Miller, Kai J

Abstract Objective Interictal epileptiform spikes (IESs) are widely used biomarkers of epileptogenic tissue in presurgical epilepsy evaluation. However, their reliability for seizure onset zone (SOZ) localization in high‐density intracranial electroencephalography (iEEG) remains inconsistent. It is underexplored whether this variability reflects methodological differences across detection algorithms or a limitation of IESs as a biomarker. This study evaluates whether IES detection alone provides sufficient spatial specificity for accurate SOZ localization in iEEG. Methods We systematically benchmarked eight established IES detection algorithms using iEEG recordings from 35 patients with drug‐resistant focal epilepsy. To provide a clinically meaningful reference, algorithm performance was evaluated against the clinically defined SOZ. To refine detection outputs and move beyond only IES detection, we applied masking strategies to isolate informative IES subsets based on rate, amplitude, frequency, and co‐occurrence with high‐frequency oscillations (HFOs). Conceptually, masking acts as a spatial refinement strategy that progressively restricts diffuse IES activity to more focal, pathologically relevant event populations. Results Despite substantial variability in detection characteristics, SOZ localization performance (ratio of events originating from SOZ divided by total number of events) converged within a narrow range (.23–.51), suggesting that IESs exhibit an intrinsic ceiling in SOZ localization performance when used alone. Amplitude‐based masking yielded modest improvements, whereas frequency‐based masking reduced performance. In contrast, IES‐HFO co‐occurrence markedly improved localization, particularly when combined with rate‐based masking, achieving a median SOZ localization ratio of .89, exceeding IESs (.37) and HFOs (.63) evaluated independently. Significance These findings demonstrate that IES‐based SOZ localization may require moving beyond detection‐only approaches. The integration of informed, biomarker‐driven masking strategies provides a more robust framework for identifying the activity most relevant to the epileptogenic network and paves the way for future incorporation into the clinical decision‐making pipeline.

Abstract Objective Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an effective therapy for frontotemporal and limbic drug‐resistant focal epilepsies. The pulvinar nucleus (PUL) is an emerging neuromodulation target for seizure networks involving the posterior quadrant and temporal lobe. This study evaluates the safety and effectiveness of combined bilateral ANT plus PUL DBS for posterior quadrant and temporal lobe epilepsies. Methods We conducted a single‐center retrospective cohort study of patients receiving combined ANT/PUL DBS between 2021 and 2025. Outcomes included median seizure rate reduction (MSR), responder rate (RR; >50% seizure frequency reduction), and stimulation‐related side effects, assessed across ANT, PUL, and concurrent ANT/PUL stimulation settings. Acute surgical complications were evaluated. Statistical significance was assessed using two‐sided Wilcoxon signed‐rank tests with Holm–Bonferroni correction. Results Nine patients with combined ANT/PUL DBS were identified, and eight patients had sufficient follow‐up for inclusion (median follow‐up = 20 months). Posterior predominant structural abnormalities were present in eight of nine patients. There were no acute surgical complications. Three instances of transient stimulation‐related side effects resolved with parameter adjustments, whereas one patient required rescue antiseizure medication in addition to programming changes. Eight patients received periods of ANT stimulation, six PUL stimulation, and seven combined ANT/PUL stimulation. Regarding overall outcome, at last follow‐up, there was a significant 80.8% MSR ( p = .0078) and 87.5% RR, with two patients receiving ANT and six ANT/PUL stimulation. Regarding target‐specific MSR, concurrent ANT/PUL DBS (68.8% MSR) showed a trend toward superior performance relative to ANT (43.3%) and PUL DBS (17.5%) alone, although subgroup analysis of target‐specific performance did not reach statistical significance. Significance Combined four‐lead ANT/PUL DBS appears safe and effective for patients with drug‐resistant posterior quadrant and temporal lobe epilepsies. Dual‐network neuromodulation may provide greater flexibility to individually optimize neuromodulation for complex seizure networks.

BACKGROUND Laser interstitial thermal therapy is a minimally invasive surgical technique commonly used for treating epileptogenic foci in patients with drug-resistant epilepsy. Densely calcified lesions pose a challenge because they prevent the placement of a laser cannula within them and act as a heat shield. A 22-year-old male presented with intractable epilepsy with imaging demonstrating a densely calcified lesion in the right medial occipitotemporal gyrus radiographically consistent with a polymorphous low-grade neuroepithelial tumor of the young. OBSERVATIONS Two laser cannulas were stereotactically positioned to flank the centrally calcified portion of the lesion at its anterior and posterior aspects. Intraoperative MR thermography during each ablation showed that the dense calcification shielded ablative heating from spreading to the other side of the lesion. The sum of the thermal ablation zones covered the entirety of the lesion. Postprocedure MRI demonstrated overlapping peripherally enhancing ablation zones, which subsumed the entirety of the calcified mass. The patient tolerated the procedure well and remained seizure free at the 14-month follow-up. LESSONS Using multiple stereotactically placed laser filaments to flank epileptogenic lesions that are densely calcified is a strategy to effectively encompass the entirety of the lesion within the combined ablation zones. https://thejns.org/doi/10.3171/CASE26184

Miller et al. maintain that thalamic SEEG can now be considered a cornerstone of standard clinical practice in individualized epilepsy care, helping to define seizure onset and spread, assess therapeutic stimulation, map connectivity, and identify target-specific biomarkers for responsive neurostimulation.

Abstract Cortico‐cortical evoked potentials (CCEPs) are an active electrophysiological technique used during intracranial electroencephalography to evaluate the effective connectivity and influence of therapeutic stimulation between distinct cortical regions and pinpoint epileptogenic zones (EZs) in patients with epilepsy. Various methodologies have been implemented to analyze CCEPs and characterize the epileptogenic networks for EZ localization. Despite its promise, their interpretation remains challenging due to the large volumes of spatially and temporally complex data generated. Early studies focused largely on qualitative descriptors and predefined, semi‐quantitative features such as waveform morphology and peak latencies. However, these methods are limited by the significant heterogeneity in CCEP waveform conformations across patients and cortical regions. The specific technique used for extraction of features, such as the spectral band power and root mean squared values, remains open to empirical refinement, as does choice of appropriate latency windows, with no consensus reached regarding the optimal approach. Graph theoretical metrics such as degree centrality, betweenness centrality, and clustering coefficients can provide a rich representation of epileptogenic network connectivity. However, these metrics are often abstract and difficult to interpret in a clinical setting or to the non‐expert, and their neuroscientific substrates remains poorly understood. The lack of standardization in stimulation protocol and data‐processing pipelines has further contributed to inconsistency in reported findings. Emerging machine learning approaches have been increasingly applied to CCEP data, offering a more data‐driven and potentially generalizable way to identify electrophysiological biomarkers of the epileptogenic effective connectivity. In this article, we discuss qualitative, quantitative, and spectral features; network‐analytical metrics; and more recently, data driven methodologies aimed at improving the interpretability and clinical utility of CCEP data.

Abstract Electrical stimulation is increasingly used to modulate brain networks for clinical purposes. The basic unit of neurostimulation, a single electrical pulse, can travel through white matter to influence connected neuronal populations. However, the mechanisms by which it influences connected populations is not well understood: stimulation may excite, inhibit, or add noise to neuronal population activity. In this study, we investigated how single pulses modulate the neuronal processing of images in a well-controlled visual paradigm. In two human subjects implanted with iEEG electrodes for clinical purposes, single pulses were delivered to electrodes in white matter tracts connected to measurement electrodes in visual cortex. Images appeared on-screen at 0, 100, or 200 ms after each pulse. Using finite impulse response modeling, we decomposed the broadband and evoked potential responses into separate components induced by electrical stimulation and by visual processing. Single pulses induced transient broadband increases followed by suppression, but they did not modulate the visual broadband responses (i.e., stimulation response was additive to visual response). In contrast, single pulses elicited prominent brain stimulation evoked potentials and they modulated the visual evoked potentials. Specifically, visual evoked potentials were larger when stimulation occurred closer to visual onset. This indicates that a single electrical pulse can increase the strength or synchrony of visual inputs. Overall, these findings suggest that the effects of electrical stimulation in the visual system are two-fold: stimulation induces additive effects on broadband power, possibly by adding noise, and it interacts with synchronous visual inputs to amplify them.

BACKGROUND AND OBJECTIVES: Stereotactic procedures are used to manage a diverse set of patients across a variety of clinical contexts. The stereotactic devices and software used in these procedures vary between surgeons, but the fundamental principles that constitute safe and accurate execution do not. The aim of this work is to describe these principles to equip readers with a generalizable knowledge base to execute and understand stereotactic procedures. METHODS: A combination of a review of the literature and empirical experience from several experienced surgeons led to the creation of this work. Thus, this work is descriptive and qualitative by nature, and the literature is used to support instead of generate the ideas of this framework. RESULTS: The principles detailed in this work are categorized based on 5 clinical domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. Illustrations and tables are used throughout to convey the concepts in an efficient manner. CONCLUSION: Stereotactic procedures are complex, requiring a thorough understanding of each step of the workflow. The concepts described in this work enable functional neurosurgeons with the fundamental knowledge necessary to provide optimal patient care.

BACKGROUND AND OBJECTIVES: Identifying and characterizing sources of targeting error in stereotactic procedures is essential to maximizing accuracy, potentially improving surgical outcomes. We aim to describe a generic framework which characterizes sources of stereotactic inaccuracy. METHODS: We assembled a list of stereotactic systems: ROSA, Neuromate, Mazor Renaissance, ExcelsiusGPS, Cirq, STarFix (FHC), Nexframe, ClearPoint, CRW, and Leksell. We searched the literature for qualitative and quantitative work identifying and quantifying potential sources of inaccuracy and describing each system's implementation using Standards for Reporting Qualitative Research guidelines. Our literature search spanned 1969 to 2024, and various studies were included, with formats ranging from phantom studies to systematic reviews. Keyword searches were conducted, and the details about each system were used to create a framework for identifying and describing the unique targeting error profile of each system. RESULTS: We describe and illustrate the details of various sources of stereotactic inaccuracies and generate a framework to unify these sources into a single framework. This framework entails 5 domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. This framework was applied to 10 stereotactic systems. CONCLUSION: This framework provides a rubric to analyze the sources of error for any stereotactic system. Illustrations allow the reader to understand sources of error conceptually so that they may apply them to their practice.