Multimodal single-neuron, intracranial EEG, and fMRI brain responses during movie watching in human patients.

We present a multimodal dataset of intracranial recordings, fMRI, and eye tracking in 20 participants during movie watching. Recordings consist of single neurons, local field potential, and intracranial EEG activity acquired from depth electrodes targeting the amygdala, hippocampus, and medial frontal cortex implanted for monitoring of epileptic seizures. Participants watched an 8-min long excerpt from the video "Bang! You're Dead" and performed a recognition memory test for movie content. 3 T fMRI activity was recorded prior to surgery in 11 of these participants while performing the same task. This NWB- and BIDS-formatted dataset includes spike times, field potential activity, behavior, eye tracking, electrode locations, demographics, and functional and structural MRI scans. For technical validation, we provide signal quality metrics, assess eye tracking quality, behavior, the tuning of cells and high-frequency broadband power field potentials to familiarity and event boundaries, and show brain-wide inter-subject correlations for fMRI. This dataset will facilitate the investigation of brain activity during movie watching, recognition memory, and the neural basis of the fMRI-BOLD signal.

A Prospective, Multicenter, Observational Study of Surgical vs Nonsurgical Management for Pituitary Apoplexy.

CONTEXT: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. OBJECTIVE: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. METHODS: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05. RESULTS: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. CONCLUSION: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect.

Endoscopic endonasal transclival clipping of a cerebellar arteriovenous malformation feeding vessel and associated aneurysm; a 2D operative video.

Positioned along the ventral surface of the pons, proximal superior cerebellar artery (SCA) aneurysms account for only 1.7% of all intracranial aneurysms [1]. Unlike more commonly encountered basilar artery aneurysms, patients often experience good outcomes when treated via endovascular coiling or surgical clipping [1,2]. These lesions frequently have a lateral projection and paucity of perforator arteries [2]. With further development of endoscopic endonasal techniques, access to this region is possible via a direct frontal exposure to the ventral brainstem, basilar artery and branching vessels. To date, there are only a limited number of reports describing an endoscopic endonasal transclival (EETC) approach for surgical clipping [3-5]. In this operative video, we detail the surgical clipping of a cerebellar arteriovenous malformation feeding vessel and an associated aneurysm using the EETC approach in a 59-year-old woman who presented with sudden onset of a severe headache. The feeding vessel and aneurysm's midline location, just below the take-off of the SCA made it a good candidate for this surgery. Major steps included in this video include 1) transsphenoidal exposure of and subsequent drilling of the clivus, 2) dural opening into the pre-pontine cistern and dissection of the aneurysm, 3) clipping of the aneurysm, and 4) multi-layered closure of the skull base defect. Overall, the patient tolerated the procedure well and was found to have no residual filling of the aneurysm or the AVM feeding vessel at 2-year follow-up. EETC is a viable surgical option for the treatment of aneurysm located along the midline of the pre-pontine cistern.

Diagnosis of Skin Disease in Moderately to Highly Pigmented Skin by Artificial Intelligence.

BACKGROUND: Triage of patients with skin diseases often includes an initial assessment by a nurse or general practitioner, followed by a dermatologist. Artificial intelligence (AI) systems have been reported to improve clinician ability to diagnose and triage skin conditions. Previous studies have also shown that diagnosis in patients with skin of color can be more challenging. PURPOSE: This study seeks to determine the performance of AI in the screening and triage of benign-neoplastic, malignant-neoplastic, and non-neoplastic skin conditions for Fitzpatrick skin types IV-VI. METHODS: A set of 163 non-standardized clinical photographs of skin disease manifestations from patients with Fitzpatrick skin types IV-VI were obtained through a publicly available dataset (Scale AI and MIT Research Lab, “Fitzpatrick 17 Dataset”). All photos were diagnosed by a specialist and categorized into three disease classes: benign-neoplastic, malignant-neoplastic, or non-neoplastic. There were 23, 14, and 122 cases of each disease class, respectively. RESULTS: Overall, the AI was able to classify the disease classes with a high degree of accuracy for the Top 1 diagnosis (86.50%). Based on its first prediction, the AI demonstrated the greatest accuracy when classifying non-neoplastic conditions (90.98%), high accuracy in detecting malignant-neoplastic conditions (77.78%), and moderate accuracy of classifying benign-neoplastic conditions (69.57%). CONCLUSION: The AI had an overall accuracy of 86.50% in diagnosing skin disease in Fitzpatrick skin types IV to VI. This is an improvement over reported clinician diagnostic accuracy of 44.3% in darker skin types. Incorporating AI into front-line screening of skin conditions could thereby assist in patient triage and shorten the time to accurate diagnosis. Schneider LG, Mamelak AJ, Tejani I, et al. Diagnosis of skin disease in moderately to highly pigmented skin by artificial intelligence. J Drugs Dermatol. 2023;22(7):647-652. doi:10.36849/JDD.7581.

Postoperative Obstructive Sleep Apnea Management Following Endoscopic Pituitary Surgery: A Systematic Review.

OBJECTIVE: There is currently no consensus on the appropriate timing of noninvasive positive pressure ventilation (PPV) resumption in patients with obstructive sleep apnea (OSA) after endoscopic pituitary surgery. We performed a systematic review of the literature to better assess the safety of early PPV use in OSA patients following surgery. METHODS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases in English were searched using the keywords: "sleep apnea," "CPAP," "endoscopic," "skull base," "transsphenoidal" and "pituitary surgery." Case reports, editorials, reviews, meta-analyses, unpublished and abstract-only articles were all excluded. RESULTS: Five retrospective studies were identified, comprising 267 patients with OSA who underwent endoscopic endonasal pituitary surgery. The mean age of patients in four studies (n = 198) was 56.3 years (SD = 8.6) and the most common indication for surgery was pituitary adenoma resection. The timing of PPV resumption following surgery was reported in four studies (n = 130), with 29 patients receiving PPV therapy within two weeks. The pooled rate of postoperative cerebrospinal fluid leak associated with PPV resumption was 4.0% (95% CI: 1.3-6.7%) in three studies (n = 27) and there were no reports of pneumocephalus associated with PPV use in the early postoperative period (<2 weeks). CONCLUSIONS: Early resumption of PPV in OSA patients after endoscopic endonasal pituitary surgery appears relatively safe. However, the current literature is limited. Additional studies with more rigorous outcome reporting are warranted to assess the true safety of re-initiating PPV postoperatively in this population.

Fluid Restriction Reduces Delayed Hyponatremia and Hospital Readmissions After Transsphenoidal Surgery.

CONTEXT: Postoperative hyponatremia leads to prolonged hospital length of stay and readmission within 30 days. OBJECTIVE: To assess 3 strategies for reducing rates of postoperative hyponatremia and analyze risk factors for hyponatremia. DESIGN: Two retrospective analyses and 1 prospective study. SETTING: Tertiary referral hospital. PATIENTS: Patients undergoing transsphenoidal surgery for pituitary adenomas and other sellar and parasellar pathologies. INTERVENTION(S): Phase 1: no intervention. Phase 2: postoperative day (POD) 7 sodium testing and patient education. Phase 3: fluid restriction to 1 L/day on discharge in addition to phase 2 interventions. MAIN OUTCOME MEASURES: Rates of early and delayed hyponatremia and readmissions. Secondary outcomes were risk factors for hyponatremia and readmission costs. RESULTS: In phase 1, 296 patients underwent transsphenoidal surgery. Twenty percent developed early and 28% delayed hyponatremia. Thirty-eight percent underwent POD 7 sodium testing. Readmission rates were 15% overall and 4.3% for hyponatremia. In phase 2 (n = 316), 22% developed early and 25% delayed hyponatremia. Eighty-nine percent complied with POD 7 sodium testing. Readmissions were unchanged although severity of hyponatremia was reduced by 60%. In phase 3 (n = 110), delayed hyponatremia was reduced 2-fold [12.7%, relative risk (RR) = 0.52] and readmissions 3-fold [4.6%, RR = 0.30 (0.12-0.73)]; readmissions for hyponatremia were markedly reduced. Hyponatremia readmission increased costs by 30%. CONCLUSIONS: Restricting fluid to 1 L/day on discharge decreases rates of delayed hyponatremia and readmissions by 50%. Standardized patient education and POD 7 sodium testing decreases severity of hyponatremia but does not impact readmission rates. These protocols should be considered standard practice for patients undergoing transsphenoidal surgery.

Treatment of Cushing Disease With Pituitary-Targeting Seliciclib.

CONTEXT: Preclinical studies show seliciclib (R-roscovitine) suppresses neoplastic corticotroph proliferation and pituitary adrenocorticotrophic hormone (ACTH) production. OBJECTIVE: To evaluate seliciclib as an effective pituitary-targeting treatment for patients with Cushing disease (CD). METHODS: Two prospective, open-label, phase 2 trials, conducted at a tertiary referral pituitary center, included adult patients with de novo, persistent, or recurrent CD who received oral seliciclib 400 mg twice daily for 4 consecutive days each week for 4 weeks. The primary endpoint in the proof-of-concept single-center study was normalization of 24-hour urinary free cortisol (UFC; ≤ 50 µg/24 hours) at study end; in the pilot multicenter study, primary endpoint was UFC normalization or ≥ 50% reduction in UFC from baseline to study end. RESULTS: Sixteen patients were consented and 9 were treated. Mean UFC decreased by 42%, from 226.4 ± 140.3 µg/24 hours at baseline to 131.3 ± 114.3 µg/24 hours by study end. Longitudinal model showed significant UFC reductions from baseline to each treatment week. Three patients achieved ≥ 50% UFC reduction (range, 55%-75%), and 2 patients exhibited 48% reduction; none achieved UFC normalization. Plasma ACTH decreased by 19% (P = 0.01) in patients who achieved ≥ 48% UFC reduction. Three patients developed grade ≤ 2 elevated liver enzymes, anemia, and/or elevated creatinine, which resolved with dose interruption/reduction. Two patients developed grade 4 liver-related serious adverse events that resolved within 4 weeks of seliciclib discontinuation. CONCLUSION: Seliciclib may directly target pituitary corticotrophs in CD and reverse hypercortisolism. Potential liver toxicity of seliciclib resolves with treatment withdrawal. The lowest effective dose requires further determination.

Surgery as a first-line option for prolactinomas.

INTRODUCTION: Treatment of prolactinomas with dopamine agonists has been the established first-line treatment option for many years, with surgery reserved for refractory cases or medication intolerance. This approach may not be the best option in many cases. AREAS COVERED: Review of the epidemiology, biology, and treatment options available for prolactinomas, including best available data on outcomes, costs, and morbidities for each therapy. These data are then used to propose a 'surgery-first' treatment approach for a subset of prolactinomas as an alternative to primary medical management. EXPERT OPINION: Based on the available data, there is a strong rationale that transsphenoidal surgery should be considered a first-line treatment option for both micro- and macro-prolactinomas that do not demonstrate high grade cavernous sinus invasion on MRI imaging, with dopamine agonists administered as a secondary therapy for tumors not in remission following surgery, and for giant tumors. This 'surgery-first' approach assumes the availability of skilled and experienced pituitary surgeons to ensure optimal outcomes. This approach should result in high cure rates and reduced DA requirements for patients not cured from initial surgery. Further, it will reduce medical costs over a patient's lifetime and the chronic morbidities associated with protracted dopamine agonist usage.

Dural Invasion as a Marker of Aggressive Pituitary Adenomas.

BACKGROUND: Predictive markers of aggressive pituitary tumors have not been consistently demonstrated. Dural invasion and invasion-associated proteins, including matrix metalloproteinase-9 (MMP9) and cofilin, have been proposed to predict aggressive behavior and recurrence, but findings to date have been inconsistent. OBJECTIVE: To assess whether microscopic dural invasion predicts aggressive pituitary adenoma behavior and whether MMP9 and cofilin expression correlates with pathological and clinical invasion markers. METHODS: We retrospectively studied 328 consecutive pituitary mass resections by a single neurosurgeon at a single center; 254 were adenomas, and 98 had dural biopsies sent for routine pathological evaluation. Assessments included clinical features, postoperative course, and immunochemical expression of MMP9, cofilin, and phospho-cofilin. Recurrence was evaluated in those with at least 12 months of postoperative follow-up. RESULTS: Dural invasion was evident in 48% of biopsy specimens and was associated with male sex, larger tumors, suprasellar extension and sphenoid sinus invasion, cranial nerve palsies, and hypogonadism. Recurrence rates and the expression of MMP9, cofilin, and phospho-cofilin did not differ between those with and without dural invasion. However, differential expression of phospho-cofilin was associated with growth hormone deficiency and compressive pituitary mass effects. CONCLUSION: Dural invasion is associated with larger tumors, suprasellar and sphenoid sinus invasion, and pituitary failure but is not predictive of a more aggressive postoperative course. Routine dural biopsy is therefore of limited benefit in predicting postoperative recurrences. Cofilin expression may be an adjunctive biomarker of invasion in recurrent tumors, but MMP9 expression does not predict tumor behavior.

Placement of Stereotactic Electroencephalography Depth Electrodes Using the Stealth Autoguide Robotic System: Technical Methods and Initial Results.

BACKGROUND: Robotic systems are gaining acceptance as a preferred tool for the placement of electrodes for stereotactic electroencephalography (SEEG) studies. OBJECTIVE: To describe the technical methods for insertion of SEEG using the Medtronic Stealth Autoguide robotic system and detailed outcomes in the initial 9 patients implanted. METHODS: Nine patients underwent placement of electrodes for SEEG studies with the use of the Autoguide system. Patients had at least 10 electrodes placed. Targets were planned on a Stealth S8 planning station, and electrodes were placed under general anesthesia. A technique for placement is described in detail. Patient outcomes and accuracy of electrode placement were evaluated. Methods to improve accuracy were investigated. Comparison of postoperative MRIs with preoperative planning MRIs was performed to determine the accuracy of electrode placement. RESULTS: One hundred two electrodes were placed in 9 patients. Methods for placement and technical nuances are detailed. The distance from the planned target to the actual position of the electrode tip was measured in 8 of the 9 patients. The mean Euclidean distance was 4.67 ± 0.27 mm. There was 1 placement-related hemorrhage deficit in the first patient, and no deaths or infections. Adequate positioning of electrodes for seizure monitoring was obtained in all patients. CONCLUSION: Autoguide can be used for placement of electrodes for SEEG studies with acceptable degrees of patient safety, accuracy, and efficiency. Considering the cost of Autoguide compared with other robotic devices, it may be attractive option.

Treatment of Aggressive Pituitary Adenomas: A Case-Based Narrative Review.

Management of aggressive pituitary adenomas is challenging due to a paucity of rigorous evidence supporting available treatment approaches. Recent guidelines emphasize the need to maximize standard therapies as well as the use of temozolomide and radiation therapy to treat disease recurrence. However, often these adenomas continue to progress over time, necessitating the use of additional targeted therapies which also impact quality of life and long-term outcomes. In this review, we present 9 cases of aggressive pituitary adenomas to illustrate the importance of a multidisciplinary, individualized approach. The timing and rationale for surgery, radiation therapy, temozolomide, somatostatin receptor ligands, and EGFR, VEGF, and mTOR inhibitors in each case are discussed within the context of evidence-based guidelines and clarify strategies for implementing an individualized approach in the management of these difficult-to-treat-adenomas.

Pituitary society expert Delphi consensus: operative workflow in endoscopic transsphenoidal pituitary adenoma resection.

PURPOSE: Surgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice. METHODS: A mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached. RESULTS: There was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured. CONCLUSIONS: Through an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed "core" steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The "optional" steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world.

A Crowdsourced Consensus on Supratotal Resection Versus Gross Total Resection for Anatomically Distinct Primary Glioblastoma.

BACKGROUND: Gross total resection (GTR) of contrast-enhancing tumor is associated with increased survival in primary glioblastoma. Recently, there has been increasing interest in performing supratotal resections (SpTRs) for glioblastoma. OBJECTIVE: To address the published results, which have varied in part due to lack of consensus on the definition and appropriate use of SpTR. METHODS: A crowdsourcing approach was used to survey 21 neurosurgical oncologists representing 14 health systems nationwide. Participants were presented with 11 definitions of SpTR and asked to rate the appropriateness of each definition. Participants reviewed T1-weighed postcontrast and fluid-attenuated inversion-recovery magnetic resonance imaging for 22 anatomically distinct glioblastomas. Participants were asked to assess the tumor location's eloquence, the perceived equipoise of enrolling patients in a randomized trial comparing gross total to SpTR, and their personal treatment plans. RESULTS: Most neurosurgeons surveyed (n = 18, 85.7%) agree that GTR plus resection of some noncontrast enhancement is an appropriate definition for SpTR. Overall, moderate inter-rater agreement existed regarding eloquence, equipoise, and personal treatment plans. The 4 neurosurgeons who had performed >10 SpTRs for glioblastomas in the past year were more likely to recommend it as their treatment plan (P < .005). Cases were divided into 3 anatomically distinct groups based upon perceived eloquence. Anterior temporal and right frontal glioblastomas were considered the best randomization candidates. CONCLUSION: We established a consensus definition for SpTR of glioblastoma and identified anatomically distinct locations deemed most amenable to SpTR. These results may be used to plan prospective trials investigating the potential clinical utility of SpTR for glioblastoma.

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.

Electrocorticography During Deep Brain Stimulation Surgery: Safety Experience From 4 Centers Within the National Institute of Neurological Disorders and Stroke Research Opportunities in Human Consortium.

BACKGROUND: Intraoperative research during deep brain stimulation (DBS) surgery has enabled major advances in understanding movement disorders pathophysiology and potential mechanisms for therapeutic benefit. In particular, over the last decade, recording electrocorticography (ECoG) from the cortical surface, simultaneously with subcortical recordings, has become an important research tool for assessing basal ganglia-thalamocortical circuit physiology. OBJECTIVE: To provide confirmation of the safety of performing ECoG during DBS surgery, using data from centers involved in 2 BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative-funded basic human neuroscience projects. METHODS: Data were collected separately at 4 centers. The primary endpoint was complication rate, defined as any intraoperative event, infection, or postoperative magnetic resonance imaging abnormality requiring clinical follow-up. Complication rates for explanatory variables were compared using point biserial correlations and Fisher exact tests. RESULTS: A total of 367 DBS surgeries involving ECoG were reviewed. No cortical hemorrhages were observed. Seven complications occurred: 4 intraparenchymal hemorrhages and 3 infections (complication rate of 1.91%; CI = 0.77%-3.89%). The placement of 2 separate ECoG research electrodes through a single burr hole (84 cases) did not result in a significantly different rate of complications, compared to placement of a single electrode (3.6% vs 1.5%; P = .4). Research data were obtained successfully in 350 surgeries (95.4%). CONCLUSION: Combined with the single report previously available, which described no ECoG-related complications in a single-center cohort of 200 cases, these findings suggest that research ECOG during DBS surgery did not significantly alter complication rates.

Infectious Complications of Expanded Endoscopic Transsphenoidal Surgery: A Retrospective Cohort Analysis of 100 Cases.

Objective To identify perioperative factors that may predict postoperative cerebrospinal fluid (CSF) leak and meningitis following expanded endoscopic transsphenoidal surgery (EETS). Study Design This is a retrospective study. This study was set at the Cedars-Sinai Medical Center, Los Angeles. A total of 78 patients who underwent EETS between January 2007 and November 2018 were participated. The main outcome measures were CSF leak and meningitis. Results A total of 78 patients underwent a total of 100 EETS procedures; 17.9 and 10.3% of patients developed postoperative CSF leaks and meningitis, respectively. Out of eight, three patients with meningitis did not develop an observable CSF leak. The risk of developing meningitis in patients with a CSF leak was significantly higher than those without a leak, with an odds ratio (OR) of 11.48 (95% confidence interval, 2.33-56.47; p = 0.004). Pituicytomas were significantly associated with meningitis compared with other pathologies. No other patient-specific factors were identified as risks for leak or meningitis, including method of skull base repair, sex, tumor volume, or body mass index, although there was a strong trend toward reduced CSF leak rates in patient with nasoseptal flaps used for skull base repair, compared with those without (9.5 vs. 25%). CSF protein was consistently elevated on the first CSF values obtained when meningitis was suspected. Conclusion CSF leak and meningitis are common complications of expanded endonasal surgery No statistically significant risk factors for developing a postoperative leak other than the pathology of pituicytoma were identified, including method of skull base repair, although the use of a vascularized nasoseptal flap did trend toward a reduced CSF leak rate. CSF protein is the most sensitive marker for the presumptive diagnosis and timely treatment of meningitis.