Citations

Objective To evaluate whether local field potential (LFP) spectral profiles can serve as a candidate “spectral fingerprint” for physiological confirmation of centromedian-parafascicular (CM–Pf) targeting during thalamic deep brain stimulation (DBS) for drug resistant epilepsy (DRE). Methods This is a retrospective study of 10 patients (20 leads) who underwent CM-DBS implantation for DRE at a single tertiary center. Postoperative CT and preoperative MRI were co-registered, normalized to the Montreal Neurological Institute (MNI) space, and reconstructed using Lead-DBS software to anatomically localize contacts. BrainSense™ Survey recordings were obtained at least 3 weeks post-implant during routine programming. LFP frequency content was analyzed, and prominent peaks were identified and classified into canonical frequency bands (theta, alpha, beta). These spectral profiles were then mapped to MRI-based anatomical localizations, and statistical tests were applied to assess associations between peak patterns, contact localizations and thalamic subregions. Results Contacts were distributed as follows: 50 in the CM, 16 in the Parafascicular (Pf), 15 in the Centrolateral, 8 in the Mediodorsal, and 7 in the Ventrolateral (VL) nuclei. Of the 10 representative spectral localizations confined to the CM/CM-Pf region, 8 (80%) displayed a distinct dual-peak spectral profile with peaks in the theta/low alpha (5.5–9 Hz) and high beta (20–30 Hz) bands (mean frequencies: 7.63 Hz and 21.02 Hz, Fisher’s exact test, p < 0.001). Single-peak profiles showed no significant association with specific nuclei ( p = 0.871). Contacts overlapping other thalamic nuclei more frequently exhibited narrow 10–15 Hz peaks ( p = 0.005) or triple-peak profiles ( p = 0.02), suggesting mixed structural contributions. Conclusion A dual- band candidate spectral pattern consisting of theta/low alpha and high beta peaks was associated with the CM-Pf region in this cohort. This finding provides early evidence supporting the feasibility of incorporating passive LFP recordings as a physiologic marker of target engagement. Future work to prospectively compare bipolar survey-based localization with monopolar recording strategies could enable development of a state-based, physiologically informed spectral atlas to refine CM-Pf targeting in thalamic neuromodulation for DRE.

Summary Outcomes for high‐risk paediatric classic Hodgkin lymphoma (cHL) improved with the addition of brentuximab vedotin (Bv) to doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (AVEPC) chemotherapy. We evaluated the prognostic implications of distant extra‐nodal sites contributing to stage IV disease. On AHOD1331 (NCT02166463), patients aged 2–21 years with high‐risk cHL (stage IIB with bulk/IIIB/IVA/IVB) were randomized to 5 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE‐PC) versus Bv‐AVEPC. Patients with stage IV disease, determined by protocol‐defined and centrally reviewed Positron Emission Tomography ‐ Computed Tomography (PET‐CT), were identified. Baseline characteristics and progression‐free survival (PFS) were compared by pattern of stage IV involvement (lung, bone, bone marrow, multiple sites and others). A total of 340 patients (median age 15 years) with stage IV disease were included. Of these patients, 173 (51%) received ABVE‐PC and 167 (49%) Bv‐AVEPC. PFS was highest with lung‐only involvement (4‐year PFS 88.6%) and lowest with bone marrow‐only involvement (4‐year PFS 71.9%). Compared to ABVE‐PC, Bv‐AVEPC improved PFS among all stage IV patients (hazard ratio [HR] 0.53, 90% confidence interval (CI) 0.33–0.85) and in the lung‐only and bone‐only subgroups. However, no PFS benefit was observed in those with bone marrow‐only involvement. Among paediatric patients with stage IV cHL, Bv‐AVEPC improved PFS across most patterns of stage IV disease, except in those with bone marrow involvement. These results will guide efforts to improve outcomes among children with stage IV cHL.

Abstract Objective. Modern stereotactic neurosurgery increasingly relies on bilateral and multi-trajectory workflows (e.g. deep brain stimulation (DBS), stereoelectroencephalography (sEEG)), which can exceed the reach and flexibility of conventional frame-based systems. Building on our skull-mounted Navinetics D1 platform, we present a stereotactic frame (Navinetics E1) intended to expand the reachable work envelope, enable independent bilateral targeting, and preserve mechanical accuracy and patient comfort. Approach. We designed the Navinetics E1 stereotactic frame using a center-of-arc architecture with five degrees of freedom per hemisphere ( X, Y, Z , Arc, Collar) and two operating modes: Double Arm (independent left/right arms for simultaneous bilateral targeting) and Single Arm (mechanically coupled arms). The system was designed in CAD and fabricated via carbon fiber-reinforced polylactic acid (PLA-CF) additive manufacturing. Collision-aware MATLAB simulations quantified work volume and admissible approach directions. Mechanical targeting accuracy was evaluated on a ground truth fixture (GTF) platform, with mixed-effects modeling to assess target- and trajectory-dependent effects. Operative feasibility was assessed through an intraoperative entry-point replication test relative to the D1 system. Main results. Compared to the D1, the E1 frame significantly expanded key geometric ranges, including, most notably, 0°–360° Collar rotation and posterior Y -axis reach, thereby increasing the work volume and trajectory range by factors of 3.39 and 8.42, respectively. Mean GTF targeting deviation was 0.78 ± 0.38 mm in Single Arm mode and 1.23 ± 0.36 mm (right) and 1.65 ± 0.47 mm (left) in Double Arm mode. Entry-point replication across 17 clinical cases achieved 76.5% success in overlapping the reference points, providing preliminary evidence of feasibility under real operative conditions. Significance. The E1 frame extends a compact skull-mounted platform to support broader stereotactic reach and trajectory while enabling independent bilateral workflows. These features may reduce intraoperative reconfiguration for complex DBS and sEEG cases. Future work will focus on increasing structural stiffness, improving angular readout/setting, and developing MRI-compatible implementations.

ABSTRACT Background Transvenous lead extraction (TLE) is a commonly performed and generally safe procedure, though procedural complexity and risk can vary based on clinical and procedural factors. Objective This study aims to identify clinical and procedural factors associated with histologic evidence of subclinical vascular injury, defined by elastin positivity on extracted leads and its clinical significance. Methods Patients undergoing TLE with a lead dwell time of ≥ 1 year were included. Extracted leads with tissue were analyzed histologically using Verhoeff–Van Gieson staining to assess the presence of elastin. Demographic data, procedural and lead characteristics, and indication for extraction were obtained. Established extraction risk scores were calculated to determine efficacy in predicting subclinical vascular injury. Results The cohort included 49 patients with 92 leads extracted. A total of 25 patients (51%) had elastin‐positive leads. Complete procedural success occurred in 95.9% of cases. The multivariate regression model did not identify any independent predictors of elastin presence, including age (OR = 1.00; 95% CI 0.95–1.05; p = 0.89), female gender (OR = 3.04; 95% CI 0.67–13.65; p = 0.14), lead dwell time (OR = 1.13; 95% CI 0.98–1.29; p = 0.07). Additionally, no scoring system, such as the CCF, EROS, MB, SAFeTY, and LECOM, predicted the presence of elastin. Conclusion Subclinical venous injury was common following TLE, yet did not predict adverse clinical outcomes, reinforcing that TLE performed in experienced centers carries a favorable safety profile. Future studies in larger cohorts are needed to further characterize the clinical utility of subclinical vascular injury.

PURPOSE Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). METHODS Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. RESULTS Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub ( P < .05 for all). CONCLUSION White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.

Primary enlargement of the cerebrospinal fluid (CSF)–filled brain ventricles, known as congenital cerebral ventriculomegaly (CCV), is a hallmark of congenital hydrocephalus. CCV is also enigmatically but frequently associated with autism and other neurodevelopmental disorders. To gain insight into the developmental genetic regulation of the human CSF-ventricular system, we conducted an integrated, multiomic study of about 2700 trio-based exomes from patients with primary CCV. We found that about 25% of cases were associated with rare, damaging de novo variants in mutation-intolerant genes, many of which are linked to other dominant Mendelian disorders. Thirty-five exome-wide significant CCV genes and dozens of other high-confidence CCV genes converged on pathways involved in ATP-dependent Brahma-related gene 1/Brahma-associated factor chromatin remodeling, histone H3 lysine 4 methylation, and phosphoinositide 3-kinase signaling. Knockout of selected CCV genes in mouse models supported that de novo variants in CCV genes caused ventriculomegaly by impairing both CSF dynamics and cortical cytoarchitecture through dysregulation of neuroprogenitor cell growth and maturation in the ventricular and subventricular zones. These findings indicated that genetic and epigenetic programs coordinate the “hand-in-glove” development of the CSF-ventricular system with that of the cerebral cortex and establish a genetic connection between CCV and neurodevelopmental disorders, potentially explaining why some patients with hydrocephalus continue to exhibit CCV and neurodevelopmental disorders despite CSF shunting. We suggest that combined brain imaging and whole-exome sequencing could enable early detection of, and intervention for, autism and other neurodevelopmental disorders.