Van Gompel, Jamie J

Abstract Context Evidence on the evolution of cardiometabolic comorbidities following surgical remission of hypercortisolism is scarce. Objective To determine the impact of surgical remission on cardiometabolic comorbidities in patients with endogenous hypercortisolism and to identify factors associated with cardiometabolic improvement. Methods Prospective single-center cohort study (2019-2025) of adults with Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS) with surgical remission of hypercortisolism. Outcomes included (1) changes in severity of hypertension, diabetes mellitus (DM), hyperlipidemia, and obesity between baseline, 3, and 12 months postremission and (2) factors associated with improvement in comorbidities. Results Among 357 patients (49% MACS, 36% pituitary CS, 10% adrenal CS, 5% ectopic CS; median age 53 years [interquartile range 42-62]; 81% women), 336 (94%) had hypertension, 241 (68%) had obesity, and 122 (35%) had DM. At a median of 12 months postsurgery, improvement in hypertension occurred in 70% (90/128) of patients with CS and 51% (60/117) of patients with MACS, DM in 90% (46/51) patients with CS and 37% (13/35) patients with MACS, and obesity in 79% (77/97) patients with CS and 20% (14/71) patients with MACS. In a multivariable analysis, higher baseline biochemical severity scores were associated with improvement in hypertension [odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1-1.5), DM (OR 2.5, 95% CI 1.7-4.1), and obesity (OR 1.5, 95% CI 1.2-1.8) at a median of 12 months postremission of hypercortisolism. Conclusion Postsurgical improvement of cardiometabolic comorbidities was observed in both patients with CS and MACS. Higher baseline biochemical severity scores were associated with higher postremission improvement in comorbidities.

Objective The effects of deep brain stimulation (DBS) manifest across multiple timescales, spanning seconds to months, and involve direct electrical effects, neuroplasticity, and network reorganization. In epilepsy, the delayed impact of DBS on seizures presents challenges for optimization. Single‐pulse stimulation and resulting brain stimulation evoked potentials (BSEPs) provide a means to assess effective connectivity and network excitability. This study integrates BSEPs and short trials of DBS during stereoelectroencephalography (sEEG) to map seizure network engagement, modulate network dynamics, and monitor excitability and interictal abnormalities for biomarker informed neuromodulation. Methods Ten individuals with drug resistant epilepsy undergoing clinical sEEG were enrolled in this retrospective cohort study of epilepsy neuromodulation biomarkers. Each patient underwent a trial of high frequency (145Hz) thalamic DBS. BSEPs were acquired before and after DBS trials. Baseline BSEP amplitude assessed seizure network engagement, and modulation of amplitude (pre vs post DBS) assessed change in network excitability. Interictal epileptiform discharges were tracked by an automated classifier. Results Baseline BSEPs delineated distinct patterns of network engagement between thalamic subfields with maximal frontotemporal engagement achieved with stimulation of the anterior nucleus of the thalamus‐ventral anterior nucleus junction. DBS delivered for >1.5 hours reduced BSEP amplitudes compared to baseline, and the degree of modulation correlated with baseline connectivity strength. Shorter DBS trials did not induce reliable BSEP amplitude suppression, but did immediately suppress interictal epileptiform discharge rates in well‐connected seizure networks. Interpretation BSEPs and trials of DBS during sEEG provide novel network biomarkers to evaluate the modulation of large‐scale networks across multiple timescales, advancing biomarker informed neuromodulation. ANN NEUROL 2026;99:748–760

Abstract Craniopharyngiomas are rare parasellar tumors, and papillary craniopharyngiomas (PCPs) represent 8 to 20% of cases. Interim analysis of retrospective data collected from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). Fourteen U.S.-based academic skull base centers between 2011 and 2023. Patients with PCPs. Demographic, imaging, surgical, and outcome variables. Ninety-nine patients with PCPs were included. The mean age was 51.8 ± 14.7, and 57.6% were male. Most tumors showed mixed cystic/solid components (67.5%), were transinfundibular (50.0%), and were treated with an endoscopic endonasal approach (74.5%), with 51.1% demonstrating gross total resection (GTR). Pituitary stalk was preserved in 51.9%. Permanent arginine vasopressin deficiency was seen in 67.1% and was associated with pituitary stalk sacrifice (p = 0.003). Cerebrospinal fluid leak was the most common nonendocrine postsurgical, 30-day complication (9.1%), reason for return to the operating room (3.1%), and reason for 90-day readmission (8.1%). Most patients (63.9%) received no adjuvant therapy; GTR was associated with decreased radiotherapy use (p = 0.0001). BRAFV600E mutation was detected in 64/69 tumors tested, although only one patient was treated with a BRAF inhibitor. A mean follow-up of 12.3 ± 14.6 months was seen for the group. RAPID consortium enabled the largest real-world clinical information dataset for PCPs. Early findings support that GTR and stalk preservation are important to outcomes. Iterative analysis and discussion of data led to the generation of a framework for future studies to fully leverage the capabilities of multicenter registries.

AbstractObjectiveNeuromodulation for pediatric refractory epilepsy (PRE) is preferred when the seizure onset zone is not amenable to surgical resection, due to multifocal onset or involvement of eloquent cortex. Given its rapidly evolving landscape, we describe our institutional experience with neurostimulation therapies including deep brain stimulation (DBS) of the anterior nucleus (DBS‐ANT), the centromedian nucleus (DBS‐CM), responsive neurostimulation (RNS), and chronic subthreshold stimulation (CSS) to treat PRE.MethodsA retrospective chart review was conducted to identify pediatric patients (≤18 years of age) who presented to our institution with PRE. Patients were included who had at least 1 year of follow‐up after neurostimulation was started. Patients with ≥50% seizure frequency reduction at last follow‐up compared to baseline were classified as responders.ResultsA total of 35 patients (21 females) were included in the series. Nine patients underwent DBS‐ANT, 9 underwent DBS‐CM (+ ANT in 7 patients), 5 underwent RNS, and 12 underwent CSS. The median age at seizure onset and surgery was 8 and 16 years, respectively. Structural lesions were the most common etiology of epilepsy (54%). Eighteen patients had prior interventions and 13 received invasive EEG. Post‐operative complications following neurostimulation implantation were noted in three patients (9%). However, no permanent deficits were noted. Median follow‐up time was 46 months (range 13–162 months). Twenty‐three patients (59%) were responders (3/9 DBS‐ANT; 7/9 DBS‐CM; 4/5 RNS; 9/12 CSS). Further, median seizure reduction was 25% (DBS‐ANT), 89% (DBS‐CM), 87% (RNS), and 88% (CSS) across the cohort. Six patients (17%) had improved subjective neurocognitive outcomes while the other 29 had stable neurocognitive outcomes.SignificanceDBS, RNS, and CSS are safe and effective options for PRE. An understanding of treatment approaches can optimize results by tailoring therapy to individual patients.Plain Language SummaryThis study investigates the use of various neurostimulation therapies for treating pediatric refractory epilepsy (PRE) including deep brain stimulation (DBS), responsive neurostimulation (RNS), and chronic subthreshold stimulation (CSS). Overall, neuromodulation was found to be effective in reducing seizures in most patients, with 59% of patients showing at least a 50% reduction in seizure frequency. Additionally, the treatments were generally safe, with few complications and no instances of permanent deficits.

AbstractObjectiveStereoelectroencephalography‐guided radiofrequency thermocoagulation (SEEG‐guided RFTC) has been increasingly used as diagnostic and therapeutic approach for drug‐resistant focal epilepsies (DREs). We aimed to describe seizure outcomes of RFTC before and after further neurosurgical intervention.MethodsRetrospective single‐institution case series of patients who underwent SEEG‐RFTC. The primary outcome was Engel class I–IV classification ([responders Engel I–III and non‐responders Engel IV]) at last follow‐up after RFTC and prior to further neurosurgical intervention (open surgical resection, laser ablation, and neuromodulation).ResultsTwenty‐five patients (median age 18.9 years) with DRE were included. The median follow‐up time after RFTC was 7.2 months, including 20 patients who underwent further intervention (median follow‐up time of 7.3 months) and 5 without intervention (median of 3.5 months). From the patients who had further intervention, 17 (85%) underwent surgical procedure (laser ablation 53%, open surgical resection 47%) (median 4.4 months) and 3 (15%) had responsive neurostimulators placed (median 6.9 months). Prior to further intervention (median follow‐up 3.5 months after RFTC), 12 (48%) patients were classified as responders (12% Engel class I, 16% class II, and 20% class III) and 13 (52%) as non‐responders. Following neurosurgical intervention, 17 (68%) patients were followed for a median time of 2.7 months and 3 were lost to follow‐up. Of eight initial RFTC responders, 87.5% and 12.5% had Engel classes I and III, respectively. Of nine who were non‐responders, 33% had Engel class I, 22% II and III, and 44% IV outcomes following further intervention. No neurologic complications were reported.SignificanceSEEG‐guided RFTC is a well‐tolerated procedure and a beneficial diagnostic approach prior to further neurosurgical interventions in patients with DRE.Plain Language SummarySEEG‐guided RFTC is a well‐tolerated procedure and in the patients who experienced initial seizure reduction (n = 8), subsequent neurosurgical intervention (surgery or neuromodulation) led to favorable seizure outcomes (87.5% seizure freedom and 12.5% worthwhile seizure improvement).

Abstract To propose a novel entity of possible intraosseous pseudoprogression in clival chordoma following proton radiation therapy (PRT). A total of 38 consecutive patients who underwent surgical resection followed by PRT for clival chordoma between January 2015 and December 2023 were analyzed retrospectively. Follow-up magnetic resonance imaging (MRI) suggesting recurrence or progression was evaluated for validity. Apparent diffusion coefficient (ADC) and tumor-to-brainstem signal intensity ratio on contrast-enhanced T1-weighted imaging (Rce) were assessed. Pseudoprogression was defined as (1) MRI signs of recurrence or progression with no pathological confirmation despite obtaining a specimen, or (2) MRI signs of recurrence or regression with spontaneous resolution/regression. Of the 11 patients with MRI findings suggestive of recurrence or progression, 3 were diagnosed with recurrence, 5 with progression, and 3 with pseudoprogression. Patients with pseudoprogression were significantly younger than those with progression (p = 0.04), and all were female. The median time to recurrence, progression, and pseudoprogression was 31, 29, and 21 months, respectively. The three pseudoprogression cases were managed with gross-total resection followed by stereotactic radiosurgery, extensive biopsy, and observation, respectively. Although statistical significance was not reached, ADC (p = 0.33) and Rce (p = 0.13) tended to be higher in pseudoprogression cases. After PRT for clival chordoma, intraosseous pseudoprogression should be considered in the differential diagnosis, particularly in relatively young female patients, although the role of ADC and Rce on MRI remains inconclusive. Multidisciplinary teams managing chordomas should take this into account when determining the aggressiveness of treatment in such cases.

Abstract Prolactinomas comprise half of all pituitary adenomas. This study explores the significance of measuring intraoperative (IO) prolactin (PRL) levels in guiding surgical decision-making and predicting operative success. Retrospective cohort study design of consecutive patients with prolactinomas who underwent transsphenoidal resection from June 2021 to May 2023. IO PRL was measured after tumor resection was completed. Remission was defined as normalization of PRL levels during follow-up without medication. Outcomes included factors associated with remission, utilizing significance thresholds at p < 0.05. Thirteen patients were included with a 5.3-month median follow-up (range, 3–15 months). Most of the tumors were microadenomas (61%), with a median preoperative PRL level of 116 ng/mL (range, 25–471). Gross total resection was achieved in 69% of patients, all of whom attained remission. The median IO PRL was 19.8 ng/mL (range, 1–329), the postoperative day 1 PRL of 3.6 ng/mL (range, 1–203), and the latest PRL at 9.3 ng/mL (range, 1–137). A ≥40% decline in IO PRL from baseline was identified as the optimal cutoff for predicting biochemical remission, with 89% sensitivity, 75% specificity, and 85% accuracy. Monitoring PRL levels intraoperatively may be a useful biomarker aiding surgeon's assessment of the extent of tumor resection and guide surgical decision-making. Further refinement of the immunoassay assay and clinical testing with more extensive prospective studies are needed.

Abstract Background While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown. Methods Aptamer-based proteomics was performed on 147 CSF samples from 74 patients; 71 of whom had grade 2–4 astrocytomas or grade 2–3 oligodendrogliomas. This included pre- versus post-resection intracranial CSF samples obtained at early (1–16 days; n = 20 patients) or delayed (86–153 days; n = 11 patients) time points for patients with glioma. Paired lumbar versus intracranial glioma CSF samples were also obtained (n = 14 patients). Results Significant differences were identified in the CSF proteome between lumbar, subarachnoid, and ventricular CSF in patients with gliomas. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome, with distinct sets of proteins present at different time points since resection. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, such as bevacizumab and immunotherapies. Conclusions The intracranial glioma CSF proteome serves as a rich and dynamic reservoir of potential biomarkers that can be used to evaluate the effects of resection and other therapies over time. All data within this study, including detailed individual clinical annotations, are shared as a resource for the neuro-oncology community to collectively address these unanswered questions and further understand glioma biology through CSF proteomics.

Abstract There are limited treatment options for individuals with drug‐resistant idiopathic generalized epilepsy (IGE). Small, limited case series suggest that centromedian thalamus deep brain stimulation (CM‐DBS) may be an effective treatment option. The optimal CM‐DBS target for IGE is underexamined. Here, we present a retrospective analysis of CM‐DBS targeting and efficacy for five patients with drug‐resistant IGE. Volume of tissue activated (VTA) overlap with CM nucleus was performed using an open‐source toolbox. Median follow‐up time was 13 months. Median convulsive seizure frequency reduction was 66%. One patient had only absence seizures, with >99% reduction in absence seizure frequency. Four patients had electrode contacts positioned within the CM nucleus target, all of whom had >50% reduction in primary semiology seizure, with 85% median seizure reduction ( p = .004, paired‐sample t test). Volumetric “sweet‐spot” mapping revealed that best outcomes were correlated with stimulation of the middle ventral CM nucleus. Connectivity strength between the sweet‐spot region and central peri‐Rolandic cortex was increased significantly relative to other cortical regions ( p = 8.6 × 10 −4 , Mann–Whitney U test). Our findings indicate that CM‐DBS can be an effective treatment for patients with IGE, highlight the importance of accurate targeting and targeting analysis, and within the context of prior work, suggest that ideal CM‐DBS targets may be syndrome specific.

BACKGROUND AND OBJECTIVES: Access to the amygdala and hippocampus (A/H) is complex. To address the limitations and invasiveness of traditional approaches, including the Transsylvian, Subtemporal, and Supracerebellar infratentorial approaches, we developed the suprapetrous infratemporal (SPIT) approach. This study describes the nuances of this approach in both cadaveric studies and clinical cases. METHODS: Three unilateral exposures were performed using microscopic and endoscopic methodologies in the SPIT approach. After cadaveric investigation, this approach was successfully implemented in representative clinical cases. RESULTS: The SPIT approach enabled direct access to the inferior A/H, circumventing the requirement for temporal lobe retraction and detachment of the temporal lobe from the dura through a subtemporal route by drilling the upper part of the mastoid, consequently mitigating tension on the vein of Labbé. This enabled a bottom-up view because one would gain with a zygomatic osteotomy and forward projection like a mini-posterior petrosal view by using a transmastoid view, without cutting down the zygomatic arch and opening the dura subtemporally, limiting patient pain and preventing case comorbidity. The SPIT approach was performed in 2 cases of mesial temporal cavernoma presenting with seizures. The lesion was visualized intraoperatively and was successfully removed in these cases. The postoperative course was excellent with no complications, and gross total resection was radiographically confirmed with Engel Class 1a seizure freedom. CONCLUSION: The SPIT approach is a complementary approach for inferior A/H disease, combining the combined middle fossa approach modified for intradural pathology. Limited drilling of the upper aspect of the mastoid with a medial dural opening at the level of the arcuate eminence provides a direct trajectory with minimal brain retraction. Additional research encompassing a larger patient cohort and extended follow-up periods is required to substantiate the advantages of SPIT in the management of inferior A/H lesions.