Citations

Intracardiac metastases from gastroenteropancreatic neuroendocrine tumors (NETs) are rare and challenging to diagnose. Lutetium (Lu)-177 DOTATATE therapy has demonstrated significant benefit in patients with metastatic NET; however, there are limited data regarding the direct impact on cardiac metastases. Patients with intracardiac metastasis from NET were evaluated. Patients were stratified by treatment with Lu-177 DOTATATE. Quantitative assessments of the progression of cardiac metastatic size (maximal diameter) and metabolic activity, as measured by maximal standardized uptake value (SUV max ), were performed on serial 68 Ga-DOTATATE PET imaging. In a cohort of 23 patients, 11 patients (47.8%) received Lu-177 DOTATATE therapy. Through a median of 2.2 years of follow-up, these patients showed some reduction in metastatic burden with a median reduction in maximal diameter of 1.0 mm (IQR: 0.0–3.0) and a median change in SUV max of −1.6 (IQR: −4.4 to 1.5). In contrast, patients who did not receive Lu-177 DOTATATE had some increase in maximal diameter of 0.5 mm (−2.0 to 2.0) and an increase in SUV max of 1.4 (−6.2 to 2.3). Overall, Lu-177 DOTATATE therapy may result in modest regression of intracardiac metastases as assessed by molecular imaging, whereas patients with cardiac metastases who did not receive therapy appeared to show progression.

Objective To develop evidence-based clinical practice guidelines for non-invasive neuromodulation devices in acute and preventive migraine treatment. Methods A systematic review was conducted across six databases from 1946 to April 2025. Randomized controlled trials evaluating Food and Drug Administration-cleared or Conformité Européenne (CE)-marked non-invasive neuromodulation devices were included. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, and recommendations were developed through consensus following GRADE Evidence-to-Decision frameworks. The working group comprised 15 senior members and six junior members. Results From 1536 initial records, 15 studies met the inclusion criteria and were finally used to develop evidence-based recommendations. Evidence quality ranged from very low to moderate. Weak recommendations were issued for SAVI Dual, Cefaly, Relivion, and Nerivio in the treatment of acute migraine attacks, and for gammaCore Sapphire, Cefaly, and Nerivio in the preventive migraine treatment. Other cleared devices received no recommendations or have no eligible studies for the GRADE assessment. The primary limitations across studies included imprecision due to small sample sizes and various methodological concerns. Additionally, expert consensus recommendations were developed for devices and clinical scenarios not adequately covered by randomized controlled trials, including potential applications in pediatric populations, vestibular migraine, chronic migraine, menstrual migraine, and medication overuse headache. Conclusion Non-invasive neuromodulation devices offer promising alternatives to drug treatment for migraine management. These devices are safe and generally well tolerated and devoid of drug interactions. While current evidence quality varies, ongoing research and technological advancements show encouraging potential. Future studies should adhere to International Headache Society guidelines for neuromodulation device trials, address proper sham controls and blinding assessment, and account for patient adherence challenges in device use. Expanded insurance coverage would enhance cost-effectiveness and device accessibility. These guidelines provide a framework for clinical decision-making while highlighting areas requiring further research.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

BACKGROUND AND OBJECTIVES: Single-session stereotactic radiosurgery (SRS) has limited role for large arteriovenous malformations (AVM). Volume-staged SRS (VS-SRS) is used to optimize outcomes, but studies reporting results are limited. METHODS: This multicenter retrospective cohort of 378 patients from 21 centers reports results of VS-SRS for the entire AVM nidus. We report favorable outcome, obliteration, hemorrhage, and permanent symptomatic adverse radiation effect rates. RESULTS: The median age was 31 years (IQR: 19-44) at the first volume stage, with patients treated in 2–4 stages. The median total nidus volume was 21 cm 3 (IQR: 13.9-30.1 cm 3 ), and a median prescription dose of 17 Gy (IQR: 16-18 Gy) was used. The median radiographic and clinical follow-up were 48 and 55 months, respectively. Seventy-seven patients (20.4%) had a favorable outcome, with the 3-year and 5-year rates being 3.9% and 18%, respectively. 127 patients (33.6%) achieved obliteration, with the 3-year and 5-year rates being 6.8% and 26%, respectively. Obliteration rates of AVMs <15 cm 3 were 81% and 31%, respectively. The latency period hemorrhage incidence rate was 3.02 cases per 100 patient-years; 52 patients (13.8%) had a bleed. Seventy-two patients (19%) had symptomatic adverse radiation effect; in 38 patients (10.1%), these were permanent. Total nidus volume, prescription dose at first stage, diffuse nidus, and prior hemorrhage were all independent affecting outcome rates. CONCLUSION: VS-SRS can be used to treat large AVMs as a standalone treatment. Obliteration rates and favorable outcomes are lower than that with smaller AVMs, and repeat treatment is often required. Optimizing treatment plans, by increasing prescription doses, reducing treatment volume at each stage, and increasing the number of stages, may lead to better outcomes.

ABSTRACTBackgroundPercutaneous transluminal angioplasty and stenting (PTAS) in patients with carotid stenosis may have potential effects on brain parenchyma. However, current studies on parenchymal changes are scarce due to the need for advanced imaging modalities. Consequently, the alterations in brain parenchyma following PTAS remain an unsolved issue.PurposeTo investigate changes to the brain parenchyma using magnetic resonance elastography (MRE).Study TypeProspective.Population13 patients (6 women and 7 men; 39 MRI imaging sessions) with severe unilateral carotid stenosis patients indicated for PTAS were recruited between 2021 and 2024.Field Strength/SequenceNoncontrast MRI sequences including MRE (spin echo) were acquired using 3 T scanners.AssessmentAll patients underwent MRE before (preprocedural), within 24 h (early postprocedural) and 3 months after (delayed postprocedural) PTAS. Preprocedural and delayed postprocedural ultrasonographic peak systolic velocity (PSV) was recorded. MRE stiffness and damping ratio were evaluated via neural network inversion of the whole brain, in 14 gray matter (GM) and 12 white matter (WM) regions.Statistical TestsStiffness and damping ratio differences between each pair of MR sessions for each subject were identified by paired sample t tests. The correlations of stiffness and damping ratio with stenosis grade and ultrasonographic PSV dynamics were evaluated by Pearson correlation coefficients. The statistical significance was defined as p < 0.05.ResultsThe stiffness of lesion side insula, deep GM, and deep WM increased significantly from preprocedural to delayed postprocedural MRE. Increasing deep GM stiffness on the lesion side was positively correlated with the DSA stenosis grade significantly (r = 0.609). The lesion side insula stiffness increments were positively correlated with PSV decrements significantly (r = 0.664).Data ConclusionRegional brain stiffness increased 3 months after PTAS. Lesion side stiffness was positively correlated with stenosis grades in deep GM and PSV decrements in the insula.Evidence Level2.Technical EfficacyStage 2.

Abstract Objective To assess the localization and lateralization values of ictal emotional features and ictal defensive behaviors in pediatric and young adult patients with frontal lobe epilepsy (FLE). Methods Children and young adults with FLE were identified from a single institution's epilepsy surgery database. Two epileptologists determined by consensus the presence of ictal emotional features (positive‐ smile, laughter, humming, singing; negative‐ fear, crying, anger, disgust, contempt, sadness) and ictal defensive behaviors (freezing with a fearful facial expression, shielding the face with hands, burying the face in a pillow, or exhibiting hyperkinetic motor behaviors like attempting to escape from bed or resisting restraint) in each patient's first video EEG (vEEG). Historic seizure semiology and vEEG reports were compared with the consensus vEEG analysis. Longitudinal changes in ictal emotional features were defined by the emergence or resolution of ictal emotional features between historic seizure semiology and re‐review of presurgical vEEG analysis. Subgroup analyses were conducted according to the seizure lateralization (left vs. right) and sublobar localization (precentral, medial, lateral, extensive) based on surgical extent. Results Twenty‐three FLE patients were included (female 39%; mean age at vEEG analysis: 11.28 years, range 1.75–20.17). The inter‐rater reliability was very good for both ictal emotional features ( κ = 0.81, 95% CI: 0.59–1) and ictal defensive behaviors ( κ = 0.91, 95% CI: 0.79–1). Ictal emotional features were observed in 10 patients (43.4%), with negative emotions present in 70% (7/10) of these cases. vEEG reports lacked documentation of ictal emotional features in two patients. Although ictal emotional features showed no statistical correlation by sublobar regions, ictal defensive behaviors were consistently seen in medial compared to lateral FLE (100% vs. 16.6%; p = 0.004). Longitudinal changes in ictal emotional features were observed in 8 (34.7%) patients. Significance Ictal emotional features were common in pediatric and young adult FLE patients and were mainly negative. Ictal defensive behaviors were more likely associated with medial FLE. Longitudinal changes in ictal emotional features occurred in about a third of pediatric and young adult patients with FLE. Plain Language Summary This study examined emotional features and defensive behaviors during seizures in children and young adults with FLE. Negative emotions were commonly seen during seizures. Ictal defensive behaviors were more frequently observed in patients with medial FLE, and recognizing these signs could help clinicians localize the seizures. Changes in emotional features were seen over time in about one‐third of children and young adult patients.

Inverted papilloma (IP) is a benign neoplasm of the nasal cavity and paranasal sinuses, known for its variable risk of recurrence and potential for developing carcinoma. Emerging evidence has shown high rates of activating EGFR mutation, and a smaller subset is associated with low-risk human papillomavirus (lrHPV). While certain morphologic features, including an inverted growth pattern, are well-established, the presence of condylomatous features, such as large fungating lesions with thick undulating surface epithelium, hyperkeratosis, cytoplasmic clearing, raisinoid nuclei, and binucleation (koilocytic changes) in low-risk HPV-associated IP suggests that these tumors may be a distinct subtype of sinonasal papilloma (SP) with features similar to low-risk HPV-associated anogenital condylomas. This study presents a series of SP with condylomatous morphology and explores the association with lrHPV, the clinicopathologic features, and the rates of carcinoma development. In total, 17 cases of SP exhibiting condylomatous morphology were retrospectively identified. We performed lrHPV and high-risk HPV (hrHPV) RNA in situ hybridization and p16 immunohistochemistry and gathered detailed clinical and pathologic data along with treatment, disease follow-up, and outcomes. These condylomatous papillomas almost all developed in active smokers, were large, were primarily located in the nasal cavity (47%), and showed frequent transformation to invasive squamous cell carcinoma (29%). This malignant transformation rate is much higher than what has been reported for inverted, exophytic, and oncocytic papillomas. The tumors were almost uniformly associated with transcriptionally-active lrHPV (94%) and were consistently negative for p16 and hrHPV. This study shows that a subgroup of IPs with condylomatous morphology have a predilection for the nasal cavity, strong association with lrHPV, and high rates of carcinoma. These findings support the concept that these tumors are a distinct (fourth) type of SP with a higher risk of malignant transformation.

Background Given the low haemorrhagic risk of intracranial low-grade dural arteriovenous fistulas (dAVFs), the benefits of routine intervention remain controversial. This study compares patient outcomes treated with stereotactic radiosurgery (SRS) versus conservative management. Method Multicentre retrospective analysis of the Consortium for Dural Arteriovenous Fistula Outcomes Research and the International Radiosurgery Research Foundation data. Inclusion criteria were (1) intracranial low-grade dAVF diagnosed by catheter-based angiography, (2) no prior dAVF-related haemorrhage and (3) management with upfront SRS (intervention group) or conservative management (observation group). The primary outcome was symptomatic improvement. Secondary outcomes included dAVF obliteration, up-conversion, haemorrhage, improvement and favourable modified Rankin Scale (mRS) at follow-up. Results 304 patients with a mean age of 56 years (SD 13.5) and a follow-up of 46.7 months (SD 45.5) were included. 135 (44.4%) were managed conservatively and 169 (55.6%) had upfront SRS. Compared with the observation group, symptomatic and mRS Score improvement (≥1-point decrease in baseline score) was more likely in the intervention group (95.1% vs 58.5%; OR=13.75 (5.61–33.69) and 37.0% vs 24.0%; OR=1.85 (1.09–3.15), respectively). These findings remained significant after multiple imputation and propensity score matching. Remaining outcomes were similar between groups. The all-cause mortality rate was 5.4% (n=16), unrelated to the dAVF or treatment. Five (3.0%) SRS-related complications were reported and resolved during the follow-up period. Conclusions SRS was associated with increased symptomatic and mRS Score improvement for low-grade dAVFs compared with conservative management. SRS had a low complication risk and did not appear to alter dAVF obliteration or haemorrhage. Future prospective trials on SRS as a first-line intervention for symptomatic low-grade dAVFs should be considered.

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the GRADE approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.