Radiomics for the non-invasive prediction of PD-L1 expression in patients with brain metastases secondary to non-small cell lung cancer.

BACKGROUND: The expression level of the programmed cell death ligand 1 (PD-L1) appears to be a predictor for response to immunotherapy using checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC). As differences in terms of PD-L1 expression levels in the extracranial primary tumor and the brain metastases may occur, a reliable method for the non-invasive assessment of the intracranial PD-L1 expression is, therefore of clinical value. Here, we evaluated the potential of radiomics for a non-invasive prediction of PD-L1 expression in patients with brain metastases secondary to NSCLC. PATIENTS AND METHODS: Fifty-three NSCLC patients with brain metastases from two academic neuro-oncological centers (group 1, n = 36 patients; group 2, n = 17 patients) underwent tumor resection with a subsequent immunohistochemical evaluation of the PD-L1 expression. Brain metastases were manually segmented on preoperative T1-weighted contrast-enhanced MRI. Group 1 was used for model training and validation, group 2 for model testing. After image pre-processing and radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. The radiomics model was trained and validated using random stratified cross-validation. Finally, the best-performing radiomics model was applied to the test data. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analyses. RESULTS: An intracranial PD-L1 expression (i.e., staining of at least 1% or more of tumor cells) was present in 18 of 36 patients (50%) in group 1, and 7 of 17 patients (41%) in group 2. Univariate analysis identified the contrast-enhancing tumor volume as a significant predictor for PD-L1 expression (area under the ROC curve (AUC), 0.77). A random forest classifier using a four-parameter radiomics signature, including tumor volume, yielded an AUC of 0.83 ± 0.18 in the training data (group 1), and an AUC of 0.84 in the external test data (group 2). CONCLUSION: The developed radiomics classifiers allows for a non-invasive assessment of the intracranial PD-L1 expression in patients with brain metastases secondary to NSCLC with high accuracy.

The use of the sodium fluorescein and YELLOW 560 nm filter for the resection of pediatric posterior fossa lesions.

PURPOSE: This study aimed to verify the feasibility, safety, and benefit of using fluorescein sodium (FL) and a YELLOW 560 nm filter in posterior fossa tumors in children. METHODS: All cases of pediatric posterior fossa tumors that have undergone surgery using fluorescein (2018-2022) have been included and were examined retrospectively. In those cases where resection of the tumor was planned, a blinded neuroradiologist distinguished gross total resection and subtotal resection according to the postoperative MRI findings. The surgical report and medical files were reviewed regarding the intraoperative staining grade and adverse events. The grade of fluorescent staining of the targeted lesion was assessed as described in the surgical reports. The screening was conducted for any reference to the degree of fluorescent staining: "intense," "medium," "slight," and "no staining." RESULTS: 19 cases have been included. In 14 cases, a complete resection was initially intended. In 11 of these cases, a gross total resection could be achieved (78.6%). Staining was described as intense in most cases (58.8%). Except for yellow-colored urine, no side effects obviously related to FL were found throughout the observation period. CONCLUSION: In combination with a specific filter, FL is a reliable, safe, and feasible tool in posterior fossa surgery in children.

Brain metastasis resection: the impact of fluorescence guidance (MetResect study).

OBJECTIVE: Maximal resection of brain metastases (BMs) improves both progression-free survival and overall survival (OS). Fluorescein sodium (FL) in combination with the YELLOW 560-nm filter is a safe and feasible method for visualizing residual tumor tissue during BM resection. The authors of this study aimed to show that use of FL would positively influence the volumetric extent of resection (EOR) and thus the survival outcome in patients undergoing BM resection. METHODS: Analyzing their institution's prospective brain tumor registry, the authors identified 539 consecutive patients with BMs (247 women, mean age 62.8 years) by using preoperative high-quality MR images for volumetric analysis. BMs were resected under white light (WL) in 293 patients (54.4%; WL group) and under FL guidance in 246 patients (45.6%; FL group). Sex, age, presurgical Karnofsky Performance Status (KPS), recursive partitioning analysis class, and adjuvant treatment modalities were well balanced between the two groups. Volumetric analysis was performed in a blinded fashion by quantifying pre- and postoperative tumor volume based on gadolinium-enhanced T1-weighted sequences. RESULTS: In the FL group, the postoperative tumor volume was significantly smaller (p = 0.01), and hence the quantitative EOR was significantly larger (p = 0.024) and OS was significantly longer (p = 0.0001) (log-rank testing). Multivariate Cox regression modeling showed that age, presurgical KPS, metastasis status, and FL-guided resection are independent prognostic factors for survival. CONCLUSIONS: Compared with WL resection, FL-guided BM resection increased resection quality, significantly improved EOR, and prolonged OS.

Factors influencing the reliability of intraoperative testing in deep brain stimulation for Parkinson's disease.

BACKGROUND: Several meta-analyses comparing the outcome of awake versus asleep deep brain stimulation procedures could not reveal significant differences concerning the postoperative improvement of motor symptoms. Only rarely information on the procedural details is provided for awake operations and how often somnolence and disorientation occurred, which might hamper the reliability of intraoperative clinical testing. The aim of our study was to investigate possible influencing factors on the occurrence of somnolence and disorientation in awake DBS procedures. METHODS: We retrospectively analyzed 122 patients with Parkinson's disease having received implantation of a DBS system at our centre. Correlation analyses were performed for the duration of disease prior to surgery, number of microelectrode trajectories, AC-PC-coordinates of the planned target, UPDRS-scores, intraoperative application of sedative drugs, duration of the surgical procedure, perioperative application of apomorphine, and the preoperative L-DOPA equivalence dosage with the occurrence of intraoperative somnolence and disorientation. RESULTS: Patients with intraoperative somnolence were significantly older (p=0.039). Increased duration of the DBS procedure (p=0.020), delayed start of the surgery (p=0.049), higher number of MER trajectories (p=0.041), and the patients' % UPDRS improvement (p=0.046) also correlated with the incidence of intraoperative somnolence. We identified the main contributing factor to intraoperative somnolence as the use of sedative drugs applied during skin incision and burr hole trepanation (p=0.019). Perioperatively applied apomorphine could reduce the occurrence of somnolent phases during the operation (p=0.026). CONCLUSION: Several influencing factors were found to seemingly increase the risk of intraoperative somnolence and disorientation, while the use of sedative drugs seems to be the main contributing factor. We argue that awake DBS procedures should omit the use of sedatives for best clinical outcome. When reporting on awake DBS surgery these factors should be considered and adjusted for, to permit reliable interpretation and comparison of DBS study results.

Mediation of Tremor Control by the Decussating and Nondecussating Part of the Dentato-Rubro-Thalamic Tract in Deep Brain Stimulation in Essential Tremor: Which Part Should Be Stimulated?

OBJECTIVES: The dentato-rubro-thalamic tract (DRTT) has been found to play a major role in the mechanisms of tremor alleviation by deep brain stimulation (DBS) in essential tremor (ET). Still, the influence of the two different parts of the DRTT, consisting of crossing and nondecussating fibers, is not yet clear with respect to tremor reduction. The aim of this study was to assess the influence of the crossing and the nondecussating part of the DRTT on tremor control in ET. MATERIALS AND METHODS: We investigated 80 electrode contacts in ten patients with ET who received bilateral DBS of the Nucleus ventralis intermedius of the thalamus (VIM). Preoperatively and with patients under general anesthesia, 3T magnetic resonance imaging scans were performed, including Diffusion Tensor Imaging scans with 64 gradient directions. We calculated the course of the two parts of the DRTT based on a workflow for probabilistic fiber tracking including protocols for correction of susceptibility- and eddy current-induced distortions. Distances of electrode contacts were correlated with clinical data from neurologic single pole testing. RESULTS: Voltage- and current-steered systems were analyzed separately. Regarding postural tremor, effective contacts showed significantly lower distances to both parts of the DRTT (crossing p < 0.001, nondecussating p < 0.05) in voltage-steered systems. Regarding intentional tremor, significant results were only found for the crossing part (p < 0.01). Regarding both tremor types, effective contacts were closer to the crossing part, unlike less effective contacts. Nonlinear regression analyses using a logistic model showed higher coefficients for the crossing part of the DRTT. Multivariate regression models including distances to both parts of the DRTT showed a significant influence of only the crossing part. Analysis of current-steered systems showed unstable data, probably because of the small number of analyzed patients. CONCLUSIONS: Our data suggest an involvement of both parts of the DRTT in tremor reduction, indicating mediation of DBS effects by both fiber bundles, although the crossing part showed stronger correlations with good clinical responses. Nevertheless, special attention should be paid to methodologic aspects when using probabilistic tractography for patient-specific targeting to avoid uncertain and inaccurate results.

CXCR2-Blocking Has Context-Sensitive Effects on Rat Glioblastoma Cell Line Outgrowth (S635) in an Organotypic Rat Brain Slice Culture Depending on Microglia-Depletion (PLX5622) and Dexamethasone Treatment.

In glioblastoma (GBM), the interplay of different immune cell subtypes, cytokines, and/or drugs shows high context-dependencies. Interrelations between the routinely applied dexamethasone (Dex) and microglia remain elusive. Here, we exploited rat organotypic brain slice co-cultures (OBSC) to examine the effects on a rat GBM cell line (S635) outgrowth resulting from the presence of Dex and pretreatment with the colony-stimulating factor receptor 1 (CSF1-R) inhibitor PLX5622: in native OBSC (without PLX5622-pretreatment), a diminished S635 spheroid outgrowth was observable, whereas Dex-treatment enhanced outgrowth in this condition compared to PLX5622-pretreated OBSC. Screening the supernatants of our model with a proteome profiler, we found that CXCL2 was differentially secreted in a Dex- and PLX5622-dependent fashion. To analyze causal interrelations, we interrupted the CXCL2/CXCR2-axis: in the native OBSC condition, CXCR2-blocking resulted in increased outgrowth, in combination with Dex, we found potentiated outgrowth. No effect was found in the PLX5622-pretreated. Our method allowed us to study the influence of three different factors-dexamethasone, PLX5622, and CXCL2-in a well-controlled, simplified, and straight-forward mechanistic manner, and at the same time in a more realistic ex vivo scenario compared to in vitro studies. In our model, we showed a GBM outgrowth enhancing synergism between CXCR2-blocking and Dex-treatment in the native condition, which was levelled by PLX5622-pretreatment.

Metabolic Heterogeneity of Brain Tumor Cells of Proneural and Mesenchymal Origin.

Brain-tumor-initiating cells (BTICs) of proneural and mesenchymal origin contribute to the highly malignant phenotype of glioblastoma (GB) and resistance to current therapies. BTICs of different subtypes were challenged with oxidative phosphorylation (OXPHOS) inhibition with metformin to assess the differential effects of metabolic intervention on key resistance features. Whereas mesenchymal BTICs varied according to their invasiveness, they were in general more glycolytic and less responsive to metformin. Proneural BTICs were less invasive, catabolized glucose more via the pentose phosphate pathway, and responded better to metformin. Targeting glycolysis may be a promising approach to inhibit tumor cells of mesenchymal origin, whereas proneural cells are more responsive to OXPHOS inhibition. Future clinical trials exploring metabolic interventions should account for metabolic heterogeneity of brain tumors.

Intraoperative imaging of brain tumors with fluorescein: confocal laser endomicroscopy in neurosurgery. Clinical and user experience.

OBJECTIVE: Confocal laser endomicroscopy (CLE) is an established tool in basic research for tissue imaging at the level of microstructures. Miniaturization and refinement of the technology have made this modality available for operative imaging with a handheld device. Sufficient image contrast is provided by the preoperative application of fluorescein sodium. The authors report their first experiences in a clinical case series using the new confocal laser endomicroscope. METHODS: Handling, operative workflow, and visualization of the CLE were critically evaluated in 12 cases of different CNS tumors. Three different imaging positions in relation to the tumor were chosen: the tumor border (I), tumor center (II), and perilesional zone (III). Respective diagnostic sampling with H & E staining and matching intraoperative neuronavigation and microscope images are provided. RESULTS: CLE was found to be beneficial in terms of high-quality visualization of fine structures and for displaying hidden anatomical details. The handling of the device was good, and the workflow was easy. CONCLUSIONS: Handling ergonomics and image acquisition are intuitive. The endomicroscope allows excellent additional visualization of microstructures in the surgical field with a minimally invasive technique and could improve safety and clinical outcomes. The new confocal laser endomicroscope is an advanced tool with the potential to change intracranial tumor surgery. Imaging of these microstructures is novel, and research with comparative validation with traditional neuropathological assessments is needed.

Brain multimodality monitoring in patients suffering from acute aneurysmal subarachnoid hemorrhage: clinical value and complications.

Brain multimodality monitoring measuring brain tissue oxygen pressure, cerebral blood flow, and cerebral near-infrared spectroscopy may help optimize the neurocritical care of patients with aneurysmal subarachnoid hemorrhage and delayed cerebral ischemia. We retrospectively looked for complications associated with the placement of the probes and checked the reliability of the different tools used for multimodality monitoring. In addition, we screened for therapeutic measures derived in cases of pathological values in multimodality monitoring in 26 patients with acute aneurysmal subarachnoid hemorrhage. Computed tomography scans showed minor hemorrhage along with the probes in 12 patients (46.2%). Missing transmission of values was observed in 34.1% of the intended time of measurement for cerebral blood flow probes and 15.5% and 16.2%, respectively, for the two kinds of probes measuring brain tissue oxygen pressure. We identified 744 cumulative alarming values transmitted from multimodality monitoring. The most frequent intervention was modifying minute ventilation (29%). Less frequent interventions were escalating the norepinephrine dosage (19.9%), elevating cerebral perfusion pressure (14.9%) or inspiratory fraction of inspired oxygen (7.5%), transfusing red blood cell concentrates (1.2%), initiating further diagnostics (2.3%) and neurosurgical interventions (1.9%). As well, 355 cases of pathological values had no therapeutic consequence. The reliability of the measuring tools for multimodality monitoring regarding a continuous transmission of values must be improved, particularly for cerebral blood flow monitoring. The overall high rate of missing therapeutic responses to pathological values derived from multimodality monitoring in patients with aneurysmal subarachnoid hemorrhage underlines the need for structured tiered algorithms. In addition, such algorithms are the basic requirement for prospective multicenter studies, which are urgently needed to evaluate the role of multimodality monitoring in treating these patients.

The burden of headache following aneurysmal subarachnoid hemorrhage: a prospective single-center cross-sectional analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) as a serious type of stroke is frequently accompanied by a so-called initial thunderclap headache. However, the occurrence of burdensome long-term headache following SAH has never been studied in detail so far. The aim of this study was to determine the prevalence and characteristics of long-term burdensome headache in good-grade SAH patients as well as its relation to health-related quality of life (HR-QOL). METHODS: All SAH cases treated between January 2014 and December 2016 with preserved consciousness at hospital discharge were prospectively interviewed regarding burdensome headache in 2018. Study participants were subsequently scrutinized by means of a standardized postal survey comprising validated pain and HR-QOL questionnaires. A retrospective chart review provided data on the initial treatment. RESULTS: A total of 93 out of 145 eligible SAH patients participated in the study (62 females). A total of 41% (38/93) of subjects indicated burdensome headache at follow-up (mean 32.6 ± 9.3 months). Comparison between patients with (HA+) and without long-term headache (HA-) revealed significantly younger mean age (47.9 ± 11.8 vs. 55.6 ± 10.3 years; p < .01) as well as more favorable neurological conditions (WFNS I/II: 95% vs. 75%; p = .03) in HA+ cases. The mean average headache of the HA+ group was 3.7 ± 2.3 (10-point numeric rating scale), and the mean maximum headache intensity was 5.7 ± 2.9. Pain and HR-QOL scores demonstrated profound alterations in HA+ compared to HA- patients. CONCLUSIONS: Our results suggest that a considerable proportion of SAH patients suffers from burdensome headache even years after the hemorrhage. Moreover, long-term headache is associated with reduced HR-QOL in these cases.

Diagnostic reliability of the Berlin classification for complex MCA aneurysms-usability in a series of only giant aneurysms.

BACKGROUND AND OBJECTIVE: The main challenge of bypass surgery of complex MCA aneurysms is not the selection of the bypass type but the initial decision-making of how to exclude the affected vessel segment from circulation. To this end, we have previously proposed a classification for complex MCA aneurysms based on the preoperative angiography. The current study aimed to validate this new classification and assess its diagnostic reliability using the giant aneurysm registry as an independent data set. METHODS: We reviewed the pretreatment neuroimaging of 51 patients with giant (> 2.5 cm) MCA aneurysms from 18 centers, prospectively entered into the international giant aneurysm registry. We classified the aneurysms according to our previously proposed Berlin classification for complex MCA aneurysms. To test for interrater diagnostic reliability, the data set was reviewed by four independent observers. RESULTS: We were able to classify all 51 aneurysms according to the Berlin classification for complex MCA aneurysms. Eight percent of the aneurysm were classified as type 1a, 14% as type 1b, 14% as type 2a, 24% as type 2b, 33% as type 2c, and 8% as type 3. The interrater reliability was moderate with Fleiss's Kappa of 0.419. CONCLUSION: The recently published Berlin classification for complex MCA aneurysms showed diagnostic reliability, independent of the observer when applied to the MCA aneurysms of the international giant aneurysm registry.

Rate and risk factors for a hyperactivity delirium in patients with aneurysmal subarachnoid haemorrhage.

Hyperactive delirium (agitation) is a common complication in patients on intensive care units and can be assessed by the Richmond Agitation and Sedation Scale (RASS) in principle. However, the role of agitation in patients with aneurysmal subarachnoid haemorrhage (SAH) is poorly understood. We performed a retrospective analysis to identify risk factors for the development of a hyperactive delirium and its functional consequences for neurological outcome. Three hundred thirty-eight patients with SAH were screened in this study resulting in 212 patients which reached at least once a RASS of 0 and were eligible for further analysis. Clinical characteristics were analysed towards the occurrence of a hyperactive delirium. Neurological outcome at discharge and follow-up was assessed using the Glasgow Outcome Scale. Seventy-eight of 212 patients (36.8%) developed a hyperactive delirium; the duration ranged from 1 to 11 days. Multivariate regression revealed initial hydrocephalus (odds ratio (OR) 3.21 95% confidence interval (CI) [1.33-7.70]; p = 0.01), microsurgical clipping (OR 3.70 95%CI 1.71-8.01]; p = 0.001), male gender (OR 1.97 95%CI [1.05-3.85]; p = 0.047) and a higher Graeb score (OR 1.11 95%CI [1.00-1.22]; p = 0.043) to be significantly associated with the development of agitation. Medical history of psychiatric disorders, alcohol or nicotine abuse showed no correlation with agitation. Cox regression analysis revealed no significant influence of agitation towards unfavourable outcome at discharge or follow-up. We provide four independent risk factors for the development of agitation in SAH patients. Our study emphasizes the specific entity of agitation in patients with SAH and underscores its relevance in neurological patients.

Early clinical course after aneurysmal subarachnoid hemorrhage: comparison of patients treated with Woven EndoBridge, microsurgical clipping, or endovascular coiling.

BACKGROUND: The Woven EndoBridge (WEB) device has been increasingly used for the treatment of intracranial aneurysms after aneurysmal subarachnoid hemorrhage (SAH). Still, recent major clinical trials on patient management after SAH have defined WEB embolization as an exclusion criterion. In an analysis of an unselected patient cohort, we evaluate the early clinical course of SAH patients after WEB treatment compared to those treated with endovascular coiling or surgical clipping. METHODS: Data of all patients with proven SAH who were either treated with a WEB device, coil embolization, or neurosurgical clipping between March 2015 and August 2018 was systematically reviewed. Clinical parameters on intensive care unit (ICU), medical history and mortality rates were evaluated and compared between the different treatment approaches. RESULTS: Of all 201 patients included, 107 patients received endovascular coil embolization, 56 patients were treated with clipping and in 38 cases a WEB device was placed. The overall mortality was 17.9%. Thirteen patients (34.2%) in the WEB group had a Hunt and Hess grade > 3. Essential medical factors showed no clinically relevant differences between the treatment groups, and the analyzed blood parameters were predominantly within physiological limits without any relevant outliers. The Hunt and Hess grade but not the treatment modality was identified as independent risk-factor associated with ICU-mortality in the overall cohort (p < 0.001). CONCLUSION: In this study, there was no difference in the early clinical course between those treated with WEB embolization, coil embolization, or neurosurgical clipping. Since WEB embolization is a valuable treatment alternative to coiling, it seems not justified to exclude this procedure from upcoming clinical SAH trials, yet the clinical long-term outcome, aneurysm occlusion, and retreatment rates have to be analyzed in further studies. CLINICAL TRIAL REGISTRATION NUMBER: not applicable.

Clinical implications and radiographic characteristics of the relation between giant intracranial aneurysms of the posterior circulation and the brainstem.

BACKGROUND: Giant intracranial aneurysms of the posterior circulation (GPCirA) are rare entities compressing the brainstem and adjacent structures. Previous evidence has shown that the amount of brainstem shift away from the cranial base is not associated with neurological deficits. This raises the question whether other factors may be associated with neurological deficits. METHODS: All data were extracted from the Giant Intracranial Aneurysm Registry, an international multicenter prospective study on giant intracranial aneurysms. We grouped GPCirA according to the mass effect on the brainstem (lateral versus medial). Brainstem compression was evaluated with two indices: (a) brainstem compression ratio (BCR) or diameter of the compressed brainstem to the assumed normal diameter of the brainstem and (b) aneurysm to brainstem ratio (ABR) or diameter of the aneurysm to the diameter of the compressed brainstem. We examined associations between neurological deficits and GPCirA characteristics using binary regression analysis. RESULTS: Twenty-eight GPCirA were included. Twenty GPCirA showed medial (71.4%) and 8 lateral compression of the brainstem (28.6%). Baseline characteristics did not differ between the groups for patient age, aneurysm diameter, aneurysm volume, modified Rankin Scale (mRS), motor deficit (MD), or cranial nerve deficits (CND). Mean BCR was 53.0 in the medial and 54.0 in the lateral group (p = 0.92). The mean ABR was 2.9 in the medial and 2.3 in the lateral group (p = 0.96). In the entire cohort, neither BCR nor ABR nor GPCirA volumes were associated with the occurrence of CND or MD. In contrast, disability (mRS) was significantly associated with ABR (OR 1.94 (95% CI 1.01-3.70; p = 0.045) and GPCirA volumes (OR 1.21 (95% CI 1.01-1.44); p = 0.035), but not with BCR. CONCLUSION: In this cohort of patients with GPCirA, neither the degree of lateral projection nor the amount of brainstem compression predicted neurological deficits. Disability was associated only with aneurysm volume. When designing treatment strategies for GPCirA, aneurysm laterality or the amount of brainstem compression should be viewed as less relevant while the high risk of rupture of such giant lesions should be emphasized. TRIAL REGISTRATION: The registry is listed at clinicaltrials.gov under the registration no. NCT02066493.

Somatosensory evoked potentials in patients with high-grade aneurysmal subarachnoid hemorrhage.

OBJECTIVE The aim of this prospective study was to investigate the value of somatosensory evoked potentials (SEPs) in predicting outcome in patients with high-grade aneurysmal subarachnoid hemorrhage (SAH). METHODS Between January 2013 and January 2015, 48 patients with high-grade SAH (Hunt and Hess Grade III, IV, or V) who were admitted within 3 days after hemorrhage were enrolled in the study. Right and left median and tibial nerve SEPs were recorded on Day 3 after hemorrhage and recorded again 2 weeks later. Glasgow Outcome Scale (GOS) scores were determined 6 months after hemorrhage and dichotomized as poor (Scores 1-3) or good (Scores 4-5). Results of SEP measurements were dichotomized (present or missing cortical responses or normal or prolonged latencies) for each nerve and side. These variables were summed and tested using logistic regression and a receiver operating characteristic curve to assess the value of SEPs in predicting long-term outcome. RESULTS At the 6-month follow-up visit, 29 (60.4%) patients had a good outcome, and 19 (39.6%) had a poor outcome. The first SEP measurement did not correlate with clinical outcome (area under the curve [AUC] 0.69, p = 0.52). At the second measurement of median nerve SEPs, all patients with a good outcome had cortical responses present bilaterally, and none of them had bilateral prolonged latencies (p = 0.014 and 0.003, respectively). In tibial nerve SEPs, 7.7% of the patients with a good GOS score had one or more missing cortical responses, and bilateral prolonged latencies were found in 23% (p = 0.001 and 0.034, respectively). The second measurement correlated with the outcome regarding each of the median and tibial nerve SEPs and the combination of both (AUC 0.75 [p = 0.010], 0.793 [p = 0.003], and 0.81 [p = 0.001], respectively). CONCLUSIONS Early SEP measurement after SAH did not correlate with clinical outcome, but measurement of median and tibial nerve SEPs 2 weeks after a hemorrhage did predict long-term outcome in patients with high-grade SAH.

Surgical treatment and outcome of TSH-producing pituitary adenomas.

BACKGROUND: Thyrotropin-producing adenomas (TSHomas) account for approximately 1-2% of all pituitary tumors. Recently, there has been debate on primary treatment as some studies suggest a high rate of hypopituitarism after transsphenoidal surgery and therefore suggest primary use of somatostatin analogs (SSA) instead. We would like to challenge this assumption by presenting our single-center experience with transsphenoidal surgery for TSHoma. METHODS: Fifteen patients treated consecutively between May 2010 and December 2016 were analyzed for long-term postoperative remission and pituitary function. RESULTS: Data on the development of TSH, fT3 and fT4 were available for 12 of 15 patients (mean follow-up was 18 months, 8 patients >12 months), showing mean TSH levels of 1.289 mU/l (0.02-2.04, SD 0.66), mean fT3 levels of 3.76 pmol/l (0.5-6.16, SD 1.8) and mean fT4 levels of 16.5 pmol/l (11.7-21.9, SD 3.66). Six of those patients were substituted with a mean of 85.4 µg L-thyroxine after a median follow-up of 20.7 months. The other six patients did not receive L-thyroxine at a median follow-up of 15.5 months. One patient with a known tumor remnant on MRI stayed euthyreotic with cabergoline at the timepoint of follow-up 22 months after the operation. Control of the corticotrop axis was also available in 12 of 15 with no patient showing a corticotroph insufficiency in the long term. CONCLUSIONS: We argue that transsphenoidal surgery for TSHoma should be considered as the treatment of choice as remission following surgery is highly probable and postoperative hypopituitarism is very unlikely if patients are referred to centers with high pituitary surgery case loads.

Maternal Aneurysmal Subarachnoid Hemorrhage During Pregnancy as an Interdisciplinary Task.

Maternal aneurysmal subarachnoid hemorrhage (aSAH) during pregnancy presents a challenge regarding treatment and management. Due to the limited number of cases there are no treatment guidelines available. Thus, treatment is usually done on a case-by-case basis. Here we report on four cases of aSAH during pregnancy, describing the different management strategies and suggesting a possible treatment algorithm. Patients treated between 2003 and 2013 in our center were included in this retrospective study. Clinical data focused on time management concerning gestation week (GW), microsurgical or endovascular treatment, and outcome of the patients and the fetuses. Results were compared to the present literature on this issue. Mean age was 30.8 years, initial Hunt & Hess (H&H) grade ranged from III to V. All patients suffered from aSAH during the 3rd trimester of pregnancy. In the four cases, two emergency Caesarean sections (CS) were performed. Two aneurysms were occluded by microsurgical clipping and one was treated endovascularly. One patient died before definitive treatment of the aneurysm could be achieved, whereas fetal mortality was 0%. The mean follow-up was 83 months. aSAH during pregnancy needs individualized interdisciplinary management. Efforts must focus on the mother so that a delay in the best available treatment for the pregnant patient is avoided. Therefore treatment modality should be primarily determined by the aneurysm itself. However, timing in terms of delivery of the fetus and aneurysm treatment is a crucial point.

Does usage of a parachute in contrast to free fall prevent major trauma?: a prospective randomised-controlled trial in rag dolls.

PURPOSE: It is undisputed for more than 200 years that the use of a parachute prevents major trauma when falling from a great height. Nevertheless up to date no prospective randomised controlled trial has proven the superiority in preventing trauma when falling from a great height instead of a free fall. The aim of this prospective randomised controlled trial was to prove the effectiveness of a parachute when falling from great height. METHODS: In this prospective randomised-controlled trial a commercially acquirable rag doll was prepared for the purposes of the study design as in accordance to the Declaration of Helsinki, the participation of human beings in this trial was impossible. Twenty-five falls were performed with a parachute compatible to the height and weight of the doll. In the control group, another 25 falls were realised without a parachute. The main outcome measures were the rate of head injury; cervical, thoracic, lumbar, and pelvic fractures; and pneumothoraxes, hepatic, spleen, and bladder injuries in the control and parachute groups. An interdisciplinary team consisting of a specialised trauma surgeon, two neurosurgeons, and a coroner examined the rag doll for injuries. Additionally, whole-body computed tomography scans were performed to identify the injuries. RESULTS: All 50 falls-25 with the use of a parachute, 25 without a parachute-were successfully performed. Head injuries (right hemisphere p = 0.008, left hemisphere p = 0.004), cervical trauma (p < 0.001), thoracic trauma (p < 0.001), lumbar trauma (p < 0.001), pelvic trauma (p < 0.001), and hepatic, spleen, and bladder injures (p < 0.001) occurred more often in the control group. Only the pneumothoraxes showed no statistically significant difference between the control and parachute groups. CONCLUSIONS: A parachute is an effective tool to prevent major trauma when falling from a great height.

Minimally invasive approach for small ventrally located intradural lesions of the craniovertebral junction.

OBJECT: The surgical management of lesions ventral to the neuraxis at the level of the craniovertebral junction (CVJ) and upper cervical spine is challenging. Here, the authors describe a minimally invasive dorsal approach for small ventrally located intradural lesions at the CVJ as an alternative for the more extensive classic transoral approach or variants of suboccipital approaches. METHODS: Between 2012 and 2014, 6 symptomatic patients with a small lesion of the ventral aspect at the CVJ level were treated using a minimally invasive dorsal approach at the University Medical Center in Hamburg-Eppendorf, Germany. The anatomical distance between the posterior atlantooccipital membrane and the posterior atlantoaxial ligament, as determined by CT images, was assessed in the treated patients and in 100 untreated persons. RESULTS: The authors treated 6 patients (mean age 54.7 years) who had a clinical presentation of mild neurological symptoms that disappeared after resection. Minimally invasive surgical dorsal access was achieved by using tubular systems and using the natural space between the occiput (C-0) and C-1, and in 1 case between C-1 and C-2, without having to remove bony structures. The postoperative course in each of the 6 patients was uneventful. The neuropatho-logical findings confirmed a meningotheliomatous meningioma (WHO Grade I) in 5 cases and an extramedullary cavernous hemangioma in 1 case. MRI confirmed complete resection of all the lesions. The atlantooccipital distances ranged from 3 to 17 mm (mean 8.98 mm) in the supine neutral position, and the atlantoaxial distances ranged from 5 to 17 mm (mean 10.56 mm). There were no significant differences between women and men (atlantooccipital p = 0.14; atlantoaxial p = 0.72). CONCLUSIONS: The results of this study demonstrate that the minimally invasive dorsal approach using the space between C-0 and C-1 or C-1 and C-2 provides direct and sufficient exposure for the safe surgical resection of small ventrally located intradural lesions at the CVJ level while reducing the necessity for musculoskeletal preparation to a minimum.

Intramedullary spinal cavernoma: clinical presentation, microsurgical approach, and long-term outcome in a cohort of 48 patients.

OBJECT Intramedullary spinal cavernoma (ISC) is a rare entity and accounts for approximately 5%-12% of all spinal vascular pathologies. The purpose of the present study was to examine the influence of clinical presentation, localization, and different surgical approaches on long-term outcome in patients treated for ISC. METHODS The authors performed a retrospective single-center study of 48 cases of ISC treated microsurgically over the past 28 years. Analyzed factors included preoperative clinical history, microsurgical strategies, neurological outcome (American Spinal Injury Association [ASIA] grade, Epstein and Cooper grade), and the occurrence of postoperative spinal ataxia. Univariate analysis was performed to identify factors influencing long-term outcome. RESULTS Preoperatively, 18.8% of all patients experienced a slow, progressive decline in neurological function and 33.3% suffered repetitive episodes of acute neurological deterioration over a time frame of months to years. Moreover, 16.7% noted the sudden onset of a severe neurological deficit, whereas 25% experienced the sudden onset of symptoms with a subsequent gradually progressive decline in neurological function. On long-term follow-up after treatment (mean ± SD, 79.3 ± 35.2 months), 70.8% of patients showed no change in neurological function, 6.3% suffered from a decline, and 22.9% improved neurologically. Thoracolumbar localization (p = 0.043), low preoperative Epstein and Cooper grade for the lower extremities (p < 0.001), and a low preoperative ASIA grade (p < 0.001) were identified as factors associated with an unfavorable outcome (ASIA Grade A-C). The rate of spinal ataxia related to surgical approach was 16.7%. CONCLUSION Postoperative neurological function in ISC patients is determined by the preoperative neurological status. On long-term follow-up after microsurgical treatment, 93.7% of patients presented with a stable or improved condition (ASIA grade); thus, definite microsurgical treatment should be considered as long as patients present with only mild symptoms after the diagnosis of symptomatic ISC.