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IntroductionConvection-enhanced delivery (CED) is a method of targeted, local drug delivery to the central nervous system (CNS) that bypasses the blood-brain barrier (BBB) and permits the delivery of high-dose therapeutics to large volumes of interest while limiting associated systemic toxicities. Since its inception, CED has undergone considerable preclinical and clinical study as a safe method for treating glioblastoma (GBM). However, the heterogeneity of both, the surgical procedure and the mechanisms of action of the agents studied—combined with the additional costs of performing a trial evaluating CED—has limited the field’s ability to adequately assess the durability of any potential anti-tumor responses. As a result, the long-term efficacy of the agents studied to date remains difficult to assess.Materials and methodsWe searched PubMed using the phrase “convection-enhanced delivery and glioblastoma”. The references of significant systematic reviews were also reviewed for additional sources. Articles focusing on physiological and physical mechanisms of CED were included as well as technological CED advances.ResultsWe review the history and principles of CED, procedural advancements and characteristics, and outcomes from key clinical trials, as well as discuss the potential future of this promising technique for the treatment of GBM.ConclusionWhile the long-term efficacy of the agents studied to date remains difficult to assess, CED remains a promising technique for the treatment of GBM.

The rapid emergence of publicly accessible artificial intelligence platforms such as large language models (LLMs) has led to an equally rapid increase in articles exploring their potential benefits and risks. We performed a bibliometric analysis of ChatGPT literature in medicine and science to better understand publication trends and knowledge gaps. Following title, abstract, and keyword searches of PubMed, Embase, Scopus, and Web of Science databases for ChatGPT articles published in the medical field, articles were screened for inclusion and exclusion criteria. Data were extracted from included articles, with citation counts obtained from PubMed and journal metrics obtained from Clarivate Journal Citation Reports. After screening, 267 articles were included in the study, most of which were editorials or correspondence with an average of 7.5 +/− 18.4 citations per publication. Published articles on ChatGPT were authored largely in the United States, India, and China. The topics discussed included use and accuracy of ChatGPT in research, medical education, and patient counseling. Among non-surgical specialties, radiology published the most ChatGPT-related articles, while plastic surgery published the most articles among surgical specialties. The average citation number among the top 20 most-cited articles was 60.1 +/− 35.3. Among journals with the most ChatGPT-related publications, there were on average 10 +/− 3.7 publications. Our results suggest that managing the inevitable ethical and safety issues that arise with the implementation of LLMs will require further research exploring the capabilities and accuracy of ChatGPT, to generate policies guiding the adoption of artificial intelligence in medicine and science.

Abulia is a common problem that manifests following various brain conditions, including brain surgeries. Abulia is felt to be related to dysfunction with the brain’s dopamine-dependent circuitry. The role of default mode network (DMN) in its pathogenesis is crucial. In this case report, we detail the presentation of abulia in an elderly woman following surgical resection of a right frontal glioblastoma involving the DMN. Connectomic imaging was used pre-operatively and post-operatively, demonstrating disruption of regions integral to the DMN and the central executive network. We observed a significant cognitive improvement following the administration of levodopa and carbidopa. Preoperative assessment of both anatomical and functional networks can help ensure surgical safety and predict postoperative deficits. This evaluation not only enhances preparedness and facilitates early case diagnosis but also expedites the initiation of prompt and potentially targeted treatments. This case highlights the potential efficacy of levodopa and carbidopa in addressing DMN dysfunction and broadly suggests the potential for connectomics-guided post-operative therapies. ●Abulia, is linked to dysfunction in dopamine-dependent brain circuitry, particularly involving the default mode network (DMN).●In this paper, an elderly woman developed abulia after resection of a right frontal lesion●Connectomic imaging revealed disruption in DMN and central executive networks.●Cognitive improvement was observed with levodopa and carbidopa treatment.●The case shows the importance of preoperative assessment of functional networks for surgical safety.

Purpose Leptomeningeal metastatic disease (LMD) from advanced malignancies has poor prognoses and limited treatments. Intrathecal therapy (ITT) protocols are available, showing variable outcomes. We reviewed the therapeutic and toxicity profiles of ITT in LMD. Methods PubMed, EMBASE, Web-of-Science, and Scopus were searched following the PRISMA-ScR guidelines to include studies reporting ITT for LMD. Clinicaltrial.gov and Cochrane were searched to identify ongoing clinical trials. Results We included 27 published studies encompassing 2161 patients and 4 ongoing trials. LMD originated from brain metastases (85.5%), lymphomas (5.4%), high-grade gliomas (4.6%), medulloblastomas (2.3%), and leukemias (2.1%). LMD was mostly diagnosed with the co-presence of neurological-related symptoms and positive imaging and/or cerebrospinal fluid cytology (60.8%). The most common ITT agents were methotrexate (35.9%), cytarabine (21.9%), and thiotepa (8.2%), standalone or combined. Patients received a median of 6.5 ITT cycles (range, 1.0–71.0) via intraventricular (58.8%) or lumbar intrathecal (41.2%) routes. The Ommaya reservoir was implanted in 38.5% cases. Concurrent systemic chemotherapy (45.2%) and/or radiotherapy (30.6%) were used. After 1–3 cycles, 44.7% patients had improved clinical status and 29.9% converted into negative cerebrospinal fluid cytology. The most common ITT-related severe adverse events were neutropenia (6.5%), meningitis (5.2%) and encephalopathy (4.5%). Median freedom from progression was 2.4 months (range, 0.1–59.5) and median overall survival 5.5 months (range, 0.1–148.0). Conclusion Current ITT protocols are variable but effective and well-tolerated in LMD. Ongoing trials are investigating dose-limiting toxicity profiles and long-term overall survival. Future studies should analyze the therapeutic and safety profiles of ITT compared to newer systemic therapies.

PurposeSupratotal resection (SpTR) of high-grade glioma (HGG), in which surgical removal of the tumor is extended outside the margins of the preoperative radiographic abnormality, has been suggested to improve overall survival (OS) and progression free survival (PFS) in patients harboring tumors of non-eloquent cortex when compared to gross total resection (GTR). While current literature demonstrates these findings without an increase in post-operative complications or neurological deficits, there remains a paucity of data examining the neuropsychological outcomes of SpTR for HGG. As quality of life dramatically influences survival rates in these patients, it is crucial for neurosurgeons, neuro-oncologists, and neuropsychiatrists to understand the behavioral and cognitive outcomes following SpTR, such that optimal treatment strategies can be tailored for each patient.MethodsWe performed a comprehensive review of the available literature regarding survival, neuropsychological, and quality of life (QOL) outcomes following SpTR for HGG. We also review neuropsychological and QOL outcomes following GTR for HGG to serve as a framework for better understanding potential implications of SpTR.ResultsWhile results are limited following SpTR for HGG, available data suggests similar outcomes to those seen in patients undergoing GTR of HGG, as well as low-grade glioma. These include a short-term decline in neuropsychological functioning post-surgically with a return to baseline across most neurocognitive domains occurring within several months. Memory and attention remain relatively diminished at long term follow-up.ConclusionsLimited data exist examining postoperative cognitive and behavioral outcomes following SpTR for HGG. While the available data suggests a return to baseline for many neurocognitive domains, attention and memory deficits may persist. However, sample sizes are relatively small and have not been examined in the context of QOL and OS/PFS. More rigorous pre- and post-surgical neuropsychological assessment will help shed light on the long-term cognitive and behavioral effects of SpTR in the setting of HGG and inform clinical care and counseling when SpTR is considered.

Language is a critical aspect of human cognition and function, and its preservation is a priority for neurosurgical interventions in the left frontal operculum. However, identification of language areas can be inconsistent, even with electrical mapping. The use of multimodal structural and functional neuroimaging in conjunction with intraoperative neuromonitoring may augment cortical language area identification to guide the resection of left frontal opercular lesions. Structural and functional connectome scans were generated using a machine learning software to reparcellate a validated schema of the Human Connectome Project Multi-Modal Parcellation (HCP-MMP) atlas based on individual structural and functional connectivity identified through anatomic, diffusion, and resting-state functional MRI (rs-fMRI). Structural connectivity imaging was analyzed to determine at-risk parcellations and seed-based analysis of regions of interest (ROIs) was performed to identify functional relationships. Two patients with left frontal lesions were analyzed, one with a WHO Grade IV gliosarcoma, and the other with an intracerebral abscess. Individual patterns of functional connectivity were identified by functional neuroimaging revealing distinct relationships between language network parcellations. Multimodal, connectome-guided resections with intraoperative neuromonitoring were performed, with both patients demonstrating intact or improved language function relative to baseline at follow-up. Follow-up imaging demonstrated functional reorganization observed between Brodmann areas 44 and 45 and other parcellations of the language network. Preoperative visualization of structural and functional connectivity of language areas can be incorporated into a multimodal operative approach with intraoperative neuromonitoring to facilitate the preservation of language areas during intracranial neurosurgery. These modalities may also be used to monitor functional recovery. •Connectome imaging can identify unique patterns of language functional connectivity.•Preoperative connectome imaging can guide operative approaches in tumors near language areas.•Functional reorganization after surgery may contribute to language preservation or improvement.

Purpose 5-aminolevulinic acid (5-ALA) has demonstrated its utility as an intraoperative imaging adjunct during fluorescence guided resection of malignant gliomas. However, literature regarding 5-ALA-guided resection for brain metastases is limited. We conducted a systematic review to evaluate the efficacy of 5-ALA fluorescence for resection of metastatic brain tumors. Methods PubMed was queried for studies involving 5-ALA and brain metastases, and results were screened following PRISMA guidelines. Articles related to 5-ALA and brain metastasis were further assessed based on inclusion and exclusion criteria and results were analyzed for 5-ALA fluorescence rates stratified by tumor primary sites and histological subtypes. Results Of 421 identified search results, 10 studies were included and a total of 631 patients analyzed. Of these studies, 60% were retrospective in design. The reported rates of 5-ALA fluorescence in included brain metastases ranged from 27.6 to 86.9%, with variability across and within tumor types. No studies concluded improved operative outcomes or survival outcomes related to 5-ALA use. Conclusions Current studies regarding 5-ALA fluorescence in brain metastases are limited and do not confirm efficacy for improving extent of resection or post-operative survival. Fluorescence is variable across and within tumor types. Further studies are necessary to evaluate whether specific tumors may benefit from 5-ALA FGS or if changes in delivery protocols or fluorescence quantification may affect intraoperative utility.

A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically reviewed clinical outcomes in glioma patients treated with one or more nutritional adjunct and/or an antimetabolite drug. A systematic review of the literature following PRISMA guidelines was performed using Pubmed from inception till February 2023. In total, 22 manuscripts on nutrition representing 828 patients were included in the review. Statistical analyses were performed to compare the outcomes of various adjuncts. The median overall survival (OS) increased for newly diagnosed (21 months) and recurrent cases (10 months) when compared to historical data. For newly diagnosed cases, a ketogenic diet had the highest median OS of all the adjuncts (42.6 months) while in recurrent cases, a low copper diet coupled with 1 g penicillamine had the highest median OS (18.5 months). However, no statistically significant difference was observed in OS or progression-free survival (PFS) of newly diagnosed or recurrent gliomas. While nutritional adjuncts may offer a therapeutic benefit in the treatment of glioma, more human subject research is needed to derive meaningful conclusions. •Nutritional adjuncts increased OS and PFS in glioma patients.•Maximum survival was achieved by ketogenic diet in primary cases.•In recurrent cases, low copper diet achieved maximal survival.

Supplementary motor area (SMA) syndrome is characterized by contralateral akinesia and mutism, and frequently occurs following resection of tumors involving the superior frontal gyrus. The frontal aslant tract (FAT), involved in functional connectivity of the supplementary area and other related large-scale brain networks, is implicated in the pathogenesis of, and recovery from, SMA syndrome. However, intraoperative neuromonitoring of the FAT is inconsistent and poorly reproducible, leading to a high rate of postoperative SMA syndrome. We report the cases of two patients harboring lesions of the superior frontal gyrus: one cavernoma and one low grade glioma. Connectome imaging revealed involvement of functional networks implicated in SMA syndrome, as well as displacement of the FAT. A connectome-guided awake craniotomy was performed in both cases, and a combinatorial approach using awake language mapping and connectome-imaging guidance facilitated gross total resection of both patient’s lesions without inducing SMA syndrome postoperatively. Functional and structural connectivity imaging through connectomics allows the identification of areas not traditionally considered eloquent, such as the SMA and FAT, and can help facilitate their preservation. Conserving the functional and structural connectivity of broader brain regions that are not traditionally deemed eloquent can improve patient outcomes. •Connectome imaging can facilitate preservation of the frontal aslant tract.•Preserving non-canonically eloquent pathways can improve outcomes.•Intraoperative navigation and connectome imaging can be integrated.

IntroductionIntra-arterial (IA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration therapeutics through a targeted vascular territory, while potentially limiting systemic toxicity. Studies have demonstrated IA methods to be safe and efficacious for a variety of therapeutics. However, further characterization of the clinical efficacy of IA therapy for the treatment of brain tumors and refinement of its potential applications are necessary.MethodsWe have reviewed the preclinical and clinical evidence supporting superselective intraarterial cerebral infusion (SSIACI) with BBB disruption for the treatment of brain tumors. In addition, we review ongoing clinical trials expanding the applicability and investigating the efficacy of IA therapy for the treatment of brain tumors.ResultsTrends in recent studies have embraced the use of SSIACI and less neurotoxic chemotherapies. The majority of trials continue to use mannitol as the preferred method of hyperosmolar BBB disruption. Recent preclinical and preliminary human investigations into the IA delivery of Bevacizumab have demonstrated its safety and efficacy as an anti-tumor agent both alone and in combination with chemotherapy.ConclusionIA drug delivery may significantly affect the way treatments are delivered to patients with brain tumors, and in particular GBM. With refinement and standardization of the techniques of IA drug delivery, improved drug selection and formulations, and the development of methods to minimize treatment-related neurological injury, IA therapy may offer significant benefits for the treatment of brain tumors.