Comparative effectiveness of stereotactic, subdural, or hybrid intracranial EEG monitoring in epilepsy surgery.

OBJECTIVE: Surgical intervention can be curative or palliative for drug-resistant focal epilepsy. However, if the seizure onset zone (SOZ) cannot be adequately localized via noninvasive tests, intracranial EEG (iEEG) recordings are often carried out to develop surgical plans in appropriate candidates. Stereotactic EEG (SEEG), subdural EEG (SDE), and SDE with depth electrodes (hybrid) are major tools used for investigation, but there is no class 1 or 2 evidence comparing the effectiveness of these modalities. METHODS: The authors identified an institutional cohort of patients who underwent iEEG monitoring between 2001 and 2022. Demographic data, preoperative clinical features, iEEG intervention, and follow-up data were identified. Primary study endpoints included the following: 1) likelihood of SOZ localization; 2) likelihood of surgical treatment after iEEG; 3) seizure outcomes; and 4) complications. RESULTS: A total of 329 patients were identified (176 in the SEEG, 60 in the SDE, and 93 in the hybrid cohort) who were followed for a median of 5.4 (IQR 6.8) years. Baseline characteristics, including demographics, mean age at epilepsy diagnosis, mean age at iEEG investigation, number of preoperative antiseizure medications, and preoperative seizure frequency, were not statistically different across the 3 cohorts. Patients in the SEEG cohort were more likely to have their SOZ localized than were the patients in the SDE group (OR 2.3) and were less likely to undergo subsequent resection (OR 0.3) or to have complications (OR 0.4), although there was no statistical difference with respect to likelihood of undergoing any subsequent neurosurgical treatment, or with respect to favorable seizure outcomes. Patients in the hybrid cohort were more likely to have SOZ localized than were patients in the SDE group (OR 3.1), but were more likely to undergo resection (OR 4.9) or any neurosurgical treatment (OR 2.5) compared to patients in the SEEG group. Patients in the hybrid cohort had better seizure outcomes compared to the SDE (OR 2.3) but not to the SEEG group. CONCLUSIONS: Patients in the SEEG group were more likely to have their SOZ localized and patients in the SDE group were more likely to undergo resection, but they did not differ with respect to seizure outcomes.

The Global Macroeconomic Burden of Burn Injuries.

BACKGROUND: Standardized estimates of global economic losses from burn injuries are lacking. The primary objective of this study was to determine the global macroeconomic consequences of burn injuries and their geographic distribution. METHODS: Using the Institute of Health Metrics and Evaluation database (2009 and 2019), mean and 95% uncertainty interval (UI) data on incidence, mortality, and disability-adjusted life-years (DALYs) from injuries caused by fire, heat, and hot substances were collected. Gross domestic product (GDP) data were analyzed together with DALYs to estimate macroeconomic losses globally using a value of lost welfare approach. RESULTS: There were 9 million global burn cases (95% UI, 6.8 to 11.2 million) and 111,000 deaths from burns (95% UI, 88,000 to 132,000 deaths) in 2019, representing a total of 7.5 million DALYs (95% UI, 5.8 to 9.5 million DALYs). This represented welfare losses of $112 billion (95% UI, $78 to $161 billion), or 0.09% of GDP (95% UI, 0.06% to 0.13%). Welfare losses as a share of GDP were highest in low- and middle-income countries (LMICs) of Oceania (0.24%; 95% UI, 0.09% to 0.42%) and Eastern Europe (0.24%; 95% UI, 0.19% to 0.30%) compared with high-income country regions such as Western Europe (0.06%; 95% UI, 0.04% to 0.09%). Mortality-incidence ratios were highest in LMIC regions, highlighting a lack of treatment access, with southern sub-Saharan Africa reporting a mortality-incidence ratio of 40.1 per 1000 people compared with 1.9 for Australasia. CONCLUSIONS: Burden of disease and resulting economic losses because of burn injuries are substantial worldwide and are disproportionately higher in LMICs. Possible effective solutions include targeted education, advocacy, and legislation to decrease incidence and investing in existing burn centers to improve treatment access.

High frequency oscillations in relation to interictal spikes in predicting postsurgical seizure freedom.

We evaluate whether interictal spikes, epileptiform HFOs and their co-occurrence (Spike + HFO) were included in the resection area with respect to seizure outcome. We also characterise the relationship between high frequency oscillations (HFOs) and propagating spikes. We analysed intracranial EEG of 20 patients that underwent resective epilepsy surgery. The co-occurrence of ripples and fast ripples was considered an HFO event; the co-occurrence of an interictal spike and HFO was considered a Spike + HFO event. HFO distribution and spike onset were compared in cases of spike propagation. Accuracy in predicting seizure outcome was 85% for HFO, 60% for Spikes, and 79% for Spike + HFO. Sensitivity was 57% for HFO, 71% for Spikes and 67% for Spikes + HFO. Specificity was 100% for HFO, 54% for Spikes and 85% for Spikes + HFO. In 2/2 patients with spike propagation, the spike onset included the HFO area. Combining interictal spikes with HFO had comparable accuracy to HFO. In patients with propagating spikes, HFO rate was maximal at the onset of spike propagation.

Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma.

Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the "immune-cold" nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.

Traditional Machine Learning Methods versus Deep Learning for Meningioma Classification, Grading, Outcome Prediction, and Segmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: Meningiomas are common intracranial tumors. Machine learning (ML) algorithms are emerging to improve accuracy in 4 primary domains: classification, grading, outcome prediction, and segmentation. Such algorithms include both traditional approaches that rely on hand-crafted features and deep learning (DL) techniques that utilize automatic feature extraction. The aim of this study was to evaluate the performance of published traditional ML versus DL algorithms in classification, grading, outcome prediction, and segmentation of meningiomas. METHODS: A systematic review and meta-analysis were conducted. Major databases were searched through September 2021 for publications evaluating traditional ML versus DL models on meningioma management. Performance measures including pooled sensitivity, specificity, F1-score, area under the receiver-operating characteristic curve, positive and negative likelihood ratios (LR+, LR-) along with their respective 95% confidence intervals (95% CIs) were derived using random-effects models. RESULTS: Five hundred thirty-four records were screened, and 43 articles were included, regarding classification (3 articles), grading (29), outcome prediction (7), and segmentation (6) of meningiomas. Of the 29 studies that reported on grading, 10 could be meta-analyzed with 2 DL models (sensitivity 0.89, 95% CI: 0.74-0.96; specificity 0.91, 95% CI: 0.45-0.99; LR+ 10.1, 95% CI: 1.33-137; LR- 0.12, 95% CI: 0.04-0.59) and 8 traditional ML (sensitivity 0.74, 95% CI: 0.62-0.83; specificity 0.93, 95% CI: 0.79-0.98; LR+ 10.5, 95% CI: 2.91-39.5; and LR- 0.28, 95% CI: 0.17-0.49). The insufficient performance metrics reported precluded further statistical analysis of other performance metrics. CONCLUSIONS: ML on meningiomas is mostly carried out with traditional methods. For meningioma grading, traditional ML methods generally had a higher LR+, while DL models a lower LR-.

Recent oncolytic virotherapy clinical trials outline a roadmap for the treatment of high-grade glioma.

Adult and pediatric high-grade gliomas (HGGs) are aggressive cancers of the central nervous system that confer dismal clinical prognoses. Standard radiation and chemotherapy have demonstrated only limited efficacy in HGGs, motivating the accelerated investigation of novel modalities such as oncolytic virus (OV) therapies. OV centered therapies work through a mixed mechanism centered on oncolysis and the stimulation of an antitumor immune response. Three recent clinical trials utilizing herpes simplex virus-1 and adenovirus-based oncolytic virotherapy demonstrated not only the safety and efficacy of OVs but also novel dosing strategies that augment OV response potential. Considering these recent trials, herein we present a roadmap for future clinical trials of oncolytic immunovirotherapy in both adult and pediatric HGG, as well as persistent roadblocks related to the assessment of OV efficacy within and between trials.

A national stratification of the global macroeconomic burden of central nervous system cancer.

OBJECTIVE: Country-by-country estimates of the macroeconomic disease burden of central nervous system (CNS) cancers are important when determining the allocation of resources related to neuro-oncology. Accordingly, in this study the authors investigated macroeconomic losses related to CNS cancer in 173 countries and identified pertinent epidemiological trends. METHODS: Data for CNS cancer incidence, mortality, and disability-adjusted life years (DALYs) were collected from the Global Burden of Disease 2019 database. Gross domestic product data were combined with DALY data to estimate economic losses using a value of lost welfare approach. RESULTS: The mortality-to-incidence ratio of CNS cancer in 2019 was 0.60 in high-income regions compared to 0.82 in Sub-Saharan Africa and 0.87 in Central Europe, Eastern Europe, and Central Asia. Welfare losses varied across both high- and low-income countries. Welfare losses attributable to CNS cancer in Japan represented 0.07% of the gross domestic product compared to 0.23% in Germany. In low- and middle-income countries, Iraq reported welfare losses of 0.20% compared to 0.04% in Angola. Globally, the DALY rate in 2019 was the same for CNS cancer as for prostate cancer at 112 per 100,000 person-years, despite a 75% lower incidence rate, equating to CNS cancer welfare losses of 182 billion US dollars. CONCLUSIONS: Macroeconomic losses vary across high- and low-income settings and appear to be region specific. These differences may be explained by differences in regional access to screening and diagnosis, population-level genetic predispositions, and environmental risk factors. Mortality-to-incidence ratios are higher in low- and middle-income countries than in high-income countries, highlighting possible gaps in treatment access. Quantification of macroeconomic losses related to CNS cancer can help to justify the spending of finite resources to improve outcomes for neuro-oncological patients globally.

Fibrous Nonunion of Odontoid Fractures: Is It Safe To Accept Nonoperative Management? A Systematic Review.

OBJECTIVE: Nonoperative management of odontoid fractures can result in solid fusion, unstable nonunion, and fibrous nonunion. Odontoid fractures with fibrous nonunion will not demonstrate dynamic instability on imaging studies. However, the safety of accepting this outcome has been debated. We have provided, to the best of our knowledge, the first systematic review of the existing literature to explore the safety of allowing fibrous nonunion as an acceptable outcome for odontoid fractures. METHODS: The PubMed and Embase databases were searched in January 2022. The outcomes were extracted and categorized according to the mortality, neurologic sequelae, pain, neck disability index, and satisfaction. RESULTS: Of a total of 700 abstracts screened, the full text of 79 reports was assessed, with 13 studies included. Of the included patients, 141 had had a fibrous nonunion, all described in observational studies. The follow-up ranged from 0.6 to 5.8 years. None of the 141 patients had experienced a neurologic event. One patient had died of trauma-related issues; however, causality was not reported. Most of the studies had reported good to excellent pain scores. Most of the neck disabilities reported had ranged from mild to moderate in severity. However, 1 study of 5 patients had reported severe disability. All the patients reported good or excellent satisfaction. CONCLUSIONS: The evidence we found supports that it is safe to forgo surgery for carefully selected patients with nonunited odontoid fractures when near-anatomic alignment is present, dynamic instability is lacking on imaging studies, the neurologic examination findings are normal, and the risk of neck injury is low. Further study is needed to define the full natural history of fibrous nonunion of odontoid fractures.

Complications and cosmetic outcomes of materials used in cranioplasty following decompressive craniectomy-a systematic review, pairwise meta-analysis, and network meta-analysis.

BACKGROUND: Optimal reconstruction materials for cranioplasty following decompressive craniectomy (DC) remain unclear. This systematic review, pairwise meta-analysis, and network meta-analysis compares cosmetic outcomes and complications of autologous bone grafts and alloplasts used for cranioplasty following DC. METHOD: PubMed, Embase, and Cochrane were searched from inception until April 2021. A random-effects pairwise meta-analysis was used to compare pooled outcomes and 95% confidence intervals (CIs) of autologous bone to combined alloplasts. A frequentist network meta-analysis was subsequently conducted to compare multiple individual materials. RESULTS: Of 2033 articles screened, 30 studies were included, consisting of 29 observational studies and one randomized control trial. Overall complications were statistically significantly higher for autologous bone compared to combined alloplasts (RR = 1.56, 95%CI = 1.14-2.13), hydroxyapatite (RR = 2.60, 95%CI = 1.17-5.78), polymethylmethacrylate (RR = 1.50 95%CI = 1.08-2.08), and titanium (Ti) (RR = 1.56 95%CI = 1.03-2.37). Resorption occurred only in autologous bone (15.1%) and not in alloplasts (0.0%). When resorption was not considered, there was no difference in overall complications between autologous bone and combined alloplasts (RR = 1.00, 95%CI = 0.75-1.34), nor between any individual materials. Dehiscence was lower for autologous bone compared to combined alloplasts (RR = 0.39, 95%CI = 0.19-0.79) and Ti (RR = 0.34, 95%CI = 0.15-0.76). There was no difference between autologous bone and combined alloplasts with respect to infection (RR = 0.85, 95%CI = 0.56-1.30), migration (RR = 1.36, 95%CI = 0.63-2.93), hematoma (RR = 0.98, 95%CI = 0.53-1.79), seizures (RR = 0.83, 95%CI = 0.29-2.35), satisfactory cosmesis (RR = 0.88, 95%CI = 0.71-1.08), and reoperation (RR = 1.66, 95%CI = 0.90-3.08). CONCLUSIONS: Bone resorption is only a consideration in autologous cranioplasty compared to bone substitutes explaining higher complications for autologous bone. Dehiscence is higher in alloplasts, particularly in Ti, compared to autologous bone.

Rare large colloid cyst obstructing the posterior third ventricle: illustrative case.

BACKGROUND: Colloid cysts of the posterior third ventricle are exceedingly rare. This location is a high-risk zone for colloid cysts because of potential obstruction of the cerebral aqueduct. OBSERVATIONS: The authors report a case of a 57-year-old man who presented with a 6-month history of progressive headache, short-term memory loss, visual blurring, and an episode of double vision. Magnetic resonance imaging (MRI) revealed a colloid cyst, 22 mm in diameter, attached to the roof of the posterior third ventricle. The posterior third ventricle was obstructed, but both foramina of Monro were patent. The entirety of the cyst was resected via a right frontal parasagittal, interhemispheric, transventricular approach through the foramen of Monro. It was not contained within the velum interpositum. The patient did not experience any postoperative deficits. LESSONS: This case supports the theoretical evidence that colloid cysts in the posterior zone of the third ventricle pose a risk for obstructive hydrocephalus. This report of a large cyst in a rare location describes a unique lesion and provides the first published MRI description.