Stereotactic radiosurgery for brain metastasis from cholangiocarcinoma.

OBJECTIVE: Accounting for approximately 15% of primary liver cancers and 3% of gastrointestinal malignancies, cholangiocarcinoma (CCA) poses a serious health concern given its high mortality rate. Managing brain metastases (BMs) from CCA is challenging because of their rarity and poor prognosis, with little guidance on treatment from the literature. In this study, the authors aimed to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in managing BMs from CCA. METHODS: This multicenter retrospective study included 13 CCA patients with 41 BMs treated with SRS from October 2006 to April 2022 at eight institutions affiliated with the International Radiosurgery Research Foundation. Inclusion criteria were a CCA diagnosis, an age over 18 years, no other malignancies, single-fraction SRS treatment for BMs, and at least one follow-up image. Data on demographics, tumor characteristics, treatment details, and outcomes were collected. The primary endpoints were local control (LC), intracranial progression-free survival (PFS), and overall survival (OS). The secondary endpoint was the development of adverse radiation effects (AREs). RESULTS: The median radiological follow-up was 5 months (range 1-18 months). At the last follow-up, LC was achieved in 39 (95.1%) of 41 BMs. New distant metastases were observed in 3 patients (23.1%), and the mean intracranial PFS was 9.4 months (95% CI 6.5-12.3 months). Six-month and 1-year OS rates were 38.5% and 11.5%, respectively, and the median OS was 6 months (95% CI 4.9-7.2 months). Concurrent immunotherapy was associated with a high risk of local failure (HR 29.665, 95% CI 1.799-489.206, p = 0.018), and the absence of systemic chemotherapy before SRS was linked to reduced OS (HR 6.658, 95% CI 1.173-37.776, p = 0.032). Regarding AREs, only 1 patient (7.7%) experienced right hemiparesis and was treated with corticosteroid therapy. CONCLUSIONS: SRS is an effective option for managing BMs in CCA patients, showing promise in LC and a high safety profile.

Long-Term Clinical Outcomes of Acute Kidney Disease in Patients Receiving Extracorporeal Membrane Oxygenation.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is widely used; however, studies on the long-term outcomes of ECMO are scarce. We investigated the long-term clinical outcomes of acute kidney disease (AKD) in patients receiving ECMO. METHODS: Electronic data (2009-2018) were retrospectively collected from a multicenter database. Patients were divided into two groups (AKD and non-AKD) according to their AKD status 8-90 days after the initiation of ECMO. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between the two groups. The primary outcomes were major adverse kidney events (MAKEs) and major adverse cardiovascular events (MACEs), and the secondary outcomes were all-cause readmission, sepsis-related readmission, infection-related readmission, and dementia. RESULTS: Total 395 patients were eligible for analysis; of them, 160 patients (40.5%) developed AKD. The AKD group had a higher risk of MAKEs (hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.68-2.53) than did the non-AKD group. Subgroup analysis revealed that the observed unfavorable effect of AKD on the risk of MAKEs was more pronounced in patients receiving venovenous ECMO than in those receiving venoarterial ECMO (HR: 5.69 vs. 1.85, respectively; P for interaction = 0.004). AKD group had a higher risk of MACE during the initial 3-year post- ECMO in comparison to those without (HR: 1.68; 95% CI: 1.22-2.30). Moreover, the risks of all-cause, sepsis-related, and infection-related readmissions were high in AKD survivors. CONCLUSIONS: AKD is associated with an increased risk of long-term MAKEs and initial 3-year MACE in ECMO recipients. In addition, AKD is associated with increased risks of all-cause, infection-related, and sepsis-related readmissions.

Distributed source modeling of stereoencephalographic measurements of ictal activity.

OBJECTIVES: Stereoelectroencephalography (SEEG) can define the epileptogenic zone (EZ). However, SEEG is susceptible to the sampling bias, where no SEEG recording is taken within a circumscribed EZ. METHODS: Nine patients with medically refractory epilepsy underwent SEEG recording, and brain resection got positive outcomes. Ictal neuronal currents were estimated by distributed source modeling using the SEEG data and individual's anatomical magnetic resonance imaging. Using a retrospective leave-one-out data sub-sampling, we evaluated the sensitivity and specificity of the current estimates using MRI after surgical resection or radio-frequency ablation. RESULTS: The sensitivity and specificity in detecting the EZ were indistinguishable from either the data from all electrodes or the sub-sampled data (rank sum test: rank sum = 23719, p = 0.13) when at least one remaining electrode contact was no more than 20 mm away. CONCLUSIONS: The distributed neuronal current estimates of ictal SEEG data can mitigate the challenge of delineating the boundary of the EZ in cases of missing an electrode implanted within the EZ and a required second SEEG exploration. SIGNIFICANCE: Distributed source modeling can be a tool for clinicians to infer the EZ by allowing for more flexible planning of the electrode implantation route and minimizing the number of electrodes.

Identification of Endothelial Cell Protein C Receptor by Urinary Proteomics as Novel Prognostic Marker in Non-Recovery Kidney Injury.

Acute kidney injury is a common and complex complication that has high morality and the risk for chronic kidney disease among survivors. The accuracy of current AKI biomarkers can be affected by water retention and diuretics. Therefore, we aimed to identify a urinary non-recovery marker of acute kidney injury in patients with acute decompensated heart failure. We used the isobaric tag for relative and absolute quantification technology to find a relevant marker protein that could divide patients into control, acute kidney injury with recovery, and acute kidney injury without recovery groups. An enzyme-linked immunosorbent assay of the endothelial cell protein C receptor (EPCR) was used to verify the results. We found that the EPCR was a usable marker for non-recovery renal failure in our setting with the area under the receiver operating characteristics 0.776 ± 0.065; 95%CI: 0.648-0.905, (p < 0.001). Further validation is needed to explore this possibility in different situations.

Glucose Metabolism of Hippocampal Subfields in Medial Temporal Lobe Epilepsy.

PURPOSE: Reduced glucose metabolism in the hippocampus is commonly observed in cases of medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS). Glucose metabolism among the various hippocampal subfields has not been thoroughly investigated. PATIENTS AND METHODS: This study examined 29 patients (18 females; 15-58 years) diagnosed with HS who underwent surgery for drug-resistant epilepsy. FreeSurfer 7.1.1 was used in the processing of MRI data and 18 F-FDG PET scans to derive volumetric data and the FDG SUVr in the whole hippocampus and hippocampal subfields, including the CA1, CA2-4, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), and subiculum. Asymmetries in the volume and SUVr between the 2 sides from the subfields of the hippocampus were defined in terms of an asymmetry index. Comparisons of the asymmetry index among these regions were performed. The correlations between asymmetry index values and postoperative outcomes and presurgical neuropsychological test results were also evaluated. RESULT: The CA1, CA2-4, subiculum, GC-ML-DG, and whole hippocampus presented reductions in volume and hypometabolism ipsilateral to MTLE. Asymmetries in volume and SUVr were significantly less pronounced in the CA1 and subiculum than in the CA2-4 or GC-ML-DG. Postoperative seizure outcomes were not correlated with the asymmetry index for volume or SUVr in any hippocampal subfield. In cases of left MTLE, scores of immediate logical memory and delayed logical memory were positively correlated with the asymmetry index for SUVr in the following subfields: CA1 ( R = 0.829, P = 0.021; R = 0.770, P = 0.043), CA2-4 ( R = 0.825, P = 0.022; R = 0.894, P = 0.007), subiculum ( R = 0.882, P = 0.009; R = 0.853, P = 0.015), GC-ML-DG ( R = 0.850, P = 0.015; R = 0.796, P = 0.032), and whole hippocampus ( R = 0.841, P = 0.018; R = 0.822, P = 0.023). In cases of right MTLE, the scores for delayed face memory were positively correlated with the asymmetry index for SUVr in the subiculum ( R = 0.935, P = 0.006). CONCLUSIONS: In cases of HS, changes in glucose metabolism levels varied among the hippocampal subfields. Asymmetries in glucose metabolism among the CA-1, CA2-4, subiculum, and GC-ML-DG subregions were correlated with scores for verbal memory among patients with left MTLE. Asymmetric glucose metabolism in the subiculum was also correlated with visual memory scores among patients with right MTLE.

Fibrate and the risk of cardiovascular disease among moderate chronic kidney disease patients with primary hypertriglyceridemia.

Introduction: Hypertriglyceridemia is the most prevalent dyslipidemia in patients with chronic kidney disease (CKD). However, research about fibrate treatment in CKD patients is limited, and assessing its benefits becomes challenging due to the frequent concurrent use of statins. Thus, this study is aimed to investigate the role of fibrate in CKD stage 3 patients with hypertriglyceridemia who did not receive other lipid-lowering agents. Methods: This study enrolled patients newly diagnosed CKD3 with LDL-C<100mg/dL and had never received statin or other lipid-lowering agents from Chang Gung Research Database. The participants were categorized into 2 groups based on the use of fibrate: fibrate group and non-fibrate group (triglyceride >200mg/dL but not receiving fibrate treatment). The inverse probability of treatment weighting was performed to balance baseline characteristics. Results: Compared with the non-fibrate group (n=2020), the fibrate group (n=705) exhibited significantly lower risks of major adverse cardiac and cerebrovascular events (MACCEs) (10.4% vs. 12.8%, hazard ratios [HRs]: 0.69, 95% confidence interval [CI]: 0.50 to 0.95), AMI (2.3% vs. 3.9%, HR: 0.52, 95% CI: 0.37 to 0.73), and ischemic stroke (6.3% vs. 8.0%, HR: 0.67, 95% CI: 0.52 to 0.85). The risk of all-cause mortality (5.1% vs. 4.5%, HR: 1.09, 95% CI: 0.67 to 1.79) and death from CV (2.8% vs. 2.3%, HR: 1.07, 95% CI: 0.29 to 2.33) did not significantly differ between the 2 groups. Conclusion: This study suggests that, in moderate CKD patients with hypertriglyceridemia but LDL-C < 100mg/dL who did not take other lipid-lowering agents, fibrates may be beneficial in reducing cardiovascular events.

Vascular compactness of unruptured brain arteriovenous malformation predicts risk of hemorrhage after stereotactic radiosurgery.

The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume < 20 cm3 versus 20-40 cm3 versus > 40 cm3; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV-V compared with grade I-III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm3) bAVMs and the diffuse Spetzler-Martin IV-V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs.

Frame-based versus robot-assisted stereo-electro-encephalography for drug-resistant epilepsy.

BACKGROUND: Stereoelectroencephalography (SEEG) is an effective presurgical invasive evaluation for drug-resistant epilepsies. The introduction of robotic devices provides a simplified, accurate, and safe alternative to the conventional SEEG technique. We report our institutional experience with robot-assisted SEEG and compare its in vivo accuracy, operation efficiency, and safety with the more traditional SEEG workflow. METHODS: All patients with medically refractory focal epilepsy who underwent SEEG depth electrode implantation between 2014 and 2022 were included in this study. Technical advancements of the robot-assisted technique are described. Analyses of patient demographics, electrode implantation accuracy, operation time, and procedure-related complications were performed. RESULTS: One hundred and sixty-six patients underwent 167 SEEG procedures. The first 141 procedures were performed using a conventional approach involving a Leksell stereotactic system, and the last 26 procedures were robot-assisted. Among the 1726 depth electrodes that were inserted, the median entry point localization error was as follows: conventional (1.0 mm; range, 0.1-33.5 mm) and robot-assisted (1.1 mm; range, 0-4.8 mm) (P = 0.17). The median target point localization error was as follows: conventional (2.8 mm; range, 0.1-49 mm) and robot-assisted (1.8 mm; range, 0-30.3 mm) (P < 0.001). The median operation time was significantly reduced with the robot-assisted workflow (90 min vs. 77.5 min; P < 0.01). Total complication rates were as follows: conventional (17.7%) and robot-assisted (11.5%) (P = 0.57). Major complication rates were 3.5% and 7.7% (P = 0.77), respectively. CONCLUSIONS: SEEG is a safe and highly accurate method that provides essential guidance for epilepsy surgery. Implementing SEEG in conjunction with multimodal planning systems and robotic devices can further increase safety margin, surgical efficiency, and accuracy.

Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients.

OBJECTIVE: The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients. METHODS: Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation. RESULTS: The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%-7.8%) at 1 year to 44% (95% CI 32%-55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%-62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%-16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed. CONCLUSIONS: The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

All-cause and immune checkpoint inhibitor-associated acute kidney injury in immune checkpoint inhibitor users: a meta-analysis of occurrence rate, risk factors and mortality.

Background: Immune checkpoint inhibitors (ICIs) have been associated with acute kidney injury (AKI). However, the occurrence rate of ICI-related AKI has not been systematically examined. Additionally, exposure to proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs) were considered as risk factors for AKI, but with inconclusive results in ICI-related AKI. Our aim was to analyse the occurrence rate of all-cause AKI and ICI-related AKI and the occurrence rates of severe AKI and dialysis-requiring AKI, and to determine whether exposure to PPIs and NSAIDs poses a risk for all-cause and ICI-related AKI. Methods: This study population was adult ICI recipients. A systematic review was conducted by searching MEDLINE, Embase and PubMed through October 2023. We included prospective trials and observational studies that reported any of the following outcomes: the occurrence rate of all-cause or ICI-related AKI, the relationship between PPI or NSAID exposure and AKI development or the mortality rate in the AKI or non-AKI group. Proportional meta-analysis and pairwise meta-analysis were performed. The evidence certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Results: A total of 120 studies comprising 46 417 patients were included. The occurrence rates of all-cause AKI were 7.4% (14.6% from retrospective studies and 1.2% from prospective clinical trials). The occurrence rate of ICI-related AKI was 3.2%. The use of PPIs was associated with an odds ratio (OR) of 1.77 [95% confidence interval (CI) 1.43-2.18] for all-cause AKI and an OR of 2.42 (95% CI 1.96-2.97) for ICI-related AKI. The use of NSAIDs was associated with an OR of 1.77 (95% CI 1.10-2.83) for all-cause AKI and an OR of 2.57 (95% CI 1.68-3.93) for ICI-related AKI. Conclusions: Our analysis revealed that approximately 1 in 13 adult ICI recipients may experience all-cause AKI, while 1 in 33 adult ICI recipients may experience ICI-related AKI. Exposure to PPIs and NSAIDs was associated with an increased OR risk for AKI in the current meta-analysis.

Brain metastasis tumor segmentation and detection using deep learning algorithms: A systematic review and meta-analysis.

BACKGROUND: Manual detection of brain metastases is both laborious and inconsistent, driving the need for more efficient solutions. Accordingly, our systematic review and meta-analysis assessed the efficacy of deep learning algorithms in detecting and segmenting brain metastases from various primary origins in MRI images. METHODS: We conducted a comprehensive search of PubMed, Embase, and Web of Science up to May 24, 2023, which yielded 42 relevant studies for our analysis. We assessed the quality of these studies using the QUADAS-2 and CLAIM tools. Using a random-effect model, we calculated the pooled lesion-wise dice score as well as patient-wise and lesion-wise sensitivity. We performed subgroup analyses to investigate the influence of factors such as publication year, study design, training center of the model, validation methods, slice thickness, model input dimensions, MRI sequences fed to the model, and the specific deep learning algorithms employed. Additionally, meta-regression analyses were carried out considering the number of patients in the studies, count of MRI manufacturers, count of MRI models, training sample size, and lesion number. RESULTS: Our analysis highlighted that deep learning models, particularly the U-Net and its variants, demonstrated superior segmentation accuracy. Enhanced detection sensitivity was observed with an increased diversity in MRI hardware, both in terms of manufacturer and model variety. Furthermore, slice thickness was identified as a significant factor influencing lesion-wise detection sensitivity. Overall, the pooled results indicated a lesion-wise dice score of 79%, with patient-wise and lesion-wise sensitivities at 86% and 87%, respectively. CONCLUSIONS: The study underscores the potential of deep learning in improving brain metastasis diagnostics and treatment planning. Still, more extensive cohorts and larger meta-analysis are needed for more practical and generalizable algorithms. Future research should prioritize these areas to advance the field. This study was funded by the Gen. & Mrs. M.C. Peng Fellowship and registered under PROSPERO (CRD42023427776).

Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

Intratumoral Hemorrhage in Vestibular Schwannomas After Stereotactic Radiosurgery: Multi-Institutional Study.

BACKGROUND AND OBJECTIVES: Intratumoral hemorrhage (ITH) in vestibular schwannoma (VS) after stereotactic radiosurgery (SRS) is exceedingly rare. The aim of this study was to define its incidence and describe its management and outcomes in this subset of patients. METHODS: A retrospective multi-institutional study was conducted, screening 9565 patients with VS managed with SRS at 10 centers affiliated with the International Radiosurgery Research Foundation. RESULTS: A total of 25 patients developed ITH (cumulative incidence of 0.26%) after SRS management, with a median ITH size of 1.2 cm 3 . Most of the patients had Koos grade II-IV VS, and the median age was 62 years. After ITH development, 21 patients were observed, 2 had urgent surgical intervention, and 2 were initially observed and had late resection because of delayed hemorrhagic expansion and/or clinical deterioration. The histopathology of the resected tumors showed typical, benign VS histology without sclerosis, along with chronic inflammatory cells and multiple fragments of hemorrhage. At the last follow-up, 17 patients improved and 8 remained clinically stable. CONCLUSION: ITH after SRS for VS is extremely rare but has various clinical manifestations and severity. The management paradigm should be individualized based on patient-specific factors, rapidity of clinical and/or radiographic progression, ITH expansion, and overall patient condition.

Visual Stimuli Modulate Local Field Potentials But Drive No High-Frequency Activity in Human Auditory Cortex.

Neuroimaging studies suggest cross-sensory visual influences in human auditory cortices (ACs). Whether these influences reflect active visual processing in human ACs, which drives neuronal firing and concurrent broadband high-frequency activity (BHFA; >70 Hz), or whether they merely modulate sound processing is still debatable. Here, we presented auditory, visual, and audiovisual stimuli to 16 participants (7 women, 9 men) with stereo-EEG depth electrodes implanted near ACs for presurgical monitoring. Anatomically normalized group analyses were facilitated by inverse modeling of intracranial source currents. Analyses of intracranial event-related potentials (iERPs) suggested cross-sensory responses to visual stimuli in ACs, which lagged the earliest auditory responses by several tens of milliseconds. Visual stimuli also modulated the phase of intrinsic low-frequency oscillations and triggered 15-30 Hz event-related desynchronization in ACs. However, BHFA, a putative correlate of neuronal firing, was not significantly increased in ACs after visual stimuli, not even when they coincided with auditory stimuli. Intracranial recordings demonstrate cross-sensory modulations, but no indication of active visual processing in human ACs.

Natural History and Histopathology of Expanding Cysts and Hematomas After Stereotactic Radiosurgery for Arteriovenous Malformations of the Brain: A Case Series.

BACKGROUND: We reviewed the clinical course and histopathologic findings for cases involving the formation of expanding cysts and/or hematomas after gamma knife surgery (GKS) for arteriovenous malformations (AVMs). METHODS: We report a single-center retrospective review of 18 patients who presented with cyst and/or hematoma expansion after GKS for AVMs between 1993 and 2023. Expanding cysts and hematomas were defined as well-demarcated cavities filled with fluid or well-marginated heterogenous hematomas presenting with expansion proximal to or in the location of the original AVM, respectively. Patient demographics, AVM characteristics, history of interventions and surgeries, and imaging and histopathologic features of expanding cysts and hematomas were collected for analysis. RESULTS: Among 1072 AVM patients treated using GKS, 18 presented with expanding cysts or hematomas during a total follow-up period of 16,757 patient-years (0.11 case/100 persons/patient-year). The time to cyst or hematoma identification was 4-13 years after initial GKS, with a mean duration of 8.6 years. Among the patients examined, 7 (38.9%) presented mainly with hematoma, 10 (55.6%) presented mainly with cysts, and 1 presented with approximately equal components of both. Among the 18 patients, 13 (72.2%) underwent craniotomy to treat cyst or hematoma expansion. All the specimens had similar histopathologic characteristics, including organizing hematoma with fresh and old hemorrhage, fibrinoid necrosis of the vessels, gliosis of normal brain tissue, infiltration of hemosiderin-laden histiocytes, and extravascular protein leakage. CONCLUSIONS: Our findings suggest that the formation of these 2 complications can be attributed to a common mechanism involving radiation-induced vascular damage in brain tissue adjacent to the AVM and subsequent chronic inflammation and capillary dilatation.

Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis.

OBJECTIVE: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. METHODS: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. RESULTS: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). CONCLUSIONS: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

Silent Corticotroph Staining Pituitary Neuroendocrine Tumors: Prognostic Significance in Radiosurgery.

BACKGROUND AND OBJECTIVES: There is conflicting evidence on the significance of adrenocorticotrophic hormone (ACTH) staining in the prognosis of nonfunctioning pituitary neuroendocrine tumors (NFpitNETs). The objective of this study was to define the effect of ACTH immunostaining on clinical and radiographic outcomes of stereotactic radiosurgery (SRS) for NFpitNETs. METHODS: This retrospective, multicenter study included patients managed with SRS for NFpitNET residuals. The patients were divided into 2 cohorts: (1) silent corticotroph (SC) for NFpitNETs with positive ACTH immunostaining and (2) non-SC NFpitNETs. Rates of local tumor control and the incidence of post-treatment pituitary and neurological dysfunction were documented. Factors associated with radiological and clinical outcomes were also analyzed. RESULTS: The cohort included 535 patients from 14 centers with 84 (15.7%) patients harboring silent corticotroph NFpitNETs (SCs). At last follow-up, local tumor progression occurred in 11.9% of patients in the SC compared with 8.1% of patients in the non-SC cohort (P = .27). No statistically significant difference was noted in new-onset hypopituitarism rates (10.7% vs 15.4%, P = .25) or visual deficits (3.6% vs 1.1%, P = .088) between the 2 cohorts at last follow-up. When controlling for residual tumor volume, maximum dose, and patient age and sex, positive ACTH immunostaining did not have a significant correlation with local tumor progression (hazard ratio = 1.69, 95% CI = 0.8-3.61, P = .17). CONCLUSION: In contemporary radiosurgical practice with a single fraction dose of 8-25 Gy (median 15 Gy), ACTH immunostaining in NFpitNETs did not appear to confer a significantly reduced rate of local tumor control after SRS.

Local control and survival after stereotactic radiosurgery for colorectal cancer brain metastases: an international multicenter analysis.

OBJECTIVE: The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM). METHODS: Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22-8.1 cm3), and the median margin dose was 20 Gy (IQR 18-22 Gy). RESULTS: The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4-4.9; p = 0.003 and HR 3.4, 95% CI 1.7-6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19-0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1-2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1-2.4; p = 0.009) were significantly associated with worse OS. CONCLUSIONS: Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.