Distribution of Psychological Instability Among Surgeons.

BACKGROUND: High emotional instability (i.e., neuroticism) is associated with poor mental health. Conversely, traumatic experiences may increase neuroticism. Stressful experiences such as complications are common in the surgical profession, with neurosurgeons being particularly affected. We compared the personality trait neuroticism between physicians in a prospective cross-sectional study. METHODS: We used an online survey using the Ten-Item Personality Inventory, an internationally validated measure of the 5-factor model of personality dimensions. It was distributed to board-certified physicians, residents, and medical students in several European countries and Canada (n = 5148). Multivariate linear regression was used to model differences between surgeons, nonsurgeons, and specialties with occasional surgical interventions with respect to neuroticism, adjusting for sex, age, age squared, and their interactions, then testing equality of parameters of adjusted predictions separately and jointly using Wald tests. RESULTS: With an expected variability within disciplines, average levels of neuroticism are lower in surgeons than nonsurgeons, especially in the first part of their career. However, the course of neuroticism across age follows a quadratic pattern, that is, an increase after the initial decrease. The acceleration of neuroticism with age is specifically significant in surgeons. Levels of neuroticism are lowest towards mid-career, but exhibit a strong secondary increase towards the end of the surgeon's career. This pattern seems driven by neurosurgeons. CONCLUSIONS: Despite initially lower levels of neuroticism, surgeons suffer a stronger increase of neuroticism together with age. Because, beyond well-being, neuroticism influences professional performance and health care systems costs, explanatory studies are mandatory to enlighten causes of this burden.

The dural vascular plexus in subdural hematoma: Illustration through a case of dural arteriovenous fistula.

Background: The initiation of chronic subdural hematoma (cSDH) is traditionally explained by rupture of bridging veins. Recent descriptions of the embryology and anatomy of the meninges and their vascularization, however, point to the dural vascular plexus (DVP) as a plausible origin of cSDH. This dural plexus is supplied by meningeal arteries. Their endovascular occlusion is efficient in cSDH treatment. Dural arteriovenous fistulae (dAVF) may also present with subdural hematoma. Case Description: A 65-year-old female patient presented with parietal parasagittal dAVF and bilateral cSDH requiring surgical disconnection followed by complete clinical and imaging resolution of dAVF and cSDH. Conclusion: In common cSDH, pressure in the DVP may be normal and subdural bleeding may occur due to mechanical traction on the DVP. In the setting of dAVF, it may be the increase in pressure due to the fistula, within the DVP, that causes subdural hematoma. The DVP, supplied by meningeal arteries, thus not only allows for convergent pathophysiological explanation of subdural bleeding in both cSDH and dAVF but may also be the actual target of the emergent endovascular treatment of cSDH trough meningeal artery embolization.

Hans Joachim Scherer: an under-recognized pioneer of glioma research in Belgium.

Hans Joachim Scherer (1906-1946) was a German pathologist who fled Germany to Belgium to work on glioma genesis, growth and progression. Despite being seldom cited, and due to the contributions discussed in this article, Hans Joachim Scherer, can be considered a founding father of contemporary neuropathology and glioma research. We discuss Scherer's achievements in glioma classification, glomerular structures of glioma, primary and secondary glioblastoma, glioma growth patterns, non-resectability of glioma, pseudopalisadic necrosis and the late occurrence of symptoms in glioma.

The expression of B7-H3 isoforms in newly diagnosed glioblastoma and recurrence and their functional role.

Short survival of glioblastoma (GBM) patients is due to systematic tumor recurrence. Our laboratory identified a GBM cell subpopulation able to leave the tumor mass (TM) and invade the subventricular zone (SVZ-GBM cells). SVZ-GBM cells escape treatment and appear to contribute to GBM recurrence. This study aims to identify proteins specifically expressed by SVZ-GBM cells and to define their role(s) in GBM aggressiveness and recurrence. The proteome was compared between GBM cells located in the initial TM and SVZ-GBM cells using mass spectrometry. Among differentially expressed proteins, we confirmed B7-H3 by western blot (WB) and quantitative RT-PCR. B7-H3 expression was compared by immunohistochemistry and WB (including expression of its isoforms) between human GBM (N = 14) and non-cancerous brain tissue (N = 8), as well as newly diagnosed GBM and patient-matched recurrences (N = 11). Finally, the expression of B7-H3 was modulated with short hairpin RNA and/or over-expression vectors to determine its functional role in GBM using in vitro assays and a xenograft mouse model of GBM. B7-H3 was a marker for SVZ-GBM cells. It was also increased in human GBM pericytes, myeloid cells and neoplastic cells. B7-H3 inhibition in GBM cells reduced their tumorigenicity. Out of the two B7-H3 isoforms, only 2IgB7-H3 was detected in non-cancerous brain tissue, whereas 4IgB7-H3 was specific for GBM. 2IgB7-H3 expression was higher in GBM recurrences and increased resistance to temozolomide-mediated apoptosis. To conclude, 4IgB7-H3 is an interesting candidate for GBM targeted therapies, while 2IgB7-H3 could be involved in recurrence through resistance to chemotherapy.

Clinical Uncertainty and Equipoise in the Management of Recurrent Glioblastoma.

BACKGROUND: A significant proportion of glioblastoma (GBM) patients are considered for repeat resection, but evidence regarding best management remains elusive. Our aim was to measure the degree of clinical uncertainty regarding reoperation for patients with recurrent GBM. METHODS: We first performed a systematic review of agreement studies examining the question of repeat resection for recurrent GBM. An electronic portfolio of 37 pathologically confirmed recurrent GBM patients including pertinent magnetic resonance images and clinical information was assembled. To measure clinical uncertainty, 26 neurosurgeons from various countries, training backgrounds, and years' experience were asked to select best management (repeat surgery, other nonsurgical management, or conservative), confidence in recommended management, and whether they would include the patient in a randomized trial comparing surgery with nonsurgical options. Agreement was evaluated using κ statistics. RESULTS: The literature review did not reveal previous agreement studies examining the question. In our study, agreement regarding best management of recurrent GBM was slight, even when management options were dichotomized (repeat surgery vs. other options; κ=0.198 [95% confidence interval: 0.133-0.276]). Country of practice, years' experience, and training background did not change results. Disagreement and clinical uncertainty were more pronounced within clinicians with (κ=0.167 [0.055-0.314]) than clinicians without neuro-oncology fellowship training (κ=0.601 [0.556-0.646]). A majority (51%) of responders were willing to include the patient in a randomized trial comparing repeat surgery with nonsurgical alternatives in 26/37 (69%) of cases. CONCLUSION: There is sufficient uncertainty and equipoise regarding the question of reoperation for patients with recurrent glioblastoma to support the need for a randomized controlled trial.

Surgical or Endovascular Management of Middle Cerebral Artery Aneurysms: A Randomized Comparison.

OBJECTIVE: There are few randomized data comparing clipping and coiling for middle cerebral artery (MCA) aneurysms. We analyzed results from patients with MCA aneurysms enrolled in the CURES (Collaborative UnRuptured Endovascular vs. Surgery) and ISAT-2 (International Subarachnoid Aneurysm Trial II) randomized trials. METHODS: Both trials are investigator-led parallel-group 1:1 randomized studies. CURES includes patients with 3-mm to 25-mm unruptured intracranial aneurysms (UIAs), and ISAT-2 includes patients with ruptured aneurysms (RA) for whom uncertainty remains after ISAT. The primary outcome measure of CURES is treatment failure: 1) failure to treat the aneurysm, 2) intracranial hemorrhage during follow-up, or 3) residual aneurysm at 1 year. The primary outcome of ISAT-2 is death or dependency (modified Rankin Scale score >2) at 1 year. One-year angiographic outcomes are systematically recorded. RESULTS: There were 100 unruptured and 71 ruptured MCA aneurysms. In CURES, 90 patients with UIA have been treated and 10 await treatment. Surgical and endovascular management of unruptured MCA aneurysms led to treatment failure in 3/42 (7%; 95% confidence interval [CI], 0.02-0.19) for clipping and 13/48 (27%; 95% CI, 0.17-0.41) for coiling (P = 0.025). All 71 patients with RA have been treated. In ISAT-2, patients with ruptured MCA aneurysms managed surgically had died or were dependent (modified Rankin Scale score >2) in 7/38 (18%; 95% CI, 0.09-0.33) cases, and 8/33 (24%; 95% CI, 0.13-0.41) for endovascular. One-year imaging results were available in 80 patients with UIA and 62 with RA. Complete aneurysm occlusion was found in 30/40 (75%; 95% CI, 0.60-0.86) patients with UIA allocated clipping, and 14/40 (35%; 95% CI, 0.22-0.50) patients with UIA allocated coiling. Complete aneurysm occlusion was found in 24/34 (71%; 95% CI, 0.54-0.83) patients with RA allocated clipping, and 15/28 (54%; 95% CI, 0.36-0.70) patients with RA allocated coiling. CONCLUSIONS: Randomized data from 2 trials show that better efficacy may be obtained with surgical management of patients with MCA aneurysms.

Conventional and advanced imaging throughout the cycle of care of gliomas.

Although imaging of gliomas has evolved tremendously over the last decades, published techniques and protocols are not always implemented into clinical practice. Furthermore, most of the published literature focuses on specific timepoints in glioma management. This article reviews the current literature on conventional and advanced imaging techniques and chronologically outlines their practical relevance for the clinical management of gliomas throughout the cycle of care. Relevant articles were located through the Pubmed/Medline database and included in this review. Interpretation of conventional and advanced imaging techniques is crucial along the entire process of glioma care, from diagnosis to follow-up. In addition to the described currently existing techniques, we expect deep learning or machine learning approaches to assist each step of glioma management through tumor segmentation, radiogenomics, prognostication, and characterization of pseudoprogression. Thorough knowledge of the specific performance, possibilities, and limitations of each imaging modality is key for their adequate use in glioma management.

The debate on apraxia and the supplementary motor area in the twentieth century.

Hand function and apraxia are equally relevant to neurosurgeons: as a symptom, as well as through the functional anatomy of "praxis" which underlies the dexterity needed for neurosurgical practice. The supplementary motor area is crucial for its understanding. Historically, Hugo Liepmann dominated the apraxia debate at the beginning of the twentieth century, a debate that has remained influential until today. Kurt Goldstein, a contemporary of Liepmann, is regularly mentioned as the first to have described the alien hand syndrome in 1909. Wilder Penfield was a key figure in exploring the role of the fronto-mesial cortex in human motor control and coined the term "supplementary motor area". It was Goldstein who not only contributed substantially to the apraxia debate more than 100 years ago; he also established the link between the dysfunction of the fronto-mesial cortex and abnormal higher motor control in humans.

Multiparameter quantitative histological MRI values in high-grade gliomas: a potential biomarker of tumor progression.

BACKGROUND: Conventional MRI poorly distinguishes brain parenchyma microscopically invaded by high-grade gliomas (HGGs) from the normal brain. By contrast, quantitative histological MRI (hMRI) measures brain microstructure in terms of physical MR parameters influenced by histochemical tissue composition. We aimed to determine the relationship between hMRI parameters in the area surrounding the surgical cavity and the presence of HGG recurrence. METHODS: Patients were scanned after surgery with an hMRI multiparameter protocol that allowed for estimations of longitudinal relaxation rate (R1) = 1/T1, effective transverse relaxation rate (R2)*=1/T2*, magnetization transfer saturation (MTsat), and proton density. The initial perioperative zone (IPZ) was segmented on the postoperative MRI. Once recurrence appeared on conventional MRI, the area of relapsing disease was delineated (extension zone, EZ). Conventional MRI showing recurrence and hMRI were coregistered, allowing for the extraction of parameters R1, R2*, MTsat, and PD in 3 areas: the overlap area between the IPZ and EZ (OZ), the peritumoral brain zone, PBZ (PBZ = IPZ - OZ), and the area of recurrence (RZ = EZ - OZ). RESULTS: Thirty-one patients with HGG who underwent gross-total resection were enrolled. MTsat and R1 were the most strongly associated with tumor progression. MTsat was significantly lower in the OZ and RZ, compared to PBZ. R1 was significantly lower in RZ compared to PBZ. PD was significantly higher in OZ compared to PBZ, and R2* was higher in OZ compared to PBZ or RZ. These changes were detected 4 to 120 weeks before recurrence recognition on conventional MRI. CONCLUSIONS: HGG recurrence was associated with hMRI parameters' variation after initial surgery, weeks to months before overt recurrence.

A case of aphasia due to temporobasal edema: Contemporary models of language anatomy are clinically relevant.

BACKGROUND: Understanding the anatomy of language in the human brain is crucial for neurosurgical decision making and complication avoidance. The traditional anatomical models of human language, relying on relatively simple and rigid concepts of brain connectivity, cannot explain all clinical observations. The clinical case reported here illustrates the relevance of more recent concepts of language networks involving white matter tracts and their connections. CASE DESCRIPTION: Postoperative edema of the ventral occipitotemporal cortex, where modern network models locate a crucial language hub, resulted in transient severe aphasia after a subtemporal approach. Both verbal comprehension and expression were lost. The resolution of edema was associated with complete recovery from phonetic and semantic dysfunction. CONCLUSION: Complete aphasia due to a functional disturbance remote from the areas of Broca and Wernicke could be explained by contemporary neuroanatomical concepts of white matter connectivity. Knowledge of network-based models is relevant in brain surgery complication avoidance.

Anatomical integrity within the inferior fronto-occipital fasciculus and semantic processing deficits in schizophrenia spectrum disorders.

The core symptoms of schizophrenia spectrum disorders (SSD) include abnormal semantic processing which may rely on the ventral language stream of the human brain. Thus, structural disruption of the ventral language stream may play an important role in semantic deficits observed in SSD patients. Therefore, we compared white matter tract integrity in SSD patients and healthy controls using diffusion tensor imaging combined with probabilistic fiber tractography. For the ventral language stream, we assessed the inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus, and uncinate fasciculus. The arcuate fasciculus and corticospinal tract were used as control tracts. In SSD patients, the relationship between semantic processing impairments and tract integrity was analyzed separately. Three-dimensional tract reconstructions were performed in 45/44 SSD patients/controls ("Bern sample") and replicated in an independent sample of 24/24 SSD patients/controls ("Basel sample"). Multivariate analyses of fractional anisotropy, mean, axial, and radial diffusivity of the left IFOF showed significant differences between SSD patients and controls (p(FDR-corr) < 0.001, ηp2 = 0.23) in the Bern sample. Axial diffusivity (AD) of the left UF was inversely correlated with semantic impairments (r = -0.454, p(FDR-corr) = 0.035). In the Basel sample, significant group differences for the left IFOF were replicated (p < .01, ηp2 = 0.29), while the correlation between AD of the left IFOF and semantic processing decline (r = -0.376, p = .09) showed a statistical trend. No significant effects were found for the dorsal language stream. This is direct evidence for the importance of the integrity of the ventral language stream, in particular the left IFOF, in semantic processing deficits in SSD.

Neurologists, neurosurgeons, and psychiatrists' personality traits: a comparison.

BACKGROUND: Clinicians in neuroscientific disciplines may present distinct personality profiles. Despite of potential relevance to clinical practice, this has not yet been studied. We therefore aimed to compare personality profiles of physicians working in the three main disciplines of clinical neuroscience, i.e., neurologists, neurosurgeons, and psychiatrists, between each other, across levels of training and to other specialties. METHODS: An online survey using the Ten-Item Personality Inventory (TIPI), an internationally validated measure of the five-factor model of personality dimensions, was distributed to board-certified physicians, residents, and medical students in several European countries and Canada. Differences in personality profiles were analyzed using multivariate analysis of variance and canonical linear discriminant analysis on age- and sex-standardized z-scores of personality traits. Single personality traits were analyzed using robust t tests. RESULTS: Of the 5148 respondents who completed the survey, 723 indicated the specialties neurology, neurosurgery, or psychiatry. Compared to all other specialties, personality profiles of training and trained physicians in these three main clinical neuroscience disciplines ("NN&P") significantly differed, with significantly higher scores in openness to experience. Within NN&P, there were significant differences in personality profiles, driven by lower neuroticism in neurosurgeons, higher conscientiousness in neurosurgeons and neurologists, and higher agreeableness in psychiatrists. Across levels of training, NN&P personality profiles did not differ significantly. CONCLUSION: The distinct clinical neuroscience personality profile is characterized by higher levels of openness to experience compared to non-neuroscience specialties. Despite high variability within each discipline, moderate, but solid differences in the personality profiles of neurologists, neurosurgeons and psychiatrists exist.

MKP1 phosphatase is recruited by CXCL12 in glioblastoma cells and plays a role in DNA strand breaks repair.

Glioblastoma (GBM) is the most frequent and aggressive primary tumor in the central nervous system. Previously, the secretion of CXCL12 in the brain subventricular zones has been shown to attract GBM cells and protect against irradiation. However, the exact molecular mechanism behind this radioprotection is still unknown. Here, we demonstrate that CXCL12 modulates the phosphorylation of MAP kinases and their regulator, the nuclear MAP kinase phosphatase 1 (MKP1). We further show that MKP1 is able to decrease GBM cell death and promote DNA repair after irradiation by regulating major apoptotic players, such as Jun-N-terminal kinase, and by stabilizing the DNA repair protein RAD51. Increases in MKP1 levels caused by different corticoid treatments should be reexamined for GBM patients, particularly during their radiotherapy sessions, in order to prevent or to delay the relapses of this tumor.

Relevance of Translation Initiation in Diffuse Glioma Biology and its Therapeutic Potential.

Cancer cells are continually exposed to environmental stressors forcing them to adapt their protein production to survive. The translational machinery can be recruited by malignant cells to synthesize proteins required to promote their survival, even in times of high physiological and pathological stress. This phenomenon has been described in several cancers including in gliomas. Abnormal regulation of translation has encouraged the development of new therapeutics targeting the protein synthesis pathway. This approach could be meaningful for glioma given the fact that the median survival following diagnosis of the highest grade of glioma remains short despite current therapy. The identification of new targets for the development of novel therapeutics is therefore needed in order to improve this devastating overall survival rate. This review discusses current literature on translation in gliomas with a focus on the initiation step covering both the cap-dependent and cap-independent modes of initiation. The different translation initiation protagonists will be described in normal conditions and then in gliomas. In addition, their gene expression in gliomas will systematically be examined using two freely available datasets. Finally, we will discuss different pathways regulating translation initiation and current drugs targeting the translational machinery and their potential for the treatment of gliomas.

Age related metabolic modifications in the migraine brain.

PURPOSE: The aim of this study was to evaluate the possibility that migraine patients exhibit specific age-related metabolic changes in the brain, which occur regardless of disease duration or the frequency of attacks. METHODS: We analysed the relation between brain glucose (18F-fluorodeoxyglucose) uptake and age in healthy volunteers (n = 20) and episodic migraine patients (n = 19). In the latter, we additionally compared the correlation between 18F-fluorodeoxyglucose uptake and disease duration and monthly migraine days. RESULTS: In contrast to controls, in migraine patients advancing age was positively correlated to increased metabolism in the brainstem (especially the posterior pons), hippocampus, fusiform gyrus and parahippocampus. Conversely, no significant correlations between cerebral metabolism and disease duration or migraine days were observed. CONCLUSIONS: Findings of this cross-sectional study show that episodic migraine patients exhibit specific metabolic brain modifications while ageing. As such, age is correlated with metabolic changes in key regions of the brain previously associated with migraine's pathophysiology to a better extent than disease duration or the number of monthly migraine days. More than the repeated headache attacks, the continuous interaction with the environment seemingly models the brain of migraine sufferers in an adaptive manner. A positive control (e.g. chronic pain) is missing in this study and therefore findings cannot be proven to be migraine-specific.

Aurora A plays a dual role in migration and survival of human glioblastoma cells according to the CXCL12 concentration.

Primary glioblastoma is the most frequent human brain tumor in adults and is generally fatal due to tumor recurrence. We previously demonstrated that glioblastoma-initiating cells invade the subventricular zones and promote their radio-resistance in response to the local release of the CXCL12 chemokine. In this work, we show that the mitotic Aurora A kinase (AurA) is activated through the CXCL12-CXCR4 pathway in an ERK1/2-dependent manner. Moreover, the CXCL12-ERK1/2 signaling induces the expression of Ajuba, the main cofactor of AurA, which allows the auto-phosphorylation of AurA.We show that AurA contributes to glioblastoma cell survival, radio-resistance, self-renewal, and proliferation regardless of the exogenous stimulation with CXCL12. On the other hand, AurA triggers the CXCL12-mediated migration of glioblastoma cells in vitro as well as the invasion of the subventricular zone in xenograft experiments. Moreover, AurA regulates cytoskeletal proteins (i.e., Actin and Vimentin) and favors the pro-migratory activity of the Rho-GTPase CDC42 in response to CXCL12. Altogether, these results show that AurA, a well-known kinase of the mitotic machinery, may play alternative roles in human glioblastoma according to the CXCL12 concentration.

Skull base reconstruction with pedicled nasoseptal flap: Technique, indications, and limitations.

Endoscopic skull base surgery allows extensive tumor resection but results in large defects requiring robust dural repair. The vascularized nasal septal flap pedicled on the posterior nasal septal artery is known to have an excellent success rate for dural defect coverage. Detailed step-by-step descriptions of the harvest and placement of this flap are scarce. Using a sketch, images, and a video, we describe a detailed method for endoscopically harvesting and placing a nasoseptal flap (NSF). We also describe the indications and the decision process leading to the use of NSF.