Accumbens coordinated reset stimulation in mice exhibits ameliorating aftereffects on binge alcohol drinking.
Alcohol use disorder (AUD) affects nearly 5% of the world's adult population. Despite treatment, AUD often manifests with relapse to binge drinking, which has been associated with corticostriatal hypersynchrony involving the nucleus accumbens (NAc).A modified "Drinking in the Dark" protocol was used to provoke binge-like alcohol drinking. We implemented Coordinated Reset Stimulation (CRS), a computationally designed, spatio-temporal stimulation algorithm, to desynchronize abnormal neuronal activity via a deep brain stimulation (DBS) electrode in the NAc of mice exhibiting binge-like alcohol drinking. Integral CRS charge injected would be 2.5% of that of conventional high-frequency DBS.NAc CRS delivery during only the initial phase of exposure to alcohol and prior to the exposure (but not during) significantly reduced binge-like drinking without interfering with social behavior or locomotor activity.NAc CRS ameliorates binge-like alcohol drinking and preliminarily exhibits sustained aftereffects that are suggestive of an unlearning of hypersynchrony.
View details for DOI 10.1016/j.brs.2021.01.015
View details for PubMedID 33524612
Anticipatory human subthalamic area beta-band power responses to dissociable tastes correlate with weight gain.
Neurobiology of disease
The availability of enticing sweet, fatty tastes is prevalent in the modern diet and contribute to overeating and obesity. In animal models, the subthalamic area plays a role in mediating appetitive and consummatory feeding behaviors, however, its role in human feeding is unknown. We used intraoperative, subthalamic field potential recordings while participants (n = 5) engaged in a task designed to provoke responses of taste anticipation and receipt. Decreased subthalamic beta-band (15-30 Hz) power responses were observed for both sweet-fat and neutral tastes. Anticipatory responses to taste-neutral cues started with an immediate decrease in beta-band power from baseline followed by an early beta-band rebound above baseline. On the contrary, anticipatory responses to sweet-fat were characterized by a greater and sustained decrease in beta-band power. These activity patterns were topographically specific to the subthalamic nucleus and substantia nigra. Further, a neural network trained on this beta-band power signal accurately predicted (AUC ≥ 74%) single trials corresponding to either taste. Finally, the magnitude of the beta-band rebound for a neutral taste was associated with increased body mass index after starting deep brain stimulation therapy. We provide preliminary evidence of discriminatory taste encoding within the subthalamic area associated with control mechanisms that mediate appetitive and consummatory behaviors.
View details for DOI 10.1016/j.nbd.2021.105348
View details for PubMedID 33781923
Intraoperative Neuromonitoring for Cerebral Arteriovenous Malformation Embolization: A Propensity-Score Matched Retrospective Database Study.
2021; 13 (1): e12946
Introduction The treatment of cerebral arteriovenous malformations (AVMs) may result in neurologic morbidity, particularly when an AVM is located in or adjacent to eloquent brain regions. Intraoperative neurophysiologic monitoring (IONM) may be utilized to reduce the risk of iatrogenic injury during endovascular AVM embolization; however, IONM for endovascular AVM embolization is not ubiquitously the standard of care. Methods Admissions for AVM embolization were assessed from the IBM MarketScan Commercial and Medicare Supplemental databases (IBM Watson Health, Somers, NY). Inclusion criterion for patients was continuous enrollment six months before and after the index encounter. The use of IONM and presence of intracranial hemorrhage (ICH) were noted. Propensity-score matched cohorts with and without IONM were generated to minimize bias between treatment groups (adjusting for age, sex, and comorbidities). Results From 2007 to 2016, there were 16,279 patients diagnosed with cerebral AVM in the MarketScan database. Embolized patients were stratified into IONM and non-IONM cohorts; there were 357 patients in the IONM cohort and 1775 patients in the non-IONM cohort. Provider types were significantly different between cohorts (p<0.005). Unruptured AVMs were significantly more likely to be embolized with adjunctive IONM (17.7%) compared to ruptured AVMs (7.9%) (p<0.005). After balancing for baseline comorbidities, there were 266 patients in the IONM cohort, and 1347 patients in the non-IONM cohort. Among unruptured AVM patients, IONM was linked to a significantly shorter length of stay (2.72 versus 4.92 days; p<0.005), significantly lower rates of complications within 30 days of discharge (0.00% versus 1.88%; p=0.038), and significantly lower total payment ($40,179 versus $50,844; p<0.0001). Conclusion Endovascular embolization for unruptured AVMs performed with adjunctive IONM was associated with shorter length of stay, lower complication rates, and hospitalization costs.
View details for DOI 10.7759/cureus.12946
View details for PubMedID 33654622
- CSF Otorrhea: A Rare Presentation of Spinal Myxopapillary Ependymoma. Neuro-Chirurgie 2021
Stereotactic Radiosurgery for Vestibular Schwannoma Outcomes in Patients With Perfect Word Recognition-A Retrospective Cohort Study.
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
To investigate tumor control rate and hearing outcomes following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) cases with perfect (100%) word recognition score (WRS).A retrospective cohort study.Tertiary referral center.Inclusion criteria were receiving primary SRS, a pretreatment WRS of 100%, and availability of both pre- and posttreatment audiometric data for evaluation.SRS delivered by Cyberknife.Tumor growth rates and audiological outcomes after SRS.The cohort consisted of 139 patients, with more than 1-year follow-up (mean 6.1 yrs). SRS tumor control rate was 87% for the whole cohort. Growth before SRS was documented in 24% (n = 34 of 139). The proportion of sporadic VS cases who maintained hearing (decline <10 dB of pure-tone audiometry or <20% of WRS) at 3 years was 50%, at 5 years was 45%, and at 10 years was 42%. In multivariate analysis, increased age was found to be predictive of increased hearing loss (p = 0.03), while the following factors were shown not to be significant: sex (p = 0.5), tumor size (p = 0.2), pre-SRS tumor growth (p = 0.5), and target volume (p = 0.42).Among patients with VS who had perfect WRS and underwent SRS, the overall tumor control rate was 87% comparable to observation. Hearing maintenance and preservation of "serviceable" hearing rates after 5 years in VS patients with perfect WRS treated by SRS is less than that when comparing to similar observation cohorts. Given this finding we do not advocate using SRS to preserve hearing, over observation, in tumors with perfect WRS.
View details for DOI 10.1097/MAO.0000000000003039
View details for PubMedID 33443977
Is Uncontrolled Diabetes Mellitus Associated with Incidence of Complications After Posterior Instrumented Lumbar Fusion? A National Claims Database Analysis.
Clinical orthopaedics and related research
Previous research has shown that diabetes mellitus (DM) is associated with postoperative complications, including surgical site infections (SSIs). However, evidence for the association between diabetes control and postoperative complications in patients with DM is mixed. Prior studies relied on a single metric for defining uncontrolled DM, which does not account for glycemic variability, and it is unknown whether a more comprehensive assessment of diabetes control is associated with postoperative complications.(1) Is there a difference in the incidence of SSI after lumbar spine fusion in patients with uncontrolled DM, defined with a comprehensive assessment of glycemic control, compared with patients with controlled DM? (2) Is there a difference in the incidence of other select postoperative complications after lumbar spine fusion in patients with uncontrolled DM compared with patients with controlled DM? (3) Is there a difference in total reimbursements between these groups?We used the PearlDiver Patient Records Database, a national administrative claims database that provides access to the full continuum of perioperative care. We included 46,490 patients with DM undergoing posterior lumbar fusion with instrumentation. Patients were required to be continuously enrolled in the database for at least 1 year before and 90 days after the index procedure. Patients were divided into uncontrolled and controlled DM cohorts, as defined by ICD-9 diagnostic codes. These are based on a comprehensive assessment of glycemic control, including consideration of patient self-monitoring of blood glucose levels, hemoglobin A1c, and the presence/severity of diabetes-related comorbidities. The cohorts differed only by age, insurance type, and Elixhauser comorbidity score. The primary outcome was the incidence of SSI, divided into superficial and deep, within 90 days postoperatively. Secondary complications included the incidence of cerebrovascular events, acute kidney injury, pulmonary embolism, pneumonia, urinary tract infection, blood transfusion, and total reimbursements. These are the sum of reimbursements occurring within 90 days of surgery, which capture the total professional and facility cost burden to the health payer (such as the insurer). We constructed multivariable logistic regression models to adjust for the effects of age, insurance type, and comorbidities.After adjusting for potentially confounding variables including age, insurance type, and comorbidities, we found that patients with uncontrolled DM had an odds ratio for deep SSI of 1.52 (95% confidence interval 1.16 to 1.95; p = 0.002). Similarly, patients with uncontrolled DM had adjusted odds ratios of 1.25 (95% CI 1.01 to 1.53; p = 0.03) for cerebrovascular events, 1.36 (95% CI 1.18 to 1.57; p < 0.001) for acute kidney injury, 1.55 (95% CI 1.16 to 2.04; p = 0.002) for pulmonary embolism, 1.30 (95% CI 1.08 to 1.54; p = 0.004) for pneumonia, 1.33 (95% CI 1.19 to 1.49; p < 0.001) for urinary tract infection, and 1.27 (95% CI 1.04 to 1.53; p = 0.02) for perioperative transfusion. Patients with uncontrolled DM had higher median 90-day total reimbursements than patients with controlled DM: USD 27,915 (interquartile range 5472 to 63,400) versus USD 10,263 (IQR 4101 to 49,748; p < 0.001).Our findings encourage surgeons to take a full diabetic history beyond the HbA1c value, including any self-monitoring of glucose measurements, time in acceptable range for continuous glucose monitors, and/or consideration of the presence/severity of diabetes-related complications before lumbar spine fusion, as HbA1c does not fully capture glycemic control or variability. We emphasize that uncontrolled DM is a clinical, rather than laboratory, diagnosis. Comprehensive diabetes histories should be incorporated into existing preoperative diabetes care pathways and elective surgery could be deferred to improve glycemic control. Future development of an index measure incorporating multidimensional measures of diabetes control (such as continuous or self-glucose monitoring, diabetes-related comorbidities) is warranted.Level III, therapeutic study.
View details for DOI 10.1097/CORR.0000000000001823
View details for PubMedID 34014844
Defining and Describing Treatment Heterogeneity in New-Onset Idiopathic Lower Back and Extremity Pain Through Reconstruction of Longitudinal Care Sequences.
The spine journal : official journal of the North American Spine Society
Despite established guidelines, long-term management of surgically-treated low back pain (LBP) and lower extremity pain (LEP) remains heterogeneous. Understanding care heterogeneity could inform future approaches for standardization of practices.To describe treatment heterogeneity in surgically-managed LBP and LEP.Retrospective study of a nationwide commercial database spanning inpatient and outpatient encounters for enrollees of eligible employer-supplied healthcare plans (2007-2016).A population-based sample of opioid-naïve adult patients with newly-diagnosed LBP or LEP were identified. Inclusion required at least 12-months of pre-diagnosis and post-diagnosis continuous follow-up.Included treatments/evaluations include conservative management (chiropractic manipulative therapy, physical therapy, epidural steroid injections), imaging (x-ray, MRI, CT), pharmaceuticals (opioids, benzodiazepines), and spine surgery (decompression, fusion).Primary outcomes-of-interest were 12-month net healthcare expenditures (inpatient and outpatient) and 12-month opioid usage.Analyses include interrogation of care sequence heterogeneity and temporal trends in sequence-initiating services. Comparisons were conducted in the framework of sequence-specific treatment sequences, which reflect the personalized order of healthcare services pursued by each patient. Outlier sequences characterized by high opioid use and costs were identified from frequently observed surgical treatment sequences using Mahalanobis distance.A total of 2,496,908 opioid-naïve adult patients with newly-diagnosed LBP or LEP were included (29,519 surgical). In the matched setting, increased care sequence heterogeneity was observed in surgical patients (0.51 vs 0.12 previously-unused interventions/studies pursued per month). Early opioid and MRI use has decreased between 2008 and 2015 but is matched by increases in early benzodiazepine and x-ray use. Outlier sequences, characterized by increased opioid use and costs, were found in 5.8% of surgical patients. Use of imaging prior to conservative management was common in patients pursuing outlier sequences compared to non-outlier sequences (96.5% vs 63.8%, p<0.001). Non-outlier sequences were more frequently characterized by early conservative interventions (31.9% vs 7.4%, p<0.001).Surgically-managed LBP and LEP care sequences demonstrate high heterogeneity despite established practice guidelines. Outlier sequences associated with high opioid usage and costs can be identified and are characterized by increased early imaging and decreased early conservative management. Elements that may portend suboptimal longitudinal management could provide opportunities for standardization of patient care.
View details for DOI 10.1016/j.spinee.2021.05.019
View details for PubMedID 34033933
The insulo-opercular cortex encodes food-specific content under controlled and naturalistic conditions.
2021; 12 (1): 3609
The insulo-opercular network functions critically not onlyin encoding taste, but also inguiding behavior based on anticipated food availability. However, there remains no direct measurement of insulo-opercular activity when humans anticipate taste. Here, we collect direct, intracranial recordings during a food task that elicits anticipatory and consummatory taste responses, and during ad libitum consumption of meals. While cue-specific high-frequency broadband (70-170Hz) activity predominant in the left posterior insula is selective for taste-neutral cues, sparse cue-specific regions in the anterior insulaare selective for palatable cues. Latency analysis reveals this insular activity is preceded by non-discriminatory activity in the frontal operculum. During ad libitum meal consumption, time-locked high-frequency broadband activity at the time of food intake discriminates food types and is associated with cue-specific activity during the task. These findings reveal spatiotemporally-specificactivity in the human insulo-opercular cortex that underlies anticipatory evaluation of food across both controlled and naturalistic settings.
View details for DOI 10.1038/s41467-021-23885-4
View details for PubMedID 34127675
An Analysis of Public Interest in Elective Neurosurgical Procedures during the COVID-19 Pandemic through Online Search Engine Trends.
In the wake of the COVID-19 pandemic, the Centers for Medicare & Medicaid Services (CMS) has recommended the temporary cessation of all elective surgeries. The effects on patients' interest of elective neurosurgical procedures are currently unexplored.Using Google Trends (GT), search terms of seven different neurosurgical procedure categories (Trauma, Spine, Tumor, Movement Disorder, Epilepsy, Endovascular, and Miscellaneous) were assessed in terms of relative search volume (RSV) between January 2015 and September 2020. Analyses of search terms were performed for over the short-term (Feb 18th, 2020-Apr 18th, 2020), intermediate-term (Jan 1st, 2020-May 31st, 2020) and long-term (Jan 2015-Sept 2020). State-level interest during phase I re-opening (Apr 28th, 2020-May 31st, 2020) was also evaluated.In the short-term, RSV of four categories (epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the intermediate-term, RSV of five categories (miscellaneous, epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the long-term, RSV of nearly all categories (endovascular, epilepsy, miscellaneous, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. Only the movement disorder procedure category had significantly higher RSV in states that reopened early.With the recommendation for cessation of elective surgeries, patient interest in overall elective neurosurgical procedures have dropped significantly. With gradual reopening, there has been a resurgence in some procedure types. GT has proven to be a useful tracker of patient interest and may be utilized by neurosurgical departments to facilitate outreach strategies.
View details for DOI 10.1016/j.wneu.2020.12.143
View details for PubMedID 33412316
Facial Nerve Paralysis Following Endovascular Embolization: A Case Report and Review of the Literature.
The Annals of otology, rhinology, and laryngology
OBJECTIVE: We report a case of facial nerve paralysis post-endovascular embolization of a sigmoid sinus dural arterio-venous fistula from initial presentation to current management and discuss the merits of observation versus decompression through a systematic review of relevant literature.PATIENT: 61 F with right facial palsy.INTERVENTION: Following a single intravenous dexamethasone injection with oral steroids over 2months, patient was observed with no additional treatment other than Botox chemodenervation and facial rehabilitation.OUTCOME AND RESULTS: The patient initially presented with complete right facial palsy (HB 6/6). Post-op CT imaging indicated Onyx (ev3, Irvine, California, USA) particles present at the geniculate segment of the facial nerve. Observation was chosen over surgical intervention. At the most current follow up of 8months, facial function has improved substantially (HB 2/6).CONCLUSION: Facial palsy is a serious, though rare, complication of transarterial endovascular embolization. With our case report and literature review, we highlight not only how conservative observation is the recommended treatment, but also that facial nerve recovery should be expected to reach near complete recovery, but not sooner than in 3months.
View details for DOI 10.1177/0003489420966611
View details for PubMedID 33135423
Medical malpractice in spine surgery: a review
2020; 49 (5): E16
Medical malpractice is an important but often underappreciated topic within neurosurgery, particularly for surgeons in the early phases of practice. The practice of spinal neurosurgery involves substantial risk for litigation, as both the natural history of the conditions being treated and the operations being performed almost always carry the risk of permanent damage to the spinal cord or nerve roots, a cardiopulmonary event, death, or other dire outcomes. In this review, the authors discuss important topics related to medical malpractice in spine surgery, including tort reform, trends and frequency of litigation claims in spine surgery, wrong-level and wrong-site surgery, catastrophic outcomes including spinal cord injury and death, and ethical considerations.
View details for DOI 10.3171/2020.8.FOCUS20602
View details for Web of Science ID 000585759900016
View details for PubMedID 33130625
Resection of Olfactory Groove Meningiomas Through Unilateral vs. Bilateral Approaches: A Systematic Review and Meta-Analysis
FRONTIERS IN ONCOLOGY
2020; 10: 560706
Introduction: Consensus is limited regarding optimal transcranial approaches (TCAs) for the surgical resection of olfactory groove meningiomas (OGMs). This systematic review and meta-analysis aims to examine operative and peri-operative outcomes of unilateral compared to bilateral TCAs for OGMs. Methods: Electronic databases were searched from inception until December 2019 for studies delineating TCAs for OGM patients. Patient demographics, pre-operative symptoms, surgical outcomes, and complications were evaluated and analyzed with a meta-analysis of proportions. Results: A total of 27 observational case series comparing 554 unilateral vs. 451 bilateral TCA patients were eligible for review. The weighted pooled incidence of gross total resection is 94.6% (95% CI, 90.7-97.5%; I2 = 59.0%; p = 0.001) for unilateral and 90.9% (95% CI, 85.6-95.4%; I2 = 58.1%; p = 0.003) for bilateral cohorts. Similarly, the incidence of OGM recurrence is 2.6% (95% CI, 0.4-6.0%; I2 = 53.1%; p = 0.012) and 4.7% (95% CI, 1.4-9.2%; I2 = 55.3%; p = 0.006), respectively. Differences in oncologic outcomes were not found to be statistically significant (p = 0.21 and 0.35, respectively). Statistically significant differences in complication rates in bilateral vs. unilateral TCA cohorts include meningitis (1.0 vs. 0.0%; p = 0.022) and mortality (3.2 vs. 0.2%; p = 0.007). Conclusions: While both cohorts have similar oncologic outcomes, bilateral TCA patients exhibit higher post-operative complication rates. This may be explained by underlying tumor characteristics necessitating more radical resection but may also indicate increased morbidity with bilateral approaches. However, evidence from more controlled, comparative studies is warranted to further support these findings.
View details for DOI 10.3389/fonc.2020.560706
View details for Web of Science ID 000585195900001
View details for PubMedID 33194626
View details for PubMedCentralID PMC7642686
Predictive Modeling of Long-Term Opioid and Benzodiazepine Use after Intradural Tumor Resection.
The spine journal : official journal of the North American Spine Society
INTRODUCTION: Despite increased awareness of the ongoing opioid epidemic, opioid and benzodiazepine use remain high after spine surgery. In particular, long-term co-prescription of opioids and benzodiazepines have been linked to high risk of overdose-associated death. Tumor patients represent a unique subset of spine surgery patients and few studies have attempted to develop predictive models to anticipate long-term opioid and benzodiazepine use after spinal tumor resection.METHODS: The IBM Watson Health MarketScan Database and Medicare Supplement were assessed to identify admissions for intradural tumor resection between 2007 and 2015. Adult patients were required to have at least 6-months of continuous pre-admission baseline data and 12-months of continuous post-discharge follow-up. Primary outcomes were long-term opioid and benzodiazepine use, defined as at least 6 prescriptions within 12 months. Secondary outcomes were durations of opioid and benzodiazepine prescribing. Logistic regression models, with and without regularization, were trained on an 80% training sample and validated on the withheld 20%.RESULTS: A total of 1,942 patients were identified. The majority of tumors were extramedullary (74.8%) and benign (62.5%). A minority of patients received arthrodesis (9.2%) and most patients were discharged to home (79.1%). Factors associated with post-discharge opioid use duration include tumor malignancy (vs benign, B=19.8 prescribed-days/year, 95% CI 1.1 to 38.5) and intramedullary compartment (vs extramedullary, B=18.1 prescribed-days/year, 95% CI 3.3 to 32.9). Pre- and peri-operative use of prescribed NSAIDs and gabapentin/pregabalin were associated with shorter and longer duration opioid use, respectively. History of opioid and history of benzodiazepine use were both associated with increased post-discharge opioid and benzodiazepine use. Intramedullary location was associated with longer duration post-discharge benzodiazepine use (B=10.3 prescribed-days/year, 95% CI 1.5 to 19.1). Among assessed models, elastic net regularization demonstrated best predictive performance in the withheld validation cohort when assessing both long-term opioid use (AUC=0.748) and long-term benzodiazepine use (AUC=0.704). Applying our model to the validation set, patients scored as low-risk demonstrated a 4.8% and 2.4% risk of long-term opioid and benzodiazepine use, respectively, compared to 35.2% and 11.1% of high-risk patients.CONCLUSIONS: We developed and validated a parsimonious, predictive model to anticipate long-term opioid and benzodiazepine use early after intradural tumor resection, providing physicians opportunities to consider alternative pain management strategies.
View details for DOI 10.1016/j.spinee.2020.10.010
View details for PubMedID 33065272
Boda Bodas and Road Traffic Injuries in Uganda: An Overview of Traffic Safety Trends from 2009 to 2017.
International journal of environmental research and public health
2020; 17 (6)
INTRODUCTION: Road traffic injuries (RTIs) are an important contributor to the morbidity and mortality of developing countries. In Uganda, motorcycle taxis, known as boda bodas, are responsible for a growing proportion of RTIs. This study seeks to evaluate and comment on traffic safety trends from the past decade.METHODS: Traffic reports from the Ugandan police force (2009 to 2017) were analyzed for RTI characteristics. Furthermore, one month of casualty ward data in 2015 and 2018 was collected from the Mulago National Referral Hospital and reviewed for casualty demographics and trauma type.RESULTS: RTI motorcycle contribution rose steadily from 2009 to 2017 (24.5% to 33.9%). While the total number of crashes dropped from 22,461 to 13,244 between 2010 and 2017, the proportion of fatal RTIs increased from 14.7% to 22.2%. In the casualty ward, RTIs accounted for a greater proportion of patients and traumas in 2018 compared to 2015 (10%/41% and 36%/64%, respectively).CONCLUSIONS: Although RTIs have seen a gross reduction in Uganda, they have become more deadly, with greater motorcycle involvement. Hospital data demonstrate a rising need for trauma and neurosurgical care to manage greater RTI patient burden. Combining RTI prevention and care pathway improvements may mitigate current RTI trends.
View details for DOI 10.3390/ijerph17062110
View details for PubMedID 32235768
- Evaluating Shunt Survival Following Ventriculoperitoneal Shunting with and without Stereotactic Navigation in Previously Shunt-Naïve Patients. World neurosurgery 2020
Metformin Potential Impact on the Growth of Vestibular Schwannomas.
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
Previous work has suggested that metformin may possess antineoplastic properties. This study aims to assess the effect of metformin on the growth of sporadic vestibular schwannomas.A retrospective cohort study was performed on patients presenting with radiologically confirmed vestibular schwannomas to Stanford medical center between January 1990 and October 2018. Patients who received metformin during the follow-up period were included and were compared with the control group who were not receiving metformin. Tumor progression and hearing loss are primary and secondary outcomes, respectively.A total of 149 patients were analyzed, with 42 patients receiving metformin. The mean age at presentation is 69.6 (±11.7) years. There are 69 (46.3%) females and 80 (53.7%) males and there is no significant age difference between the groups. Tumor size at presentation is similar between both groups, 8 mm (4-13) in control group and 7.5 mm (4-14) in metformin group. The average follow-up period is 34.2 months (18.3-57.8) and 30.3 months (13.6-69.8) in the metformin and control cohorts, respectively, and they are not significantly different. No significant differences between both groups were found in final American Academy of Otolaryngology - Head and Neck Surgery hearing outcome or poor audiogram outcome. Metformin users are significantly less likely to present with tumor growth at final follow-up compared with nonmetformin users (28.6 versus 49.5%, respectively; p = 0.02).This preliminary result suggests metformin may reduce vestibular schwannoma tumor growth rate and shows potential promise as a novel chemotherapeutic agent. Further studies are needed to validate this finding.
View details for DOI 10.1097/MAO.0000000000002545
View details for PubMedID 31913209
Utilization of Novel High-Resolution, MRI-Based Vascular Imaging Modality for Preoperative Stereoelectroencephalography Planning in Children: A Technical Note.
Stereotactic and functional neurosurgery
Stereoelectroencephalography (SEEG) is a powerful intracranial diagnostic tool that requires accurate imaging for proper electrode trajectory planning to ensure efficacy and maximize patient safety. Computed tomography (CT) angiography and digital subtraction angiography are commonly used, but recent developments in magnetic resonance angiography allow for high-resolution vascular visualization without added risks of radiation. We report on the accuracy of electrode placement under robotic assistance planning utilizing a novel high-resolution magnetic resonance imaging (MRI)-based imaging modality.Sixteen pediatric patients between February 2014 and October 2017 underwent SEEG exploration for epileptogenic zone localization. A gadolinium-enhanced 3D T1-weighted spoiled gradient recalled echo sequence with minimum echo time and repetition time was applied for background parenchymal suppression and vascular enhancement. Electrode placement accuracy was determined by analyzing postoperative CT scans laid over preoperative virtual electrode trajectory paths. Entry point, target point, and closest vessel intersection were measured.For any intersection along the trajectory path, 57 intersected vessels were measured. The mean diameter of an intersected vessel was 1.0343 ± 0.1721 mm, and 21.05% of intersections involved superficial vessels. There were 157 overall intersection + near-miss events. The mean diameter for an involved vessel was 1.0236 ± 0.0928 mm, and superficial vessels were involved in 20.13%. Looking only at final electrode target, 3 intersection events were observed. The mean diameter of an intersected vessel was 1.0125 ± 0.2227 mm. For intersection + near-miss events, 24 were measured. An involved vessel's mean diameter was 1.1028 ± 0.2634 mm. For non-entry point intersections, 45 intersected vessels were measured. The mean diameter for intersected vessels was 0.9526 ± 0.0689 mm. For non-entry point intersections + near misses, 126 events were observed. The mean diameter for involved vessels was 0.9826 ± 0.1008 mm.We believe this novel sequence allows better identification of superficial and deeper subcortical vessels compared to conventional T1-weighted gadolinium-enhanced MRI.
View details for DOI 10.1159/000503693
View details for PubMedID 32062664
Dual antiplatelet therapy after carotid artery stenting: trends and outcomes in a large national database.
Journal of neurointerventional surgery
While dual antiplatelet therapy (dAPT) is standard of care following carotid artery stenting (CAS), the optimal dAPT regimen and duration has not been established.We canvassed a large national database (IBM MarketScan) to identify patients receiving carotid endarterectomy (CEA) or CAS for treatment of ischemic stroke or carotid artery stenosis from 2007 to 2016. We performed univariable and multivariable regression methods to evaluate the impact of covariates on post-CAS stroke-free survival, including post-discharge antiplatelet therapy.A total of 79 084 patients diagnosed with ischemic stroke or carotid stenosis received CEA (71 178; 90.0%) or CAS (7906; 10.0%). After adjusting for covariates, <180 days prescribed post-CAS P2Y12-inhibition was associated with increased risk for stroke (<90 prescribed days HR=1.421, 95% CI 1.038 to 1.946; 90-179 prescribed days HR=1.484, 95% CI 1.045 to 2.106). The incidence of hemorrhagic complications was higher during the period of prescribed P2Y12-inhibition (1.16% per person-month vs 0.49% per person-month after discontinuation, P<0.001). The rate of extracranial hemorrhage was nearly six-fold higher while on dAPT (6.50% per patient-month vs 1.16% per patient-month, P<0.001), and there was a trend towards higher rate of intracranial hemorrhage that did not reach statistical significance (5.09% per patient-month vs 3.69% per patient-month, P=0.0556). Later hemorrhagic events beyond 30 days post-CAS were significantly more likely to be extracranial (P=0.028).Increased duration of post-CAS dAPT is associated with lower rates of readmissions for stroke, and with increased risk of hemorrhagic complications, particularly extracranial hemorrhage. The potential benefit of prolonging dAPT with regard to ischemic complications must be balanced with the corresponding increased risk of predominantly extracranial hemorrhagic complications.
View details for DOI 10.1136/neurintsurg-2020-016008
View details for PubMedID 32414894
Contemporaneous evaluation of patient experience, surgical strategy, and seizure outcomes in patients undergoing stereoelectroencephalography or subdural electrode monitoring.
Intracranial electrographic localization of the seizure onset zone (SOZ) can guide surgical approaches for medically refractory epilepsy patients, especially when the presurgical workup is discordant or functional cortical mapping is required. Minimally invasive stereotactic placement of depth electrodes, stereoelectroencephalography (SEEG), has garnered increasing use, but limited data exist to evaluate its postoperative outcomes in the context of the contemporaneous availability of both SEEG and subdural electrode (SDE) monitoring. We aimed to assess the patient experience, surgical intervention, and seizure outcomes associated with these two epileptic focus mapping techniques during a period of rapid adoption of neuromodulatory and ablative epilepsy treatments.We retrospectively reviewed 66 consecutive adult intracranial electrode monitoring cases at our institution between 2014 and 2017. Monitoring was performed with either SEEG (n = 47) or SDEs (n = 19).Both groups had high rates of SOZ identification (SEEG 91.5%, SDE 88.2%, P = .69). The majority of patients achieved Engel class I (SEEG 29.3%, SDE 35.3%) or II outcomes (SEEG 31.7%, SDE 29.4%) after epilepsy surgery, with no significant difference between groups (P = .79). SEEG patients reported lower median pain scores (P = .03) and required less narcotic pain medication (median = 94.5 vs 594.6 milligram morphine equivalents, P = .0003). Both groups had low rates of symptomatic hemorrhage (SEEG 0%, SDE 5.3%, P = .11). On multivariate logistic regression, undergoing resection or ablation (vs responsive neurostimulation/vagus nerve stimulation) was the only significant independent predictor of a favorable outcome (adjusted odds ratio = 25.4, 95% confidence interval = 3.48-185.7, P = .001).Although both SEEG and SDE monitoring result in favorable seizure control, SEEG has the advantage of superior pain control, decreased narcotic usage, and lack of routine need for intensive care unit stay. Despite a heterogenous collection of epileptic semiologies, seizure outcome was associated with the therapeutic surgical modality and not the intracranial monitoring technique. The potential for an improved postoperative experience makes SEEG a promising method for intracranial electrode monitoring.
View details for DOI 10.1111/epi.16762
View details for PubMedID 33236777
Patterns of Opioid and Benzodiazepine Use in Opioid-Naive Patients with Newly Diagnosed Low Back and Lower Extremity Pain.
Journal of general internal medicine
BACKGROUND: The morbidity and mortality associated with opioid and benzodiazepine co-prescription is a pressing national concern. Little is known about patterns of opioid and benzodiazepine use in patients with acute low back pain or lower extremity pain.OBJECTIVE: To characterize patterns of opioid and benzodiazepine prescribing among opioid-naive, newly diagnosed low back pain (LBP) or lower extremity pain (LEP) patients and to investigate the relationship between benzodiazepine prescribing and long-term opioid use.DESIGN/SETTING: We performed a retrospective analysis of a commercial database containing claims for more than 75 million enrollees in the USA.PARTICIPANTS: Participants were adult patients newly diagnosed with LBP or LEP between 2008 and 2015 who did not have a red flag diagnosis, had not received an opioid prescription in the 6months prior to diagnosis, and had 12months of continuous enrollment after diagnosis.MAIN OUTCOMES AND MEASURES: Among patients receiving at least one opioid prescription within 12months of diagnosis, we defined discrete patterns of benzodiazepine prescribing-continued use, new use, stopped use, and never use. We tested the association of these prescription patterns with long-term opioid use, defined as six or more fills within 12months.RESULTS: We identified 2,497,653 opioid-naive patients with newly diagnosed LBP or LEP. Between 2008 and 2015, 31.9% and 11.5% of these patients received opioid and benzodiazepine prescriptions, respectively, within 12months of diagnosis. Rates of opioid prescription decreased from 34.8% in 2008 to 27.0% in 2015 (P<0.001); however, prescribing of benzodiazepines only decreased from 11.6% in 2008 to 10.8% in 2015. Patients with continued or new benzodiazepine use consistently used more opioids than patients who never used or stopped using benzodiazepines during the study period (one-way ANOVA, P<0.001). For patients with continued and new benzodiazepine use, the odds ratio of long-term opioid use compared with those never prescribed a benzodiazepine was 2.99 (95% CI, 2.89-3.08) and 2.68 (95% CI, 2.62-2.75), respectively.LIMITATIONS: This study used administrative claims analyses, which rely on accuracy and completeness of diagnostic, procedural, and prescription codes.CONCLUSION: Overall opioid prescribing for low back pain or lower extremity pain decreased substantially during the study period, indicating a shift in management within the medical community. Rates of benzodiazepine prescribing, however, remained at approximately 11%. Concurrent prescriptions of benzodiazepines and opioids after LBP or LEP diagnosis were associated with increased risk of long-term opioid use.
View details for DOI 10.1007/s11606-019-05549-8
View details for PubMedID 31720966
- Expenditures and Health Care Utilization Among Adults With Newly Diagnosed LowBack and Lower Extremity Pain JAMA NETWORK OPEN 2019; 2 (5)
Robot-assisted versus manual navigated stereoelectroencephalography in adult medically-refractory epilepsy patients.
2019; 159: 106253
Stereoelectroencephalography (SEEG) has experienced a recent growth in adoption for epileptogenic zone (EZ) localization. Advances in robotics have the potential to improve the efficiency and safety of this intracranial seizure monitoring method. We present our institutional experience employing robot-assisted SEEG and compare its operative efficiency, seizure reduction outcomes, and direct hospital costs with SEEG performed without robotic assistance using navigated stereotaxy.We retrospectively identified 50 consecutive adult SEEG cases at our institution in this IRB-approved study, of which 25 were navigated with image guidance (hereafter referred to as "navigated") (02/2014-10/2016) and 25 were robot-assisted (09/2016-12/2017). A thorough review of medical/surgical history and operative records with imaging and trajectory plans was done for each patient. Direct inpatient costs related to each technique were compared.Most common seizure etiologies for patients undergoing navigated and robot-assisted SEEG included non-lesional and benign temporal lesions. Despite having a higher mean number of leads-per-patient (10.2 ± 3.5 versus 7.2 ± 2.6, P = 0.002), robot-assisted cases had a significantly shorter mean operative time than navigated cases (125.5±48.5 versus 173.4±84.3 min, P = 0.02). Comparison of robot-assisted cases over the study interval revealed no significant difference in mean operative time (136.4±51.4 min for the first ten cases versus 109.9±75.8 min for the last ten cases, P = 0.25) and estimated operative time-per-lead (13.4±6.0 min for the first ten cases versus 12.9±7.7 min for the last ten cases, P = 0.86). The mean depth, radial, target, and entry point errors for robot-assisted cases were 2.12±1.89, 1.66±1.58, 3.05±2.02 mm, and 1.39 ± 0.75 mm, respectively. The two techniques resulted in equivalent EZ localization rate (navigated 88 %, robot-assisted 96 %, P = 0.30). Common types of epilepsy surgery performed consisted of implantation of responsive neurostimulation (RNS) device (56 %), resection (19.1 %), and laser ablation (23.8 %) for navigated SEEG. For robot-assisted SEEG, either RNS implantation (68.2 %) or laser ablation (22.7 %) were performed or offered. A majority of navigated and robot-assisted patients who underwent epilepsy surgery achieved either Engel Class I (navigated 36.8 %, robot-assisted 31.6 %) or II (navigated 36.8 %, robot-assisted 15.8 %) outcome with no significant difference between the groups (P = 0.14). Direct hospital cost for robot-assisted SEEG was 10 % higher than non-robotic cases.This single-institutional study suggests that robotic assistance can enhance efficiency of SEEG without compromising safety or precision when compared to image guidance only. Adoption of this technique with uniform safety and efficacy over a short period of time is feasible with favorable epilepsy outcomes.
View details for DOI 10.1016/j.eplepsyres.2019.106253
View details for PubMedID 31855826
Randomized Controlled Trials in Functional Neurosurgery-Association of Device Approval Status and Trial Quality.
Neuromodulation : journal of the International Neuromodulation Society
Randomized controlled trials (RCTs) have been critical in evaluating the safety and efficacy of functional neurosurgery interventions. Given this, we sought to systematically assess the quality of functional neurosurgery RCTs.We used a database of neurosurgical RCTs (trials published from 1961 to 2016) to identify studies of functional neurosurgical procedures (N = 48). We extracted data on the design and quality of these RCTs and quantified the quality of trials using Jadad scores. We categorized RCTs based on the device approval status at the time of the trial and tested the association of device approval status with trial design and quality parameters.Of the 48 analyzed functional neurosurgery RCTs, the median trial size was 34.5 patients with a median age of 51. The most common indications were Parkinson's disease (N = 20), epilepsy (N = 10), obsessive-compulsive disorder (N = 4), and pain (N = 4). Most trials reported inclusion and exclusion criteria (95.8%), sample size per arm (97.9%), and baseline characteristics of the patients being studied (97.9%). However, reporting of allocation concealment (29.2%), randomization mode (66.7%), and power calculations (54.2%) were markedly less common. We observed that trial quality has improved over time (Spearman r, 0.49). We observed that trials studying devices with humanitarian device exemption (HDE) and experimental indications (EI) tended to be of higher quality than trials of FDA-approved devices (p = 0.011). A key distinguishing quality characteristic was the proportion of HDE and EI trials that were double-blinded, compared to trials of FDA-approved devices (HDE, 83.3%; EI, 69.2%; FDA-approved, 35.3%). Although more than one-third of functional neurosurgery RCTs reported funding from industry, no significant association was identified between funding source and trial quality or outcome.The quality of RCTs in functional neurosurgery has improved over time but reporting of specific metrics such as power calculations and allocation concealment requires further improvement. Device approval status but not funding source was associated with trial quality.
View details for DOI 10.1111/ner.13083
View details for PubMedID 31828896
Optogenetic Modulation for the Treatment of Traumatic Brain Injury.
Stem cells and development
Although research involving traumatic brain injury (TBI) has traditionally focused on the acute clinical manifestations, new studies provide evidence for chronic and progressive neurological sequelae associated with TBI, highlighting the risk of persistent, and sometimes life-long, consequences for affected patients. Several treatment modalities to date have demonstrated efficacy in experimental models. However, there is currently no effective treatment to improve neural structure repair and functional recovery of TBI patients. Optogenetics represents a potential molecular tool for neuromodulation and monitoring cellular activity with unprecedented spatial resolution and millisecond temporal precision. In this review, we discuss the conceptual background and preclinical evidence of optogenetics for neuromodulation, and translational applications for TBI treatment are considered.
View details for DOI 10.1089/scd.2019.0187
View details for PubMedID 31559914
Graft Materials and Biologics for Spinal Interbody Fusion.
2019; 7 (4)
Spinal fusion is the most widely performed procedure in spine surgery. It is the preferred treatment for a wide variety of pathologies including degenerative disc disease, spondylolisthesis, segmental instability, and deformity. Surgeons have the choice of fusing vertebrae by utilizing cages containing autografts, allografts, demineralized bone matrices (DBMs), or graft substitutes such as ceramic scaffolds. Autografts from the iliac spine are the most commonly used as they offer osteogenic, osteoinductive, and osteoconductive capabilities, all while avoiding immune system rejection. Allografts obtained from cadavers and living donors can also be advantageous as they lack the need for graft extraction from the patient. DBMs are acid-extracted organic allografts with osteoinductive properties. Ceramic grafts containing hydroxyapatite can be readily manufactured and are able to provide osteoinductive support while having a long shelf life. Further, bone-morphogenetic proteins (BMPs), mesenchymal stem cells (MSCs), synthetic peptides, and autologous growth factors are currently being optimized to assist in improving vertebral fusion. Genetic therapies utilizing viral transduction are also currently being devised. This review provides an overview of the advantages, disadvantages, and future directions of currently available graft materials. The current literature on growth factors, stem cells, and genetic therapy is also discussed.
View details for DOI 10.3390/biomedicines7040075
View details for PubMedID 31561556
Robotic-Assisted Spine Surgery: History, Efficacy, Cost, And Future Trends.
Robotic surgery (Auckland)
2019; 6: 9–23
Robot-assisted spine surgery has recently emerged as a viable tool to enable less invasive and higher precision surgery. The first-ever spine robot, the SpineAssist (Mazor Robotics Ltd., Caesarea, Israel), gained FDA approval in 2004. With its ability to provide real-time intraoperative navigation and rigid stereotaxy, robotic-assisted surgery has the potential to increase accuracy while decreasing radiation exposure, complication rates, operative time, and recovery time. Currently, robotic assistance is mainly restricted to spinal fusion and instrumentation procedures, but recent studies have demonstrated its use in increasingly complex procedures such as spinal tumor resections and ablations, vertebroplasties, and deformity correction. However, robots do require high initial costs and training, and thus, require justification for their incorporation into common practice. In this review, we discuss the history of spinal robots along as well as currently available systems. We then examine the literature to evaluate accuracy, operative time, complications, radiation exposure, and costs - comparing robotic-assisted to traditional fluoroscopy-assisted freehand approaches. Finally, we consider future applications for robots in spine surgery.
View details for DOI 10.2147/RSRR.S190720
View details for PubMedID 31807602
View details for PubMedCentralID PMC6844237
Expenditures and Health Care Utilization Among Adults With Newly Diagnosed Low Back and Lower Extremity Pain.
JAMA network open
2019; 2 (5): e193676
Low back pain (LBP) with or without lower extremity pain (LEP) is one of the most common reasons for seeking medical care. Previous studies investigating costs in this population targeted patients receiving surgery. Little is known about health care utilization among patients who do not undergo surgery.To assess use of health care resources for LBP and LEP management and analyze associated costs.This cohort study used a retrospective analysis of a commercial database containing inpatient and outpatient data for more than 75 million individuals. Participants were US adults who were newly diagnosed with LBP or LEP between 2008 and 2015, did not have a red-flag diagnosis, and were opiate naive prior to diagnosis. Dates of analysis were October 6, 2018, to March 7, 2019.Newly diagnosed LBP or LEP.The primary outcome was total cost of care within the first 6 and 12 months following diagnosis, stratified by whether patients received spinal surgery. An assessment was performed to determine whether patients who did not undergo surgery received care in accordance with proposed guidelines for conservative LBP and LEP management. Costs resulting from use of different health care services were estimated.A total of 2 498 013 adult patients with a new LBP or LEP diagnosis (median [interquartile range] age, 47 [36-58] years; 1 373 076 [55.0%] female) were identified. More than half (55.7%) received no intervention. Only 1.2% of patients received surgery, but they accounted for 29.3% of total 12-month costs ($784 million). Total costs of care among the 98.8% of patients who did not receive surgery were $1.8 billion. Patients who did not undergo surgery frequently received care that was inconsistent with clinical guidelines for LBP and LEP: 32.3% of these patients received imaging within 30 days of diagnosis and 35.3% received imaging without a trial of physical therapy.The findings suggest that surgery is rare among patients with newly diagnosed LBP and LEP but remains a significant driver of spending. Early imaging in patients who do not undergo surgery was also a major driver of increased health care expenditures. Avoidable costs among patients with typically self-limited conditions result in considerable economic burden to the US health care system.
View details for PubMedID 31074820
Stereoelectroencephalography in children: a review.
2018; 45 (3): E7
Stereoelectroencephalography (SEEG) is an intracranial diagnostic measure that has grown in popularity in the United States as outcomes data have demonstrated its benefits and safety. The main uses of SEEG include 1) exploration of deep cortical/sulcal structures; 2) bilateral recordings; and 3) 3D mapping of epileptogenic zones. While SEEG has gradually been accepted for treatment in adults, there is less consensus on its utility in children. In this literature review, the authors seek to describe the current state of SEEG with a focus on the more recent technology-enabled surgical techniques and demonstrate its efficacy in the pediatric epilepsy population.
View details for PubMedID 30173607
The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra
2018; 13 (2): e0191436
Presynaptic cannabinoid-1 receptors (CB1-R) bind endogenous and exogenous cannabinoids to modulate neurotransmitter release. CB1-Rs are expressed throughout the basal ganglia, including striatum and substantia nigra, where they play a role in learning and control of motivated actions. However, the pattern of CB1-R expression across different striatal compartments, microcircuits and efferent targets, and the contribution of different CB1-R-expressing neurons to this pattern, are unclear. We use a combination of conventional techniques and novel genetic models to evaluate CB1-R expression in striosome (patch) and matrix compartments of the striatum, and in nigral targets of striatal medium spiny projection neurons (MSNs). CB1-R protein and mRNA follow a descending dorsolateral-to-ventromedial intensity gradient in the caudal striatum, with elevated expression in striosomes relative to the surrounding matrix. The lateral predominance of striosome CB1-Rs contrasts with that of the classical striosomal marker, the mu opioid receptor (MOR), which is expressed most prominently in rostromedial striosomes. The dorsolateral-to-ventromedial CB1-R gradient is similar to Drd2 dopamine receptor immunoreactivity and opposite to Substance P. This topology of CB1-R expression is maintained downstream in the globus pallidus and substantia nigra. Dense CB1-R-expressing striatonigral fibers extend dorsally within the substantia nigra pars reticulata, and colocalize with bundles of ventrally extending, striosome-targeted, dendrites of dopamine-containing neurons in the substantia nigra pars compacta (striosome-dendron bouquets). Within striatum, CB1-Rs colocalize with fluorescently labeled MSN collaterals within the striosomes. Cre recombinase-mediated deletion of CB1-Rs from cortical projection neurons or MSNs, and MSN-selective reintroduction of CB1-Rs in knockout mice, demonstrate that the principal source of CB1-Rs in dorsolateral striosomes is local MSN collaterals. These data suggest a role for CB1-Rs in caudal dorsolateral striosome collaterals and striosome-dendron bouquet projections to lateral substantia nigra, where they are anatomically poised to mediate presynaptic disinhibition of both striosomal MSNs and midbrain dopamine neurons in response to endocannabinoids and cannabinomimetics.
View details for DOI 10.1371/journal.pone.0191436
View details for Web of Science ID 000425604300010
View details for PubMedID 29466446
View details for PubMedCentralID PMC5821318