Functional Characterization of Brain Tumor-Initiating Cells and Establishment of GBM Preclinical Models that Incorporate Heterogeneity, Therapy, and Sex Differences
Abstract Glioblastoma (GBM) is the most common primary brain cancer in adults where tumor cell heterogeneity and sex differences influence clinical outcomes. Here, we functionally characterize three male and three female patient-derived GBM cell lines, identify protumorigenic BTICs, and create novel male and female preclinical models of GBM. Cell lines were evaluated on the following features: proliferation, stemness, migration, tumorigenesis, clinical characteristics, and sensitivity to radiation, TMZ, rhTNFSF10 (rhTRAIL), and rhBMP4. All cell lines were classified as GBM according to epigenetic subtyping, were heterogenous and functionally distinct from one another, and re-capitulated features of the original patient tumor. In establishing male and female preclinical models, it was found that two male-derived GBM cell lines (QNS108 and QNS120) and one female-derived GBM cell line (QNS315) grew at a faster rate in female mice brains. One male-derived GBM cell line (QNS108) decreased survival in female mice in comparison with male mice. However, no survival differences were observed for mice injected with a female-derived cell line (QNS315). In summary, a panel of six GBM patient-derived cell lines were functionally characterized, and it was shown that BTIC lines can be used to construct sex-specific models with differential phenotypes for additional studies.
Concussion in soccer: a comprehensive review of the literature
Sports-related concussion has been examined extensively in collision sports such as football and hockey. However, historically, lower-risk contact sports such as soccer have only more recently garnered increased attention. Here, we review articles examining the epidemiology, injury mechanisms, sex differences, as well as the neurochemical, neurostructural and neurocognitive changes associated with soccer-related concussion. From 436 titles and abstracts, 121 full texts were reviewed with a total of 64 articles identified for inclusion. Concussion rates are higher during competitions and in female athletes with purposeful heading rarely resulting in concussion. Given a lack of high-level studies examining sports-related concussion in soccer, clinicians and scientists must focus research efforts on large-scale data gathering and development of improved technologies to better detect and understand concussion.
Ex vivo virtual and 3D printing methods for evaluating an anatomy‐based spinal instrumentation technique for the 12th thoracic vertebra
AbstractIntroductionThree‐dimensional printing and virtual simulation both provide useful methods of patient‐specific anatomical modeling for assessing and validating surgical techniques. A combination of these two methods for evaluating the feasibility of spinal instrumentation techniques based on anatomical landmarks has not previously been investigated.Materials and MethodsNineteen anonymized CT scans of the thoracic spine in adult patients were acquired. Maximum pedicle width and height were recorded, and statistical analysis demonstrated normal distributions. The images were converted into standard tessellation language (STL) files, and the T12 vertebrae were anatomically segmented. The intersection of two diagonal lines drawn from the lateral and medial borders of the T12 transverse process (TP) to the lateral border of the pars and inferolateral portion of the TP was identified on both sides of each segmented vertebra. A virtual screw was created and insertion into the pedicle on each side was simulated using the proposed landmarks. The vertebral STL files were then 3D‐printed, and 38 pedicles were instrumented according to the individual posterior landmarks used in the virtual investigation.ResultsThere were no pedicle breaches using the proposed anatomical landmarks for insertion of T12 pedicle screws in the virtual simulation component. The technique was further validated by additive manufacturing of individual T12 vertebrae and demonstrated no breaches or model failures during live instrumentation using the proposed landmarks.ConclusionsEx vivo modeling through virtual simulation and 3D printing provides a powerful and cost‐effective means of replicating vital anatomical structures for investigation of complex surgical techniques.
O4‐10‐01: CHARACTERIZING CELL TYPE‐SPECIFIC EXPRESSION SIGNATURES IN BRAIN USING SINGLE CELL RNA SEQUENCING
OBJECTIVEEpilepsy is common among patients with supratentorial brain tumors; approximately 40%–70% of patients with glioma develop brain tumor–related epilepsy (BTRE). Intraoperative localization of the epileptogenic zone during surgical tumor resection (real-time data) may improve intervention techniques in patients with lesional epilepsy, including BTRE. Accurate localization of the epileptogenic signals requires electrodes with high-density spatial organization that must be placed on the cortical surface during surgery. The authors investigated a 360° high-density ring-shaped cortical electrode assembly device, called the “circular grid,” that allows for simultaneous tumor resection and real-time electrophysiology data recording from the brain surface.METHODSThe authors collected data from 99 patients who underwent awake craniotomy from January 2008 to December 2018 (29 patients with the circular grid and 70 patients with strip electrodes), of whom 50 patients were matched-pair analyzed (25 patients with the circular grid and 25 patients with strip electrodes). Multiple variables were then retrospectively assessed to determine if utilization of this device provides more accurate real-time data and improves patient outcomes.RESULTSMatched-pair analysis showed higher extent of resection (p = 0.03) and a shorter transient motor recovery period during the hospitalization course (by approximately 6.6 days, p ≤ 0.05) in the circular grid patients. Postoperative versus preoperative Karnofsky Performance Scale (KPS) score difference/drop was greater for the strip electrode patients (p = 0.007). No significant difference in postoperative seizures between the 2 groups was present (p = 0.80).CONCLUSIONSThe circular grid is a safe, feasible tool that grants direct access to the cortical surgical surface for tissue resection while simultaneously monitoring electrical activity. Application of the circular grid to different brain pathologies may improve intraoperative epileptogenic detection accuracy and functional outcomes, while decreasing postoperative complications.
Medial Temporal Encephalocele and Medically Intractable Epilepsy: A Tailored Inferior Temporal Lobectomy and Case Report
Abstract BACKGROUND AND IMPORTANCE Temporal lobe encephaloceles are increasingly recognized as a potential cause of medically refractory epilepsy and surgical treatment has proven effective. Resection of the encephalocele and associated cortex is often sufficient to provide seizure control. However, it is difficult to determine the extent of adjacent temporal lobe that should be resected. We present a case report and our technique of a tailored inferior temporal pole resection. CLINICAL PRESENTATION A 32-yr-old man with an 11-yr history of medically refractory epilepsy. Prolonged electroencephalography (EEG) revealed frequent left and rare right frontotemporal sharp waves. Numerous seizures were captured with EEG, all of which originated from the left temporal region. Statistical parametric mapping (SPM) subtraction ictal–interictal SPECT coregistered with magnetic resonance imaging (MRI) (SISCOM) demonstrated ictal hyperperfusion in the anterior left temporal lobe. MRI showed 2 encephaloceles in the left anterior temporal lobe with the accompanying bony defects in the floor of the middle cranial fossa apparent on the computed tomography scan. The patient underwent left temporal craniotomy with intraoperative electrocorticography, resection of the encephaloceles, and a tailored inferior temporal lobectomy (IFTL) and repair of the middle fossa defects. At 7 mo follow up he reported seizure-freedom since surgery. CONCLUSION Resection of temporal encephalocele and adjacent cortex is safe and effective procedure for select patients with medically refractory epilepsy. This video demonstrates our technique which provides a more standardized approach to the resection.
Intraoperative Seizures in Awake Craniotomy for Perirolandic Glioma Resections That Undergo Cortical Mapping
Background Perirolandic motor area gliomas present invasive eloquent region tumors within the precentral gyrus that are difficult to resect without causing neurologic deficits. Study Aims This study evaluates the role of awake craniotomy and motor mapping on neurologic outcome and extent of resection (EOR) of tumor in the perirolandic motor region. It also analyzes preoperative risk factors for intraoperative seizures. Methods We evaluated 57 patients who underwent an awake craniotomy for a perirolandic motor area eloquent region glioma. Patients who had positive mapping (PM) or intraoperative identification of motor regions in the cortex using direct cortical stimulation were compared with patients with no positive motor mapping following direct cortical stimulation and negative mapping (NM). Preoperative risks, intraoperative seizures, perioperative outcomes, tumor characteristics, and EOR were also compared. A logistic regression model was used to evaluate the predictors for intraoperative seizures in this patient cohort. Results Overall, 33 patients were in the PM cohort; 24 were in the NM cohort. Our study showed an 8.8% incidence of intraoperative seizures during cortical and subcortical mapping for awake craniotomies in the perirolandic motor area, none of which aborted the case. PM patients had significantly more intraoperative and postoperative seizures (15.5% and 30.3%, respectively) compared with the NM patients (0% and 8.3%, respectively; p = 0.046 and 0.044). New transient postoperative motor deficits were found more often in the PM group (51.5%) versus the NM group (12.5%; p = 0.002). A univariate logistic regression showed that PM (odds ratio [OR]: 1.16; 95% confidence interval [CI], 1.01–1.34; p = 0.035) and preoperative tumor volume (OR: 0.998; 95% CI, 0.996–0.999; p = 0.049) were significant predictors for intraoperative seizures in patients with perirolandic gliomas. Conclusion Awake craniotomies in the perirolandic motor region can be safely performed with a similar incidence of intraoperative seizures as reported for the language cortex. PM in this region may increase the likelihood of perioperative seizures or motor deficits compared with NM. Craniotomies that minimize cortical exposure for perirolandic gliomas that may not localize motor regions can still allow for extensive tumor resection with a good postoperative outcome.
High-frequency oscillations in awake patients undergoing brain tumor-related epilepsy surgery