bluuebunny/crossref_metadata_2025 huggingface dataset:
147 Cranial Nerve Metastasis Treated with Stereotactic Radiosurgery: A Single Institution Experience
Authors: Shahsavari Nastaran , Ahmad Maleeha , Ding Victoria , Pollom Erqi , Han Summer , Soltys Scott G. , Chang Steven D. , Meola Antonio
Published: March 2022

INTRODUCTION:

Cranial nerves are rarely affected in patients with solid, extra-axial malignant tumors. Involvement of the cranial nerves can severely impact the patient’s symptoms and quality of life. Cancer invasion of cranial nerves typically occurs either as leptomeningeal disease (LMD) by CSF spread or as direct spread (DS) from the primary and metastatic head and neck tumors.

METHODS:

All patients with cranial nerve metastases treated with SRS at our institution between April 2003 and February 2021 were retrospectively identified from electronic health records. Clinical assessment and magnetic resonance imaging (MRI) were performed pre-SRS, and 1 to 3 months post-SRS. Kaplan-Meier estimator was used for evaluating overall and progression-free survival (OS and PFS) at 6 months and the log-rank test was applied to compare survival by each disease subgroup.

RESULTS:

Our study cohort consisted of 17 patients including 8 LMD and 9 DS patients. The median age was 60.9 years at initial SRS. In total, 30 cranial nerve metastases were treated with SRS. The median duration of follow-up was 17 months. Among 13 pre-SRS symptomatic patients, symptoms improved in 5 patients (38.4%), remained unchanged in 7 patients (53.8%), and worsened in one patient (7.6%). Local tumor control was achieved in 12 patients (70.6%). Three patients died within 6 months of the initial SRS date, all of whom belonged to the LMD group. Overall survival at 6 months was 82.4% for the entire cohort, with 62.5% and 100% for the LMD and DS subgroups, respectively (P = 0.048). There was insufficient evidence to suggest a difference in progression-free survival between subgroups (p = 0.198).

CONCLUSION:

Our study shows that SRS may be an effective treatment for cranial nerve metastasis providing 70.6% local tumor control, and clinical stability or improvement in over 92% of symptomatic cases.
152 Intraoperative Detection of IDH Mutation Status and Residual Tumor in Glioma
Authors: Garcia Diogo P. , Brown Hannah , Chen Rong , Jentoft Mark E. , Middlebrooks Erik , Chaichana Kaisorn L. , Quinones-Hinojosa Alfredo , Cooks Graham
Published: March 2022

INTRODUCTION:

Maximizing surgical resection in gliomas is associated with a survival benefit, which can be negated by surgery-inflicted neurological deficits, making it imperative to achieve extensive resection without compromising non-infiltrated tissue. Current technologies are sub-optimal in providing intra-operative molecular characterization.

METHODS:

This is a prospective cohort study using intraoperative DESI-MS analysis of smears produced from freshly obtained brain tumor biopsy samples under neuro-navigation guidance to evaluate IDH mutation status via 2-hydroxyglutarate (2-HG) intensity and TCP via measurement of N-acetylaspartic acid (NAA) intensity and characteristic lipid profiles. Blinded review of the smears by a senior neuropathologist was used for validation of IDH mutation status and TCP estimates.

RESULTS:

A total of 465 tumor biopsies from 77 enrolled patients have been collected and analyzed. Evaluation of TCP in an optimization stage based on NAA intensity in 203 biopsies yielded sensitivity, specificity, and accuracy values of 91, 76, and 83%, while assessment through lipid profiling yielded 76, 85, and 81%, respectively. Assessment of IDH mutation status from 71 core biopsies resulted in sensitivity, specificity, and accuracy values of 89, 100 and 94%, respectively. Further optimization of IDH assessment by measurement of the relative intensity of 2-HG against its endogenous standard, glutamate, in nine patients yielded 100% sensitivity, specificity, and accuracy.

CONCLUSION:

We present preliminary results from the first and largest study using DESI-MS to intraoperatively evaluate TCP and IDH mutation status in gliomas. Prospectively, we propose a further modification to allow estimation of TCP and IDH mutation status in surgical cavities without the need of a biopsy by placing a surgical material (e.g. cottonoid) along the surgical margin and transferring material from the blot to a microscope slide prior to DESI-MS analysis.
154 Pituitary Adenomas Evade Apoptosis via Noxa Degradation in Cushing’s Disease
Authors: Asuzu David , Alvarez Reinier , Mandal Debjani , Chittiboina Prashant
Published: March 2022

INTRODUCTION:

Cushing’s disease (CD) arising from ACTH-secreting pituitary adenomas is associated with severe morbidity and mortality. Pathogenic mechanisms of sporadic CD are poorly understood. Using novel syngeneic, pairwise transcriptomic analysis of surgical tissues, we identified transcriptional upregulation of PMAIP1 (encoding pro-apoptotic noxa) in CD adenomas compared to adjacent normal gland.

METHODS:

We investigated noxa protein levels by immunohistochemistry in 10 CD adenoma/normal pairs and by Western blotting in two syngeneic pairs of primary human cell lines from CD adenomas. We validated our key findings in ATT20 murine pituitary corticotroph tumor cells and in corticotroph-enriched murine cell lines mCortEFGF. Proteasomal-mediated degradation was assessed by cycloheximide chase assay. Bortezomib was used for proteasomal inhibition. Cell viability was assessed using CellTiterGlo (Promega).

RESULTS:

Despite PMAIP1 mRNA overexpression in CD, we found consistently low noxa protein in CD adenomas compared to surrounding normal glands but not in growth hormone secreting adenomas or prolactinomas. A cycloheximide assay demonstrated proteasomal-mediated noxa degradation mCortEFGF cells, which was rescued by proteasomal inhibition using bortezomib. Bortezomib treatment decreased cell viability and induced apoptosis in mCortEFGF cells, and also inhibited growth with apoptosis induction in CD adenoma primary cells.

CONCLUSION:

We identified proteasomal-mediated noxa degradation as a mechanism of escape from apoptosis in CD adenomas despite PMAIP1 transcriptional upregulation. Proteasomal inhibition using bortezomib rescued noxa protein levels and induced apoptosis in a dose-dependent fashion. Bortezomib, an FDA approved medication for mantle cell lymphoma, may represent a novel therapeutic target for patients with CD.
157 Supramarginal Resection Impact on Overall Survival for IDH-Wildtype Glioblastoma According to Their Cell Density Distribution and Infiltration Profile: A Mathematical Model
Authors: Vivas-Buitrago Tito , Domingo Ricardo , Tripathi Shashwat , De Biase Gaetano , Ramos-Fresnedo; Desmond A. Brown Andres , Akinduro Oluwaseun , Sherman Wendy , Sabsevitz David S. , Bendok Bernard R. , Parney Ian F. , Chaichana Kaisorn L. , Swanson Kristin R. , Quinones-Hinojosa Alfredo
Published: March 2022

INTRODUCTION:

Supramarginal resection of the T2-FLAIR beyond the T1 contrast enhancement has been suggested to further improve overall survival in glioblastoma (GBM) patients, with a potentially enhanced role in IDH-wildtype. GBMs present with high variability in tumor cell density, distribution, and infiltration patterns evidenced in imaging and histological analysis. Preoperative estimation of GBM grow kinetics with advanced mathematical models can provide further insight for surgical planning.

METHODS:

Volumetric measurements from T1 contrast-enhancing (CE) and T2-FLAIR regions of interest from retrospective pre and postoperative MRIs of patients that underwent a gross total resection of the CE were obtained. Tumor invasiveness profile (proliferation/diffusion (ρ/D) ratio) was calculated using the following formula: where VFL and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were then split into nodular (ND), moderately diffuse (MD), and highly diffuse (HD) subgroups based on their tumor invasiveness profile. SMR extension and survival analyses were performed among groups.

RESULTS:

101 patients met the criteria for this study. Tumors were classified as ND (n = 34), MD (n = 34), and HD (n = 33) tumors. On multivariate analysis, increasing SMR had a significant positive correlation with OS only in MD and HD tumors (HR 0.98; 95% CI, 0.98–0.99; p = 0.05, and HR 0.98; 95% CI, 0.97–0.99; p = 0.02), respectively. On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10%-59%, and 30%-90%, for ND, MD, and HD, respectively.

CONCLUSION:

SMR impact on overall survival in this cohort of IDH-wildtype is significantly influenced by the degree of tumor invasiveness. The results of this study showed increased overall survival with increasing SMR for moderate and highly invasive tumors. Further analysis with SMR grouped in 10% intervals demonstrated an increase in overall survival for all groups, with a lower SMR extension to benefit nodular tumors.
158 Comparison of Cost and Complication Rates for Profiling Hospital Performance in Lumbar Fusion for Spondylolisthesis
Authors: Greenberg Jacob K. , Olsen Margaret , Dibble Christopher , Zhang Justin , Pennicooke Brenton Henry , Yamaguchi Ken , Kelly Michael , Hall Bruce , Ray Zack
Published: March 2022

INTRODUCTION:

Despite growing interest among payers in profiling both the cost and safety of common surgeries, such as lumbar fusion, there is sparse evidence describing the statistical reliability of such measures when applied to lumbar fusion for spondylolisthesis.

METHODS:

We used State Inpatient Databases from nine states to study patients undergoing lumbar fusion for spondylolisthesis from 2010-2017. The study outcome was the statistical reliability of three distinct quality/value metrics. Statistical reliability was measured as the amount of variation between hospitals relative to the total amount of variation for each measure. Total variation includes both between-hospital variation (“signal”) and within-hospital variation (“statistical noise”). Thus, reliability equals signal over (signal plus noise) and ranges from 0-1. We evaluated the reliability of each measure by study year and examined the number of hospitals meeting different thresholds of reliability.

RESULTS:

We included 66,571 elective lumbar fusion surgeries performed at 244 hospitals. 12.0% of patients experienced a complication within 90 days of surgery, including 7.8% with a serious complication. The median reliability of 90-day cost ranged from 0.97-0.99 across study years. By comparison, the median reliability for the overall complication metric ranged from 0.22-0.44, and the reliability of the serious complication measure ranged from 0.30-0.49 across the study years. While some low-volume hospitals had reliabilities for cost as low as 0.51, at least 96% of hospitals had high (>0.7) reliability for cost in any year. By comparison, the reliability of the overall and serious complication rate varied substantially by hospital case volume, and only 0-9% and 0-11% of hospitals had high (>0.7) reliability in any year.

CONCLUSION:

90-day inpatient costs following lumbar fusion for spondylolisthesis are highly reliable for assessing variation across hospitals, whereas overall and serious complications are only moderately reliable for profiling performance.
160 Administrative Data are Unreliable for Ranking Hospital Performance Based on Serious Complications After Spine Fusion
Authors: Greenberg Jacob K. , Olsen Margaret , Poe John , Dibble Christopher , Yamaguchi Ken , Kelly Michael , Hall Bruce , Ray Zack
Published: March 2022

INTRODUCTION:

While payers are increasingly focused on implementing pay- for-performance measures, quality metrics must reliably reflect true differences in performance among the hospitals profiled.

METHODS:

tWe used State Inpatient Databases from nine states to characterize serious complications after elective cervical and thoracolumbar fusion. Hierarchical logistic regression was used to risk-adjust differences in case mix, along with variability from low case volumes. The statistical reliability of this risk-stratified complication rate (RSCR) was assessed as the amount of variation between hospitals relative to the total amount of variation for each measure, calculated separately by fusion type and year. In other words, statistical reliability reflected the amount of variation between hospitals that was not due to chance alone. Finally, we estimated the proportion of hospitals that had sufficient case volumes to obtain reliable (>0.7) complication estimates.

RESULTS:

From 2010-2017 we identified 154,078 cervical and 213,133 thoracolumbar fusion surgeries. 4.2% of cervical fusion patients had a serious complication, and the median RSCR increased from 4.2% in 2010 to 5.5% in 2017. The reliability of the RSCR for cervical fusion was poor and varied substantially by year (range 0.04-0.28). Overall, 7.7% of thoracolumbar fusion patients experienced a serious complication, and the median RSCR varied from 6.8%-8.0% during the study period. Although still modest, the RSCR reliability was higher for thoracolumbar fusion (range 0.16-0.43). Depending on the study year, 0-4.5% of hospitals had sufficient cervical fusion case volume to report reliable (> 0.7) estimates, whereas 15-36% of hospitals reached this threshold for thoracolumbar fusion.

CONCLUSION:

A metric of serious complications was unreliable for benchmarking cervical fusion outcomes and only modestly reliable for thoracolumbar fusion.
164 Racial Disparities in Surgical Recommendations for Primary Central Nervous System Tumors
Authors: Butterfield Jack , Golzarian Sina , Johnson Reid A. , Fellows Emily , Dhawan Sanjay , Marcotte Erin , Venteicher Andrew S.
Published: March 2022

INTRODUCTION:

Racial disparities in treatment and outcomes disproportionately affect patients of color in many surgical fields. There is limited research on these disparities within the field of neurosurgery and most studies report solely on outcomes, not management, of populations at a single institution.

METHODS:

The National Cancer Institute Surveillance, Epidemiology, and End Results database (1971-2015) was used to collect demographic and clinical variables on patients with meningioma (n = 63674), glioblastoma (n = 35258), pituitary adenoma (n = 27506), vestibular schwannoma (n = 11525), astrocytoma (n = 5402), or oligodendroglioma (n = 3977). Univariate and multivariate logistic regression were performed to identify factors independently associated with recommendation against surgical resection.

RESULTS:

Independent of age at diagnosis, sex, tumor histology, grade, and size, Black patients with meningioma (OR 1.20, 95% CI 1.12-1.27, p < 0.001), glioblastoma (OR 1.15, 95% CI 1.02-1.30, p = 0.023), pituitary adenoma (OR 1.19, 95% CI 1.11-1.28, p < 0.001), and vestibular schwannoma (OR 1.56, 95% CI 1.26-1.93, p < 0.001) were more likely to be recommended against surgical resection compared to White patients. Results were consistent after accounting for patient insurance status and rural-urban continuum code for the county of treatment.

CONCLUSION:

On review of the NCI SEER database, Black patients were more likely to be recommended against surgery compared to White patients for a number of primary CNS neoplasms, independent of clinical and demographic factors. Further research is needed to identify specific contributions to this inequity.
165 National Reduction in Cerebral Arteriovenous Malformation Treatment Correlated with Increased Rupture Incidence
Authors: Luther Evan , McCarthy David J. , Burks Joshua D. , Govindarajan Vaidya , Silva Michael A. , Lang Michael J. , Gross Bradley A. , Starke Robert M.
Published: March 2022

INTRODUCTION:

In 2014 “A Randomized Trial of Unruptured Brain Arteriovenous Malformations” (ARUBA) concluded that medical management alone was superior to interventional therapy for adult patients with unruptured brain arteriovenous malformations (AVMs).

METHODS:

154,297 weighted AVM admissions were identified in the United States from 2003 to 2017 in the National Inpatient Sample. Annual AVM intervention and rupture rates were computed and multivariable logistic regression assessed likelihood of AVM intervention pre- and post-ARUBA. Segmented regression identified significant change-points and fitted segmented linear models for annual intervention and rupture rates. Pearson and Spearman coefficients examined correlation between annual AVM intervention and rupture rates.

RESULTS:

For unruptured AVMs, intervention proportion and likelihood of receiving intervention decreased following ARUBA (28.1% to 22.3%, P < 0.0001; adjusted odds ratio 0.857, 95% CI 0.751-0.977, P = 0.02). Ruptured AVM admissions increased from 14.7% to 18.6% after ARUBA (P < 0.0001). Between 2003 and 2017, segmented linear regression identified one significant change-point in unruptured AVM intervention rate between 2014 and 2015. Average annual percent change for rupture incidence and intervention rate increased by 0.49% (P=0.0001) and decreased by 1.17% (P = 0.0001), respectively. Annual AVM intervention rates had a strong inverse correlation with annual AVM rupture incidence (Pearson coefficient = -0.82, P = 0.0002). In 2017, the annual AVM rupture rate (20.6%) surpassed the annual AVM intervention rate (19.7%) for the first time.

CONCLUSION:

Following ARUBA, the odds of intervention for unruptured AVMs have decreased while ruptured AVM incidence has increased. These findings are inversely correlated suggesting that less unruptured AVM treatments may lead to a substantial increase in AVM rupture incidence.
167 Reversible VWF Inhibitor Lyses MCA Occlusion 6 Hours after Large Vessel Occlusion Stroke
Authors: Zakeri Amanda S. , Wheeler Debra , Milks Michael , Kini Aarushi , Carfora Arianna , Joseph Matthew , Gnyawali Surya , Anderson Cole , Stork Taggart , Shujaat Mohammad , Nimjee Shahid M.
Published: March 2022

INTRODUCTION:

Acute ischemic stroke (AIS) is the leading cause of combined morbidity and mortality worldwide. Recombinant tissue plasminogen activator (rtPA) represents the only approved pharmacological treatment for AIS but is limited to treating those within 4.5 hours of stroke onset because of the risk of intracranial hemorrhage. Moreover, it is ineffective in treating large vessel occlusion (LVO) stroke. For this population, endovascular mechanical thrombectomy (MT) effectively recanalizes the occlusion but is limited to highly-specialized hospitals, leaving the vast majority without timely acute treatment.

METHODS:

Utilizing a canine embolic middle cerebral artery occlusion (eMCAO) model of LVO stroke, we assessed DTRI-031 on vessel recanalization after 6 hours of LVO stroke by digital subtraction angiography (DSA). We also measured the effect of recanalization on infarct volume (efficacy) and hemorrhage (safety) using magnetic resonance imaging (MRI). Finally, we assessed the ability of DTRI-025, an oligonucleotide that binds DTRI-031 to reverse DTRI-031 activity.

RESULTS:

DTRI-031 administration after 6 hours of LVO stroke resulted in >TICI 2A in 62.5% and >TICI 2B in 50% of canines (n = 8). Negative control group demonstrated no revascularization (n = 7). Recanalization resulted in reduced infarct volume compared to negative control (p < 0.05, unpaired t-test). None of the animals that received DTRI-031 had intracranial hemorrhage on MRI. Finally, DTRI-025 completely reversed the activity of DTRI-031 within 5 minutes of administration in both whole blood impedance aggregometry (WBA) and PFA-100.

CONCLUSION:

DTRI-031 effectively recanalizes LVO after 6 hours of stroke onset with reduced infarct volume and no incidence of hemorrhage. DTRI-025 rapidly reverses DTRI-031. This drug/reversal agent combination represents a robust yet safe approach to treat AIS.
168 International Study of Intracranial Aneurysm Embolization Using the Woven EndoBridge (WEB) Device: Results of the WorldWideWEB Consortium
Authors: Adeeb Nimer
Published: March 2022

INTRODUCTION:

Pooled data from several registries have shown satisfactory efficacy of the WEB device to treat wide-neck aneurysms. The present study is the most extensive multi-center collaboration that endeavors to investigate the angiographic and clinical outcomes of real-world treatment of intracranial aneurysms with the device.

METHODS:

The World-Wide-WEB consortium is a retrospective multicenter collaboration of international centers with no limitation on aneurysm location or rupture status. Both bifurcation and sidewall aneurysms were included. Angiographic and clinical outcomes and complications were assessed among all consecutive patients along with determinants of adequate aneurysm occlusion (i.e. complete occlusion or neck remnant).

RESULTS:

The cumulative population comprised 674 patients (median age 61.3 years; 71.3% female) with 686 intracranial aneurysms. MCA bifurcation (30.2%) was the most common location. Adequate occlusion was observed in 85.7% of aneurysms at the last follow-up. Aneurysm retreatment was required in 7.9% of aneurysms. Thromboembolic complications were encountered in 7.6% of patients, but only 2.0% had permanent neurological deficits, while 3.1% had hemorrhagic complications. We identified subarachnoid hemorrhage, immediate remnant aneurysm (as compared to complete occlusion), and minor compaction or major compaction (as compared to no compaction) as significant determinants for lower rates of adequate aneurysm occlusion on last follow up (p < 0.01).

CONCLUSION:

This report suggests an adequate efficacy and safety profile of the WEB comparableto the currently availablesurgical andotherendovascular techniques fortreatment ofintracranial aneurysms.
172 No Difference in Reoperation Rates for Adjacent Segment Disease (Operative ASD) in Posterior Cervical Fusions Stopping at C7 Versus T1/T2: A Cohort of 875 Patients
Authors: Guppy Kern H. , Brara Harsimran S. , Royse Kathryn E. , Fennessy Jacob , Norheim Elizabeth , Harris Jessica
Published: March 2022

INTRODUCTION:

The biomechanics at of the cervicothoracic junction (CTJ) have shown that adjacent segment disease (ASD) can occur more frequently if fusions are stopped at C7 although there is varying clinical evidence to support this belief.

METHODS:

A retrospective cohort study from the Kaiser Permanente Spine Registry was completed on adult patients (=18 years old) with the diagnosis of cervical degenerative disc disease, cervical trauma, or cervical deformity who underwent primary PCFs stopping at -C7 or -T1/T2. Reoperation for adjacent segment disease (operative ASD) was the primary outcome and patients were followed until operative ASD, membership termination, death, or 03/31/2020. Time-dependent crude and adjusted, multivariable Cox-Proportional Hazards models were used to evaluate operative ASD rates with adjustment for covariates or risk change estimates more than 10%.

RESULTS:

The cohort consisted of 875 patients with PCFs (between C3 to T1/T2) stopping at either -C7 (n = 470) or -T1/T2 (n = 405) with average follow-up of 4.6 (±3.3) years and average time to operative ASD of 2.7 (±2.8) years. Crude overall incidence rates for stopping at -C7 (2.12% (1.02%-3.86%)) and -T1/T2 (2.48% (1.25%-4.40%)) were comparable with no statistical difference in risk (adjHR = 1.47, 95% CI = 0.61-3.53, p = 0.39). Additionally, we observed no differences in the probability of operative ASD in time-dependent models accounting for a competing risk of membership termination (Grey’s Test p = 0.448).

CONCLUSION:

In our cohort of 875 patients with PCFs ranging from C3 to T1/T2 stopping at -C7 or -T1/T2, with an average follow-up of >4 years, we found no statistical difference in reoperation rates for adjacent segment disease (operative ASD). This is one of the largest series of patients in the literature on reoperation rates for adjacent segment disease in PCFs stopping at -C7 versus -T1/T2.
173 Hydrogel Matrix Human Stem Cell Based Nucleus Pulposus Intervertebral Disc Regeneration
Authors: Perez-Cruet Mick J. , Chaudhry Rasul , Chieng Lee O. , McKee Christina , Rapp Aaron
Published: March 2022

INTRODUCTION:

Degenerative disc disease (DDD) is one of the major causes of chronic debilitating low back pain. DDD is characterized by changes in cell populations that result in loss of extracellular matrix (ECM) water holding capacity of the nucleus pulposus. DDD can lead to translation of physiologic loads from the anterior 2/3 to the posterior 1/3 of the spinal column resulting in stress placed on the facets and ligamentum flavum resulting in hypertrophy and canal stenosis. Novel stem cell regenerative therapies could restore the anterior column load via nucleus pulposus regeneration.

METHODS:

A hydrogel scaffold was created composed of self-assembling polyethylene glycol (PEG) functionalized with acrylate and thiol end groups. The scaffold was impregnated with nucleus pulposus (NP) cells differentiated from human umbilical cord mesenchymal stem cells (MSCs). Impregnated NP-scaffolds were then implanted into an ex vivo rabbit model of DDD and the viability and function of NP cells analyzed.

RESULTS:

The NP-scaffolds limited leakage and retained the cells in the NP region of the degenerated disc. Both the NP-scaffold and disc environment promoted differentiation of the MSCs into cells types capable of producing the ECM including sulfated glycoaminoglycans at levels higher than MSCs injected into the intervertebral disc. NP-scaffold cells also expressed chrondrogenic markers like SOX9, COL2 and ACAN at higher levels as well as NP markers FOXF1, K19, and Vimentin determined by real-time polymerase chain reaction (PCR) and immunostaining.

CONCLUSION:

This study demonstrated that a hydrogen scaffold impregnated with NP cells was much more effective at disc regeneration than NP cells alone and can lead to novel therapies for treating DDD.
177 Impact of Socioeconomics on Loss to Follow-up Following Emergent Surgery for Acute Subdural Hematoma
Authors: Guidry Bradley , Tang Alan R. , Thomas Harrison , Sermarini Anthony , Dambrino Robert J. , Yengo-Kahn Aaron M. , Chambless Lola B. , Morone Peter J. , Chotai Silky
Published: March 2022

INTRODUCTION:

Loss to follow-up (LTF) represents an obstacle in the post-surgical management of patients following acute subdural hematoma (aSDH) evacuation. Identifying the factors associated with LTF is required to improve patient care. We sought to examine potential factors with an emphasis on socioeconomic status (SES).

METHODS:

A retrospective analysis of patients treated surgically for aSDH from 2009-2019 at a level 1 regional trauma center was conducted. The primary outcome was LTF, defined as being scheduled but not receiving any follow-up care post-discharge. The main exposure was Area Deprivation Index (ADI), a neighborhood level composite of education, employment, housing quality, and poverty; this was used to measure SES with higher ADI corresponding to lower SES. Additional candidate factors were identified in the literature and through univariate comparisons of group characteristics. To reduce the number of variables, principal components analysis (PCA) was used; the first six principal components (PCs) contained 82% of the total variance. Multivariable logistic regression was performed to identify the PCs associated with LTF.

RESULTS:

Of the 172 patients included in the study, 36 patients were LTF (21%). The predominant PCs were as follows: increasing age, craniotomy instead of craniectomy, and decreased LOS in PC1; ADI and distance to hospital in PC2; unfavorable discharge mRS and non-home disposition in PC3; uninsured/Medicaid status and increased LOS in PC4; number of comorbidities in PC5; and transfer from OSH and use of craniectomy instead of craniotomy for PC6. In multivariable analysis for LTF, greater ADI and distance to hospital via PC2 (P = 0.009) and uninsured/Medicaid status and increased LOS via PC4 (P = 0.009) were associated with increased odds of LTF.

CONCLUSION:

Socioeconomic factors including increased neighborhood disadvantage, increased distance to hospital and uninsured/Medicaid status impact LTF following emergent surgery for aSDH. These patients with limited resources are at increased risk of losing continuity of care. The health care system must direct efforts to reduce healthcare disparity in these high-risk population.
179 Clinical Outcomes From a Single-Site Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury
Authors: Martin Joel , Curtis Erik , Cleary Daniel , Mendoza Michelle , Jamieson Catriona , Marsala Martin , Ciacci Joseph D.
Published: March 2022

INTRODUCTION:

We previously reported safe implantation and improvement in motor and sensory scores using neural stem cell line (NSC) NSI-566 in chronic thoracic complete spinal cord injury (SCI) patients.

METHODS:

A total of four subjects received NSI-566 spinal cord implantation. All subjects tolerated the procedure well with no serious adverse events in the immediate post-procedure period. Prospective data have been collected including ISNCSCI scores, functional and pain surveys, SCIM scores, electromyography (EMG), Brain Motor Control Assessment (BMCA), and serial MRI.

RESULTS:

Two patients experienced improvements in neurological level of injury (NLI), motor score, and sensory score. BMCA showed newly developed muscle responsiveness in lower limbs to reinforcement maneuvers in one patient. Three subjects experienced new EMG activity in lower muscle groups. Two patients had overall decreased pain scores post-operatively, which included both discomfort and allodynia in the transition zone, surgical site pain, and neuropathic and nociceptive pain elsewhere. MR imaging showed no radiographical evidence of immediate or delayed complications after the stem cell injections.

CONCLUSION:

Our current clinical data demonstrate that spinal grafting of the human NSI-566 cell line in chronic spinal trauma patients is safe with no detectable side effects identified at 60 months after cell delivery. Despite the small sample size, the key strengths of the study are the extensive follow-up period and the timeline of treatment. Like other Phase I studies, this study was intended to provide proof of safety and tolerability and proof of concept data that will justify the next cohort.
181 Frameless Neuronavigation With Computer Vision and Real Time Tracking for Bedside External Ventricular Drain Placement: A Cadaveric Study
Authors: Robertson Faith C. , Sha Raahil , Amich Jose , Lee Benjamin , Lal Avinash , Calvachi Paola , Wu Kyle , Gormley William , Weaver James , Tokuda Junichi
Published: March 2022

INTRODUCTION:

A major obstacle to improving ventriculostomy safety and accuracy with image guidance technologies is the lack of a rapidly deployable, real-time registration and tracking system for a moving patient.

METHODS:

Computer vision technology was used to develop an algorithm for near continuous, automatic, and marker-less image registration. The program fuses a subject’s pre-procedure CT scan to live 3D camera images (Snap-Surface), and movement is incorporated by artificial intelligence driven recalibration (Real-Track). Surface registration error (SRE) and target registration error (TRE) were calculated for five cadaver heads that underwent serial movements (fast and slow velocity roll, pitch, and yaw motions), and several test conditions. Six catheters were placed in each cadaver (30 placements). Post-procedure CT scans allowed comparison of planned and actual catheter position for user error calculation.

RESULTS:

Registration was successful for all five cadaveric specimens (average SRE 0.429 mm, ±0.108). Accuracy of TRE was under 1.2mm throughout specimen movements of low and high velocities of roll, pitch, and yaw movements, with the slowest recalibration time of 0.23 seconds. There were no statistically significant differences in SRE when the specimens were draped or fully undraped (p-value = 0.336). Addition of bright light or performance under dim light did not significantly affect SRE (p-value = 0.742 and 0.859, respectively). Average TRE for catheter placements was 0.862 mm (±0.322), and average user error for the was 1.674 mm (±1.195).

CONCLUSION:

This computer vision-based registration system provides real-time tracking of cadaveric heads with recalibration time of less than one-quarter of a second with sub-millimetric accuracy, and enabled catheter placements with millimetric accuracy. Using this approach to guide bedside ventriculostomy could reduce complications, improve safety, and could be extrapolated to other frameless stereotactic applications in awake, non-immobilized patients.
182 Predictors of Six-Month Inability to Return to Work in Previously Employed Subjects After Mild Traumatic Brain Injury: A TRACK-TBI Pilot Study
Authors: Yue John K. , Phelps Ryan R. L. , Hemmerle Debra P. , Upadhyayula Pavan S. , Winkler Ethan A. , Deng Hansen , Chang Diana , Vassar Mary , Taylor Sabrina , Schnyer David , Lingsma Hester F. , Puccio Ava , Yuh Esther , Mukherjee Pratik , Huang Michael C. , Ngwenya Laura B. , Valadka Alex B. , Markowitz Amy , Okonkwo David O. , Manley Geoffrey T.
Published: March 2022

INTRODUCTION:

Return to work (RTW) is an important milestone of mild traumatic brain injury (mTBI) recovery.

METHODS:

Adult subjects from the prospective multicenter TRACK-TBI Pilot study with mTBI (GCS 13-15) who were employed at baseline, with completed three-and six-month RTW status, and three-month Acute Concussion Evaluation (ACE), were extracted. Univariate and multivariable analyses were performed for six-month RTW, focusing on baseline employment, three-month RTW, and three-month ACE domains (physical, cognitive, sleep, and/or emotional postconcussional symptoms (PCS)). Odds ratios (OR) and 95% confidence intervals [CI] were reported.

RESULTS:

In 152 patients aged 40.7 ± 15.0 years, 72% were employed full-time at baseline. Three- and six-month RTW were 77.6% and 78.9%, respectively. At three months, 59.2%, 47.4%, 46.1% and 31.6% scored positive for ACE physical, cognitive, sleep, and emotional PCS domains, respectively. Three-month RTW predicted six-month RTW (OR = 19.80, 95% CI [7.61-51.52]). On univariate analysis, scoring positive in any three-month ACE domain predicted inability for six-month RTW (OR = 0.10-0.11). On multivariable analysis, emotional symptoms predicted inability to six-month RTW (OR = 0.19 [0.04-0.85]). Subjects who scored positive in all four ACE domains were more likely to be unable to RTW at six-months (4 domains: RTW = 58.3%, vs. 0-to-3 domains: RTW = 9.5%; multivariable OR = 0.09 [0.02-0.33]).

CONCLUSION:

Three-month post-injury is an important time point at which RTW status and PCS should be assessed, as both are prognostic markers for six-month RTW. Clinicians should be particularly vigilant of patients presenting with emotional symptoms and/or with symptoms across multiple PCS categories, as these patients are at further risk of inability to RTW and may benefit from targeted evaluation and support.
183 Predicting Vasospasm and Mortality in Early Severe TBI: A Model Using Serum Cytokines and Clinical Data
Authors: Rindler Rima S. , Robertson Henry , DeYampert LaShondra , Eshraghi Sheila , Schobel-McHugh; Eric Elster Seth , Boulis Nicholas M. , Grossberg Jonathan A.
Published: March 2022

INTRODUCTION:

It is difficult to predict outcomes in patients with severe traumatic brain injury (sTBI) using current clinical tools.

METHODS:

Adult civilian patients were prospectively enrolled in the sTBI arm of the Surgical Critical Care Initiative (SC2i). Patient clinical and serum inflammatory and neuronal protein data were combined and evaluated using the machine learning methods of LASSO and CART to construct parsimonious models for predicting development of post-traumatic vasospasm and mortality. Cross validations were performed to assess the robustness of conclusions. Missing data were imputed with random forest techniques; only variables with less than 10% missingness were included.

RESULTS:

There were 53 patients, of whom 36 (67.9%) developed vasospasm and 10 (18.9%) died. The mean age was 39.2; 22.6% were female. There were an equal number of white (25) and black (25) patients. For vasospasm, LASSO identified Eotaxin and Marshall classification of traumatic brain injury as predictors (XV AUC = 0.77). CART identified S100B as a predictor (full data AUC = 0.75). For mortality, LASSO identified S100B and sRAGE (XV AUC = 0.97), while CART identified S100B (full data AUC = 0.912).

CONCLUSION:

Inflammatory and glial-specific protein levels following sTBI may have predictive value that exceeds conventional clinical variables for certain outcomes. Eotaxin, S100B and radiographic findings highly predict development of post-traumatic vasospasm. S100B and sRAGE highly predict mortality. These results warrant validation in a prospective cohort.
184 Placental Mesenchymal Stromal Cells Seeded on an Extracellular Matrix Scaffold Improve Motor Function Recovery After Acute Spinal Cord Injury
Authors: Kulubya Edwin , Jackson Jordan , Bhaskara Mounika , Kumar Priya , Pivetti Christopher , Avallone Samantha , Paxton Zachary , Reed Camille , Mor Sirjan , Wang Aijun , Farmer Diana
Published: March 2022

INTRODUCTION:

Spinal cord injury (SCI) is a devasting disease associated with severe disability and no effective cure. SCI involves a primary traumatic injury followed by a secondary injury characterized by inflammation, ischemia, and formation of a glial scar. Cellular therapies aim to minimize the secondary injury by protecting the remaining cells and promoting neuronal and glial regeneration. We have shown placental mesenchymal stromal cells (PMSCs) applied in utero improve ambulatory function and preserve motor neurons in an ovine model of spina bifida and have begun a first-in-human clinical trial for fetal spina bifida.

METHODS:

Female Sprague Dawley rats were given a right C5 hemi-contusion injury using an RWD Precise Impactor and 8 rats served as sham surgery controls. Immediately following injury, rats were treated with an ECM only (n = 9) or an ECM seeded with 3 x 105 PMSCs (PMSC-ECM, n = 11). Weekly motor function testing included Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale testing by blinded reviewers. After 8 weeks, rats were euthanized, and tissue collected for histology.

RESULTS:

Four second trimester PMSC cell lines were evaluated with our established anti-apoptotic neuroprotection assay and a single cell line was chosen based on increased neurite outgrowths. Within the PMSC-ECM group, rats had statistically significant improvement in their IBB scores between week 1 and week 8 (p = 0.002) compared to ECM only group, where rats did not show improvement (p = 0.063). When comparing IBB scores between groups at week 8, PMSC-ECM rats had a significantly higher IBB score compared to ECM only rats (p = 0.015).

CONCLUSION:

PMSCs improved motor function recovery in a rodent model of SCI. Further studies include immunohistochemical analysis and delivering PMSC derived exosomes as a cell-free treatment.
186 Dorsal Root Ganglion Stimulation as Rescue Therapy for Intractable Pain Following Failed Spinal Cord Stimulation
Authors: Mandelberg Nataniel , Chapman Kenneth , Spiegel Matthew , van Helmond Noud , Patel Kiran , Yang Ajax , Deer Timothy R. , Mogilner Alon Y.
Published: March 2022

INTRODUCTION:

Despite the demonstrated benefits of spinal cord stimulation (SCS) in patient suffering from chronic pain, loss of efficacy continues to be the primary reason for explant. In order to restore relief in these failed patients, delivery of alternative electrical current can be considered to ‘salvage’ the therapy. Dorsal root ganglion stimulation (DRG-S) is a neuromodulatory technique which acts on a different anatomic target, thereby yielding distinct mechanisms of action and should be considered for such salvage therapy.

METHODS:

This was multicenter retrospective chart review over years 2016-2020 of habituated SCS patients who were later salvaged with DRG-S. Primary endpoints were health related quality of life metrics. Data was gathered preop salvage DRG-S and compared to patients’ last follow-up.

RESULTS:

Fifty-five failed SCS patients were salvaged with DRG-S. The median age was 57 and the most common diagnoses were complex regional pain syndrome and failed back surgery syndrome. Failed waveforms included tonic (n = 27), high frequency (n = 9) and burst (n = 19). The majority of DRG-S leads were placed at bilateral T12 and S1. The mean follow up duration of salvage DRG-S was 27 months. All indices were significantly improved with salvage DRG-S. Numeric rating scale scores decreased from mean 8.7 to 3.8, with 80% of patients achieving at least one minimum clinically important difference ( = 30% improvement). Mean Oswestry disability index scores improved from 65 to 31, signifying an improvement from mostly crippled to moderate disability. EQ5D-5L improved from 0.402 to 0.732. Oral morphine equivalents declined from mean 62 to 38.

CONCLUSION:

These data strongly support DRG-S efficacy in the stable treatment of pain in patients who have previously failed to receive persistent benefit from dorsal column SCS. DRG-S therapy reduces pain and disability while improving quality of life.
193 Arachnoid Cysts as Genetically-encoded Harbingers of Neurodevelopmental Pathology
Authors: Kundishora Adam , Kiziltug Emre , Allington Garrett , Allocco August A. , Smith Hannah , Ocken Jack , Moreno-De-Luca Andres , DiLuna Michael , Jin Sheng C. , Kahle Kristopher
Published: March 2022

INTRODUCTION:

Arachnoid cysts (ACs) are the most common congenital intracranial lesions. While familial cases implicate genetic factors, their ultimate cause remains unknown. Herein, we describe a multi-omics approach to disease state characterization including traditional whole exome sequencing, integrative genomics with analytics of large bulk-RNA and single cell RNA sequencing (scRNAseq) data, and a novel phenomics technique using natural language processing and Human Phenotypic Ontological (HPO) language clustering.

METHODS:

Whole exome sequencing was performed on 1560 individuals (520 parent-offspring "trios"). Genes with likely pathogenic mutations were defined as those with >1 de novo variant (DNV) reaching threshold for exome-wide significance (p<2.5 x 10-6) and having high pLI score (>0.9). This high-confidence pathogenic gene set and a secondary probable pathogenic gene set (>1 DNV, regardless of exome-wide significance or pLI score) were analyzed in bulk-RNA and scRNAseq datasets to assess spatiotemporal and cell-type relationships of gene expression. Phenomic analysis was conducted by subjecting patient medical records to a natural-language-processing (NLP) algorithm. Phenotypes were catalogued with the Human Phenotype Ontology (HPO) language tree and mapped with uniform manifold approximation and projection (UMAP) clustering.

RESULTS:

7 genes reached our pathogenic threshold, ADNP, ARIDB1, KDM5C, PURA, FOXP1, MAP2K1, and SCN2A. Strikingly, all but SCN2A play critical roles in epigenetic regulation of gene expression in the developing brain. Bulk-RNA datasets reveal that these genes converge in networks essential for chromatin remodeling and mRNA processing. scRNAseq datasets revealed an association with excitatory and inter-neurons known to play a role in developmental delay. HPO clustering revealed four major phenotypic clusters defined by neurodevelopmental delay (NDD), seizures, both or asymptomatic. In a subgroup of traditionally phenotyped patients, there was statistically significant enrichment of neuraxial phenotypes - including NDD - among those harboring DNVs.

CONCLUSION:

This novel association between ACs and multiple epigenetic regulators of gene expression provides the first insight into intracranial AC pathobiology. HPO clustering reveals clinically relevant subsets of ACs and implies that traditionally symptomatic or asymptomatic ACs may be harbingers of genetically-driven aberrant neurodevelopment.
196 Multi-omic Convergence of Human Craniosynostosis Genes Within a Developmental Bone-Dura-Brain Nexus
Authors: Kiziltug Emre , Allington Garrett , Kawaguchi Riki , Panchagnula Shreyas , Geschwind Daniel , Kahle Kristopher
Published: March 2022

INTRODUCTION:

Craniosynostosis (CS) is the premature fusion of the calvarial sutures and has long been considered mostly an aesthetic disorder, despite many affected children experiencing neurocognitive deficiencies and seizures. The two types of CS, syndromic and non-syndromic, present with significant genetic clinical heterogeneity, suggesting a complex interplay of genetic and environmental causes. Given the neurodevelopmental symptoms observed in CS patients, we hypothesized the genes involved in the pathophysiology of CS may play a key role in the functional development of the brain.

METHODS:

We applied a multimodal integrative genomic approach to examine the functional relationships as well as the spatiotemporal and cellular interactions of all currently known craniosynostosis-associated genes (CSGs) and also explored whether they are linked to other neurodevelopmental disorders (NDD). To this end, we constructed gene co-expression modules using a bulk-RNA expression dataset with 27 human brains encompassing 16 human brain regions across fetal development into early childhood. We further used scRNA-seq datasets derived from embryonic mouse meninges, calvarial sutures and developmental human brain to identify cell-types enriched with CSGs.

RESULTS:

The set of co-expression modules significantly enriched with CSGs were highly expressed during mid-gestation and in primary motor, somatosensory and prefrontal cortices, and the ganglionic eminence. Moreover, some of these modules were also significantly enriched with autism-spectrum disorder (ASD) and NDD genes. The most significant modules were associated with histone-3 lysine-4 methylation, neural crest differentiation, endochondral ossification and reactive astrogliosis. The mouse meninges scRNAseq analysis showed enrichment in pial and dural fibroblasts. The whole-brain scRNA-seq analysis showed CSGs were enriched in medial ganglionic eminence (MGE)-derived cortical interneurons, astrocytes and oligodendrocyte precursors during mid-fetal brain development.

CONCLUSION:

CSGs may contribute to pathogenesis through epigenetic dysregulation, disrupted neural crest differentiation facilitated by neuroglial cells and MGE interneuron migration very early during development. These processes are in confluence with premature suture fusion mediated by dural and pial fibroblasts.
204 Anatomical Modeling of Two-Trajectory Laser Amygdalohippocampotomy
Authors: Liu David D. , Lauro Peter , Leary Owen P. , Zheng Bryan , Phillips Ronald , Roth Julie , Blum Andrew , Segar David J. , Asaad Wael
Published: March 2022

INTRODUCTION:

Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) is typically performed with one laser trajectory to target the medial temporal lobe (MTL). MTL structures such as piriform and entorhinal cortex are epileptogenic, but due to their relative geometry, are difficult to target with one trajectory while simultaneously maintaining adequate ablation of the amygdala and hippocampus.

METHODS:

Magnetic resonance imaging (MRI) from the Human Connectome Project (HCP) was used to create subject-specific target structures consisting of hippocampus, amygdala, and piriform/entorhinal/perirhinal cortex. An algorithm searched for safe potential trajectories along the hippocampal axis (catheter one) and along the amygdala-piriform axis (catheter two) and compared this to a single trajectory optimized over all structures. The proportion of each structure ablated at various burn radii was evaluated. A cohort of 11 consecutive patients with mTLE received two laser LITT.

RESULTS:

The two-laser trajectory approach was superior at nearly all burn radii for all hippocampal subfields and amygdala nuclei (p < 0.05). Two-laser trajectories achieved full ablation of MTL cortical structures at physiologically realistic burn radii, while one-laser trajectories could not. 5 patients with at least 1 year follow-up (mean = 21.8 months) experienced Engel class I outcomes; 6 patients with less than 1 year follow-up (mean = 6.6 months) are on track for Engel I outcomes.

CONCLUSION:

Large-scale artificial intelligence search through high-quality HCP imaging data reveals the theoretical advantage of two-laser LITT over one-laser LITT.