Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis.

BACKGROUND: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. METHODS: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included. RESULTS: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. CONCLUSIONS: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.

Defining benchmark outcomes for transsphenoidal surgery of pituitary adenomas: a multicenter analysis.

IMPORTANCE: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available. OBJECTIVE: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas. DESIGN: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed. SETTING: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values. RESULTS: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%. CONCLUSIONS: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context.

A Multicenter, Propensity Score-Matched Assessment of Endoscopic Versus Microscopic Approaches in the Management of Pituitary Adenomas.

BACKGROUND AND OBJECTIVES: There is considerable controversy as to which of the 2 operating modalities (microsurgical or endoscopic transnasal surgery) currently used to resect pituitary adenomas (PAs) is the safest and most effective intervention. We compared rates of clinical outcomes of patients with PAs who underwent resection by either microsurgical or endoscopic transnasal surgery. METHODS: To independently assess the outcomes of each modality type, we sought to isolate endoscopic and microscopic PA surgeries with a 1:1 tight-caliper (0.01) propensity score-matched analysis using a multicenter, neurosurgery-specific database. Surgeries were performed between 2017 and 2020, with data collected retrospectively from 12 international institutions on 4 continents. Matching was based on age, previous neurological deficit, American Society of Anesthesiologists (ASA) score, tumor functionality, tumor size, and Knosp score. Univariate and multivariate analyses were performed. RESULTS: Among a pool of 2826 patients, propensity score matching resulted in 600 patients from 9 surgery centers being analyzed. Multivariate analysis showed that microscopic surgery had a 1.91 odds ratio (OR) ( P = .03) of gross total resection (GTR) and shorter operative duration ( P < .01). However, microscopic surgery also had a 7.82 OR ( P < .01) for intensive care unit stay, 2.08 OR ( P < .01) for intraoperative cerebrospinal fluid (CSF) leak, 2.47 OR ( P = .02) for postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was an independent predictor for longer postoperative stay (ß = 2.01, P < .01). Overall, no differences in postoperative complications or 3- to 6-month outcomes were seen by surgical approach. CONCLUSION: Our international, multicenter matched analysis suggests microscopic approaches for pituitary tumor resection may offer better GTR rates, albeit with increased intensive care unit stay, CSF leak, SIADH, and hospital utilization. Better prospective studies can further validate these findings as matching patients for outcome analysis remains challenging. These results may provide insight into surgical benchmarks at different centers, offer room for further registry studies, and identify best practices.

Chiari I Malformation and Sleep-Disordered Breathing.

Sleep-disordered breathing (SDB) is a frequent symptomatic feature of pediatric Chiari I, reported in at least 24% of patients presenting to neurosurgeons. Here the epidemiology, natural history, pathophysiology, and diagnosis of SDB in Chiari I is reviewed. Diagnosis requires polysomnography, which should be pursued in young or symptomatic patients or those with prominent imaging findings. Review of case series of surgical decompression suggest that surgical decompression can improve SDB in selected patients.

Determining the time frame of maximum clinical improvement in surgical decompression for cervical spondylotic myelopathy when stratified by preoperative myelopathy severity: a cervical Quality Outcomes Database study.

OBJECTIVE: While surgical decompression is an important treatment modality for cervical spondylotic myelopathy (CSM), it remains unclear if the severity of preoperative myelopathy status affects potential benefit from surgical intervention and when maximum postoperative improvement is expected. This investigation sought to determine if retrospective analysis of prospectively collected patient-reported outcomes (PROs) following surgery for CSM differed when stratified by preoperative myelopathy status. Secondary objectives included assessment of the minimal clinically important difference (MCID). METHODS: A total of 1151 patients with CSM were prospectively enrolled from the Quality Outcomes Database at 14 US hospitals. Baseline demographics and PROs at baseline and 3 and 12 months were measured. These included the modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), quality-adjusted life-years (QALYs) from the EQ-5D, and visual analog scale from the EQ-5D (EQ-VAS). Patients were stratified by preoperative myelopathy severity using criteria established by the AO Spine study group: mild (mJOA score 15-17), moderate (mJOA score 12-14), or severe (mJOA score < 12). Univariate analysis was used to identify demographic variables that significantly varied between myelopathy groups. Then, multivariate linear regression and linear mixed regression were used to model the effect of severity and time on PROs, respectively. RESULTS: For NDI, EQ-VAS, and QALY, patients in all myelopathy cohorts achieved significant, maximal improvement at 3 months without further improvement at 12 months. For mJOA, moderate and severe myelopathy groups demonstrated significant, maximal improvement at 3 months, without further improvement at 12 months. The mild myelopathy group did not demonstrate significant change in mJOA score but did maintain and achieve higher PRO scores overall when compared with more advanced myelopathy cohorts. The MCID threshold was reached in all myelopathy cohorts at 3 months for mJOA, NDI, EQ-VAS, and QALY, with the only exception being mild myelopathy QALY at 3 months. CONCLUSIONS: As assessed by statistical regression and MCID analysis, patients with cervical myelopathy experience maximal improvement in their quality of life, neck disability, myelopathy score, and overall health by 3 months after surgical decompression, regardless of their baseline myelopathy severity. An exception was seen for the mJOA score in the mild myelopathy cohort, improvement of which may have been limited by ceiling effect. The data presented here will aid surgeons in patient selection, preoperative counseling, and expected postoperative time courses.

The effects of avoiding extended antimicrobial drain prophylaxis on Clostridioides difficile and postprocedural infection rates: a 5-year retrospective.

OBJECTIVE: Postprocedural infection is a consequential complication of neurosurgical intervention. Periprocedural antimicrobial prophylaxis is routinely administered to prevent infection, and in some cases, continued for extended periods while surgical drains remain in place. However, there is little evidence that extended antimicrobial administration is necessary to reduce postprocedural infection, and extended antimicrobials can be associated with harm, such as Clostridioides difficile infection. The authors sought to evaluate whether shortening the duration of postprocedural antimicrobial prophylaxis would decrease the incidence of C. difficile infection without increasing the incidence of postprocedural infection. METHODS: In this retrospective study, two general neurosurgical cohorts were examined. In one cohort, postoperative antimicrobial prophylaxis was limited to 24 hours; in the other, some patients received extended postoperative antimicrobial prophylaxis while surgical drains or external ventricular drains (EVDs) remained in place. Rates of infection with C. difficile as well as postprocedural infection after surgery and EVD placement were compared. RESULTS: Seven thousand two hundred four patients undergoing 8586 surgical procedures and 413 EVD placements were reviewed. The incidence of C. difficile infection decreased significantly from 0.5% per procedural encounter to 0.07% with the discontinuation of extended postprocedural antibiotics within 90 days of a procedure. Rates of postprocedural infection and EVD infection did not significantly change. Results were similar in subgroups of patients with closed suction drains as well as cranial and spine subgroups. CONCLUSIONS: Discontinuation of extended antimicrobial prophylaxis was associated with a significant decrease in the incidence of C. difficile infection without a concomitant change in postprocedural infections or EVD-associated infection. This study provides evidence in support of specialtfy-wide discontinuation of extended postoperative antimicrobial prophylaxis, even in the presence of closed suction drains.

Melanoma brain metastasis mimicking cortical laminar necrosis.

Background: Metastatic lesions to the brain are common in patients with melanoma. Imaging characteristics can support the diagnosis of metastatic melanoma, but alternative diagnoses should be considered. Case Description: Here, we present a case of a 57-year-old man in whom a metastatic melanoma initially mimicked the imaging characteristics of cortical laminar necrosis. Conclusion: This comprises the first report of melanoma brain metastasis presenting with these imaging characteristics and emphasizes the importance of maintaining a high index of suspicion for metastatic lesions in patients with known cancer.

Neurocysticercosis Presenting as an Isolated Suprasellar Lesion.

BACKGROUND: Although extraparenchymal neurocysticercosis (NCC) is well established, presentation in the suprasellar space is rare. When presenting in the suprasellar space, the imaging characteristics may mimic more common lesions including craniopharyngioma and Rathke cleft cyst depending on the life cycle of the parasite. Although antiparasitic medical therapy may be effective for viable NCC, it is not routinely employed for calcified NCC. CASE DESCRIPTION: This report presents a 39-year-old male patient who presented with profound visual decline secondary to a partially calcified suprasellar NCC. Suprasellar NCC was presumed based on specific radiologic findings, which are discussed. Medical therapy was not offered because of the proximity to the optic chiasm and the partial calcification of the lesion leading to the presumption that the mass was nonviable. The patient underwent successful endoscopic endonasal resection of the suprasellar NCC and experienced significant improvement in vision. Despite the calcification, pathological evaluation revealed that a portion remained viable. CONCLUSIONS: Regardless of the life cycle stage, endonasal resection offers a minimally invasive approach for suprasellar NCC; treatment can be tailored to the patient's presentation and stage of infection.

Revision thoracolumbar surgery for flat back deformity: staged ALIF and posterior column osteotomies to avoid three-column osteotomy.

Three-column osteotomies (3COs) can achieve significant alignment correction when revising fixed sagittal plane deformities; however, the technique is associated with high complication rates. The authors demonstrate staged anterior-posterior surgery with L5-S1 ALIF (below a prior L3-5 fusion) and multilevel Smith-Petersen osteotomies to circumvent the morbidity associated with 3CO. The patient was a 67-year-old male with three prior lumbar surgeries who presented with back and leg pain. Imaging demonstrated lumbar flat back deformity and sagittal imbalance. The narrated video details key radiological measurements, operative planning and rationale, surgical steps, and outcomes. The patient provided written, informed consent for publication of this illustrative case. The video can be found here: https://youtu.be/wv4W9D9fUPc.

Surgery for Pediatric Pituitary Adenomas.

Pituitary adenomas are a rare but important central nervous system tumor in children. Because of differences in growth and development, the manifestations of pituitary adenomas in children may differ from those seen in adults. Unlike adult patients, the pediatric population more often presents with clinically secretory adenomas. Although medical management is first-line treatment of prolactinomas, transsphenoidal surgery is appropriate for most children with Cushing disease and gigantism. Although some pediatric patients present surgical challenges because of small anatomic dimensions or an incompletely developed sphenoid sinus, transsphenoidal surgery can be safely and effectively undertaken in most children, with low complication rates.

Resting state connectivity in neocortical epilepsy: The epilepsy network as a patient-specific biomarker.

OBJECTIVE: Localization related epilepsy (LRE) is increasingly accepted as a network disorder. To better understand the network specific characteristics of LRE, we defined individual epilepsy networks and compared them across patients. METHODS: The epilepsy network was defined in the slow cortical potential frequency band in 10 patients using intracranial EEG data obtained during interictal periods. Cortical regions were included in the epilepsy network if their connectivity pattern was similar to the connectivity pattern of the seizure onset electrode contact. Patients were subdivided into frontal, temporal, and posterior quadrant cohorts according to the anatomic location of seizure onset. Jaccard similarity was calculated within each cohort to assess for similarity of the epilepsy network between patients within each cohort. RESULTS: All patients exhibited an epilepsy network in the slow cortical potential frequency band. The topographic distribution of this correlated network activity was found to be unique at the single subject level. CONCLUSIONS: The epilepsy network was unique at the single patient level, even between patients with similar seizure onset locations. SIGNIFICANCE: We demonstrated that the epilepsy network is patient-specific. This is in keeping with our current understanding of brain networks and identifies the patient-specific epilepsy network as a possible biomarker in LRE.

Saccades Trigger Predictive Updating of Attentional Topography in Area V4.

During natural behavior, saccades and attention act together to allocate limited neural resources. Attention is generally mediated by retinotopic visual neurons; therefore, specific neurons representing attended features change with each saccade. We investigated the neural mechanisms that allow attentional targeting in the face of saccades. Specifically, we looked for predictive changes in attentional modulation state or receptive field position that could stabilize attentional representations across saccades in area V4, known to be necessary for attention-dependent behavior. We recorded from neurons in monkeys performing a novel spatiotopic attention task, in which performance depended on accurate saccade compensation. Measurements of attentional modulation revealed a predictive attentional "hand-off" corresponding to a presaccadic transfer of attentional state from neurons inside the attentional focus before the saccade to those that will be inside the focus after the saccade. The predictive nature of the hand-off ensures that attentional brain maps are properly configured immediately after each saccade.

Perisaccadic Updating of Visual Representations and Attentional States: Linking Behavior and Neurophysiology.

During natural vision, saccadic eye movements lead to frequent retinal image changes that result in different neuronal subpopulations representing the same visual feature across fixations. Despite these potentially disruptive changes to the neural representation, our visual percept is remarkably stable. Visual receptive field remapping, characterized as an anticipatory shift in the position of a neuron's spatial receptive field immediately before saccades, has been proposed as one possible neural substrate for visual stability. Many of the specific properties of remapping, e.g., the exact direction of remapping relative to the saccade vector and the precise mechanisms by which remapping could instantiate stability, remain a matter of debate. Recent studies have also shown that visual attention, like perception itself, can be sustained across saccades, suggesting that the attentional control system can also compensate for eye movements. Classical remapping could have an attentional component, or there could be a distinct attentional analog of visual remapping. At this time we do not yet fully understand how the stability of attentional representations relates to perisaccadic receptive field shifts. In this review, we develop a vocabulary for discussing perisaccadic shifts in receptive field location and perisaccadic shifts of attentional focus, review and synthesize behavioral and neurophysiological studies of perisaccadic perception and perisaccadic attention, and identify open questions that remain to be experimentally addressed.

Hippocampal morphology in lithium and non-lithium-treated bipolar I disorder patients, non-bipolar co-twins, and control twins.

BACKGROUND: Bipolar I disorder is a highly heritable psychiatric illness with undetermined predisposing genetic and environmental risk factors. We examined familial contributions to hippocampal morphology in bipolar disorder, using a population-based twin cohort design. METHODS: We acquired high-resolution brain MRI scans from 18 adult patients with bipolar I disorder [BPI; mean age 45.6 ± 8.69 (SD); 10 lithium-treated], 14 non-bipolar co-twins, and 32 demographically matched healthy comparison twins. We used three-dimensional radial distance mapping techniques to visualize hippocampal shape differences between groups. RESULTS: Lithium-treated BPI patients had significantly larger global hippocampal volume compared to both healthy controls (9%) and non-bipolar co-twins (12%), and trend-level larger volumes relative to non-lithium-treated BPI patients (8%). In contrast, hippocampal volumes in non-lithium-treated BPI patients did not differ from those of non-bipolar co-twins and control twins. 3D surface maps revealed thicker hippocampi in lithium-treated BPI probands compared with control twins across the entire anterior-to-posterior extent of the cornu ammonis (CA1 and 2) regions, and the anterior part of the subiculum. Unexpectedly, co-twins also showed significantly thicker hippocampi compared with control twins in regions that partially overlapped those showing effects in the lithium treated BPI probands. CONCLUSIONS: These findings suggest that regionally thickened hippocampi in bipolar I disorder may be partly due to familial factors and partly due to lithium-induced neurotrophy, neurogenesis, or neuroprotection. Unlike schizophrenia, hippocampal alterations in co-twins of bipolar I disorder probands are likely to manifest as subtle volume excess rather than deficit, perhaps indicating protective rather than risk effects.

Attention doesn't slide: spatiotopic updating after eye movements instantiates a new, discrete attentional locus.

During natural vision, eye movements can drastically alter the retinotopic (eye-centered) coordinates of locations and objects, yet the spatiotopic (world-centered) percept remains stable. Maintaining visuospatial attention in spatiotopic coordinates requires updating of attentional representations following each eye movement. However, this updating is not instantaneous; attentional facilitation temporarily lingers at the previous retinotopic location after a saccade, a phenomenon known as the retinotopic attentional trace. At various times after a saccade, we probed attention at an intermediate location between the retinotopic and spatiotopic locations to determine whether a single locus of attentional facilitation slides progressively from the previous retinotopic location to the appropriate spatiotopic location, or whether retinotopic facilitation decays while a new, independent spatiotopic locus concurrently becomes active. Facilitation at the intermediate location was not significant at any time, suggesting that top-down attention can result in enhancement of discrete retinotopic and spatiotopic locations without passing through intermediate locations.

The role of closure in defining the "objects" of object-based attention.

Many recent studies have concluded that the underlying units of visual attention are often discrete objects whose boundaries constrain the allocation of attention. However, relatively few studies have explored the particular stimulus cues that determine what counts as an "object" of attention. We explore this issue in the context of the two-rectangles stimuli previously used by many investigators. We first show, using both spatial-cuing and divided-attention paradigms, that same-object advantages occur even when the ends of the two rectangles are not drawn. This is consistent with previous reports that have emphasized the importance of individual contours in guiding attention, and our study shows that such effects can occur in displays that also contain grouping cues. In our divided-attention experiment, however, this contour-driven same-object advantage was significantly weaker than that obtained with the standard stimulus, with the added cue of closure--demonstrating that contour-based processes are not the whole story. These results confirm and extend the observation that same-object advantages can be observed even without full-fledged objects. At the same time, however, these studies show that boundary closure-one of the most important cues to objecthood per se-can directly influence attention. We conclude that object-based attention is not an all-or-nothing phenomenon; object-based effects can be independently strengthened or weakened by multiple cues to objecthood.