Mirsattari, Seyed M.

Background: Neurological diseases share overlapping systemic and molecular features, but the specificity and interpretation of cross-disease metabolomic signatures remain uncertain. Methods: We analyzed summary-level Nightingale NMR metabolomic and genetic data from 274,241 UK Biobank participants across eight neurological endpoints. The disease rankings used here were derived from baseline plasma metabolites predicting future incident disease rather than from contemporaneous diagnostic case–control contrasts. Results: Among 57 priority metabolites with genome-wide significant instruments (2472 SNPs; mean F = 162.4), nine ranked in the top 30 for at least seven of the eight endpoints, defining a shared pre-diagnostic neurological signature confirmed as non-random cross-endpoint convergence by permutation testing (p < 0.0001). Because we did not perform a quantitative non-neurological disease control analysis, this signature should not be interpreted as neurologically specific and may partly reflect systemic morbidity, renal function, body composition, or frailty-related physiology. Forward Mendelian randomization across 45 metabolite–disease pairs found no Bonferroni-significant causal effects; three nominal protective associations are consistent with the number of false-positive findings expected under multiple testing and require replication. Conclusions: These results support a shared systemic, pre-diagnostic metabolic signature across the neurological disease spectrum, while the null MR findings and specificity limitations favor interpretation as a biomarker or prodromal downstream signal rather than a proven causal mechanism. External prospective validation is essential.

BACKGROUND The authors aimed to evaluate the feasibility/safety of stereo-electroencephalography (SEEG) and SEEG-guided radiofrequency thermocoagulation (RFTC) in patients with drug-resistant epilepsy previously implanted with neuromodulation devices, using a retrospective cohort design evaluating patients treated at the Mayo Clinic Florida Epilepsy Center. OBSERVATIONS Nine patients (mean age 36.3 ± 10.9 years, 33% female) with prior implantation of neuromodulation devices were included. A vagus nerve stimulator was present in 8 of 9 patients, and 4 patients had undergone previous intracranial neuromodulation. Five patients underwent SEEG-RFTC. The mean SEEG monitoring duration was 6.5 ± 2.9 days. No intraoperative or procedural complications occurred, including hardware-related issues. No permanent or significant neurological/cognitive deficits occurred. One patient experienced transient postoperative neurological symptoms attributed to perilesional edema. Seizure reduction ranged from 50% to 75% following SEEG-RFTC. LESSONS SEEG and SEEG-RFTC are feasible in patients who have implanted neuromodulation devices, including intracranial implants. These procedures may be performed without interference with existing hardware and provide meaningful seizure reduction in highly refractory populations. Further studies with larger cohorts and longer follow-up are needed to better define efficacy and patient selection. https://thejns.org/doi/10.3171/CASE26376

Purpose: Subcortical functional brain mapping is a valuable technique, especially involving lesions within or near white matter tracts. Motor and language deficits caused by intraoperative damage to these subcortical fibers are associated with worse outcomes. However, there are variable approaches to performing subcortical functional brain mapping. This systematic review was performed to better understand indications and optimal stimulation parameters. Methods: A systematic review was performed by PRISMA guidelines, using PubMed, Scopus, and Medline databases. Search dates ranged from inception to November 30th, 2024. Studies included adults who underwent subcortical electrical stimulation for functional brain mapping. Results: A total of 55 articles (249 patients, mean age 44.8 years, 114 female) were included. The most common pathology was brain tumor (96.3%), primarily gliomas and metastases, and 24.4% of all cases had a history of epilepsy. The most frequently mapped white matter tracts were the arcuate fasciculus, corticospinal/pyramidal tract, and inferior fronto-occipital fasciculus, involving motor, language, and cognitive functions. Bipolar stimulation (50–60 Hz, 0.5–1 millisecond, 1–10 mA) was preferred over monopolar stimulation. Among 147 patients with outcome data, 89.1% did not suffer permanent adverse outcomes including neurologic deficits, although long-term outcomes were inconsistently reported. Conclusions: The methodologic variability of subcortical functional brain mapping and lack of long-term follow-up reported limits determination of optimal parameter selection for electrical stimulation although common trends are reported. Functional brain mapping approaches may be guided by the tract and network involved. Further studies are needed to develop a standardized approach and more definitive guideline to its performance.

OBJECTIVE The aim of this study was to compare 3 electrode designs—a novel 22-contact circular grid, standard 6-contact strip, and high-density (HD) grid between 32 and 64 contacts—for the detection of epileptiform activity during awake craniotomy. METHODS This study included patients who underwent functional brain mapping with and without direct electrical stimulation during awake craniotomy. Demographic, clinical, and electrocorticography (ECoG) data were collected. RESULTS A total of 194 patients were included, with 264 instances of electrode use: 113 circular grid, 96 strip electrode, and 55 HD grid. The HD grid (15%) was used less to record ECoG during direct electrical stimulation than the circular grid (80%, p < 0.001) and strip electrodes (69%, p < 0.001). Sporadic interictal epileptiform activity was better detected with circular (45%, p < 0.001) and HD (40%, p = 0.006) grids compared with strip electrodes (16%). Spontaneous seizures were recorded more frequently with the circular grid (16%, p = 0.018) compared with the strip electrode (9.4%) and HD grid (1.8%). Afterdischarges were more frequently detected by the circular grid (69%, p = 0.031) and with circular and HD grids (combined) compared with strip electrodes (67% vs 48%, p = 0.024), at lower median intensity (3 mA vs 5 mA, p < 0.001). Multivariable analyses demonstrated circular grids (p < 0.001) to be more sensitive in detecting spontaneous epileptiform activity than strip and HD grid electrodes, and grids (circular and HD) to be better in recording stimulus-induced epileptiform activity (p = 0.01). CONCLUSIONS This study demonstrates a higher rate of detection of epileptiform activity with circular and standard grids when compared with strip electrodes. The standard HD grid was used less during electrical stimulation, demonstrating the importance of both the number of contacts and design array when considering optimal conditions for ECoG and functional brain mapping.

This paper develops and characterizes an adaptive hybrid Electrodynamic Intelligence (EDI) Neuro-Patch, a biohybrid interface uniting the physical, electrical, and functional dimensions of neural plasticity. Unlike conventional neuromorphic systems that simulate synaptic learning algorithmically, the hybrid EDI approach treats charge-flux interactions within memristive neurons as the substrate of computation itself. In this framework, axonal conduction and synaptic integration occur from continuous electrodynamic evolution, where memory, adaptation, and signal propagation are inseparable physical processes. The hybrid neuro-patch combines a solid-state conductive upper layer for rapid signal modulation with a lower iontronic layer providing slow, adaptive reconfiguration. Controlled programming pulses induce state transitions, allowing path learning through field-mediated adaptation rather than digital feedback. By integrating devicelevel electrodynamics with cortical network dynamics we establish a quantitative framework linking voltage, conductance, and path reconfiguration across scales from nanometers to cortical circuits. The simulations demonstrate emergent network stabilization and adaptive routing, suggesting that hybrid EDI neuro-patch could provide self-organizing implants for restoring and maintaining stable neural function through the intrinsic physics. By demonstrating that memory, adaptation, and signal propagation are inseparable physical processes rather than algorithmic constructs, the hybrid EDI neuro-patch highlights a new framework for self-organizing neural computation. This approach provides a pathway toward adaptive implants able of restoring and maintaining stable neural function through the intrinsic physics of matter with potential applications in epilepsy suppression, spinal injury bridging, and adaptive prosthetic control. Beyond its immediate clinical utility, a modular, scalable design could provide a platform for next-generation biohybrid or synthetic brain architectures, neuromorphic computation, and distributed neural networks with a clear pathway toward advanced brain–machine interfaces.

Abstract Statistical learning (SL) is a powerful mechanism that supports the ability to extract regularities from environmental input. Yet, its neural underpinnings are not well understood. Previous EEG studies of SL have found that the brain tracks regularities by synchronizing its activity with the presented stimuli—a phenomenon known as neural entrainment. However, EEG lacks the spatial resolution to unveil the specific brain regions where this process takes place. In our study, 18 patients with drug-resistant epilepsy who were implanted with intracranial electrodes for presurgical investigation listened to a continuous speech stream containing embedded trisyllabic words. Neural entrainment was measured at the syllable and word frequencies, with the latter providing an online index of learning. SL was further assessed through both explicit and implicit behavioral measures. Behaviorally, we found evidence of learning at the group level in both tasks. At the neural level, our analyses revealed three temporal tuning profiles: 25% of contacts showed entrainment at the syllable frequency, 11% of contacts showed entrainment at both the word and syllable frequencies, and 4% showed entrainment only to the word frequency. Word entrainment, indicating sensitivity to word structures, was most commonly found in auditory and language-related regions, including insula, middle temporal gyrus, superior temporal gyrus, and supramarginal gyrus. In contrast, evidence for neural entrainment in the hippocampus was weak. Overall, these results support the idea that speech-based SL is largely supported by modality-specific brain regions.

Abstract Purpose Cenobamate is approved for treating focal epilepsy and has potential for treating tumor‐related epilepsy (TRE) based on potential anti‐tumor effects, though there is little data on efficacy and safety in this patient population. Methods This was a retrospective, multi‐center study of patients with TRE who were prescribed cenobamate as adjunctive treatment between January 2020 and November 2024 at Mayo Clinic in Florida, Minnesota, and Arizona. Drug efficacy was assessed, and factors that were predictive of response to treatment were analyzed. Results A total of 17 patients were included, with 12 being drug resistant. The median seizure frequency for the entire group before starting cenobamate treatment was 12 (IQR = 4–64) per month, and after treatment at last follow‐up was 3 (IQR = 1–15) per month, with an overall 56.3% reduction. Four patients (23.5%) were seizure‐free, and 7 (41.1%) patients were responders (at least 50% seizure reduction). No adverse events were reported for patients on concurrent chemotherapy. Responders had significantly fewer seizures per month compared to non‐responders (5.72 ± 10.29 vs. 27.33 ± 30.17; p = .030). No clinical factors were predictive of responsiveness (or lack thereof) to cenobamate. Conclusions This study demonstrates that adjunctive therapy with cenobamate treatment for TRE is a feasible and potentially effective option. Clinical history, including drug resistance, did not predict drug efficacy. No adverse effects were reported in those treated with chemotherapy. Further studies are needed to validate treatment response and safety.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.