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Background: White matter signal abnormalities have been associated with traumatic brain injury (TBI) and repetitive head impacts (RHI) in contact sports (e.g. American football, rugby). However, previous studies of mixed martial arts (MMA) fighters from the Professional Fighters Brain Health Study have not found greater white matter signal abnormalities in fighters versus controls. Objective: This study aims to explore the varying white matter effects of football/rugby and MMA by analyzing how football/rugby history in mixed martial arts fighters may relate to white matter signal abnormalities, helping to further our understanding of sport-specific brain health risks. Methods: Baseline visits for 90 active, professional, male mixed martial arts fighters and 27 unexposed male controls were cross-sectionally analyzed. Wilcoxon and Kruskal–Wallis tests compared demographics and white matter signal abnormalities, and multivariable regression models examined the associations between football/rugby history and white matter signal abnormality burden in fighters, adjusting for age, education, race, fights, MRI scanner, and supratentorial volume. Results: 37/90 fighters had football/rugby history (mean: 4 years; range: 1–12 years). White matter signal abnormalities were significantly greater in fighters with football/rugby history compared to fighters without football/rugby history (Wilcoxon, p = 0.0190). Football/rugby history was significantly associated with white matter signal abnormality burden >75th percentile (OR: 12, CI: 3.3–61, p < 0.001) and >50th percentile (OR: 3.2, CI: 1.2–9.4, p = 0.024) in fighters. Years of football/rugby were also significantly associated with white matter signal abnormalities. Conclusion: Our findings expand on previous literature by demonstrating a significant relationship between white matter signal abnormalities (WMSAs) and football/rugby history but not MMA. Furthermore, our study suggests an added risk for WMSAs in MMA fighters with a history of football/rugby. Future research should further evaluate WMSAs in contact sports, helping to inform athletes, regulatory bodies, and healthcare providers of the potential brain health risks of contact sports. [ABSTRACT FROM AUTHOR]

Background: Boxing exposes fighters to head impacts and potential traumatic brain injury (TBI). Though research has explored the neuropsychiatric consequences of contact sports, there is limited research into Excessive Daytime Sleepiness (EDS) and its relationship to other outcomes, such as impulsiveness and depression. Therefore, this study aimed to describe EDS in retired boxers using the Epworth Sleepiness Scale (ESS) and to examine how boxing and sleepiness relate to impulsiveness and depression symptomatology. Methods: 86 male retired professional boxers from the Professional Fighters Brain Health Study (PFBHS) met the inclusion criteria. Adjusted multivariable models analyzed relationships between professional boxing bouts, EDS (ESS), impulsiveness (Barratt Impulsiveness Scale Version 11 (BIS-11)), and/or depression (Patient Health Questionnaire-9 (PHQ-9)). A causal mediation analysis was performed to assess whether boxing bouts and ESS scores predicted BIS-11 and PHQ-9 scores. Results: Mean age was ∼51 years, fighters averaged ∼36 professional bouts, and ESS mean(SD) was 7.5(5.3). ESS scores were significantly associated with raw BIS-11 (Beta = 1.26, 95%CI = 0.77–1.75, p < 0.001) and ordinal PHQ-9 (OR = 1.20, 95%CI = 1.11–1.31, p < 0.001) scores in adjusted models, and the significant relationship between boxing bouts and BIS-11/PHQ-9 was mediated by ESS. Conclusions: EDS in retired male professional boxers may be strongly associated with other neuropsychiatric sequelae of TBI (impulsiveness and depression). Sleepiness; sleep; boxing; contact sports; impulsiveness; impulsivity; depression; Epworth sleepiness scale box [ABSTRACT FROM AUTHOR]

Simple Summary: Medulloblastoma is the most common malignant brain tumor in the pediatric population. Despite the utilization of aggressive treatment modalities, including surgery, chemotherapy, and radiation therapy, patients with medulloblastoma still have a poor prognosis. Moreover, these modalities are associated with dramatic life-long complications. Hence, this calls for the development of novel therapeutic agents that can more effectively and safely target this tumor and improve the survival and quality of life for patients. The molecular-based classification of medulloblastoma into WNT activated, SHH activated, group 3, and group 4 opened the door for research endeavors that aim to study the specific cellular, molecular, and neurodevelopmental characteristics of each subtype. This review aims to summarize the literature on the different profiles of these subtypes, elaborate on the pharmacologic therapies that have been investigated to target each, and suggest potential combination therapies that can offer superior outcomes. Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with medulloblastoma remains dismal. Additionally, the high doses of radiation and the chemotherapeutic agents used are associated with significant short- and long-term complications and adverse effects, most notably neurocognitive delay. Hence, there is an urgent need for the development and clinical integration of targeted treatment regimens with greater efficacy and superior safety profiles. Since the adoption of the molecular-based classification of medulloblastoma into wingless (WNT) activated, sonic hedgehog (SHH) activated, group 3, and group 4, research efforts have been directed towards unraveling the genetic, epigenetic, transcriptomic, and proteomic profiles of each subtype. This review aims to delineate the progress that has been made in characterizing the neurodevelopmental and molecular features of each medulloblastoma subtype. It further delves into the implications that these characteristics have on the development of subgroup-specific targeted therapeutic agents. Furthermore, it highlights potential future avenues for combining multiple agents or strategies in order to obtain augmented effects and evade the development of treatment resistance in tumors. [ABSTRACT FROM AUTHOR]

BACKGROUND. Rapid diagnosis to facilitate urgent intervention is critical for treatment of acute spinal cord injury (SCI). We hypothesized that a multi-analyte blood biomarker would support point-of-care SCI diagnosis, correlate with injury severity, and predict long-term neurologic outcomes. METHODS. Droplet digital PCR (ddPCR) assays were designed to amplify differentially hypomethylated genomic loci in spinal cord tissue. An optimized ddPCR assay was applied to cell-free DNA (cfDNA) from plasma samples collected from prospectively enrolled acute SCI patients. Targeted proteomic profiling was also performed. Spinal cord--derived cfDNA and plasma proteins were tested for their association with SCI and ability to predict conversion in American Spinal Injury Association (ASIA) score at 6 months. RESULTS. A bespoke ddPCR assay detected spinal cord--derived cfDNA in plasma of 50 patients with acute SCI (AUC: 0.89, 95% CI 0.83-0.95, P < 0.0001). Levels of cfDNA were highest in patients with the most severe injury, i.e., ASIA A, compared with those with ASIA B (P = 0.04), ASIA C (P = 0.009), and ASIA D injuries (P < 0.001). Dimensionality reduction identified 4 candidate proteins (FABP3, REST, IL-6, NF-H) that were integrated with spinal cord--derived cfDNA to derive the Spinal Cord Injury Index (SCII), which has high sensitivity and specificity for SCI diagnosis (AUC: 0.91, 95% CI 0.82-0.99, P < 0.0001), correlates with injury severity (P < 0.0001), and predicts 6-month neurologic improvement (AUC: 0.77, 95% CI 0.61--0.93, P = 0.006). CONCLUSION. The detection of spinal cord--derived cfDNA and plasma protein alterations as part of a multi-analyte blood test can inform SCI diagnosis and prognosis. FUNDING. North American Spine Society Young Investigator Award; Morton Cure Paralysis Fund. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with an extremely poor prognosis. There is a dire need to develop effective therapeutics to overcome the intrinsic and acquired resistance of GBM to current therapies. The process of developing novel anti-neoplastic drugs from bench to bedside can incur significant time and cost implications. Drug repurposing may help overcome that obstacle. A wide range of drugs that are already approved for clinical use for the treatment of other diseases have been found to target GBM-associated signaling pathways and are being repurposed for the treatment of GBM. While many of these drugs are undergoing pre-clinical testing, others are in the clinical trial phase. Since GBM stem cells (GSCs) have been found to be a main source of tumor recurrence after surgery, recent studies have also investigated whether repurposed drugs that target these pathways can be used to counteract tumor recurrence. While several repurposed drugs have shown significant efficacy against GBM cell lines, the blood–brain barrier (BBB) can limit the ability of many of these drugs to reach intratumoral therapeutic concentrations. Localized intracranial delivery may help to achieve therapeutic drug concentration at the site of tumor resection while simultaneously minimizing toxicity and side effects. These strategies can be considered while repurposing drugs for GBM. [ABSTRACT FROM AUTHOR]

Objective: Oligodendrogliomas present challenges in management despite their favorable prognosis. Optimal therapeutic strategies are not well-established. We aimed to characterize current practice patterns and identify areas of discordance in oligodendroglioma management., Methods: A 20-question survey was distributed February-July 2023 to four professional neurosurgery/neuro-oncology societies to assess practices in oligodendroglioma management. The survey collected data on demographics, diagnostic practices, and treatment decisions. Data analysis was performed using chi-square/Fisher's exact tests., Results: Sixty-three physicians responded, representing 12 countries. Diagnostic practices were consistent among respondents. However, variations in management recommendations were observed. Providers were divided between rarely (36.5%), sometimes (25.4%), and often (30.2%) using TMZ as sole chemotherapy for patients with newly diagnosed oligodendroglioma. For patients with subtotal resection of grade 2 oligodendroglioma, 33.3% of providers recommended upfront radiation/chemotherapy, 27.0% recommended observation, and the remaining 39.7% were divided among options including surgery, chemotherapy, and clinical trials. European providers more frequently recommended surgery (33.3% vs 0.0%), whereas radiation/chemotherapy (35.7% vs 26.7%) or observation (31.0% vs 13.3%) were more commonly recommended by US/Canada providers (p=0.009). Providers also disagreed on adjuvant therapy for grade 3 oligodendroglioma. 47.6% recommended radiation/PCV, and 33.3% recommended radiation/TMZ. This decision varied by region, with European providers more frequently recommending radiation/PCV (86.7% vs 33.3%), and US/Canadian providers more frequently recommending radiation/TMZ (40.5% vs 6.7%; p=0.004)., Conclusion: This study underscores the complexity of oligodendroglioma management and the importance of ongoing research to refine therapeutic strategies. Further studies, especially with the introduction of IDH inhibitors in the practice, are warranted to track practice patterns and reassess recommendations., (Copyright © 2025. Published by Elsevier Inc.)

It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain., Competing Interests: Declaration of interests B.V., K.W.K., and N.P. are founders of Thrive Earlier Detection, an Exact Sciences Company. K.W.K., N.P., and C.D. are consultants to Thrive Earlier Detection. B.V., K.W.K., N.P., and C.D. hold equity in Exact Sciences. B.V., K.W.K., and N.P. are founders of and own equity in ManaT Bio. K.W.K. and N.P. are consultants to and own equity in Haystack Oncology, Neophore, and Personal Genome Diagnostics. K.W.K., B.V., and N.P. hold equity in and are consultants to CAGE Pharma. B.V. is a consultant to and holds equity in Catalio Capital Management and may be a consultant to and hold equity in Haystack Oncology. B.V. owns equity in CAGE, Neophore, and Personal Genome Diagnostics. C. Bettegowda is a consultant to Depuy-Synthes, Bionaut Labs, Haystack Oncology, and Galectin Therapeutics. C. Bettegowda is a co-founder of OrisDx. C. Bettegowda and C.D. are co-founders of Belay Diagnostics. The companies named above, as well as other companies, have licensed previously described technologies related to the work described in this paper from Johns Hopkins University. B.V., K.W.K., N.P., C. Bettegowda, and C.D. are inventors on some of these technologies. Licenses to these technologies are or will be associated with equity or royalty payments to the inventors as well as to Johns Hopkins University. Patent applications on the work described in this paper may be filed by Johns Hopkins University. The terms of all these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. M.H. is on the data safety monitoring board for Parexel and Advarra and has received an honorarium from Pfizer. K.S. received an honorarium from Springworks Therapeutics and receives research funding from Springworks Therapeutics. J.N. receives research funding from Merck, AstraZeneca, BMS, Amgen, Novartis, and Roche/Genetech and is a consulting/advisory board for Merck, AstraZeneca, BMS, Amgen, Novartis, Roche/Genetech, Takeda, Pfizer, Daiichi Sankyo, and NGM Biosciences. C.J. is a co-founder with equity interest in Egret Therapeutics and receives research support from Biohaven., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Oligodendrogliomas are a subtype of adult diffuse glioma characterized by their better responsiveness to systemic chemotherapy than other high-grade glial tumors. The World Health Organization (WHO) 2021 brain tumor classification highlighted defining molecular markers, including 1p19q codeletion and IDH mutations which have become key in diagnosing and treating oligodendrogliomas. The management for patients with oligodendrogliomas includes observation or surgical resection potentially followed by radiation and chemotherapy with PCV (Procarbazine, Lomustine, and Vincristine) or Temozolomide. However, most of the available research about oligodendrogliomas includes a mix of histologically and molecularly diagnosed tumors. Even data driving our current management guidelines are based on post-hoc subgroup analyses of the 1p19q codeleted population in landmark prospective trials. Therefore, the optimal treatment paradigm for molecularly defined oligodendrogliomas is incompletely understood. Many questions remain open, such as the optimal timing of radiation and chemotherapy, the response to different chemotherapeutic agents, or what genetic factors influence responsiveness to these agents. Ultimately, oligodendrogliomas are still incurable and new therapies, such as targeting IDH mutations, are necessary. In this opinion piece, we present relevant literature in the field, discuss current challenges, and propose some studies that we think are necessary to answer these critical questions., Competing Interests: CB is a consultant for Depuy-Synthes, Bionaut Labs and Galectin Therapeutics and a co-founder of OrisDx. KR: Research support from Elekta AB, Accuray, Canon; Data Safety Monitoring Board for BioMimetix; Travel expenses from Brainlab, Elekta AB, Accuray, Icotec, RSS; Honorarium for speaking engagement NCCN, Accuray. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rincon-Torroella, Rakovec, Materi, Raj, Vivas-Buitrago, Ferres, Reyes Serpa, Redmond, Holdhoff, Bettegowda and González Sánchez.)

Objective: Internal neurolysis (IN) and intraoperative glycerin rhizotomy (ioGR) are emerging surgical options for patients with trigeminal neuralgia without neurovascular contact. The objective of this study was to compare the neurological outcomes of patients who underwent IN with those of patients who underwent ioGR., Methods: The authors retrospectively reviewed all patients who underwent IN or ioGR for trigeminal neuralgia at our institution. Patient demographic characteristics and immediate postoperative outcomes, as well as long-term neurological outcomes, were compared., Results: Of 1044 patients who underwent open surgical treatment for trigeminal neuralgia, 56 patients underwent IN and 91 underwent ioGR. Of these 147 patients, 37 had no evidence of intraoperative neurovascular conflict. All patients who underwent IN and 96.7% of patients who underwent ioGR had immediate postoperative pain relief. At last follow-up, patients who underwent IN had lower Barrow Neurological Institute (BNI) pain intensity scores (p = 0.05), better BNI facial numbness scores (p < 0.01), and a greater degree of pain improvement (p = 0.05) compared with those who underwent ioGR. Patients who underwent IN also had significantly lower rates of symptomatic pain recurrence (p < 0.01) at last follow-up over an average of 9.5 months., Conclusions: IN appears to provide patients with a greater degree of pain relief, lower rates of facial numbness, and lower rates of pain recurrence compared with ioGR. Future prospective studies will better characterize long-term pain recurrence and outcomes.

Introduction: Treatments for brain cancer have radically evolved in the past decade due to a better understanding of the interplay between the immune system and tumors of the central nervous system (CNS). However, glioblastoma multiforme (GBM) remains the most common and lethal CNS malignancy affecting adults. Areas covered: The authors review the literature on glioblastoma pharmacologic therapies with a focus on trials of combination chemo-/immunotherapies and drug delivery platforms from 2015 to 2021. Expert opinion: Few therapeutic advances in GBM treatment have been made since the Food and Drug Administration (FDA) approval of the BCNU-eluting wafer, Gliadel, in 1996 and oral temozolomide (TMZ) in 2005. Recent advances in our understanding of GBM have promoted a wide assortment of new therapeutic approaches including combination therapy, immunotherapy, vaccines, and Car T-cell therapy along with developments in drug delivery. Given promising preclinical data, these novel pharmacotherapies for the treatment of GBM are currently being evaluated in various stages of clinical trials.