Citations

Abstract Objective Noninvasive brain stimulation (NIBS) provides a treatment option for patients not eligible for surgical intervention or who seek low‐risk approaches and may be used in the hospital, clinic, and at home. Our objective is to summarize our single‐center experience with multiple NIBS approaches for the treatment of focal epilepsy. Methods A retrospective chart review identified drug‐resistant focal epilepsy patients who received NIBS as an epilepsy treatment at Mayo Clinic in Rochester, MN. Patients were typically treated as follows: (1) for TMS, 1 Hz stimulation was applied for five consecutive days in the neuromodulation clinic, (2) for outpatient tDCS, stimulation was applied for five consecutive days in the clinic, followed by optional treatment at home, and (3) for inpatient tDCS, stimulation was applied for three consecutive days. We analyzed continuous EEG data for the inpatient tDCS cohort and available HD‐EEG data for outpatient cohorts to quantify changes in interictal epileptiform discharges (IEDs) as a result of stimulation. Outcomes were assessed at 1 month for TMS and outpatient tDCS and 1 week for inpatient tDCS. Results Twenty‐four patients were treated with TMS ( n = 10) and tDCS ( n = 14, 9 as outpatients). The median age was 40 years (range 15–73). The median seizure reduction following stimulation was 50%. Fourteen patients (58%) were responders to treatment (TMS = 4/10, tDCS Outpatient = 7/9, tDCS Inpatient = 3/5). Five outpatient tDCS participants elected to continue treatment at home. Four TMS and four outpatient tDCS patients underwent high‐density EEG before and after 5 days of therapy. Following stimulation, IED rate was reduced in 4/5 inpatient tDCS patients, 4/4 outpatient tDCS patients, and 4/4 TMS patients. Two patients experienced an increase in seizure frequency (1 following TMS and 1 following outpatient tDCS), which returned to baseline 4–6 weeks after stimulation treatments were discontinued. Significance TMS and tDCS are potential treatment approaches for drug‐resistant focal epilepsy patients in the hospital, clinic, and home. They have a favorable safety profile and can lead to a reduction in IED rates and seizures. These results suggest further studies are needed to examine NIBS as a treatment for epilepsy. Plain Language Summary Noninvasive brain stimulation, such as transcranial magnetic stimulation and transcranial direct current stimulation, offers new treatment options for patients with focal seizures. This study reviewed the experience at Mayo Clinic using noninvasive brain stimulation in the hospital, clinic, and at‐home settings to treat seizures. The results showed an overall 50% median seizure reduction, and 58% of patients had at least a 50% reduction in seizures. Noninvasive brain stimulation is a promising treatment approach with a favorable safety profile.

The role of second-look endoscopy and debridement (SLED) remains uncertain in children due to the perceived need for additional general anesthesia following their initial functional endoscopic sinus surgery (FESS) while mitigating risks and healthcare costs. This comprehensive review synthesizes current evidence on SLED in children, focusing on its practice pattern and treatment outcomes. This review was designed and performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Protocol. Independent queries of the PubMed Central, MEDLINE, and Bookshelf databases were performed. A total of 53 relevant, unique articles were initially identified; 12 articles were ultimately deemed appropriate for inclusion in final analysis. The most common indication for FESS was chronic rhinosinusitis or recurrent sinus infections while that for SLED under general anesthesia varied from institutional practice patterns to surgeon preference. No meaningful comparison of outcomes was possible as the “success rates” of FESS with or without SLED were largely based on unvalidated questionnaires and equally subjective surgeon assessments. Even when looking at outcomes based on revision rates, FESS with SLED was considered successful between 60.5% and 95.6% of the time, with a mean of 84.2%, while FESS without SLED was successful between 71.0% to 96.4% of the time, with a mean of 86.3%. However, no randomized, controlled studies were available in the pediatric literature pertaining to FESS with or without SLED. Moreover, it became apparent that previous conclusions on the utility of SLED were based on the outcomes of FESS following one single SLED under general anesthesia vs. no SLED. As such, there is an unmet need to examine the utility of serial, office-based SLED in children to better elucidate its utility in pediatric FESS.

Background Orbital decompression is an essential tool for reducing proptosis in thyroid eye disease (TED), yet the impact of surgical approach and preoperative factors on outcomes remains uncertain. Objective To compare proptosis reduction following different orbital decompression techniques, identify additional risk factors that may play a role in surgical orbital decompression outcomes, and develop clinical decision-making recommendations based on these results. Methods A retrospective analysis was performed on TED patients who underwent endoscopic medial wall, orbital floor, and/or open lateral wall decompression. We evaluated the influence of preoperative comorbidities, anatomic and laboratory values, and surgical approach on postdecompression Hertel exophthalmometry outcomes. Results Analysis encompassed 130 orbits from 80 patients, 83% female, 48 with preoperative diplopia, and mean age of 54.4 years. Preoperative Hertel measurement was predictive of extent of proptosis reduction ( P < .0001), indicating that higher initial Hertel measurement predicts greater absolute reduction following surgical intervention. Surgical technique correlated with outcome on univariate analysis ( P = .04), but not multivariate ( P = .13) analyses. When categorized into preoperative Hertel ranges, combined endoscopic medial and open lateral wall decompression resulted in mean proptosis reduction of 3.13 mm for range 20.01 to 24 mm and 3.85 mm for range 24.01 to 28 mm. Three-wall decompression resulted in mean proptosis reduction of 2.49 mm for and 3.84 mm for these ranges, respectively. Variables such as smoking, body mass index, orbital wall height, and TRAb level, did not affect outcomes. Nine patients had new onset diplopia. Conclusions Preoperative Hertel exophthalmometry is the strongest predictor of proptosis reduction following orbital decompression in TED. Surgical technique appears to be less impactful on outcome than expected. Surgical decision making should be individualized based on patient goals; these findings can be used to achieve proptosis reduction and limit the risk of new onset diplopia.

Background Atrial dysfunction is a risk factor for atrial arrhythmia and can be detected by atrial strain imaging in patients with biventricular circulation. However, the role of atrial strain imaging for risk stratification of atrial arrhythmia in patients with Fontan palliation has not been studied, despite the high prevalence and prognostic implications of atrial arrhythmia in this population. We hypothesized that pulmonary venous atrial strain was associated with new‐onset and recurrent atrial arrhythmia in Fontan physiology. Method and Results This is a retrospective study of adults with Fontan palliation and no prior history of atrial arrhythmia who underwent atrial strain imaging by speckle tracking echocardiography (2003–2023). New‐onset and recurrent atrial arrhythmias were ascertained from baseline encounter to last follow‐up. Of 404 patients, atrial reservoir strain assessment was feasible in 329 patients (81%), with modest intra‐ and interobserver agreement. The median atrial reservoir strain was 18% (interquartile range, 13%–24%), and atrial dysfunction (atrial reservoir strain <28%) was present in 294 (89%). Atrial reservoir strain <15% was associated with new‐onset atrial arrhythmia (adjusted hazard ratio [HR], 1.59 [95% CI, 1.09–2.34]; P =0.009), and recurrent atrial arrhythmia (adjusted HR, 2.01 [95% CI, 1.06–3.93]; P =0.003). Rhythm control therapy was associated with lower risk of recurrence compared with rate control therapy (adjusted HR, 0.92 [95% CI, 0.86–0.98]; P =0.003). Conclusions Atrial dysfunction was common and was associated with new‐onset and recurrent atrial arrhythmias. The higher prevalence of atrial arrhythmias in patients with reduced atrial strain and the apparent protective effect of rhythm control therapy suggest that rhythm control therapy may be the preferred treatment in patients with reduced atrial strain.

Nonspecific symptoms and other diagnostic challenges lead to underdiagnosis of cardiac amyloidosis (CA). Artificial intelligence (AI) could help address these challenges, but a summary of the performance of these tools is lacking. This narrative review of published literature describes the performance of AI tools that use data from ECGs and echocardiography to improve identification of CA and challenges that hinder adoption of these tools. Thirteen studies met inclusion criteria with sample sizes ranging from 50 to 2451 patients. Four studies used ECG data, 8 used echocardiography data, and 1 used both. The CA gold standard was typically defined as a CA diagnosis in an institutional or other database but the requirements for these diagnoses were heterogenous across studies, and many did not distinguish among CA subtypes. AI model development varied considerably, and only 4 studies included external validation. The ability of models to predict CA ranged from 0.71 to 1.00, sensitivity ranged from 16% to 100%, and specificity from 75% to 100%. Only 1 study reported model performance across strata of sex, age, race, and CA type. Persistent challenges to AI adoption include usability, cost, value added, electronic health record/information technology interoperability, patient‐related factors, regulation, and privacy and liability. Published studies on AI for improved identification of CA show favorable performance measures but numerous methodologic and other challenges must be addressed before these tools are more widely adopted.

Abstract INTRODUCTION β‐synuclein is a promising blood marker to track synaptic degeneration in Alzheimer's disease (AD) but changes in preclinical AD are unclear. METHODS We investigated serum β‐synuclein in 69 cognitively unimpaired mutation non‐carriers, 78 cognitively unimpaired AD mutation carriers (asymptomatic AD), and 31 symptomatic mutation carriers from the Dominantly Inherited Alzheimer Network. RESULTS β‐synuclein levels were already higher in asymptomatic AD mutation carriers compared to non‐carriers and highest in symptomatic carriers. Longitudinal trajectories and correlation analyses indicated that β‐synuclein levels start to rise after amyloid deposition preceding axonal degeneration, brain atrophy and hypometabolism, and cognitive decline. β‐synuclein levels were associated with cognitive impairment and gradually increased with declining cognition. DISCUSSION Our study supports the use of blood β‐synuclein to track synaptic changes in preclinical AD and as a surrogate marker for cognitive impairment which might be used in early diagnosis and to support patient selection and monitoring of treatment effects in clinical trials. Highlights Blood β‐synuclein levels were already higher in asymptomatic Alzheimer's disease (AD) mutation carriers. Blood β‐synuclein levels were highest in symptomatic AD mutation carriers. Blood β‐synuclein levels start to rise 11 years before symptom onset. Rise of β‐synuclein precedes axonal degeneration, brain atrophy, and cognitive decline. β‐synuclein levels gradually increased with declining cognition.

Glioblastoma (GBM) is an exceedingly aggressive primary brain tumor defined by rapid growth, extensive infiltration, and resistance to standard therapies. A central factor driving these malignancies is the subpopulation of glioblastoma stem cells (GSCs), which possess self-renewal capacity, multipotency, and the ability to regenerate tumor heterogeneity. GSCs contribute to key hallmarks of GBM pathobiology, including relentless progression, resistance to chemotherapy and radiotherapy, and inevitable recurrence. GSCs exhibit distinct molecular signatures, enhanced DNA repair, and metabolic adaptations that protect them against conventional treatments. Moreover, they reside within specialized niches—such as perivascular or hypoxic microenvironments—that sustain stemness, promote immunosuppression, and facilitate angiogenesis. Recent discoveries highlight signaling pathways like Notch, Wnt/β-catenin, Hedgehog, STAT3-PARN, and factors such as TFPI2 and HML-2 as critical regulators of GSC maintenance, plasticity, and immune evasion. These findings underscore the complexity of GSC biology and their pivotal role in driving GBM heterogeneity and therapeutic failure. Emerging therapeutic strategies aim to target GSCs through multiple avenues, including surface markers, immunotherapeutics (e.g., CAR T cells), metabolic vulnerabilities, and combination regimens. Advances in patient-derived organoids, single-cell omics, and 3D co-culture models enable more accurate representation of the tumor ecosystem and personalized therapeutic approaches. Ultimately, improved understanding of GSC-specific targets and the tumor microenvironment promises more effective interventions, paving the way toward better clinical outcomes for GBM patients.