Decoding the clinical effects of low-grade glioma-induced cortical excitability.

OBJECTIVE: Patients with low-grade glioma (LGG) in eloquent regions often present with seizures, and findings on detailed neuropsychological testing are often abnormal. This study evaluated the association between cortical excitability, seizures, and cognitive function in patients with LGG. METHODS: LGG patients who underwent transcranial magnetic stimulation (TMS) from January 2021 to December 2022 were studied. Cortical excitability was measured using the resting motor thresholds (RMTs) of the upper and lower extremities. Early postoperative seizures served as the seizure endpoint. Neuropsychological assessment was completed prior to surgery contemporaneous with the TMS studies. RESULTS: A total of 31 patients were analyzed for seizure outcome. Median (interquartile range [IQR]) upper-extremity RMT was 39% (34%-46%) of maximum stimulator output, and the median (IQR) lower-extremity RMT was 69% (51%-79%). Lower-extremity RMT was higher in patients with early postoperative seizures, especially in those with motor region tumors (p = 0.02); however, RMT was not associated with seizures at presentation or long-term seizure control. A total of 26 patients completed neuropsychological assessment. There were significant negative correlations between upper-extremity RMT and psychomotor processing speed (Wechsler Adult Intelligence Scale-Fourth Edition [WAIS-IV] Processing Speed Index r = -0.42, p = 0.031; WAIS-IV Coding r = -0.41, p = 0.036; WAIS-IV Symbol Search r = -0.39, p = 0.048), executive function (Trail Making Test Part B r = -0.41, p = 0.036), and hand dexterity (Grooved Pegboard Test r = -0.50, p = 0.047). CONCLUSIONS: RMT was positively correlated with early postoperative seizure risk and negatively correlated with psychomotor processing speed, executive function, and hand dexterity. These findings support the theory of local and regional resting oscillatory network dysfunction from a glioma-brain network.

Lateral ventricle subependymoma resected with a transcallosal approach: illustrative case.

BACKGROUND: Subependymomas are World Health Organization grade I tumors, and 30% occur in the lateral ventricles. Surgery is the mainstay of treatment, and the transcallosal or transcortical/transsulcal approaches are preferred for those tumors occurring near the foramen of Monro or atrium. Visualization, proximity to the fornix and basal ganglia, hydrocephalus, and brain retraction during surgery make these operations challenging. The authors present the case of a 65-year-old male with a subependymoma located in the left lateral ventricle. The tumor was completely resected using an interhemispheric/transcallosal approach. OBSERVATIONS: The authors analyze the anatomopathological features of subependymoma, along with the clinical behavior and therapeutic options. The authors discuss in detail the advantages and disadvantages of the interhemispheric/transcallosal approach for resection of these tumors. LESSONS: Subependymomas are slow-growing lesions with an indolent yet complicated course making surgical removal challenging yet feasible using the correct techniques. The interhemispheric transcallosal approach offers an excellent route for the resection of large subependymomas, but there is still a significant risk for postoperative complications.

Postoperative Serum Cortisol and Cushing Disease Recurrence in Patients With Corticotroph Adenomas.

CONTEXT: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized. OBJECTIVE: To analyze postoperative serum cortisol and recurrence rates in Cushing disease. METHODS: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables. RESULTS: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001). CONCLUSION: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.

Vascular anomalies in patients with growth hormone-secreting pituitary adenomas: illustrative case report and systematic review of the literature.

PURPOSE: Endonasal resection is the first-line treatment for patients harboring growth hormone (GH)-secreting pituitary adenomas. The complexity of the parasellar neurovascular structures makes pre-operative diagnostic imaging essential to understanding the anatomy of this region. We aimed to describe vascular anomalies in acromegalic patients and emphasize their relevance for surgery and preoperative planning. METHODS: A systematic review following the PRISMA statement was performed in July 2021. RESULTS: Thirty-three studies were evaluated. Elevated GH and insulin-like growth factor-1 (IGF-1) levels are linked to the occurrence of cardiovascular risk factors. This is attributed to endothelial dysfunction, mainly caused by changes in flow-mediated dilatation (FMD), which is probably the main cause of vascular anomalies in acromegaly. The occurrence of protrusions of the internal carotid artery (ICA) (35-53%), a narrow intercarotid distance, and an asymmetrical course was described. In 13-18% of acromegalic patients, the presence of an intracerebral aneurysm could be reported (incidence in the general population:0.8-1.3%). The selected studies were however performed with a small patient sample (range:1-257). We present a case report of a 57y/o male patient with anomalies of the ICA ("kissing carotid arteries") harboring a GH-secreting adenoma, which was resected via an endoscopic endonasal approach. CONCLUSIONS: There is an association between acromegaly and endothelial dysfunction, which increases cardiovascular risk factors and vascular anomalies. Preoperative vascular imaging, e.g., CT angiography, should be implemented as a standard to identify patients at risk and estimate surgical morbidity. However, no evidence-based recommendations exist so far, so future studies are necessary.

Tumor sound, auditory cues, and tissue pathology in glioma surgery: a proof-of-concept study.

OBJECTIVE: Visual, tactile, and auditory cues are used during surgery to differentiate tissue type. Auditory cues in glioma surgery have not been studied previously. The objectives of this study were 1) to evaluate the feasibility of recording sound generated by the suction device during glioma surgery in matched tissue samples, and 2) to characterize the acoustic variation that occurs in different tissue samples. METHODS: This was a prospective observational proof-of-concept study. Recordings were attempted in 20 patients in order meet the accrual target of 10 patients with matched sound and tissue data. For each patient, three 30- to 60-second recordings were made at these sites: normal white matter, infiltrative margin, and tumor. Tissue samples at each site were then reviewed by experienced neuropathologists, and agreement with surgical identification was estimated with the kappa statistic. Acoustic parameters were characterized for each sample. RESULTS: Data from 20 patients were analyzed. Patient-related or technical issues resulted in missing data for 10 patients, but the final 10 patients had both audio and tissue data for analysis. Among all tissue samples, fair agreement was observed between surgeon identification and actual pathology (κ = 0.24, standard error 0.096, p = 0.006). Acoustic data suggested that 1) the acoustic stimulus is broadband, 2) acoustic features are somewhat consistent within cases, 3) high-entropy values indicate irregularity of sound over time, and 4) bimodal pitch distributions could differentially reflect cues of interest. CONCLUSIONS: This study supports the feasibility of collecting intraoperative data on acoustic features during glioma surgery, and it provides an example of how an analysis could be performed to compare different types of tissues.

Ergonomics in Endoscopic Transsphenoidal Surgery: A Survey of the North American Skull Base Society.

Objective Different surgical set-ups for endoscopic transsphenoidal surgery (ETS) have been described, but studies on their ergonomics are limited. The aim of this article is to describe present trends in the ergonomics of ETS. Design and Participants A 33-question, web-based survey was sent to North American Skull Base Society members in 2018 and 116 responded to it (16% of all members). Most respondents were from North America (76%), in academic practice (87%), and neurosurgeons (65%); they had more than 5 years of experience in ETS (73%), had received specific training (66%), and performed at least 5 procedures/mo (55%). Results Mean reported time for standard and complex procedures were 3.7 and 6.3 hours, respectively. The patient's body is usually positioned in a straight, supine position (84%); the head is in a neutral position (46%) or rotated to the side (38%). Most surgeons perform a binostril technique, work with a partner (95%), and operate standing (94%), holding suction (89%) and dissector (83%); sometimes the endoscope is held by the primary surgeon (22-24%). The second surgeon usually holds the endoscope (72%) and irrigation (42%). During tumor removal most surgeons stand on the same side (65-66%). Many respondents report strain at the dorsolumbar (50%) or cervical (26%) level. Almost one-third of surgeons incorporate a pause during surgery to stretch, and approximately half exercise to be fit for surgery; 16% had sought medical attention for ergonomic-related symptoms. Conclusion Most respondents value ergonomics in ETS. The variability in surgical set-ups and the relatively high report of complaints underline the need for further studies to optimize ergonomics in ETS.

A Surgical Perspective on the Association between Cystic Lesions of the Pineal Gland (Descartes' Seat of the Soul) and the Pituitary (the Master Gland).

Introduction Rene Descartes (1596-1650), the famous philosopher and scientist, identified the pineal gland as the only cerebral structure not represented bilaterally, the "seat of the soul"; and the source of rational thought. Pineal cysts (PCs) are often incidentally identified in MRI studies, with a reported prevalence of 1 to 4.3%. Rathke cleft cysts (RCCs) are pituitary lesions accounting for <1% of intracranial masses. There are scant data in the literature addressing any association between these two midline cystic lesions. Methods We reviewed the medical records of patients presenting at our institution from April 2008 through February 2020, whose records indicated a diagnosis of RCC, and those whose records included pineal lesions. Our objective was to evaluate the association between these two midline lesions. Brain MRI studies were reviewed for the presence of PCs; only patients with PCs that measured ≥5 mm in diameter were included. Results We identified 116 patients with RCCs, and 34 patients with PCs, treated from April 2008 through February 2020. Among the RCC group, 14/116 patients (12%) had PCs. Among the PC group, 3/34 patients (8.8%) had RCCs. Overall, 17 patients (11.3%) had concomitant RCCs and PCs. The mean maximal diameter of the PCs was 7.5 mm (range = 5-17 mm), whereas the mean maximal diameter of RCCs was 13 mm (range = 5-40 mm). Conclusion The incidental diagnosis of cystic lesions of the pineal and pituitary gland is increasingly reported, primarily because of advances in current diagnostic modalities. Our data demonstrated no clear consensual association between pineal and pituitary cysts.

Characterization of a paradoxical post-operative increase in serum cortisol in Cushing disease.

PURPOSE: In Cushing disease, early post-operative serum cortisol fluctuations have not been adequately characterized, and their association with initial remission and recurrence is unclear. METHODS: A retrospective cohort study of patients with Cushing disease was conducted at two institutions. A "riser" was defined a priori as a paradoxical increase in serum cortisol with an immediate incremental increase in serum cortisol over three consecutive cortisol draws separated by roughly 6-h (definition 1). Post hoc analyses used a definition of two consecutive increases (definition 2). Risers were compared to non-risers for initial remission and time-to-recurrence. RESULTS: A total of 505 patients with Cushing disease were screened, and 469 had adequate data for group assignment. Analysis of post-operative cortisol showed a subgroup of "risers" with a frequency of 3.6% for definition 1 and 42.6% for definition 2. In these patients, cortisol levels were significantly higher until approximately 36 h post-operatively, and cortisol had a significantly longer mean serum half-life. In the post hoc analysis, definition 2 risers had a lower remission rate compared to non-risers (162/196, 82.7%, versus 243/264, 92.0%) with an odds ratio of 0.41 (0.23-0.73; p = 0.003). For both definitions, recurrence was similar between groups. CONCLUSIONS: We found that almost half of Cushing disease patients experienced a temporary increase in serum cortisol level during the early post-operative period. Serum cortisol half-life was longer, and the remission rates were lower, however, recurrence rates were similar to non-risers.

Cyst Type Differentiates Rathke Cleft Cysts From Cystic Pituitary Adenomas.

PURPOSE: A classification system for cystic sellar lesions does not exist. We propose a novel classification scheme for these lesions based on the heterogeneity of the cyst wall/contents and the presence of a solid component on imaging. METHODS: We retrospectively reviewed 205 patients' medical records (2008-2020) who underwent primary surgery for a cystic sellar lesion. Cysts were classified a priori into 1 of 4 cyst types based on the heterogeneity of the cyst wall/contents and the presence of a solid component imaging. There was high interrater reliability. Univariable and multivariable models were used to estimate the ability of cyst type to predict the two most common diagnoses: Rathke cleft cyst (RCC) and cystic pituitary adenoma. RESULTS: The frequencies of RCC and cystic pituitary adenoma in our cohort were 45.4% and 36.4%, respectively. Non-neoplastic lesions (e.g., arachnoid cysts and RCC) were more likely to be Type 1 or 2, whereas cystic neoplasms (e.g., pituitary adenomas and craniopharyngiomas) were more likely to be Type 3 or 4 (p<0.0001). Higher cyst types, compared to Type 1, had higher odds of being cystic pituitary adenomas compared to RCCs (OR: 23.7, p=0.033, and 342.6, p <0.0001, for Types 2 and 4, respectively). Lesions with a fluid-fluid level on preoperative MRI also had higher odds of being pituitary adenomas (OR: 12.7; p=0.023). Cystic pituitary adenomas were more common in patients with obesity (OR: 5.0, p=0.003) or symptomatic hyperprolactinemia (OR: 11.5; p<0.001, respectively). The multivariable model had a positive predictive value of 82.2% and negative predictive value of 86.4%. CONCLUSION: When applied to the diagnosis of RCC versus cystic pituitary adenoma, higher cystic lesion types (Type 2 & 4), presence of fluid-fluid level, symptomatic hyperprolactinemia, and obesity were predictors of cystic pituitary adenoma. Further validation is needed, but this classification scheme may prove to be a useful tool for the management of patients with common sellar pathology.

Professor Rathke's gift to neurosurgery: the cyst, its diagnosis, surgical management, and outcomes.

PURPOSE: Rathke cleft cysts (RCC) are a target for transsphenoidal surgery when symptomatic; however, the surgical techniques and outcomes continue to be of interest. Our goal is to highlight nuances in diagnosis, surgical philosophy and techniques, and outcomes. METHODS: We retrospectively reviewed a single surgeon experience in a contemporary series of RCC from April 2008 through December 2019. The clinical presentation, radiographic studies, intraoperative findings, histopathological diagnosis, postoperative complications, and outcome data were recorded and analyzed. RESULTS: A total of 131 endoscopic endonasal operations were performed on 116 patients (30 male, 86 female), with an average age of 39 years. We identified 102 patients without prior surgery, and 14 patients with prior surgery elsewhere. Postoperative complications included transient diabetes insipidus (DI) (n = 23, 20%), permanent DI (n = 5, 4%), SIADH (n = 6, 5%), epistaxis (n = 6, 5%), postoperative infection (n = 3, 2.5%), postoperative CSF leak (n = 1, < 1%), intrasellar hematoma (n = 1, < 1%), and stroke (n = 1, < 1%). Visual improvement was observed in 74% (n = 31/42) of patients presenting with visual loss, and headache improvement in 86% (n = 80/93). Overall, the recurrence rate in our cohort was 11%, with a lower recurrence rate seen in males (p = 0.02). The median follow-up duration was 15.2 months (interquartile range 1.7-52.3) CONCLUSION: Our results reflect the philosophy of a conservative surgical approach, designed to preserve normal pituitary function, and avoid DI, while achieving the maximal feasible resection. Evacuation of the cyst contents and meticulous sampling of the cyst wall when possible for histopathological diagnosis are crucial. The postoperative relief of symptoms and signs is gratifying, as are the overall rates of recurrence and outcomes.

Predictors of postoperative biochemical remission in acromegaly.

PURPOSE: Acromegaly is a rare neuroendocrine condition that can lead to significant morbidity. Despite China's vast population size, studies on acromegaly remain sparse. This study aimed to investigate the clinical characteristics and predictors of biochemical remission after surgery for acromegaly using the China Acromegaly Patient Association (CAPA) database. METHODS: A retrospective nationwide study was conducted using patient-reported data from CAPA database between 1998 and 2018. The principal component analysis (PCA) and logistic regression analysis were employed to determine independent predictors of biochemical remission at 3 months in patients after surgery. RESULTS: Of the 546 surgical cases (mean age: 36.8 years; 59.5% females), macroadenomas and invasive tumors (Knosp score 3-4) were 83.9% and 64.1%, respectively. Ninety-five percent of patients were treated with endonasal surgery and 36.8% exhibited biochemical remission at 3-months postoperatively. The following independent predictors of biochemical remission were identified: preoperative growth hormone (GH) levels between 12 and 28 µg/L [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.37-0.92; p = 0.021], preoperative GH levels > 28 µg/L (OR = 0.55; 95% CI, 0.34-0.88; p = 0.013), macroadenoma (OR = 0.56; 95% CI, 0.32-0.96; p = 0.034), giant adenomas (OR = 0.14; 95% CI, 0.05-0.38; p < 0.001), Knosp score 3-4 (OR = 0.37; 95% CI, 0.24-0.57; p < 0.001), and preoperative medication usage (OR = 2.32; 95% CI, 1.46-3.70; p < 0.001). CONCLUSIONS: In this nationwide study spanning over two decades, we highlight that higher preoperative GH levels, large tumor size, and greater extent of tumor invasiveness are associated with a lower likelihood of biochemical remission at 3-months after surgery, while preoperative medical therapy increases the chance of remission.

Rabbit Elastase Aneurysm: Imaging and Histology Correlates for Inflammation and Healing.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage remains a devastating event with poorly understood pathophysiology. Previous studies have suggested that aneurysm wall inflammation may play a part in the development and potential rupture of aneurysms. The rabbit elastase aneurysm model is a well-established model, which produces aneurysms closely mimicking human cerebral aneurysms in flow dynamics and histopathology. The primary aim of this study was to correlate inflammatory changes after aneurysm formation using sequential vessel wall imaging with histopathologic analysis. A secondary aim was to evaluate the potential effect of gender and anti-inflammatory treatment with aspirin on this inflammatory response. METHODS: Twenty-seven New Zealand rabbits underwent surgery to create an aneurysm using elastase infusion at the right common carotid artery origin. Vessel wall imaging and histopathologic analysis was obtained at different time points after aneurysm creation. The rabbits were also randomized by gender and to treatment groups with or without aspirin. RESULTS: Histopathologic analysis revealed 3 distinct phases after aneurysm formation. These phases were an initial inflammatory phase, followed by a regeneration phase, and finally a connective tissue deposition phase. Vessel wall imaging demonstrated 2 distinct imaging patterns. No appreciable differences were seen in histology or imaging when comparing gender or treatment with aspirin. CONCLUSIONS: Inflammatory changes induced by the rabbit elastase aneurysm model can be correlated with histopathologic findings and observed on noninvasive vessel wall imaging. This may provide a method to study the inflammatory pathway as it pertains to aneurysmal development and subsequent rupture.

Gender Disparities in Surgical Treatment of Axis Fractures in Older Adults.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Gender appears to play in important role in surgical outcomes following acute cervical spine trauma, with current literature suggesting males have a significantly higher mortality following spine surgery. However, no well-adjusted population-based studies of gender disparities in incidence and outcomes of spine surgery following acute traumatic axis injuries exist to our knowledge. We hypothesized that females would receive surgery less often than males, but males would have a higher 1-year mortality following isolated traumatic axis fractures. METHODS: We performed a retrospective cohort study using Medicare claims data that identified US citizens aged 65 and older with ICD-9 (International Classification of Diseases, Ninth Revision) code diagnosis corresponding to isolated acute traumatic axis fracture between 2007 and 2014. Our primary outcome was defined as cumulative incidence of surgical treatment, and our secondary outcome was 1-year mortality. Propensity weighted analysis was performed to balance covariates between genders. Our institutional review board approved the study (IRB #16-0533). RESULTS: There was no difference in incidence of surgery between males and females following acute isolated traumatic axis fractures (7.4 and 7.5 per 100 fractures, respectively). Males had significantly higher 1-year weighted mortality overall (41.7 and 28.9 per 100 fractures, respectively, P < .001). CONCLUSION: Our well-adjusted data suggest there was no significant gender disparity in incidence of surgical treatment over the study period. The data also support previous observations that males have worse outcomes in comparison to females in the setting of axis fractures and spinal trauma regardless of surgical intervention.

Postoperative Day 1 Morning Cortisol Value as a Biomarker to Predict Long-term Remission of Cushing Disease.

CONTEXT: Recurrence of Cushing disease (CD) can occur even decades after surgery. Biomarkers to predict recurrence of CD after surgery have been studied but are inconclusive. OBJECTIVE: The aim of our study was to identify specific biomarkers that can predict long-term remission after neurosurgery. DESIGN: Identification of specific biomarkers to predict long-term remission of CD was performed by logistic regression analysis followed by Kaplan-Meier survival analysis, using recurrence as the dependent variable. SETTING: A total of 260 patients with CD identified from our institutional research patient data registry search tool and from patients who presented to our longitudinal multidisciplinary clinic between May 2008 and May 2018 underwent statistical analysis. INTERVENTIONS: Data on clinical features, neuro-imaging study, pathology, biochemistry, and treatments were collected by reviewing digital chart records. MAIN OUTCOME MEASURE: Postoperative cortisol as a biomarker to predict long-term remission after surgical treatment for CD. RESULTS: By logistic regression analysis, postoperative day 1 (POD1) morning (5-10 am) serum cortisol, female sex, and proliferative index had significant association with CD recurrence (odds ratio [OR] = 1.025, 95% CI: 1.002-1.048, P = .032). In contrast, the postoperative nadir cortisol (OR = 1.081, 95% CI: 0.989-1.181, P = .086), urinary free cortisol (OR = 1.032, 95% CI: 0.994-1.07, P = .098), and late night salivary cortisol (OR = 1.383, 95% CI: 0.841-2.274, P = .201) had no significant correlation with recurrence. A significant association between POD1 morning serum cortisol and long-term CD remission was verified by Kaplan-Meier analysis when using POD1 morning serum cortisol <5 µg/dL as the cut-off. CONCLUSIONS: The POD1 morning serum cortisol level has a significant association with CD recurrence.

Corticotroph hyperplasia and Cushing disease: diagnostic features and surgical management.

OBJECTIVE: This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes. METHODS: Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups. RESULTS: The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma). Normal pituitary acinar architecture was highly variable. Corticotroph hyperplasia was diagnosed based on the presence of expanded acini showing retained reticulin architecture and predominant staining for adrenocorticotropic hormone. Crooke's hyaline change was seen in 46.7% of specimens, and its frequency was equal in nonlesional tissue of both groups. The two groups differed only by MRI findings (equivocal/diffuse lesion in 46% of hyperplasia and 17% of adenoma; p = 0.03). Diagnostic uncertainty in the hyperplasia group resulted in additional confirmatory testing by 24-hour urinary free cortisol. Total lesion removal was infrequent in patients with hyperplasia compared to those with adenoma (33% vs 65%; p = 0.03). Initial biochemical remission was similar (67% in hyperplasia and 85% in adenoma; p = 0.11). There was no difference in hypothalamic-pituitary-adrenal axis recovery or disease recurrence. The median follow-up was 1.9 years (IQR 0.7-7.6 years) for the hyperplasia group and 1.2 years (IQR 0.4-2.4 years) for the adenoma group. Lack of a discrete lesion and diagnostic uncertainty were the only significant predictors of hyperplasia (sensitivity 53.3%, specificity 97.7%, positive predictive value 88.9%, negative predictive value 85.7%). An adjusted Cox proportional hazards model showed similar recurrence-free survival in the two groups. CONCLUSIONS: This study suggests an association between biochemically proven Cushing disease and histopathologically proven corticotroph hyperplasia. Imaging and operative findings can be ambiguous, and, compared to typical adenomas with a pseudocapsule, the surgical approach is more nuanced. Nevertheless, if treated appropriately, biochemical outcomes may be similar.

Response Activation and Inhibition in Patients With Prolactinomas: An Electrophysiological Study.

Impairment of executive function has been reported in patients with prolactinomas. However, few studies have investigated the electrophysiological mechanisms of response activation and response inhibition in these patients. In this study, we employ an event-related potentials (ERPs) technique to quantitatively assess response activation and inhibition before and after the surgical treatment of prolactinomas. A 64-electrode electroencephalogram (EEG) skullcap was used to record the brain activity in 20 pre-operative patients, 20 follow-up post-operative patients, and 20 healthy controls (HCs) while performing the visual Go/Nogo task. As expected, we identified P300 across all study populations that could reflect response activation and inhibition. Across the three groups, the Nogo stimuli evoked larger frontal-central P300 than the Go stimuli did. In contrast, the Go trials elicited larger parietal P300 than the Nogo trials did. The peak latency of P300 was significantly delayed in both the pre-operative and the post-operative groups compared to the HCs. The amplitude of P300 in both the Go and the Nogo conditions was significantly decreased in the pre-operative patients compared with that of the HCs. At 6 months post-operatively, the prolactinoma patients showed an increase in amplitude of P300 during both the Go and the Nogo tasks. These findings indicate that the prolactinoma patients suffer from deficits in response activation and inhibition, which could be improved by surgical treatment.

Optimizing pre-, intra-, and postoperative management of patients with sellar pathology undergoing transsphenoidal surgery.

OBJECTIVE: Perioperative management of patients with sellar lesions is complex, requiring input from a multidisciplinary team of specialists for ongoing management of both endocrinological and neurosurgical issues. Here, the authors reviewed the experience of a single multidisciplinary center over 10 years to identify key postoperative practices that ensure positive outcomes for patients with sellar lesions who undergo transsphenoidal surgery. METHODS: The authors performed a retrospective review of all transsphenoidal operations carried out by the senior author at a single center from April 2008 through November 2018. They included only adult patients and recorded perioperative management. They also reviewed the evolution of clinical practices for perioperative care at their institution to identify strategies for ensuring positive patient outcomes, and they reviewed the literature on select related topics. RESULTS: In total, 1023 operations in 928 patients were reviewed. Of these, 712 operations were for pituitary adenomas (69.6%), and 122 were for Rathke cleft cysts (11.9%). The remainder included operations for craniopharyngiomas (3.6%), arachnoid cysts (1.7%), pituitary tumor apoplexy (1.0%), and other sellar pathologies (12.2%). Among the reviewed operations, the median hospital stay was 3 days (IQR 2-3). Patient management details during the pre-, intra-, and postoperative periods were identified, including both shared characteristics of all patients undergoing transsphenoidal surgery and unique characteristics that are specific to certain lesion types or patient populations. CONCLUSIONS: Patients with sellar lesions who undergo transsphenoidal surgery require complex, multidisciplinary perioperative care to monitor for common adverse events and to improve outcomes, but there is a dearth of high-quality evidence guiding most perioperative practices. Here, the authors reviewed practices at their institution across more than 1000 transsphenoidal operations that may help ensure successful patient outcomes.

Comparative Propensity-Weighted Mortality After Isolated Acute Traumatic Axis Fractures in Older Adults.

INTRODUCTION: In older patients with axis fractures, the survival benefit from surgery is unclear due to high baseline mortality. Comparative effectiveness research can provide evidence from population level cohorts. Propensity weighting is the preferred methodology for reducing bias when analyzing national administrative cohort data for these purposes but has not yet been utilized for this important surgical conundrum. We estimate the effect of surgery on mortality after isolated acute traumatic axis fracture in older adults. MATERIALS AND METHODS: We used a retrospective population-based cohort of Medicare patients and generated a propensity score-weighted nonsurgical cohort and compared mortality with and without surgery. This balanced the comorbid conditions of the treatment groups. Incident fractures were defined using a predetermined algorithm based on enrollment, code timing, and billing location. The primary outcome was adjusted all-cause 1-year mortality. RESULTS: From 12 372 beneficiaries with 1-year continuous enrollment and a coded axis fracture, 2676 patients met final inclusion/exclusion criteria. Estimated incidence was 16.5 per 100 000 person-years overall in 2014 (95% confidence interval [CI]: 15.0-18.0) and was stable from 2008 through 2014. Patients with axis fracture had a mean age of 82.8 years, 30.2% were male, and 91.9% were Caucasian. Mortality was 3.8 times higher (CI 3.6-4.1) compared with the general population of older US adults. Propensity-weighted mortality at 1 year for nonsurgical patients was 26.7 of 100 (CI: 24.5-29.0). Mortality for surgical patients was significantly lower (19.7/100; CI 14.5-25.0). Risk difference was 7.0 fewer surgical deaths per 100 patients (CI: 1.3-12.7). Surgical patients aged 65 to 74 years had the largest difference in mortality with 11.2 fewer deaths per 100 (CI: 1.1-21.3). DISCUSSION: Patients with axis fractures are predominantly older Caucasian women and have a higher mortality rate than the general population. Propensity-weighted mortality at 1-year was lower in the surgical patients with the largest risk difference occurring in patients 65 to 74 years old. CONCLUSIONS: Surgery may provide an independent survival benefit in patients aged 65 to 75 years, and the mortality difference diminishes thereafter.

Mapping cognitive and emotional networks in neurosurgical patients using resting-state functional magnetic resonance imaging.

Neurosurgery has been at the forefront of a paradigm shift from a localizationist perspective to a network-based approach to brain mapping. Over the last 2 decades, we have seen dramatic improvements in the way we can image the human brain and noninvasively estimate the location of critical functional networks. In certain patients with brain tumors and epilepsy, intraoperative electrical stimulation has revealed direct links between these networks and their function. The focus of these techniques has rightfully been identification and preservation of so-called "eloquent" brain functions (i.e., motor and language), but there is building momentum for more extensive mapping of cognitive and emotional networks. In addition, there is growing interest in mapping these functions in patients with a broad range of neurosurgical diseases. Resting-state functional MRI (rs-fMRI) is a noninvasive imaging modality that is able to measure spontaneous low-frequency blood oxygen level-dependent signal fluctuations at rest to infer neuronal activity. Rs-fMRI may be able to map cognitive and emotional networks for individual patients. In this review, the authors give an overview of the rs-fMRI technique and associated cognitive and emotional resting-state networks, discuss the potential applications of rs-fMRI, and propose future directions for the mapping of cognition and emotion in neurosurgical patients.

Cost of prenatal versus postnatal myelomeningocele closure for both mother and child at 1 year of life.

OBJECTIVE: Prenatal myelomeningocele (MMC) closure has been performed in the United States for 2 decades. While prior work has focused on clinical outcomes of prenatal MMC closure, the cost of this procedure in comparison with that of postnatal MMC closure is unclear. The authors' aim was to compare the cost of prenatal versus postnatal MMC closure for both the child and mother at 1 year. METHODS: A prospective database of patients undergoing prenatal and postnatal MMC closure between 2011 and 2018 with 1-year follow-up was retrospectively reviewed. Charge data for relevant admissions were converted to a cost estimate using the authors' institution's Medicare hospital-specific cost-to-charge ratio. Children, mothers, and mother/child pairs were considered separately. The primary outcome was cost. Secondary outcomes included the need for hydrocephalus treatment, length of stay (LOS), and readmissions. Other covariates included gestational age at birth, MMC lesion level, and obstetric complications. RESULTS: The median cost of care for children in the prenatal group was greater, although not significantly so, at $58,406.71 (IQR $16,900.24-$88,951.01) compared with $49,889.95 (IQR $38,425.18-$115,163.86) for children in the postnatal group (p = 0.204). The median cost for mothers in the prenatal group was significantly greater at $24,548.29 (IQR $20,231.55-$36,862.31) compared with $5087.30 (IQR $4430.72-$5362.56) (p < 0.001). The median cost for mother/child pairs in the prenatal group was $102,377.75 (IQR $37,384.30-$118,527.74) compared with $55,667.82 (IQR $42,840.78-$120,058.06) (p = 0.45). Children in the prenatal group had a lower gestational age at birth (235.81 days vs 265.77 days, p < 0.001) and fewer readmissions (33.3% vs 72.7%, p < 0.001), and hydrocephalus treatment was less common (33.3% vs 90.9%, p < 0.001). Index LOS did not differ between children in the prenatal and postnatal groups (26.8 days vs 23.5 days, p = 0.63). Mothers in the prenatal group had longer LOS (15.92 days vs 4.68 days, p < 0.001) and more readmissions (18.5% vs 0.0%, p = 0.06). CONCLUSIONS: The median cost of prenatal versus postnatal MMC closure did not significantly differ from a hospital perspective at 1 year, although variability in cost was high for both groups. When considering the mother alone, prenatal MMC closure was costlier. Future work is needed to assess cost from a patient and societal perspective both at 1 year and beyond.