bluuebunny/crossref_metadata_2025 huggingface dataset:
100 Somatic Mosaicism of a PDGFRB Activating Variants in Intracranial, Coronary, Aortic and Radial Vascular Beds
Authors: McAvoy Malia , Parada Carolina , El-Ghazali Fatima , Toglia Daphne , Ruzevick Jacob , Emerson Samuel , Karasozen Yigit , Busald Tina , Nazem Ahmad , Suranowitz Shaun , Shalhub Sherene , Marshall Desiree , Tyrtova Evgeniya , Eaton Jessica C. , Nistal Dominic A. , Swaminathan Shreya , Gonzalez-Cuyar Luis , Dorschner Michael , Ferreira Manuel
Published: March 2022

INTRODUCTION:

Activating variants in platelet-derived growth factor receptor beta (PDGFRB) are associated with aneurysms. Our group previously described a patient with multiple fusiform intracranial aneurysms who was found to have a somatic mosaic variant in PDGFRB. The relationship between the mosaic effects of PDGFRB variants and the vascular phenotypes is not well understood.

METHODS:

Following death due to subarachnoid hemorrhage, samples from the index patient’s intracranial, coronary, aortic, and radial arteries were biopsied and preserved. DNA was extracted and alternate allele fractions (AAF) of PDGFRB variants were determined using digital droplet PCR. Histopathological analysis was performed by a board-certified neuropathologist.

RESULTS:

A total of 80 biopsies were obtained. The AAFs of variant PDGFRB in the vertebral artery, basilar artery, and P1 segment aneurysms were 28.7%, 16.4%, and 17.8%, respectively. The AAF of the coronary and radial artery aneurysms were 22.3% and 20.6%, respectively. AAFs of normal vascular biopsies of the intracranial circulation, coronary arteries, and aorta ranged from 0 to 4.3%, 0 to 0.3%, and 0 to 35%, respectively. The PDGFRB variant was absent from lymphocyte DNA and normal tissue, confirming it to be a non-germline somatic variant. Expression of PDGFRB within the radial artery aneurysmal tissue was localized to CD31 negative, non-endothelial cell origin.

CONCLUSION:

Somatic mosaic expression of PDGFRB within CD31 negative cells is associated with development of fusiform aneurysms. The role of targeted therapy with tyrosine kinase inhibitors to locally alter the biology of aneurysm development in fusiform aneurysms with PDGFRB mutations should be further studied.
126 Regulator of G Protein Signaling 4 (RGS4) Gene Expression is Upregulated in the Superficial Spinal Dorsal Horn and in Dorsal Root Ganglion Neurons in a Murine Model of Neuropathic Pain
Authors: Zimering Jeffrey H. , Pryce Kerri , Margetis Konstantinos , Zachariou Venetia
Published: March 2022

INTRODUCTION:

Regulator of G protein signaling 4 (RGS4), a potent negative regulator of G-protein coupled receptor signaling, is a key gene in the maintenance of mechanical and cold allodynia associated with chronic pain states in mice. RGS4 is abundantly expressed across the pain matrix, and is upregulated in response to peripheral inflammation and nerve injury.

METHODS:

To understand the dynamics of RGS4 gene expression after nerve injury, we perform the spared-nerve injury (SNI) model of neuropathic pain in C57BL/6. At 21 days (DRG) or 2.5 months (spinal cord) post-surgery (SNI vs sham), animals were sacrificed and specimens were harvested for tissue processing. RNAScope, an ultrasensitive RNA ISH method, was used to visualize and quantify single-molecule expression of RGS4, prodynorphin/PDYN (exclusively expressed by inhibitory dorsal horn interneurons), and somatostatin/SST (expressed by excitatory interneurons) within the cellular topography of the lumbar superficial dorsal horn.

RESULTS:

RGS4 expression increased significantly in the dorsal horn following spared-nerve injury (p = 0.0384). In sham-treated mice, there were no differences in cell-type-specific (PDYN vs. SST) RGS4 expression patterns in the dorsal horn (p = 0.4170). Cell-type-specific RGS4 expression in the dorsal horn was significantly different (F (2,27) = 8.353; p = 0.0015; one-way ANOVA) following SNI. SNI-induced RGS4 expression was significantly enriched in PDYN vs SST-expressing interneurons (p = 0.0300), and overall RGS4 expression was significantly downregulated in SST-expressing cells compared to all cells (p = 0.0012). In addition, neuronal-specific RGS4 expression was significantly increased in the DRG in SNI vs Sham-injured mice (p = 0.0050).

CONCLUSION:

Our data suggest that upregulation of RGS4 expression in the superficial dorsal horn and DRG may play a crucial role in maintenance of chronic pain following nerve injury.
139 Evaluating the Evidence: A Systematic Review of Targeted Muscle Reinnervation for Post-Amputation Phantom and Residual Limb Pain
Authors: Ryan Casey A. , Bhanja Debarati , McNutt Sarah , Daggubati Lekhaj C. , Rizk Elias B.
Published: March 2022

INTRODUCTION:

Over 2 million amputees in the US suffer from chronic pain related to their residual or phantom limb. Nerve ablation and neuroma excisions with transposition of remaining nerve fascicles into a more favorable microenvironment are two current pain-reducing procedures for post-amputation phantom and residual limb pain (PAP). Targeted Muscle Reinnervation (TMR) is an emerging technique that removes the terminal neuroma and attaches the nerve to a nearby motor neuron. This approach has gained wide acceptance for PAP, despite no clear consensus on the superiority of TMR over other approaches.

METHODS:

Eligible studies were attained using the PRISMA guidelines including those that evaluated TMR for treatment of PAP. The primary outcome was pain resolution. A computerized search of MEDLINE/ PubMed, Ovid and Embase from inception to March 2021 was conducted for the terms “Targeted Muscle Reinnervation” AND (“pain” OR “neuroma”). Two independent researchers evaluated each study, assigning a level of evidence according to the American Association of Neurology (AAN) algorithm; a third independent researcher resolved any discrepancies with assignments. Data extracted included the level of amputation, time from amputation to TMR, time from TMR to follow-up and reported pain scale(s).

RESULTS:

Of the 23 studies included in the analysis, only one study was a randomized controlled study (level I) with 28 patients, and three studies were level II evidence. The remaining 19 studies were found to be level IV evidence. The RCT results demonstrated that the difference in pain scale scores in the TMR versus the standard of care group was not statistically significant. The low-level studies suffered from high selection bias, lack of comparison cohorts, inconsistent outcomes, variable procedure locations, and variable time from amputation to TMR. Only 16 (69.6%) studies used validated patient-reported pain scales, including numerical rating scale and/ or PROMIS.

CONCLUSION:

There is insufficient and poor evidence to recommend TMR over standard neuroma excision for the reduction of PAP. The literature remains inconsistent due to the lack of validated pain scale data and variable results based on the amputation/ TMR site. This highlights the importance for a national registry to compare outcomes across surgical techniques.
145 A Matched Cohort Comparison of Survival After Radiosurgery for Non-Small Cell Lung Cancer Patients with One Versus More than Twenty Brain Metastases
Authors: Wei Zhishuo , Niranjan Ajay , Abou-Al-Shaar Hussam , Lunsford L. Dade
Published: March 2022

INTRODUCTION:

Confusion remains as to whether it is the number or the cumulative volume of brain metastases that affects survival of patients with metastatic non-small cell lung cancer (NSCLC). We retrospectively compared outcomes after stereotactic radiosurgery (SRS) in patients with a solitary metastasis matched by volume to patients with = 20 metastases with the same cumulative tumor volume.

METHODS:

From 2014 to 2020, 26 NSCLC patients (925 tumors) underwent Gamma knife® SRS for = 20 metastases in a single procedure (median margin dose = 16 Gy, median cumulative tumor volume = 4.52 cc). During the same interval 57 patients underwent SRS for a single metastasis (median margin dose = 18 Gy, median volume = 4.74 cc). The overall survival (OS), local tumor control (TC), adverse radiation effects (ARE), and incidence of new tumor development were compared.

RESULTS:

When controlled for the same tumor volume, we found no significant difference in median OS between patients with = 20 brain metastases (median survival = 15 months) compared to single metastasis patients (median survival = 12 months, p = 0.3). In the solitary tumor cohort, two of 57 tumors (3.5%) progressed whereas in the = 20 cohort only 3 of 925 treated tumors (0.3%) showed progression (p = 0.0013). The rate of new tumor development was significantly higher in patients with = 20 tumors (***p = 0.0001). Seventeen out of 26 (65%) patients in = 20 cohort developed new metastases that required salvage SRS compared to 8 out of 57 (14%) patients in the solitary tumor group. There was no significant difference in the rate of ARE between these groups (7.5% for = 20 tumors vs. 8.7% for single metastasis).

CONCLUSION:

Compared to patients with solitary tumors, patients with = 20 tumors showed significantly better LC with similar OS. We support the revision of guidelines that select SRS eligible patients based on the cumulative volume rather than number of their brain metastatic disease.
148 Does Stereoelectroencephalograghy (SEEG) Add Value in Patients with Lesional Epilepsy?
Authors: Morsi Amr , Golubovsky Joshua , Sharma Akshay , Bulacio Juan , McGovern Robert A. , Jehi Lara , Bingaman William E.
Published: March 2022

INTRODUCTION:

Stereoelectroencephalograghy (SEEG) has been gaining popularity as an effective invasive monitoring modality for epileptogenic zone (EZ) localization. The need and indications for SEEG in patients with evident brain lesions is debated.

METHODS:

Retrospective case-control cohort study of 131 patients with lesional MRFE who underwent resective surgery from 2010-2017. Seventy one patients had SEEG followed by resection, and 60 had no SEEG. 3T MRI was used for pre and post-operative evaluation. Volumetric analysis of resection cavities was conducted using T1 volumetric, T2 FLAIR sequences and BrainLAB software.

RESULTS:

Mean age at time of surgery was 30.1 years, epilepsy duration was 18.2 years, monthly seizure frequency was 31.7 and length of follow up was 3.1 years. Comparing SEEG vs non SEEG; mean seizure frequency per month was 80.3 vs 35.1 (P value 0.67) and mean number of failed anti-seizure medications was 6.8 vs 5.8. (P value 0.03). Mean lesion and resection volumes for SEEG and non-SEEG were 16.2 vs 23.7 cm3 and 28.1 vs 43.6 cm3 respectively. Comparing patients with seizure recurrence and patients who remained seizure free, mean number of failed anti-seizure medications 6.86 vs 5.75 (P value 0.01) and mean number of electrodes implanted were 8.1 vs 5.0 (P value 0.005).

CONCLUSION:

In our study, seizure outcomes did not correlate with final resection volume following SEEG evaluation. The higher number of failed anti-seizure medications was the only variable found to correlate with worse outcome.
200 Unbiased Interrogation of Whole Brain Circuits Identifies Neurons That Restore Walking After Spinal Cord Injury
Authors: Cho Newton , Squair Jordan W. , James Nicholas , Baud Laetitia , Leonhartsberger Anna , Sveistyte Kristina , Galan Katia , Barraud Quentin , Goubran Maged , Batti Laura , Pagès Stéphane , Gautier Matthieu , Hutson Thomas , Kathe Claudia , Bichat Arnaud , Rizzo Olivier , Hodara Michael , Bloch Jocelyne , Courtine Grégoire
Published: March 2022

INTRODUCTION:

Currently, there is no cure for locomotor deficits after spinal cord injury (SCI). Despite advances in spinal cord modulation with epidural electrical stimulation, there remains a paucity of therapies targeting the brain due to a poor understanding of the brain’s role post-SCI. Recently developed tissue clearing and light sheet imaging techniques have permitted unbiased three-dimensional interrogation of whole brain circuits, which has opened unexplored avenues for SCI-related brain interrogation.

METHODS:

We established a novel brain interrogation pipeline for SCI by optimizing mouse whole brain clearing, imaging, and atlas registration after a spontaneous recovery lateral hemisection model. We examined both whole brain cell activity and connectivity with the lumbar cord using cFos immunolabelling and virus-mediated projection tracing, respectively, to identify a functionally and anatomically dynamic region correlating with recovery. We interrogated the locomotor role of this region with optogenetics and chemogenetics. In a more clinically relevant rat contusion SCI, we assessed the translatability of deep brain electrical stimulation (DBS) of this region by leveraging an established bipedal robotic interface and rehabilitation paradigm.

RESULTS:

We unexpectedly uncovered the lateral hypothalamus (LH) to be a functionally and anatomically dynamic region post-SCI correlating with recovery. Optogenetic stimulation of mouse LHVglut2 neurons significantly augmented locomotor function, which required medullary reticular formation (MRF) Vglut2-positive neurons. In line with previously demonstrated sparing of MRF-to-spinal cord projections after contusion SCI, we found that LH DBS in rats post-contusion SCI could acutely robustly augment bipedal rat locomotor function.

CONCLUSION:

This is the first demonstration of the LH's role in locomotion post-SCI. The LH is a novel DBS target that robustly augmented locomotor function, dependent on LH and brainstem glutamatergic cells.
201 Tractography Analysis of Deep Brain Stimulation for Obsessive-Compulsive Disorder
Authors: Avecillas-Chasin Josue M. , Choi Ki S. , Mayberg Helen S. , Figee Martijn , Kopell Brian H.
Published: March 2022

INTRODUCTION:

Deep brain stimulation of the anterior limb of the internal capsule (ALIC-DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Animal tracing studies and human tractography suggest that the putative ALIC target for OCD impacts brain circuits for reward, affect and inhibitory control, including projections to orbitofrontal (OFC) and ventromedial (vmPFC) cortex, ventrolateral cortex (vlPFC), dorsal anterior cingulate cortex (dACC), dorsal medial cortex (dmPFC) and dorsolateral prefrontal cortex (dlPFC). The recent development of directional segmented DBS leads may allow for selective stimulation of these ALIC-projections.

METHODS:

We generated structural connectivity maps of therapeutic stimulation using probabilistic tractography in OCD patients treated with ALIC-DBS. Response was defined as = 35% improvement in YBOCS after routine clinical parameter optimization. We also generated the volume of tissue activation (VTA) based on the stimulation parameters at the last follow-up. We estimated probability of connections between the VTA and each projection to the prefrontal regions (vmPFC/OFC, vlPFC, dlPFC, dmPFC, and dACC) in responders and non-responders. To further explore how connectivity would explain clinical improvement, we correlated connectivity values from stimulation sites to cortical regions to the percentage of change in YBOCS using Spearman correlation. Finally, we developed directional tractography activation models and explored personalized circuit-specific targeting and stimulation for patients with directional DBS-leads.

RESULTS:

All patients with ALIC DBS displayed stimulation of OFC/vmPFC and dmPFC connections. However, non-responders had incomplete stimulation of vlPFC, dACC and dlPFC compared to responders. Correlation analysis revealed that fibers from the dorsolateral ALIC to vlPFC were positively associated with improvement in Y-BOCS scores, while connections from ventral ALIC to vmPFC were negatively associated. We were able to successfully construct a stimulation tractography model of directional segmented lead configurations along the medial-lateral axis, which we used for personalized DBS targeting and programming in our most recent patients. Early observations suggest that this directional precision-strategy allows for fast improvement in patient-specific symptom domains for reward, affect and inhibitory control.

CONCLUSION:

Our findings suggest that the therapeutic benefit of ALIC DBS for OCD is associated with stimulation of a subset of specific ALIC WM pathways, which can be selectively targeted using directional DBS-systems.
202 Overlapping Functional and Stereotactic Surgery: A Retrospective Cohort Study of 1-Year Complications
Authors: Greven Alex C. M. , Douglas James A. M. , Malcolm James G. , Campbell Melissa , Lamanna Jason J. , Bray David P. , Howard Brian M. , Willie Jon T. , Boulis Nicholas M. , Gross Robert E.
Published: March 2022

INTRODUCTION:

Overlapping surgery, when one attending surgeon manages two overlapping operating rooms and is present for all of the critical portions of each procedure, is an important policy that improves healthcare access for patients and case volumes for surgeons and surgical trainees. Despite several studies demonstrating the safety and efficacy of overlapping neurosurgical operations, the practice of overlapping surgery remains controversial. To date, there are no studies that investigate long term complication rates of overlapping functional and stereotactic neurosurgical procedures.

METHODS:

851 functional neurosurgical cases were divided into two cohorts: non-overlapping (n = 374) and overlapping (n = 477). The Anesthesia Society of America (ASA) score was used to compare the pre-operative risk for both cohorts. A complication was any surgically related reason that required readmission, reoperation, or an unplanned emergency department or clinic visit that required intervention. Complications were stratified into infectious and non-infectious. Chi-square and independent samples t-tests were used to determine significance.

RESULTS:

The mean ASA score was the same for both cohorts (2.7 +/- 0.6). There were no statistically significant differences in total complication rates (12% vs. 13%, p=0.74) or infectious complication rates (4% vs. 6%, p=0.27) between non-overlapping and overlapping cases. Infections accounted for the highest percentage of complications in both cohorts (33% vs. 44%, p = 0.26). There were no statistically significant differences between mean in-OR time (204 minutes vs. 206 minutes, p = 0.44) or mean skin-to-skin time (127 minutes vs. 129 minutes, p = 0.75) between non-overlapping and overlapping cases.

CONCLUSION:

There is no increased risk of 1-year complications or increased OR time for overlapping functional and stereotactic neurosurgical procedures compared to non-overlapping procedures.
205 Optimization of DBS Electrode Position With Multisite Microelectrode Recordings, Macrostimulation, and Atlas-Based Prediction Maps Visualized in 3D
Authors: Paulo Danika L. , Narasimhan Saramati , Gonzalez Hernan F. J. , Rodriguez William , Li Rui , Konrad Peter , Neimat Joseph S. , Shah Hamid M. , Bick Sarah K. B. , D'Haese Pierre , Dawant Benoit M. , Englot Dario J.
Published: March 2022

INTRODUCTION:

Deep brain stimulation (DBS) at our institution is performed with a custom-made miniature stereotactic frame (STarFix, FHC) with the patient kept awake during electrode implantation to perform microelectrode recordings (MER) and macrostimulation testing. Pre-operative targets are selected with guidance from atlas-based efficacy prediction maps. Multisite intraoperative microelectrode recordings (MER) and macrostimulation data are collected, visualized in 3D in real-time, and integrated into selection of a final target.

METHODS:

A sample of 490 patients treated with DBS at Vanderbilt from 2011-2021 with 892 individual leads were included. During surgery, FHC microelectrodes are implanted in 2-3 test tracks on each side and microelectrode recordings are collected. Atlas-based prediction maps based on position and efficacy of previous cases help guide targeting. Macrostimulation data is collected at multiple depths along the same tracks, with efficacy quantified in quartiles and side effects noted. Preoperative maps and intraoperative data are visualized in 3D with color and integrated in real time to guide optimal FEP selection. Basic statistics were used to calculate percentages and means.

RESULTS:

Of 892 individual leads, 467 (52%) had FEP in the center track and 225 of those had FEP within 1mm of planned target depth. MER was collected in 435 (49%) of test tracks with 380 (43%) recordings collected in the FEP track. Stimulation data was collected for all leads and 867 (97%) of FEP tracks.

CONCLUSION:

Although planned targets were carefully selected preoperatively based on anatomy, coordinates, and guidance from atlas-based efficacy maps, FEP differed from anticipated target in 75% of cases. This discrepancy supports use of multisite MER and stimulation testing and the value of keeping patients awake to complete testing, optimizing their FEP in real-time based on maximal efficacy and minimal side effects. Finally, atlas-based prediction maps help guide initial targeting.
213 5-Aminolevulinic Acid for Enhanced Surgical Visualization of High-Grade Gliomas: A Prospective, Multicenter Study
Authors: Schupper Alexander J. , Baron Rebecca , Cheung William , Rodriguez Jessica , Kalkanis Steven N. , Chohan Mohammad , Nahed Brian V. , Zacharia Brad E. , Jensen Randy L. , Olsen Jeffrey , Sherman Jonathan , Prince Gabrielle , Carter Bob S. , Germano Isabelle M. , Hadjipanayis Constantinos G. , Yong Raymund L.
Published: March 2022

INTRODUCTION:

Greater extent of resection is associated with longer overall survival in patients with high grade gliomas (HGG). 5-aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative agent for HGG tissue.

METHODS:

This single-arm, prospective study included adults aged 18-80 with Karnofsky performance status (KPS)>60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status recorded by the surgeon. Patients were followed for six weeks postoperatively for adverse events, changes in the neurological exam, and KPS. We performed multivariate analyses of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables.

RESULTS:

Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events occurred at a rate of 4.3%. There were 2 unrelated deaths. KPS was significantly lower at 48 hours and 2 weeks, but was not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume.

CONCLUSION:

PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well-tolerated, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.
307 The Hospital Frailty Risk Score Independently Predicts Increased Complication Rates and Healthcare Resource Utilization After Endovascular Treatment of Ruptured Aneurysms
Authors: Koo Andrew B. , Elsamadicy Aladine A. , Sarkozy Margot , Sherman Josiah , Reeves Benjamin , Freedman Isaac G. , Antonios Joseph P. , Sujijantarat Nanthiya , Renado Daniela , Hebert Ryan M. , Malhotra Ajay , Matouk Charles C.
Published: March 2022

INTRODUCTION:

Frailty has emerged as an important indicator of patients who are at greater risk of adverse healthcare outcomes. The Hospital Frailty Risk Score (HFRS) was recently developed utilizing ICD-10 diagnostic codes to identify frailty using routine administrative hospital data but has not been applied to the evaluation of patients with ruptured intracranial aneurysms (IAs).

METHODS:

A retrospective cohort study was performed using the 2016-2017 National Inpatient Sample (NIS) database. All adult patients (=18 years) undergoing endovascular treatment for IAs after subarachnoid hemorrhage were identified using ICD-10-CM diagnostic and procedural codes. Patients were categorized into three HFRS-based frailty cohorts: Low (HFRS<5), Intermediate (HFRS=5 and <15), and High (HFRS=15). Patient demographics, comorbidities, treatment modality, perioperative complications, LOS, discharge disposition, and total cost of hospital admission were assessed. A multivariate logistic regression analyses were used to identify independent predictors of prolonged LOS, increased cost and non-routine discharge.

RESULTS:

Of the 16,290 patients identified, 4,200 (25.8%) were found to be Low frailty, 9,505 (58.3%) were Intermediate, and 2,585 (15.9%) were High by HFRS criteria. A greater proportion of patients in the Intermediate and High frailty cohorts experienced greater than one perioperative complication than Low frailty (Low: 16.4% vs Intermediate: 61.7% vs High: 87.6%, p < 0.001). There is a step-wise increase in mean LOS (Low: 12.2 ± 9.4 days vs Intermediate: 19.0 ± 14.8 days vs High: 26.9 ± 19.3 days, p < 0.001), mean total hospital cost (Low: $62,642 ± 39,552 vs Intermediate:$98,415 ± 63,042 vs High: $132,087 ± 75,263, p < 0.001), and non-routine discharge (Low: 20.0% vs Intermediate: 46.5% vs High: 73.9%, p < 0.001) with increasing frailty. On multivariate regression analysis, similar step-wise impact was found with increasing frailty in prolonged LOS [Intermediate: OR 1.56 (p = 0.02) and High: OR 2.82 (p < 0.001)], hospital cost [High: OR 2.01 (p = 0.001)], and non-routine discharge [Intermediate:OR 1.59 (p < 0.001) and High: OR 3.12 (p < 0.001)].

CONCLUSION:

Our study is the first to use the HFRS to assess the impact of frailty on patients undergoing endovascular treatment of ruptured IAs. We found that greater frailty was associated with increased complications, prolonged LOS, higher costs, and non-routine discharge.
309 Oscillating Between Gratitude and Fear: Lived Experience of Aneurysmal Subarachnoid Hemorrhage Survivors
Authors: Gulek Bernice G. , Haberman Mel , Oneal Gail , James Lois
Published: March 2022

INTRODUCTION:

Aneurysmal subarachnoid hemorrhage (ASAH) is a devastating stroke that affects young adults at a mean age of 55 and mortality rate of 32%. Those who survive are subjected to short- and long-term consequences and the description of self-accounts of experiences are lacking.

METHODS:

This qualitative study utilized Husserl’s descriptive phenomenology methodology. Participants were recruited from an academic medical center outpatient neurosurgery clinic. A semi-structured interview guide and biodemographic background questionnaire guided data collection. Verbatim texts were analyzed according to Giorgi five-step method. The City of Hope Health-Related Quality of Life Theoretical Model gave structure to open-ended interviews, literature review, and for synthesis of results.

RESULTS:

Characteristics of the 16 participants included a median age of 56 years, predominantly female (81%), and six weeks to nine years since aneurysm rupture. Three major qualitative themes were uncovered that explained the structure of the general experience. The salient experiences reported by participants included psychological trauma, difficulty of symptom management, uncertainty, change in social relationships, and being unprepared for life after discharge. Other experiences discovered were difficulty in finding resources, fear of recurrence, social support as critical, and spirituality as a protective factor for wellbeing.

CONCLUSION:

Dimensions of the City of Hope Health-Related Quality of Life Model surfaced as essential, describing life after ASAH, when compared to the study’s conceptual model. The results highlight the need for multidisciplinary comprehensive post discharge support services, programs acknowledging the salience of all dimensions of health-related quality of life, and matching data-based standardized interventions to core sets of patient-reported short- and long-term outcomes.
316 Optimizing Safety in Robotic Lumbar Instrumented Fusions: A Risk Factor Analysis of Robotic Failures
Authors: Ashayeri Kimberly , Norris Zoe , Mottole Nicole , Patel Hershil , Balouch Eaman , O’Malley Nicholas , Frempong-Boadu Anthony , Eisen Leon , Buckland Aaron , Protopsaltis Themistocles
Published: March 2022

INTRODUCTION:

There may be early complications with robot-guided lumbar fusions (RGLF). This study determines risk factors for robot-related complications and suggests optimal OR workflow.

METHODS:

Single-institution retrospective review of 525 RGLFs. Univariate analysis (independent samples t-tests, chi-squared analysis) assessed demographics, Hounsfield units (HU), procedural characteristics, and OR workflow as risk factors for robot registration failures and pedicle screw malpositioning. Multivariate logistic regression of significant factors was conducted. Subanalysis of Anterior Lumbar Interbody Fusion (ALIF) with RGLF was conducted. Receiver operating characteristic (ROC) curve determined thresholds for independent risk factors.

RESULTS:

All RGLF: Lower L1-HU and L5-S1 inclusion were significant risk factors for registration failure on univariate analysis. Placing pedicle screws directly after CT acquisition (PS after CT) and before interbody placement showed fewer registration failures. On multivariate analysis, L1-HU (Odds Ratio (OR): 1.012; p = 0.006), L5-S1 inclusion (OR: 2.795; p = 0.033) were independent risk factors. PS after CT improved registration (OR: 0.145; p = 0.004). Age and female gender were risk factors for pedicle screw malpositioning on univariate analysis. PS after CT showed fewer pedicle screw malpositions on univariate and multivariate (OR: 0.146; p = 0.006) analysis. ALIF with RGLF: PS after CT had fewer registration failures. Low L1-HU units was a risk for registration failure on univariate and multivariate (OR: 1.022; p = 0.001) analysis. ROC analysis of L1-HU showed a 145.85 cutoff. Age and hyperlordotic interbody use were risk factors for pedicle screw malposition on univariate analysis.

CONCLUSION:

Early robot-related complications may be avoided by recognizing risks. PS after CT, before interbody placement may avoid complications including pedicle screw malpositioning. Poor bone quality can lead to registration failures.
321 Mesenchymal Stem Cell-derived Exosomes Improve Functional Recovery in Rats After Traumatic Brain Injury with a Broad Therapeutic Window
Authors: Mahmood Asim , Zhang Yanlu , Zhang Yi , Zhang Zhenggang , Chopp Michael , Xiong Ye
Published: March 2022

INTRODUCTION:

Mesenchymal stem cell (MSC)-derived exosomes are emerging as an important therapy in regenerative medicine with broad applications.

METHODS:

Male rats were injured with controlled cortical impact. In the dose-response study, a single intravenous injection of exosomes (50, 100, 200 µg/rat) or vehicle (n = 8/group) was administered 1 day after TBI. In the therapeutic window study, an intravenous injection of 100 µg exosomes or vehicle was administered on days 1, 4, or 7 after injury (n = 8/group). Neurological function was assessed using Neurological Severity Scores (NSSs), Footfault and Morris Water Maze (MWM) tests. Animals were sacrificed 35 days after TBI and tissues were analyzed using immunohistological studies.

RESULTS:

Compared to the vehicle, regardless of the dose and delay in treatment, exosome treatment significantly improved sensorimotor and cognitive function (NSS, MWM & Footfault tests), reduced hippocampal cell loss, promoted angiogenesis and neurogenesis, and reduced neuroinflammation. Maximum therapeutic benefit was seen with 100 µg dose. The time-dependent treatment data demonstrated that although 1-day post TBI treatment provided greatest improvement, significant functional and histological benefit was also seen with the other two delayed treatments (4 & 7 days post TBI).

CONCLUSION:

These results indicate that exosomes have a wide range of effective doses for treatment of TBI with a therapeutic window of at least 7 days post-injury. This efficacy of delayed treatment enhances the promise of exosome treatment as a potential therapeutic intervention for TBI.
328 Induced Spreading Depolarizations Produce Exaggerated Electrophysiologic Pathology in a Rat Model of Traumatic Brain Injury
Authors: Best Faith , Hopkins Tracy , Hartings Jed , Ngwenya Laura B.
Published: March 2022

INTRODUCTION:

Spreading depolarizations (SDs) are waves of cortical depolarization that cause loss of ion homeostasis, brain silencing, and are prognostic of worse functional outcome in traumatic brain injury (TBI) patients. SDs occur in ∼50% of surgical TBI patients and have potential to spread from areas of injured brain into less-injured or “uninjured” cortex. Understanding differences in how injured versus uninjured cortex responds to SD waves can provide insight for therapeutic targets.

METHODS:

Adult Long Evans rats were subjected to either a moderate lateral fluid percussion injury (LFPI) or a sham injury. Beginning 103.4 ± 28.4 minutes after injury or sham, an electrode was placed at the site of injury (or sham) and electrocorticographic activity was recorded for two hours. SDs were induced every 15 minutes using 1M potassium chloride (KCl) soaked cotton balls placed on a frontal craniectomy separate from the recording site. Saline soaked cotton balls were used as a control.

RESULTS:

A total of 37 SDs were induced in the uninjured group and 32 SDs were induced in the injured group. No SDs were recorded in saline controls. There was no difference in the average time from KCl application to the start of the SD between groups (sham = 136.2, LFPI = 113.9, p = 0.4219). There was also no difference in average amplitude of the direct current (DC) shift (sham = 10.33, LFPI = 13.26, p = 0.1402). However, the injured group had longer average duration of DC shifts (sham = 53.54, LFPI = 99.22, p < 0.0001), longer average depression durations (sham = 206.6, LFPI = 265.8, p = 0.001), and larger average depth of depression (sham = 0.6824, LFPI = 0.8399, p = 0.0018).

CONCLUSION:

Our study revealed electrophysiologic differences between SDs induced in injured versus uninjured animals. Further studies are needed to determine the impact of these differences on neuronal damage and functional outcome.
334 Phase Synchrony within the Right Prefrontal Cortex Predicts Severity of Major Depression
Authors: Xiao Jiayang , Myers John , Metzger Brian , Pirtle Victoria , Mathura Raissa , Allawala Anusha , Adkinson Joshua , Rey Hernan , Goodman Wayne , Pouratian Nader , Bijanki Kelly R. , Sheth Sameer A.
Published: March 2022

INTRODUCTION:

Widespread alteration of brain networks has been observed in people with major depression. Although many conventional treatments are available, nearly one-third of patients could become treatment-resistant. Therefore, a clearer understanding of brain networks in depression is needed in order to develop more effective treatments. As part of an ongoing trial utilizing stereo-EEG (sEEG) intracranial recordings to inform deep brain stimulation (DBS) for treatment-resistant depression (TRD), we measured neural activity in the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (OFC).

METHODS:

Treatment-resistant depression patients (n = 2) were implanted with frontotemporal sEEG electrodes and DBS leads in the ventral capsule/ventral striatum and sub-callosal cingulate. We acquired several measurements of depression severity throughout a 9-day inpatient monitoring period using the computerized adaptive test for depression inventory (CAT-DI). We measured connectivity using the phase locking value (PLV) between oscillations in the right dlPFC and OFC during resting state. Then we examined the relationship between depression severity and peak PLV within alpha band (8-12 Hz).

RESULTS:

We examined the connectivity between the deepest grey matter contact in the right dlPFC and in the right OFC. Peak PLV in alpha band was correlated with CAT-DI score under eyes-open condition in patient 1 and patient 2.

CONCLUSION:

Phase synchrony between right dlPFC and right OFC is involved in the severity of major depression. Increased dlPFC-OFC phase synchrony may relate to increased mood control or management.
339 Influence of SEEG on Temporal Lobectomy
Authors: Kondylis Efstathios , Hsieh Jason K. , Sundar Swetha J. , Sarmey Nehaw , Schmidt Eric , Rammo Richard , Bulacio Juan , Jehi Lara , Bingaman William E.
Published: March 2022

INTRODUCTION:

Seizure outcomes after surgical resection in temporal lobe epilepsy (TLE) are historically better in the presence of a discrete MRI lesion, as the surgical hypothesis is better informed by imaging. The role of intracranial monitoring via stereotactic electroencephalography vs. proceeding directly to surgery in this patient population remains under debate.

METHODS:

SEEG usage trends were investigated for 391 consecutive patients who had temporal lobectomy performed from 2015 to 2020. Correlation with Engel scores at 1 year post-op was performed using chi-square for 259 patients in whom this data was available.

RESULTS:

Sparing of mesial structures was more common in patients who had SEEG (35% vs 20%, p < 0.01). There was a nonsignificant trend towards better outcomes in patients who did not have SEEG (63.5% Engel 1 vs 50.5%, p < 0.55). MRI abnormalities were significantly more prevalent in the cohort that underwent SEEG (92% vs. 58%, p < 0.001), and there was no significant association between the presence of MRI abnormality and outcome (p = 0.59).

CONCLUSION:

We found no statistically significant difference in seizure freedom in patients who undergo temporal lobectomy with SEEG in the presurgical workup. This likely results from SEEG being used when the surgical hypothesis is difficult to formulate, reflected by the increased prevalence of distinct imaging abnormalities in the non-SEEG cohort. Thus it seems that the use of SEEG helps close the gap in outcomes for patients with non-lesional temporal lobe epilepsy. There was no difference in outcomes associated with the decision to spare mesial structures, indicating this effect likely stems from patient selection for surgery. Our future work will look into the connection between SEEG and volumes of surgical resection.
340 Simultaneous Preservation of Language and Executive Function in the Dominant Hemisphere
Authors: Aabedi Alexander A. , Grant Lauren , Kaur Jasleen , Kakaizada Sofia , Andrews John P. , Weissman Daniel , Brang David , Hervey-Jumper Shawn L.
Published: March 2022

INTRODUCTION:

Although awake brain mapping is the gold-standard for the preservation of neurological function in patients with tumors in eloquent regions, it is resource-intensive, costly, and exposes patients to additional perioperative risks. Therefore, the tasks used to map out the brain should be carefully selected and limited to cognitive processes that will be permanently impaired if those brain regions are violated. Impairments in language and executive function are common after tumor resection and are associated with decreased survival. However, mapping of each of those functions separately is often infeasible and antithetical to the delivery of high-value care.

METHODS:

Each participant underwent awake craniotomy with intraoperative mapping using a single lexical retrieval task. Linear mixed-effects modeling was used to assess for a return to preoperative functional levels in language and executive function at preoperative, two days postoperative, and greater than one-month postoperative intervals.

RESULTS:

Participants had lesions in regions that placed them at risk for long-term functional impairments including the perisylvian language network and anterior cingulate gyrus. In the immediate postoperative setting, participants had substantial declines in language and overall executive function performance. However, at longer (i.e., >1 month) testing intervals, performance on both domains returned to baseline levels. Longitudinal changes in picture naming performance were predictive of changes in a measure of executive function that indexes cognitive flexibility.

CONCLUSION:

In patients undergoing resection of brain tissue in the dominant hemisphere, separate mapping of language and executive functions may not be necessary so long as a task that reliably recruits both is implemented during awake brain mapping.
350 Incidence and Long-term Health Care Utilization Associated with Pseudomeningocoele Repair Following Vestibular Schwanomma Resection: A National Database Analysis
Authors: Sharma Mayur , Aljuboori Zaid , Wang Dengzhi , Ugiliweneza Beatrice , Boakye Maxwell , Williams Brian Jeremy , Andaluz Norberto O.
Published: March 2022

INTRODUCTION:

Long-term health care utilization of patients who developed CSF leak and Pseudomeningocoele (PSM) following Vestibular Schwanomma (VS) surgery is not well defined.

METHODS:

MarketScan database were queried using the International Classification of Diseases, Ninth and Tenth Revisions and Current Procedural Terminology 4, from 2000 to 2018. We included patients 18 years of age with PSM diagnosis with at least 2 years of continuous enrollment. Outcomes analyzed were hospital admissions, outpatient services, medication refills and their associated payments.

RESULTS:

Of 1460 patients, 96.6% (n = 1411) had no PSM following surgery for VS, 2.4% (n = 35) were in s-PSM and only 0.95% (n = 14) were in ns-PSM cohorts. Patients in the s-PSM cohort incurred higher hospital readmission rate, outpatient payments compared to those in nd-PSM and ns-PSM cohorts at 6 months, 1-year and 2 –years following the following VS resection. At 1-year following VS resection, median combined payments for s-PSM cohort were $74,683 compared to $42,664 for ns-PSM and $9476 for nd-PSM cohort, p < 0.0001 Similarly, at 2-years, median combined payments median combined payments for s-PSM cohort were $83,351 compared to $63,942 for ns-PSM and $18,839 for nd-PSM cohort, p < 0.0001.

CONCLUSION:

Patients in s-PSM cohort incurred 8 times and 4.4 times the combined payments at 1- and 2-years respectively compared to nd-PSM cohort. Also, patients in ns-PSM cohort incurred 4.5 times and 3.4 times the payments compared to nd-PSM cohort.
362 What Determines the Time Needed for Initial Complete Resolution of Facial Contractions Following Microvascular Decompression for Hemifacial Spasm?
Authors: Al Menabbawy Ahmed , El Refaee Ehab , Elwy Reem , Baldauf Jörg , Schroeder Henry W. S.
Published: March 2022

INTRODUCTION:

Hemifacial spasm (HFS) causes unilateral intermittent and involuntary contractions of facial muscles attributable to compression at the root exit zone of the facial nerve. Microvascular decompression (MVD) is the most effective treatment option for patients with primary HFS. However, the time needed for initial complete resolution of the symptoms varies between patients undergoing the MVD.

METHODS:

We performed a retrospective review of our prospectively maintained database including all HFS patients who underwent de-novo MVD with a minimum follow-up of six months. We excluded patients with a non-arterial etiology of compression. We assessed postoperative outcome clinically based on patient reported symptom severity as a percentage of preoperative symptoms severity. We performed survival analysis and Cox regression to identify the factors significantly affecting the time needed to initial resolution of the symptoms. Statistical analysis was performed using R software version 3.6.3.

RESULTS:

349 patients were included. The mean (SD) follow-up was 55 (36) months. 308 patients (88.3%) demonstrated initial postoperative recovery which occurred in 50% of the cases at a median of 5 days (95%CI 5-7) after surgery, however 93 of whom reported some recurrent symptoms during their postoperative course. AICA, AICA VA compression, or development of postoperative facial palsy independently showed a statistically significant lower hazard of no initial resolution of symptoms compared to other compression etiologies, and evident peripheral indentation of the facial nerve in contrast showed an increased hazard of no initial resolution of symptoms compared to brainstem or no indentation.

CONCLUSION:

AICA compressions, and development of postoperative facial palsy predict a more favorable outcome. Compared to central brain stem indentation of the facial nerve, peripheral indentation is associated with longer time to initial resolution of symptoms.
365 Sciatica of Non-Disc Origin
Authors: Schmidt Bradley T. , Kanarek Andrew , Blakenbaker Donna , Hanna Amgad S.
Published: March 2022

INTRODUCTION:

Sciatica resulting from piriformis muscle compression may respond to surgical decompression of the sciatic nerve via piriformis release. The topic has been very controversial. Pre-operative evaluation with MRI is useful to identify potential changes in either the piriformis muscle or the sciatic nerve that may help confirm the diagnosis of piriformis syndrome.

METHODS:

A retrospective analysis of all patients who underwent piriformis release to decompress the sciatic nerve. All surgeries were performed using a transgluteal approach. All patients (15) had preoperative localization of the piriformis muscle via percutaneous wire placement by interventional radiology using either CT or ultrasound guidance. 30 patients, who had MRI scans of their pelvis unrelated to sciatica, served as the control cohort. We also looked for signal changes in the sciatic nerve seen on MRI, piriformis muscle thickness, and pre versus post-operative numeric rating scale (NRS) assessment.

RESULTS:

Between treatment and control cohorts, there was no difference in basic demographics (other than age). In comparing the surgical and control cohorts, we found that a significant number of patients in the surgical cohort had the sciatic nerve riding over the ischial spine. Distance between the midpoint of the sciatic nerve to the ischial spine was also significantly lower in the surgical cohort. Piriformis thickness was essentially identical between the cohorts. In comparing pre and postoperative NRS pain scores, the aggregate of surgically treated patients had a significant improvement in their pain scores by approximately 4 points. Subgroup analysis of the surgical cohort demonstrated trends toward a larger improvement in NRS when the distance between the midpoint of the sciatic nerve to the ischial spine was <9mm, BMI <25, and piriformis thickness <2cm.

CONCLUSION:

Identifying clear MRI findings related to the sciatic nerve and its trajectory through the pelvis can potentially help identify patients who will better respond to surgery.