Incidence, risk factors, and clinical implications of postoperative blood in or near the resection cavity after glioma surgery.

Introduction: Postoperative hematomas that require reoperation are a serious, but uncommon complication to glioma surgery. However, smaller blood volumes are frequently observed, but their clinical significance is less known. Research question: What are the incidence rates, risk factors, and patient-reported outcomes of all measurable blood in or near the resection cavity on postoperative MRI in diffuse glioma patients? Material and methods: We manually segmented intradural and extradural blood from early postoperative MRI of 292 diffuse glioma resections. Potential associations between blood volume and tumor characteristics, demographics, and perioperative factors were explored using non-parametric methods. The assessed outcomes were generic and disease-specific patient-reported HRQoL. Results: Out of the 292 MRI scans included, 184 (63%) had intradural blood, and 212 (73%) had extradural blood in or near the resection cavity. The median blood volumes were 0.4 mL and 3.0 mL, respectively. Intradural blood volume was associated with tumor volume, intraoperative blood loss, and EOR. Extradural blood volume was associated with age and tumor volume. Greater intradural blood volume was associated with less headache and cognitive improvement, but not after adjustments for tumor volume. Discussion and conclusions: Postoperative blood on early postoperative MRI is common. Intradural blood volumes tend to be larger in patients with larger tumors, more intraoperative blood loss, or undergoing subtotal resections. Extradural blood volumes tend to be larger in younger patients with larger tumors. Postoperative blood in or near the resection cavity that does not require reoperation does not seem to affect HRQoL in diffuse glioma patients.

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.

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.

Brain infarction following meningioma surgery-incidence, risk factors, and impact on function, seizure risk, and patient-reported quality of life.

In this study, we seek to explore the incidence of and potential risk factors for postoperative infarctions after meningioma surgery, in addition to the possible association with new neurological deficits, seizures, and health-related quality of life (HRQoL). A single-center cohort study was conducted, where all patients operated for an intracranial meningioma at our institution between 2007 and 2020 were screened for inclusion. Clinical data were prospectively collected in a local tumor registry, and HRQoL was assessed using both generic and disease-specific instruments. In total, 327 meningioma operations were included, and early postoperative MRIs showed peritumoral infarctions in 114 (34.9%). Median infarction volume was 4.5 ml (interquartile range 2.0-9.5) and 43 (37.7%) of the infarctions were rim-shaped, 44 (38.6%) were sector-shaped, 25 (21.9%) were a combination of rim- and sector-shaped, and two (1.8%) were remote infarctions. Permanent neurological deficits were seen in 22 patients (6.7%) and deficits were associated with infarctions (p < 0.001). There was no difference in frequency of registered postoperative epilepsy between patients with versus without infarctions. Patients with infarctions reported more future uncertainty; otherwise, there were no significant differences in disease specific HRQoL between patients with versus without infarctions. In this study, we found that peritumoral infarctions after meningioma resection are common. Most patients with permanent neurological deficits had infarctions. Yet, most infarctions were small, and although sometimes symptomatic on individual level, infarctions did not lead to significant deterioration of HRQoL on group level.

Glioblastoma Surgery Imaging-Reporting and Data System: Validation and Performance of the Automated Segmentation Task.

For patients with presumed glioblastoma, essential tumor characteristics are determined from preoperative MR images to optimize the treatment strategy. This procedure is time-consuming and subjective, if performed by crude eyeballing or manually. The standardized GSI-RADS aims to provide neurosurgeons with automatic tumor segmentations to extract tumor features rapidly and objectively. In this study, we improved automatic tumor segmentation and compared the agreement with manual raters, describe the technical details of the different components of GSI-RADS, and determined their speed. Two recent neural network architectures were considered for the segmentation task: nnU-Net and AGU-Net. Two preprocessing schemes were introduced to investigate the tradeoff between performance and processing speed. A summarized description of the tumor feature extraction and standardized reporting process is included. The trained architectures for automatic segmentation and the code for computing the standardized report are distributed as open-source and as open-access software. Validation studies were performed on a dataset of 1594 gadolinium-enhanced T1-weighted MRI volumes from 13 hospitals and 293 T1-weighted MRI volumes from the BraTS challenge. The glioblastoma tumor core segmentation reached a Dice score slightly below 90%, a patientwise F1-score close to 99%, and a 95th percentile Hausdorff distance slightly below 4.0 mm on average with either architecture and the heavy preprocessing scheme. A patient MRI volume can be segmented in less than one minute, and a standardized report can be generated in up to five minutes. The proposed GSI-RADS software showed robust performance on a large collection of MRI volumes from various hospitals and generated results within a reasonable runtime.

Brain infarctions after glioma surgery: prevalence, radiological characteristics and risk factors.

BACKGROUND: Prevalence, radiological characteristics, and risk factors for peritumoral infarctions after glioma surgery are not much studied. In this study, we assessed shape, volume, and prevalence of peritumoral infarctions and investigated possible associated factors. METHODS: In a prospective single-center cohort study, we included all adult patients operated for diffuse gliomas from January 2007 to December 2018. Postoperative infarctions were segmented using early postoperative MRI images, and volume, shape, and location of postoperative infarctions were assessed. Heatmaps of the distribution of tumors and infarctions were created. RESULTS: MRIs from 238 (44%) of 539 operations showed restricted diffusion in relation to the operation cavity, interpreted as postoperative infarctions. Of these, 86 (36%) were rim-shaped, 103 (43%) were sector-shaped, 40 (17%) were a combination of rim- and sector-shaped, and six (3%) were remote infarctions. Median infarction volume was 1.7 cm3 (IQR 0.7-4.3, range 0.1-67.1). Infarctions were more common if the tumor was in the temporal lobe, and the map shows more infarctions in the periventricular watershed areas. Sector-shaped infarctions were more often seen in patients with known cerebrovascular disease (47.6% vs. 25.5%, p = 0.024). There was a positive correlation between infarction volume and tumor volume (r = 0.267, p < 0.001) and infarction volume and perioperative bleeding (r = 0.176, p = 0.014). Moreover, there was a significant positive association between age and larger infarction volumes (r = 0.193, p = 0.003). Infarction rates and infarction volumes varied across individual surgeons, p = 0.037 (range 32-72%) and p = 0.026. CONCLUSIONS: In the present study, peritumoral infarctions occurred in 44% after diffuse glioma operations. Infarctions were more common in patients operated for tumors in the temporal lobe but were not more common following recurrent surgeries. Sector-shaped infarctions were more common in patients with known cerebrovascular disease. Increasing age, larger tumors, and more perioperative bleeding were factors associated with infarction volumes. The risk of infarctions and infarction volumes may also be surgeon-dependent.

Glioblastoma Surgery Imaging-Reporting and Data System: Standardized Reporting of Tumor Volume, Location, and Resectability Based on Automated Segmentations.

Treatment decisions for patients with presumed glioblastoma are based on tumor characteristics available from a preoperative MR scan. Tumor characteristics, including volume, location, and resectability, are often estimated or manually delineated. This process is time consuming and subjective. Hence, comparison across cohorts, trials, or registries are subject to assessment bias. In this study, we propose a standardized Glioblastoma Surgery Imaging Reporting and Data System (GSI-RADS) based on an automated method of tumor segmentation that provides standard reports on tumor features that are potentially relevant for glioblastoma surgery. As clinical validation, we determine the agreement in extracted tumor features between the automated method and the current standard of manual segmentations from routine clinical MR scans before treatment. In an observational consecutive cohort of 1596 adult patients with a first time surgery of a glioblastoma from 13 institutions, we segmented gadolinium-enhanced tumor parts both by a human rater and by an automated algorithm. Tumor features were extracted from segmentations of both methods and compared to assess differences, concordance, and equivalence. The laterality, contralateral infiltration, and the laterality indices were in excellent agreement. The native and normalized tumor volumes had excellent agreement, consistency, and equivalence. Multifocality, but not the number of foci, had good agreement and equivalence. The location profiles of cortical and subcortical structures were in excellent agreement. The expected residual tumor volumes and resectability indices had excellent agreement, consistency, and equivalence. Tumor probability maps were in good agreement. In conclusion, automated segmentations are in excellent agreement with manual segmentations and practically equivalent regarding tumor features that are potentially relevant for neurosurgical purposes. Standard GSI-RADS reports can be generated by open access software.

Clinical Course in Chronic Subdural Hematoma Patients Aged 18-49 Compared to Patients 50 Years and Above: A Multicenter Study and Meta-Analysis.

Objective: Chronic Subdural Hematoma (cSDH) is primarily a disease of elderly, and is rare in patients <50 years, and this may in part be related to the increased brain atrophy from 50 years of age. This fact may also influence clinical presentation and outcome. The aim of this study was to study the clinical course with emphasis on clinical presentation of cSDH patients in the young (<50 years). Methods: A retrospective review of a population-based cohort of 1,252 patients operated for cSDH from three Scandinavian neurosurgical centers was conducted. The primary end-point was difference in clinical presentation between the patients <50 y/o and the remaining patients (≥50 y/o group). The secondary end-points were differences in perioperative morbidity, recurrence and mortality between the two groups. In addition, a meta-analysis was performed comparing clinical patterns of cSDH in the two age groups. Results: Fifty-two patients (4.2%) were younger than 50 years. Younger patients were more likely to present with headache (86.5% vs. 37.9%, p < 0.001) and vomiting (25% vs. 5.2%, p < 0.001) than the patients ≥50 y/o, while the ≥50 y/o group more often presented with limb weakness (17.3% vs. 44.8%, p < 0.001), speech impairment (5.8% vs. 26.2%, p = 0.001) and gait disturbance or falls (23.1% vs. 50.7%, p < 0.001). There was no difference between the two groups in recurrence, overall complication rate and mortality within 90 days. Our meta-analysis confirmed that younger patients are more likely to present with headache (p = 0.015) while the hemispheric symptoms are more likely in patients ≥50 y/o (p < 0.001). Conclusion: Younger patients with cSDH present more often with signs of increased intracranial pressure, while those ≥50 y/o more often present with hemispheric symptoms. No difference exists between the two groups in terms of recurrence, morbidity, and short-term mortality. Knowledge of variations in clinical presentation is important for correct and timely diagnosis in younger cSDH patients.

Perioperative quality of life in functionally dependent glioblastoma patients: A prospective study.

OBJECTIVE: Functionally dependent patients with glioblastoma have a poor prognosis which may in part be due to a negative treatment selection. Prospective data on patient-reported quality of life (QoL) following surgery, together with an updated survival analysis, are lacking with regard to functionally dependent glioblastoma patients. MATERIALS AND METHODS: Adult patients (≥ 18 years) with a histologically confirmed primary glioblastoma with preoperative Karnofsky Performance Status (KPS) ≤ 60, who were treated between January 1, 2007 and March 30, 2014, were eligible for inclusion. EuroQol 5D (EQ-5D) was scored before surgery and at 4-6 weeks postoperatively. A control group of 20 independent (i.e., KPS ≥ 70) adult primary glioblastoma patients was constructed. RESULTS: Among the 27 patients included, only 22 patients were willing to participate in QoL research, with complete QoL follow-up data obtained for 16. There were 22 resections and 5 biopsies. In resection cases, the median extent of resection was 93% (IQR 78-99), with gross-total resection achieved in 24%. In the 16 patients with complete QoL data, the EQ-5D index score increased from 0.34 ± 0.38 preoperatively to 0.45 ± 0.32 postoperatively (p = 0.30), with 3 patients that deteriorated in QoL following surgery. Median survival was 7.3 months (95%, CI: 4.6-9.9, n = 27), and the perioperative mortality was 7%. Treatment characteristics between dependent and independent patients were similar, as were the unfavorable outcomes defined as QoL reduction, QoL drop-out, and dead before QoL assessment (41% vs. 45%, p = 0.79). However, a difference was seen in 6-month survival (42% vs. 15%, p = 0.05). CONCLUSION: In most functionally dependent patients with glioblastoma, cytoreductive surgery is possible, and improved or unchanged postoperative QoL may be seen in approximately half of the cases. This must be weighed against the risk of complications and the modest effect of cytoreductive surgery.

Surgical strategies in low-grade gliomas and implications for long-term quality of life.

Reports on long-term health related quality of life (HRQL) after surgery for World Health Organization grade II diffuse low-grade gliomas (LGG) are rare. We aimed to compare long-term HRQL in two hospital cohorts with different surgical strategies. Biopsy and watchful waiting was favored in one hospital, while early resections guided with three-dimensional (3D) ultrasound was favored in the other. With a population-based approach 153 patients with histologically verified LGG treated from 1998-2009 were included. Patients still alive were contacted for HRQL assessment (n=91) using generic (EQ-5D; EuroQol Group, Rotterdam, The Netherlands) and disease specific (EORTC QLQ-C30 and BN20; EORTC Quality of Life Department, Brussels, Belgium) questionnaires. Results on HRQL were available in 79 patients (87%), 25 from the hospital that favored biopsy and 54 from the hospital that favored early resection. Among living patients there was no difference in EQ-5D index scores (p=0.426). When imputing scores defined as death (zero) in patients dead at follow-up, a clinically relevant difference in EQ-5D score was observed in favor of early resections (p=0.022, mean difference 0.16, 95% confidence interval 0.02-0.29). In EORTC questionnaires pain, depression and concern about disruption in family life were more common with a strategy of initial biopsy only (p=0.043, p=0.032 and p=0.045 respectively). In long-term survivors an aggressive surgical approach using intraoperative 3D ultrasound image guidance in LGG does not lower HRQL compared to a more conservative surgical approach. This finding further weakens a possible role for watchful waiting in LGG.

Animal study assessing safety of an acoustic coupling fluid that holds the potential to avoid surgically induced artifacts in 3D ultrasound guided operations.

BACKGROUND: Use of ultrasound in brain tumor surgery is common. The difference in attenuation between brain and isotonic saline may cause artifacts that degrade the ultrasound images, potentially affecting resection grades and safety. Our research group has developed an acoustic coupling fluid that attenuates ultrasound energy like the normal brain. We aimed to test in animals if the newly developed acoustic coupling fluid may have harmful effects. METHODS: Eight rats were included for intraparenchymal injection into the brain, and if no adverse reactions were detected, 6 pigs were to be included with injection of the coupling fluid into the subarachnoid space. Animal behavior, EEG registrations, histopathology and immunohistochemistry were used in assessment. RESULTS: In total, 14 animals were included, 8 rats and 6 pigs. We did not detect any clinical adverse effects, seizure activity on EEG or histopathological signs of tissue damage. CONCLUSION: The novel acoustic coupling fluid intended for brain tumor surgery appears safe in rats and pigs under the tested circumstances.