Laura Prolo, MD, PhD

View details for DOI 10.1093/noajnl/vdad038

View details for PubMedID 37207118

View details for PubMedCentralID PMC10191190

Abstract

Cancer immunotherapies have unique toxicities. Establishment of grading scales and standardized grade-based treatment algorithms for toxicity syndromes can improve the safety of these treatments, as observed for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) in patients with B cell malignancies treated with chimeric antigen receptor (CAR) T cell therapy. We have observed a toxicity syndrome, distinct from CRS and ICANS, in patients treated with cell therapies for tumors in the central nervous system (CNS), which we term tumor inflammation-associated neurotoxicity (TIAN). Encompassing the concept of 'pseudoprogression,' but broader than inflammation-induced edema alone, TIAN is relevant not only to cellular therapies, but also to other immunotherapies for CNS tumors. To facilitate the safe administration of cell therapies for patients with CNS tumors, we define TIAN, propose a toxicity grading scale for TIAN syndrome and discuss the potential management of this entity, with the goal of standardizing both reporting and management.

View details for DOI 10.1038/s41591-023-02276-w

View details for PubMedID 37024595

View details for PubMedCentralID 7238960

Abstract

In 2001, the National Academy of Medicine, formerly known as the Institute of Medicine (IOM), published their seminal work, Crossing the Quality Chasm: A New Health System for the 21st Century. In this work, the authors called for improved safety, effectiveness, patient-centeredness, timeliness, efficiency, and equity in the United States' healthcare system. Two decades after the publication of this work, healthcare costs continue to rise, but outcomes lag other nations. The objective of this narrative review is to describe research efforts in pediatric neurosurgery with respect to the six quality aims proposed by the IOM, and highlight additional research opportunities.PubMed, Google Scholar, and EBSCOhost were queried to identify studies in pediatric neurosurgery that have addressed the aims proposed by the IOM. Studies were summarized and synthesized to develop a set of research opportunities to advance quality of care.Twenty-three studies were reviewed which focused on the six quality aims proposed by the IOM. Out of these studies, five research opportunities emerged: (1) To examine performance of tools of care, (2) To understand processes surrounding care delivery, (3) To conduct cost-effectiveness analyses for a broader range of neurosurgical conditions, (4) To identify barriers driving healthcare disparities, and (5) To understand patients' and caregivers' experiences receiving care, and subsequently develop tools and programs to address their needs and preferences.There is a growing body of literature examining quality in pediatric neurosurgical care across all aims proposed by the IOM. However, there remains important gaps in the literature that, if addressed, will advance the quality of pediatric neurosurgical care delivery.

View details for DOI 10.1007/s00381-022-05821-z

View details for PubMedID 36695845

Abstract

Recurrence of brain tumors in children after the initial course of treatment remains a problem. This study evaluated the efficacy and safety of reirradiation using stereotactic radiosurgery (SRS) in patients with recurrent pediatric primary brain tumors.This IRB-approved retrospective review included pediatric patients with recurrent primary brain tumors treated at Stanford University from 2000 to 2019 using frameless SRS. Time to local failure (LF) and distant intracranial failure (DIF) were measured from the date of SRS and analyzed using competing risk analysis. Overall survival (OS) and progression-free survival (PFS) were analyzed with the Kaplan-Meier method.In total, 37 patients aged 2-24 years (median age 11 years at recurrence) were treated for 48 intracranial tumors. Ependymoma (38%) and medulloblastoma (22%) were the most common tumor types. The median (range) single fraction equivalent dose of SRS was 16.4 (12-24) Gy. The median (range) follow-up time was 22.9 (1.5-190) months. The median OS of all patients was 36.8 months. Eight of 40 (20%) lesions with follow-up imaging locally recurred. The 2-year cumulative incidence of LF after reirradiation with SRS was 12.8% (95% CI 4.6%-25.4%). The 2-year cumulative incidence of DIF was 25.3% (95% CI 12.9%-39.8%). The median PFS was 18 months (95% CI 8.9-44). Five (10.4%) patients developed toxicities potentially attributed to SRS, including cognitive effects and necrosis.Reirradiation using SRS for recurrent pediatric brain tumors appears safe with good local control. Innovations that improve overall disease control should continue because survival outcomes after relapse remain poor.

View details for DOI 10.3171/2022.8.FOCUS22361

View details for PubMedID 36321285

View details for Web of Science ID 000888571000135

View details for Web of Science ID 000888571001208

Abstract

Craniosynostosis is characterized by the premature fusion of at least one cranial suture. Although evidence suggests that patients with both syndromic and nonsyndromic craniosynostosis may benefit from developmental, behavioral, and mental health support, data on utilization of healthcare services are lacking. In this study the authors compared utilization of mental health care, rehabilitation therapies, and other specialty medical services among children with craniosynostosis, children with plagiocephaly, and healthy controls.The Optum Clinformatics Data Mart database was queried to identify 1340 patients with craniosynostosis, of whom 200 had syndromic craniosynostosis. Long-term utilization of mental health care, rehabilitation therapies, and other medical services up to the age of 6 years was calculated. Rates of utilization were compared to healthy controls (n = 1577) and children with plagiocephaly (n = 1249).Patients with syndromic and nonsyndromic craniosynostosis used mental health care, occupational therapy, speech-language pathology, and other medical services at similar rates (p = 0.1198, p > 0.9999, p = 0.1097, and p = 0.8119, respectively). Mental health services were used more frequently by patients with craniosynostosis (11.0% in patients with syndromic craniosynostosis and 7.5% in those with nonsyndromic craniosynostosis) compared to patients in the plagiocephaly (5.0%, p = 0.0020) and healthy control (2.9%, p < 0.0001) cohorts. Rehabilitation therapies were more frequently used by patients with syndromic craniosynostosis and plagiocephaly (16.0% and 14.1%, respectively), which was significantly higher than use by healthy controls (p < 0.0001). Other medical subspecialty services (developmental pediatrics, ophthalmology, optometry, and audiology) were used by 37.0% of patients with craniosynostosis, compared with 20.9% (p < 0.0001) and 15.1% (p < 0.0001) of patients with plagiocephaly and healthy controls, respectively. Among patients with craniosynostosis, utilization did not differ by race or household income, but it was not uniform by age. Whereas ophthalmology utilization did not differ by age (p = 0.1003), mental health care was most commonly used among older children (p = 0.0107).In this study, the authors demonstrate that rates of utilization of mental health care, rehabilitation therapies, and other medical subspecialty services are similar between patients with syndromic and those with nonsyndromic craniosynostosis, but higher than in healthy controls. Although surgical correction may be considered an isolated event, providers and parents need to monitor all children with craniosynostosis-syndromic and nonsyndromic-for developmental and mental health support longitudinally. Future work should explore risk factors driving utilization, including suture involvement, repair type, and comorbidities.

View details for DOI 10.3171/2022.2.PEDS2253

View details for PubMedID 35426826

Abstract

Intracranial growing teratoma syndrome is a rare phenomenon characterized by enlargement of a germ cell tumor during or after adjuvant therapy despite normalization of tumor markers.1,2 It has been suggested that chemotherapy acts on the nonteratomatous components or induces differentiation of the immature germ cells to mature teratomatous phenotype.3 An 8-year-old boy presented with headache, emesis, and blurry vision. Neuroimaging revealed hydrocephalus with multiple central nervous system masses: pineal gland, suprasellar region, and spine (T8). Elevated serum and cerebrospinal fluid levels of alpha-fetoprotein and beta-human chorionic gonadotropin were found. A ventriculoperitoneal shunt was placed. Despite chemotherapy and decreasing tumor markers, the pineal mass rapidly enlarged, and the patient became somnolent. He underwent microsurgical resection with the diagnosis of mixed germ cell tumor. During his second chemotherapy cycle, the patient endorsed worsening vision and panhypopituitarism. Imaging demonstrated enlargement and honeycomb appearance of the suprasellar mass. The patient and family consented to the procedure, and an endoscopic endonasal approach was performed to access the retroinfundibular region. Removal of the nonfunctional pituitary gland and dorsum sellae was performed. Careful dissection of the tumor from the optic apparatus, hypothalamus, and perforating arteries allowed total resection. Reconstruction with fascia lata and nasoseptal flap was performed. Mature teratoma was found histologically. Postoperative course was complicated by flap hemorrhage resolved by surgical revision. Postoperative imaging showed complete resection. The patient was discharged without other complications and was making excellent recovery. To the best of our knowledge, this is the first reported case of hypothalamic intracranial growing teratoma syndrome successfully treated using an endoscopic endonasal approach.

View details for DOI 10.1227/ons.0000000000000166

View details for PubMedID 35383719

Abstract

The natural history of seizure risk after brain tumor resection is not well understood. Identifying seizure-naive patients at highest risk for postoperative seizure events remains a clinical need. In this study, the authors sought to develop a predictive modeling strategy for anticipating postcraniotomy seizures after brain tumor resection.The IBM Watson Health MarketScan Claims Database was canvassed for antiepileptic drug (AED)- and seizure-naive patients who underwent brain tumor resection (2007-2016). The primary event of interest was short-term seizure risk (within 90 days postdischarge). The secondary event of interest was long-term seizure risk during the follow-up period. To model early-onset and long-term postdischarge seizure risk, a penalized logistic regression classifier and multivariable Cox regression model, respectively, were built, which integrated patient-, tumor-, and hospitalization-specific features. To compare empirical seizure rates, equally sized cohort tertiles were created and labeled as low risk, medium risk, and high risk.Of 5470 patients, 983 (18.0%) had a postdischarge-coded seizure event. The integrated binary classification approach for predicting early-onset seizures outperformed models using feature subsets (area under the curve [AUC] = 0.751, hospitalization features only AUC = 0.667, patient features only AUC = 0.603, and tumor features only AUC = 0.694). Held-out validation patient cases that were predicted by the integrated model to have elevated short-term risk more frequently developed seizures within 90 days of discharge (24.1% high risk vs 3.8% low risk, p < 0.001). Compared with those in the low-risk tertile by the long-term seizure risk model, patients in the medium-risk and high-risk tertiles had 2.13 (95% CI 1.45-3.11) and 6.24 (95% CI 4.40-8.84) times higher long-term risk for postdischarge seizures. Only patients predicted as high risk developed status epilepticus within 90 days of discharge (1.7% high risk vs 0% low risk, p = 0.003).The authors have presented a risk-stratified model that accurately predicted short- and long-term seizure risk in patients who underwent brain tumor resection, which may be used to stratify future study of postoperative AED prophylaxis in highest-risk patient subpopulations.

View details for DOI 10.3171/2022.1.FOCUS21751

View details for PubMedID 35364580

View details for Web of Science ID 000783218700040

Abstract

Neonatal intraventricular hemorrhage (IVH) is a major cause of mortality and morbidity, particularly following premature birth. Even after the acute phase, posthemorrhagic hydrocephalus is a long-term complication, frequently requiring permanent ventriculoperitoneal shunt (VPS) placement. Currently, there are no risk classification methods integrating the constellation of clinical data to predict short- and long-term prognosis in neonatal IVH. To address this need, the authors developed a two-part machine learning approach for predicting short- and long-term outcomes after diagnosis of neonatal IVH. Integrating both maternal and neonatal characteristics, they developed a binary classifier to predict short-term mortality risk and a clinical scale to predict the long-term risk of VPS placement.Neonates with IVH were identified from the Optum Clinformatics Data Mart administrative claims database. Matched maternal and childbirth characteristics were obtained for all patients. The primary endpoints of interest were short-term (30 day) mortality and long-term VPS placement. Classification of short-term mortality risk was evaluated using 5 different machine learning approaches and the best-performing method was validated using a withheld validation subset. Prediction of long-term shunt risk was performed using a multivariable Cox regression model with stepwise variable selection, which was subsequently converted to an easily applied integer risk scale.A total of 5926 neonates with IVH were identified. Most patients were born before 32 weeks' gestation (67.2%) and with low birth weight (81.2%). Empirical 30-day mortality risk was 10.9% across all IVH grades and highest among grade IV IVH (34.3%). Among the neonates who survived > 30 days, actuarial 12-month postdiagnosis risk of shunt placement was 5.4% across all IVH grades and 31.3% for grade IV IVH. The optimal short-term risk classifier was a random forest model achieving an area under the receiver operating characteristic curve of 0.882 with important predictors ranging from gestational age to diverse comorbid medical conditions. Selected features for long-term shunt risk stratification were IVH grade, respiratory distress syndrome, disseminated intravascular coagulation, and maternal preeclampsia or eclampsia. An integer risk scale, termed the Shunt Prediction After IVH in Neonates (SPAIN) scale, was developed from these 4 features, which, evaluated on withheld cases, demonstrated improved risk stratification compared with IVH grade alone (Harrell's concordance index 0.869 vs 0.852).In a large cohort of neonates with IVH, the authors developed a two-pronged, integrated, risk classification approach to anticipate short-term mortality and long-term shunt risk. The application of such approaches may improve the prognostication of outcomes and identification of higher-risk individuals who warrant careful surveillance and early intervention.

View details for DOI 10.3171/2021.11.PEDS21390

View details for PubMedID 35090135

Abstract

Robot-assisted stereoelectroencephalography (sEEG) is frequently employed to localize epileptogenic zones in patients with medically refractory epilepsy (MRE). Its methodology is well described in adults, but less so in children. Given the limited information available on pediatric applications, the objective is to describe the unique technical challenges and considerations of sEEG in the pediatric population. In this report, we describe our institutional experience with the technical aspects of robot-assisted sEEG in an exclusively pediatric epilepsy surgery unit, focusing on pre-, intra-, and post-operative nuances that are particular to the pediatric population. The pediatric population presents several unique challenges in sEEG, including reduced skull thickness relative to adults, incomplete neurologic development, and often special behavioral considerations. Pre-operative selection of putative epileptogenic zones requires careful multidisciplinary decision-making. Intraoperative attention to nuances in positioning, clamp selection, registration, and electrode placement are necessary. Activity considerations and electrode migration and removal are key post-operative considerations. Robot-assisted sEEG is a valuable tool in the armamentarium of techniques to characterize MRE. However, special considerations must be given to the pediatric population to optimize safety and efficacy.

View details for DOI 10.1007/s00381-021-05384-5

View details for PubMedID 34716458

Abstract

OBJECTIVE: Optimal management of pediatric Chiari malformation type I (CM-I) is much debated, chiefly due to the lack of validated tools for outcome assessment, with very few tools incorporating patient-centered measures of health-related quality of life (HRQOL). Although posterior fossa decompression (PFD) benefits a subset of patients, prediction of its impact across patients is challenging. The primary aim of this study was to investigate the role of patient-centered HRQOL measures in the assessment and prediction of outcomes after PFD.METHODS: The authors collected HRQOL data from a cohort of 20 pediatric CM-I patients before and after PFD. The surveys included assessments of selected Patient-Reported Outcomes Measurement Information System (PROMIS) health domains and were used to generate the PROMIS preference (PROPr) score, which is a measure of HRQOL. PROMIS is a reliable standardized measure of HRQOL domains such as pain, fatigue, depression, and physical function, which are all relevant to CM-I. The authors then compared the PROPr scores with Chicago Chiari Outcome Scale (CCOS) scores derived from time-matched clinical documentation. Finally, the authors used the PROPr scores as an outcome measure to predict postsurgical HRQOL improvement at 1 year on the basis of patient demographic characteristics, comorbidities, and radiological and physical findings. The Wilcoxon signed-rank test, Mann-Whitney U-test, and Kendall's correlation were used for statistical analysis.RESULTS: Aggregate analysis revealed improvement of pain severity after PFD (p = 0.007) in anatomical patterns characteristic of CM-I. Most PROMIS domain scores trended toward improvement after surgery, with anxiety and pain interference reaching statistical significance (p < 0.002 and p < 0.03, respectively). PROPr scores also significantly improved after PFD (p < 0.008). Of the baseline patient characteristics, preexisting scoliosis was the most accurate negative predictor of HRQOL improvement after PFD (median -0.095 vs 0.106, p < 0.001). A correlation with modest magnitude (Kendall's tau range 0.19-0.47) was detected between the patient-centered measures and CCOS score.CONCLUSIONS: The authors observed moderate improvement of HRQOL, when measured using a modified panel of PROMIS question banks, in this pilot cohort of pediatric CM-I patients after PFD. Further investigations are necessary to validate this tool for children with CM-I and to determine whether these scores correlate with clinical and radiographic findings.

View details for DOI 10.3171/2021.8.PEDS21228

View details for PubMedID 34715646

Abstract

Measurement of intracranial pressure (ICP) during cerebrospinal fluid (CSF) drainage with an external ventricular drain (EVD) typically requires stopping the flow during measurement. However, there may be benefits to simultaneous ICP measurement and CSF drainage. Several studies have evaluated whether accurate ICP measurements can be obtained while the EVD is open. They report differing outcomes when it comes to error, and hypothesize several sources of error. This study presents an investigation into the fluidic sources of error for ICP measurement with concurrent drainage in an EVD. Our experiments and analytical model both show that the error in pressure measurement increases linearly with flow rate and is not clinically significant, regardless of drip chamber height. At physiologically relevant flow rates (40 mL/hr) and ICP set points (13.6 - 31.3 cmH2O or 10 - 23 mmHg), our model predicts an underestimation of 0.767 cmH2O (0.56 mmHg) with no observed data point showing error greater than 1.09 cmH2O (0.8 mmHg) in our experiment. We extrapolate our model to predict a realistic worst-case clinical scenario where we expect to see a mean maximum error of 1.06 cmH2O (0.78 mmHg) arising from fluidic effects within the drainage system for the most resistive catheter. Compared to other sources of error in current ICP monitoring, error in pressure measurement due to drainage flow is small and does not prohibit clinical use. However, other effects such as ventricular collapse or catheter obstruction could affect ICP measurement under continuous drainage and are not investigated in this study.

View details for DOI 10.7759/cureus.15324

View details for PubMedID 34221772

View details for PubMedCentralID PMC8239198

View details for DOI 10.7759/cureus.15324

View details for Web of Science ID 000656251900014

View details for DOI 10.1161/STROKEAHA.121.036616

Abstract

INTRODUCTION: Patients with complete spinal cord injury (SCI) may develop concurrent sequalae that interact and share symptoms; thus, a careful approach to diagnosis and management of new symptoms is crucial.CASE PRESENTATION: A patient with prior T4 complete SCI presented with progressive autonomic nervous system (ANS) dysfunction. The initial differential diagnosis included syringomyelia and lumbar Charcot arthropathy. He had comorbid heterotopic ossification (HO) of the left hip. Surprisingly, his autonomic symptoms resolved following resection of the HO. In hindsight, loss of motion through the hip caused by HO may have led to hinging through a previously asymptomatic lumbar Charcot joint, causing dysautonomia.DISCUSSION: ANS dysfunction is a disabling sequela of complete SCI and has a broad differential diagnosis. Hip immobility may be an indirect and overlooked cause due to the mechanical relationship between the hip and the lumbar spine.

View details for DOI 10.1038/s41394-020-0286-5

View details for PubMedID 32404876

View details for DOI 10.1016/j.wneu.2020.01.138

View details for PubMedID 31996335

Abstract

Cavernous malformations (CMs) are commonly treated cerebrovascular anomalies in the pediatric population; however, the data on radiographic recurrence of pediatric CMs after surgery are limited. The authors aimed to study the clinical presentation, outcomes, and recurrence rate following surgery for a large cohort of CMs in children.Pediatric patients ( 18 years old) who had a CM resected at a single institution were identified and retrospectively reviewed. Fisher's exact test of independence was used to assess differences in categorical variables. Survival curves were evaluated using the Mantel-Cox method.Fifty-three patients aged 3 months to 18 years underwent resection of 74 symptomatic CMs between 1996 and 2018 at a single institution. The median length of follow-up was 5.65 years. Patients most commonly presented with seizures (45.3%, n = 24) and the majority of CMs were cortical (58.0%, n = 43). Acute radiographic hemorrhage was common at presentation (64.2%, n = 34). Forty-two percent (n = 22) of patients presented with multiple CMs, and they were more likely to develop de novo lesions (71%) compared to patients presenting with a single CM (3.4%). Both radiographic hemorrhage and multiple CMs were independently prognostic for a higher risk of the patient requiring subsequent surgery. Fifty percent (n = 6) of the 12 patients with both risk factors required additional surgery within 2.5 years of initial surgery compared to none of the patients with neither risk factor (n = 9).Patients with either acute radiographic hemorrhage or multiple CMs are at higher risk for subsequent surgery and require long-term MRI surveillance. In contrast, patients with a single CM are unlikely to require additional surgery and may require less frequent routine imaging.

View details for DOI 10.3171/2020.2.PEDS19543

View details for PubMedID 32357336

Abstract

Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.Older patients (age4 yr) experienced improved overall survival compared to younger patients (age<4 yr) (hazard ratio [HR]=0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR=3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR=0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P=.041); extent of resection was not associated with survival in younger patients (P=.880).Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.

View details for DOI 10.1093/neuros/nyaa023

View details for PubMedID 32110805

View details for DOI 10.1016/B978-0-12-812777-3.00010-6

View details for Web of Science ID 000538678900010

View details for DOI 10.1016/j.wneu.2018.03.210

View details for Web of Science ID 000436519600197

Abstract

BACKGROUND: Since the 1980s, numerous operations have replaced posterior lumbar interbody fusion (PLIF) with human bone. These operations often involve expensive implants and complex procedures. Escalating expenditures in lumbar fusion surgery warrant re-evaluation of classical PLIF with allogeneic ilium and without instrumentation. The purpose of this study was to determine the long-term fusion rate and clinical outcomes of PLIF with allogeneic bone (allo-PLIF).METHODS: Between 1981 and 2006, 321 patients aged 12-80 years underwent 339 1-level or 2-level allo-PLIFs for degenerative instability and were followed for 1-28 years. Fusion status was determined by radiographs and as available, by computed tomography scans. Clinical outcome was assessed by the Economic/Functional Outcome Scale.RESULTS: Of the 321 patients, 308 were followed postoperatively (average 6.7 years) and 297 (96%) fused. Fusion rates were lower for patients with substance abuse (89%, P= 0.007). Clinical outcomes in 87% of patients were excellent (52%) or good (35%). Economic/Functional Outcome Scale scores after initial allo-PLIF on average increased 5.2 points. Successful fusion correlated with nearly a 2-point gain in outcome score (P= 0.001). A positive association between a patient characteristic and outcome was observed only with age 65 years and greater, whereas negative associations in clinical outcomes were observed with mental illness, substance abuse, heavy stress to the low back, or industrial injuries. The total complication rate was7%.CONCLUSIONS: With 3 decades of follow-up, we found that successful clinical outcomes are highly correlated with solid fusion using only allogeneic iliac bone.

View details for PubMedID 29631080

View details for PubMedID 29174077

Abstract

Transcervical approaches to the upper cervical spine are challenging because several upper anterior neurovascular structures need to be displaced to provide access. Although various techniques have been described, the anterolateral approach is one of the safest and most effective methods available to access the anterior C2-C3 disc space. Despite the approach's efficacy, however, it can cause postoperative complications because of, at least partly, the inter-surgeon differences in the methods by which the larynx and hypopharynx are displaced medially.We present a case report of a patient treated with a modified anterolateral approach to C2-C3. The approach provided excellent visualization while protecting vital structures. The patient recovered without any postoperative dysphagia or other surgical complications.The anterolateral approach to C2-C3 described herein safely protects the contents of the submandibular triangle while providing a wide exposure for direct access to the C2-C3 disc space. 2015 Wiley Periodicals, Inc. Head Neck 37: E115-E119, 2015.

View details for DOI 10.1002/hed.23951

View details for Web of Science ID 000359605700004

View details for PubMedID 25522016

Abstract

Transcervical approaches to the upper cervical spine are challenging because several upper anterior neurovascular structures need to be displaced to provide access. Although various techniques have been described, the anterolateral approach is one of the safest and most effective methods available to access the anterior C2-C3 disc space. Despite the approach's efficacy, however, it can cause postoperative complications because of, at least partly, the inter-surgeon differences in the methods by which the larynx and hypopharynx are displaced medially.We present a case report of a patient treated with a modified anterolateral approach to C2-C3. The approach provided excellent visualization while protecting vital structures. The patient recovered without any postoperative dysphagia or other surgical complications.The anterolateral approach to C2-C3 described herein safely protects the contents of the submandibular triangle while providing a wide exposure for direct access to the C2-C3 disc space. 2015 Wiley Periodicals, Inc. Head Neck 37: E115-E119, 2015.

View details for DOI 10.1002/hed.23951

View details for PubMedID 25522016

Abstract

The mechanism of release and the role of l-aspartate as a central neurotransmitter are controversial. A vesicular release mechanism for l-aspartate has been difficult to prove, as no vesicular l-aspartate transporter was identified until it was found that sialin could transport l-aspartate and l-glutamate when reconstituted into liposomes. We sought to clarify the release mechanism of l-aspartate and the role of sialin in this process by combining l-aspartate uptake studies in isolated synaptic vesicles with immunocyotchemical investigations of hippocampal slices. We found that radiolabeled l-aspartate was taken up into synaptic vesicles. The vesicular l-aspartate uptake, relative to the l-glutamate uptake, was twice as high in the hippocampus as in the whole brain, the striatum, and the entorhinal and frontal cortices and was not inhibited by l-glutamate. We further show that sialin is not essential for exocytosis of l-aspartate, as there was no difference in ATP-dependent l-aspartate uptake in synaptic vesicles from sialin-knockout and wild-type mice. In addition, expression of sialin in PC12 cells did not result in significant vesicle uptake of l-aspartate, and depolarization-induced depletion of l-aspartate from hippocampal nerve terminals was similar in hippocampal slices from sialin-knockout and wild-type mice. Further, there was no evidence for nonvesicular release of l-aspartate via volume-regulated anion channels or plasma membrane excitatory amino acid transporters. This suggests that l-aspartate is exocytotically released from nerve terminals after vesicular accumulation by a transporter other than sialin.

View details for DOI 10.1096/fj.12-206300

View details for Web of Science ID 000315585200038

View details for PubMedID 23221336

View details for PubMedCentralID PMC3574276

View details for DOI 10.1038/452035a

View details for Web of Science ID 000253671900033

View details for PubMedID 18322516