Complications of intracerebroventricular chemotherapy via subgaleal reservoir in primary central nervous system lymphoma: A single-institution experience on 1247 installations in 94 consecutive patients.

The implantation of a subgaleal reservoir intracerebroventricular (ICV port) in order to apply ICV chemotherapy in patients with leptomeningeal cancer may be complicated by misplacement of the device, pericatheter leucencephalopathy, hemorrhage and iatrogenic ventriculitis/meningitis. Here we analyzed the occurrence of such complications in patients with primary central nervous system lymphoma (PCNSL) treated with systemic and ICV methotrexate- and cytarabine-based chemotherapy. We retrospectively reviewed the medical records of 94 consecutive patients (1247 installations), who had received an ICV port for intraventricular chemotherapy for treatment of histologically confirmed PCNSL at our institution between September 2005 and October 2018. Infectious and noninfectious complications were systematically recorded including clinical, laboratory, and imaging data. In 9/94 patients (9.6%), a misplacement of the ICV port seen on the postoperative computed tomography scan was corrected immediately and chemotherapy was then continued as planned. In 5/94 patients (5.3%), symptomatic noninfectious complications were observed (four patients with symptomatic pericatheter leucencephalopathy and one patient with surgical scar dehiscence with CSF leak). In 8/94 patients (8.5%), asymptomatic white matter lesions around the catheter were visible on cerebral magnetic resonance imaging after completion of therapy. The rate of infectious complications was 6/94 patients (6.4%). No complication was lethal or required intensive care monitoring. This retrospective study shows that complications of ICV treatment have to be expected in a fraction of patients, however, in this series these complications were manageable and did not result in long-term deficits.

[Surgical treatment and radiation therapy of brain metastases]. / Chirurgische Behandlung und Strahlentherapie von Hirnmetastasen.

The aim of this work is to outline the principles of interdisciplinary treatment of brain metastases. Interdisciplinary treatment is determined by the clinical situation, anatomical conditions and tumor entity and has the goal of reducing toxicity. Magnetic resonance imaging, computed tomography (CT) and positron emission tomography-CT are used to diagnose brain metastases. Neurosurgery is used for accessible, symptomatic metastases. For localized metastases, including multiple metastases, that are surgically inaccessible, radiosurgery is used. If possible, partial brain irradiation is preferred to whole-brain irradiation. Protection of the hippocampus during whole-brain radiotherapy reduces therapy toxicity. In emergency situations, steroids provide effective support and a neurosurgical intervention may be life-saving. The options for systemic drug therapy are increasing.

Open-Label Phase II Evaluation of Imatinib in Primary Inoperable or Incompletely Resected and Recurrent Glioblastoma.

PURPOSE: Preclinical studies indicated that imatinib may have single-agent activity in glioblastoma through inhibition of tyrosine kinase activity and also that it might enhance the efficacy of radiotherapy. We therefore sought to investigate clinical efficacy in patients with newly diagnosed and recurrent glioblastoma in combination with radiotherapy. METHODS: We conducted a nonrandomized, 2-arm, open-label phase II trial including patients aged 18 years or older with an ECOG performance status of 0-2 that were either newly diagnosed (arm A) with a measurable tumor (i.e., after incomplete resection or biopsy) or that were diagnosed with progression of a glioblastoma after initial therapy (arm B). Patients in arm A received 600 mg/day imatinib in combination with hypofractionated radiotherapy (2.5 Gy per fraction, 22 fractions). Patients in arm B received 600 mg/day imatinib alone or in combination with re-irradiation at various doses. In case tumor progression occurred, CCNU was added (2 cycles, 100 mg/m2) to imatinib. The primary end point was progression-free survival (PFS). The secondary end point was safety, defined as per Common Terminology Criteria for Adverse Events (version 2.0). Overall survival (OS) was analyzed as an exploratory end point. RESULTS: Fifty-one patients were enrolled, of which 19 were included in arm A and 32 in arm B. The median follow-up was 4 (0.5-30) months in arm A and 6.5 (0.3-51.5) months in arm B. The median PFS was 2.8 months (95% CI 0-8.7) in arm A and 2.1 months (95% CI 0-11.8) in arm B. The median OS was 5.0 (0.8-30) months (95% CI 0-24.1) in arm A and 6.5 (0.3-51.5) months (95% CI 0-32.5) in arm B. The major grade 3 events were seizure (present in 17 patients), pneumonia (11 patients), and vigilance decrease (7 patients). CONCLUSIONS: Imatinib showed no measurable activity in patients with newly diagnosed or recurrent glioblastoma.

Posterolateral myelotomy for intramedullary spinal cord tumors: the other way to do it?

BACKGROUND AND PURPOSE: To evaluate posterolateral myelotomy (PLM) as a surgical method for all cases of intramedullary spinal cord tumors (IMSCT) by assessing the surgical and functional outcomes of patients treated in our clinic. MATERIALS AND METHODS: Patients with IMSCT who underwent surgery using PLM from 2013 to 2018 were reviewed retrospectively. Objective and quantitative assessment of the preoperative, postoperative, and follow-up neurological status was performed by using the modified McCormick functional schema and sensory pain scale. RESULTS: A total of 33 operations were performed on 27 patients who met the inclusion criteria. The mean grade on the McCormick functional schema increased insignificantly from 2.0 preoperatively to 2.3 immediately postoperatively and decreased back to 2.1 at the follow-up examination. Just one patient exhibited a transient proprioception deficit. Significant pain relief was observed as expressed in an improvement of mean grade on the sensory pain scale. Only in two cases was late neuropathic pain reported. A gross total resection/subtotal resection (GTR/STR) was achieved in all cases of hemangioblastoma and cavernoma, while for the majority of astrocytomas, only partial removal was accomplished. For ependymoma, which represents the most common IMSCT, a GTR/STR was realized in 12 cases (86%). A statistically significant difference (p = 0.027) was found when comparing the extent of tumor resection (EOR) between the two most common IMSCT, i.e., ependymoma and astrocytoma. CONCLUSION: PLM may be considered a reliable surgical method for IMSCT, as it combines a satisfactory EOR with reduced risk of tissue damage and excellent pain relief.

Red blood cell transfusion probability and associated costs in neurosurgical procedures.

BACKGROUND: The extent of red blood cell units (RBC) needed for different neurosurgical procedures and the time point of their administration are widely unknown, which results in generously cross-matching prior to surgery. However, RBC are increasingly requested in the aging western populations, and blood donations are significantly reduced. Therefore, the knowledge of the extent and time point of administration of RBC is of major importance. METHODS: This is a retrospective single center analysis. The incidence of RBC transfusion during surgery or within 48 h after surgery was analyzed for all neurosurgical patients within 3 years. Costs for cross-matched and transfused RBC were calculated and risk factors for RBC transfusion analyzed. RESULTS: The risk of intraoperative RBC administration was low for spinal and intracranial tumor resections (1.87%) and exceeded 10% only in spinal fusion procedures. This was dependent on the number of fused segments with an intraoperative transfusion risk of > 12.5% with fusion of more than three levels. Multiple logistic regression analysis showed a significantly increased risk for RBC transfusion for female gender (p = 0.006; OR 1.655), higher age (N = 4812; p < 0.0001; OR 1.028), and number of fused segments (N = 737; p < 0.0001; OR 1.433). Annual costs for cross-matching were 783,820.88 USD and for intraoperative RBC administration 121,322.13 USD. CONCLUSIONS: Neurosurgical procedures are associated with a low number of RBC needed intraoperatively. Only elective spine fusion procedures with ≥ 3 levels involved and AVM resections seem to require cross-matching of RBC. The present data may allow changing the preoperative algorithm of RBC cross-matching in neurosurgical procedures and help to save resources and costs.

Reliability and scientific use of a surgical planning software for anterior cervical discectomy and fusion (ACDF).

PURPOSE: Software-based planning of a spinal implant inheres in the promise of precision and superior results. The purpose of the study was to analyze the measurement reliability, prognostic value, and scientific use of a surgical planning software in patients receiving anterior cervical discectomy and fusion (ACDF). METHODS: Lateral neutral, flexion, and extension radiographs of patients receiving tailored cages as suggested by the planning software were available for analysis. Differences of vertebral wedging angles and segmental height of all cervical segments were determined at different timepoints using intraclass correlation coefficients (ICC). Cervical lordosis (C2/C7), segmental heights, global, and segmental range of motion (ROM) were determined at different timepoints. Clinical and radiological variables were correlated 12 months after surgery. RESULTS: 282 radiographs of 35 patients with a mean age of 53.1 ± 12.0 years were analyzed. Measurement of segmental height was highly accurate with an ICC near to 1, but angle measurements showed low ICC values. Likewise, the ICCs of the prognosticated values were low. Postoperatively, there was a significant decrease of segmental height (p < 0.0001) and loss of C2/C7 ROM (p = 0.036). ROM of unfused segments also significantly decreased (p = 0.016). High NDI was associated with low subsidence rates. CONCLUSIONS: The surgical planning software showed high accuracy in the measurement of height differences and lower accuracy values with angle measurements. Both the prognosticated height and angle values were arbitrary. Global ROM, ROM of the fused and intact segments, is restricted after ACDF.

Core herniation after implantation of a cervical artificial disc: case report.

INTRODUCTION: Cervical artificial discs (CADs) represent an established surgical option in selected patients with cervical spinal disc degeneration. Though CADs have been available for many years, there is a lack of information concerning long-term safety, durability and implant-related failure rates. MATERIALS AND METHODS: The authors describe the failure of a M6-C CAD (Spinal Kinetics, Sunnyvale, CA, USA). RESULTS: Eight years after implantation of a CAD of the M6 type, a 39-year-old female presented with new clinical signs of cervical myelopathy. Radiologically, medullar compression due to posterior core herniation was the suspected cause. The damaged CAD was removed and the segment fused. During revision surgery, rupture of the posterior structures could be detected. Possible mechanisms leading to implant failure are discussed. CONCLUSION: As there is no standard regarding clinical and radiological follow-up for patients with CADs, radiological long-term follow-up investigations seem to be justified for exclusion of implant failure.

Influence of cervical bone mineral density on cage subsidence in patients following stand-alone anterior cervical discectomy and fusion.

PURPOSE: Anterior cervical discectomy and fusion (ACDF) is a common procedure for the treatment of cervical degenerative diseases. However, cage subsidence remains a frequent problem. We therefore investigated if cage design and site-specific bone mineral density (BMD) contribute to the rate and direction of subsidence following ACDF. METHODS: Patients were prospectively included and received two different cages (groups 1 and 2) using minimization randomization. The degree and direction of cage subsidence were determined using plain radiographs. Neck pain intensity on the visual analogue scale (VAS), the neck disability index (NDI), and the patient satisfaction index were recorded up to 12 months after surgery. RESULTS: 88 patients were analysed with a mean age of 53.7 ± 11.8 years. BMD values decreased in craniocaudal direction from 302.0 ± 62.2 to 235.5 ± 38.9 mg/cm(3). Both groups showed significant height gain after the operation (both p < 0.001), followed by height loss at 3 months (both p < 0.05) and at 3-12 months after the operation (both p > 0.05). Both groups showed improvement of VAS neck pain intensity (both p < 0.05) and NDI (both p < 0.05). The direction of cage subsidence was similar, no correlations were found between cage subsidence and BMD or various clinical parameters. CONCLUSIONS: Implant geometry of both cages and variations of the operative procedure promoted a relatively high degree of cage subsidence. Further studies are necessary to identify a relation of BMD and subsidence using optimized implant geometry and by controlling additional intraoperative variables.

Dynamic Autoregulatory Response After Aneurysmal Subarachnoid Hemorrhage and Its Relation to Angiographic Vasospasm and Clinical Outcome.

BACKGROUND: Impaired cerebral autoregulation (CA) is increasingly recognized to contribute to sequelae after aneurysmal subarachnoid hemorrhage (SAH). The current study characterizes the course of the dynamic autoregulation index (ARI) during the first 8 days after SAH and its coherence with angiographic vasospasm (VS) and clinical outcome. METHODS: Fifty-one patients with SAH were prospectively included within 48 h after the ictus. The ARI was determined daily for each hemisphere with the thigh cuff test. The degree of cerebral VS was evaluated based on a baseline digital subtraction angiography (DSA) after the ictus and a follow-up DSA on day 8. The clinical outcome was determined by the Modified Rankin Scale (mRS), the Glasgow Outcome Scale Extended (GOSE), and the National Institute of Health Stroke Scale (NIHSS) at discharge from the intensive care unit. RESULTS: Impaired CA significantly correlated with unfavorable clinical outcome scores (mRS, p = 0.0021; GOSE, p = 0.0027; NIHSS, p = 0.0091). ARI-values of patients with a favorable clinical outcome (mRS 0-3) showed a significant improvement during the first 8 days (+0.1964/day; p = 0.0148) compared to a significant decrease of ARI-values in patients with an unfavorable clinical outcome (-0.2976/day; p = 0.0182). The degree of CA impairment significantly correlated with the severity of VS in the middle cerebral artery (p = 0.0184). CONCLUSIONS: Early deterioration of CA significantly correlates with unfavorable clinical outcome and severity of angiographic vasospasm. Dynamic CA measurements might represent an important tool in stratifying therapy guidelines in patients after SAH.

Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?

Human glioblastomas may be hierarchically organized. Within this hierarchy, glioblastoma-initiating cells have been proposed to be more resistant to radiochemotherapy and responsible for recurrence. Here, established stem cell markers and stem cell attributed characteristics such as self-renewal capacity and tumorigenicity have been profiled in primary glioblastoma cultures to predict radiosensitivity. Furthermore, the sensitivity to radiotherapy of different subpopulations within a single primary glioblastoma culture was analyzed by a flow cytometric approach using Nestin, SRY (sex-determining region Y)-box 2 (SOX2) and glial fibrillary acidic protein. The protein expression of Nestin and SOX2 as well as the mRNA levels of Musashi1, L1 cell adhesion molecule, CD133, Nestin, and pleiomorphic adenoma gene-like 2 inversely correlated with radioresistance in regard to the clonogenic potential. Only CD44 protein expression correlated positively with radioresistance. In terms of proliferation, Nestin protein expression and Musashi1, pleiomorphic adenoma gene-like 2, and CD133 mRNA levels are inversely correlated with radioresistance. Higher expression of stem cell markers does not correlate with resistance to radiochemotherapy in the cancer genome atlas glioblastoma collective. SOX2 expressing subpopulations exist within single primary glioblastoma cultures. These subpopulations predominantly form the proliferative pool of the primary cultures and are sensitive to irradiation. Thus, profiling of established stem cell markers revealed a surprising result. Except CD44, the tested stem cell markers showed an inverse correlation between expression and radioresistance. Markers used to define glioma-initiating cells (GIC) are generally not defining a more resistant, but rather a more sensitive group of glioma cells. An exemption is CD44 expression. Also proliferation of the GIC culture itself was not systematically associated with radiosensitivity or - resistance, but a SOX-2 positive, proliferative subgroup within a GIC culture is showing the highest radiosensitivity.

Clinical relevance of neuroforaminal patency after anterior cervical discectomy and fusion.

BACKGROUND: We sought to investigate the clinical relevance of neuroforaminal patency and facet degeneration one year after anterior cervical discectomy and fusion (ACDF). Previous studies were characterized by imprecise techniques and fragmentary measurements, and most lacked reliable clinical data and correlation analyses. METHODS: Patients with cervical mono- or bi-level degenerative pathology were prospectively included. Neuroforaminal size and segmental height were determined quantitatively, and the degree of facet degeneration was assessed qualitatively before and one year after the operation, by computed tomography. Clinical data, such as the severity of neck and arm pain, were assessed on a visual analogue scale (VAS) from 0 to 10, and neck disability index (NDI) was recorded before and one year after the operation. Their correlation with radiological data was investigated. RESULTS: Seventy-nine patients aged 53.3 ± 11.3 years were included. One year after surgery, median VAS pain intensity was still significantly improved (neck, from 5 to 1; right arm, from 2 to 1; left arm, from 4 to 1) as was NDI (from 40 to 20). Neuroforaminal size showed a reduction on both sides (left, 0.0289 ± 0.09 cm(2); right, 0.0149 ± 0.08 cm(2)). One year after the operation, segmental height decreased and facet degeneration increased from measures taken before the operation. No correlations were found between neuroforaminal stenosis or the degree of facet degeneration and various clinical outcome parameters. CONCLUSIONS: The decrease in segmental height one year after ACDF leads in turn to secondary neuroforaminal stenosis and progressive facet degeneration. Of the various neuroforaminal variables used, none revealed a threshold value indicative of the presence or severity of radicular arm pain. This absence of correlation between imaging and clinical information is important and should be considered when allocating patients for surgical interventions.

Effect of transcutaneous auricular vagal nerve stimulation on the fatigue syndrome in patients with gastrointestinal cancers - FATIVA: a randomized, placebo-controlled pilot study protocol.

BACKGROUND: Cancer-related fatigue (CRF) is defined as a "distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning." CRF is frequently observed in cancer patients even before the initiation of tumor therapy. Its cause is not clear, but in addition to primary effects of therapy, a tumor-induced elevated level of inflammatory cytokines may play a role. Transcutaneous auricular vagal nerve stimulation (taVNS) is a noninvasive way to activate central nervous pathways and modulate pain perception and the immune system. It has positive effects on autoimmune conditions and can also improve fatigue associated with Sjogren's syndrome. It is the main purpose of this feasibility study to investigate the feasibility of daily taVNS against CRF. Therefore, the stimulation protocol of the newly introduced smartphone app of the manufacturer is evaluated. Additionally, the effect taVNS on CRF and quality of life (QoL) shall be evaluated. METHODS: Thirty adult patients with gastrointestinal tumors during or after treatment, relevant CRF (Hornheide questionnaire) and life expectancy > 1 year, are enrolled. Patients are randomized to treatment or sham arm and be informed that they will either feel the stimulation or not. Treatment group will receive left-sided tragus above-threshold stimulation with 25 Hz, 250 µs pulse width, and 28-s/32-s on/off paradigm for 4 h throughout the day for 4 weeks. Sham group will receive no stimulation via a nonfunctional electrode. A daily stimulation protocol with time and average intensity is automatically created by a smartphone app connected to the stimulator via Bluetooth®. Multidimensional Fatigue Inventory-20, Short-Form 36 and Beck Depression Inventory questionnaires will be filled out before and after 4 weeks of stimulation. DISCUSSION: Primarily, the patients' daily stimulation time and intensity will be evaluated through the electronic protocol after 4 weeks. Secondarily, the effect of taVNS on cancer-related fatigue and QoL will be measured through the questionnaires. As taVNS seems to modulate inflammatory cytokines, this noninvasive method may - if accepted by the patients - be a promising adjunct in the treatment of cancer-related fatigue. TRIAL REGISTRATION: The study was approved by local ethics committee (21-7395) and registered at the DRKS database (DRKS00027481).

Shunt Dependence after Intraventricular Hemorrhage and Intraventricular Fibrinolysis with uPA versus rt-PA.

BACKGROUND: We compare the effect of urokinase (urokinase-type plasminogen activator [uPA]) versus alteplase (recombinant tissue plasminogen activator [rt-PA]) for intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) on ventriculoperitoneal shunt (VPS) dependence, functional outcome, and complications in the management of IVH. METHODS: We retrospectively reviewed the patients admitted with IVH or intracerebral hemorrhage (ICH) with IVH within 7 years in three different departments and found 102 patients who met the inclusion criteria. The primary end points were VPS dependence and Glasgow outcome score (GOS) at 3 months. Secondary end points were rate of rebleeding under IVF and incidence of treatment-related complications. Patients were divided into three groups: group I comprised patients treated with external ventricular drain (EVD) and IVF with uPA; group II comprised patients treated with EVD and IVF with rt-PA; and group III comprised patients treated with EVD alone. RESULTS: In all, 9.8% patients needed VPS: 12.2% in group I and 15.0% in group II, with no statistically significant difference. VPS patients had higher values of the modified Graeb score (mGS), IVH score, and IVH volume. We saw a trend for a better outcome in group II, with six patients achieving a GOS of 4 or 5 after 3 months. The mortality rate was higher in groups I and III. We found no statistical difference in the complication rate between groups I and II. Logistic regression analysis revealed that higher mGS and age predicted worse prognosis concerning mortality. The risk for death rose by 7.8% for each year of age. Any additional mGS point increased the chances of death by 9.7%. CONCLUSION: Our data suggest that both uPA and rt-PA are safe and comparable regarding incidence of communicating hydrocephalus, and age and mGS are predictive for mortality.

Development and first results of a national databank on care and treatment outcome after traumatic brain injury.

PURPOSE: In absence of comprehensive data collection on traumatic brain injury (TBI), the German Society for Neurosurgery (DGNC) and the German Society for Trauma Surgery (DGU) developed a TBI databank for German-speaking countries. METHODS: From 2016 to 2020, the TBI databank DGNC/DGU was implemented as a module of the TraumaRegister (TR) DGU and tested in a 15-month pilot phase. Since its official launch in 2021, patients from the TR-DGU (intermediate or intensive care unit admission via shock room) with TBI (AIS head ≥ 1) can be enrolled. A data set of > 300 clinical, imaging, and laboratory variables, harmonized with other international TBI data collection structures is documented, and the treatment outcome is evaluated after 6- and 12 months. RESULTS: For this analysis, 318 patients in the TBI databank could be included (median age 58 years; 71% men). Falls were the most common cause of injury (55%), and antithrombotic medication was frequent (28%). Severe or moderate TBI were only present in 55% of patients, while 45% suffered a mild injury. Nevertheless, intracranial pathologies were present in 95% of brain imaging with traumatic subarachnoid hemorrhages (76%) being the most common. Intracranial surgeries were performed in 42% of cases. In-hospital mortality after TBI was 21% and surviving patients could be discharged after a median hospital stay of 11 days. At the 6-and 12 months follow-up, a favorable outcome was achieved by 70% and 90% of the participating TBI patients, respectively. Compared to a European cohort of 2138 TBI patients treated in the ICU between 2014 and 2017, patients in the TBI databank were already older, frailer, fell more commonly at home. CONCLUSION: Within five years, the TBI databank DGNC/DGU of the TR-DGU could be established and is since then prospectively enrolling TBI patients in German-speaking countries. With its large and harmonized data set and a 12-month follow-up, the TBI databank is a unique project in Europe, already allowing comparisons to other data collection structures and indicating a demographic change towards older and frailer TBI patients in Germany.

Aneurysmal subarachnoid hemorrhage (aSAH) results in low prevalence of neuro-endocrine dysfunction and NOT deficiency.

Neuro-endocrine deficiencies have been argued to be common sequelae after aneurysmal subarachnoid hemorrhage (aSAH). As this, however, does not resemble our clinical experience, we studied the incidence of neuro-endocrine and neuropsychological deficits after aSAH. Twenty-six patients (20 females) were prospectively screened for neuro-endocrine and neuropsychological deficits 3, 6 and 12 months after aSAH. GH, IGF-1, prolactin, LH, FSH, estradiol, testosterone, ACTH as well as cortisol during ACTH-stimulation were assessed. Neuropsychological analysis covered verbal comprehension, short term and working memory, visuospatial construction, figural memory, psychomotor speed, attention, and concentration. During the study period 5 individuals demonstrated neuro-endocrine dysfunction. Hypogonadotrophic hypogonadism resolved spontaneously in 2 patients and central hypothyroidism in one of these patients during the study. After 12 months three patients presented low IGF-1 levels. 73.9% of our cohort was affected by neuropsychological deficits during follow-up. At 3, 6 and 12 months the prevalences were 56.5, 52.6 and 42.1%, respectively. Interestingly, all patients with neuro-endocrine dysfunction presented impaired clinical outcome with a GOS 4 at some time point of the study (GOS 4 vs. 5, 45.5% vs. 0, P = 0.007). We found a low prevalence of neuro-endocrine and a high prevalence of neuropsychological deficits in patients 3, 6 and 12 months after aSAH without significant interrelation. Spontaneous recovery of neuro-endocrine alterations most likely presents an adaption to or dysfunction after severe illness. This hypothesis is strengthened by the fact that only patients with inferior clinical outcome after aSAH as assessed by GOS demonstrated neuro-endocrine dysfunction.

Correlation of clinical outcome and angiographic vasospasm with the dynamic autoregulatory response after aneurysmal subarachnoid hemorrhage.

BACKGROUND: A certain correlation between unfavorable clinical outcome, incidence of vasospasm, and impaired pressure autoregulation in patients following aneurysmal subarachnoid hemorrhage (aSAH) has been suggested. However, determination of vasospasm is inaccurate and the measurement technique of cerebral vasoreactivity seems not to have been sufficiently validated. Therefore, a correlation of clinical outcome and the extent of angiographic VS was performed using an established autoregulation test. MATERIAL AND METHODS: Proximal and global angiographic vasospasm (pVS, gVS) were determined in bilateral M1 segments. Dynamic tests of pressure autoregulation were performed 1 day before and after, and on the day of angiography using Aaslid's thigh leg cuff test. Patient outcome was assessed using the Extended Glasgow Outcome Scale (GOSE). KEY RESULTS: Complete datasets were available for 22 patients. Mean autoregulatory indices (ARI) around the day of angiography were 3.9 ± 2.3. Proximal mean reduction of vessel diameter was -23.3% ± 9.1%. Global vasospasm was not present in 10 hemispheres, mild in 15, moderate in 15, and severe in 4. Hemispheric ARI values and angiographic data showed a significant correlation (pVS -0.382, p = 0.015; gVS -0.477, p = 0.002). The degree of angiographic vasospasm and low ARI values correlated significantly with an unfavorable outcome (0.677, p = 0.001). CONCLUSION: Incidence of angiographic vasospasm and impaired clinical outcome seems to be related to impaired pressure autoregulation following aSAH.

A novel concept for smart trepanation.

Trepanation of the skull is a common procedure in craniofacial and neurosurgical interventions, allowing access to the innermost cranial structures. Despite a careful advancement, injury of the dura mater represents a frequent complication during these cranial openings. The technology of computer-assisted surgery offers different support systems such as navigated tools and surgical robots. This article presents a novel technical approach toward an image- and sensor-based synergistic control of the cutting depth of a manually guided soft-tissue-preserving saw. Feasibility studies in a laboratory setup modeling relevant skull tissue parameters demonstrate that errors due to computed tomography or magnetic resonance image segmentation and registration, optical tracking, and mechanical tolerances of up to 2.5 mm, imminent to many computer-assisted surgery systems, can be compensated for by the cutting tool characteristics without damaging the dura. In conclusion, the feasibility of a computer-controlled trepanation system providing a safer and efficient trepanation has been demonstrated. Injuries of the dura mater can be avoided, and the bone cutting gap can be reduced to 0.5 mm with potential benefits for the reintegration of the bone flap.

Cortisol awakening response and pain-related fear-avoidance versus endurance in patients six months after lumbar disc surgery.

Recent research indicates that stress-induced, prolonged deviations in basal adrenocortical activity might contribute to ongoing/recurrent pain following lumbar disc surgery. Further, fear-avoidance and endurance responses to pain (FAR and ER) are regarded as important risk factors for pain after surgery. In patients with non-specific low back pain, FAR appear to possibly increase pain-related arousal, whereas ER may have an arousal-lowering effect, indicated by adrenocortical activity. The current study explores the relationship between basal adrenocortical activity and FAR and ER. Thirty-six patients 6 months after lumbar disc surgery participated. Basal adrenocortical activity was assessed through the cortisol awakening response (CAR), using salivary samples collected on two consecutive days. FAR and ER were estimated using questionnaires. While the ER variables pain-persistence behavior and positive mood despite pain showed negative associations with the CAR, the FAR variables fear-avoidance beliefs and avoidance of social activity were positively correlated with it. Additionally, higher CAR levels were found in patients with high versus patients with low fear-avoidance beliefs and, conversely, in patients with low versus high positive mood and pain persistence. These results indicate that FAR may increase the individuals' level of pain-related stress among patients after disc surgery, while ER may lower it.

An aneurysm clipping training module for the neurosurgical training simulator NeuroSim.

Having introduced NeuroSim, the prototype of a neurosurgical training simulator at MMVR18, we present our first medical training module. NeuroSim is based on virtual reality and uses real-time algorithms for simulating tissue. It provides a native interface by using a real surgical microscope and original instruments. Having implemented some abstract tasks to train basic skills like hand-eye coordination or the handling of the microscope last year, we now present a medical module where an aneurysm has to be clipped. NeuroSim has been developed in cooperation with the neurosurgical clinic of the University of Heidelberg and VRmagic GmbH in Mannheim.

Pre- and postoperative self-reported and objectively assessed neurocognitive functioning in lower grade glioma patients.

Due to the tumor itself or its therapy glioma patients may complain on cognitive impairment, while validated neuropsychological testing (NPT) capturing specific neuropsychological domains does not indicate "objective" dysfunction. Little is known on the relevance of this disturbance for patients' everyday life. We aimed to address whether glioma patients treated with state-of-the-art neurosurgical techniques complain on neuropsychological impairment and whether these subjective complaints are disclosed in formal NPT. We assessed both, "objective" and "subjective" neurocognitive functioning in 13 patients with newly diagnosed WHO grade 2 and 3 gliomas, operated between 06/2018 and 12/2020. All underwent both, preoperative and follow-up NPT as well as a semi-structured interview on subjective complaints and specific questionnaires (post-therapeutic) on attention, memory and executive functioning. On group level, no significant changes between preoperative and post-therapeutic NPT occurred. On the individual level, in 3/13 patients new post-therapeutic deficits in objective NPT were detected in specific domains (verbal memory, non-verbal memory, verbal fluency). By contrast, 8/13 patients reported on "subjective" memory impairments post-therapeutically. Furthermore, on specific questionnaires cognitive and emotional executive dysfunction and increased fatigue occurred in patients relative to normative data. Although the findings have to be replicated in larger populations, a discrepancy between "subjective" and "objective" measures was evident. While subjective neurocognitive impairment may simply not represent a true dysfunction, an alternative explanation might be that established standardized NPT is not suitable to detect subtle dysfunction in this population. "Subjective" and "objective" neurocognitive functioning might represent distinct constructs, which should complement each other in patient-centered Neuro-Oncology.