The glymphatic system for neurosurgeons: a scoping review.

The discovery of the glymphatic system has revolutionized our understanding of cerebrospinal fluid (CSF) circulation and interstitial waste clearance in the brain. This scoping review aims to synthesize the current literature on the glymphatic system's role in neurosurgical conditions and its potential as a therapeutic target. We conducted a comprehensive search in PubMed and Scopus databases for studies published between January 1, 2012, and October 31, 2023. Studies were selected based on their relevance to neurosurgical conditions and glymphatic function, with both animal and human studies included. Data extraction focused on the methods for quantifying glymphatic function and the main results. A total of 67 articles were included, covering conditions such as idiopathic normal pressure hydrocephalus (iNPH), idiopathic intracranial hypertension (IIH), subarachnoid hemorrhage (SAH), stroke, intracranial tumors, and traumatic brain injury (TBI). Significant glymphatic dysregulation was noted in iNPH and IIH, with evidence of impaired CSF dynamics and delayed clearance. SAH studies indicated glymphatic dysfunction with the potential therapeutic effects of nimodipine and tissue plasminogen activator. In stroke, alterations in glymphatic activity correlated with the extent of edema and neurological recovery. TBI studies highlighted the role of the glymphatic system in post-injury cognitive outcomes. Results indicate that the regulation of aquaporin-4 (AQP4) channels is a critical target for therapeutic intervention. The glymphatic system plays a critical role in the pathophysiology of various neurosurgical conditions, influencing brain edema and CSF dynamics. Targeting the regulation of AQP4 channels presents as a significant therapeutic strategy. Although promising, the translation of these findings into clinical practice requires further human studies. Future research should focus on establishing non-invasive biomarkers for glymphatic function and exploring the long-term effects of glymphatic dysfunction.

Incidence, management, and outcome of incidental meningioma: what has happened in 10 years?

PURPOSE: The aim of this study was to study the use of brain scanning, and the subsequent findings of presumed incidental meningioma in two time periods, and to study differences in follow-up, treatment, and outcome. METHODS: Records of all performed CT and MRI of the brain during two time periods were retrospectively reviewed in search of patients with presumed incidental meningioma. These patients were further analyzed using medical health records, with the purpose to study clinical handling and outcome during a 3 year follow up. RESULTS: An identical number of unique patients underwent brain imaging during the two time periods (n = 22 259 vs. 22 013). In 2018-2019, 25% more incidental meningiomas were diagnosed compared to 2008-2009 (n = 161 vs. 129, p = 0.052). MRI was used more often in 2018-2019 (26.1 vs. 12.4%, p = 0.004), and the use of contrast enhancement, irrespective of modality, also increased (26.8 vs. 12.2%, p < 0.001). In the most recent cohort, patients were older (median 79 years vs. 73 years, p = 0.03). Indications showed a significant increase of cancer without known metastases among scanned patients. 29.5 and 35.4% of patients in the cohorts were deceased 3 years after diagnosis for causes unrelated to their meningioma. CONCLUSIONS: Despite the same number of unique patients undergoing brain scans in the time periods, there was a trend towards more patients diagnosed with an incidental asymptomatic meningioma in the more recent years. This difference may be attributed to more contrast enhanced scans and more scans among the elderly but needs to be further studied. Patients in the cohort from 2018 to 2019 more often had non-metastatic cancer, with their cause of scan screening for metastases. There was no significant difference in management decision at diagnosis, but within 3 years of follow up significantly more patients in the latter cohort had been re-scanned. Almost a third of all patients were deceased within 3 years after diagnosis, due to causes other than their meningioma.

Segmentation of glioblastomas in early post-operative multi-modal MRI with deep neural networks.

Extent of resection after surgery is one of the main prognostic factors for patients diagnosed with glioblastoma. To achieve this, accurate segmentation and classification of residual tumor from post-operative MR images is essential. The current standard method for estimating it is subject to high inter- and intra-rater variability, and an automated method for segmentation of residual tumor in early post-operative MRI could lead to a more accurate estimation of extent of resection. In this study, two state-of-the-art neural network architectures for pre-operative segmentation were trained for the task. The models were extensively validated on a multicenter dataset with nearly 1000 patients, from 12 hospitals in Europe and the United States. The best performance achieved was a 61% Dice score, and the best classification performance was about 80% balanced accuracy, with a demonstrated ability to generalize across hospitals. In addition, the segmentation performance of the best models was on par with human expert raters. The predicted segmentations can be used to accurately classify the patients into those with residual tumor, and those with gross total resection.

Long-term follow up of patients with WHO grade 2 oligodendroglioma.

PURPOSE: Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival. METHODS: All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival. RESULTS: 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0-19.6). Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02-1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02-1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70-11.78, p = 0.002). In our material, surgical strategy was not associated with survival. CONCLUSION: Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival.

Six-Month Follow-up of a Trial of Spinal Cord Burst Stimulation vs Placebo Stimulation and Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery.

This follow-up study examines back pain­related disability at 6 months following a randomized trial of spinal cord burst stimulation for chronic radicular pain after lumbar spine surgery.

Tailoring vascular phenotype through AAV therapy promotes anti-tumor immunity in glioma.

Glioblastomas are aggressive brain tumors that are largely immunotherapy resistant. This is associated with immunosuppression and a dysfunctional tumor vasculature, which hinder T cell infiltration. LIGHT/TNFSF14 can induce high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), suggesting that its therapeutic expression could promote T cell recruitment. Here, we use a brain endothelial cell-targeted adeno-associated viral (AAV) vector to express LIGHT in the glioma vasculature (AAV-LIGHT). We found that systemic AAV-LIGHT treatment induces tumor-associated HEVs and T cell-rich TLS, prolonging survival in αPD-1-resistant murine glioma. AAV-LIGHT treatment reduces T cell exhaustion and promotes TCF1+CD8+ stem-like T cells, which reside in TLS and intratumoral antigen-presenting niches. Tumor regression upon AAV-LIGHT therapy correlates with tumor-specific cytotoxic/memory T cell responses. Our work reveals that altering vascular phenotype through vessel-targeted expression of LIGHT promotes efficient anti-tumor T cell responses and prolongs survival in glioma. These findings have broader implications for treatment of other immunotherapy-resistant cancers.

The clinical value of proneural, classical and mesenchymal protein signatures in WHO 2021 adult-type diffuse lower-grade gliomas.

OBJECTIVES: Accumulating evidence shows that mesenchymal transition of glioblastomas is associated with a more aggressive course of disease and therapy resistance. In WHO2021-defined adult-type diffuse gliomas of lower grade (dLGG), the transition of the tumor phenotype over time, has not been studied. Most efforts to correlate proneural, classical or mesenchymal phenotype with outcome in dLGG were made prior to the WHO 2021 classification. Here, we set out to investigate if phenotype predicted survival and tumor recurrence in a clinical cohort of dLGGs, re-classified according to the 2021 WHO criteria. METHODS: Using a TMA-based approach with five immunohistochemical markers (EGFR, p53, MERTK, CD44 and OLIG2), we investigated 183 primary and 49 recurrent tumors derived from patients with previously diagnosed dLGG. Of the 49 relapses, nine tumors recurred a second time, and one a third time. RESULTS: In total, 71.0% of all tumors could be subtyped. Proneural was most dominant in IDH-mut tumors (78.5%), mesenchymal more common among IDH-wt tumors (63.6%). There was a significant difference in survival between classical, proneural and mesenchymal phenotypes in the total cohort (p<0.001), but not after molecular stratification (IDH-mut: p = 0.220, IDH-wt: p = 0.623). Upon recurrence, proneural was retained in 66.7% of the proneural IDH-mut dLGGs (n = 21), whereas IDH-wt tumors (n = 10) mainly retained or gained mesenchymal phenotype. No significant difference in survival was found between IDH-mut gliomas remaining proneural and those shifting to mesenchymal phenotype (p = 0.347). CONCLUSION: Subtyping into classical, proneural and mesenchymal phenotypes by five immunohistochemical markers, was possible for the majority of tumors, but protein signatures did not correlate with patient survival in our WHO2021-stratified cohort. At recurrence, IDH-mut tumors mainly retained proneural, while IDH-wt tumors mostly retained or gained mesenchymal signatures. This phenotypic shift, associated with increased aggressiveness in glioblastoma, did not affect survival. Group sizes were, however, too small to draw any firm conclusions.

Circulating Brain Injury Biomarkers: A Novel Method for Quantification of the Impact on the Brain After Tumor Surgery.

BACKGROUND: Clinical methods to quantify brain injury related to neurosurgery are scarce. Circulating brain injury biomarkers have recently gained increased interest as new ultrasensitive measurement techniques have enabled quantification of brain injury through blood sampling. OBJECTIVE: To establish the time profile of the increase in the circulating brain injury biomarkers glial fibrillary acidic protein (GFAP), tau, and neurofilament light (NfL) after glioma surgery and to explore possible relationships between these biomarkers and outcome regarding volume of ischemic injury identified with postoperative MRI and new neurological deficits. METHODS: In this prospective study, 34 adult patients scheduled for glioma surgery were included. Plasma concentrations of brain injury biomarkers were measured the day before surgery, immediately after surgery, and on postoperative days 1, 3, 5, and 10. RESULTS: Circulating brain injury biomarkers displayed a postoperative increase in the levels of GFAP ( P < .001), tau ( P < .001), and NfL ( P < .001) on Day 1 and a later, even higher, peak of NFL at Day 10 ( P = .028). We found a correlation between the increased levels of GFAP, tau, and NfL on Day 1 after surgery and the volume of ischemic brain tissue on postoperative MRI. Patients with new neurological deficits after surgery had higher levels of GFAP and NfL on Day 1 compared with those without new neurological deficits. CONCLUSION: Measuring circulating brain injury biomarkers could be a useful method for quantification of the impact on the brain after tumor surgery or neurosurgery in general.

Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden.

INTRODUCTION: The use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life. METHODS AND ANALYSIS: PRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints. ETHICS AND DISSEMINATION: To implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05190172).

Overview and recent advances in incidental meningioma.

INTRODUCTION: Meningioma has a prevalence around 1% in the population, and with the increasing use and availability of diagnostic imaging modalities, incidental meningiomas are increasingly detected. There is no clear consensus on their management, although several guidelines suggest firsthand active monitoring if no aggravating factors emerge. However, no collective guidelines on follow-up interval exist. AREAS COVERED: This narrative review covers the epidemiology, diagnosis, growth prediction, and management strategies of incidental meningioma. EXPERT OPINION: Overdiagnosis and excessive follow-up are potential pitfalls in the management of incidental meningioma. An MRI after 6-12 months could be reasonable to rule out rapid growth and differential diagnoses. Using the available prognostic models, one might later suggest more active monitoring for certain patient groups harboring specific radiological features predictive of growth. However, detecting growth may not necessarily be clinically significant as all larger non-growing meningiomas have at one point been small. Too much follow-up may place an unnecessary burden on patients and the health-care system and could be a driver toward overtreatment. It must be contemplated whether growth is an acceptable primary outcome measure or if there are other factors more relevant to consider in this often benign tumor entity.

Learning Curve Analysis and Adverse Events After Implementation of Neurosurgical Laser Ablation Treatment: A Population-Based Single-Institution Consecutive Series.

OBJECTIVE AND METHODS: We conducted a retrospective review of the first 30 patients treated with stereotactic laser ablation (SLA) at our institution since the introduction of the technique in September 2019. We aimed to analyze our initial results and potential learning curve by investigating precision and lesion coverage and assessing the frequency and nature of adverse events according to the Landriel-Ibanez classification for neurosurgical complications. RESULTS: Indications were de novo gliomas (23%), recurrent gliomas (57%), and epileptogenic foci (20%). There was a trend toward improvement of lesion coverage and target deviation, and a statistically significant improvement in entry point deviation, over time. Four patients (13.3%) experienced a new neurological deficit, where three patients had transient and one patient had permanent deficits, respectively. Our results show a learning curve on precision measures over the first 30 cases. Based on our results the technique can safely be implemented at centers with experience in stereotaxy.

Meningioma classification by immunohistochemistry: A replicability study.

Introduction: Meningiomas account for nearly 40% of intracranial tumors. Recently, the immunohistochemistry (IHC) markers S100B, SCGN, ACADL and MCM2 have been shown to be associated with underlying biological subtypes of meningioma (MG1-MG4). We aimed to evaluate these IHC markers in a clinical setting. Research question: Are the new proposed IHC markers clinically useful? Methods: In total, 244 patients with meningiomas with tissue in TMAs were included and the IHC markers S100B, SCGN, ACADL and MCM2 were analyzed. Two sets of analyses were performed; the first included all samples with any staining considered positive, the second only samples with >10% immunopositivity. PFS and OS were analyzed in correlation to immunopositivity in the second analysis set. Results: In the first set of analyses only 26.2% of samples could be to allocate to one group. No further analyses were performed with this selection. In the second set of analyses 52.0% could be allocated to a group. There was an enrichment of WHO grade 2 and 3 tumors in MG3 and MG4 as compared to MG1 (24.1% and 25.7% vs. 12.1%). Both the molecular group (p â€‹= â€‹0.032) and WHO grade (p â€‹= â€‹0.005) had significant impact on PFS, but only WHO grade predicted OS (p â€‹= â€‹0.033). Conclusion: We studied the proposed new method of classifying meningiomas into groups MG1, MG2, MG3 and MG4 using IHC markers, but found difficulties applying the classification system in our material mainly due to lack of exclusivity of markers. Thus, in its present form the classification method lacks clinical applicability.

Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse Low-Grade Glioma.

PURPOSE: In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible. METHODS: In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR. RESULTS: Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis. CONCLUSION: Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.

Effect of Irrigation Fluid Temperature on Recurrence in the Evacuation of Chronic Subdural Hematoma: A Randomized Clinical Trial.

Importance: The effect of a physical property of irrigation fluid (at body vs room temperature) on recurrence rate in the evacuation of chronic subdural hematoma (cSDH) needs further study. Objective: To explore whether irrigation fluid temperature has an influence on cSDH recurrence. Design, Setting, and Participants: This was a multicenter randomized clinical trial performed between March 16, 2016, and May 30, 2020. The follow-up period was 6 months. The study was conducted at 3 neurosurgical departments in Sweden. All patients older than 18 years undergoing cSDH evacuation during the study period were screened for eligibility in the study. Interventions: The study participants were randomly assigned by 1:1 block randomization to the cSDH evacuation procedure with irrigation fluid at room temperature (RT group) or at body temperature (BT group). Main Outcomes and Measures: The primary end point was recurrence requiring reoperation within 6 months. Secondary end points were mortality, health-related quality of life, and complication frequency. Results: At 6 months after surgery, 541 patients (mean [SD] age, 75.8 [9.8] years; 395 men [73%]) had a complete follow-up according to protocol. There were 39 of 277 recurrences (14%) requiring reoperation in the RT group, compared with 16 of 264 recurrences (6%) in the BT group (odds ratio, 2.56; 95% CI, 1.38-4.66; P < .001). There were no significant differences in mortality, health-related quality of life, or complication frequency. Conclusions and Relevance: In this study, irrigation at body temperature was superior to irrigation at room temperature in terms of fewer recurrences. This is a simple, safe, and readily available technique to optimize outcome in patients with cSDH. When irrigation is used in cSDH surgery, irrigation fluid at body temperature should be considered standard of care. Trial Registration: ClincalTrials.gov Identifier: NCT02757235.

Methodological Approaches to Ketogenic Dietary Treatments in Glioma Patients from a Nutritional Point of View.

Ketogenic diets (KD) have received increasing interest in neuro-oncology based on their ability to inhibit glioma growth In Vitro and their established role in medically refractory seizures. This review analyses the methodological aspects of KD treatment alongside standard care for patients with gliomas from a nutritional point of view. A literature search was performed in March 2022 searching PubMed and Scopus. We identified 13 articles including 187 patients with a histological-new or recurrent-diagnosis of glioma and treated by KD during the course of the disease. Dietary treatments were categorized as the classical ketogenic diet (CKD), the Modified Atkins diet (MAD), and the medium-chain triglyceride (MCT) diet. We identified a large variation in dietary characteristics regarding restriction of carbohydrates, ketogenic ratio, and additional dietary support. This striking heterogenicity in the methodological approaches of KD treatments made it problematic to compare effects between the included studies. Therefore, a standardized definition of KD for patients with glioma and a consensus on methodological implementation is needed. It would also be desirable to further investigate to what extent KD treatment can be optimized to secure optimal nutrient status and patient satisfaction.

Experiences of language and communication after brain-tumour treatment: A long-term follow-up after glioma surgery.

The purpose of this study was to explore how persons having received various treatments for glioma, a type of brain tumour, experience their language, speech, and communication in everyday life. Twelve persons with low-grade glioma and one with high-grade glioma who had undergone tumour resection in 2014-2016 in different tumour locations were interviewed using a semi-structured protocol. The video-recorded interviews were transcribed and analysed using qualitative content analysis, which revealed three manifest categories, nine sub-categories and one latent theme. Participants experienced changed communication that affected word finding, motor speech and comprehension. They also expressed how communication required a greater effort; time and context were important factors and participants felt frustrated with their communication. Further, they were dealing with changes and used multiple strategies to manage communication. For most participants it did not affect their everyday life, but it was not like before. In addition, participants adapted their way of living to manage illness-related problems. Uncertainty was a latent theme which emanated from the participants' illness experience, reflecting how living with a slow-growing brain tumour affects life-decisions and views of perceived symptoms. Discussion of how results can be interpreted in relation to previous research and health care are included.

Changes in clinical management of diffuse IDH-mutated lower-grade gliomas: patterns of care in a 15-year period.

BACKGROUND: Isocitrate dehydrogenase (IDH) mutated diffuse lower-grade gliomas (dLGG) are infiltrating brain tumors and increasing evidence is in favor of early multimodal treatment. In a Scandinavian population-based setting, we wanted to study treatment patterns over the last 15 years, focusing on the short-term postoperative course to better understand the potential negative consequences of treatment. METHODS: Patients ≥ 18 years with primary IDH-mutated dLGG grade 2 and 3, operated between January 2007-June 2021 were identified. Patients were divided into subgroups (2007-2011, 2012-2016, and 2017-2021) and comparisons regarding tumor- and disease characteristics, treatment, and postoperative outcome were performed. RESULTS: We identified 202 patients (n = 61, 2007-2011; n = 72, 2012-2016; n = 69, 2017-2021), where of 193 underwent resection without change in proportion of resections over time. More patients underwent complete resections in recent times (6.1%; 15.7%; 26.1%, respectively; p = 0.016). Forty-two patients had any neurological deficit postoperatively (14.8%; 23.6%; 23.2%; p = 0.379), mostly minor and transient. Differences in oncological therapy were seen between the investigated subgroups. Early radiotherapy alone (32.8%; 7%; 2.9%; p < 0.001), concomitant chemoradiotherapy (23%; 37.5%; 17.4%; p = 0.022), sequential chemoradiotherapy (0%; 18%; 49.3%; p < 0.001), and no adjuvant treatment (42.6%; 23.6%; 18.8%; p = 0.009) shifted during the studied period. Increasingly more patients received proton radiotherapy compared to photon radiotherapy during the later time periods (p < 0.001). CONCLUSION: Complete resections were performed more often in later time periods without an apparent increase in surgical morbidity. Early adjuvant oncological treatment shifted towards providing chemotherapy and combined chemoradiotherapy more often in later time periods. Protons replaced photons as the radiation modality of choice.

Effect of Spinal Cord Burst Stimulation vs Placebo Stimulation on Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery: A Randomized Clinical Trial.

Importance: The use of spinal cord stimulation for chronic pain after lumbar spine surgery is increasing, yet rigorous evidence of its efficacy is lacking. Objective: To investigate the efficacy of spinal cord burst stimulation, which involves the placement of an implantable pulse generator connected to electrodes with leads that travel into the epidural space posterior to the spinal cord dorsal columns, in patients with chronic radiculopathy after surgery for degenerative lumbar spine disorders. Design, Setting, and Participants: This placebo-controlled, crossover, randomized clinical trial in 50 patients was conducted at St Olavs University Hospital in Norway, with study enrollment from September 5, 2018, through April 28, 2021. The date of final follow-up was May 20, 2022. Interventions: Patients underwent two 3-month periods with spinal cord burst stimulation and two 3-month periods with placebo stimulation in a randomized order. Burst stimulation consisted of closely spaced, high-frequency electrical stimuli delivered to the spinal cord. The stimulus consisted of a 40-Hz burst mode of constant-current stimuli with 4 spikes per burst and an amplitude corresponding to 50% to 70% of the paresthesia perception threshold. Main Outcomes and Measures: The primary outcome was difference in change from baseline in the self-reported Oswestry Disability Index (ODI; range, 0 points [no disability] to 100 points [maximum disability]; the minimal clinically important difference was 10 points) score between periods with burst stimulation and placebo stimulation. The secondary outcomes were leg and back pain, quality of life, physical activity levels, and adverse events. Results: Among 50 patients who were randomized (mean age, 52.2 [SD, 9.9] years; 27 [54%] were women), 47 (94%) had at least 1 follow-up ODI score and 42 (84%) completed all stimulation randomization periods and ODI measurements. The mean ODI score at baseline was 44.7 points and the mean changes in ODI score were -10.6 points for the burst stimulation periods and -9.3 points for the placebo stimulation periods, resulting in a mean between-group difference of -1.3 points (95% CI, -3.9 to 1.3 points; P = .32). None of the prespecified secondary outcomes showed a significant difference. Nine patients (18%) experienced adverse events, including 4 (8%) who required surgical revision of the implanted system. Conclusions and Relevance: Among patients with chronic radicular pain after lumbar spine surgery, spinal cord burst stimulation, compared with placebo stimulation, after placement of a spinal cord stimulator resulted in no significant difference in the change from baseline in self-reported back pain-related disability. Trial Registration: ClinicalTrials.gov Identifier: NCT03546738.

Preoperative Brain Tumor Imaging: Models and Software for Segmentation and Standardized Reporting.

For patients suffering from brain tumor, prognosis estimation and treatment decisions are made by a multidisciplinary team based on a set of preoperative MR scans. Currently, the lack of standardized and automatic methods for tumor detection and generation of clinical reports, incorporating a wide range of tumor characteristics, represents a major hurdle. In this study, we investigate the most occurring brain tumor types: glioblastomas, lower grade gliomas, meningiomas, and metastases, through four cohorts of up to 4,000 patients. Tumor segmentation models were trained using the AGU-Net architecture with different preprocessing steps and protocols. Segmentation performances were assessed in-depth using a wide-range of voxel and patient-wise metrics covering volume, distance, and probabilistic aspects. Finally, two software solutions have been developed, enabling an easy use of the trained models and standardized generation of clinical reports: Raidionics and Raidionics-Slicer. Segmentation performances were quite homogeneous across the four different brain tumor types, with an average true positive Dice ranging between 80 and 90%, patient-wise recall between 88 and 98%, and patient-wise precision around 95%. In conjunction to Dice, the identified most relevant other metrics were the relative absolute volume difference, the variation of information, and the Hausdorff, Mahalanobis, and object average symmetric surface distances. With our Raidionics software, running on a desktop computer with CPU support, tumor segmentation can be performed in 16-54 s depending on the dimensions of the MRI volume. For the generation of a standardized clinical report, including the tumor segmentation and features computation, 5-15 min are necessary. All trained models have been made open-access together with the source code for both software solutions and validation metrics computation. In the future, a method to convert results from a set of metrics into a final single score would be highly desirable for easier ranking across trained models. In addition, an automatic classification of the brain tumor type would be necessary to replace manual user input. Finally, the inclusion of post-operative segmentation in both software solutions will be key for generating complete post-operative standardized clinical reports.