Clear neuroimaging margin at the brain-tumor interface is associated with gross total resection and longer survival in non-enhancing diffuse gliomas.

BACKGROUND: This study aimed to determine whether the presence of distinct glioma margins on preoperative imaging is correlated with improved intraoperative identification of tumor-brain interfaces and overall improved surgical outcomes of non-enhancing gliomas. METHODS: This is a retrospective study of all primary glioma resections at our institution between 2000-2020. Tumors with contrast enhancement or with final pathology other than diffuse infiltrative glial neoplasm (WHO II or WHO III) were excluded. Tumors were stratified into two groups: those with distinct radiographical borders between tumor and brain, and those with ill-defined radiographical margins. Multivariate analysis was performed to determine the impact of clear preoperative margins on the primary outcome of gross-total resection. RESULTS: Within the study period, 59 patients met inclusion criteria, of which 31 (53%) had distinct margins. These patients were predominantly younger (37.6 vs. 48.1 years, P=0.007). Tumor and other patient characteristics were similar in both cohorts, including gender, laterality, size, location, tumor type, grade, and surgical adjuncts utilized (P>0.05). Multivariate regression identified that distinct preoperative margins correlated with increased rates of gross total resection (P=0.02). Distinct margins on preoperative neuroimaging also correlated positively with surgeon identification of intra-operative margins (P<0.0001), fewer deaths over the study period (P=0.01), and longer overall survival (P=0.03). CONCLUSIONS: Distinct glioma-parenchyma margins on preoperative imaging are associated with improved surgical resection for diffuse gliomas, as distinct margins may correlate with distinguishable glioma-brain interfaces intraoperatively. Further prospective studies may discover additional clinical uses for these findings.

Advances in computational and translational approaches for malignant glioma.

Gliomas are the most common primary brain tumors in adults and carry a dismal prognosis for patients. Current standard-of-care for gliomas is comprised of maximal safe surgical resection following by a combination of chemotherapy and radiation therapy depending on the grade and type of tumor. Despite decades of research efforts directed towards identifying effective therapies, curative treatments have been largely elusive in the majority of cases. The development and refinement of novel methodologies over recent years that integrate computational techniques with translational paradigms have begun to shed light on features of glioma, previously difficult to study. These methodologies have enabled a number of point-of-care approaches that can provide real-time, patient-specific and tumor-specific diagnostics that may guide the selection and development of therapies including decision-making surrounding surgical resection. Novel methodologies have also demonstrated utility in characterizing glioma-brain network dynamics and in turn early investigations into glioma plasticity and influence on surgical planning at a systems level. Similarly, application of such techniques in the laboratory setting have enhanced the ability to accurately model glioma disease processes and interrogate mechanisms of resistance to therapy. In this review, we highlight representative trends in the integration of computational methodologies including artificial intelligence and modeling with translational approaches in the study and treatment of malignant gliomas both at the point-of-care and outside the operative theater in silico as well as in the laboratory setting.

Deep Brain Stimulation for the Treatment of Hemichorea: Case Series and Literature Review.

Background: Hemichorea (HC) and its severe form hemiballismus (HB) are rare movement disorders which can be medically refractory to treatments and may need surgical intervention. Case Report: We report 3 patients with HC-HB who had meaningful clinical improvement with unilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi). We identified 8 prior cases of HC-HB treated with GPi-DBS, and a majority of these patients experienced significant improvement in their symptoms. Discussion: GPi-DBS can be considered in medically refractory HC-HB in carefully selected patients. However, data is limited to small case series and further studies are needed.

Deep Brain Stimulation for Cockayne Syndrome-Associated Movement Disorder.

Cockayne syndrome (CS) is a rare progeroid disorder characterized by multisystem degeneration, including neurological dysfunction, for which deep brain stimulation (DBS) is a proposed treatment. This study represents only the third case of DBS for CS-associated movement disorder and the first in which both proposed targets had devices implanted, allowing for direct comparison. A case of DBS for CS-associated movement disorder is presented. Previous literature documents two cases with one targeting the ventral intermediate nucleus of the thalamus (VIM) and the other targeting the globus pallidus interna (GPi). Our patient underwent stimulation of GPi nuclei followed by repositioning to VIM nuclei with improved symptom control using VIM stimulation. In all cases, there was a significant clinical benefit without off-target effects. CS-associated movement disorder exhibits phenotypic variability for which DBS is a viable treatment. Target selection should be driven by clinical phenotype.

Fulminant non-infectious peri-electrode edema after deep brain stimulation system implantation in a pediatric patient.

Non-infectious peri-electrode edema is a rare complication after implantation of a deep brain stimulation (DBS) electrode. DBS is frequently used in the management of movement disorders with increasing interest surrounding its value in more rare disorders associated with movement abnormalities. This is the report of a 10-year-old male with Cockayne syndrome who acutely developed symptomatic non-infectious, non-hemorrhagic peri-electrode edema 18 days postoperatively from implantation of a DBS system targeting the bilateral globus pallidus internus. CT head confirmed extensive vasogenic edema along the entire length of the left electrode, and infectious workup was negative. The patient required admission to the pediatric intensive care unit for management utilizing steroid, hypertonic, and hyperosmolar therapy due to the amount of mass effect. Symptoms reduced over a 7-day hospital stay and were completely resolved at 1 month without removal of the DBS system. Management of this rare entity remains controversial and often involves the use of steroids and anti-epileptic prophylaxis. This represents the first case of non-infectious peri-electrode edema reported in a pediatric patient and is especially notable for its fulminant nature.

Estimating the prevalence of neurosurgical interventions in adults with spina bifida using the Health Facts data set: implications for transition planning and the development of adult clinics.

OBJECTIVE: As the care of patients with spina bifida continues to evolve, life expectancy is increasing, leading to a critical need for transition planning from pediatric-based to adult-based care. The burden of neurosurgical care for adults with spina bifida remains unknown. In this study, the authors sought to use a large national data set to estimate the prevalence of neurosurgical interventions in adults with spina bifida. METHODS: This study utilized Health Facts, which is a de-identified proprietary data set abstracted from all Cerner electronic health records. It includes 69 million unique patients with > 500 million encounters in 580 centers. Validation, technical exclusions, and data filters were applied to obtain an appropriate cohort of patients. The ICD-9 and ICD-10 codes for all types of spinal dysraphism, as well as the Current Procedural Terminology (CPT) codes for hydrocephalus procedures, spinal cord untethering, and Chiari decompression, were queried and records were retrieved. Demographic variables along with differences in age groups and temporal trends were analyzed. RESULTS: Overall, 24,764 unique patients with ≥ 1 encounter with a spinal dysraphism diagnosis between 2000 and 2017 were identified. The pediatric cohort included 11,123 patients with 60,027 separate encounters, and the adult cohort included 13,641 patients with 41,618 separate encounters. The proportion of females was higher in the adult (62.9%) than in the pediatric (51.4%) cohort. Annual encounters were stable from 2 to 18 years of age, but then decreased by approximately half with a precipitous drop after age 21 years. The sex distribution of adults and children who underwent procedures was similar (54.6% female adults vs 52.4% female children). Surgical interventions in adults were common. Between 2013 and 2017, there were 4913 procedures for hydrocephalus, with 2435 (49.6%) adult patients. Similarly, 273 (33.3%) of the 819 tethered cord procedures were performed in adults, as were 307 (32.9%) of 933 Chiari decompressions. CONCLUSIONS: The Health Facts database offered another option for studying care delivery and utilization in patients aging with spina bifida. The median age of this population has now reached early adulthood, and a significant number of neurosurgical procedures were performed in adults. An abrupt drop in the rate of encounters occurred at 21 years of age, possibly reflecting transition issues such as access-to-care problems and lack of coordinated care.

Clinical and Radiologic Outcomes of Thoracolumbar Fusions Using Intraoperative CT Guidance and Stereotactic Navigation in a Spinal Trauma Population: An Analysis of 58 Patients.

STUDY DESIGN: Retrospective review of prospectively collected single-institution database. OBJECTIVE: To analyze the clinical and radiographic outcomes of posterior thoracolumbar fusions using intraoperative computed tomography (CT)-guidance and stereotactic navigation in thoracolumbar spinal trauma. SUMMARY OF BACKGROUND DATA: Pedicle screw instrumentation is utilized for stabilization in thoracolumbar fusions. Suboptimal placement may lead to neurovascular complications, pseudarthrosis, postoperative pain, and the need for revision surgery. Image-guided spinal surgery is commonly used to improve accuracy, particularly for complex anatomy such as encountered with traumatic fractures. METHODS: We retrospectively identified 58 patients undergoing posterior thoracolumbar fusions using intraoperative CT and stereotactic navigation for traumatic fractures from 2010 to 2017 at a single institution. Pedicle screw accuracy, realignment, clinical outcomes, and ease of use were retrospectively reviewed. Accuracy was assessed on postplacement or postoperative CT. Breach grades included: grade 1 (<2 mm), grade 2 (2-4 mm), and grade 3 (>4 mm). RESULTS: A total of 58 patients were identified having undergone 58 operations, which involved placement of 519 pedicle screws. Traumatic fracture patterns and levels of injury were varied. Accurate pedicle screw placement was found in 95.8% and was stable over time. Breach included: grade 1 in 19 screws, grade 2 in 2 screws, and grade 3 in 1 screw. No neurovascular complications were noted. No revision surgery was performed for misplacement. A subgroup of 6 ankylosing spondylitis patients were identified having undergone 6 operations with 63 pedicle screws. Accurate pedicle screw placement was found in 93.7%. CONCLUSION: Intraoperative CT-guidance and stereotactic navigation can overcome the difficulty associated with thoracolumbar trauma resulting in complex anatomy with malalignment and unpredictable trajectories. Intraoperative CT can be used with stereotactic guidance or for intraoperative verification of free-hand screw placement with repositioning as needed. CT-guidance maintains the benefit of reduced fluoroscopic exposure while improving accuracy of instrumentation and reducing reoperation for screw malposition.

Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities.

Gliomas represent the most common malignant primary brain tumors, and a high-grade subset of these tumors including glioblastoma are particularly refractory to current standard-of-care therapies including maximal surgical resection and chemoradiation. The prognosis of patients with these tumors continues to be poor with existing treatments and understanding treatment failure is required. The dynamic interplay between the tumor and its microenvironment has been increasingly recognized as a key mechanism by which cellular adaptation, tumor heterogeneity, and treatment resistance develops. Beyond ongoing lines of investigation into the peritumoral cellular milieu and microenvironmental architecture, recent studies have identified the growing role of mechanical properties of the microenvironment. Elucidating the impact of these biophysical factors on disease heterogeneity is crucial for designing durable therapies and may offer novel approaches for intervention and disease monitoring. Specifically, pharmacologic targeting of mechanical signal transduction substrates such as specific ion channels that have been implicated in glioma progression or the development of agents that alter the mechanical properties of the microenvironment to halt disease progression have the potential to be promising treatment strategies based on early studies. Similarly, the development of technology to measure mechanical properties of the microenvironment in vitro and in vivo and simulate these properties in bioengineered models may facilitate the use of mechanical properties as diagnostic or prognostic biomarkers that can guide treatment. Here, we review current perspectives on the influence of mechanical properties in glioma with a focus on biophysical features of tumor-adjacent tissue, the role of fluid mechanics, and mechanisms of mechanical signal transduction. We highlight the implications of recent discoveries for novel diagnostics, therapeutic targets, and accurate preclinical modeling of glioma.

Cytoreductive surgery in the management of newly diagnosed glioblastoma in adults: a systematic review and evidence-based clinical practice guideline update.

TARGET POPULATION: These recommendations apply to adults with newly diagnosed or suspected glioblastoma. QUESTION: What is the effect of extent of surgical resection on patient outcome in the initial management of adult patients with suspected newly diagnosed glioblastoma? RECOMMENDATION: Level II: Maximal cytoreductive surgery is recommended in adult patients with suspected newly diagnosed supratentorial glioblastoma with gross total resection defined as removal of contrast enhancing tumor. Level III: Biopsy, subtotal resection, or gross total resection is suggested depending on medical comorbidities, functional status, and location of tumor if maximal resection may cause significant neurologic deficit. QUESTION: What is the role of cytoreductive surgery in adults with newly diagnosed bi-frontal "butterfly" glioblastoma? RECOMMENDATION: Level III: Resection of newly diagnosed bi-frontal "butterfly" glioblastoma is suggested to improve overall survival over biopsy alone. QUESTION: What is the goal of cytoreductive surgery in elderly adult patients with newly diagnosed glioblastoma? RECOMMENDATION: Level III: Elderly patients (> 65 years) show survival benefit with gross total resection and it is suggested they undergo cytoreductive surgery. QUESTION: What is the role of advanced intraoperative guidance techniques in cytoreductive surgery in adults with newly diagnosed glioblastoma? RECOMMENDATION: Level III: The use of intraoperative guidance adjuncts such as intraoperative MRI (iMRI) or 5-aminolevulinic acid (5-ALA) are suggested to maximize extent of resection in newly diagnosed glioblastoma. There is insufficient evidence to make a suggestion on the use of fluorescein, indocyanine green, or intraoperative ultrasound.

Treatment of pediatric unstable os odontoideum with adjacent degenerative cyst: case presentation and literature review.

Degenerative cysts associated with an unstable os odontoideum in pediatric patients are uncommon lesions. Reported treatments of such lesions have varied and yielded mixed results with the optimal surgical strategy remaining unclear. The authors report the clinical and surgical outcome of a 13-year-old patient presenting with degenerative cyst adjacent to an abnormal os odontoideum motion segment. The patient was asymptomatic from this lesion which was an incidental finding while undergoing workup for atypical headaches. Clinical and radiologic findings, operative details, and postoperative outcome are described. The patient was successfully treated with posterior cervical fusion without direct cyst decompression. Complete resolution of the cyst was demonstrated on magnetic resonance imaging at 6 months. Computed tomography 8 months postoperatively showed solid bony fusion and normal alignment. Regarding treatment goals in pediatric patients with os odontoideum degenerative cysts, the current case and literature review supports posterior instrumented fusion without direct surgical cyst resection.

Multiple paraspinal intramuscular myxomas: case report.

Intramuscular myxomas (IMMs) are rare benign tumors of mesenchymal origin that are most often located in large skeletal muscles, particularly of the thigh. They have also been reported within the paraspinal musculature and should be considered in the differential diagnosis of a paraspinal mass. These lesions can cause neurological symptoms due to mass effect. This is a report of a 52-year-old man with multiple paraspinal tumors that exhibited concerning growth on serial imaging studies. To the authors' knowledge, this represents the first report of a patient with multiple paraspinal myxomas. CT-guided biopsy followed by surgical excision of the largest mass was performed. Histopathological analysis was consistent with an IMM. Patients with multiple IMMs often have an underlying genetic syndrome such as Mazabraud syndrome, McCune-Albright syndrome, or Carney complex. Despite variable growth patterns and associations with genetic syndromes, multiple IMMs have had no documented cases of malignant transformation into myxoid sarcoma; therefore, surgical excision should be considered based on a patient's individual symptoms.

Emerging temporal trends in tissue plasminogen activator use: Results from the BASIC project.

OBJECTIVE: To explore temporal trends in tissue plasminogen activator (tPA) administration for acute ischemic stroke (AIS) in a biethnic community without an academic medical center and variation in trends by age, sex, ethnicity, and stroke severity. METHODS: Cases of AIS were identified from 7 hospitals in the Brain Attack Surveillance in Corpus Christi (BASIC) project, a population-based surveillance study between January 1, 2000, and June 30, 2012. tPA, demographics, and stroke severity as assessed by the NIH Stroke Scale (NIHSS) were ascertained from medical records. Temporal trends were explored using generalized estimating equations, and adjustment made for age, sex, ethnicity, and NIHSS. Interaction terms were included to test for effect modification. RESULTS: There were 5,277 AIS cases identified from 4,589 unique individuals. tPA use was steady at 2% and began increasing in 2006, reaching 11% in subsequent years. Stroke severity modified temporal trends (p = 0.003) such that cases in the highest severity quartile (NIHSS > 8) had larger increases in tPA use than those in lower severity quartiles. Although ethnicity did not modify the temporal trend, Mexican Americans (MAs) were less likely to receive tPA than non-Hispanic whites (NHWs) due to emerging ethnic differences in later years. CONCLUSIONS: Dramatic increases in tPA use were apparent in this community without an academic medical center. Primary stroke center certification likely contributed to this rise. Results suggest that increases in tPA use were greater in higher severity patients compared to lower severity patients, and a gap between MAs and NHWs in tPA administration may be emerging.

Denicotinized versus average nicotine tobacco cigarette smoking differentially releases striatal dopamine.

INTRODUCTION: Nicotine has long been recognized as a necessary but insufficient component of tobacco cigarettes to maintain a psychophysiological need to smoke. This study examined venous plasma concentrations effects of nicotine in cigarette smoking after overnight abstinence to release striatal dopamine (DA). METHODS: Twenty-two male smokers smoked either denicotinized (denic) or average nicotine (nic) cigarettes under single blind conditions. Each was given [(11)C]raclopride and scanned in a positron emission tomography (PET) facility. RESULTS: Smoking either denic or nic cigarettes released striatal DA. Denic cigarette smoking released DA primarily in the right striatum, whereas nic cigarette smoking released DA in both striata, but especially in the left. Increases in venous plasma nicotine concentrations correlated positively with increased DA release in the left caudate nucleus. Smoking denic cigarettes reduced craving as much as smoking nic cigarettes. Craving reduction after nic tobacco smoking correlated with increases in plasma nicotine. CONCLUSIONS: Nonnicotine factors in tobacco smoking produce important right brain effects. Nicotine is a pharmacological factor during tobacco smoking that releases bilateral striatal DA, but more in the left brain.