Youssef E. Sibih

A hallmark of glioblastoma (GBM) is disease recurrence that occurs in all patients despite resection, radiation, and chemotherapy. A critical challenge in GBM treatment is the management of recurrent disease for which no standard of care exists. Predicting the location of GBM recurrence may improve the efficiency of advanced-stage therapies. We present an artificial intelligence (AI)–based model to predict the recurrence risk of unprocessed surgical tissues at initial resection. AI-informed label-free optical microscopy was used to generate a normalized tumor infiltration value (AI-infiltration) for optical images of samples taken from resection cavity margins. These values, in combination with clinical, radiographic, and molecular variables, were used to build a predictive model of focal recurrence. In a cohort of 80 patients, comprising 367 samples and 133,454 unique images, GBM infiltration was significantly higher in margin samples from recurrent sites ( P = 0.03) compared with those from nonrecurrent sites. A random forest machine learning classifier predicted site recurrence with an average area under the receiver operating characteristic curve of 87% ± 10.0 for the training cohort and 80% (95% confidence interval: 0.64 to 0.97) for the validation cohort. AI-infiltration was the strongest contributor to recurrence prediction, outperforming tumor molecular features. Model performance remained high regardless of tumor location, resulting in random forest model predictions of recurrence at 5 and 10 millimeters of each sample. These findings represent the potential of AI to predict sites of tumor recurrence, thereby improving accessibility to targeted, precision, and multimodal therapy for the highest-risk areas of disease.

Intraoperative hemostasis and dural closure are critical components of neurosurgical procedures, directly affecting operative time, blood loss, neurological outcomes, and the risk of cerebrospinal fluid leak, infection, and reoperation. Over the past 2 decades, there has been rapid expansion in the availability of hemostatic adjuncts, dural substitutes, and liquid sealants. Despite widespread adoption, product selection is frequently guided by surgeon preference and institutional practice rather than a detailed understanding of material composition, mechanism of action, and product-specific limitations. This qualitative review provides a neurosurgery-focused, product-level comparison of commonly used intraoperative hemostatic agents, dural substitutes, and dural sealants, with emphasis on composition, mechanism of action, indications, advantages, limitations, safety considerations, and cost. A comprehensive literature search was conducted using PubMed, Embase, United States Food and Drug Administration device summaries, manufacturer instructions for use, and key clinical trials and observational studies. Products were categorized into 3 groups: intraoperative hemostatic adjuncts, dural substitutes and graft materials, and liquid dural sealants and adhesives. The review encompasses gelatin-based products, oxidized regenerated cellulose, collagen-based agents, flowable gelatin-thrombin matrices, topical thrombin preparations, autologous and nonautologous dural grafts, and fibrin- and polyethylene glycol-based sealants. Selection of these materials should be guided by anatomic considerations, patient-specific factors, and best available evidence. This review serves as a practical reference to support informed intraoperative decision-making in neurosurgical practice.

Prior studies have examined return-to-play (RTP) rates and performance outcomes following meniscus surgery in professional basketball players but have largely focused on earlier eras. With advancements in surgical techniques, rehabilitation, and player management strategies, updated insights into postoperative outcomes are needed. We hypothesized that National Basketball Association (NBA) players would demonstrate a higher return-to-play (RTP) rate than the ~80% reported in 2010, with short-term performance declines but recovery by the second postoperative season. We also evaluated the impact of age, body mass index (BMI), and position on outcomes. NBA players who sustained isolated meniscal tears and underwent surgery between 2010 and 2023 were identified through public databases. Performance metrics—including games played, minutes per game (MPG), player efficiency rating (PER), and distance covered per game—were assessed preoperatively and at one and two years postoperatively. Multivariable linear regression analyzed associations between age, BMI, position, and outcomes. Of 47 eligible players, 43 (90.7%) returned to NBA play. Players missed a median of 17 ± 34 games postoperatively and continued their careers for an average of 4.7 ± 3.4 seasons. The percentage of games played per season significantly declined at one (60.9%, p < 0.001) and two years (64.2%, p < 0.01) postoperatively versus pre-injury (79%), a novel finding. MPG and PER declined at one year (22.3 vs. 26.0, p = 0.02; 14.6 vs. 16.4, p = 0.04) but recovered by year two (23.8 MPG, 15.8 PER; both p > 0.1). Older age correlated with reduced games played, MPG, and PER. BMI and position had no significant impact. NBA players demonstrate high RTP rates after meniscus surgery. While playing time and efficiency recover by year two, reduced availability persists, likely reflecting ongoing workload management strategies.

Diffuse gliomas remodel neuronal circuits with prognostic and therapeutic significance for patients. Electrophysiologic measures of cortical excitability hold promise for monitoring disease progression and evaluating therapeutic responses. The power law exponent (aperiodic slope) reflects the balance between excitatory and inhibitory activity within neuronal networks, a critical aspect of normal brain function often disrupted in neurological conditions. Despite its potential, the significance of the aperiodic slope in glioma-infiltrated tissue and its underlying cellular processes has not been fully investigated. Here, we integrate multi-modal electrophysiological analysis with transcriptomic profiling to analyze the aperiodic slope in both normal and glioma-infiltrated cortex. We determine that glioma infiltration induces a flattening of the aperiodic slope, indicating a shift toward excitation dominance that varies according to tumor subtype and correlates with impairments in semantic naming. Single-nucleus RNA sequencing revealed that cortical regions with flat aperiodic slope exhibit transcriptional programs enriched in glutamatergic signaling, membrane depolarization, and excitatory synaptic transmission. The aperiodic slope responds to pharmacologically induced changes in cortical inhibition during propofol administration, a GABA_A agonist. Our results establish the aperiodic slope as a robust biomarker of glioma-associated excitation-inhibition imbalance, with potential applications in tumor classification and treatment monitoring.

Neuronal-glioma interactions are increasingly recognized as critical in the development and progression of central nervous system tumors. Recent research highlights that gliomas can integrate into neural circuits through various mechanisms, including the synaptogenic factor thrombospondin-1 (TSP-1). This new mechanistic understanding of cancer neuroscience allows for novel insights into target discovery. Critically, therapies that modulate neuron-tumor interactions remain agnostic to other oncogenic changes within tumor cells yet may still target fundamental drivers of tumor growth. In line with these findings and controlling for critical confounding variables, we demonstrate a survival benefit associated with gabapentin (an antagonist of TSP-1) following surgical resection of newly diagnosed glioblastoma. This retrospective, multi-institutional cohort study included 1,072 patients, with a discovery cohort of 693 patients and an additional 379 patients from a separate site for external validation. Furthermore, our findings indicate that gabapentin administration is associated with reduced serum TSP-1 levels, suggesting its potential as a future biomarker.

Gliomas are infiltrative brain tumors that often involve functional tissue. While maximal safe resection is critical for maximizing survival, this is challenged by the difficult intraoperative discrimination between tumor-infiltrated and normal structures. Surgical expertise is essential for identifying safe margins, and while the intraoperative pathological review of frozen tissue is possible, this is a time-consuming task. Advances in intraoperative stimulation mapping have aided surgeons in identifying functional structures and, as such, has become the gold standard for this purpose. However, intraoperative margin assessment lacks a similar consensus. Nonetheless, recent advances in intraoperative imaging techniques and tissue examination methods have demonstrated promise for the accurate and efficient assessment of tumor infiltration and margin delineation within the operating room, respectively. In this review, we describe these innovative technologies that neurosurgeons should be aware of.

A cancer diagnosis is life altering and frequently associated with both acute and long-lasting psychosocial and behavioral distress for patients. The impact of a diffuse glioma diagnosis on mental health is an important aspect of the patient experience with their disease. This needs to be understood by neurosurgeons so these concerns can be appropriately addressed in a timely fashion and integrated into the multidisciplinary care of neuro-oncology patients. The relatively grave prognosis associated with diffuse gliomas, the morbidity associated with treatment, and the constant threat of developing a new neurological deficit all can negatively affect a patient’s mental ability to cope and ultimately manifest in mental health disorders such as anxiety and depression. The objective of this systematic review was to describe the variety of behavioral health disorders patients may experience following a glioma diagnosis and discuss possible treatment options. The PubMed, Web of Science, Embase, and PsycINFO databases were searched through July 1, 2022, using broad search terms, which resulted in 5028 studies that were uploaded to Covidence systematic review software. Duplicates, non–English-language studies, and studies with irrelevant outcomes or incorrect design were removed (n = 3167). A total of 92 articles reporting behavioral health outcomes in brain tumor patients were categorized and extracted for associations with overall mental health, anxiety, depression, distress, stress, pharmacology, interventions, and mental health in caregivers. The authors identified numerous studies reporting the prevalence of mental health disorders and their negative influence in this population. However, there is a paucity of literature on therapeutic options for patients. Given the strong correlation between patient quality of life and mental well-being, there is a considerable need for early recognition and treatment of these behavioral health disorders to optimize everyday functioning for patients.

Gliomas are infiltrative primary brain tumors that often invade functional cortical and subcortical regions, and they mandate individualized brain mapping strategies to avoid postoperative neurological deficits. It is well known that maximal safe resection significantly improves survival, while postoperative deficits minimize the benefits associated with aggressive resections and diminish patients’ quality of life. Although non-invasive imaging tools serve as useful adjuncts, intraoperative stimulation mapping (ISM) is the gold standard for identifying functional cortical and subcortical regions and minimizing morbidity during these challenging resections. Current mapping methods rely on the use of low-frequency and high-frequency stimulation, delivered with monopolar or bipolar probes either directly to the cortical surface or to the subcortical white matter structures. Stimulation effects can be monitored through patient responses during awake mapping procedures and/or with motor-evoked and somatosensory-evoked potentials in patients who are asleep. Depending on the patient’s preoperative status and tumor location and size, neurosurgeons may choose to employ these mapping methods during awake or asleep craniotomies, both of which have their own benefits and challenges. Regardless of which method is used, the goal of intraoperative stimulation is to identify areas of non-functional tissue that can be safely removed to facilitate an approach trajectory to the equator, or center, of the tumor. Recent technological advances have improved ISM’s utility in identifying subcortical structures and minimized the seizure risk associated with cortical stimulation. In this review, we summarize the salient technical aspects of which neurosurgeons should be aware in order to implement intraoperative stimulation mapping effectively and safely during glioma surgery.

The spread of protein aggregates during disease progression is a common theme underlying many neurodegenerative diseases. The microtubule-associated protein tau has a central role in the pathogenesis of several forms of dementia known as tauopathies—including Alzheimer’s disease, frontotemporal dementia and chronic traumatic encephalopathy¹. Progression of these diseases is characterized by the sequential spread and deposition of protein aggregates in a predictable pattern that correlates with clinical severity². This observation and complementary experimental studies^3,4 have suggested that tau can spread in a prion-like manner, by passing to naive cells in which it templates misfolding and aggregation. However, although the propagation of tau has been extensively studied, the underlying cellular mechanisms remain poorly understood. Here we show that the low-density lipoprotein receptor-related protein 1 (LRP1) controls the endocytosis of tau and its subsequent spread. Knockdown of LRP1 significantly reduced tau uptake in H4 neuroglioma cells and in induced pluripotent stem cell-derived neurons. The interaction between tau and LRP1 is mediated by lysine residues in the microtubule-binding repeat region of tau. Furthermore, downregulation of LRP1 in an in vivo mouse model of tau spread was found to effectively reduce the propagation of tau between neurons. Our results identify LRP1 as a key regulator of tau spread in the brain, and therefore a potential target for the treatment of diseases that involve tau spread and aggregation.