 mm and 8 mm tissue depth during rest, 5 and 10 minutes of moderate bicycle exercise following a 10-minute recovery period. Without the bandage, results matched the known physiological changes indicating higher blood backflow from superficial and deep veins. Underneath the elastic bandage, we observed lower post-capillary filling pressures during exercise. However, after the bandage was removed in the post-exercise period, all obtained parameters of microcirculation remained increased, indicating a higher amount of local venous blood volume in this area. Our observations might be the result of external compression, thermoregulatory and exercise-dependent vascular mechanisms. With the O2C device, a promising new non- invasive technique of measuring local microcirculation in soft tissue exists. This study gives new insights in the field of non-invasive diagnostics with special regard to the influence of elastic bandages on local microcirculation. Key PointsIt can be demonstrated that a novel non-invasive laser-Doppler spectrophotometry system allows the determination of capillary-venous microcirculation in an in-vivo study during exercise-rest cycles.The results received with this technique indicate that a) without an elastic thigh bandage, turnover rates of capillary and post-capillary microperfusion in skin and subcutaneous fat tissue increase under physical exertion, b) skin blood flow decreases while subcutaneous blood flow remained constant in the subsequent recovery phase. While wearing the bandage, c) venous back flow during exercise is increased, whereas d) in the recovery phase, microcirculation remained increased in both tissue depths after removing the bandage.In conclusion, the elastic bandage has a negative impact on local microcirculation and capillary-venous back flow, which is possibly due to a displacement of blood volume into the deep venous system and heat accumulation impairing the thermoregulatory response at the same time.

Clinical Results and Quality of Life After Transcortical Versus Transcallosal Resection of Adult Lateral and Third Ventricle Lesions: Long-Term Outcome.

BACKGROUND: Resection of intraventricular tumors can be achieved using 2 main operative approaches: transcallosal or transcortical. This study aims to describe preoperative and postoperative factors as well as quality of life (QoL) based on long-term results in these patients. METHODS: Patients underwent surgery of primary intraventricular lesions between 2007 and 2020 via a transcortical (group A) or transcallosal (group B) route. The main clinical parameters were completeness of resection, overall survival, surgical complications, postoperative neurologic deficits, and seizure rates. QoL was assessed using a modified questionnaire Short-Form 36 inventory. RESULTS: Forty patients (19 women and 21 men) met the inclusion criteria. Group A consisted of 26 patients (12 women and 14 men; median age 45.5 years ± 16.7 standard deviation) and had lower preoperative tumor volume (confounder) compared with group B (7 women and 7 men; age 50.0 ± 17.4 years). Gross total resection was achieved in 65% in group A and 71% in group B. Follow-up was 7.8 ± 3.9 years. New seizures/permanent neurologic deficits occurred in 27%/15% (group A) and 29%/29% (group B) and surgical complications in 23% of patients. Group B had a higher degree of memory impairment (21%) compared with group A (10%). QoL impairment was present in both groups mainly regarding physical role function and mental health index. CONCLUSIONS: Keeping in mind the limitations, transcallosal surgery was associated with a higher probability of neurologic deficits and memory impairment in our series. However, it had fewer surgical complications with similar gross total resection and seizure rates.

Cerebral abscess due to Listeria monocytogenes infection in silent diabetes mellitus: Case presentation, treatment and patient outcome.

Introduction: Invasive listeriosis most often presents as bacteremia or neurolisteriosis. Cerebral infection mostly manifests as meningitis or meningoencephalitis, but cerebral abscesses are a rare manifestation. Case presentation: We present the rare case of a 51-year old patient with progressive right sided hemiparesis caused by a cerebral abscess due to Listeria monocytogenes infection. The initially suspected cerebral ischemia or bleeding was ruled out. Magnetic resonance imaging led to the suspected diagnosis of an angiocentric lymphoma. An open cerebral biopsy revealed an intracranial abscess formation. After abscess evacuation and identification of Listeria monocytogenes, anti-infective treatment with ampicillin and gentamicin was started. After repeated cerebral imaging with signs of ongoing tissue inflammation after 6 weeks we chose to prolong the therapy with oral amoxicillin until resolution of signs of intracerebral inflammation after 12 weeks, documented by repeated cerebral magnetic resonance imaging. During hospitalization, the patient was diagnosed with diabetes mellitus type II and treatment was initiated. The patient was discharged without any persistent neurologic deficits. Discussion: For the treatment of bacterial brain abscesses, 4-6 weeks of intravenous antimicrobial treatment after surgical drainage are recommended. However, first line therapy of invasive cerebral listeriosis is not well established. We decided to use a combined treatment using ampicillin and gentamicin, followed by prolonged oral treatment due to ongoing tissue inflammation. Conclusion: No evidence-based treatment recommendations are available for brain abscess caused by Listeria monocytogenes. We report a case with favorable outcome after anti-infective ampicillin- and gentamicin-based therapy. Systematic assessment of treatment would be desirable.

Long-Term Clinical and Radiologic Outcome Following Surgical Treatment of Lumbar Spondylodiscitis: A Retrospective Bicenter Study.

BACKGROUND AND STUDY AIMS: Spinal instrumentation for spondylodiskitis (SD) remains highly controversial. To date, surgical data are limited to relatively small case series with short-term follow-up data. In this study, we wanted to elucidate the biomechanical, surgical, and neurologic long-term outcomes in these patients. MATERIAL AND METHODS: A retrospective analysis from two German primary care hospitals over a 9-year period (2005-2014) was performed. The inclusion criteria were (1) pyogenic lumbar SD, (2) minimum follow-up of 1 year, and (3) surgical instrumentation. The clinical and radiologic outcome was assessed before surgery, at discharge, and at a minimum of 12 months of follow-up. Follow-up included physical examination, laboratory results, CT and MRI scans, as well as assessment of quality of life (QoL) using short-form health survey (SF-36) inventory, Oswestry Disability Questionnaire, and visual analog scale (VAS) spine score. RESULTS: Complete data were available in 70 patients (49 males and 21 females, with an age range of 67±12.3 years) with a median follow-up of 6.6 ± 4.2 years. Follow-up data were available in 70 patients after 1 year, in 58 patients after 2 years, and in 44 patients after 6 years. Thirty-five patients underwent posterior stabilization and decompression alone and 35 patients were operated on in a two-stage 360-degree interbody fusion with decompression. Pre- and postoperative angles of the affected motion segment were 17.6 ± 10.2 and 16.1 ± 10.7 degrees in patients with posterior instrumentation only and 21.0 ± 10.2 and 18.3 ± 10.5 degrees in patients with combined anterior/posterior fusion. Vertebral body subsidence was seen in 12 and 6 cases following posterior instrumentation and 360-degree instrumentation, respectively. Nonfusion was encountered in 22 and 11 cases following posterior instrumentation and 360-degree instrumentation, respectively. The length of hospital stay was 35.0 ± 24.5 days. Surgery-associated complication rate was 18% (12/70). New neurologic symptoms occurred in 7% (5/70). Revision surgery was performed in 3% (2/70) due to screw misplacement/hardware failure and in 3% (2/70) due to intraspinal hematoma. Although patients reported a highly impaired pain deception and vitality, physical mobility was unaffected and pain disability during daily activities was moderate. CONCLUSION: Surgical treatment of SD with a staged surgical approach (if needed) is safe and provides very good long-term clinical and radiologic outcome.