Van Gompel, Jamie J

ABSTRACT Objective Pituitary carcinoma (PC) is defined by the presence of metastasis from a pituitary tumour. PC is rare, therefore information regarding survival and factors influencing survival are limited. We sought to assess overall survival following the diagnosis of PC and to determine factors associated with outcome. Design Retrospective case series. Patients Patients with PC who attended the Mayo clinic between 1997 and 2025. Measurements Information regarding patient demographics, tumour characteristics, management and outcomes were extracted. Results In total 25 patients (11 women, 44%) were diagnosed with PC (median age 56 years, range, 44–78). The most common cell type was a corticotroph tumour ( n = 15, 60%). All but one patient had pituitary directed surgery and all received pituitary adenoma (PA) directed radiation therapy. Metastases were identified a median 6 years (range, 1–32) after initial PA diagnosis. At last follow‐up, 10 (40%) patients were alive, 12 (48%) died of PC, and 3 (12%) died from other causes. The median survival time of patients from PC diagnosis was 3 years. The 1‐, 5‐ and 10‐year survival rates were 59%, 37% and 15%, respectively. Increased survival probability was associated with temozolomide treatment ( n = 9) at some point in treatment plan ( p = 0.026), the use of systemic therapy vs locoregional treatment ( p = 0.045), female sex ( p = 0.011), and in nonfunctional tumours ( p = 0.023). Conclusion PC carries a poor prognosis, with a median survival of only 3 years. Improved survival was associated with temozolomide exposure, female sex, and nonfunctional tumour subtype and underscores the prognostic relevance of tumour biology and treatment approach.

Abstract To characterize invasive neuromodulation for insular drug‐resistant epilepsy, we retrospectively evaluated 22 patients treated with responsive neurostimulation (RNS; n = 14) or chronic subthreshold stimulation (CSS; n = 8). Stereoelectroencephalography was performed in 20 cases (91%). Median baseline seizure frequency was 10.5/month. Forty‐one percent had prior epilepsy surgery. At year 3, median seizure reduction (MSR) was 83% ( p = .01, Wilcoxon signed‐rank test), with a responder rate (RR) of 77%; MSR was 92% for CSS and 75% for RNS. There were no significant differences in MSR ( p ≥ .4) or RR ( p > .9) when comparing RNS versus CSS. Three patients achieved seizure freedom by year 3. Patients undergoing combined insular–thalamic stimulation ( n = 5) demonstrated an MSR of 84%, 86%, and 88% at 1, 2, and 3 years; seizure reduction in thalamocortical versus cortical‐only stimulation was not different ( p ≥ .1). Parasagittal lead trajectories achieved closer insular proximity than transopercular trajectories ( p < .0001, Mann–Whitney U ‐test). Median charge density at last follow‐up was 1.3 μC/cm 2 . There were no acute surgical complications and all stimulation‐related side effects resolved with programming adjustments. This study expands the limited literature on insular neuromodulation by demonstrating effectiveness of RNS and CSS, suggesting potential benefit from combined thalamocortical targeting, and defining parasagittal trajectories as a surgical approach for optimal lead proximity.

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.

ABSTRACT Background Cerebrospinal fluid (CSF) leak after retrosigmoid vestibular schwannoma resection remains a challenging complication. Historically, surgeons reopened the prior retrosigmoid incision for transmastoid repair because the safety of creating a separate postauricular incision was uncertain, with concerns regarding wound breakdown and infection. However, limited data support this practice, and a focused mastoid incision may offer improved access and patient tolerance. This study evaluated wound healing outcomes following transmastoid repair using a new postauricular incision for persistent CSF leak after retrosigmoid surgery in patients without serviceable hearing. Methods We retrospectively reviewed 27 patients who underwent transmastoid repair for persistent postoperative CSF leak after retrosigmoid craniotomy for vestibular schwannoma (2000–2025). Demographics, operative details, timing of leak diagnosis and repair, wound complications, readmissions, antibiotic use, and culture results were analyzed. Results Median age was 48 years (IQR 41–56); 67% were male, and mean BMI was 29.0 kg/m 2 . Mastoid obliteration was performed in 96%, with fat grafting in 93%. A new postauricular incision was used in all cases. Median time to leak diagnosis was 13 days (IQR 4–79), and median time to repair was 2 days (IQR 1–5). One patient (3.7%) developed a superficial wound abscess; no dehiscence or flap necrosis occurred. At median follow‐up of 34 months (IQR 2.9–87.7), all wounds were healed. CSF leak recurred in two patients (7.4%) and three (11.1%) required reoperation. Conclusion A separate postauricular incision for transmastoid CSF leak repair was not associated with increased wound morbidity. Durable wound healing was achieved in all patients, with 93% legal control, supporting this anatomy‐driven approach. Level of Evidence 4

BACKGROUND AND OBJECTIVES: Endoscopic transnasal surgery offers a minimally invasive alternative to transcranial approaches for accessing midline skull base lesions involving the petrous apex and petroclival region. However, lateral access, particularly behind the petrous internal carotid artery (ICA), remains limited. The contralateral transmaxillary (CTM) approach provides a more direct surgical trajectory, more parallel to the petrous ICA. Yet, lateral access through this approach can be restricted by anatomic barriers, including the pterygoid process and lateral buttress of the maxillary sinus. We aimed to evaluate the contralateral transmaxillary-transpterygoid (CTMP) approach, with and without the lateral buttress removal (CTMP-LBR), to determine whether these modifications could enhance surgical access to the petroclival region. METHODS: Ten sides from 5 formalin-fixed, latex-injected cadaveric specimens were dissected to compare CTM, CTMP, and CTMP-LBR approaches. Petrous bone drilling was directed posterolaterally behind the petrous ICA toward the region medial to the cochlea. In addition, 30 sides from computed tomography angiography scans were analyzed to obtain radiographic measurements for each approach. RESULTS: Compared with CTM, both CTMP and CTMP-LBR significantly increased access for retrocarotid petrous bone drilling ( P < .001) and yielded a wider surgical angle relative to midline ( P < .001), in both cadaveric and radiographic analyses. In dissections, 20% of sides required CTM only, 50% benefited from CTMP, and 30% required CTMP-LBR to achieve adequate lateral access. Radiographic analysis revealed that CTMP required a median of 4 mm of pterygoid drilling, whereas CTMP-LBR required 9 mm and enabled a trajectory parallel to the petrous ICA with only 11 mm of soft tissue displacement. Patients with smaller angles between the petrous ICA and the horizontal plane were significantly more likely to benefit from CTMP over CTM ( P = .005). CONCLUSION: Modification of the CTM approach with pterygoid drilling and optional LBR improves retrocarotid access. Preoperative evaluation of the petrous ICA angle may help optimize patient-specific planning in endoscopic petroclival surgery.

Abstract Objective This study was undertaken to evaluate the safety and effectiveness of responsive thalamic stimulation as adjunctive therapy for drug‐resistant idiopathic generalized epilepsy (IGE) with generalized tonic–clonic seizures (GTCSs). Methods NAUTILUS is a prospective, multicenter, single‐blind, randomized sham‐controlled pivotal trial. Patients were ≥12 years of age with drug‐resistant IGE and ≥2 GTCSs over a 3‐month baseline. Bilateral depth leads were targeted to the centromedian thalamus. One month later, patients were randomized to Active (responsive stimulation, n = 44) or Sham (no stimulation, n = 43). The effectiveness evaluation period (EEP) began 3 months postimplant through 1 year. After a second GTCS in the EEP, patients transitioned to open‐label active stimulation. The primary safety endpoint was the serious adverse device‐related event (SADE) rate at 84 days postimplant. The primary effectiveness endpoint was time‐to‐second‐GTCS during the EEP. Additional endpoints included median percent change in days with any generalized seizure, GTCS frequency, and responder rate (RR). Results Eighty‐seven patients were implanted across 23 US centers. The SADE rate was significantly below the performance goal (6.9%, p < .0001), with no adverse effects on cognition, mood, or sleep. The prespecified primary effectiveness endpoint was not significant. However, a post hoc mixed‐effects model considering all EEP days demonstrated greater GTCS reduction in the originally randomized Active group (61%) compared to patients originally randomized to Sham (49%, p = .030). Eighteen‐month outcomes included 76.8% median GTCS reduction, 62.5% RR, 40% GTCS‐free at that timepoint, and 77.8% median reduction in days with any generalized seizure. More than 90% of patients and 86% of physicians reported improvement on Global Impression of Change scales. Significance NAUTILUS is the first randomized controlled neuromodulation trial in IGE. Responsive thalamic stimulation provided a clinically meaningful and durable reduction in seizures with an acceptable safety profile, offering a much‐needed option for drug‐resistant IGE.

Abstract In epilepsy patients lacking magnetic resonance imaging‐visible lesions such as focal cortical dysplasia (FCD), surgical resections target regions with abnormal electroencephalographic (EEG) activity. However, histopathological identification of subtle cortical architectural abnormalities in these specimens remains challenging. We investigated whether artificial intelligence (AI)‐based morphometric and spatial analysis of NeuN‐stained cortical sections could detect neuronal architectural disorganization in epilepsy resections, including regions without definitive histologic dysplasia. Whole slide images were generated from 83 FCD regions and 19 neurologically normal autopsy controls. Regions of interest were annotated in QuPath as FCD, FCD‐adjacent, FCD‐distant, apparently normal (abnormal EEG without histologic dysplasia), and true normal (autopsy controls). NeuN‐positive neurons were detected using QuPath (90% sensitivity, 12% false positive rate). Spatial and morphometric features—including neuronal clustering, distribution inhomogeneity, and nuclear morphology—were extracted and used to train a multinomial, Least Absolute Shrinkage and Selection Operator‐regularized regression classifier. The classifier achieved 70.6% accuracy in subregion classification and 88.2% accuracy in overall specimen diagnosis. Notably, regions with abnormal EEG but lacking histologic dysplasia exhibited quantifiable architectural disorganization similar to those seen in areas adjacent to FCD and distinct from control tissue. AI‐driven analysis of neuronal morphology and spatial distribution reveals subtle cortical disorganization in epilepsy resections, including in histologically ambiguous regions. Further investigation is warranted to determine if this methodology can enhance the diagnostic yield of neuropathological evaluation and support more precise surgical targeting in epilepsy.

ABSTRACT Background Preoperative vascular embolization (PVE) is commonly used in managing juvenile nasopharyngeal angiofibroma (JNA) to improve outcomes. However, few studies have evaluated how embolization patterns and vascular features affect prognosis. Methods A 15‐year retrospective review was performed on 44 patients with JNA undergoing surgery at one institution. Data included demographics, vascular supply, embolization techniques, surgical outcomes, and recurrence. Results Forty‐three patients underwent PVE. Most tumors were embolized transarterially (93.0%) using polyvinyl alcohol‐based agents (79.1%). The internal maxillary artery was most commonly embolized (93.0%). Internal carotid artery supply was present in 34.9%, and more than two vessels were embolized in 23.3%. Postembolization tumor blush occurred in 60.5%, with a median of 5% of the pre‐embolization blush remaining after embolization. Neither internal carotid involvement, number of vessels embolized, nor residual blush significantly impacted operative time, surgical outcomes, or recurrence. Conclusion With effective embolization, vascular complexity might not affect JNA resection outcomes. Multicenter studies are required to confirm those findings.

Abstract This review aims to update recent advancements in the management and treatment of olfactory neuroblastoma (ONB) based on discussions and topics highlighted during the 2024 North American Skull Base Society session “Literature Review: What's New in Olfactory Neuroblastoma?” A systematic review was conducted using PubMed/MEDLINE, focusing on relevant studies published between January 2022 and June 2024. Data were organized into themes: prognostication and staging, surgical concepts, biomarkers/genomics, imaging, syndrome of inappropriate antidiuretic hormone release and hyponatremia, chemotherapy, and radiotherapy. Out of 289 initial records, 46 studies met eligibility criteria. Key findings include the proposed integration of Hyams grading and dural infiltration with traditional staging for better prognostic accuracy, a shift toward less invasive surgical techniques while maintaining clear resection margins, and the identification of biomarkers for improved diagnosis and targeted therapy. Advanced imaging modalities like DOTA-peptide tomography (positron emission tomography–computed tomography/magnetic resonance imaging) were highlighted for their diagnostic value. Variability in induction chemotherapy outcomes underscores the need for personalized treatment plans, and new radiotherapy techniques offer promising results with improving morbidity. Recent advancements in ONB management have enhanced prognostic accuracy, molecular diagnostics, imaging techniques, and treatment outcomes. Continuous research is necessary to optimize these strategies and further improve patient survival and quality of life.