Guidelines for optimal utilization of social media for brain tumor stakeholders.

OBJECTIVE: Effective use of social media (SM) by medical professionals is vital for better connections with patients and dissemination of evidence-based information. A study of SM utilization by different stakeholders in the brain tumor community may help determine guidelines for optimal use. METHODS: Facebook, Twitter, and YouTube were searched by using the term "Brain Tumor." Platform-specific metrics were determined, including audience size, as a measure of popularity, and mean annual increase in audience size, as a measure of performance on SM. Accounts were categorized on the basis of apparent ownership and content, with as many as two qualitative themes assigned to each account. Correlations of content themes and posting behavior with popularity and performance metrics were assessed by using the Pearson's test. RESULTS: Facebook (67 pages and 304,581 likes) was predominantly used by organizations (64% of pages). Top themes on Facebook, Twitter, and YouTube were charity and fundraising (67% of pages), education and research (72% of accounts), and experience sharing and support seeking (48% of videos, 60% of views, and 82% of user engagement), respectively. On Facebook, only the presence of other concurrent platforms influenced a page's performance (rho = 0.59) and popularity (rho = 0.61) (p < 0.05). On Twitter, the number of monthly tweets (rho = 0.66) and media utilization (rho = 0.78) were significantly correlated with increased popularity and performance (both p < 0.05). Personal YouTube videos (30% of videos and 61% of views) with the theme of experience sharing and support seeking had the highest level of engagement (60% of views, 70% of comments, and 87% of likes). CONCLUSIONS: Popularity and prevalence of qualitative themes differ among SM platforms. Thus, optimal audience engagement on each platform can be achieved with thematic considerations. Such considerations, along with optimal SM behavior such as media utilization and multiplatform presence, may help increase content popularity and thus increase community access to neurooncology content provided by medical professionals.

An exploratory study into the influence of laterality and location of hippocampal sclerosis on seizure prognosis and global cortical thinning.

In mesial temporal lobe epilepsy (mTLE), the correlation between disease duration, seizure laterality, and rostro-caudal location of hippocampal sclerosis has not been examined in the context of seizure severity and global cortical thinning. In this retrospective study, we analyzed structural 3 T MRI from 35 mTLE subjects. Regions of FLAIR hyperintensity (as an indicator of sclerosis)-based on 2D coronal FLAIR sequences-in the hippocampus were manually segmented, independently and in duplicate; degree of segmentation agreement was confirmed using the DICE index. Segmented lesions were used for separate analyses. First, the correlation of cortical thickness with disease duration and seizure focus laterality was explored using linear model regression. Then, the relationship between the rostro-caudal location of the FLAIR hyperintense signal and seizure severity, based on the Cleveland Clinic seizure freedom score (ccSFS), was explored using probabilistic voxel-wise mapping and functional connectivity analysis from normative data. The mean DICE Index was 0.71 (range 0.60-0.81). A significant correlation between duration of epilepsy and decreased mean whole brain cortical thickness was identified, regardless of seizure laterality (p < 0.05). The slope of cortical volume loss over time, however, was greater in subjects with right seizure focus. Based on probabilistic voxel-wise mapping, FLAIR hyperintensity in the posterior hippocampus was significantly associated with lower ccSFS scores (greater seizure severity). Finally, the right hippocampus was found to have greater brain-wide connectivity, compared to the left side, based on normative connectomic data. We have demonstrated a significant correlation between duration of epilepsy and right-sided seizure focus with global cortical thinning, potentially due to greater brain-wide connectivity. Sclerosis along the posterior hippocampus was associated with greater seizure severity, potentially serving as an important biomarker of seizure outcome after surgery.

Propensity Score Matching: A Powerful Tool for Analyzing Observational Nonrandomized Data.

In using observational, nonrandomized data, there is often interest in studying the effect of a particular treatment on a specific outcome. However, the imbalance of potential confounding variables between the treatment groups can distort the relationship between treatment and outcome. Propensity score matching is one, increasingly utilized, method to help account for such imbalances, allowing for a more accurate estimation of the influence of treatment on outcome. In this paper, we provide the clinician with an overview of propensity score matching techniques and provide a practical example of how this has been used in clinical research relevant to spine surgery.

Blood-Brain Barrier Disruption in Neuro-Oncology: Strategies, Failures, and Challenges to Overcome.

The blood-brain barrier (BBB) presents a formidable challenge in the development of effective therapeutics in neuro-oncology. This has fueled several decades of efforts to develop strategies for disrupting the BBB, but progress has not been satisfactory. As such, numerous drug- and device-based methods are currently being investigated in humans. Through a focused assessment of completed, active, and pending clinical trials, our first aim in this review is to outline the scientific foundation, successes, and limitations of the BBBD strategies developed to date. Among 35 registered trials relevant to BBBD in neuro-oncology in the ClinicalTrials.gov database, mannitol was the most common drug-based method, followed by RMP-7 and regadenoson. MR-guided focused ultrasound was the most common device-based method, followed by MR-guided laser ablation, ultrasound, and transcranial magnetic stimulation. While most early-phase studies focusing on safety and tolerability have met stated objectives, advanced-phase studies focusing on survival differences and objective tumor response have been limited by heterogeneous populations and tumors, along with a lack of control arms. Based on shared challenges among all methods, our second objective is to discuss strategies for confirmation of BBBD, choice of systemic agent and drug design, alignment of BBBD method with real-world clinical workflow, and consideration of inadvertent toxicity associated with disrupting an evolutionarily-refined barrier. Finally, we conclude with a strategic proposal to approach future studies assessing BBBD.

Identification of neural networks preferentially engaged by epileptogenic mass lesions through lesion network mapping analysis.

Lesion network mapping (LNM) has been applied to true lesions (e.g., cerebrovascular lesions in stroke) to identify functionally connected brain networks. No previous studies have utilized LNM for analysis of intra-axial mass lesions. Here, we implemented LNM for identification of potentially vulnerable epileptogenic networks in mass lesions causing medically-refractory epilepsy (MRE). Intra-axial brain lesions were manually segmented in patients with MRE seen at our institution (EL_INST). These lesions were then normalized to standard space and used as seeds in a high-resolution normative resting state functional magnetic resonance imaging template. The resulting connectivity maps were first thresholded (pBonferroni_cor < 0.05) and binarized; the thresholded binarized connectivity maps were subsequently summed to produce overall group connectivity maps, which were compared with established resting-state networks to identify potential networks prone to epileptogenicity. To validate our data, this approach was also applied to an external dataset of epileptogenic lesions identified from the literature (EL_LIT). As an additional exploratory analysis, we also segmented and computed the connectivity of institutional non-epileptogenic lesions (NEL_INST), calculating voxel-wise odds ratios (VORs) to identify voxels more likely to be functionally-connected with EL_INST versus NEL_INST. To ensure connectivity results were not driven by anatomical overlap, the extent of lesion overlap between EL_INST, and EL_LIT and NEL_INST was assessed using the Dice Similarity Coefficient (DSC, lower index ~ less overlap). Twenty-eight patients from our institution were included (EL_INST: 17 patients, 17 lesions, 10 low-grade glioma, 3 cavernoma, 4 focal cortical dysplasia; NEL_INST: 11 patients, 33 lesions, all brain metastases). An additional 23 cases (25 lesions) with similar characteristics to the EL_INST data were identified from the literature (EL_LIT). Despite minimal anatomical overlap of lesions, both EL_INST and EL_LIT showed greatest functional connectivity overlap with structures in the Default Mode Network, Frontoparietal Network, Ventral Attention Network, and the Limbic Network-with percentage volume overlap of 19.5%, 19.1%, 19.1%, and 12.5%, respectively-suggesting them as networks consistently engaged by epileptogenic mass lesions. Our exploratory analysis moreover showed that the mesial frontal lobes, parahippocampal gyrus, and lateral temporal neocortex were at least twice as likely to be functionally connected with the EL_INST compared to the NEL_INST group (i.e. Peak VOR > 2.0); canonical resting-state networks preferentially engaged by EL_INSTs were the Limbic and the Frontoparietal Networks (Mean VOR > 1.5). In this proof of concept study, we demonstrate the feasibility of LNM for intra-axial mass lesions by showing that ELs have discrete functional connections and may preferentially engage in discrete resting-state networks. Thus, the underlying normative neural circuitry may, in part, explain the propensity of particular lesions toward the development of MRE. If prospectively validated, this has ramifications for patient counseling along with both approach and timing of surgery for lesions in locations prone to development of MRE.

The Role of Stereotactic Radiosurgery in the Management of Brain Metastases From a Health-Economic Perspective: A Systematic Review.

BACKGROUND: Stereotactic radiosurgery (SRS) is an effective option in the management of brain metastases, offering improved overall survival to whole-brain radiation therapy (WBRT). However, given the need for active surveillance and the possibility of repeated interventions for local/distant brain recurrences, the balance between clinical benefit and economic impact must be evaluated. OBJECTIVE: To conduct a systematic review of health-economic analyses of SRS for brain metastases, compared with other existing intervention options, to determine the cost-effectiveness of this treatment across different clinical scenarios. METHODS: The MEDLINE, EMBASE, Cochrane, CRD, and EconLit databases were searched for health-economic analyses, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using terms relevant to brain metastases and radiation-based therapies. Simple cost analysis studies were excluded. Quality analysis was based on BMJ Consolidated Health Economics Reporting Standards (CHEERS) checklist. RESULTS: Eleven eligible studies were identified. For lesions with limited mass effect, SRS was more cost-effective than surgical resection (6 studies). In patients with Karnofsky performance scale (KPS) >70 and good predicted survival, SRS was cost-effective compared to WBRT (7 studies); WBRT became cost-effective with poor performance status or low anticipated life span. Following SRS, routine magnetic resonance imaging surveillance saved $1326/patient compared to symptomatic imaging due to reduced surgical salvage and hospital stay (1 study). CONCLUSION: Based on our findings, SRS is cost-effective in the management of brain metastases, particularly in high-functioning patients with longer expected survival. However, before an optimal care pathway can be proposed, emerging factors such as tumor molecular subtype, diagnosis-specific graded prognostic assessment, neuroprognostic score, tailored surveillance imaging, and patient utilities need to be studied in greater detail.

The Cost-Effectiveness of 5-ALA in High-Grade Glioma Surgery: A Quality-Based Systematic Review.

BACKGROUND: High-grade gliomas (HGGs) are aggressive tumors that inevitably recur due to their diffusely infiltrative nature. Intraoperative adjuncts such as 5-aminolevulinic acid (5-ALA) have shown promise in increasing extent of resection. As the prospect of increased use of 5-ALA rises, a systematic overview of the health economics of this adjunct is critical. METHODS: Medline, EMBASE, Centre for Reviews and Dissemination, EconPapers, and Cochrane databases were searched for keywords relating to glioma, cost-effectiveness, and 5-ALA. Primary studies reporting on the health economics or cost-effectiveness of 5-ALA compared to white light surgery in HGG were included. Quality was assessed using the British Medical Journal guidelines. RESULTS: Three studies were identified. All were European and conducted from the perspective of national healthcare systems. Two studies demonstrated the cost-utility of 5-ALA compared to white light (C$12,817 and C$13,508/quality-adjusted life-years (QALYs)). One assessed the cost-utility per gross total resection (C$6,813). Both these values were below the national cost-effectiveness thresholds for each respective study. The third study demonstrated no significant difference in cost of 5-ALA in glioblastoma resection (C$14,732) compared to prior to its routine use (C$15,936). The quality of these studies ranged from moderate to average. None of these studies considered patient perspective or indirect costs in their analysis. CONCLUSIONS: Growing evidence exists examining the health economic benefit of 5-ALA as an intraoperative adjunct for HGG resection. Additional studies within the Canadian context using 5-ALA, specifically incorporating patient and societal perspectives into the cost-utility analyses, are necessary to solidify this line of evidence.

Comparing Effects of Treatment: Controlling for Confounding.

BACKGROUND: Determining true causal links between an intervention and an outcome forms an imperative task in research studies in neurosurgery. Although the study results sometimes demonstrate clear statistical associations, it is important to ensure that this represents a true causal link. A confounding variable, or confounder, affects the association between a potential predictor and an outcome. OBJECTIVE: To discuss what confounding is and the means by which it can be eliminated or controlled. METHODS: We identified neurosurgical research studies demonstrating the principles of eliminating confounding by means of study design and data analysis. RESULTS: In this report, we outline the role of confounding in neurosurgical studies after giving an overview of its identification. We report on the definition of confounding and effect modification, and the differences in the 2. We explain study design techniques to eliminate confounding, including simple, block, stratified, and minimization randomization, along with restriction of sample and matching. Data analysis techniques of eliminating confounding include regression analysis, propensity scoring, and subgroup analysis. CONCLUSION: Understanding confounding is important for conducting a good research study. Study design techniques provide the best way to control for confounders, but when not possible to alter study design, data analysis techniques can also provide an effective control.

The Effect of Older Age on the Perioperative Outcomes of Spinal Fusion Surgery in Patients With Lumbar Degenerative Disc Disease With Spondylolisthesis: A Propensity Score-Matched Analysis.

BACKGROUND: Degenerative spondylolisthesis (DS) is often treated with lumbar spinal fusion (LSF). However, there is concern that the morbidity of LSF may be prohibitively high in older adults. OBJECTIVE: To evaluate the impact of advanced age on the safety of LSF for DS. METHODS: Patients who underwent LSF for DS were retrospectively identified from National Surgical Quality Improvement Program datasets for 2011 to 2015 using Current Procedural Terminology codes. Data on demographic characteristics, comorbidities, surgical factors, and 30-d morbidity and mortality were collected. Propensity score matching (nearest neighbor) was performed with age (<70 vs ≥70 yr) as the dependent variable and sex, type of fusion procedure, number of levels fused, diabetes, smoking, hypertension, and chronic steroid use as covariates. Outcomes were compared between age <70 and ≥70 groups. RESULTS: The study cohort consisted of 2238 patients (n = 1119, age <70; n = 1119, age ≥70). The 2 age groups were balanced for key covariates including sex, race, diabetes, hypertension, CHF, smoking, chronic steroid use, type of fusion, and number of levels. Rates of all complications were similar between younger and older age groups, except urinary tract infection, which was more frequent among the ≥70 age group (OR 2.32, P = .009). Further, patients in the older age group were more likely to be discharged to a rehabilitation (OR 2.94, P < .001) or skilled care (OR 3.66, P < .001) facility, rather than directly home (OR 0.25, P < .001). CONCLUSION: LSF may be performed safely in older adults with DS. Our results suggest older age alone should not exclude a patient from undergoing lumbar fusion for DS.

Clinical phenotypes associated with outcomes following deep brain stimulation for childhood dystonia.

OBJECTIVE: Although deep brain stimulation (DBS) is an accepted treatment for childhood dystonia, there is significant heterogeneity in treatment response and few data are available to identify ideal surgical candidates. METHODS: Data were derived from a systematic review and individual patient data meta-analysis of DBS for dystonia in children that was previously published. Outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale for movement (BFMDRS-M) and for disability (BFMDRS-D). The authors used partial least squares, bootstrapping, and permutation statistics to extract patterns of contributions of specific preoperative characteristics to relationship with distinct outcomes, in all patients and in patients with primary and secondary dystonia separately. RESULTS: Of 301 children undergoing DBS for dystonia, 167 had primary dystonia, 125 secondary dystonia, and 9 myoclonus dystonia. Three dissociable preoperative phenotypes (latent variables) were identified and associated with the following: 1) BFMDRS-M at last follow-up; 2) relative change in BFMDRS-M score; and 3) relative change in BFMDRS-D score. The phenotype of patients with secondary dystonia, with a high BFMDRS-M score and truncal involvement, undergoing DBS at a younger age, was associated with a worse postoperative BFMDRS-M score. Children with primary dystonia involving the trunk had greater improvement in BFMDRS-M and -D scores. Those with primary dystonia of shorter duration and proportion of life with disease, undergoing globus pallidus DBS, had greater improvements in BFMDRS-D scores at long-term follow-up. CONCLUSIONS: In a comprehensive, data-driven, multivariate analysis of DBS for childhood dystonia, the authors identified novel and dissociable patient phenotypes associated with distinct outcomes. The findings of this report may inform surgical candidacy for DBS.

MGMT Testing in Glioblastomas: Pitfalls and Opportunities.

Gliomas, that do not respond to alkylating agent chemotherapy, can be made more sensitive to chemotherapy through promotor mediated epigenetic silencing of the MGMT gene. MGMT is one of the important markers in glioblastomas as it not only predicts response to therapy but may also be used as an independent prognostic marker. As such, MGMT is gaining increasing traction in diagnosis, prognostication, and therapeutic decision-making for these highly malignant gliomas. Although, MGMT promotor methylation status is becoming more commonly used in neuro-oncology; this test remains imperfect. Because of its increasing use in clinical practice and research, it is integral that we are aware of its pitfalls and complications. Currently, there are many ways to detect a patient's MGMT promotor methylation status, including: quantitative PCR, methylation-specific PCR, pyrosequencing, real time PCR with high resolution melt, and the infinitum methylation EPIC beadChip. The technical aspects, shortcomings, and optimal approach to interpreting the results of each method will be discussed. Furthermore, given that none of these methods have been prospectively validated, the challenge of equivocal cases will be discussed, and technical and logistic strategies for overcoming these challenges will be proposed. Finally, the difficulty in validating these methods, establishing standardized practice, and considerations of the cost of these competing methods will be explored.

Medical and socioeconomic predictors of quality of life in myelomeningocele patients with shunted hydrocephalus.

INTRODUCTION: Children with myelomeningocele (MMC) often develop hydrocephalus, and the combination of these conditions can lead to psychosocial, cognitive, and physical health issues that decrease their health-related quality of life (HRQOL). The goal of the present study was to understand the QOL in patients with MMC and shunted hydrocephalus. METHODS: Data from the Toronto Hydrocephalus QOL Database was acquired between 2004 and 2009 using parent-completed questionnaires and, when appropriate, child-completed questionnaires: Hydrocephalus Outcome Questionnaire (HOQ) and the Health Utilities Index. We identified several medical and socioeconomic factors potentially relevant to the outcome measure (e.g., level of myelomeningocele, length of stay in hospital, and shunt-related hospital admissions; family functioning, income, parental education, employment status, etc.). Linear regression models were used to examine associations between potential predictor variables and HRQOL, with P < 0.05 in the multivariate model suggesting significance. RESULTS: The analysis consisted of 131 patients (mean age = 12.6, SD = 3.7). The mean HUI score was 0.51, and the mean HOQ overall health score was 0.67. There was a significant association between lower age and higher HOQ social-emotional health (P = 0.03) and HUI scores (P = 0.03), lower anatomical level of myelomeningocele and higher HUI scores (P = 0.01), better family functioning and higher HOQ overall health scores (P = 0.004), and higher family income and higher HOQ overall health, physical health, and HUI scores (P = 0.001, P = 0.003, and P = 0.02, respectively). CONCLUSION: Myelomeningocele patients with shunted hydrocephalus can have a poor health-related quality of life. Our results indicate a strong association of income and family functioning on quality of life, along with younger age and lower level of myelomeningocele.

Analysis of surgical and MRI factors associated with cerebellar mutism.

The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. Therefore, we aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with individuals who did not acquire CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). A total of 22 patients (11 with and 11 without CM) were included. Medulloblastoma was the most common pathology among CM patients (91%); the remaining 9% were diagnosed with a pilocytic astrocytoma. Tumor attachment to the floor of the fourth ventricle (OR 6; 95% CI 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR 5; 95% CI 0.5-236.5) were found to have the highest measures of association with CM. Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia have a relatively higher prevalence in patients with CM. Collectively, our work calls for a larger multi-institutional cohort study of CM patients to encourage further investigation of the determinants and management of CM in order to potentially minimize its development and predict onset.