Surgical Treatment of Spinal Meningiomas in the Elderly (≥75 Years): Which Factors Affect the Neurological Outcome? An International Multicentric Study of 72 Cases

(1) Background: With the increasing life expectancy in the Western world, an increasing number of old patients presents with spinal meningioma. Considering the benign nature of these tumors, the functional outcome remains of great importance, since more people reach old age in general conditions of well-being and satisfactory autonomy. (2) Methods: We conducted an international multicenter retrospective study to investigate demographic, clinical and radiological data in a population of elderly patients (≥75 years of age) undergoing surgery for SM from January 2000 to December 2020 in four European referral centers. The aim was to identify prognostic and predictive factors for a good postoperative functional outcome. (3) Results: 72 patients were included in the study. Complete tumor resection (Simpson I or II) was achieved in 67 (95.7%) cases. Intraoperative complications were reported in 7 (9.9%) patients while postoperative complications were found in 12 (16.7%). An excellent general postoperative status (McCormick I and II) was achieved in 65.3%. Overall, surgical resection had a good impact on patients’ functional outcome (86.1% either showing an improvement or maintaining a good preoperative status). Uni- and multivariate analyses found that both age and preoperative modified McCormick independently correlated with relative outcome (coeff = −0.058, p = 0.0251; coeff = 0.597, p < 0.0001) and with postoperative status (coeff = 0.058, p = 0.02507; coeff = 0.402, p = 0.00027), respectively. (4) Conclusions: Age and preoperative modified McCormick were found to be independent prognostic factors. Nevertheless, advanced age (≥75), per se, did not seem to contraindicate surgery, even in those with severe preoperative neurological deficits. The functional results sustain the need for surgical resection of SM in the elderly

Sleep Is Compromised in −12° Head Down Tilt Position

Recent studies are elucidating the interrelation between sleep, cranial perfusion, and cerebrospinal fluid (CSF) circulation. Head down tilt (HDT) as a simulation of microgravity reduces cranial perfusion. Therefore, our aim was to assess whether HDT is affecting sleep (clinicaltrials.gov; identifier NCT 02976168). 11 male subjects were recruited for a cross-over designed study. Each subject participated in two campaigns each comprising 3 days and 2 nights. Intervention started on the second campaign day and consisted of maintenance of horizontal position or −12° HDT for 21 h. Ultrasound measurements were performed before, at the beginning and the end of intervention. Polysomnographic measurements were assessed in the second night which was either spent in horizontal posture or at −12° HDT. Endpoints were sleep efficiency, sleep onset latency, number of sleep state changes and arousals, percentages of N3, REM, light sleep stages and subjective sleep parameters. N3 and REM sleep reduced by 25.6 and 19.1 min, respectively (P = 0.002, g = -0.898; P = 0.035, g = -0.634) during −12° HDT. Light sleep (N1/2) increased by 33.0 min at −12° HDT (P = 0.002, g = 1.078). On a scale from 1 to 9 subjective sleep quality deteriorated by 1.3 points during −12° HDT (P = 0.047, g = -0.968). Ultrasonic measurement of the venous system showed a significant increase of the minimum (P = 0.009, P &lt; 0.001) and maximum (P = 0.004, P = 0.002) cross-sectional area of the internal jugular vein at −12° HDT. The minimum cross-sectional area of the external jugular vein differed significantly between conditions over time (P = 0.001) whereas frontal skin tissue thickness was not significantly different between conditions (P = 0.077, P = 0.811). Data suggests venous congestion at −12° HDT. Since subjects felt comfortable with lying in −12° HDT under our experimental conditions, this posture only moderately deteriorates sleep. Obviously, the human body can almost compensate the several fold effects of gravity in HDT posture like an affected CSF circulation, airway obstruction, unusual patterns of propioception and effects on the cardiovascular system

The impact of translation control of protein synthesis on neuroblastoma and medulloblastoma progression

Neuroblastoma and medulloblastoma, malignant tumors of the nervous system, are the most common childhood solid tumors and leading cause of childhood related cancer deaths. A subset of these tumors, collectively characterized by MYC of MYCN amplification or overexpression, bears dismal prognosis with a ten-year survival rate around 50%. However, the discovery of molecularly informed targeted therapies represents a major challenge in current cancer research, and these are currently unavailable for children affected by neuroblastoma and medulloblastoma. It is sobering that for most children who suffer relapse, there are few if any therapeutic options available, with most patients receiving the same type of therapy that failed in the first place. While MYC-driven oncogenic transformation is known to determine adverse patient outcome, it also induces a high metabolic demand that impairs cell survival under acute nutrient deprivation (ND). We previously reported that eukaryotic Elongation Factor Kinase 2 (eEF2K), the master regulator of mRNA translation elongation, is critical for cell adaptation to ND. We therefore set out to determine if eEF2K is required for the progression of MYC-driven childhood cancer. Our in vitro and in vivo results revealed that MYCN and MYC driven neuroblastoma and medulloblastoma rely on eEF2K to overcome nutrient starvation. We surveyed clinical samples of neuroblastoma and medulloblastoma, and we observed high eEF2K activity to be significantly associated with MYC family members overexpression. Mechanistically, through multiple proteomics experiments coupled with RNAseq, we found that eEF2K regulates the synthesis of several components of the mitochondrial electron transport chain. As a result, eEF2K deficient cells displayed inefficient super complex assembly and oxidative phosphorylation. Overall, our work identifies novel targetable pathways contributing to the progression of MYC driven neuronal tumors. Future studies should investigate the combination of eEF2K inhibition with caloric restriction mimetics, as a targeted therapeutic approach for MYC driven tumors.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat

Pediatric Brain Tumours : Lessons from the Immune Microenvironment

In spite of recent advances in tumour molecular subtyping, pediatric brain tumours (PBTs) remain the leading cause of cancer-related deaths in children. While some PBTs are treatable with favourable outcomes, recurrent and metastatic disease for certain types of PBTs remains challenging and is often fatal. Tumour immunotherapy has emerged as a hopeful avenue for the treatment of childhood tumours, and recent immunotherapy efforts have been directed towards PBTs. This strategy has the potential to combat otherwise incurable PBTs, while minimizing off-target effects and long-term sequelae. As the infiltration and activation states of immune cells, including tumour-infiltrating lymphocytes and tumour-associated macrophages, are key to shaping responses towards immunotherapy, this review explores the immune landscape of the developing brain and discusses the tumour immune microenvironments of common PBTs, with hopes of conferring insights that may inform future treatment design.Medicine, Faculty ofNon UBCPathology and Laboratory Medicine, Department ofReviewedFacultyResearcherPostdoctora

RNA modifications in brain tumorigenesis

RNA modifications are emerging as critical regulators in cancer biology, thanks to their ability to influence gene expression and the predominant protein isoforms expressed during cell proliferation, migration, and other pro-oncogenic properties. The reversibility and dynamic nature of post-transcriptional RNA modifications allow cells to quickly adapt to microenvironmental changes. Recent literature has revealed that the deregulation of RNA modifications can promote a plethora of developmental diseases, including tumorigenesis. In this review, we will focus on four key post-transcriptional RNA modifications which have been identified as contributors to the pathogenesis of brain tumors: m6A, alternative polyadenylation, alternative splicing and adenosine to inosine modifications. In addition to the role of RNA modifications in brain tumor progression, we will also discuss potential opportunities to target these processes to improve the dismal prognosis for brain tumors.Medicine, Faculty ofNon UBCPathology and Laboratory Medicine, Department ofReviewedFacult

Craniocervical fractures management in case of craniocervical pneumatization : case report and review of the literature

Introduction Extensive craniocervical pneumatization (CCP) refers to an abnormal pneumatization extended from the temporal bone into adjacent bone structures, especially the skull base and the craniocervical junction. The etiology remains controversial; however several studies reported a correlation with recurrent Valsalva maneuvers or Eustachian tube dysfunction. Although some cases requiring surgical treatment have been reported, conservative treatment remains the gold standard. The authors aimed to describe a case of CCP, complicated by a spontaneous fracture of a pneumatized left occipital condyle. Furthermore, they reviewed all previously reported cases of fractures in CCP in order to propose a standardized approach to this pathology. Methods A total of 148 studies were retrieved. Of those, 23 studies (including 26 patients in addition to our case) were included in the review. These studies consisted of case reports or small case series (up to 3 patients). Results In 3 patients (11.1%), bone pneumatization involved C0; all remaining patients had both C0 and C1 pneumatization, while in 7 cases (25.9%), an extension to C2 and/or C3 was reported. Radiological follow-up was performed in 20 patients (74.1%), showing in all of the cases either stability (6 patients, 22.2%), improvement, or complete resolution (6 patients, 22.2% vs 8 patients, 29.7%). Two patients underwent surgical intervention. Conclusions This review suggests that fractures secondary to CCP are extremely rare and are associated to a good clinical and radiological outcome with conservative treatment. Ear, nose, and throat (ENT) evaluation is recommended to detect cases who need treatment for a subjacent middle ear disease.</p

Isolated subarachnoid hemorrhage in mild traumatic brain injury: is a repeat CT scan necessary? A single-institution retrospective study

Traumatic brain injury (TBI) with isolated subarachnoid hemorrhage (iSAH) is a common finding in the emergency department. In many centers, a repeat CT scan is routinely performed 24 to72 h following the trauma to rule out further radiological progression. The aim of this study is to assess the clinical utility of the repeat CT scan in clinical practice