CellKine clinical trial: first report from a phase 1 trial of allogeneic bone marrow-derived mesenchymal stem cells in subjects with painful lumbar facet joint arthropathy.

Background: Lumbar facet joint arthropathy (LFJA) is a major cause of low back pain (LBP), with current treatments offering limited long-term benefits. Bone marrow-derived mesenchymal stem cells (BM-MSCs) show promise due to their immunomodulatory and trophic effects, potentially addressing underlying degenerative processes in LFJA. Objectives: This initial report describes the outcomes of the first treated patient in an ongoing mutidisciplinary phase 1 clinical trial evaluating the safety and feasibility of intra-articular allogeneic BM-MSCs for painful LFJA. Methods: Following enrollment in our IRB-approved protocol, symptomatic LFJA was confirmed through double blocks on L4 and L5 medial branches. Two 1-mL syringes, each containing 10 million BM-MSCs, were prepared in the cGMP facility and administered bilaterally to the patient's L4-L5 lumbar facet joints. The patient underwent standardized follow-ups, including clinical examinations and functional and imaging assessments for 2 years, utilizing patient-reported outcomes measurement information system-computer adaptive tests (PROMIS CATs), visual analogue scale, Oswestry disability index, work functional status and opioid pain medication use, and MR imaging Fenton-Czervionke score. Results: The patient tolerated the procedure well, with no drug-related adverse events during the study period. Pain, spine function, and work functional status improved at multiple follow-ups. This patient also reported improvements in mental and social health, along with a notable improvement in the grade of facet synovitis observed at the one-year follow-up MRI evaluation. Conclusions: This case report suggests the safety and feasibility of administering intra-articular allogeneic BM-MSCs, offering therapeutic benefits for pain management and functional activities.

Correlating SPECT-CT activity in lumbar facet joints with response to lumbar medial branch and L5 dorsal ramus blocks.

Introduction: Lumbar facet arthritis is a significant source of back pain and impaired function that is amenable to treatment with medial branch radiofrequency neurotomy (RFN). Identifying appropriate patients for this treatment requires integration of information from the history, physical exam, and diagnostic imaging, but the current diagnostic standard for facet-mediated pain is positive comparative medial branch blocks (MBBs). Lumbar SPECT-CT has recently been evaluated as a potential predictor of positive MBBs with mixed results. The purpose of this retrospective analysis was to determine if the level of concordance between SPECT-CT uptake and facet joints targeted with MBB was associated with a positive block. Methods: A retrospective review was performed to identify all patients undergoing lumbar MBB within 12 months after having a lumbar SPECT-CT. Each procedure was classified into one of four categories based on the level of concordance between facet joints demonstrating increased 99mTc uptake on SPECT-CT and those being blocked: 1) Complete Concordance (all joints demonstrating increased uptake were blocked and no additional joints blocked); 2) Partial Concordance (all joints demonstrating increased uptake were blocked, with at least one joint not demonstrating increased uptake blocked); 3) Partial Discordance (at least one but not all joints demonstrating increased uptake were blocked); 4) Complete Discordance (all blocks performed at joints not demonstrating increased uptake). Statistical analysis was performed to determine if the level of concordance between increased uptake on SPECT-CT and joints undergoing MBB was associated with a positive block using cutoffs of 50 % and 80 % pain relief. Results: A total of 180 procedures were analyzed (23 % Complete Concordance, 22 % Partial Concordance, 31 % Partial Discordance, 24 % Complete Discordance) and all groups demonstrated improvement in pain Numeric Rating Scale (NRS) scores. There was no significant association between level of concordance and having a positive block using thresholds of 50 % pain relief, χ 2(3, N = 180) = 4.880, p = .181; or 80 % pain relief, χ 2(3, N = 180) = 1.272, p = .736. Conclusion: SPECT-CT findings do not accurately predict positive lumbar MBB but may provide valuable information that can be considered with other factors when deciding which joints to treat.

Correlating SPECT-CT activity in cervical facet joints with positive response to cervical medial branch blocks.

Introduction: Cervical facet arthritis is a significant source of neck pain and impaired function that is amenable to treatment with medial branch radiofrequency neurotomy (RFN). Identifying appropriate patients for this treatment requires integration of information from the history, physical exam and diagnostic imaging, but the current diagnostic standard for facet-mediated pain is positive comparative medial branch blockade (MBB). SPECT-CT has recently been evaluated as a potential predictor of positive medial branch blocks with mixed results. The purpose of this retrospective analysis was to determine if a relationship exists between increased uptake on SPECT-CT of a given cervical facet joint and a positive MBB. Methods: A retrospective review was performed to identify all patients undergoing cervical MBB within 12 months after having a cervical SPECT-CT. Each procedure was categorized as either Concordant (all facet joints demonstrating increased 99mTc uptake on SPECT-CT were blocked) or Discordant (at least one facet joint demonstrating increased 99mTc uptake on SPECT-CT was not blocked or block was performed in a patient that had no increased uptake on SPECT-CT). Statistical analysis was performed to determine if concordance between facet joints demonstrating increased uptake on SPECT-CT and those undergoing MBB was associated with a positive block using cutoffs of 50% and 80% pain relief. Results: A total of 43 procedures were analyzed (25% Concordant, 75% Discordant) and both groups demonstrated improvement in pain Numeric Rating Scale (NRS) scores. No significant association between concordance and positive MBB was identified at thresholds of 50% (p = .481) and 80% (p = 1.000) pain relief. Conclusion: SPECT-CT findings do not accurately predict positive cervical MBB but may provide valuable information that can be considered with other factors when deciding which joints to treat.

Cell-specific cross-talk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone.

Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to the lateral ventricles (LVs) is more aggressive, potentially because of subventricular zone contact. Despite this, cross-talk between GBM and neural stem/progenitor cells (NSC/NPCs) is not well understood. Using cell-specific proteomics, we show that LV-proximal GBM prevents neuronal maturation of NSCs through induction of senescence. In addition, GBM brain tumor-initiating cells (BTICs) increase expression of cathepsin B (CTSB) upon interaction with NPCs. Lentiviral knockdown and recombinant protein experiments reveal that both cell-intrinsic and soluble CTSB promote malignancy-associated phenotypes in BTICs. Soluble CTSB stalls neuronal maturation in NPCs while promoting senescence, providing a link between LV-tumor proximity and neurogenesis disruption. Last, we show LV-proximal CTSB up-regulation in patients, showing the relevance of this cross-talk in human GBM biology. These results demonstrate the value of proteomic analysis in tumor microenvironment research and provide direction for new therapeutic strategies in GBM.

Effects of PreOperative radiotherapy in a preclinical glioblastoma model: a paradigm-shift approach.

PURPOSE: PreOperative radiotherapy (RT) is commonly used in the treatment of brain metastasis and different cancer types but has never been used in primary glioblastoma (GBM). Here, we aim to establish, describe, and validate the use of PreOperative RT for the treatment of GBM in a preclinical model. METHODS: Rat brains were locally irradiated with 30-Gy, hypofractionated in five doses 2 weeks before or after the resection of intracranial GBM. Kaplan-Meier analysis determined survival. Hematoxylin-eosin staining was performed, and nuclei size and p21 senescence marker were measured in both resected and recurrent rodent tumors. Immunohistochemistry assessed microglia/macrophage markers, and RNAseq analyzed gene expression changes in recurrent tumors. Akoya Multiplex Staining on two human patients from our ongoing Phase I/IIa trial served as proof of principle. RESULTS: PreOperative RT group median survival was significantly higher than PostOperative RT (p < 0.05). Radiation enlarged cytoplasm and nuclei in PreOperative RT resected tumors (p < 0.001) and induced senescence in PostOperative RT recurrent tumors (p < 0.05). Gene Set Enrichment Analysis (GSEA) suggested a more proliferative profile in PreOperative RT group. PreOperative RT showed lower macrophage/microglia recruitment in recurrent tumors (p < 0.01) compared to PostOperative RT. Akoya Multiplex results indicated TGF-ß accumulation in the cytoplasm of TAMs and CD4 + lymphocyte predominance in PostOperative group. CONCLUSIONS: This is the first preclinical study showing feasibility and longer overall survival using neoadjuvant radiotherapy before GBM resection in a mammalian model. This suggests strong superiority for new clinical radiation strategies. Further studies and trials are required to confirm our results.

Implementation of a Standardized Interdisciplinary Perioperative Protocol for Patients Undergoing Transsphenoidal Surgery: Impact on Patient Outcomes.

INTRODUCTION: Advances in endoscopic endonasal transsphenoidal surgery have led to improved postoperative outcomes after pituitary adenoma resection, including reduced length of stay, complications and readmission rates, without compromising safety and satisfaction. METHODS: Our team implemented a perioperative protocol in January 2021 for patients undergoing endoscopic, transsphenoidal pituitary surgery. This study compares preoperative characteristics and postoperative outcomes in 279 patients between 2016 and 2022 (128 preprotocol and 151 postprotocol). Our protocol includes interdisciplinary preoperative evaluations, unified communication, cortisol thresholds for postoperative glucocorticoid replacement, and fluid restriction to prevent delayed hyponatremia. RESULTS: Median age was 54 ± 17 years with 50.8% female patients. There were 229 (82.1%) macroadenomas (>1 cm) and 50 (17.9%) microadenomas/cysts (<1 cm). Mean diameter was 18 (transverse), 18 (craniocaudal), 16 (anteroposterior) mm. Tumor types included 125 (44.8%) gonadotroph, 46 (16.4%) adrenocorticotroph, 40 (14.3%) lactotroph, 26 (9.3%) Rathke cysts, 19 (6.8%) somatotroph, 13 (4.6%) nondiagnostic, 3 (1%) somatotroph-lactotroph, 3 (1%) mammosomatotroph, 2 (0.71%) null cell, and 2 (0.7%) thyrotroph adenomas. Postprotocol, 74.2% of patients were discharged on postoperative day 1 compared with 46.1% preprotocol (P < 0.0001). Transient arginine vasopressin deficiency decreased from 10.4% (preprotocol) to 4.6% postprotocol (P = 0.101). Hyponatremia occurred in 13.3% pre-protocol and 4.6% postprotocol. Emergency department visits dropped from 9.4% to 3.9%, and readmissions decreased from 7.8% to 2.6%. Persistent arginine vasopressin deficiency affected 2.3% preprotocol and 1.3% postprotocol patients. Cerebrospinal fluid leaks occurred in 8.5% preprotocol and 7.3% postprotocol. CONCLUSIONS: Implementing an interdisciplinary, perioperative protocol for transsphenoidal endoscopic pituitary surgery improves length of stay while minimizing readmissions and surgery-related complications.

Awake Robotic Minimally Invasive Transforaminal Lumbar Interbody Fusion Under Spinal Anesthesia: A Prospective Study with 1-Year Follow-up.

BACKGROUND: We describe our protocol and outcomes of awake robotic minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under spinal anesthesia. METHODS: We conducted a prospective study of 10 consecutive patients undergoing awake robotic single-level MIS-TLIF with the Mazor X robot. We prospectively collected patient-reported outcomes (back and leg pain visual analog scale and Oswestry Disability Index) preoperatively at 1-month and 1-year follow-ups and assessed fusion and screw placement accuracy with a 1-year computed tomography (CT) scan. RESULTS: Median age was 61 years (interquartile range [IQR] = 57.7-66). Median body mass index was 27 kg/m2. No intraoperative complications were reported. Most (9/10) patients were discharged home, and 50% discharged on the day of surgery. Median length of stay was 16.5 hours (IQR = 5-35.5). Median follow-up was 12.5 months (IQR = 12-13.5), with 9 patients having at least 12-month follow-up, with CT scans documenting good screw placement (Gertzbein-Robbins grade A) and solid bony fusion. Median preoperative back pain visual analog scale score was 7.8 (IQR = 6.9-8) versus 1.5 (IQR = 0-3.2) at 1-month post operation, P < 0.01, and 0 (IQR = 0-1) at 1-year follow-up, P < 0.01; median preoperative leg pain 8 (IQR = 7.4-8) versus 0 (IQR = 0-1.2) at 1-month post operation, P < 0.01, and 0 (IQR = 0-2) at 1-year follow-up, P < 0.01; median preoperative Oswestry Disability Index 47.5 (IQR = 27.8-57.5) versus 4 (IQR = 0-16) at 1-month postoperation, P < 0.01, and 0 (IQR = 0-7) at 1-year follow-up, P < 0.01. Median preoperative disk height of the index level was 8 mm (IQR = 2.4-9.5) versus 11.4 mm (IQR = 9.2-11.2) postoperatively,P < 0.01. Median preoperative lordosis of the index level was 5 degrees (IQR = 3.4-8.5) versus 10.1 degrees (7.3-12.2) postoperatively, P < 0.01. CONCLUSIONS: Our study showed significant improvement in patient-reported outcomes at 1-month and 1-year follow-ups after awake robotic MIS-TLIF, as well as solid bony fusion on CT scans.

Secretome from iPSC-derived MSCs exerts proangiogenic and immunosuppressive effects to alleviate radiation-induced vascular endothelial cell damage.

BACKGROUND: Radiation therapy is the standard of care for central nervous system tumours. Despite the success of radiation therapy in reducing tumour mass, irradiation (IR)-induced vasculopathies and neuroinflammation contribute to late-delayed complications, neurodegeneration, and premature ageing in long-term cancer survivors. Mesenchymal stromal cells (MSCs) are adult stem cells that facilitate tissue integrity, homeostasis, and repair. Here, we investigated the potential of the iPSC-derived MSC (iMSC) secretome in immunomodulation and vasculature repair in response to radiation injury utilizing human cell lines. METHODS: We generated iPSC-derived iMSC lines and evaluated the potential of their conditioned media (iMSC CM) to treat IR-induced injuries in human monocytes (THP1) and brain vascular endothelial cells (hCMEC/D3). We further assessed factors in the iMSC secretome, their modulation, and the molecular pathways they elicit. RESULTS: Increasing doses of IR disturbed endothelial tube and spheroid formation in hCMEC/D3. When IR-injured hCMEC/D3 (IR ≤ 5 Gy) were treated with iMSC CM, endothelial cell viability, adherence, spheroid compactness, and proangiogenic sprout formation were significantly ameliorated, and IR-induced ROS levels were reduced. iMSC CM augmented tube formation in cocultures of hCMEC/D3 and iMSCs. Consistently, iMSC CM facilitated angiogenesis in a zebrafish model in vivo. Furthermore, iMSC CM suppressed IR-induced NFκB activation, TNF-α release, and ROS production in THP1 cells. Additionally, iMSC CM diminished NF-kB activation in THP1 cells cocultured with irradiated hCMEC/D3, iMSCs, or HMC3 microglial lines. The cytokine array revealed that iMSC CM contains the proangiogenic and immunosuppressive factors MCP1/CCL2, IL6, IL8/CXCL8, ANG (Angiogenin), GROα/CXCL1, and RANTES/CCL5. Common promoter regulatory elements were enriched in TF-binding motifs such as androgen receptor (ANDR) and GATA2. hCMEC/D3 phosphokinome profiling revealed increased expression of pro-survival factors, the PI3K/AKT/mTOR modulator PRAS40 and ß-catenin in response to CM. The transcriptome analysis revealed increased expression of GATA2 in iMSCs and the enrichment of pathways involved in RNA metabolism, translation, mitochondrial respiration, DNA damage repair, and neurodevelopment. CONCLUSIONS: The iMSC secretome is a comodulated composite of proangiogenic and immunosuppressive factors that has the potential to alleviate radiation-induced vascular endothelial cell damage and immune activation.

International Hackathon as a Tool to Augment Education, Collaboration, and Innovation in Global Neurosurgery.

BACKGROUND AND OBJECTIVES: Health care providers' exposure to global surgical disparities is limited in current nursing and/or medical school curricula. For instance, global health is often associated with infectious diseases or maternal health without acknowledging the growing need for surgical care in low- and middle-income countries (LMICs). We propose an international virtual hackathon based on neurosurgical patient cases in under-resourced settings as an educational tool to bring awareness to global surgical disparities and develop relationships among trainees in different countries. METHODS: Participants were recruited through email listservs, a social media campaign, and prize offerings. A 3-day virtual hackathon event was administered, which included workshops, mentorship, keynote panels, and pitch presentations to judges. Participants were presented with real patient cases and directed to solve a barrier to their care. Surveys assessed participants' backgrounds and event experience. The hackathon was executed through Zoom at Harvard Innovation Lab in Boston, MA, on March 25 to 27, 2022. Participants included medical students, with additional participants from business, engineering, or current health care workers. RESULTS: Three hundred seven applications were submitted for 100 spots. Participants included medical students, physicians, nurses, engineers, entrepreneurs, and undergraduates representing 25 countries and 82 cities. Fifty-one participants previously met a neurosurgeon, while 39 previously met a global health expert, with no difference between LMIC and high-income countries' respondents. Teams spent an average of 2.75 hours working with mentors, and 88% of postevent respondents said the event was "very" or "extremely conducive" to networking. Projects fell into 4 categories: access, language barriers, education and training, and resources. The winning team, which was interdisciplinary and international, developed an application that analyzes patient anatomy while performing physical therapy to facilitate remote care and clinical decision-making. CONCLUSION: An international virtual hackathon can be an educational tool to increase innovative ideas to address surgical disparities in LMICs and establish early collaborative relationships with medical trainees from different countries.

Assessment of High-fidelity Anatomical Models for Performing Pterional Approach: A Practical Clinic in American Association of Neurological Surgeons Meeting 2024.

BACKGROUND: Over the last decade, simulation models have been increasingly applied as an adjunct for surgical training in neurosurgery. We aim through a practical course at a national neurosurgical conference to evaluate 3D non-cadaveric simulation models along with augmented reality for learning and practicing the pterional craniotomy approach among a wide variety of participants including medical students, neurosurgery residents, and attending neurosurgeons. METHODS: Our course was conducted during an international neurosurgery meeting with 93 participants but the course surveys (pre- and post-course) were completed by 42 participants. RESULTS: Most participants were medical students (31; 73.8%). Participants with no experience (the majority) in cadaver lab dissections, craniotomy as first operator, and as second operator represented 12 (27.9%), 29 (69%), and 22 (52.4%), respectively. Participants with moderate experience in cadaver lab dissections were 23 (53.5%). Post-course survey respondents noted positive feedback in most items queried including enhancement of familiarity and acquiring skills, confidence with neurosurgery instruments, confidence with microscope, part of standard training, traditional training, and lifelong training. CONCLUSIONS: Simulation model combining augmented reality with physical simulation for hybrid experience can be a promising and valuable tool especially for medical students or early career neurosurgical residents.

Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.

Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes. Twenty-four Shank3-mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete Shank3 transcript structure. We apply an integrative approach combining cDNA-capture and long-read sequencing to profile the SHANK3 transcriptome in humans and mice. We unexpectedly discover an extremely complex SHANK3 transcriptome. Specific SHANK3 transcripts are altered in Shank3-mutant mice and postmortem brain tissues from individuals with autism spectrum disorder. The enhanced SHANK3 transcriptome significantly improves the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest that both deterministic and stochastic transcription of the genome is associated with SHANK family genes.

A Wireless Battery-Free Implant With Optical Telemetry for In Vivo Cortical Stimulation.

We present a 100 µm-thick, wireless, and battery-free implant for brain stimulation through a U.S. Food and Drug Administration-approved collagen dura substitute without contact with the brain's surface, while providing visible-light spectrum telemetry to track the onset of stimulation. The device is fabricated on a 16 × 6.67 mm2 biocompatible parylene/PDMS substrate and is encapsulated with a 2 µm-thick transparent parylene layer that enables the relay of the LED brightness. The in vivo rodent testing confirmed the implant's ability to trigger motor response while generating observable brightness through the skin. The results reveal the prospect of wireless stimulation with enhanced safety by eliminating contact between the implant and the brain, with optical telemetry for facilitated tracking.

Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry.

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.

Transcriptional Determinism and Stochasticity Contribute to the Complexity of Autism Associated SHANK Family Genes.

Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes. Twenty-four Shank3 mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete Shank3 transcript structure. We applied an integrative approach combining cDNA-capture and long-read sequencing to profile the SHANK3 transcriptome in human and mice. We unexpectedly discovered an extremely complex SHANK3 transcriptome. Specific SHANK3 transcripts were altered in Shank3 mutant mice and postmortem brains tissues from individuals with ASD. The enhanced SHANK3 transcriptome significantly improved the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest the stochastic transcription of genome associated with SHANK family genes.

Alfred Washington Adson: Perspectives on Intracranial Neurosurgery and the Responsibilities of the Neurosurgeon.

In a period when the budding field of neurosurgery was believed to have little promise, Dr Alfred Washington Adson founded and led the first neurosurgical department at Mayo Clinic. He was not without reservations-surgical intervention for neurological conditions was rarely pursued because of poor outcomes and high complication rates, and Dr Adson acknowledged his early concerns about the future of neurosurgery in his memoirs. However, his education, mentorship, his training, and his first neurosurgical cases helped to shape the impact he ultimately had on the field and his legacy as a neurosurgeon. Dr Adson trained with several renowned Mayo general surgeons, notably his mentor Dr Emil Beckman, whose desire for operative precision shaped Dr Adson's drive to develop his own skills as a surgeon. Two years into his residency, he became the youngest staff surgeon and was tasked with managing the neurosurgical cases at Mayo. The five neurosurgical cases overseen by Dr Adson in the next year illuminated the opportunity for neurosurgery to drastically improve the lives of patients. Dr Adson, given the option of continuing as either a general surgeon or a neurosurgeon, ultimately chose to pursue neurosurgery. This article seeks to provide a historical perspective on the neurosurgeon Dr Alfred Washington Adson using primary and secondary accounts from the Mayo archives, highlighting his contributions to the early understanding of intracranial pathology and how his early experiences as a trainee developed into a personal passion for self-improvement, education, and advocacy for health care in America.

Preoperative Risk Assessment Before Elective Craniotomy: Are Aspirin, Arrhythmias, Deep Venous Thromboses, and Hyperglycemia Contraindications to Surgery?

OBJECTIVE: Perioperative risk assessment and stratification before craniotomy is necessary to identify and optimize modifiable risk factors. Due to the high costs of diagnostic testing and concerns for delaying surgery, some have questioned whether and when surgery delays are warranted and supported by the current body of literature. The objective of this scoping review was to evaluate the available evidence on the prognostic value of preoperative risk assessment before anesthesia for elective craniotomy. METHODS: In this scoping review, we reviewed 156 papers that assess preoperative risk assessment before elective craniotomy, of which 27 papers were included in the final analysis. RESULTS: There is little high-quality evidence to suggest significant risk reduction when 4 common preexisting abnormalities are present: preoperative chronic aspirin therapy, cardiac arrhythmias, deep vein thrombosis, or hyperglycemia. CONCLUSIONS: The risk of delaying craniotomy should ultimately be weighed against the perceived risks associated the patient's comorbid conditions and should be considered on an individualized basis.

Spontaneous rhinorrhea and idiopathic intracranial hypertension: a complex and challenging association.

INTRODUCTION: Spontaneous CSF leak is a known complication of idiopathic intracranial hypertension (IIH). Patients with CSF rhinorrhea present a unique challenge within the IIH population, as the occurrence of a leak can mask the typical IIH symptoms and signs, complicating the diagnosis. Treatment of leaks in this population can also be challenging, with the risk of rhinorrhea recurrence if intracranial hypertension is not adequately treated. OBJECTIVE: The aim of this narrative review was to examine current literature on the association between spontaneous CSF rhinorrhea leaks and IIH, focusing on key clinical features, diagnostic approaches, management strategies, and outcomes. MATERIAL AND METHODS: A literature search was executed using the PubMed and Scopus databases. The search was confined to articles published between January 1985 and August 2023; extracted data was then analysed to form the foundation of the narrative review. RESULTS: This search yielded 26 articles, comprising 943 patients. Average age was 46.8 ± 6.5 years, and average body mass index was 35.8 ± 4.8. Most of the patients were female (74.33%). Presenting symptoms were rhinorrhea, headaches and meningitis. The most common imaging findings were empty sella and encephalocele. The standard treatment approach was endoscopic endonasal approach for correction of CSF rhinorrhea leak, and shunt placement was also performed in 128 (13%) patients. Recurrences were observed in 10% of cases. CONCLUSIONS: The complex relationship between spontaneous CSF leaks and IIH is a challenge that benefits from multidisciplinary evaluation and management for successful treatment. Treatments such as endoscopic repair, acetazolamide, and VP/ /LP shunts reduce complications and recurrence. Personalised plans addressing elevated intracranial pressure are crucial for successful outcomes.

EZH2 Inhibition Sensitizes IDH1R132H-Mutant Gliomas to Histone Deacetylase Inhibitor.

Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation is an important diagnostic tool for tumor diagnosis and prognosis; however, its role in glioma development, and its impact on response to therapy, is not fully understood. We developed a murine model of proneural IDH1R132H-mutated glioma that shows elevated production of 2-hydroxyglutarate (2-HG) and increased trimethylation of lysine residue K27 on histone H3 (H3K27me3) compared to IDH1 wild-type tumors. We found that using Tazemetostat to inhibit the methyltransferase for H3K27, Enhancer of Zeste 2 (EZH2), reduced H3K27me3 levels and increased acetylation on H3K27. We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.

Radiologic Classification of Hippocampal Sclerosis in Epilepsy.

Temporal lobe epilepsy is a common form of epilepsy that is often associated with hippocampal sclerosis (HS). Although HS is commonly considered a binary assessment in radiologic evaluation, it is known that histopathologic changes occur in distinct clusters. Some subtypes of HS only affect certain subfields, resulting in minimal changes to the overall volume of the hippocampus. This is likely a major reason why whole hippocampal volumetrics have underperformed versus expert readers in the diagnosis of HS. With recent advancements in MRI technology, it is now possible to characterize the substructure of the hippocampus more accurately. However, this is not consistently addressed in radiographic evaluations. The histologic subtype of HS is critical for prognosis and treatment decision-making, necessitating improved radiologic classification of HS. The International League Against Epilepsy (ILAE) has issued a consensus classification scheme for subtyping HS histopathologic changes. This review aims to explore how the ILAE subtypes of HS correlate with radiographic findings, introduce a grading system that integrates radiologic and pathologic reporting in HS, and outline an approach to detecting HS subtypes by using MRI. This framework will not only benefit current clinical evaluations, but also enhance future studies involving high-resolution MRI in temporal lobe epilepsy.