bluuebunny/crossref_metadata_2025_split huggingface dataset:
436 Transforaminal Endoscopic Decompression for Foraminal Stenosis: Single-Arm Meta-Analysis and Systematic Review
Authors: Liu Yanting , Van Isseldyk Facundo , Kotheeranurak Vit , Kim Jin-sung , Chul Choi Kyung , Bae Jun Seok , Quillo-Olvera Javier 
Published: March 2023

INTRODUCTION:
The objective of this single-arm systematic review was to assess the effectiveness of transforaminal endoscopic foraminal decompression (TEFD) in patients with symptomatic LFS.

METHODS:
The meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The Medicine, PubMed, Web of Science, and Embase databases were searched from inception to February 20, 2022. Primary research results were Visual Analog Scale (VAS) scores, Oswestry Disability Index scores (ODI), MacNab Criteria (MNC) scores, and reported adverse events (AEs). Subgroup analyses were performed on the primary outcome to evaluate the potential effects of several clinical factors that affected the results.

RESULTS:
Of the 2020 studies identified, nine met the inclusion criteria, and 316 participants were eligible for meta-analysis. The meta-analysis results found that transforaminal endoscopic surgery for the treatment of LFS was associated with a significant improvement in postoperative 12-month clinical indicators: 8 studies reported improvements in VAS scores: -5.38, ODI scores: -40.44, and MNC scores: OR (odds ratio) = 0.86; 8 studies reported 11.53% AEs occurred in a total of 295 patients, and the most commonly reported event was transient postoperative dysesthesia, which occurred in 26 patients in a total of six studies with 240 patients (10.83%).

CONCLUSIONS:
Transforaminal endoscopic surgery positively affects postoperative LFS patients' clinical indicators; however, high-level literature with randomized controlled trials is needed to confirm this technique's applicability in LFS.
440 10 kHz Spinal Cord Stimulation (SCS) Provides Significant, Durable Pain Relief for Patients with Painful Diabetic Neuropathy (PDN): 24-Month Results
Authors: Petersen Erika A. , Stauss Thomas , Scowcroft James , Jaasma Michael , White Judith , Sills Shawn , Amirdelfan Kasra , Guirguis Maged , Xu Jijun , Yu Cong , Nairizi Ali , Patterson Denis , Creamer Michael , Galan Vincent , Bundschu Richard , Mehta Neel , Sayed Dawood , Lad Nandan P. , DiBenedetto David , Sethi Khalid Ahmed , Wu Paul , Argoff Charles , Nasr Christian , Taylor Rod , Caraway David , Mekhail Nagy 
Published: March 2023

INTRODUCTION:
Approximately 37 million Americans have diabetes, 1 with 25-30% experiencing PDN. 2 High-frequency (10 kHz) SCS has been shown to provide substantial symptom relief for PDN, 3 and here we report durability of these outcomes to 24 months (24M).

METHODS:
This prospective, multicenter, RCT evaluated 10 kHz SCS with these key inclusion criteria: PDN symptoms ≥12 M refractory to medications, lower limb pain intensity ≥5 cm (0-10 cm visual analog scale [VAS]), and hemoglobin A1c ≤ 10%. Patients (n = 216) were randomized 1:1 to 10 kHz SCS plus CMM or CMM alone, with optional crossover at 6M.

RESULTS:
At 6M, patients receiving 10 kHz SCS experienced average pain relief of 76.1% (95% CI: 70.5–81.6%), which increased to 82.0% (95% CI: 77.3–86.6%) at 24M. At 24M, 10 kHz SCS patients experienced 70% decreases in pain-associated sleep disturbance and interference with mood and daily activities. At 24M, neurological improvements were observed in 72% of patients receiving 10 kHz SCS. After 6M, 93% of eligible CMM patients elected to cross over to 10 kHz SCS, while zero 10 kHz patients crossed over. With 10 kHz SCS, both groups experienced similar, significant reductions in pain and pain-associated interference. There were zero device explants due to lack of efficacy and eight (5.2%) procedure-related infections (n = 3 resolved with antibiotics; n=5 explanted), which is within the range reported for SCS in non-diabetic patients (2.5-10%).4

CONCLUSIONS:
This is the largest RCT to date for SCS management of PDN. The 24M results support that 10 kHz SCS can provide safe, durable pain and symptom relief for PDN.

REFERENCES:
1 CDC. National Diabetes Statistics Report; 2022. 2 Finnerup et al. Lancet Neurol 2015; 14(2):162-73. 3 Petersen et al. Diabetes Care; 45(1):e3-e6. 4 Eldabe et al. Pain Med 2016; 17(2):325-36.
442 Reversible Cognitive Dysfunction and Neuropsychiatric Symptoms in Patients With Chiari Malformation Type I
Authors: Henry Luke , McDowell Michael Maurice , Stephenson Tina , Crittenden J. Bret , Bird Amy , Fernandez-de Thomas Ricardo Jose , Strick Peter , Friedlander Robert Max 
Published: March 2023

INTRODUCTION:
Chiari malformation type I (CMI) is a congenital/acquired structural condition where the cerebellar tonsils herniate through the foramen magnum, resulting in cerebellar and lower medulla/upper cervical spinal cord compression. Symptoms typically include occipital headaches, however, additional symptoms have been reported by symptomatic patients. We have observed a proportion reporting cognitive dysfunction and neuropsychiatric symptoms, which appear to improve following posterior fossa decompression (PFD).

METHODS:
Patients completed comprehensive neuropsychological evaluations, including a 90-minute standardized assessment of cognitive function across multiple domains and a self-reported assessment of neuropsychiatric symptoms, pre- and approximately 6-months post-surgery.

RESULTS:
This prospective study included patients with CMI who opted to undergo PFD surgery and reported cognitive or neuropsychiatric impairment between 2015 to 2021. All patients completed a comprehensive pre-operative neuropsychological assessment. A parallel assessment was completed at 6-month post-operative follow-up. 112 patients (Mage = 35.1 years; SD = 10.4) were included in pre-operative analyses, and of these, 31 patients (Mage = 32.5 years; SD = 10.5) were included in paired pre-post-operative analyses. Pre-operatively, CMI patients performed significantly worse than a standard norm on measures of executive function, attention, visuospatial memory, verbal memory, and neuropsychiatric symptoms.

CONCLUSIONS:
This is the first study to 1) demonstrate significant impairments in cognitive function and neuropsychiatric symptoms in CMI patients pre-operatively, and 2) show significant improvements in these domains at post-operative follow-up. This work calls attention to a significant proportion of CMI patients who suffer debilitating and life altering symptoms and provides compelling evidence for a role of the cerebellum in such conditions. In addition to CMI, cerebellar pathology should be considered as potential neuroanatomical site for patients with cognitive and neuropsychiatric impairment from other etiologies.
444 Extraction and Analysis of Speech Features to Understand Audio Phenotypes of Pain
Authors: Duey Akiro , Rana Aakanksha , Hussein Helweh , Siddi Francesca , Onnela J.P. , Smith Timothy R. 
Published: March 2023

INTRODUCTION:
Pain evaluation of spine patients remains largely a subjective assessment in practice, but artificial intelligence provides the potential for objective pain assessment tools.

METHODS:
This study enrolled spine patients from a general neurosurgical clinic. Patients were asked to download the Beiwe smartphone application and prompted to complete pain surveys at home once per day and speech recordings once per week during the study. The pain surveys asked patients to rate their pain on a scale from 0 to 10. For the speech recordings, patients were asked to read a passage from a well-known novel. Patients were included in the study if they completed at least one speech recording and pain survey within 24 hours of each other. Audio features were extracted from the speech recordings using the Parselmouth library, and 13 Mel-frequency cepstral coefficients (MFCCs) were extracted using the Librosa package. The mean MFCC values were calculated for each speech recording. These speech features were then analyzed using a linear mixed model with pain as the model output and a random intercept for each patient.

RESULTS:
In total, there were 384 speech recordings from 60 patients. The linear mixed model was significantly associated with two MFCCs – MFCC 2 (Coef: 0.552; 95% CI: [0.254, 0.850]; p < 0.001) and MFCC 12 (Coef: -0.286; 95% CI: [-0.538, -0.034]; p = 0.026). However, we observed that none of the other available audio features were significantly associated with pain scores.

CONCLUSIONS:
This preliminary study shows that MFCCs 2 and 12 are of potential interest for phenotyping speech and objective pain assessment.
447 Modulation of Patient Reported Outcomes and Opioid Consumption Following Open Craniotomy: The Efficacy and Safety of Subcutaneous Sumatriptan
Authors: Woodward Josha , Kelly Ryan Matthew , Patiel Aahaska , Herbst Julia , Meza Samuel , Koro Lacin , Keegan Kevin , Panos Nicholas , Munich Stephan , Munoz Lorenzo , Sani Sepehr 
Published: March 2023

INTRODUCTION:
Traditional pain management regimens following open craniotomy commonly employ opioid medications. As a medication class, opioids present a considerable adverse effect profile and the potential for medication abuse. Alternative medication regimens to better address post-craniotomy pain while mitigating opioid-related adverse effects are insufficiently studied. However, as a dural-based 5-HT1D receptor agonist that regulates vasoconstriction and inflammatory peptide signaling, sumatriptan shows promise to improve pain scores and reduce opioid requirements.

METHODS:
This is a single academic center, retrospective cohort study of 130 consecutive adult patients undergoing open craniotomy between 7/2015 and 8/2021. Patients were divided between a Control and Sumatriptan cohort contingent upon administration of a single 6mg subcutaneous injection of sumatriptan within 1-hour of surgery completion and prior to opioid administration. Opioid consumption at 6, 12 and 24-hours postoperative and admission total, inpatient length of stay (LOS) and 30-day global representation/readmission were evaluated.

RESULTS:
130 patients were equally divided between the Sumatriptan and Control cohorts for analysis. No difference in baseline demographics was noted. A significant reduction of mean pain score at 6, 12 and 24-hours following surgery substantially favored the Sumatriptan cohort (p < 0.05). Further, a nonsignificant reduction in opioid requirements was observed at all timepoints favoring the sumatriptan cohort (p > 0.05). 30-day global ED evaluation and readmission rates between cohorts were similar (p > 0.05). Overall LOS in the Sumatriptan and Control cohorts were 5.3 ± 3.6 vs 6.5 ± 5.6 days (p > 0.05). No difference in the rate of incisional or intracerebral hemorrhage was noted between cohorts (p > 0.05).

CONCLUSIONS:
In the present study, patients in the Sumatriptan cohort demonstrated enhanced pain control and reduced opioid requirements suggesting sumatriptan represents a safe and efficacious agent for the modulation of pain following open craniotomy.
453 Neuromodulation of the Centromedian Nucleus of the Thalamus for the Treatment of Generalized Drug-Resistant Epilepsy: Novel Insights Into the Targeting and the Anti-Seizure Mechanism From a Tractographic Study
Authors: Remore Luigi , Omidbeigi Mahmoud , Tsolaki Evangelia , Wei Wenxin , Chodakiewitz Michael , Eliashiv Dawn , Nariai Hiroki , Fallah Aria , Bari Ausaf A. 
Published: March 2023

INTRODUCTION:
Neuromodulation of the centromedian nucleus (CM) has been investigated with promising results for the treatment of generalized drug-resistant epilepsy (gDRE). Recent evidence suggests a more clinically beneficial “sweet-spot” corresponding to the thalamic area between the antero-lateral CM and the posterior subdivision of the ventrolateral nucleus. However, it is unclear if this region can be considered a new target or still a subcomponent of CM.

METHODS:
We analyzed diffusion and structural MRI scans from 9 DRE patients, who underwent CM-stimulation surgery. CM masks from the THOMAS atlas and 2 spherical ROIs from the MNI coordinates of the sweet-spot and the cold-spot in Warren et al. 2022 were used as seed regions for probabilistic tractography (FSL software). 42 cortical and subcortical areas were selected as target regions and divided in 5 groups: sensorimotor, associative, basal ganglia, infratentorial and limbic structures. Mean structural connectivity was calculated using descriptive statistics and statistical significance was tested with a standard t-test. Statistical comparison among the 3 seed regions was conducted using ANOVA.

RESULTS:
For each seed, statistically significant (p < 0.05) connections were found for all the 5 groups. When comparing the 3 seeds, the CM and the cold-spot had stronger connections with the postcentral and the superior temporal cortices, the brainstem, the caudate and the amygdala; the sweet-spot with the precentral and the superior frontal cortices, the cerebellum, the putamen and the nucleus accumbens. However, no statistically significant differences resulted among the 3 seeds.

CONCLUSIONS:
CM has widespread connections with both cortical and subcortical structures. The sweet-spot seems to correspond to the parvocellular part of CM on the border with the ventrolateral nucleus. CM connections with frontal and prefrontal areas and the cerebellum may underlie the beneficial effect against generalized seizures.
457 CD39 Expression in the Glioblastoma Microenvironment does not Affect T Cell Exhaustion or Survival
Authors: Zheng Allison , Pappu Ananya , Gill Sabraj , Stelter Isabella , Aghi Manish Kumar 
Published: March 2023

INTRODUCTION:
Glioblastoma (GBM), the most common malignant brain tumor, is notable for its dysfunctional T-cells. The initial optimism of Immune checkpoint inhibitors has been tempered as these agents have not been successful in treating GBM. CD39 is the first enzyme in the breakdown of ATP to adenosine and is highly upregulated in GBM. CD39 is also thought to contribute to T-cell exhaustion. However, inhibiting the CD39 ATP breakdown pathway did not improve survival in mice, even with PD-1 inhibition, leading to uncertainty about whether non-enzymatic functions of CD39 give it a role in T-cell exhaustion in GBM.

METHODS:
We performed intracranial injections of SB28 and GL261 GBM cell lines into CD39 global nulls (KO) and C57BL/6J (WT) mice and measured survival. Another cohort of mice were similarly injected and sacrificed after 2 weeks. These tumors were analyzed for T-cell exhaustion markers using flow cytometry.

RESULTS:
There was no survival benefit seen in either cell line when compared to wild type mice. The immune cell profile was not found to be statistically different between KO and WT mice. Next, expression of known exhaustion markers such as PD-1, TIM3, and LAG3 on tumor infiltrating lymphocytes (TILs) were analyzed. Expression of TIM3 and 2B4 were found to be increased in CD39KO TILs compared to WT (p < 0.01). Additionally, numerous exhaustion markers such as LAG3, TIGIT, and CTLA4 were decreased on TILs compared to peripheral blood T-cells in tumor-bearing mice (p < 0.01).

CONCLUSIONS:
These results suggest that CD39 lacks a direct impact on GBM outcomes but may affect the expression of other exhaustion markers. Further studies will continue to investigate the interaction between immune checkpoint molecules in GBM.
458 Assessment of MGMT Methylation Status Using High-Performance Liquid Chromatography in Newly Diagnosed Glioblastoma
Authors: Hanihara Mitsuto , Miyake Kunio , Watanabe Atsushi , Yamada Yuriko , Oishi Naoki , Kawataki Tomoyuki , Inukai Takeshi , Kondo Tetsuo , Kinouchi Hiroyuki 
Published: March 2023

INTRODUCTION:
The utility of O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation status as a prognostic marker in patients with glioblastoma (GBM) has been established. However, the number of CpG sites that must be methylated to cause transcriptional silencing remains unclear, and no significant consensus exists on the optimal method of assessing MGMT methylation.

METHODS:
W analyzed the MGMT methylation status of 28 isocitrate dehydrogenase–wild-type GBMs treated with temozolomide using ion-exchange HPLC and bisulfite sequencing using frozen samples. We designed three primers for separate regions (regions 1–3) that had 21 to 38 CpGs for PCR and validated the MGMT promoter methylation status.

RESULTS:
There was a strong correlation between HPLC and bisulfite sequencing results (R = 0.794). The optimal cutoff values for MGMT methylation in HPLC were determined to allow differentiation of patient prognosis by receiver operating characteristic curve analysis. The cutoff values were 34.15% for region 1, 8.84% for region 2, and 36.72% for region 3. Kaplan–Meyer curve analysis estimated that the most differentiated prognosis was enabled in the setting of 8.84% methylation of MGMT in region 2. Progression-free survival and overall survival were significantly longer for patients in this setting of region 2 methylation (p = 0.00365 and p = 0.00258, respectively).

CONCLUSIONS:
The combination of our HPLC method and the original primer setting provides a new standard method for determination of MGMT methylation status in patients with GBM and is useful for refining MGMT-based drug selection.
464 Alternative RNA Splicing Changes Underlie Meningioma DNA Methylation Groups
Authors: Leclair Nathan , Choudhury Abrar , Magill Stephen , Shen Erica , Bulsara Ketan R. , Raleigh David R. , Anczukow Olga 
Published: March 2023

INTRODUCTION:
Meningiomas are the most common primary intracranial tumor. They are associated with genetic mutations found across broad epigenetic or transcriptomic groups. Alternative RNA splicing (AS) is a critical step in gene expression that involves the differential inclusion of sequences into the mature mRNA. Dysregulation of AS is a hallmark of human tumors, but its contributions to meningioma tumorigenesis are incompletely understood. In particular, whether meningioma DNA-methylation groups are associated with specific downstream changes in AS is unknown.

METHODS:
AS events from 184 meningiomas were characterized using rMATS, a computational tool that quantifies percent splicing event inclusion (PSI) from short-read RNA-sequencing. Differential gene expression was quantified using DESeq2.

RESULTS:
Our analysis revealed 135 differentially spliced events in Immune-enriched vs. Hypermitotic meningiomas, 126 events in Immune-enriched vs. Merlin-intact meningiomas, and 185 events in Merlin-intact vs. Hypermitotic meningiomas. Hierarchical clustering of samples based on differential splicing events separated Hypermitotic from Merlin-intact and Immune-enriched meningiomas. The proto-oncogenes Misshapen-like Kinase 1 (MINK1) and Nuclear Auto-antigenic Sperm Protein (NASP) were differentially spliced across WHO grades, DNA methylation groups, and in primary vs. recurrent meningiomas and correlated with recurrence free survival. Differential gene expression analysis revealed alterations in the expression of several splicing factors across methylation groups, including those involved in tumorigenesis (MEX3A, SNRPE, SRSF5).

CONCLUSIONS:
AS promotes differential isoform expression across clinically important DNA-methylation groups of meningiomas. Our analyses capture a splicing signature that correlates with meningioma aggressiveness, identifies prognostic splicing events in known human proto-oncogenes (MINK1, NASP), and uncovers their potential upstream regulators. Validation of how these events impact meningioma tumorigenesis may allow for the development of novel diagnostic tests and therapies targeting AS.
468 Relationship Between Tumor Location and Quality and Extent of Resection in the Surgical Treatment of Myxopapillary Ependymoma
Authors: Joiner Evan F. , Greenwald Phoebe , Neira Justin Anthony , Kostadinov Jane , Khandji Alexander , Mandigo Christopher Eliot , Angevine Peter D. , McCormick Paul C. 
Published: March 2023

INTRODUCTION:
Myxopapillary ependymomas (MPE) are benign spinal tumors that present substantial heterogeneity with respect to size, location, and marginal integrity. These factors influence both extent and technique of tumor resection as well as the risk of tumor recurrence and CSF dissemination.

METHODS:
A retrospective review of all patients treated surgically for MPE at a tertiary care center from 1998 to 2021 was performed.

RESULTS:
Fifty-six patients (32 male, 24 female; age 21 to 77 years, mean 45.8 years) were included in the study. Sixty primary surgical procedures were performed (4 patients underwent a second surgery for removal of pre-existing sacral drop metastases). The quality and extent of resection was categorized as en bloc gross total resection (eGTR, n = 15), marginal GTR (mGTR, n = 17), piecemeal GTR (pGTR, n = 6), piecemeal near total resection (pNTR, n = 9), and subtotal resection (STR, n = 13). Fourteen of 15 eGTRs and all 17 mGTRs were accomplished in patients with tumors at or above L3. In contrast, 3/6 pGTRs, 5/9 pNTRs, and 10/13 STRs occurred in patients with tumors below L3 (p < 0.001 for Fisher’s exact test). Tumor recurrence was noted in 1/15 patients who received eGTR, 1/17 who received mGTR, 0/6 who received pGTR, 1/9 who received pNTR, and 9/13 who received STR (p < 0.001).

CONCLUSIONS:
MPEs are heterogeneous neoplasms. The quality and extent of resection is often dictated by tumor location, which in turn correlates with the marginal integrity of the tumor. Tumors located below L3 are more often poorly marginated—allowing for only subtotal or piecemeal resection—while tumors at or above L3 are more likely to be amenable to eGTR or mGTR.
473 Role of Neutrophils and Neutrophil Extracellular Traps in Subarachnoid Hemorrhage in Mice
Authors: Zeineddine Hussein A. , Honarpisheh Pedram , Hong Sungha , Dienel Ari , Thankamanipandit Peeyush , Blackburn Spiros L. , Aronowski Jaroslaw , Mcbride Devin 
Published: March 2023

INTRODUCTION:
Aneurysmal subarachnoid hemorrhage (aSAH) continues to be a devastating disease. The role of neutrophils and neutrophil extracellular traps (NETs) have been investigated in other cerebrovascular disorders. Recent evidence suggest that neutrophils might play a role in outcomes after aSAH.

METHODS:
Subarachnoid hemorrhage model: The endovascular perforation model was utilized to induce SAH in mice. Flow cytometry: Flow cytometry technique was utilized to quantify neutrophils. Neutrophils were identified as CD45+Cd11b+Ly6G+ cells. NETosis assay: Neutrophils were assayed for their NETosis potential using a previously described method. The ratio of PMA (SYTOX+) to DMSO (SYTOX+) defined the NETosis induction. RNAseq: RNA sequencing was performed on neutrophils isolated from skull and femur bone marrow. Immunohistochemistry: NETs were assessed using classical IHC techniques and in vivo microscopy. Neurobehavior score: Mice were assessed daily for their behavior score using previously reported techniques.

RESULTS:
Neutrophils infiltrate brain within 24 hours and normalize by day 5. RNAseq demonstrates segregation of skull and femur bone marrow neutrophils following SAH. SAH induces a NETosis phenotype in skull neutrophils. NETs form starting day 1 after injury and persist until at least day 7. Neutrophil depletion and NETs inhibition attenuates early brain injury after SAH. Patients developing DCI have significantly higher blood markers of NETs.

CONCLUSIONS:
Neutrophils infiltrate the brain within the first 24 hours with NETs forming as early as day 1. Depletion of neutrophils and NET inhibition mitigated early brain injury following SAH. Blood markers of NETs are elevated in DCI patients and may be used as predictors of DCI. This highlights NETs as potential therapeutic target for patients with SAH and paves the way for future studies.