Public Health.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder with significant environmental factors, including diet, that influence its onset and progression. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored the KD's molecular impact for markers of AD therapeutic potential. The BEAM diet study simultaneously profiled the KD's effect on the lipidome, blood and cerebrospinal metabolome, and microbiome of both cognitively impaired and cognitively normal individuals.

Developing Topics.

Background: Evidence for abnormal amyloid-β (Aβ) plaque accumulation is necessary prior to initiating anti-amyloid therapy in early symptomatic Alzheimer's disease (AD). While the clinical trials for lecanemab and related drugs utilized positron emission tomography (PET) to demonstrate brain amyloidosis, current appropriate use recommendations for clinical practice consider PET or cerebrospinal fluid (CSF) biomarkers as satisfactory for this purpose. Here, we present four clinical cases where CSF biomarker results were discordant from amyloid PET, with the potential to result in erroneous treatment targeting.

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

Bevacizumab exerts dose-dependent risk for intracranial hemorrhage in patients with malignant gliomas.

Purpose: Bevacizumab, an anti-VEGF monoclonal antibody, has become a mainstay therapeutic in the management of malignant glioma. It is unknown if the risk of intracranial hemorrhage (ICH), a major complication associated with bevacizumab use, is dose-dependent.

Methods: This was a single institution retrospective analysis of patients treated with bevacizumab for the management of gliomas between 2009 and 2022.

Neurosurgical Implications of Targeting Hypoxia-Inducible Factor 2α in Hemangioblastomas with Belzutifan.

Objective: To highlight the neurosurgical implications of the hypoxia-inducible factor-2α- targeting agent belzutifan in the management of both von-Hippel Lindau (VHL)-associated and sporadic hemangioblastomas (HBLs).

Methods: The literature was queried for VHL, HBLs, and belzutifan. A summary of recent uses of belzutifan and currently ongoing clinical trials that are investigating the use of belzutifan in the treatment of HBLs is presented.

Serum and CSF metabolomics analysis shows Mediterranean Ketogenic Diet mitigates risk factors of Alzheimer's disease.

Alzheimer's disease (AD) is influenced by a variety of modifiable risk factors, including a person's dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD's metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment.

A Case of Long-Term Survival After Glioblastoma, IDH-Wild Type.

Introduction: Glioblastoma is a uniformly lethal primary central nervous system neoplasm. Despite the increased understanding of its pathophysiology and treatment advancements, median overall survival for patients with glioblastoma, IDH-wild type remains 14 to 21 months from diagnosis.

Case Report: We present the case of a 48-year-old female who presented with a focal seizure and was found to have a right frontal lobe mass on the brain magnetic resonance imaging.

Bihemispheric Seizure Without Generalization.

A 70-year-old male without prior psychiatric history presented with recurrent episodes (<60 seconds each, every 5-10 minutes) of left hemibody and right lower extremity jerking movements concerning for seizure with preserved awareness (Video). Examination showed left hemiparesis (leg > arm) in addition to right lower extremity weakness. Computed tomography showed a right parafalcine acute subdural hematoma (SDH).

Proton versus photon craniospinal irradiation for adult medulloblastoma: A dosimetric, toxicity, and exploratory cost analysis.

Background: This study aimed to determine whether proton craniospinal irradiation (CSI) decreased the dose to normal tissue and resulted in less toxicity than photon CSI for adult patients.

Methods: This single-institution retrospective analyzed differences in radiation doses, acute toxicity, and cost between proton and CSI for adult medulloblastoma patients.

Results: Of 39 total patients, 20 were treated with photon CSI prior to 2015, and 19 were treated with proton CSI thereafter.

Proton Craniospinal Irradiation with Immunotherapy in Two Patients with Leptomeningeal Disease from Melanoma.

Introduction: Proton craniospinal irradiation (pCSI) is a treatment option for leptomeningeal disease (LMD), which permits whole neuroaxis treatment while minimizing toxicity. Despite this, patients inevitably experience progression. Adding systemic therapy to pCSI may improve outcomes.

Recurrent Pleomorphic Xanthoastrocytoma Presenting With Diffuse Leptomeningeal Spread.

We report a case highlighting key clinical, CSF, and imaging findings of recurrent pleomorphic xanthoastrocytoma with leptomeningeal spread.

A Modified Mediterranean Ketogenic Diet mitigates modifiable risk factors of Alzheimer's Disease: a serum and CSF-based metabolic analysis.

Alzheimer's disease (AD) is influenced by a variety of modifiable risk factors, including a person's dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD's metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment.

An untapped window of opportunity for glioma: targeting therapy-induced senescence prior to recurrence.

High-grade gliomas are primary brain tumors that are incredibly refractory long-term to surgery and chemoradiation, with no proven durable salvage therapies for patients that have failed conventional treatments. Post-treatment, the latent glioma and its microenvironment are characterized by a senescent-like state of mitotic arrest and a senescence-associated secretory phenotype (SASP) induced by prior chemoradiation. Although senescence was once thought to be irreversible, recent evidence has demonstrated that cells may escape this state and re-enter the cell cycle, contributing to tumor recurrence.

Plasma exchange as a tool for removal of bevacizumab: Highlighting application for urgent surgery.

Background: Bevacizumab is commonly used to manage cerebral edema associated with brain tumors. However, its long half-life poses challenges for patients requiring urgent surgery due to wound complications. We present a case of utilizing therapeutic plasma exchange (TPE) to remove bevacizumab in a patient with recurrent glioblastoma requiring urgent surgery.

Withdrawal of bevacizumab is associated with rebound growth of vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis patients.

Background: Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS). In patients with VS associated with NF2, vascular endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option. The aim of this study is to retrospectively evaluate NF2 patient responses to bevacizumab on VS growth and symptom progression.

Management and Long-term Outcomes of Adults With Medulloblastoma: A Single-Center Experience.

Background And Objectives: Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood.

Improving Neurology Inpatient Fall Rate: Effect of a Collaborative Interdisciplinary Quality Improvement Initiative.

Objective: To reduce unwitnessed inpatient falls on the neurology services floor at an academic medical center by 20% over 15 months.

Patients And Methods: A 9-item preintervention survey was administered to neurology nurses, resident physicians, and support staff. Based on survey data, interventions targeting fall prevention were implemented.

Glioma Metabolic Feedback In Situ: A First-In-Human Pharmacodynamic Trial of Difluoromethylornithine + AMXT-1501 Through High-Molecular Weight Microdialysis.

Background And Objectives: No new drug has improved survival for glioblastoma since temozolomide in 2005, due in part to the relative inaccessibility of each patient's individualized tumor biology and its response to therapy. We have identified a conserved extracellular metabolic signature of enhancing high-grade gliomas enriched for guanidinoacetate (GAA). GAA is coproduced with ornithine, the precursor to protumorigenic polyamines through ornithine decarboxylase (ODC).

The Current Status, Challenges, and Future Potential of Therapeutic Vaccination in Glioblastoma.

Glioblastoma (GBM) is the most common malignant primary brain tumor and confers a dismal prognosis. With only two FDA-approved therapeutics showing modest survival gains since 2005, there is a great need for the development of other disease-targeted therapies. Due, in part, to the profound immunosuppressive microenvironment seen in GBMs, there has been a broad interest in immunotherapy.

Effects of a ketogenic and low-fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease.

Introduction: The ketogenic diet (KD) is an intriguing therapeutic candidate for Alzheimer's disease (AD) given its protective effects against metabolic dysregulation and seizures. Gut microbiota are essential for KD-mediated neuroprotection against seizures as well as modulation of bile acids, which play a major role in cholesterol metabolism. These relationships motivated our analysis of gut microbiota and metabolites related to cognitive status following a controlled KD intervention compared with a low-fat-diet intervention.