Long non-coding RNAs (lncRNAs) are progressively being perceived as prominent molecular agents controlling multiple aspects of neuronal (patho)physiology. Amongst these is the HOX transcript antisense intergenic RNA, often abbreviated as HOTAIR. HOTAIR epigenetically regulates its target genes via its interaction with two different chromatin-modifying agents; histone methyltransferase polycomb-repressive complex 2 and histone demethylase lysine-specific demethylase 1. Parenthetically, HOTAIR elicits trans-acting sponging function against multiple micro-RNA species. Oncological research studies have confirmed the pathogenic functions of HOTAIR in multiple cancer types, such as gliomas and proposed it as a pro-oncological lncRNA. In fact, its expression has been suggested to be a predictor of the severity/grade of gliomas, and as a prognostic biomarker. Moreover, a propound influence of HOTAIR in other aspects of brain heath and disease states is just beginning to be unravelled. The objective of this review is to recapitulate all the relevant data pertaining to the regulatory roles of HOTAIR in neuronal (patho)physiology. To this end, we discuss the pathogenic mechanisms of HOTAIR in multiple neuronal diseases, such as neurodegeneration, traumatic brain injury and neuropsychiatric disorders. Finally, we also summarize the results from the studies incriminating HOTAIR in the pathogeneses of gliomas and other brain cancers. Implications of HOTAIR serving as a suitable therapeutic target in neuropathologies are also discussed.

The association between alcohol intake and the risk of glioma has been widely studied, but these results have yielded conflicting findings. Therefore, we conducted this systematic review and updated meta-analysis to systematically evaluate the association between alcohol intake and the risk of glioma. A systematic literature search of relevant articles published in PubMed, Web of Science, CNKI and Wan fang databases up to December 2021 was conducted. Pooled estimated of relative risk (RR) and 95 % CI were calculated using fixed-effects models. A total of eight articles with three case–control studies involving 2706 glioma cases and 2 189 927 participants were included in this meta-analysis. A reduced risk of glioma was shown for the low–moderate alcohol drinking v. non-drinking (RR = 0·87; 95 % CI (0·78, 0·97); P = 0·014). In addition, there was no evidence of an increased risk of glioma in the heavy alcohol drinking compared with non-drinking (RR = 0·89; 95 % CI (0·67, 1·18); P = 0·404). The findings suggest an inverse association between low–moderate alcohol drinking and the risk of glioma, in the absence, however, of a dose–response relationship. More prospective studies are needed to provide further insight into the association between alcohol drinking and glioma risk.

Traumatic brain injury (TBI) was first proposed as a potential risk factor for developing a glioma in the 1800s, and conditions for establishing a causal relationship between brain injury and gliomas have since been proposed. Given the medical and legal ramifications, the current literature was reviewed to better understand this possible association. Articles that examined the relationship between TBI and glioma formation in adults and were published in English between 1978 and 2022 were reviewed. There were 19 case reports of 25 patients and 16 observational studies. The case reports describe glioma formation at the precise site of prior brain injury in continuity with traumatic scar; the observational studies report conflicting findings, but they largely demonstrate no association. Most of the observational studies are limited by their retrospective nature, but we identified one prospective cohort study which found a positive association. Altogether, we suggest that glioma formation after TBI is a rare occurrence that warrants further study.

Corpus callosum (CC) is the primary fiber system bridging the cerebral hemispheres and is of critical importance for glioma migration which downgrades the prognosis. Here we present the specific pattern of CC restructuring in glioma patients. We probe that the magnetic resonance imaging-based fiber count decrease can be a ready noninvasive indicator of glioma aggressivity and prognosis. We find that to maintain the callosal neural transmission efficiency, the optimum architectural density of white matter fibers remains unchanged, even though there is gross fiber loss. This adaptation occurs by CC’s isotonic restructuration, a protective compensatory behavior for maintaining CC’s optimal functional efficiency despite malignant infiltration.

In this systematic review and dose–response meta-analysis, we aimed to assess whether coffee and tea consumption is related to the risk of glioma. We performed a systematic literature search using PubMed, Embase, Scopus and the EuropePMC from the inception of database up until 1 October 2020. Exposures in the present study were coffee and tea consumption, the main outcome was the incidence of glioma. The present study compares the association between the exposure of coffee and tea with the incidence of glioma, and the results are reported in relative risks (RR). There are 12 unique studies comprising of 1 960 731 participants with 2987 glioma cases. Higher coffee consumption was associated with a statistically non-significant trend towards lower risk of glioma (RR 0·77 (95 % CI 0·55, 1·03), P= 0·11; I2:75·27 %). Meta-regression showed that the association between coffee and glioma was reduced by smoking (P= 0·029). Higher tea consumption was associated with a lower risk of glioma (RR 0·84 (95 % CI 0·71, 0·98), P= 0·030; I2:16·42 %). Sensitivity analysis by removal of case–control studies showed that higher coffee consumption (RR 0·85 (95 % CI 0·72, 1·00), P= 0·046; I2:0 %) and higher tea consumption (RR 0·81 (95 % CI 0·70, 0·93), P= 0·004; I2:0 %, Pnon-linearity = 0·140) were associated with lower risk of glioma. Dose–response meta-analysis showed that every one cup of coffee per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 0·99), P= 0·016, Pnon-linearity = 0·054) and every one cup of tea per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 1·00), P= 0·048). This meta-analysis showed apparent association between coffee and tea intake and risk of glioma.

A 70-year-old man presented to the Emergency Department reporting the acute onset of non-fluent aphasia, hyposthenia, and hemi-anesthesia of the right body. Brain computerized tomography revealed a subcortical hypodense lesion in the middle cerebral artery territory. Neck ultrasounds of internal and external carotid arteries and of the vertebral arteries showed a focal moderate stenosis of the left internal carotid artery due to a soft atheromasic plaque. These findings that were initially consistent with a diagnosis of an ischemic stroke were not confirmed by magnetic resonance (MR). The latter showed an hyperintense lesion on FLAIR and T2-weighted sequences located in the left centrum semiovale, corona radiata, and thalamus, with a well-defined regular rim and a mild compressive effect on the lateral ventricle, with diffusivity restriction but without ADC reduction and with a punctate and serpiginous gadolinium enhancement on T1 sequences (Figure 1). Within the first day of observation, the patient started complaining progressive mental deterioration, in absence of any other possible causes, and a total body CT scan excluded any other organ involvement. Patient was then referred to the neurosurgeon in order to perform a brain biopsy. The neuropathology was compatible with the diagnosis of cerebral lymphomatoid granulomatosis (LG) (Figure 1).

Technological advances in the field of molecular genetics have improved the ability to classify brain tumors into subgroups with distinct clinical features and important therapeutic implications. The World Health Organization’s newest update on classification of gliomas (2016) incorporated isocitrate dehydrogenase 1 and 2 mutations, ATRX loss, 1p/19q codeletion status, and TP53 mutations to allow for improved classification of glioblastomas, low-grade and anaplastic gliomas. This paper reviews current advances in the understanding of diffuse glioma classification and the impact of molecular markers and DNA methylation studies on survival of patients with these tumors. We also discuss whether the classification and grading of diffuse gliomas should be based on histological findings, molecular markers, or DNA methylation subgroups in future iterations of the classification system.

No study is available that has assessed the association of dietary diversity score (DDS) and alternative healthy eating index (AHEI) with glioma. The present study aimed to assess this association in Iranian adults. Overall, 128 pathologically confirmed cases of glioma were enrolled from hospitals and 256 age- and sex-matched controls were recruited from other wards of the hospital between 2009 and 2011. Dietary assessment was done using a validated block-format 123-item semi-quantitative FFQ. Dietary indices including DDS and AHEI-2010 were constructed according to standard methods. After controlling for potential confounders, a significant inverse association was found between DDS and risk of glioma (OR 0·42, 95 % CI 0·19, 0·94). Such finding was also seen when further adjustment was made for BMI; such that participants in the highest quartile of DDS were 56 % less likely to have glioma compared with those in the lowest quartile (OR 0·44, 95 % CI, 0·20, 0·97). In addition, a significant inverse association was found between adherence to AHEI and glioma; such that in the fully adjusted model, participants in the fourth quartile of AHEI had 74 % lower risk of glioma compared with those in the first quartile (OR 0·26, 95 % CI 0·12, 0·56). In conclusion, we found that greater adherence to the healthy, as measured by AHEI, and diverse, as measured by DDS, diets was associated with decreased odds of glioma.

Background: Bevacizumab has been used in recurrent glioblastoma (rGBM) since 2010 in Canada. Given its cost, potential toxicities, and unclear efficacy, further studies are required to better define suitable candidates for therapy. Methods: A single-center retrospective review of patients started on bevacizumab for rGBM from 2012 to 2015 was performed. Patient demographics, tumor characteristics, treatment regimen, and dates of clinical progression and death were collected. Overall survival (OS) and progression-free survival (PFS) were used as clinical outcomes and estimates. Radiological response was assessed using modified Response Assessment in Neuro-Oncology criteria. Results: A total of 80 patients were included. There were 67 reported deaths, and the median OS was 9.2 months (95% confidence interval [CI95%]=7.0-10.1 months), with a 12-month OS of 31% (CI95%=21.9-43.5%). Some 79 patients were included for analysis of clinical progression, among whom 61 had documented clinical progression. The median clinical PFS was 4.6 months (CI95%=3.8-6.4 months), and the 6-month clinical PFS was 39% (CI95%=29.0-52.9%). Addition of chemotherapy did not improve clinical outcomes. A total of 68 patients were included for radiological progression analysis, with 58 radiological progressions. The median radiological PFS was 5.8 months (CI95%=4.2-6.7 months), and the 6-month radiological PFS was 46% (CI95%=35.6-60.0%). Conclusions: This is the first reported Canadian experience with bevacizumab for rGBM. Our clinical outcomes are consistent with published data from multicenter phase II and III trials on bevacizumab in rGBM. More research is required to determine which subtype(s) of patients with rGBM could benefit from bevacizumab upon recurrence.

Glioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival time of <24 months. This figure remains constant, despite significant progress in medical research and treatment. The lack of an efficient anti-tumor immune response and the micro-invasive nature of the glioma malignant cells have been explained by a multitude of immune-suppressive mechanisms, proven in different models. These immune-resistant capabilities of the tumor result in a complex interplay this tumor shares with the immune system. We present a short review on the immunology of GBM, discussing the different unique pathological and molecular features of GBM, current treatment modalities, the principles of cancer immunotherapy and the link between GBM and melanoma. Current knowledge on immunological features of GBM, as well as immunotherapy past and current clinical trials, is discussed in an attempt to broadly present the complex and formidable challenges posed by GBM.

Data on the association of adherence to the Dietary Approaches to Stop Hypertension (DASH)-style and glioma are scarce. We aimed to examine the association between adherence to the DASH-style diet and glioma in Iranian adults. In this study, 128 pathologically confirmed cases of glioma were recruited from hospitals and 256 age- and sex-matched controls were enrolled from other wards of the hospital. Dietary intakes were assessed using a 126-item validated FFQ. Adherence to the DASH-style diet was followed considering the healthy and non-healthy foods emphasised in the DASH dietary pattern. After controlling for potential confounders, individuals with the greatest adherence to the DASH diet were 72 % less likely to have glioma compared with those with the lowest adherence (OR 0·28; 95 % CI 0·13, 0·57). Individuals with the highest consumption of fruits had lower odds for having glioma compared with those with the lowest intake (OR 0·31; 95 % CI 0·14, 0·68). A protective association was also observed between consumption of legumes and nuts and risk of glioma (OR 0·23; 95 % CI 0·10, 0·53). We found a significant positive association between red and processed meat (OR 2·60; 95 % CI 1·16, 5·81) and salt intakes (OR 2·87; 95 % CI 1·30, 6·34) and risk of glioma, after taking all potential confounders into account. Adherence to the DASH-style dietary pattern was inversely associated with glioma. In addition, some components of the DASH diet, including red meats and salt intakes, were positively associated with glioma. Consumption of nuts and legumes as well as fruits was inversely associated with glioma. Prospective cohort studies are required to confirm our findings.