Citations

AbstractObjectiveNeck metastases are a poor prognostic factor in olfactory neuroblastoma (ONB). Pathologic dural invasion (pathDI) may increase the risk of neck metastases due to invasion of dural lymphatics. We aim to evaluate the prognostic value of pathDI in predicting rates of neck metastases and recurrence using a large, multicenter database of ONB patients.Data sourcesRetrospective review of a prospective, multicenter database of electronic health records of all patients who presented with ONB between 2005 and 2021 at nine tertiary academic care centers within North America.Review methodsClinicopathologic features including modified Kadish staging systems, margin status, treatment modalities, Hyams grading, follow‐up time, and survival.ResultsOf 258 ONB patients, 189 patients met the inclusion criteria. The 10‐year neck recurrence‐free survival (neck‐RFS) rates were 85.7% (75.6‒97.3) and 61.8% (47.9‒79.8) for patients without and with pathDI, respectively (p = 0.018). Time‐to‐event multivariable regression analysis found pathDI to have an odds ratios of 9.7 (95% confidence interval [CI] 1.2–80.4, p = 0.04) for neck‐RFS and 9.5 for RFS at any site (95% CI 1.1–83.3, p = 0.04).ConclusionIn multivariable analysis, the presence of pathDI appears to be the strongest predictor of neck recurrence and recurrence at any site. Future studies exploring the benefit of elective neck dissection or radiation for patients with pathDI may impact disease management.

Abstract While serial sampling of glioma tissue is rarely performed before recurrence, cerebrospinal fluid (CSF) can be acquired serially to evaluate candidate monitoring and pharmacodynamic biomarkers in patients with gliomas. However, the impact of key variables to consider in longitudinal CSF, including anatomical location and post-surgical changes, remains unknown. To that end, pre- versus post-resection intracranial CSF samples from patients with gliomas were obtained at early (1-16 days; n=20) or delayed (86-153 days; n=11) timepoints, as well as lumbar-versus-intracranial glioma CSF samples (n=14). Using aptamer-based proteomics, we identified significant differences in the glioma CSF proteome between lumbar, subarachnoid, and ventricular CSF. Indeed, intracranial CSF in paired lumbar/intracranial samples had nearly 1600 unique aptamers, regardless of which intracranial location was compared to the paired lumbar CSF, including in enrichment style analyses that evaluated the overlap between protein states. Importantly, resection had a significant, evolving longitudinal impact on the CSF proteome, with subsets of proteins associated with early versus delayed post-resection changes, many of which were enriched for inflammatory-related pathways. Interestingly, despite increased contamination from surgical debris, enrichment for plasma-associated proteins decreased with resection (FDR: 0.000), suggesting that a portion of the baseline glioma panel could be derived from plasma-originating analytes due to blood-brain barrier disruption. Despite these challenges, our data still revealed preliminary candidate monitoring biomarkers, such as brevican, that increased with progression (example patient: fold-change of 3.58x and 2.08x through lomustine and bevacizumab, respectively), but not pseudoprogression (Fold change less than 1.5). Serial intracranial CSF samples suggested the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, including bevacizumab and pembrolizumab. In conclusion, our available data to date suggest that the intracranial glioma CSF proteome provides an abundant and evolving source of candidate biomarkers to longitudinally discern the impact of resection and systemic treatments.

Abstract BACKGROUND Pituitary adenomas are often effectively managed with medical therapy, surgery, and radiation therapy. However, up to 15% of pituitary neoplasms exhibit rapid growth, invasive behavior, or, rarely, metastasize despite optimal standard treatments. Temozolomide is associated with a survival benefit for patients with these aggressive pituitary tumors. METHODS We present a case series of 8 patients with an aggressive pituitary tumor (APT) or pituitary carcinoma (PC) treated with temozolomide. RESULTS Eight patients (3 female, median age at diagnosis 44) with APT (n=6) or PC (n=2) were treated. A variety of pituitary tumor types were represented (1 prolactinoma, 5 corticotroph adenomas, 1 gonadotroph adenoma, 1 thyrotropinoma). Prior to temozolomide initiation, patients underwent a median 5 treatments including medical management (n=4), surgery (n=7), radiation therapy (n=7). Temozolomide was started at median 3.5 recurrence. Median treatment duration was 6 cycles (n=6, 150-200 mg/m2 days 1-5, 28-day cycles; n=1, 75 mg/m2, days 1-21, 28-day cycles). Seven patients experienced progression after temozolomide treatment, median progression-free survival (PFS) was 4 months. One patient remains on treatment, progression-free at 5 months. MGMT methylation status was assessed for 3 tumors. Among 2 patients with MGMT promoter methylated tumors, PFS was 4 months for one patient, the other remains on treatment. For one patient with MGMT promoter unmethylated corticotroph adenoma, PFS was 9 months. No ≥ grade 4 toxicities were noted. Most common toxicities were nausea (n=5), thrombocytopenia (n=3), and fatigue (n=2). CONCLUSION In this group of heavily pretreated patients, temozolomide monotherapy was well-tolerated and associated with median PFS of 4 months. Interestingly, PC patients had longer PFS at 9 months and 24 months. Our findings support use of single-agent temozolomide chemotherapy for patients with APT/PC, but further prospective analysis is needed to identify patients more likely to benefit from treatment and optimal timing of chemotherapy initiation.

OBJECTIVE Imaging surveillance with serial MRI, or a "wait-and-scan" approach, is a management option for patients with small or medium-sized vestibular schwannomas (VSs). Prior publications have indicated no distinct quality of life advantage to upfront treatment compared with initial wait-and-scan management. However, imaging surveillance is dependent on patient adherence to follow-up. In this study, the authors aimed to identify rates and predictors of patient loss to follow-up during wait-and-scan management of sporadic VS. METHODS A single-center study was conducted including all patients from 2013 to 2018 who had undergone upfront imaging surveillance of sporadic VS. Patient data were retrospectively obtained from the electronic medical record. Outcomes of interest included loss to follow-up unrelated to death and inconsistent adherence to imaging surveillance recommendations. Logistic regression analyses were conducted to evaluate factors associated with loss to follow-up. RESULTS Over a 6-year study period, 270 patients underwent initial imaging surveillance of a sporadic VS. The median tumor diameter was 8.6 mm (range 1–28.9 mm). At the time of censoring, 106 patients (39.3%) had received treatment, 157 (58.1%) had been advised to continue follow-up, and 7 (2.6%) had died of non–VS-related causes. In total, 73 patients (27.0%) were completely lost to follow-up prior to the first treatment or death. Additionally, 60 patients (22.2%) missed at least 1 MRI follow-up or imaging follow-up was delayed by more than 1 year. Multivariable logistic regression identified an out-of-state residence (OR 3.05, 95% CI 1.58–5.89, p = 0.0009) and a smaller tumor size (unit OR per 1-mm increase in size, OR 0.88, 95% CI 0.83–0.95, p = 0.0006) to be associated with loss to follow-up. Patients living ≥ 350 miles from the hospital or with tumors ≤ 3 mm at the time of initial clinic evaluation were most likely to be lost to follow-up. Only a smaller tumor size was associated with an increased risk of inconsistent imaging follow-up (unit OR per 1-mm increase in size, OR 0.92, 95% CI 0.87–0.98, p = 0.007). CONCLUSIONS Patients undergoing imaging surveillance of VS are at risk for loss to follow-up and inconsistent imaging surveillance. Patients with smaller tumors or those living farther away from the treating institution are at highest risk for being lost to follow-up.

Abstract Disclosure: R. Sandooja: None. J. Saini: None. R. Gregg garcia: None. C. Zhang: None. S. Achenbach: None. E. Atkinson: None. J. Van Gompel: None. W.F. Young: None. I. Bancos: None. Hydrocortisone vs Prednisone During Recovery Following Surgical Cure for Endogenous Hypercortisolism: A Longitudinal Observational Study Introduction: Glucocorticoid withdrawal syndrome (GWS) is a constellation of symptoms that occurs after successful surgery for endogenous hypercortisolism. The objective of this study is to compare hydrocortisone versus prednisone on GWS symptoms. Methods: Study design: Single-center prospective longitudinal cohort study, 2019-2023. Participants: Adults with Cushing syndrome (CS) and mild autonomous cortisol secretion (MACS) with post-operative adrenal insufficiency treated with either hydrocortisone or prednisone for glucocorticoid replacement. Measurements: Clinical and biochemical severity scores for hypercortisolism were calculated. Quality of life (QOL) was assessed using Short Form-36 (SF-36) and Cushing QOL surveys. GWS was assessed using weekly AddiQoL surveys for the first 12 weeks after surgery. Results: Of 131 patients, 91 (69%) patients were treated with hydrocortisone and 40 (31%) with prednisone. No differences in age (median age 51 vs 53 years, P=0.62), sex (84 vs 85% women, P=0.83), etiology of hypercortisolism (ACTH-dependent: 44% vs 48%, P=0.26), clinical severity of hypercortisolism (median score 13 vs 12, P=0.97), or biochemical severity of hypercortisolism (median score of 6 in both, P=0.31) were noted between groups. When assessed at 4-, 8-, and 12-weeks post-surgery, the prevalence and trajectory of symptoms (fatigue, myalgias/arthralgias, sleep, headaches, nausea, weakness) were similar in patients treated with hydrocortisone and prednisone (P>0.05 for all). However, patients treated with prednisone were less likely to report mood changes (8.5% vs 20.9%, P= 0.004) compared to those treated with hydrocortisone. When compared to the presurgical baseline, the overall Cushing QOL score 12 weeks post-surgery improved in both groups (mean delta 8.9 vs 13.0, P=0.21). No differences in the hydrocortisone vs prednisone treatment were found in the SF-36 physical component score (mean delta of -1.7 vs 0.3, P=0.23) and SF-36 mental component score (mean delta 2.3 vs 5.0, P=0.22). Using multivariable analysis, age (estimate 0.22, P= 0.005), clinical severity score (estimate -0.73, P<0.001), female sex (estimate -5.45, P= 0.046) but not glucocorticoid type (estimate -0.06, P=0.98) were associated with the overall GWS symptom burden at 12 weeks. Conclusion: Use of prednisone after curative surgery for hypercortisolism was associated with lower mood symptoms, but did not impact the overall severity or trajectory of other symptoms associated with GWS. Baseline clinical severity of hypercortisolism, age, and female sex were associated with GWS burden. Presentation: 6/1/2024

BACKGROUND AND OBJECTIVES: Corpus callosotomy is an effective procedure approach for treating medication-resistant drop seizures, which pose a significant challenge in patients with epilepsy. Laser interstitial thermal therapy offers an alternative to open surgery for performing corpus callosotomy that may limit approach-related comorbidities. Practices vary regarding the number of laser filaments used and staging; outcome data for pediatric patients remain relatively limited. METHODS: We illustrate a set of 4 standardized trajectories for performing MRI-guided stereotactic laser corpus callosotomy (SLCC). For this retrospective cohort study in a pediatric neurosurgery practice, the medical records and imaging were reviewed for 10 consecutive patients who had medication-refractory drop seizures and underwent SLCC. Data collected and analyzed included patient and epilepsy characteristics, procedural details, surgical approaches, and clinical follow-up results. RESULTS: Over 2 years, complete, single-stage SLCC was performed in 8 patients, and posterior completion SLCC was performed in 2 patients who had previously had open anterior corpus callosotomy. Four laser fibers were used in four-eighth complete SLCC, and 3 fibers were used in four-eighth complete SLCC. Seven of 10 patients were discharged from the hospital on postoperative day 1, with only 1 requiring a maximum stay of 6 days. Five of 9 evaluable patients reported no drop seizures at the last clinical follow-up. In the other 4 patients, 1 experienced them only rarely, another experienced less than 25% preoperative frequency, and the remaining 2 had less than a 50% improvement. In addition, improvement in other seizure types exceeded 50% in 8 of 9 patients. Notably, no perioperative or postoperative complications were observed, nor were there any sustained neurological deficits reported. CONCLUSION: Complete SLCC can be safely and effectively performed in pediatric patients. It is comparable in effectiveness with open surgery but has lower complication rates and shorter hospitalization.

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.

AbstractObjectiveNeuromodulation is a viable option for patients with drug‐resistant epilepsies. We reviewed the management of patients with two deep brain neurostimulators. In addition, patients implanted with a device targeting the centromedian‐parafascicular (CM‐Pf) nuclear complex supplements this report to provide an illustrative case to implantation and programming a patient with three active devices.MethodsA narrative review using PubMed and Embase identified patients with drug‐resistant epilepsy implanted with more than one neurostimulator was performed. Combinations of vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS) were identified. We provide a background of a newly reported case of an adult with a triple implant eventually responding to CM‐Pf DBS as the third implant following suboptimal benefit from VNS and RNS.ResultsIn review of the literature, dual‐device therapy is increasing in reports of use with combinations of VNS, RNS, and DBS to treat patients with drug‐resistant epilepsy. We review dual‐device implants with thalamic DBS device combinations, functional neural networks, and programming patients with dual devices. CM‐Pf is a new target for DBS and has shown a variable response in focal epilepsy. We report the unique case of 28‐year‐old male with drug‐resistant focal epilepsy who experienced a 75% seizure reduction with CM‐Pf DBS as his third device after suboptimal responses to VNS and RNS. After 9 months, he also experienced seizure freedom from recurrent focal to bilateral tonic–clonic seizures. No medical or surgical complications or safety issues were encountered.ConclusionWe demonstrate safety and feasibility in an adult combining active VNS, RNS, and CM‐Pf DBS. Patients with dual‐device therapy who experience a suboptimal response to initial device use at optimized settings should not be considered a neuromodulation “failure.” Strategies to combine devices require a working knowledge of brain networks.

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.