Management of glioblastoma in elderly patients: A review of the literature.

High grade gliomas are the most common primary aggressive brain tumours with a very poor prognosis and a median survival of less than 2 years. The standard management protocol of newly diagnosed glioblastoma patients involves surgery followed by radiotherapy, chemotherapy in the form of temozolomide and further adjuvant temozolomide. The recent advances in molecular profiling of high-grade gliomas have further enhanced our understanding of the disease. Although the management of glioblastoma is standardised in newly diagnosed adult patients there is a lot of debate regarding the best treatment approach for the newly diagnosed elderly glioblastoma patients. In this review article we attempt to summarise the findings regarding surgery, radiotherapy, chemotherapy, and their combination in order to offer the best possible management modality for this group of patients. Elderly patients 65-70 with an excellent functional level could be considered as candidates for the standards treatment consisting of surgery, standard radiotherapy with concomitant and adjuvant temozolomide. Similarly, elderly patients above 70 with good functional status could receive the above with the exception of receiving a shorter course of radiotherapy instead of standard. In elderly GBM patients with poorer functional status and MGMT promoter methylation temozolomide chemotherapy can be considered. For elderly patients who cannot tolerate chemotherapy, hypofractionated radiotherapy is an option. In contrast to the younger adult patients, it seems that a careful individualised approach is a key element in deciding the best treatment options for this group of patients.

Site matters: Image-guided percutaneous sampling of intervertebral disc results in increased positive diagnostic yield in spondylodiscitis.

Spondylodiscitis is a common referral to spinal on call services. Identification of the causative organism is vital in order to dictate the appropriate antibiotic treatment. In this context, the surgical and interventional radiology team is often asked to perform a diagnostic biopsy. The aim of the present study was to assess whether the sampling location affects the diagnostic yield. Our results suggest that the overall positive diagnostic yield was 35%. When disc material was included in the sample the diagnostic yield significantly improved to 47%. Bone sampling alone had a positive yield of 15%. Age, pre-biopsy CRP, pre-biopsy use of antibiotics did not seem to affect the likelihood of obtaining a positive yield. These results suggests that when performing image guided biopsies for suspected cases of spondylodiscitis the inclusion of disc material is important.

Reflections on the future of telemedicine and virtual spinal clinics in the post COVID-19 era.

•Both patients and surgeons seem to show significant satisfaction with virtual spinal clinics.•Virtual spinal clinics may be an important adjunct to traditional face-to-face clinics.•Limitations in physical examination constitute main concern.•Patient selection is an important factor in deciding who is a suitable candidate for a virtual spinal clinic.•Medicolegal concerns need to be adequately addressed if spinal virtual clinics are to be routinely used.

Direct Comparison Between the Kawase Approach and Retrosigmoid Intradural Suprameatal Corridor to Access the Petroclival Region Using Computed Tomography Quantitative Volumetric Analysis: A Cadaveric Study.

OBJECTIVE: The anterior petrosectomy, also known as the Kawase approach, and the retrosigmoid intradural suprameatal approach (RISA) have both been used to reduce the petrous apex and access the petroclival region. Our goal was to compare the volumes and 3-dimensional shapes of bony resection obtained through each approach while trying to resemble realistic surgical settings. METHODS: Five cadaveric specimens totaling 10 sides were dissected and analyzed. In every specimen, 1 side was used for the Kawase approach while the opposite side was used for the RISA. Petrosectomy volumes were assessed by comparing preoperative and postoperative thin-sliced computed tomography scans. RESULTS: Petrosectomy volumes were significantly larger through the Kawase approach than through the RISA (0.82 ± 0.11 vs. 0.49 ± 0.07 cm3, P < 0.001). In addition, surgical maneuverability and freedom were greater in the Kawase operative variant. Lastly, the morphology of the bony window achieved through each approach was clearly different: trapezoid for the anterior petrosectomy versus elongated ellipsoid for the RISA. CONCLUSIONS: The Kawase approach invariably results in larger volumes of bony removal than the RISA operative variant, and the volume of petrosectomy that is spatially congruent is only partially identical. The Kawase corridor is best suited for middle fossa lesions that extend into the posterior fossa, while the RISA is suitable for pathologies mainly residing in the posterior fossa and extending into the Meckel cave.

A stepwise laboratory manual for the dissection and illustration of limbic and paralimbic structures: lessons learned from the Klingler's technique.

BACKGROUND: Three-dimensional relationships within the limbic and paralimbic areas are often hard to grasp. Relevant anatomical structures exhibit a complicated architecture and connectivity and therefore surgical approaches targeting lesions or functional resections in this area pose a distinct challenge. PURPOSE: To provide an educational, comprehensive, systematic and stepwise manual for the dissection and illustration of major limbic structures since there is a gap in the pertinent literature. Further, we aim to offer a thorough yet simplified roadmap for laboratory and intraoperative dissections. METHODS: Twenty (20) normal adult, formalin-fixed cerebral hemispheres were studied through the fiber dissection technique and under the microscope. Stepwise and in tandem medial to lateral and lateral to medial dissections were performed in all specimens aiming to reveal the morphology and spatial relationships of major limbic and paralimbic areas. RESULTS: Fourteen (14) consecutive, discrete and easily reproducible laboratory anatomical steps are systematically described to reveal the intricate anatomy of the limbic and paralimbic structures and their main connections. CONCLUSION: This study offers for the first time in the pertinent literature a focused, step-by-step laboratory manual for the dissection and illustration of the limbic and paralimbic structures. The overreaching goal is to supplement the novice and experienced anatomist and neurosurgeon with a thorough and systematic reference to facilitate laboratory or intraoperative dissections.

PDGF-R inhibition induces glioblastoma cell differentiation via DUSP1/p38MAPK signalling.

Glioblastoma (GBM) is the most common and fatal primary brain tumour in adults. Considering that resistance to current therapies leads to limited response in patients, new therapeutic options are urgently needed. In recent years, differentiation therapy has been proposed as an alternative for GBM treatment, with the aim of bringing cancer cells into a post-mitotic/differentiated state, ultimately limiting tumour growth. As an integral component of cancer development and regulation of differentiation processes, kinases are potential targets of differentiation therapies. The present study describes how the screening of a panel of kinase inhibitors (KIs) identified PDGF-Rα/ß inhibitor CP-673451 as a potential differentiation agent in GBM. We show that targeting PDGF-Rα/ß with CP-673451 in vitro triggers outgrowth of neurite-like processes in GBM cell lines and GBM stem cells (GSCs), suggesting differentiation into neural-like cells, while reducing proliferation and invasion in 3D hyaluronic acid hydrogels. In addition, we report that treatment with CP-673451 improves the anti-tumour effects of temozolomide in vivo using a subcutaneous xenograft mouse model. RNA sequencing and follow-up proteomic analysis revealed that upregulation of phosphatase DUSP1 and consecutive downregulation of phosphorylated-p38MAPK can underlie the pro-differentiation effect of CP-673451 on GBM cells. Overall, the present study identifies a potential novel therapeutic option that could benefit GBM patients in the future, through differentiation of residual GSCs post-surgery, with the aim to limit recurrence and improve quality of life.

Definition of an Inflammatory Biomarker Signature in Plasma-Derived Extracellular Vesicles of Glioblastoma Patients.

Glioblastoma (GB) is an aggressive type of tumour for which therapeutic options and biomarkers are limited. GB diagnosis mostly relies on symptomatic presentation of the tumour and, in turn, brain imaging and invasive biopsy that can delay its diagnosis. Description of easily accessible and effective biomarkers present in biofluids would thus prove invaluable in GB diagnosis. Extracellular vesicles (EVs) derived from both GB and stromal cells are essential to intercellular crosstalk in the tumour bulk, and circulating EVs have been described as a potential reservoir of GB biomarkers. Therefore, EV-based liquid biopsies have been suggested as a promising tool for GB diagnosis and follow up. To identify GB specific proteins, sEVs were isolated from plasma samples of GB patients as well as healthy volunteers using differential ultracentrifugation, and their content was characterised through mass spectrometry. Our data indicate the presence of an inflammatory biomarker signature comprising members of the complement and regulators of inflammation and coagulation including VWF, FCGBP, C3, PROS1, and SERPINA1. Overall, this study is a step forward in the development of a non-invasive liquid biopsy approach for the identification of valuable biomarkers that could significantly improve GB diagnosis and, consequently, patients' prognosis and quality of life.

Introducing the Posterior Condylar Emissary Vein as an Effective Surgical Landmark for Optimizing the Standard Retrosigmoid Approach: An Anatomo-Imaging Study.

OBJECTIVE: There is a lack of definite anatomical landmarks for the inferior extension of the standard retrosigmoid approach. In this study, we evaluated whether the posterior condylar emissary vein (PCEV) can be used as an intraoperative landmark for optimizing the surgical corridor. METHODS: We performed the standard retrosigmoid approach on 5 formalin-fixed and latex-injected cadaveric specimens and measured the distance between the PCEV near its bony canal and the vertebral artery (VA). In addition, vascular reconstructions of thin-sliced preoperative computed tomography (CT) scans were studied in 40 patients and the relationship between these 2 vessels was evaluated. An illustrative case is also included. RESULTS: The PCEV was consistently identified on both sides of cadaveric specimens and in 87.5% and 82.5% of the left and right sides of the included CT scans, respectively. The average distance between the part of the PCEV near its osseous canal and the VA was measured to be between 8.4 mm and 8.6 mm in the specimens and between 9.2 mm and 9.3 mm in the CT scans. This distance offers a safe and effective plane of dissection during the standard retrosigmoid approach and allows easy access to the foramen magnum. CONCLUSIONS: The PCEV near its bony canal proved to be an easy, straightforward, safe, and effective operative landmark with which the surgeon can extend the soft tissue dissection and bony exposure towards the foramen magnum. This maneuver provides ample access to the cisterna magna for cerebrospinal fluid drainage and increases visibility and surgical maneuverability to the entire cerebellopontine angle.

Effects of brain radiotherapy on cognitive performance in adult low-grade glioma patients: A systematic review.

Grade II gliomas are slow growing tumours that usually affect younger patients. The mainstream treatment modality at present is surgical. The role of radiation therapy in the management of grade II gliomas has been the subject of considerable debate. Radiation therapy has a proven potential to prolong progression free and overall survival in high-risk patients, but may also produce long-term cognitive deficits. Since grade II glioma patients are expected to live several years, retention of cognitive capacity and quality of life is an equally important endpoint as prolonging progression free survival. Our overarching goal is to critically review the available evidence on the possible neuropsychological effects of postoperative radiotherapy in adult grade II glioma patients. We performed a systematic literature search in Medline, Embase and Cochrane databases up to 1st of May 2020 for studies assessing the cognitive effects of radiation therapy on grade II glioma patients. Eleven studies meeting our inclusion criteria provide either negative or contradictory data regarding the cognitive domains affected, while major confounding variables remain incompletely addressed. The available evidence does not adequately support the notion that current radiation therapy protocols independently produce substantial cognitive decline in grade II glioma patients and therefore it would be premature to argue that radiation associated cognitive morbidity outweighs the benefit of prolonged survival. A large prospective study incorporating a full battery of neuropsychological testing, sufficiently long-term follow-up period and tight control of confounders is due to provide high quality data.

'Super-Enrichment' Reveals Dose-Dependent Therapeutic Effects of Environmental Stimulation in a Transgenic Mouse Model of Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is caused by a tandem repeat expansion and involves progressive cognitive decline, psychiatric abnormalities and motor deficits. Disease onset and progression in HD mice can be substantially delayed by a housing environment with enhanced sensorimotor and cognitive stimulation. However, the proposed benefits of environmental enrichment (EE) are always taken in the context of 'deprived' standard housing and investigation is warranted into the graded effects of enrichment. OBJECTIVE: To assess if a higher level of environmental stimulation ('super-enrichment') has additional benefits compared to home-cage EE in HD mice. METHODS: One group of R6/1 transgenic HD mice and wild-type (WT) littermates were home-cage enriched (EE group). A second group also had enriched home cages, but from 6 weeks of age were exposed to a large 'super-enrichment' arena (SuperE group) three times per week. A range of motor tests (open field, rotarod, clasping) were conducted from 8 weeks of age and, at the end of the experiment, grip strength was assessed and post-mortem measures were taken (brain weight, striatal volume, dopamine receptor activation and aggregate density). RESULTS: SuperE improved the reduction of exploration in the open field, ameliorated impaired grip strength in home-cage enriched HD mice and delayed, but did not abolish, the onset of rear-paw clasping compared to EE. SuperE increased brain weight compared to EE in HD mice and reduced striatal dopamine D1 receptor agonist-induced c-fos expression, regardless of genotype. Body weight, rotarod performance, aggregate formation and striatal volume in SuperE groups were no different compared to EE groups. CONCLUSIONS: The beneficial effects of sensorimotor and cognitive stimulation are graded and extend beyond merely compensating for the deprivation of standard home cages in specific motor-related phenotypes in HD. Our findings highlight the importance of environmental enrichment quality and quantity and the translational value of stimulating living conditions as experience-dependent modulators of pathogenesis in HD and other brain disorders.

Extramedullary relapse of multiple myeloma in the thyroid cartilage.

Multiple myeloma involving the thyroid cartilage is a very uncommon disease entity. Only 10 cases have been reported in the international literature to date and as such it constitutes a rare and challenging diagnosis to make. We report the case of a 63-year-old man with a background of malignant melanoma and multiple myeloma both of which were in remission at the time of presentation. The patient presented with hoarseness and a large neck mass that turned out to be an extramedullary deposit of his previously treated multiple myeloma indicating disease relapse. The differential diagnosis of a mass in the thyroid cartilage is discussed. Despite its rarity, this diagnosis should be considered even in patients with no history of multiple myeloma, as it can arise de-novo in the thyroid cartilage (extramedullary plasmacytoma). The importance of the multidisciplinary team (MDT) approach as well as recent advances in treatment are also discussed.

An unusual basal skull injury resulting in CSF leak and a novel method to repair.

We report a case of accidental intracranial insertion of a foreign body through the nose resulting in dural tear and subsequent CSF leak. We also describe the surgical approach to remove it and a new method to seal the dural defect.

Deficits in experience-dependent cortical plasticity and sensory-discrimination learning in presymptomatic Huntington's disease mice.

Huntington's disease (HD) is one of a group of neurodegenerative diseases caused by an expanded trinucleotide (CAG) repeat coding for an extended polyglutamine tract. The disease is inherited in an autosomal dominant manner, with onset of motor, cognitive, and psychiatric symptoms typically occurring in midlife, followed by unremitting progression and eventual death. We report here that motor presymptomatic R6/1 HD mice show a severe impairment of somatosensory-discrimination learning ability in a behavioral task that depends heavily on the barrel cortex. In parallel, there are deficits in barrel-cortex plasticity after a somatosensory whisker-deprivation paradigm. The present study demonstrates deficits in neocortical plasticity correlated with a specific learning impairment involving the same neocortical area, a finding that provides new insight into the cellular basis of early cognitive deficits in HD.

Impaired learning-dependent cortical plasticity in Huntington's disease transgenic mice.

Huntington's disease (HD) is a genetically transmitted neurodegenerative disorder. The neuropathology in HD is a selective neuronal cell death in several brain regions including cortex. Although changes in synaptic plasticity were shown within the hippocampus and striatum of HD transgenic mice, there are no studies considering neocortical synaptic plasticity abnormalities in HD. We examined the impact of the HD transgene upon learning-dependent plasticity of cortical representational maps. The effect of associative learning, in which stimulation of a row of vibrissae was paired with appetitive stimulus, upon functional representations of vibrissae in the barrel cortex, was investigated with 2-deoxyglucose brain mapping in presymptomatic R6/1 HD mice. In wild-type mice, cortical representation of the row of vibrissae involved in the training was expanded, while in HD mice the representation of this row was not expanded. The results suggest that presymptomatic R6/1 HD transgenic mice show deficits in plasticity of primary somatosensory cortex.