Feasibility of Fluid Responsiveness Assessment in Patients at Risk for Increased Intracranial Pressure.

Background: Effective fluid management is important for patients at risk of increased intracranial pressure (ICP). Maintaining constant cerebral perfusion represents a challenge, as both hypovolemia and fluid overload can severely impact patient outcomes. Fluid responsiveness tests, commonly used in critical care settings, are often deemed potentially hazardous for these patients due to the risk of disrupting cerebral perfusion. Methods: This single-center, prospective, clinical observational study enrolled 40 patients at risk for increased ICP, including those with acute brain injury. Informed consent was obtained from each participant or their legal guardians before inclusion. The study focused on the dynamics of ICP and cerebral perfusion pressure (CPP) changes during the Passive Leg Raise Test (PLRT) and the End-Expiratory Occlusion Test (EEOT). Results: The results demonstrated that PLRT and EEOT caused minor and transient increases in ICP, while consistently maintaining stable CPP. EEOT induced significantly lower ICP elevations, making it particularly suitable for use in high-risk situations. Conclusions: PLRT and EEOT can be considered feasible and safe for assessing fluid responsiveness in patients at risk for increased ICP. Notably, EEOT stands out as a preferred method for high-risk patients, offering a dependable strategy for fluid management without compromising cerebral hemodynamics.

Stereotactic frame-based biopsy of infratentorial lesions via the suboccipital-transcerebellar approach with the Zamorano-Duchovny stereotactic system-a retrospective analysis of 79 consecutive cases.

OBJECTIVE: Lesions of the posterior fossa (brainstem and cerebellum) are challenging in diagnosis and treatment due to the fact that they are often located eloquently and total resection is rarely possible. Therefore, frame-based stereotactic biopsies are commonly used to asservate tissue for neuropathological diagnosis and further treatment determination. The aim of our study was to assess the safety and diagnostic success rate of frame-based stereotactic biopsies for lesions in the posterior fossa via the suboccipital-transcerebellar approach. METHODS: We performed a retrospective database analysis of all frame-based stereotactic biopsy cases at our institution since 2007. The aim was to identify all surgical cases for infratentorial lesion biopsies via the suboccipital-transcerebellar approach. We collected clinical data regarding outcomes, complications, diagnostic success, radiological appearances, and stereotactic trajectories. RESULTS: A total of n = 79 cases of stereotactic biopsies for posterior fossa lesions via the suboccipital-transcerebellar approach (41 female and 38 male) utilizing the Zamorano-Duchovny stereotactic system were identified. The mean age at the time of surgery was 42.5 years (± 23.3; range, 1-87 years). All patients were operated with intraoperative stereotactic imaging (n = 62 MRI, n = 17 CT). The absolute diagnostic success rate was 87.3%. The most common diagnoses were glioma, lymphoma, and inflammatory disease. The overall complication rate was 8.7% (seven cases). All patients with complications showed new neurological deficits; of those, three were permanent. Hemorrhage was detected in five of the cases having complications. The 30-day mortality rate was 7.6%, and 1-year survival rate was 70%. CONCLUSIONS: Our data suggests that frame-based stereotactic biopsies with the Zamorano-Duchovny stereotactic system via the suboccipital-transcerebellar approach are safe and reliable for infratentorial lesions bearing a high diagnostic yield and an acceptable complication rate. Further research should focus on the planning of safe trajectories and a careful case selection with the goal of minimizing complications and maximizing diagnostic success.

Deep learning aided preoperative diagnosis of primary central nervous system lymphoma.

The preoperative distinction between glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) can be difficult, even for experts, but is highly relevant. We aimed to develop an easy-to-use algorithm, based on a convolutional neural network (CNN) to preoperatively discern PCNSL from GBM and systematically compare its performance to experienced neurosurgeons and radiologists. To this end, a CNN-based on DenseNet169 was trained with the magnetic resonance (MR)-imaging data of 68 PCNSL and 69 GBM patients and its performance compared to six trained experts on an external test set of 10 PCNSL and 10 GBM. Our neural network predicted PCNSL with an accuracy of 80% and a negative predictive value (NPV) of 0.8, exceeding the accuracy achieved by clinicians (73%, NPV 0.77). Combining expert rating with automated diagnosis in those cases where experts dissented yielded an accuracy of 95%. Our approach has the potential to significantly augment the preoperative radiological diagnosis of PCNSL.

Association of early surgery and absence of ataxia with full recovery after spinal intramedullary ependymoma resection.

OBJECTIVE: Spinal intramedullary ependymomas (IEs) represent a well-defined tumor entity usually warranting resection. Factors that determine full long-term neurological recovery after resection are seldomly reported on in larger clinical series. In this study, the authors aimed to highlight the neurological outcome of patients with IEs after resection, with a focus on full neurological recovery, and to explore possible risk factors for the absence of neurological amelioration to an optimal function after surgical treatment. METHODS: A single-center retrospective analysis of all patients undergoing surgery for IEs between 2007 and 2021 was performed. Data collection included patient demographics, symptoms, clinical findings, histopathological diagnosis, surgical procedures, complications, and neurological outcome. Patients harboring a favorable outcome (modified McCormick Scale [mMS] grade of I) were compared with patients with a less favorable outcome (mMS grade ≥ II) at the final follow-up. RESULTS: In total, 72 patients with a histologically diagnosed IE were included. IEs in those patients (41 males, 31 females; median age 51 [IQR 40-59] years) mostly occurred in the cervical (n = 40, 56%) or thoracic (n = 23, 32%) spine. Upon admission, motor deficits or gait deficits (mMS grade ≥ II) were present in 29 patients (40%), with a median mMS grade of II (IQR I-II). Gross-total resection was achieved in 60 patients (90%), and the rate of surgical complications was 7%. Histopathologically, 67 tumors (93%) were classified as WHO grade 2 ependymomas, 3 (4%) as WHO grade 1 subependymomas, and 2 (3%) as WHO grade 3 anaplastic ependymomas. After a mean follow-up of 863 ± 479 days, 37 patients (51%) had a fully preserved neurological function and 62 patients (86%) demonstrated an mMS grade of I or II. Comparison of favorable with unfavorable outcomes revealed an association of early surgery (within a year after symptom onset), the absence of ataxia or gait disorders, and a low mMS grade with full neurological recovery at the final follow-up. A subgroup of patients (n = 15, 21%) had nonresolving deterioration at the final follow-up, with no significant differences in relevant variables compared with the rest of the cohort. CONCLUSIONS: The data presented solidify the role of early surgery in the management of spinal IEs, especially in patients with mild neurological deficits. Furthermore, the presence of gait disturbance or ataxia confers a higher risk of incomplete long-term recovery after spinal ependymoma resection. Because a distinct subgroup of patients had nonresolving deterioration, even when presenting with an uneventful history, further analyses into this subgroup of patients are required.

The use of quantitative pupillometry in brain death determination: preliminary findings.

PURPOSE: Quantitative pupillometry (QP) has been increasingly applied in neurocritical care as an easy-to-use and reliable technique for evaluating the pupillary light reflex (PLR). Here, we report our preliminary findings on using QP for clinical brain death (BD) determination. MATERIALS: This retrospective study included 17 patients ≥ 18 years (mean age, 57.3 years; standard deviation, 15.8 years) with confirmed BD, as defined by German Guidelines for the determination of BD. The PLR was tested using the NPi®-200 Pupillometer (Neuroptics, Laguna Hill, USA), a handheld infrared device automatically tracking and analyzing pupil dynamics over 3 s. In addition, pupil diameter and neurological pupil index (NPi) were also evaluated. RESULTS: Intracerebral bleeding, subarachnoid hemorrhage, and hypoxic encephalopathy were the most prevalent causes of BD. In all patients, the NPi was 0 for both eyes, indicating the cessation of mid-brain function. The mean diameter was 4.9 mm (± 1.3) for the right pupil and 5.2 mm (±1.2) for the left pupil. CONCLUSIONS: QP is a valuable tool for the BD certification process to assess the loss of PLR due to the cessation of brain stem function. Furthermore, implementing QP before the withdrawal of life-sustaining therapy in brain-injured patients may reduce the rate of missed organ donation opportunities. Further studies are warranted to substantiate the feasibility and potential of this technique in treating patients and identify suitable candidates for this technique during the BD certification process.

Anterior Access to the Cervicothoracic Junction via Partial Sternotomy: A Clinical Series Reporting on Technical Feasibility, Postoperative Morbidity, and Early Surgical Outcome.

Surgical access to the cervicothoracic junction (CTJ) is challenging. The aim of this study was to assess technical feasibility, early morbidity, and outcome in patients undergoing anterior access to the CTJ via partial sternotomy. Consecutive cases with CTJ pathology treated via anterior access and partial sternotomy at a single academic center from 2017 to 2022 were retrospectively reviewed. Clinical data, perioperative imaging, and outcome were assessed with regards to the aims of the study. A total of eight cases were analyzed: four (50%) bone metastases, one (12.5%) traumatic instable fracture (B3-AO-Fracture), one (12.5%) thoracic disc herniation with spinal cord compression, and two (25%) infectious pathologic fractures from tuberculosis and spondylodiscitis. The median age was 49.9 years (range: 22-74 y), with a 75% male preponderance. The median Spinal Instability Neoplastic Score (SINS) was 14.5 (IQR: 5; range: 9-16), indicating a high degree of instability in treated cases. Four cases (50%) underwent additional posterior instrumentation. All surgical procedures were performed uneventfully, with no intraoperative complications. The median length of hospital stay was 11.5 days (IQR: 9; range: 6-20), including a median of 1 day in an intensive care unit (ICU). Two cases developed postoperative dysphagia related to stretching and temporary dysfunction of the recurrent laryngeal nerve. Both cases completely recovered at 3 months follow-up. No in-hospital mortality was observed. The radiological outcome was unremarkable in all cases, with no case of implant failure. One case died due to the underlying disease during follow-up. The median follow-up was 2.6 months (IQR: 23.8; range: 1-45.7 months). Our series indicates that the anterior approach to the cervicothoracic junction and upper thoracic spine via partial sternotomy can be considered an effective option for treatment of anterior spinal pathologies, exhibiting a reasonable safety profile. Careful case selection is essential to adequately balance clinical benefits and surgical invasiveness for these procedures.

Decompressive craniectomy as a second/third-tier intervention in traumatic brain injury: A multicenter observational study.

OBJECTIVES: RESCUEicp studied decompressive craniectomy (DC) applied as third-tier option in severe traumatic brain injury (TBI) patients in a randomized controlled setting and demonstrated a decrease in mortality with similar rates of favorable outcome in the DC group compared to the medical management group. In many centers, DC is being used in combination with other second/third-tier therapies. The aim of the present study is to investigate outcomes from DC in a prospective non-RCT context. METHODS: This is a prospective observational study of 2 patient cohorts: one from the University Hospitals Leuven (2008-2016) and one from the Brain-IT study, a European multicenter database (2003-2005). In thirty-seven patients with refractory elevated intracranial pressure who underwent DC as a second/third-tier intervention, patient, injury and management variables including physiological monitoring data and administration of thiopental were analysed, as well as Extended Glasgow Outcome score (GOSE) at 6 months. RESULTS: In the current cohorts, patients were older than in the surgical RESCUEicp cohort (mean 39.6 vs. 32.3; p < 0.001), had higher Glasgow Motor Score on admission (GMS < 3 in 24.3% vs. 53.0%; p = 0.003) and 37.8% received thiopental (vs. 9.4%; p < 0.001). Other variables were not significantly different. GOSE distribution was: death 24.3%; vegetative 2.7%; lower severe disability 10.8%; upper severe disability 13.5%; lower moderate disability 5.4%; upper moderate disability 2.7%, lower good recovery 35.1%; and upper good recovery 5.4%. The outcome was unfavorable in 51.4% and favorable in 48.6%, as opposed to 72.6% and 27.4% respectively in RESCUEicp (p = 0.02). CONCLUSION: Outcomes in DC patients from two prospective cohorts reflecting everyday practice were better than in RESCUEicp surgical patients. Mortality was similar, but fewer patients remained vegetative or severely disabled and more patients had a good recovery. Although patients were older and injury severity was lower, a potential partial explanation may be in the pragmatic use of DC in combination with other second/third-tier therapies in real-life cohorts. The findings underscore that DC maintains an important role in managing severe TBI.

Routine ICU admission after brain tumor surgery: retrospective validation and critical appraisal of two prediction scores.

BACKGROUND: Routine admission to an intensive care unit (ICU) following brain tumor surgery has been a common practice for many years. Although this practice has been challenged by many authors, it has still not changed widely, mainly due to the lack of reliable data for preoperative risk assessment. Motivated by this dilemma, risk prediction scores for postoperative complications following brain tumor surgery have been developed recently. In order to improve the ICU admission policy at our institution, we assessed the applicability, performance, and safety of the two most appropriate risk prediction scores. METHODS: One thousand consecutive adult patients undergoing elective brain tumor resection within 19 months were included. Patients with craniotomy for other causes, i.e., cerebral aneurysms and microvascular decompression, were excluded. The decision for postoperative ICU-surveillance was made by joint judgment of the operating surgeon and the anesthesiologist. All data and features relevant to the scores were extracted from clinical records and subsequent ICU or neurosurgical floor documentation was inspected for any postoperative adverse events requiring ICU admission. The CranioScore derived by Cinotti et al. (Anesthesiology 129(6):1111-20, 5) and the risk assessment score of Munari et al. (Acta Neurochir (Wien) 164(3):635-641, 15) were calculated and prognostic performance was evaluated by ROC analysis. RESULTS: In our cohort, both scores showed only a weak prognostic performance: the CranioScore reached a ROC-AUC of 0.65, while Munari et al.'s score achieved a ROC-AUC of 0.67. When applying the recommended decision thresholds for ICU admission, 64% resp. 68% of patients would be classified as in need of ICU surveillance, and the negative predictive value (NPV) would be 91% for both scores. Lowering the thresholds in order to increase patient safety, i.e., 95% NPV, would lead to ICU admission rates of over 85%. CONCLUSION: Performance of both scores was limited in our cohort. In practice, neither would achieve a significant reduction in ICU admission rates, whereas the number of patients suffering complications at the neurosurgical ward would increase. In future, better risk assessment measures are needed.

Automatic Planning Tools for Lumbar Pedicle Screws: Comparison and Validation of Planning Accuracy for Self-Derived Deep-Learning-Based and Commercial Atlas-Based Approaches.

BACKGROUND: This ex vivo experimental study sought to compare screw planning accuracy of a self-derived deep-learning-based (DL) and a commercial atlas-based (ATL) tool and to assess robustness towards pathologic spinal anatomy. METHODS: From a consecutive registry, 50 cases (256 screws in L1-L5) were randomly selected for experimental planning. Reference screws were manually planned by two independent raters. Additional planning sets were created using the automatic DL and ATL tools. Using Python, automatic planning was compared to the reference in 3D space by calculating minimal absolute distances (MAD) for screw head and tip points (mm) and angular deviation (degree). Results were evaluated for interrater variability of reference screws. Robustness was evaluated in subgroups stratified for alteration of spinal anatomy. RESULTS: Planning was successful in all 256 screws using DL and in 208/256 (81%) using ATL. MAD to the reference for head and tip points and angular deviation was 3.93 ± 2.08 mm, 3.49 ± 1.80 mm and 4.46 ± 2.86° for DL and 7.77 ± 3.65 mm, 7.81 ± 4.75 mm and 6.70 ± 3.53° for ATL, respectively. Corresponding interrater variance for reference screws was 4.89 ± 2.04 mm, 4.36 ± 2.25 mm and 5.27 ± 3.20°, respectively. Planning accuracy was comparable to the manual reference for DL, while ATL produced significantly inferior results (p < 0.0001). DL was robust to altered spinal anatomy while planning failure was pronounced for ATL in 28/82 screws (34%) in the subgroup with severely altered spinal anatomy and alignment (p < 0.0001). CONCLUSIONS: Deep learning appears to be a promising approach to reliable automated screw planning, coping well with anatomic variations of the spine that severely limit the accuracy of ATL systems.

CT-Navigated Spinal Instrumentations-Three-Dimensional Evaluation of Screw Placement Accuracy in Relation to a Screw Trajectory Plan.

Background and Objectives: In the literature, spinal navigation and robot-assisted surgery improved screw placement accuracy, but the majority of studies only qualitatively report on screw positioning within the vertebra. We sought to evaluate screw placement accuracy in relation to a preoperative trajectory plan by three-dimensional quantification to elucidate technical benefits of navigation for lumbar pedicle screws. Materials and Methods: In 27 CT-navigated instrumentations for degenerative disease, a dedicated intraoperative 3D-trajectory plan was created for all screws. Final screw positions were defined on postoperative CT. Trajectory plans and final screw positions were co-registered and quantitatively compared computing minimal absolute differences (MAD) of screw head and tip points (mm) and screw axis (degree) in 3D-space, respectively. Differences were evaluated with consideration of the navigation target registration error. Clinical acceptability of screws was evaluated using the Gertzbein−Robbins (GR) classification. Results: Data included 140 screws covering levels L1-S1. While screw placement was clinically acceptable in all cases (GR grade A and B in 112 (80%) and 28 (20%) cases, respectively), implanted screws showed considerable deviation compared to the trajectory plan: Mean axis deviation was 6.3° ± 3.6°, screw head and tip points showed mean MAD of 5.2 ± 2.4 mm and 5.5 ± 2.7 mm, respectively. Deviations significantly exceeded the mean navigation registration error of 0.87 ± 0.22 mm (p < 0.001). Conclusions: Screw placement was clinically acceptable in all screws after navigated placement but nevertheless, considerable deviation in implanted screws was noted compared to the initial trajectory plan. Our data provides a 3D-quantitative benchmark for screw accuracy achievable by CT-navigation in routine spine surgery and suggests a framework for objective comparison of screw outcome after navigated or robot-assisted procedures. Factors contributing to screw deviations should be considered to assure optimal surgical results when applying navigation for spinal instrumentation.

Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation: The SETPOINT2 Randomized Clinical Trial.

Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation. Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation. Design, Setting, and Participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10. Patients were randomized between July 28, 2015, and January 24, 2020, at 26 US and German neurocritical care centers. The final date of follow-up was August 9, 2020. Interventions: Patients were assigned to an early tracheostomy strategy (n = 188) or to a standard tracheostomy (control group) strategy (n = 194). Main Outcomes and Measures: The primary outcome was functional outcome at 6 months, based on the modified Rankin Scale score (range, 0 [best] to 6 [worst]) dichotomized to a score of 0 (no disability) to 4 (moderately severe disability) vs 5 (severe disability) or 6 (death). Results: Among 382 patients randomized (median age, 59 years; 49.8% women), 366 (95.8%) completed the trial with available follow-up data on the primary outcome (177 patients [94.1%] in the early group; 189 patients [97.4%] in the standard group). A tracheostomy (predominantly percutaneously) was performed in 95.2% of the early tracheostomy group in a median of 4 days after intubation (IQR, 3-4 days) and in 67% of the control group in a median of 11 days after intubation (IQR, 10-12 days). The proportion without severe disability (modified Rankin Scale score, 0-4) at 6 months was not significantly different in the early tracheostomy vs the control group (43.5% vs 47.1%; difference, -3.6% [95% CI, -14.3% to 7.2%]; adjusted odds ratio, 0.93 [95% CI, 0.60-1.42]; P = .73). Of the serious adverse events, 5.0% (6 of 121 reported events) in the early tracheostomy group vs 3.4% (4 of 118 reported events) were related to tracheostomy. Conclusions and Relevance: Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months. However, the wide confidence intervals around the effect estimate may include a clinically important difference, so a clinically relevant benefit or harm from a strategy of early tracheostomy cannot be excluded. Trial Registration: ClinicalTrials.gov Identifier: NCT02377167.

Development and validation of an automated planning tool for navigated lumbosacral pedicle screws using a convolutional neural network.

BACKGROUND CONTEXT: Navigation and robotic systems have been increasingly applied to spinal instrumentation but dedicated screw planning is a time-consuming prerequisite to tap the full potential of these techniques. PURPOSE: To develop and validate an automated planning tool for lumbosacral pedicle screw placement using a convolutional neural network (CNN) to facilitate the planning process. STUDY DESIGN/SETTING: Retrospective analysis and processing of CT and screw planning data randomly selected from a consecutive registry of CT-navigated instrumentations from a single academic institution. PATIENT SAMPLE: Data from 179 cases was processed for CNN training and validation (155 for training, 24 for validation) leveraging a total of 1182 screws (1052 for training, 130 for validation). OUTCOME MEASURES: Quantitative and qualitative (Gertzbein-Robbins classification [GR]) validation via comparison of automatically and manually planned reference screws, inter-rater and intra-rater variability. METHODS: Annotated data from CT-navigated instrumentation was used to train a CNN operating in a vertebra instance-based approach employing a state-of-the-art U-Net framework. Internal five-fold cross-validation and external validation on an independent cohort not previously involved in training was performed. Quantitative validation of automatically planned screws was performed in comparison to corresponding manually planned screws by calculating the minimal absolute difference (MAD) of screw head and tip points, length and diameter, screw direction and Dice coefficient. Results were evaluated in relation to inter-rater and intra-rater variability of manual screw planning. RESULTS: Automated screw planning was successful in all targeted 130 screws. Compared with manually planned screws as a reference, mean MAD of automatically planned screws was 4.61±2.27 mm for screw head, 3.96±2.19 mm for tip points and 5.51±3.64° for screw direction. These differences were either statistically comparable or significantly smaller when compared with interrater variability of manual screw planning (p>.99 for head point and direction, p=.004 for tip point, respectively). Mean Dice coefficient of 0.61±0.16 indicated significantly greater agreement of automatic screws with the manual reference compared with interrater agreement (Dice 0.56±0.18, p<.001). Automatically planned screws were marginally shorter (MAD 3.4±3.2 mm) and thinner (MAD mean 0.3±0.6 mm) compared with the manual reference, but with statistical significance (p<.0001, respectively). Automatically planned screws were GR grade A in 96.2% in qualitative validation. Planning time was significantly shorter with the automatic approach (0:41 min vs. 6:41 min, p<.0001). CONCLUSIONS: We derived and validated a fully automated planning tool for lumbosacral pedicle screws using a CNN. Our validation showed noninferiority to manual screw planning and provided sufficient accuracy to facilitate and expedite the screw planning process. These results offer a high potential to improve workflows in spine surgery when integrated into navigation or robotic assistance systems.

Spinal oncologic paraparesis: Analysis of neurological and surgical outcomes in patients with intramedullary, extramedullary, and extradural tumors.

Objectives: Paraparesis due to oncologic lesions of the spine warrants swift neurosurgical intervention to prevent permanent disability and hence maintain independence of affected patients. Clinical parameters that predict a favorable outcome after surgical intervention could aid decision-making in emergency situations. Methods: Patients who underwent surgical intervention for paraparesis (grade of muscle strength <5 according to the British Medical Research Council grading system) secondary to spinal neoplasms between 2006 and 2020 were included in a single-center retrospective analysis. Pre- and postoperative clinical data were collected. The neurological status was assessed using the modified McCormick Disability Scale (mMcC) Score. In a univariate analysis, patients with favorable (discharge mMcC improved or stable at <3) and non-favorable outcome (discharge mMcC deteriorated or stable at >2) and different tumor anatomical compartments were statistically compared. Results: 117 patients with oncologic paraparesis pertaining to intramedullary lesions (n=17, 15%), intradural extramedullary (n=24, 21%) and extradural lesions (n=76, 65%) with a mean age of 65.3 ± 14.6 years were included in the analysis. Thoracic tumors were the most common (77%), followed by lumbar and cervical tumors (13% and 12%, respectively). Surgery was performed within a mean of 36±60 hours of admission across all tumors and included decompression over a median of 2 segments (IQR:1-3) and mostly subtotal tumor resection (n=83, 71%). Surgical and medical complications were documented in 9% (n=11) and 7% (n=8) of cases, respectively. The median hospital length-of-stay was 9 (7-13) days. Upon discharge, the median mMcC score had improved from 3 to 2 (p<0.0001). At last follow-up (median 180; IQR 51-1080 days), patients showed an improvement in their mean Karnofsky Performance Score (KPS) from 51.7±18.8% to 65.3±20.4% (p<0.001). Localization in the intramedullary compartment, a high preoperative mMcC score, in addition to bladder and bowel dysfunction were associated with a non-favorable outcome (p<0.001). Conclusion: The data presented on patients with spinal oncologic paraparesis provide a risk-benefit narrative that favors surgical intervention across all etiologies. At the same time, they outline clinical factors that confer a less-favorable outcome like intramedullary tumor localization, a high McCormick score and/or bladder and bowel abnormalities at admission.

Analysis of a Surgical Series of 21 Cerebral Radiation Necroses.

BACKGROUND: There is no standard approach to differentiate cerebral radiation necrosis from tumor recurrence and no standard treatment pathway for symptomatic lesions. In addition, reports on histology-proven radiation necrosis and the underlying pathophysiology are scarce and highly relevant. METHODS: Our monocentric, retrospective analysis included 21 histology-proven cerebral radiation necroses. Our study focused on 1) potential risk factors for the development of radiation necrosis, 2) radiologic and histopathologic features of individual necroses, and 3) the suitability of previously reported magnetic resonance imaging (MRI)-based methods to identify radiation necroses based on specific structural image features. RESULTS: Average time between radiation treatment and development of necrosis was 4.68 years (95% confidence interval, 0.19-9.55 years). Matching available MRI data sets with those of patients with tumor lesions, we compared specificity and sensitivity of 3 previously reported methods to identify radionecrosis based on imaging criteria. In our hands, none of these methods reached a sensitivity ≥70%. Radionecrosis presented with large edema and showed increased levels of cell proliferation, as inferred by Ki-67 staining. Surgical removal of radiation necrosis proved to be a safe approach with low permanent morbidity (<5%) and no mortality. CONCLUSIONS: Although the overall incidence of cerebral radiation necrosis is low, our data suggest an increasing incidence over the last 2 decades, which is likely associated with the use of stereotactic radiotherapy. There are no imaging standards to identify radiation necrosis on standard MRI with structural sequences. Surgical removal of radiation necrosis is associated with low morbidity and mortality.

Optimal Cerebral Perfusion Pressure: Targeted Treatment for Severe Traumatic Brain Injury.

Identification of individual therapy targets is critical for traumatic brain injury (TBI) patients. Clinical outcomes depend on cerebrovascular autoregulation (CA) impairment. Here, we compare the effectiveness of optimal cerebral perfusion pressure (CPPopt)-targeted therapy in younger (<45 years of age) and elderly (≥45 years of age) TBI patients. Single-center multi-modal invasive arterial blood pressure(t), intracranial pressure (ICP)(t), cerebral perfusion pressure CPP(t), and CPPopt(t) monitoring (n = 81) was performed. ICM+ software was used for continuous CPPopt(t) status assessment by identification of pressure reactivity index (PRx). The most significant prognostic factors were age, Glasgow Coma Scale, serum glucose, and duration of longest CA ompairment event (LCAI) when PRx(t) >0.5 within 24 h after admission. The modeled accuracies for favorable and unfavorable outcome prediction were 86.5% and 90.9%, respectively. Age above 45 years and averaged ICP during all monitoring time above 21.3 mm Hg was associated with unfavorable outcome of an individual patient. Averaged CPP values close to CPPopt were associated with a better outcome in younger patients. Averaged ΔCPPopt <-5.0 mm Hg, averaged PRx >0.36, and LCAI >100 min were significantly associated with mortality for the younger patients. The critical values of averaged PRx >0.26 and LCAI >61 min were significantly associated with mortality for the elderly group. Autoregulation-guided treatment was important for individual TBI management, especially in younger patients. Further randomized multi-center studies are needed to prove final benefit.

Evaluation of three automatic brain vessel segmentation methods for stereotactical trajectory planning.

BACKGROUND AND OBJECTIVE: Stereotactical procedures require exact trajectory planning to avoid blood vessels in the trajectory path. Innovation in imaging and image recognition techniques have facilitated the automatic detection of blood vessels during the planning process and may improve patient safety in the future. To assess the feasibility of a vessel detection and warning system using currently available imaging and vessel segmentation techniques. METHODS: Image data were acquired from post-contrast, isovolumetric T1-weighted sequences (T1CE) and time.-of-flight MR angiography at 3T or 7T from a total of nine subjects. Vessel segmentation by a combination of a vessel-enhancement filter with subsequent level-set segmentation was evaluated using three different methods (Vesselness, FastMarching and LevelSet) in 45 stereotactic trajectories. Segmentation results were compared to a gold-standard of manual segmentation performed jointly by two human experts. RESULTS: The LevelSet method performed best with a mean interclass correlation coefficient (ICC) of 0.76 [0.73, 0.81] compared to the FastMarching method with ICC 0.70 [0.67, 0.73] respectively. The Vesselness algorithm achieved clearly inferior overall performance with a mean ICC of 0.56 [0.53, 0.59]. The differences in mean ICC between all segmentation methods were statistically significant (p < 0.001 with post-hoc p < 0.026). The LevelSet method performed likewise good in MPRAGE and 3T-TOF images and excellent in 7T-TOF image data. The negative predictive value (NPV) was very high (>97%) for all methods and modalities. Positive predictive values (PPV) were found in the overall range of 65-90% likewise depending on algorithm and modality. This pattern reflects the disposition of all segmentation methods - in case of misclassification - to produce preferentially false-positive than false-negative results. In a clinical setting, two to three potential collision warnings would be given per trajectory on average with a PPV of around 50%. CONCLUSIONS: It is feasible to integrate a clinically meaningful vessel detection and collision warning system into stereotactical planning software. Both, T1CE and MRA sequences are suitable as image data for such an application.

Management of Patients with Acute Subdural Hemorrhage During Treatment with Direct Oral Anticoagulants.

BACKGROUND: Anticoagulation therapy is a major risk factor for unfavorable patient outcomes following (traumatic) intracranial hemorrhage. Direct oral anticoagulants (DOAC) are increasingly used for the prevention and treatment of thromboembolic diseases. Data on patients treated for acute subdural hemorrhage (SDH) during anticoagulation therapy with DOAC are limited. METHODS: We analyzed the medical records of consecutive patients treated at our institution for acute SDH during anticoagulation therapy with DOAC or vitamin K antagonists (VKA) during a period of 30 months. Patient characteristics such as results of imaging and laboratory studies, treatment modalities and short-term patient outcomes were included. RESULTS: A total of 128 patients with preadmission DOAC (n = 65) or VKA (n = 63) intake were compared. The overall 30-day mortality rate of this patient cohort was 27%, and it did not differ between patients with DOAC or VKA intake (26% vs. 27%; p = 1.000). Similarly, the rates of neurosurgical intervention (65%) and intracranial re-hemorrhage (18%) were comparable. Prothrombin complex concentrates were administered more frequently in patients with VKA intake than in patients with DOAC intake (90% vs. 58%; p < 0.0001). DOAC treatment in patients with acute SDH did not increase in-hospital and 30-day mortality rates compared to VKA treatment. CONCLUSIONS: These findings support the favorable safety profile of DOAC in patients, even in the setting of intracranial hemorrhage. However, the availability of specific antidotes to DOAC may further improve the management of these patients.

Frame-based stereotactic biopsies using an intraoperative MR-scanner are as safe and effective as conventional stereotactic procedures.

BACKGROUND: Frame-based stereotactic biopsy (FBSB) is a minimally-invasive and effective procedure for the diagnosis of brain lesions and will likely gain clinical importance. Since FBSB procedures comprise a variety of imaging and sampling methods, it is necessary to compare the safety and effectiveness of individual techniques. OBJECTIVE: To assess the safety and effectiveness of FBSB using 1.5T iMRI as a one-stop procedure under general anesthesia without intraoperative histological examination. METHODS: In this single-center, retrospective analysis, 500 consecutive FBSBs using iMRI were compared to a historic control of 100 biopsies with traditional workflows (computed tomography (CT) with MRI image fusion). All procedures were performed under general anesthesia. Data on surgical procedures, pre- and postoperative neurologic patient status, complications and diagnostic yield were extracted from clinical records. RESULTS: Complication rates and diagnostic yield showed no significant differences between both groups. Mortality was 0.6%, 95% CI = [0.12%, 1.74%], in the iMRI and 0.0% [0.00%, 3.62%], in the control group with a morbidity of 5.4% [3.6%, 7.8%] and 6.0% [2.2%, 12.6%] and a diagnostic yield of 96.8% [94.9%, 98.2%] and 96.0% [90.1%, 98.9%]. Mean procedure duration was 124 [121, 127] minutes using iMRI and 112 [106, 118] minutes in the control group. CONCLUSION: FBSB using 1.5T iMRI under general anesthesia is a safe and effective procedure and is equivalent to traditional stereotactic workflows with respect to complication rate and diagnostic yield.

Intraoperative Stereotactic Magnetic Resonance Imaging for Deep Brain Stimulation Electrode Planning in Patients with Movement Disorders.

OBJECTIVE: Implantation of deep brain stimulation (DBS) electrodes requires stereotactic imaging. Stereotactic magnetic resonance imaging (MRI) for DBS surgery has become more popular and intraoperative MRI scanners have become more available. We report on our cohort of movement disorder patients who underwent intraoperative stereotactic MRI-only DBS electrode implantation. METHODS: A review of our DBS database for eligible patients over a study period of 8 years was performed. Stereotactic accuracy was calculated as a directional error and the Euclidean distance between planned and controlled electrode positions. Number and choice of microelectrodes, procedural times and complications were documented. RESULTS: n = 86 surgeries in n = 81 patients with Parkinson's Disease (PD), essential tremor and dystonia were performed and n=167 electrodes were implanted. Mean Euclidean distance between planned and controlled target was 2.1mm (±0.6). The directional error showed that electrodes were implanted more medial (0.3mm ± 0.9), posterior (0.5mm ± 1.0) and inferior (0.6mm ±1.0) compared to plan. There were no significant differences for stereotactic accuracy between targets, hemispheres or order of implantation. No significant correlations between Euclidean distance and number of microelectrode tracts or volume of intracranial air were observed. N = 539 microelectrodes were applied. In 28.7% non-center trajectories were chosen. Length of tremor (-61 minutes) and PD (-121 minutes) surgeries could be reduced significantly over the course of the study period. N = 1 (1.2%) intracranial hemorrhage occurred. N = 1 (0.6%) electrode had to be repositioned for lack of clinical effect. CONCLUSION: Intraoperative stereotactic MRI for DBS surgery is feasible with high stereotactic accuracy and low rates of complication.

Oncolytic H-1 Parvovirus Shows Safety and Signs of Immunogenic Activity in a First Phase I/IIa Glioblastoma Trial.

Oncolytic virotherapy may be a means of improving the dismal prognosis of malignant brain tumors. The rat H-1 parvovirus (H-1PV) suppresses tumors in preclinical glioma models, through both direct oncolysis and stimulation of anticancer immune responses. This was the basis of ParvOryx01, the first phase I/IIa clinical trial of an oncolytic parvovirus in recurrent glioblastoma patients. H-1PV (escalating dose) was administered via intratumoral or intravenous injection. Tumors were resected 9 days after treatment, and virus was re-administered around the resection cavity. Primary endpoints were safety and tolerability, virus distribution, and maximum tolerated dose (MTD). Progression-free and overall survival and levels of viral and immunological markers in the tumor and peripheral blood were also investigated. H-1PV treatment was safe and well tolerated, and no MTD was reached. The virus could cross the blood-brain/tumor barrier and spread widely through the tumor. It showed favorable pharmacokinetics, induced antibody formation in a dose-dependent manner, and triggered specific T cell responses. Markers of virus replication, microglia/macrophage activation, and cytotoxic T cell infiltration were detected in infected tumors, suggesting that H-1PV may trigger an immunogenic stimulus. Median survival was extended in comparison with recent meta-analyses. Altogether, ParvOryx01 results provide an impetus for further H-1PV clinical development.