European survey on neurosurgical management of primary central nervous system lymphomas and preoperative corticosteroid therapy.

Introduction: Preoperative corticosteroid therapy (CST) is common in primary central nervous system lymphoma (PCNSL) and may complicate histopathological diagnosis. There is an ongoing debate on the best management after preoperative CST. Research question: We aimed to survey how different European neurosurgical units treat PCNSL patients after preoperative CST. Methods: An English-language survey consisting of 21 questions addressing the management of patients with suspected PCNSL and preoperative CST was sent to European hospitals. The survey also included three clinical cases to assess the decision-making process in a clinical setting. Results: The survey was completed by 74 European hospitals. There was no clear consensus on how to treat a patient with PCNSL after CST. Accordingly, 24.3% responded that they would generally defer surgery regardless of a possible radiological response, 47.3% would defer surgery only if there is regression in preoperative MRI and the remaining 28.4% would defer surgery only if the tumor had completely vanished. Furthermore, there were distinct discrepancies in responses of neurosurgical units regarding their general management approach and their case-based decision in the three example cases. The results of our survey also showed regional differences and differences in treatment decisions between high-, intermediate- and low-volume centers. Discussion and conclusion: There was no clear consensus on how to treat patients with suspected PCNSL and preoperative CST. Furthermore, most centers also showed inconsistencies in their responses regarding their general approach as well as individual patient treatment. More high-quality evidence-based recommendations are needed to improve consensus and thus patient care.

Pituitary Adenoma Surgery Survey: Neurosurgical Centers and Pituitary Adenomas.

Objective: Pituitary adenoma surgery has evolved rapidly in recent decades. This study aims to determine current practice across a wide range of European neurosurgical centers. Methods: A list of eligible departments performing pituitary adenoma surgery was created. The survey consisted of 58 questions. For analysis, the departments were divided into four subgroups: academic/nonacademic, high-volume/low-volume, "mainly endoscopic/mainly microscopic practice," and geographical regions. Results: Data from 254 departments from 34 countries were obtained. In 108 centers (42.5%), <30 pituitary adenomas were operated per year. Twenty (7.9%) centers performed >100 adenoma surgeries per year. Number of neurosurgeons performing endonasal surgeries are as follows: 1 in 24.9% of centers and 2 in 49.8% of centers. All residents assisted endonasal surgeries in 126 centers (49.8%). In 28 centers (21.1%), all residents performed endonasal surgery under supervision during residency. In 141 centers (56.8%), the endoscopic approach was used in >90% of the surgeries. Regular pituitary board (either weekly or once a month) meetings were held in 147 centers (56.3%). Nonfunctioning adenomas represent >70% of pituitary caseload in 149 centers (58.7%). Conclusions: In our survey, most centers perform less than 100 surgeries for pituitary adenomas. In most centers, pituitary surgeries are performed by one or two neurosurgeons. Residents have a limited exposure to this type of surgery, and the formal pituitary board is not a standard. Nonfunctioning adenomas make up most of surgically treated adenomas. This study can serve as a benchmark for further analyses of pituitary adenoma centers in Europe.

Endocrinological aspects of pituitary adenoma surgery in Europe.

Hormone-secreting adenomas are treated in many neurosurgical centers within Europe. The goal of the survey is to understand variance in practice management of pituitary tumors amongst neurosurgical centers. A list of departments performing pituitary surgery was created. The survey consisted of 58 questions. This study focuses on neurosurgical care of hormone-secreting adenomas. For analysis, the departments were divided into four subgroups: academic/non-academic, high-volume/low-volume, "mainly endoscopic/mainly microscopic practice" and geographical regions. Data from 254 departments from 34 countries were obtained. Most centers surgically treat 1-5 hormone-secreting adenomas per year. In prolactinomas this is the case in 194 centers, (76.4%), in GH-secreting adenomas: 133 centers, (52.4%), ACTH-secreting adenomas: 172 centers, (69.8%). Surgery as a primary treatment of prolactinomas is considered in 64 centers (25.2%). In 47 centers (18.8%), GH-secreting microadenomas are often treated pharmacologically first. Debulking surgery for an invasive GH-secreting adenoma in which hormonal remission is not a realistic goal of the surgery and the patient has no visual deficit surgery is always or mostly indicated in 156 centers (62.9%). Routine postoperative hydrocortisone replacement therapy is administered in 147 centers (58.6%). Our survey shows that in most centers, few hormone-secreting adenomas are treated per year. In about 25% of the centers, prolactinoma surgery may be regarded as first-line treatment; in about 20% of the centers, medical treatment is the first-line treatment for GH-secreting adenomas. Pretreatment for ACTH-secreting adenomas is routinely used in 21% of centers. This survey may serve as plea for neurosurgical care centralization of hormone-secreting adenomas.

What is the current clinical practice in pituitary adenoma surgery in Europe? European Pituitary Adenoma Surgery Survey (EU-PASS) results-technical part.

Pituitary adenoma surgery has evolved rapidly in recent decades, changing clinical practice markedly and raising new challenges. There is no current consensus or guidelines for perioperative care that includes possible complication management. This study aims to determine current practice across European neurosurgical centres. We created a list of eligible departments performing pituitary adenoma surgery based on cooperation with EANS, national neurosurgical societies, and personal communication with local neurosurgeons. We contacted the chairpersons from each department and asked them (or another responsible neurosurgeon) to fill out the survey. The survey consisted of 58 questions. For further analysis, departments were divided into subgroups: "academic"/ "non-academic centre", "high-volume"/"low-volume", "mainly endoscopic"/ "mainly microscopic"/ "mixed practise", and by geographical regions. Data from 254 departments from 34 countries were obtained. The average time to complete the survey was 18 min. Notably, the endoscopic approach is the predominant surgical approach in Europe, used in 56.8% of the centres. In routine cases without intraoperative cerebrospinal fluid leak, high-volume centres are less pedantic with sellar closure when compared with low-volume centres (p < 0.001). On the other hand, when a postoperative cerebrospinal fluid leak occurs, high-volume centres are more active and indicate early reoperation (p = 0.013). Less than 15% of the participating centres perform early postoperative MRI scans. Marked variation was noted among different groups of respondents and some contentious issues are discussed. Such information can encourage useful debate about the reasons for the variations seen and perhaps help develop standardised protocols to improve patient outcomes. A future research focus is to compare European results with other regions.

Atomic Force Microscope Nanoindentation Analysis of Diffuse Astrocytic Tumor Elasticity: Relation with Tumor Histopathology.

This study aims to investigate the influence of isocitrate dehydrogenase gene family (IDH) mutations, World Health Organization (WHO) grade, and mechanical preconditioning on glioma and adjacent brain elasticity through standard monotonic and repetitive atomic force microscope (AFM) nanoindentation. The elastic modulus was measured ex vivo on fresh tissue specimens acquired during craniotomy from the tumor and the peritumoral white matter of 16 diffuse glioma patients. Linear mixed-effects models examined the impact of tumor traits and preconditioning on tissue elasticity. Tissues from IDH-mutant cases were stiffer than those from IDH-wildtype ones among anaplastic astrocytoma patients (p = 0.0496) but of similar elasticity to IDH-wildtype cases for diffuse astrocytoma patients (p = 0.480). The tumor was found to be non-significantly softer than white matter in anaplastic astrocytomas (p = 0.070), but of similar elasticity to adjacent brain in diffuse astrocytomas (p = 0.492) and glioblastomas (p = 0.593). During repetitive indentation, both tumor (p = 0.002) and white matter (p = 0.003) showed initial stiffening followed by softening. Stiffening was fully reversed in white matter (p = 0.942) and partially reversed in tumor (p = 0.015). Tissue elasticity comprises a phenotypic characteristic closely related to glioma histopathology. Heterogeneity between patients should be further explored.

Mechanical properties of human glioma.

Brain gliomas represent some of the most aggressive tumors encountered by modern medicine and, despite major efforts to optimize early diagnosis and treatment, the prognosis remains poor. Due to the complex structure of the brain and the unique mechanical properties of the extracellular matrix, gliomas invade and expand into the brain parenchyma, along white matter tracts and within perivascular spaces, usually sparing normal vessels. Different methods have been developed to study the mechanical properties of gliomas in a wide range of scales, from cells and the microscale to tissues and the macroscale. In this review, the current view on glioma mechanics is presented and the methods used to determine glioma mechanical properties are outlined. Their principles and current state of affairs are discussed.

Modeling and Targeting Alzheimer's Disease With Organoids.

Human neurodegenerative diseases, such as Alzheimer's disease (AD), are not easily modeled in vitro due to the inaccessibility of brain tissue and the level of complexity required by existing cell culture systems. Three-dimensional (3D) brain organoid systems generated from human pluripotent stem cells (hPSCs) have demonstrated considerable potential in recapitulating key features of AD pathophysiology, such as amyloid plaque- and neurofibrillary tangle-like structures. A number of AD brain organoid models have also been used as platforms to assess the efficacy of pharmacological agents in disease progression. However, despite the fact that stem cell-derived brain organoids mimic early aspects of brain development, they fail to model complex cell-cell interactions pertaining to different regions of the human brain and aspects of natural processes such as cell differentiation and aging. Here, we review current advances and limitations accompanying several hPSC-derived organoid methodologies, as well as recent attempts to utilize them as therapeutic platforms. We additionally discuss comparative benefits and disadvantages of the various hPSC-derived organoid generation protocols and differentiation strategies. Lastly, we provide a comparison of hPSC-derived organoids to primary tissue-derived organoids, examining the future potential and advantages of both systems in modeling neurodegenerative disorders, especially AD.

Chemotherapy and diffuse low-grade gliomas: a survey within the European Low-Grade Glioma Network.

BACKGROUND: Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial. METHODS: An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients. RESULTS: The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression. CONCLUSIONS: The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues.

Theory of Mind impairment in focal versus generalized epilepsy.

Theory of Mind (ToM) is a critical component of social cognition, and thus, its impairment may adversely affect social functioning and quality of life. Recent evidence has suggested that it is impaired in epilepsy. What is not clear, however, is whether it is related to particular types of epilepsy or other factors. We undertook the present study to explore ToM in patients with focal versus those with generalized epilepsy, the particular pattern of ToM deficits, and the potential influence of antiepileptic medication load. Our sample included 149 adults: 79 patients with epilepsy (34 with generalized epilepsy and 45 with focal epilepsy) and 70 healthy controls. Theory of Mind tasks included a) comprehension of hinting, b) comprehension of sarcasm and metaphor, c) comprehension of false beliefs and deception, d) recognition of faux pas, and e) a visual ToM task in cartoon form. We found significant ToM impairment in the group with focal epilepsy relative to the performance of both the healthy group and the group with generalized epilepsy on all tasks, with the exception of faux pas, on which the group with generalized epilepsy also performed more poorly than the healthy group. Additionally, early age at seizure onset, but not antiepileptic drug (AED) load, was associated with ToM performance. Our findings suggest that focal temporal and frontal lobe, but not generalized, epilepsies were associated with impaired ToM. This may reflect the neuroanatomical abnormalities in the relevant neuronal networks and may have implications for differential cognitive-behavioral interventions based on epilepsy type.

Functional Brain Connectivity during Multiple Motor Imagery Tasks in Spinal Cord Injury.

Reciprocal communication of the central and peripheral nervous systems is compromised during spinal cord injury due to neurotrauma of ascending and descending pathways. Changes in brain organization after spinal cord injury have been associated with differences in prognosis. Changes in functional connectivity may also serve as injury biomarkers. Most studies on functional connectivity have focused on chronic complete injury or resting-state condition. In our study, ten right-handed patients with incomplete spinal cord injury and ten age- and gender-matched healthy controls performed multiple visual motor imagery tasks of upper extremities and walking under high-resolution electroencephalography recording. Directed transfer function was used to study connectivity at the cortical source space between sensorimotor nodes. Chronic disruption of reciprocal communication in incomplete injury could result in permanent significant decrease of connectivity in a subset of the sensorimotor network, regardless of positive or negative neurological outcome. Cingulate motor areas consistently contributed the larger outflow (right) and received the higher inflow (left) among all nodes, across all motor imagery categories, in both groups. Injured subjects had higher outflow from left cingulate than healthy subjects and higher inflow in right cingulate than healthy subjects. Alpha networks were less dense, showing less integration and more segregation than beta networks. Spinal cord injury patients showed signs of increased local processing as adaptive mechanism. This trial is registered with NCT02443558.

Investigating the Role of Alpha and Beta Rhythms in Functional Motor Networks.

It is recognized that lower electroencephalography (EEG) frequencies correspond to distributed brain activity over larger spatial regions than higher frequencies and are associated with coordination. In motor processes it has been suggested that this is not always the case. Our objective was to explore this contradiction. In our study, seven healthy subjects performed four motor tasks (execution and imagery of right hand and foot) under EEG recording. Two cortical source models were defined, model «A¼ with 16 regions of interest (ROIs) and model «B¼ with 20 ROIs over the sensorimotor cortex. Functional connectivity was calculated by Directed Transfer Function for alpha and beta rhythm networks. Four graph properties were calculated for each network: characteristic path length (CPL), clustering coefficient (CC), density (D) and small-world-ness (SW). Different network modules and in-degrees of nodes were also calculated and depicted in connectivity maps. Analysis of variance was used to determine statistical significance of observed differences in the network properties between tasks, between rhythms and between ROI models. Consistently on both models, CPL and CC were lower and D was higher in beta rhythm networks. No statistically significant difference was observed for SW between rhythms or for any property between tasks on any model. Comparing the models we observed lower CPL for both rhythms, lower CC in alpha and higher CC in beta when the number of ROIs increased. Also, denser networks with higher SW were correlated with higher number of ROIs. We propose a non-exclusive model where alpha rhythm uses greater wiring costs to engage in local information progression while beta rhythm coordinates the neurophysiological processes in sensorimotor tasks.

A Systematic Review of Investigations into Functional Brain Connectivity Following Spinal Cord Injury.

Background: Complete or incomplete spinal cord injury (SCI) results in varying degree of motor, sensory and autonomic impairment. Long-lasting, often irreversible disability results from disconnection of efferent and afferent pathways. How does this disconnection affect brain function is not so clear. Changes in brain organization and structure have been associated with SCI and have been extensively studied and reviewed. Yet, our knowledge regarding brain connectivity changes following SCI is overall lacking. Methods: In this study we conduct a systematic review of articles regarding investigations of functional brain networks following SCI, searching on PubMed, Scopus and ScienceDirect according to PRISMA-P 2015 statement standards. Results: Changes in brain connectivity have been shown even during the early stages of the chronic condition and correlate with the degree of neurological impairment. Connectivity changes appear as dynamic post-injury procedures. Sensorimotor networks of patients and healthy individuals share similar patterns but new functional interactions have been identified as unique to SCI networks. Conclusions: Large-scale, multi-modal, longitudinal studies on SCI patients are needed to understand how brain network reorganization is established and progresses through the course of the condition. The expected insight holds clinical relevance in preventing maladaptive plasticity after SCI through individualized neurorehabilitation, as well as the design of connectivity-based brain-computer interfaces and assistive technologies for SCI patients.

Towards Rehabilitation Robotics: Off-the-Shelf BCI Control of Anthropomorphic Robotic Arms.

Advances in neural interfaces have demonstrated remarkable results in the direction of replacing and restoring lost sensorimotor function in human patients. Noninvasive brain-computer interfaces (BCIs) are popular due to considerable advantages including simplicity, safety, and low cost, while recent advances aim at improving past technological and neurophysiological limitations. Taking into account the neurophysiological alterations of disabled individuals, investigating brain connectivity features for implementation of BCI control holds special importance. Off-the-shelf BCI systems are based on fast, reproducible detection of mental activity and can be implemented in neurorobotic applications. Moreover, social Human-Robot Interaction (HRI) is increasingly important in rehabilitation robotics development. In this paper, we present our progress and goals towards developing off-the-shelf BCI-controlled anthropomorphic robotic arms for assistive technologies and rehabilitation applications. We account for robotics development, BCI implementation, and qualitative assessment of HRI characteristics of the system. Furthermore, we present two illustrative experimental applications of the BCI-controlled arms, a study of motor imagery modalities on healthy individuals' BCI performance, and a pilot investigation on spinal cord injured patients' BCI control and brain connectivity. We discuss strengths and limitations of our design and propose further steps on development and neurophysiological study, including implementation of connectivity features as BCI modality.

Biopsy versus resection in the management of malignant gliomas: a systematic review and meta-analysis.

OBJECT: The aim of this study was to answer the question whether quality of life and progression-free and overall survival are increased in adults with supratentorial malignant glioma who are treated with cytoreductive resection as compared with those who only undergo biopsy. METHODS: A literature search of the electronic databases MEDLINE, EMBASE, and CENTRAL was performed to identify relevant studies published before May 2008. Hand-searching of reference lists of the identified studies and relevant review articles was also performed. A study was considered eligible, regardless of study design (prospective or retrospective), if: 1) quality of life and/or progression-free and/or overall survival was compared among adult patients undergoing biopsy or resection, and 2) patient age and Karnofsky Performance Scale scores were not significantly different among the 2 groups compared. RESULTS: One randomized controlled trial and 4 retrospective studies (involving a total of 1111 patients) were found eligible for this systematic review. A meta-analysis of the eligible studies demonstrated a significant increase in overall survival in the patients treated with resection instead of biopsy (hazard ratio 0.61, 95% CI 0.52-0.71, p < 0.0001, fixed-effect model). Although statistical pooling was not feasible, the available data suggest that quality of life was increased in patients treated with resection rather than biopsy, while there did not seem to be any significant difference in progression-free survival between the 2 groups. CONCLUSIONS: Based on the best available evidence, it appears that cytoreductive resection in adults with supratentorial malignant glioma is associated with improved overall survival as compared with biopsy. However, well-designed prospective studies are needed for more solid conclusions to be drawn.

Intra-operative MRI (iop-MR) for brain tumour surgery.

Image-guided neurosurgery is an important development in the management of brain tumours. Intra-operative imaging is an extension of this modality. It is important because it compensates for brain shift, allows accurate navigation, and gives verification of what has been done surgically before the patient leaves the operating room. It extends the capacity of image-guided surgery significantly. This paper describes the use intra-operative imaging using MR for brain tumour surgery, the devices presently available for doing this, and potential future applications of intra-operative imaging. It describes in some detail the specific indications for intra-operative imaging including biopsy, resection of intra-axial tumours, and identification and resection of some extra-axial tumours. The description includes the advantages and disadvantages of using intra-operative MRI in this setting.

Spontaneous spinal cord herniation: recurrence after 10 years.

BACKGROUND CONTEXT: Transdural spontaneous spinal cord herniation is a very rare nosological entity, which despite recent reports in the medical literature remains often misdiagnosed preoperatively. Usually it affects the thoracic segment, protrudes ventrally, presents clinically as a progressive Brown-Séquard syndrome and carries a favorable surgical outcome. PURPOSE: To describe a rare case of delayed recurrence of spontaneous spinal cord herniation despite excellent outcome for 10 years, and discussion of management and observation issues. STUDY DESIGN/SETTING: Case report/University Hospital. METHODS: We describe the management of a patient with spontaneous spinal cord herniation that presented initially with a Brown-Séquard syndrome and has been treated successfully with surgery. After 10 years free of symptoms, the patient developed progressive paraparesis and urinary incontinence because of recurrence of the herniation at the same level. RESULTS: Despite technical challenges, during the second operation the enlarged ventral dural defect was meticulously closed and the patient's neurological condition presents 9-month postsurgery considerable improvement. To our best knowledge, recurrences of spontaneous spinal cord herniation are extremely rare. CONCLUSIONS: The reported case underlines the necessity to be aware of this rare but treatable spinal disease, notify the possibility of late recurrences and the need of long-term follow-up even if initial outcome is favorable.