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Background: Headache is a common symptom in patients with pituitary adenomas. Research on whether resection of pituitary adenomas via the endoscopic endonasal approach (EEA) affects headaches is limited, and the pathophysiology of headaches associated with pituitary adenomas remains unclear. This study aimed to determine if resection of pituitary adenomas via the EEA improves headaches and investigate factors that may be associated with headaches in patients with pituitary adenoma., Methods: A prospectively collected database of 122 patients undergoing resection of pituitary adenoma via the EEA was analyzed. Patient-reported headache severity was collected prospectively using the Headache Impact Test (HIT-6) at preoperative baseline and 4 postoperative time points (3 weeks, 6 weeks, 3 months, and 6 months)., Results: Adenoma size and subtype, cavernous sinus invasion, and hormonal status were not associated with preoperative headache burden. In patients with preoperative headaches (HIT-6 score >36), significant decreases in HIT-6 score were observed postoperatively at 6 weeks (5.5-point improvement, 95% CI 1.27-9.78, P < 0.01), 3 months (3.6-point improvement, 95% CI 0.01-7.18, P < 0.05), and 6 months (7.5-point improvement, 95% CI 3.43-11.46, P < 0.01). The only factor associated with headache improvement was cavernous sinus invasion (P = 0.003). Adenoma size and subtype and hormonal status were not associated with postoperative headache burden., Conclusions: Resection via the EEA is associated with significant improvement in headache-related impact on patient functioning from ≥6 weeks after surgery. Patients with cavernous sinus invasion are more likely to experience improvement in headaches. The mechanism of headaches associated with pituitary adenoma still requires clarification., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Incorrect level spinal surgery is an avoidable complication, with significant ramifications. Several pre-operative spinal marking techniques have been described to aid intraoperative localisation., Methods: A systematic search of Ovid MEDLINE, and EMBASE was performed from inception to July 2022. All publications describing cases of internal spinal marking were included for further analysis. 22 articles describing 503 patients satisfied our eligibility criteria., Results: A number of localisation techniques, including endovascular coiling (n = 16), fiducials (n = 177), dye (n = 109), needle/fixed wire (n = 199), cement (n = 4), and gadolinium tubes (n = 1) were described. The highest rates of technical success were observed with endovascular coiling, fiducials, cement and dye (100 %), and complication rates were lowest with endovascular coiling, fiducials and cement (0 %)., Conclusions: Overall, internal spinal marking was effective and safe. When considering practicality and efficacy, fiducial marking appears the optimal technique, as it can be performed in the outpatient setting under local anaesthesia. This review demonstrates the need for more targeted investigation into localisation methods in spinal surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: MR imaging is key in the diagnostic work-up of Cushing disease. The sensitivity of MR imaging in Cushing disease is not known nor is the prognostic significance of "MR imaging-negative" disease., Purpose: Our aim was to determine the overall sensitivity and prognostic significance of MR imaging localization of Cushing disease., Data Sources: We performed a systematic review of the MEDLINE and PubMed databases for cohort studies reporting the sensitivity of MR imaging for the detection of adenomas in Cushing disease., Study Selection: This study included 57 studies, comprising 5651 patients., Data Analysis: Risk of bias was assessed using the methodological index for non-randomized studies criteria. Meta-analysis of proportions and pooled subgroup analysis were performed., Data Synthesis: Overall sensitivity was 73.4% (95% CI, 68.8%-77.7%), and the sensitivity for microadenomas was 70.6% (66.2%-74.6%). There was a trend toward greater sensitivity in more recent studies and with the use of higher-field-strength scanners. Thinner-section acquisitions and gadolinium-enhanced imaging, particularly dynamic sequences, also increased the sensitivity. The use of FLAIR and newer 3D spoiled gradient-echo and FSE sequences, such as spoiled gradient-echo sequences and sampling perfection with application-optimized contrasts by using different flip angle evolutions, may further increase the sensitivity but appear complementary to standard 2D spin-echo sequences. MR imaging detection conferred a 2.63-fold (95% CI, 2.06-3.35-fold) increase in remission for microadenomas compared with MR imaging-negative Cushing disease., Limitations: Pooled analysis is limited by heterogeneity among studies. We could not account for variation in image interpretation and tumor characteristics., Conclusions: Detection on MR imaging improves the chances of curative resection of adenomas in Cushing disease. The evolution of MR imaging technology has improved the sensitivity for adenoma detection. Given the prognostic importance of MR imaging localization, further effort should be made to improve MR imaging protocols for Cushing disease., (© 2023 by American Journal of Neuroradiology.)

Background: Predicting extent of resection before pituitary surgery is imperative for operative planning and patient counseling. In the era of endoscopic endonasal transsphenoidal surgery (EEA), a specific, reliable tool for predicting resection of macroadenomas would have widespread applications., Objective: To identify factors that predict resection of pituitary macroadenomas through the EEA., Methods: A prospectively maintained, multicenter database of 277 consecutive macroadenomas resected through the EEA was analyzed. Multivariate logistic regression identified predictors of gross total resection (GTR). A simple scoring system, the Hardy, Age, Clival, Knosp, Depth (HACKD) Score, was developed and tested., Results: GTR was achieved in 82.3% (228/277) of cases. Older than 50 years (odds ratio [OR] 2.96, P = .01), clival extension (OR 5.87, P < .01), Hardy grade C or D suprasellar extension (OR 3.91, P = .01), Knosp grade 3 or 4 cavernous sinus invasion (OR 7.62, P < .01), and tumor depth >20 mm (OR 5.14, P < .01) were all associated with subtotal resection. The HACKD score, awarding 1 point each for Hardy grade C or D, and older than 50 years, and 2 points each for clival extension, Knosp grades 3 or 4, and tumor depth >20 mm, demonstrated excellent discriminative ability (AUROC 0.887, 95% CI: 0.839-0.934). The rate of GTR progressively decreased with a higher HACKD score. Rates of GTR were 95.8% (182/190) for low (HACKD ≤2), 59.5% (44/74) for moderate (HACKD 3-5), and 15.4% (2/13) for high (HACKD 6+) HACKD scores., Conclusion: The HACKD score is a simple and accurate tool based on the largest study analyzing predictors of GTR in pituitary macroadenomas operated through the EEA., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Water balance is fundamental to all homeostasis. The hypothalamic-pituitary-adrenal axis influences water balance through the effects of corticotropin-releasing hormone and cortisol on arginine vasopressin secretion and the peripheral effects of cortisol on hemodynamics and renal water handling. In this review, we explored the complex interplay of glucocorticoids with water balance, with particular attention to hyponatremia and pituitary surgery., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Patient quality of life (QOL) is an important metric of surgical success. To guide therapeutic advances in pituitary adenoma surgery, a validated, comprehensive instrument to quantify QOL is required. We aim to evaluate the validity of the 35 item anterior skull base questionnaire (ASBQ-35) in patients undergoing pituitary adenoma surgery. A total of 168 patients undergoing endoscopic resection of pituitary adenomas underwent longitudinal QOL assessment using the ASBQ-35 and the 22-item Sinonasal Outcomes Test (SNOT-22) over the first postoperative year. Validity of the ASBQ-35 was assessed by internal consistency, test-retest reliability, responsiveness to clinical change, and concurrent validity with the SNOT-22. Internal consistency of the ASBQ-35 was excellent, with a Cronbach's alpha > 0.95 across all timepoints. Test-retest reliability between 3 and 6 months (ICC = 0.82, p < 0.001) and 6 months and 12 months (ICC = 0.78, p < 0.001) was robust. Concurrent validity with SNOT-22 was strong across all timepoints (absolute Pearson r ≥ 0.63, p < 0.001). Mean ASBQ-35 scores were significantly worse at 3 weeks compared to preoperative baseline (mean difference - 0.28, p < 0.01); however, by 12 months, scores had significantly improved (mean difference + 0.24, p < 0.01), indicating that the scale is responsive to clinical change. Each of the 6 domains of the ASBQ, and all 35 component questions, contributed to the discriminative of the ASBQ to measure QOL during the first postoperative year. The ASBQ-35 is a valid, comprehensive tool for assessing QOL after endoscopic pituitary adenoma surgery. Each component of the ASBQ-35 contributed to the overall assessment of QOL during the first postoperative year., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hyponatremia is a common and potentially dangerous complication of transsphenoidal surgery. Prophylactic postoperative fluid restriction has been trialled as a method to reduce the incidence of postoperative hyponatremia., Methods: A systematic review of the literature was performed in accordance with the PRISMA statement. Risk of bias was assessed using the MINORS criteria. Meta-analysis was performed using the random-effects model., Results: A total of 6 retrospective cohort studies were available for analysis. Fluid restriction was commonly between 1000 and 1500 ml/day and limited to the first postoperative week. Overall, the rate postoperative hyponatremia was fourfold less in the fluid restricted cohorts (3.4 % vs 11.2 %, OR 0.24 (95 %CI 0.15-0.38), p < 0.01). There was no difference in readmission rates (1.4 % vs 3.9 %, OR 0.32 (95 %CI 0.09-1.13), p = 0.08) or postoperative diabetes insipidus (14.5 % vs 18.6 %, OR 0.82 (95 %CI 0.50-1.36), p = 0.45) between fluid restricted and control cohorts., Conclusion: Prophylactic postoperative fluid restriction is a cheap, easily implemented intervention that appears to reduce the rate of postoperative hyponatremia, but not necessarily re-admission rates. Whether these prevented cases of hyponatremia are clinically significant remains to be demonstrated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Control of cerebral blood flow (CBF) is crucial to the management of neurocritically ill patients. Small studies which have examined the role of cardiac output (CO) as a determinant of CBF have inconsistently demonstrated evidence of cardio-cerebral coupling. Putative physiological mechanisms underpinning such coupling include changes in arterial blood pressure pulsatility, which would produce vasodilation through increased oscillatory wall-shear-stress and baroreceptor mediated reflex sympatholysis, and changes in venous backpressure which may improve cerebral perfusion pressure. We sought to summarize and contextualize the literature on the relationship between CO and CBF and discuss the implications of cardio-cerebral coupling for neurocritical care. A systematic review of the literature yielded 41 studies; all were of low-quality and at high-risk of bias. Results were heterogenous, with evidence for both corroboration and confutation of a relationship between CO and CBF in both normal and abnormal cerebrovascular states. Common limitations of studies were lack of instantaneous CBF measures with reliance on transcranial Doppler-derived blood flow velocity as a surrogate, inability to control for fluctuations in established determinants of CBF (eg, PaCO 2 ), and direct effects on CBF by the interventions used to alter CO. Currently, the literature is insufficiently robust to confirm an independent relationship between CO and CBF. Hypothetically, the presence of cardio-cerebral coupling would have important implications for clinical practice. Manipulation of CBF could occur without the risks associated with extremes of arterial pressure, potentially improving therapy for those with cerebral ischemia of various etiologies. However, current literature is insufficiently robust to confirm an independent relationship between CO and CBF, and further studies with improved methodology are required before therapeutic interventions can be based on cardio-cerebral coupling., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The relationship between lumbar disc herniation (LDH) size and the severity of preoperative pain and its impact on postoperative recovery is incompletely understood. This study was conducted to investigate the association between herniated disc fragment weight and pain before and after microdiscectomy., Methods: A consecutive series of patients from an ongoing randomised controlled trial (ACTRN12616001360404) were included in this study. Included patients were aged between 18 and 75, had a clinical diagnosis of radiculopathy, and MRI evidence of a concordant single-level lumbar disc herniation. All patients underwent standard microdiscectomy without aggressive discectomy or curettage of the endplates. Disc fragment weight was measured intraoperatively., Results: A total of 122 patients with a mean age of 49.5 ± 12.8 years, were included. The median weight of disc fragment was 0.545 g (95% CI 0.364 - 0.654 g). There was no relationship between disc weight and the duration of symptoms (p = 0.409) severity of preoperative leg pain (p = 0.070) or preoperative back pain (p = 0.884). Disc fragment weight was demonstrated to have no correlation with clinically significant postoperative leg pain improvement (p = 0.535) or back pain (p = 0.991). Additional LDH factors, including radiological percentage of canal compromise (p = 0.714), herniation classification (p = 0.462), and vertebral level (p = 0.788) were also shown to have no effect on leg pain outcomes., Conclusions: Disc fragment weight had no effect on the severity of pain at presentation or after microdiscectomy. Patients benefit from surgery equally, regardless of the size of LDH., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Craniopharyngiomas are morbid tumors that significantly reduce patients' quality of life (QoL). The lifelong burden of endocrine, visual, hypothalamic, and limbic dysfunction can have disastrous consequences for the physical and psychosocial health of patients. Elucidating the factors that influence QoL could guide therapeutic interventions to improve patient well-being., Methods: A systematic review was performed in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement using the PubMed and Medline databases. Studies that had reported patient QoL using validated metrics in both adult and pediatric populations were included. Bias and methodological rigor were assessed using the MINORS (methodological index for nonrandomized studies) criteria., Results: A total of 25 studies, including 2025 patients, were available for review. Most studies were small, retrospective, cohort studies with a high risk of bias. The QoL of the patients with craniopharyngioma was lower than that of the general population. Hypothalamic involvement was consistently the strongest predictor of QoL. Endocrinopathy contributed to morbidity but could be ameliorated by hormone replacement therapy. Social and emotional dysregulation and a poor memory are common complaints after surgery, and iatrogenic damage to the infundibulum, hypothalamus, limbic system, and frontal lobes might underlie these concerns. Sleep-wake cycle dysfunction and hypothalamic obesity are serious consequences of hypothalamic damage., Conclusions: An experienced multidisciplinary team is necessary to optimally manage the complex cases of these patients. The poor QoL of patients with craniopharyngioma is multifactorial. However, the contribution of iatrogenesis is not insubstantial. Improved surgical techniques, focusing on hypothalamic preservation, and adjuvant treatment options are required to improve the well-being of these patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Patients with pituitary lesions experience decrements in quality of life (QoL) and treatment aims to arrest or improve QoL decline., Objective: To detect associations with QoL in trans-nasal endoscopic skull base surgery patients and train supervised learning classifiers to predict QoL improvement at 12 months., Methods: A supervised learning analysis of a prospective multi-institutional dataset (451 patients) was conducted. QoL was measured using the anterior skull base surgery questionnaire (ASBS). Factors associated with QoL at baseline and at 12-month follow-up were identified using multivariate logistic regression. Multiple supervised learning models were trained to predict postoperative QoL improvement with five-fold cross-validation., Results: ASBS at 12-month follow-up was significantly higher (132.19,SD = 24.87) than preoperative ASBS (121.87,SD = 25.72,p<0.05). High preoperative scores were significantly associated with institution, diabetes and lesions at the planum sphenoidale / tuberculum sella site. Patients with diabetes were five times less likely to report high preoperative QoL. Low preoperative QoL was significantly associated with female gender, a vision-related presentation, diabetes, secreting adenoma and the cavernous sinus site. Top quartile change in postoperative QoL at 12-month follow-up was negatively associated with baseline hypercholesterolemia, acromegaly and intraoperative CSF leak. Positive associations were detected for lesions at the sphenoid sinus site and deficient preoperative endocrine function. AdaBoost, logistic regression and neural network classifiers yielded the strongest predictive performance., Conclusion: It was possible to predict postoperative positive change in QoL at 12-month follow-up using perioperative data. Further development and implementation of these models may facilitate improvements in informed consent, treatment decision-making and patient QoL., Competing Interests: The authors have declared that no competing interests exist.

Objective: Incidental, asymptomatic pituitary adenomas require nuanced, shared decision-making, which is limited by a poor understanding of their natural history and effects on quality of life (QOL). A greater understanding of the effects of surgery would inform evidence-based care., Methods: A multicenter review of consecutive pituitary adenomas resected via an endoscopic endonasal approach (EEA) between late 2016 and mid-2021 was performed, with prospective, longitudinal QOL assessment (at 3 and 6 weeks and at 3, 6, and 12 months) postoperatively using the 35-item Anterior Skull Base Questionnaire., Results: Of 366 adenomas resected during the study period, 52 (14.2%) were incidentally discovered, of which 51 (98.1%) were macroadenomas. Preoperative QOL in patients with these incidentalomas was better than in those with adenomas presenting with endocrinopathy (p < 0.01), visual failure (p = 0.02), or headache (p = 0.03). Surgery was performed due to visual field deficits (13.5%, n = 7); ophthalmoplegia (1.9%, n = 1); radiological compression or contact of the optic apparatus (63.5%, n = 33); functional status (growth hormone-secreting tumor) (5.8%, n = 3); and clinically significant growth (15.4%, n = 8). Surgical outcomes were excellent, with vision improved in 100% (7/7) and complete resection in 84.6% (44/52). There were 2 (3.8%) cases of new cortisol deficiency, 3 (5.8%) cases of transient postoperative diabetes insipidus, and 4 (7.7%) cases of postoperative hyponatremia. There were no perioperative complications and no cases of postoperative CSF leakage. QOL transiently decreased during the first 3 weeks after surgery, then improved to above baseline levels by 3 months (p = 0.03) and continued to improve throughout the first postoperative year (p = 0.03). All surgical indications demonstrated an overall mean improvement in QOL at 3 months. QOL benefits were not affected by age or tumor size., Conclusions: Resection of pituitary adenomas via the EEA provided a tangible benefit for patients within 3 months. Surgery via the EEA is safe, effective, and beneficial for patients with pituitary incidentalomas meeting accepted criteria for intervention.

Brain computed tomography (CTB) scans are widely used to evaluate intracranial pathology. The implementation and adoption of CTB has led to clinical improvements. However, interpretation errors occur and may have substantial morbidity and mortality implications for patients. Deep learning has shown promise for facilitating improved diagnostic accuracy and triage. This research charts the potential of deep learning applied to the analysis of CTB scans. It draws on the experience of practicing clinicians and technologists involved in development and implementation of deep learning-based clinical decision support systems. We consider the past, present and future of the CTB, along with limitations of existing systems as well as untapped beneficial use cases. Implementing deep learning CTB interpretation systems and effectively navigating development and implementation risks can deliver many benefits to clinicians and patients, ultimately improving efficiency and safety in healthcare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There is a paucity of high quality evidence regarding the routine placement of lumbar drain (LD) in reducing post-operative (op) cerebrospinal fluid (CSF) leak after extended endoscopic trans-sphenoidal resection of anterior skull base lesions. In this study, we sought to compare the incidence of post-op CSF leak between patients with upfront LD insertion and those without it. This was a prospective randomized controlled trial conducted over a period of 5 years with patients undergoing extended endoscopic trans-sphenoidal surgery randomly assigned to either LD insertion at the time of surgery, or no LD placement. Thirty-eight patients with anterior skull base tumors were accrued from three tertiary hospitals of Melbourne. Post-op leak was confirmed by β2-transferrin-positive rhinorrhea, and/or worsening pneumocephalus on brain imaging. Skull base defect size and pedicled nasoseptal flap viability were assessed on post-op CT and MRI, respectively. There was no significant difference in post-op CSF leak incidence between the two subgroups (12.50% in LD arm vs. 9.10% in no LD arm). Patients with LD insertion however, demonstrated substantially raised complication rates, longer hospital lengths of stay and lower subjective quality of life measures at 12 months compared with those without LD. In conclusion, routine placement of LD at the time of surgery for extended anterior skull base trans-nasal approach did not reduce the risk of post-op CSF leak. Discretion is warranted when using LD as an adjunct due to its associated morbidities, prolonged hospital stay and adverse effect on patients' subjective outcome measures., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To establish the effect of endoscopic endonasal surgery (EES) on quality-of-life (QoL) in symptomatic Rathke cleft cyst (RCC)., Methods: Analysis of 38 patients with RCC treated by EES, with regular overall (ASBQ-35) and sinonasal-specific (SNOT-22) QoL assessment during the first postoperative year. A systematic literature review of large case series was performed with pooled analysis., Results: In our series, mean age was 53.6 years with a female predominance (73.7%). Larger cysts were seen in males (p < 0.01), those with hypogonadism (p = 0.04), and visual dysfunction (p = 0.04). Complete normalisation of vision was seen in 83.3%. Persistence of visual dysfunction postoperatively was associated with diabetes (p = 0.005), hypertension (p = 0.02), suprasellar only location (p = 0.001), and monocular field cut (p = 0.02). Surgery did not significantly effect hormonal function. Sinonasal QoL transiently worsened after surgery, resolving within 3 weeks. A parallel transient worsening of overall QoL normalised by 6 weeks, and remained at preoperative baseline thereafter. These results were comparable to the literature, where 76.4% demonstrated improvement of vision and 13.1% had recurrence after treatment. There was no significant difference in outcomes between EES and microscopic approaches., Conclusions: We report longitudinal QoL outcomes in RCC for the first time. Vision commonly improves with surgery, but endocrinopathy is likely to persist. Microvascular risk-factors may compromise visual improvement. Surgery causes a transient worsening of sinonasal symptoms that resolves within 3-6 weeks, but patients may not experience significant improvement in QoL within the first postoperative year., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Surgery for pituitary adenoma is indicated for relief of mass effect and control of endocrinopathy. Setting benchmarks for visual and hormonal outcomes is important for monitoring performance of surgical centres, while understanding the preoperative factors that predict endocrine cure and visual improvement facilitates tailored counselling for patients prior to surgery. A prospective, consecutive cohort of surgically managed (endoscopic transsphenoidal) pituitary adenoma (n = 304) were analysed. Preoperative and postoperative endocrine and visual field assessments were performed and compared to demographic, imaging and pathological data. Larger adenomas tended to have preoperative endocrine deficiency (p < 0.001) and visual field defects (p < 0.001). The largest tumours did not experience normalisation of their endocrinopathy or visual fields with surgery. Of the adenomas with normal preoperative endocrine function, 92.0% (126/137) maintained this postoperatively; only 2 of the 11 patients with new hypopituitarism required long-term hormone replacement. Functional tumour cure was achieved in 65.2% (86/116) after surgery; 74.4% (32/43) of acromegalics and 70.0 (35/50) of Cushing's disease patients achieved hormonal control. All patients with isolated hyperprolactinaemia from stalk effect normalised with surgery, while only 15.9% (7/44) with hypopituitarism recovered normal endocrine function. New hypopituitarism was predicted by younger age and functional adenoma, particularly Cushing's disease. Resolution of endocrinopathy was less likely with reoperative cases and those with cavernous sinus invasion (Knosp grade > 2) or preoperative ophthalmoplegia. One-third of the cohort (102/304, 33.6%) had a preoperative field cut, most commonly an incomplete (51.0%) or complete (31.4%) bitemporal hemianopsia. Only two patients (2/304, 0.7%) had visual field worsening after surgery, while 71.6% (73/102) experienced partial or complete resolution of their field cut after surgery. Complete resolution of visual field defect was predicted by younger age and incomplete bitemporal hemianopsia. Surgery is a safe and effective therapy for pituitary adenomas. Nearly all patients experience improvement in visual fields, especially the young and those with incomplete bitemporal defects. Reoperative cases and those with cavernous sinus involvement (high Knosp grade/ophthalmoplegia) are less likely to have resolution of endocrinopathy. Visual worsening, new ophthalmoplegia or endocrinopathy were rare complications of surgery., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A local sphenoid mucosal flap (SMF) is naturally raised during endonasal exposure of the sella. Typically, these flaps are repositioned; however, they could be used in place of a nasoseptal flap (NSF) for closure of low-grade CSF leaks. In this study, we aim to establish the safety and efficacy of SMF closure for low-grade CSF leaks and to assess the impact on sinonasal quality of life (QoL) compared to NSF closure. In a consecutive, prospective cohort of anterior skull base pathology, data regarding sellar and suprasellar extension (Hardy grade), cavernous sinus invasion (Knosp grade), intraoperative (Kelly grade) and postoperative CSF leak, and sino-nasal QoL data (SNOT-22) were analysed. Of 187 patients with no/low flow (Kelly 0-1) intraoperative CSF leak, 127 (67.9%) received a SMF and 60 (32.1%) received a NSF. A total of 141/187 (75.4%) had no intraoperative leak, while 46/187 (24.6%) had grade-1 leaks. SMF were used in 70.9% (100/141) of cases without intraoperative leak, and 58.7% (27/46) of cases with Kelly grade-1 leaks. Hardy grade 4, grade E and Knosp grade 4 lesions were all more commonly closed with a NSF (p < 0.05). Two patients (1.1%) had postoperative CSF leaks, both in the SMF group, and both after no discernible intraoperative leak. Sinonasal QoL was below baseline for up to 3 months postoperatively. SMF cases tended to have better sinonasal QoL for up to 6 weeks after surgery. Thus, in the largest cohort to date, SMF are a safe alternative to NSF for closure low-grade skull base defects. Sinonasal QoL was better in the first 6 weeks after SMF closure than NSF closure., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hydrocephalus is the symptomatic endpoint of a variety of disease processes. Simple hydrodynamic models have failed to explain the entire spectrum of cerebrospinal fluid (CSF) disorders. Physical principles argue that for ventricles to expand, they must be driven by a force, Fishman's transmantle pressure gradient (TMPG). However, the literature to date, reviewed herein, is heterogenous and fails to consistently measure a TMPG. The venous system, like CSF, traverses the cerebral mantle, and thus analogous transparenchymal and transvenous pressure gradients have been described, reliant on the differential haemodynamics of the deep and superficial venous systems. Interpreting CSF disorders through these models provides new insights into the possible pathophysiological mechanisms underlying these diseases. However, until more sophisticated testing is performed, these models should remain heuristics., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The objective of this study was to establish the effect of endoscopic endonasal surgery on longitudinal quality of life (QOL) in patients with anterior skull base meningioma., Methods: A prospectively collected cohort of consecutively operated anterior skull base meningiomas was analyzed. All cases were performed using the endoscopic endonasal approach (EEA). Sinonasal-specific and overall QOL were measured using the 22-Item Sinonasal Outcome Test and the Anterior Skull Base Questionnaire longitudinally (at 3 weeks, 6 weeks, and 3, 6, and 12 months) across the first postoperative year. The relationship between surgical and QOL outcomes to clinical and radiological characteristics was analyzed using multivariate regression., Results: Fifty cases were available, with a mean age of 61.5 years and female predominance (74.0%). Visual dysfunction and headache were the most common presenting symptoms, and tumors commonly took origin from the planum (46.0%), tuberculum (44.0%), and olfactory groove (24.0%). Median tumor volume was 4.6 cm3. Visual improvement was noted in 73.1% of cases with preoperative field deficits, while nonimprovement was associated with greater tumor height (p = 0.04). Gross-total resection was not possible in patients with 360° vessel encasement and high-grade cavernous sinus extension with ophthalmoplegia. Postoperative diabetes insipidus was observed only in cases with suprasellar extension. Sinonasal-specific QOL worsened transiently after surgery but returned to baseline levels after 3 weeks. Olfaction and taste scores returned to preoperative baseline scores within the year. Overall QOL at presentation was worse in those with larger tumors (p = 0.04) and visual failure (p = 0.04) and better in those presenting with headache (p = 0.04). Transient worsening of QOL was seen in the first 3 weeks, which returned to baseline by 6 weeks, and then improved to above preoperative levels at 6 months and beyond. Worse QOL at baseline (p = 0.01) and visual improvement (p = 0.01) predicted QOL improvement after surgery., Conclusions: Longitudinal QOL in anterior skull base meningioma has been examined for the first time. Endoscopic endonasal surgery improves overall QOL after a transient 3-week worsening due to the sinonasal morbidity of the approach. Visual function is intimately tied to QOL, with worse vision associated with worse preoperative QOL, and QOL improving in parallel with visual restoration after surgery. The EEA is associated with better visual outcomes and should be the preferred approach in accessible tumors.

Background: Patient-reported quality of life (QOL) is a vital metric for surgical success., Objective: To assess the effect of surgery on QOL in the largest prospectively collected, longitudinal cohort of surgically managed pituitary adenomas., Methods: A consecutive surgical adenoma cohort (n = 304) between late 2016 and mid-2020 underwent a scheduled overall (Anterior Skull Base Questionnaire-35) and sinonasal-specific (Sinonasal Outcome Test-22) QOL assessment. Scores were stratified by adenoma subtype and analyzed for clinical predictors of QOL changes., Results: The average age was 53.8 ± 16 yr, and 53% of participants were female. 60.9% of adenomas were nonfunctioning while adrenocorticotropic hormone adenomas (16.4%), growth hormone adenomas (14.1%), and prolactinomas (5.9%) were the most prevalent secreting adenomas. Baseline overall QOL differed between tumor types (P = .006), with adrenocorticotropic hormone adenomas worse than growth hormone adenomas (P = .03) and nonfunctioning pituitary adenomas (NFPA) (P < .001). Sinonasal QOL worsened in the 3 wk after surgery but returned to baseline by 6 wk and beyond. Overall QOL worsened at 3 wk after surgery (P < .001) but significantly improved from baseline by 3 mo (P = .009) and beyond (P < .001). Emotional functioning improved soon after surgery, followed by performance and pain, and then, by 6 mo, physical function and vitality. Predictors of improved QOL were sellar/suprasellar lesions (P = .01), prolactinomas (P = .003), and NFPA (P = .04). Conversely, new postoperative hypopituitarism (P = .04) and larger adenoma volume (P = .04) predicted QOL worsening., Conclusion: QOL is worsened after surgery at early time points. Prolactinomas and NFPA enjoy significant QOL improvements from surgery as early as 3 mo postoperatively. Other functional tumors may experience early benefits in younger patients without hypopituitarism and when isolated to the sellar/suprasellar region. These findings provide valuable information for counseling patients and setting expectations for surgery., (Copyright © Congress of Neurological Surgeons 2021. All rights reserved.)

Small trials have demonstrated promising results utilising intravenous milrinone for the treatment of delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH). Here we summarise and contextualise the literature and discuss the future directions of intravenous milrinone for DCI. A systematic, pooled analysis of literature was performed in accordance with the PRISMA statement. Methodological rigour was analysed using the MINORS criteria. Extracted data included patient population; treatment protocol; and clinical, radiological, and functional outcome. The primary outcome was clinical resolution of DCI. Eight hundred eighteen patients from 10 single-centre, observational studies were identified. Half (n = 5) of the studies were prospective and all were at high risk of bias. Mean age was 52 years, and females (69%) outnumbered males. There was a similar proportion of low-grade (WFNS 1-2) (49.7%) and high-grade (WFNS 3-5) (50.3%) SAH. Intravenous milrinone was administered to 523/818 (63.9%) participants. Clinical resolution of DCI was achieved in 375/424 (88%), with similar rates demonstrated with intravenous (291/330, 88%) and combined intra-arterial-intravenous (84/94, 89%) therapy. Angiographic response was seen in 165/234 (71%) receiving intravenous milrinone. Hypotension (70/303, 23%) and hypokalaemia (31/287, 11%) were common drug effects. Four cases (0.5%) of drug intolerance occurred. Good functional outcome was achieved in 271/364 (74%) patients. Cerebral infarction attributable to DCI occurred in 47/250 (19%), with lower rates in asymptomatic spasm. Intravenous milrinone is a safe and feasible therapy for DCI. A signal for efficacy is demonstrated in small, low-quality trials. Future research should endeavour to establish the optimal protocol and dose, prior to a phase-3 study., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Introduction: Frailty is a state of physiological vulnerability that negatively influences surgical outcomes. The effect of frailty on pituitary adenoma surgery, however, is not clear, and patients may be wrongly denied surgery because they are "too frail". We examined the effects of frailty on surgical outcome and quality-of-life (QoL) in patients undergoing endoscopic transsphenoidal resection of pituitary adenomas., Methods: A prospective, consecutive cohort of surgically managed pituitary adenoma was analysed. Frailty was defined by the 5-factor modified Frailty Index (mFI-5) and the Charlson Comorbidity Index (CCI). QoL was measured by the anterior skull base questionnaire (ASBQ) and sinonasal outcomes test (SNOT)., Results: Of 304 patients with pituitary adenomas, 42 (13.8%) were frail (mFI5 of > 1). Frail patients tended to have smaller adenomas (p < 0.0001) with less suprasellar extension (p < 0.0001). Both overall (ASBQ) and sinonasal-specific (SNOT) QoL were not affected by frailty on multivariate analysis. Endocrine and visual outcomes were similarly not worsened by frailty. Overall, medical complications were uncommon, and perioperative morbidity or mortality was not significantly greater in the frail group., Conclusion: Frail patients experience the same QoL benefits from surgery as their non-frail counterparts, and have equivalently successful visual and endocrine outcomes. Frailty should not be seen as a barrier to successful surgical management of pituitary adenomas., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To identify risk factors for the development of postoperative diabetes insipidus (DI) in a modern cohort of endoscopic endonasal transsphenoidal surgery., Methods: Analysis of prospectively collected data of 449 consecutive patients operated on for anterior skull base pathology. DI was defined as a polyuria (> 250 ml/h for ≥ 2 consecutive hours) polydipsia syndrome associated with hypotonic urine with or without hypernatraemia. Multivariate logistic regression was used to identify predictors of postoperative DI. A simple scoring system was then created., Results: Postoperative DI occurred in 46 (10.2%) patients. The development of DI did not affect quality of life. Predictors of DI on multivariate analysis included suprasellar extension (OR 2.2; p = 0.04), age < 50 years (OR 2.8; p = 0.003), craniopharyngioma histology (OR 6.7; p = 0.002), and Kelly grade 3 intraoperative CSF leak (OR 2.1; p = 0.04). The SALT score was created based on these characteristics, with one point awarded for each feature present, and predicted DI with fair to good predictive value in our cohort (AUROC 0.735 (95%CI 0.65-0.82)). The rates of postoperative DI were 4.0%, 6.5%, 15.0%. 36.8% and 85.7% for SALT scores of zero, one, two, three, and four, respectively., Conclusions: The SALT score predicts postoperative DI with fair to good accuracy, and now requires prospective external validation. Improved prediction of DI could optimize resource allocation and facilitate individualised preoperative patient counselling. We also provide our algorithm for diagnosis and treatment of DI., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Knowledge of anatomy and its variations is the key to safe and efficient surgery. The endoscopic endonasal route to the sella has evolved to become the preferred route to access a wide variety of diseases. We describe the skeletal, vascular, and neural anatomic variations that could be encountered from the nasal phase, through the sphenoid phase, to the sellar phase of the operative exposure. A preoperative checklist is also provided., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Disorders of tonicity, hyponatraemia and hypernatraemia, are common in neurosurgical patients. Tonicity is sensed by the circumventricular organs while the volume state is sensed by the kidney and peripheral baroreceptors; these two signals are integrated in the hypothalamus. Volume is maintained through the renin-angiotensin-aldosterone axis, while tonicity is defended by arginine vasopressin (antidiuretic hormone) and the thirst response. Edelman found that plasma sodium is dependent on the exchangeable sodium, potassium and free-water in the body. Thus, changes in tonicity must be due to disproportionate flux of these species in and out of the body. Sodium concentration may be measured by flame photometry and indirect, or direct, ion-sensitive electrodes. Only the latter method is not affected by changes in plasma composition. Classification of hyponatraemia by the volume state is imprecise. We compare the tonicity of the urine, given by the sodium potassium sum, to that of the plasma to determine the renal response to the dysnatraemia. We may then assess the activity of the renin-angiotensin-aldosterone axis using urinary sodium and fractional excretion of sodium, urate or urea. Together, with clinical context, these help us determine the aetiology of the dysnatraemia. Symptomatic individuals and those with intracranial catastrophes require prompt treatment and vigilant monitoring. Otherwise, in the absence of hypovolaemia, free-water restriction and correction of any reversible causes should be the mainstay of treatment for hyponatraemia. Hypernatraemia should be corrected with free-water, and concurrent disorders of volume should be addressed. Monitoring for overcorrection of hyponatraemia is necessary to avoid osmotic demyelination., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Pyramidal weakness, that is, the weakness that preferentially spares the antigravity muscles, is considered an integral part of the upper motor neuron syndrome. Despite its name, pyramidal weakness has very little to do with the pyramidal tract, and preeminent texts on neurology, neuroanatomy, and clinical examination differ considerably in their descriptions and localization of this enigmatic finding. Evidence from human and nonhuman primate studies demonstrates that lesions confined only to the corticospinal (pyramidal) tract cause significant deficits in fine motor control of the hand, but do not cause posturing or patterned weakness of the extremities. Lesioning of the corticofugal fibers, particularly the corticoreticular and corticopontine tracts, leads to dysbalanced output from reticulospinal, and vestibulospinal systems, which along with changes in rubrospinal tract output balance, probably accounts for the pyramidal weakness pattern. Importantly, this would delineate that pyramidal weakness could only be incited by lesions above the brainstem. It has also been suggested that the inherently greater strength of the antigravity musculature is the substrate for pyramidal weakness, independent of any preferential motor innervation. These hypotheses require further testing in myometric studies with carefully selected participants., (© 2020 American Association of Clinical Anatomists.)

Tumour to tumour metastasis is a rare event, especially in the pituitary. Metastases to pituitary adenomas most commonly occurs in late stage disease, commonly presenting with visual field defects and adenohypophyseal dysfunction. The most frequent primary cancers are lung, breast and renal carcinoma which deposit most commonly in prolactinomas, somatotropinomas, gonadotropinomas. In nearly 40% of cases, sellar symptoms are the harbinger to the diagnosis of primary malignancy. The abnormal vascularity and growth promoting microenvironment of pituitary adenomas may encourage metastatic seeding and proliferation of these "collision tumours". Here, we present a case of a breast carcinoma metastasis to a pituitary null-cell adenoma in the setting of immunotherapy. Infundibular thickening in the setting of immunotherapy is often ascribed to hypophysitis, but our case highlights that metastatic spread should be part of the differential diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Tension pneumocephalus (TP) is a rare but feared complication of endoscopic endonasal skull base surgery. In contrast to simple pneumocephalus, which is common after endoscopic transnasal approaches and managed conservatively, TP represents a neurosurgical emergency and mandates urgent decompression., Case Description: Here we present 2 cases of TP as a consequence of positive pressure ventilation following endoscopic endonasal skull base surgery. Both occurred during resuscitation for postoperative hypoxia. These cases prompted the development of an institution-wide protocol to identify and manage patients at risk of TP after extended skull base approaches., Conclusions: To our knowledge, these are the only such cases of postoperative TP following positive pressure ventilation in the literature., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The endoscopic endonasal approach to the skull base avoids some of the surgical morbidity associated with a transcranial approach, however it often results in large skull-base defects requiring secure closure. The nasoseptal flap has become the preferred method for closure of such defects but may be associated with its own morbidity., Methods: A consecutive cohort of patients with skull base pathology with prospectively collected quality of life data using ASBQ and SNOT was analysed. They were grouped into those who received a nasoseptal flap and those who did not. Pre-operative total ASBQ and SNOT scores, and their individual components, were compared to data collected at days 1, 3, and 7; six-weeks; and 3, 6, and 12-months postoperatively., Results: Of 158 patients available for analysis, nasoseptal flaps were performed in 52 (33%). Average follow-up (±standard deviation) was 8.1 ± 3.9 months for ASBQ data and 8.2 ± 3.8 months for SNOT data. In the first post-operative week, nasal symptoms and otalgia were worse in the flap group. At six-weeks and beyond, there was no difference between groups in overall ASBQ or SNOT scores, or in the rate of clinically-significant improvement in SNOT or ASBQ scores or their components., Conclusion: In the largest cohort of patients to date, the use of a nasoseptal flap is associated with nasal symptoms and otalgia in the acute post-operative period, but is not associated with any long-term detriment to quality of life after endoscopic skull base surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Intraoperative localization in spinal surgery is essential to facilitate the best surgical outcome and to avoid wrong-site surgery. Intraoperative fluoroscopy is generally adequate, but anatomical variation, body habitus, and the inherent difficulties of fluoroscopy at certain levels may lead the surgeon astray. Here, the authors present their technique for preoperative localization that relies solely on fixed anatomical landmarks using CT-guided, percutaneously placed radiopaque markers. In the outpatient setting, low-dose CT scanning of the neuraxis is performed to identify fixed landmarks and, under local anesthesia and CT guidance, a pushable microcoil is inserted through a Chiba needle into the periosteum of the pedicle at the level of interest. The patient returns home with no precautions while the coil is in situ, and then the patient returns sometime later for surgery. Intraoperatively, typically a single lateral radiograph is required to visualize the coil and the level. Preoperative placement of radiopaque markers at the level of interest is an effective tool for avoiding wrong-site surgery, especially in circumstances in which fluoroscopy may be troublesome. The authors' method is accurate, effective, and expeditious and can be performed easily in the outpatient setting.

Study Design: Prospective cohort study., Objectives: Evidence on predicting the success of indirect decompression via extreme lateral interbody fusion (XLIF) is scarce. The authors investigated if patients who could achieve a pain-free position preoperatively would derive clinical benefit from XLIF without direct decompression., Methods: Data from 50 consecutive patients who underwent XLIF with and without direct decompression by a single surgeon from January 2014 to August 2017 was collected. Primary outcome is the rate of failure of patients who underwent XLIF without direct decompression, characterized by persistence of pain postoperatively that required reoperations within 6 months postoperatively. Secondary outcomes are clinical outcomes and patient-reported quality of life outcome data, including visual analogue scale for leg (VASL) and back (VASB) pain, Oswetry Disability Index (ODI), and Physical Component Score (PCS) and Mental Component Score (MCS) of SF-12, for up to 2 years postoperatively., Results: One patient with preoperative dynamic posture-related pain who underwent XLIF without direct decompression subsequently had a reoperation due to persisting pain. Statistically significant improvement was achieved across all patient reported outcomes ( P < .05): improvement of 68% for VASL, 61% for VASB, 50% for ODI, 33% for PCS, and 11% for MCS of SF-12 at last follow-up. Six patients had thigh symptoms that resolved., Conclusion: The simple clinical criterion based on postural pain status preoperatively may help clinicians in patient selection for indirect decompression of XLIF without the need for direct decompression. Further studies with larger cohorts are warranted to establish the validity of the algorithm., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Reliability study., Objective: To evaluate the applicability and reliability of 9.4T magnetic resonance imaging (MRI) in the assessment of degenerative disc disease compared with 3T MRI., Summary of Background Data: MRI is a reliable indicator of biochemical changes in the intervertebral disc (IVD) including hydration status, proteoglycan content, and disc degeneration compared with anatomical and histological studies. High-field 9.4T MRI has been shown to provide superior resolution and anatomical detail. However, it has not been tested against current standard MRI techniques., Methods: Disc degeneration was initiated in 36 skeletally mature ewes 6 months prior to necropsy via validated surgical IVD injury models using either scalpel injury or drill-bit injury techniques at lumbar spine levels L2/3 and L3/4 with L1/2, L4/5, and L5/6 serving as control discs. All ex vivo IVDs were examined with 9.4T MRI and 3T MRI. All scans were analyzed using the Pfirrmann grading system by four independent observers. Intra- and interobserver reliability was assessed using kappa statistics and Spearman correlation., Results: Inter- and intraobserver agreement for 9.4T MRI was excellent, both at κ 0.91 (P < 0.001). Comparatively, 3T interobserver reliability demonstrated substantial agreement at κ 0.61 (P < 0.001). Complete agreement was obtained in 92.7% to 100% of discs at 9.4T compared with 69.7% to 83.1% at 3T. A difference of one grade or more occurred in 6.7% at 9.4T and 39.3% at 3T. 9.4T MRI scored 97.3% of discs as grade 1 to 2 compared with 71.3% at 3T. 3T MRI tended to over-score the extent of disc degeneration with 28.6% of discs scored as grade 3 or higher compared with 2.7% at 9.4T MRI., Conclusion: 9.4T MRI study of IVD degeneration using the Pfirrmann grading system demonstrated excellent inter- and intraobserver reliability. Comparatively, 3T MRI demonstrated a tendency to over score the extent of disc degeneration. This improved reliability of 9.4T MRI holds great potential for its clinical applications., Level of Evidence: 3.

This study aimed to assess the correlation of sagittal balance parameters measured intraoperatively, against the gold standard post-operative standing full spine X-ray. A secondary aim was to create a predictive algorithm, that could be used intraoperatively to predict the post-operative balance. 49 patients, who underwent thoracolumbar spinal fusion over a 12-month period were included in this study. Standing full-spine X-rays were obtained both pre and post-surgical fixation. Parallel intraoperative X-rays were taken with the c-arm centred on femoral heads, operative level, S1 and L1. The sagittal parameters pelvic incidence (PI), lumbar lordosis (LL), spino-pelvic mismatch (PI-LL), and sagittal vertical axis were then measured and the correlations statistically analysed. For prone positioned patients the mean LL was 59.9° ± 10.6° intraoperatively (post-fixation) and post-operatively 55.4° ± 10.9° with a mean difference of -4.5° ± 6.1° (p-value < 0.001). For laterally positioned patients the mean LL was 50.9° ± 8.6° intraoperatively and 53.1° ± 10.1° postoperatively for a mean difference of -2.3° ± 6.5° (p-value = 0.117). The linear regression analysis resulted in a predictive algorithm that can be utilised intraoperatively to predict the post-operative standing pelvic mismatch for prone positioned patients. In conclusion, measuring spino-pelvic parameters of sagittal balance intraoperatively can be used to estimate postoperative standing full spine x-ray result. Specifically, in the prone position, the surgeon should aim for intraoperative lordosis that is 4.5° more than the desired post-operative lordosis. The predictive formula provides a direct method to quickly calculate the post-operative pelvic mismatch intraoperatively., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Study Design: Large animal research., Objective: Lumbar discectomy is the most commonly performed spinal surgical procedure. We investigated 2 large animal models of lumbar discectomy in order to study the regenerative capacity of mesenchymal stem cells following disc injury., Methods: Twelve adult ewes underwent baseline 3-T magnetic resonance imaging (MRI) followed by lumbar intervertebral disc injury by either drill bit (n = 6) or annulotomy and partial nucleotomy (APN) (n = 6). Necropsies were performed 6 months later. Lumbar spines underwent 3-T and 9.4-T MRI prior to histological, morphological and biochemical analysis., Results: Drill bit-injured (DBI) and APN-injured discs demonstrated increased Pfirrmann grades relative to uninjured controls ( P < .005), with no difference between the 2 models. Disc height index loss was greater in the APN group compared with the DBI group ( P < .005). Gross morphology injury scores were higher in APN than DBI discs ( P < .05) and both were higher than controls ( P < .005). Proteoglycan was reduced in the discs of both injury models relative to controls ( P < .005), but lower in the APN group ( P < .05). Total collagen of the APN group disc regions was higher than DBI and control discs ( P < .05). Histology revealed more matrix degeneration, vascular infiltration, and granulation in the APN model., Conclusion: Although both models produced disc degeneration, the APN model better replicated the pathobiology of human discs postdiscectomy. We therefore concluded that the APN model was a more appropriate model for the investigation of the regenerative capacity of mesenchymal stem cells administered postdiscectomy., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Sellar arachnoid cysts are a rare occurrence but may impinge on vital parasellar anatomy and thus are often symptomatic. The etiology of sellar arachnoid cysts is contentious, fueled by heterogeneity in cyst wall structure and contents between cases. The "ball-valve" mechanism is 1 of 2 predominant theories describing their formation, which contends that an aperture in the diaphragm allows cerebrospinal fluid to enter the cyst, propelled by pulsatile flow, but its egress is obscured by the pituitary during the ebb of the pressure wave., Case Description: Here we present a case of a 51-year-old female with a symptomatic sellar arachnoid cyst. She underwent an endoscopic transsphenoidal fenestration which alleviated her symptoms., Conclusions: Intraoperative video evidence during arachnoid cyst fenestration supports the "ball-valve" theory of sellar arachnoid cyst development., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The pituitary gland is an unusual site for metastatic spread, but as patients with metastatic malignancy are living longer, it may become more prevalent. Compression of important anatomy adjacent to the sella may produce disabling symptoms and endocrine derangement, leading to significant morbidity., Methods: An ambispective review of patient records between 2013 and 2017 from three neurosurgical centres was performed. After identifying cases, further investigation was performed to evaluate patient demographic, symptoms at presentation, radiological and histological findings, management, and outcome., Results: Our investigation identified 12 patients with pituitary metastasis. The average age of the cases was 63.4 years, with breast (n = 4) and lung (n = 4) being the most common primary cancers. In half the cases there was a history of metastatic disease, while in one-quarter of cases, pituitary symptoms were the first sign of malignancy. Adenohypophyseal dysfunction (83%), diabetes insipidus (DI) (75%), headache (67%) and visual field defects (67%) were the most common findings at presentation. Glucocorticoid replacement increased the sensitivity for diagnosis of DI. All cases were contrast enhancing on MRI and the endoscopic trans-sphenoidal approach was preferred for biopsy and debulking., Conclusions: The pituitary should not be overlooked as a site of metastasis and sellar symptoms may be the first presentation of neoplastic disease. Any biochemical or clinical sign of pituitary pathology in a patient with known cancer should raise suspicion for sellar metastasis. Moreover, the development of DI or ophthalmoplegia from any pituitary lesion is suggestive of metastatic disease even in patients with no known primary.

Background: The reporting of adverse events (AEs) in neurosurgery uses inconsistent definitions and subjective grading systems. A standardized system for recording and describing AEs would allow valid comparisons to be drawn between different institutions, using different technologies, at different times. The Spinal Adverse Events Severity System - Neuro (SAVES-N) system is a modification of the well-validated SAVES-V2 system that encompasses complications from both cranial and spinal surgery. The objective of this study was to assess the interobserver reliability of SAVES-N in spinal and cranial neurosurgery., Methods: Ten vignettes, including cranial and spinal neurosurgical cases, were assessed by groups of consultant neurosurgeons (n = 5) and neurosurgical registrars (n = 5) using the SAVES-N system. Interobserver reliability for the presence of AEs, the type of AE, and the SAVES severity grade of the AE were calculated using Gwet's AC2 and Fleiss' kappa and were interpreted using the thresholds described by Landis and Koch., Results: Neurosurgeons had almost-perfect agreement (Gwet AC2 = 0.93), whereas registrars had substantial agreement (Gwet's AC2 = 0.74) in determining the presence or absence of AEs. Both neurosurgeons (Fleiss' kappa = 0.78) and registrars (Fleiss' kappa = 0.70) demonstrated substantial agreement within their groups as to the type of AE. Similarly, neurosurgeons (Gwet's AC2 = 0.94) and registrars (Gwet's AC2 = 0.81) both graded the severity of the AE with almost perfect agreement., Conclusions: The results of this study demonstrate that the scope of the well-validated SAVES-V2 system may be broadened to cranial neurosurgical cases by SAVES-N with substantial to almost-perfect interobserver reliability., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Pituitary adenomas are common, often asymptomatic tumours that are diagnosed incidentally by magnetic resonance imaging (MRI) of the brain. There is considerable variation in the reporting of pituitary MRI, in part because there is no consensus as to what information should be included in such reports. Synoptic reporting consists of using structured checklists to standardize communication. It has been adopted in the surgical pathology literature and more recently in the breast imaging field. The purpose of this study was to assess what parameters of a pituitary MRI report were useful to surgeons and in doing so, to propose a synoptic reporting template., Methods: We used the Delphi technique to obtain group consensus between three neuroradiologists, three otolaryngologists and three anterior skull base neurosurgeons across three tertiary Melbourne hospitals. Answers from the three speciality groups were then converted into numerical scores for analysis., Results: There was statistically significant consensus between specialties over which characteristics were deemed most important. These were T1 pre- and post-contrast sequences in the coronal and sagittal planes, the degree of displacement of the optic chiasm, invasion of the medial wall of the cavernous sinus, the size and pneumatization pattern of the sphenoid sinus and the differential diagnosis of aneurysm. There were also significant differences between groups., Conclusions: There are similarities and differences between what radiologists, otolaryngologists and neurosurgeons deem as important features when reporting pituitary MRI. A synoptic reporting system template is proposed to improve consistency in pituitary imaging reports., (© 2018 Royal Australasian College of Surgeons.)

Purpose: We have previously reported a small series on the closure of large myelomeningocele (MMC) defects with a keystone design perforator island flap (KDPIF) in a paediatric neurosurgical centre in Australia. We are now presenting an updated longer term follow-up of an expanded series demonstrating longer term durability of this vascularized flap for large myelomeningocele defects., Methods: The prospective data from the Monash Neurosurgical Database were used to select all cases of MMC between December 2008 and September 2016. Retrospective analysis of the neurosurgical database revealed an additional three patients who underwent KDPIF closure at the Monash Medical Centre for MMC repair at birth., Results: Wound healing was satisfactory in all six cases. With delayed follow-up, there was no associated skin flap separation, skin flap dehiscence, skin flap necrosis, cerebro-spinal fluid leak, however two infections were encountered, both resolved with conservative management including antibiotics and simple washout., Conclusion: In this expanded case series with increased longevity of follow-up, the keystone design perforator island flap remains a robust alternative for closure of large myelomeningocele defects.

Background Context: Neural compression associated with lumbar disc herniation is usually managed surgically by microdiscectomy. However, 10%-20% of patients re-present with debilitating back pain, and approximately 15% require further surgery., Purpose: Using an ovine model of microdiscectomy, the present study investigated the relative potential of pentosan polysulfate-primed mesenchymal progenitor cells (pMPCs) or MPC alone implanted into the lesion site to facilitate disc recovery., Study Design: An ovine model of lumbar microdiscectomy was used to compare the relative outcomes of administering MPCs or pMPCs to the injury site postsurgery., Methods: At baseline 3T magnetic resonance imaging (MRI) of 18 adult ewes was undertaken followed by annular microdiscectomy at two lumbar disc levels. Sheep were randomized into three groups (n=6). The injured controls received no further treatment. Defects of the treated groups were implanted with a collagen sponge and MPC (5×10 5 cells) or pMPC (5×10 5 cells). After 6 months, 3T MRI and standard radiography were performed. Spinal columns were dissected, individual lumbar discs were sectioned horizontally, and nucleus pulposus (NP) and annulus fibrosus (AF) regions were assessed morphologically and histologically. The NP and AF tissues were dissected into six regions and analyzed biochemically for their proteoglycans (PGs), collagen, and DNA content., Results: Both the MPC- and pMPC-injected groups exhibited less reduction in disc height (p<.05) and lower Pfirrmann grades (p≤.001) compared with the untreated injury controls, but morphologic scores for the pMPC-injected discs were lower (p<.05). The PG content of the AF injury site region (AF1) of pMPC discs was higher than MPC and injury control AF1 (p<.05). At the AF1 and contralateral AF2 regions, the DNA content of pMPC discs was significantly lower than injured control discs and MPC-injected discs. Histologic and birefringent microscopy revealed increased structural organization and reduced degeneration in pMPC discs compared with MPC and the injured controls., Conclusions: In an ovine model 6 months after administration of pMPCs to the injury site disc PG content and matrix organization were improved relative to controls, suggesting pMPCs' potential as a postsurgical adjunct for limiting progression of disc degeneration after microdiscectomy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Lumbar microdiscectomy is the most commonly performed spine surgery procedure. Over time it has evolved to a minimally invasive procedure. Traditionally patients were advised to restrict activity following lumbar spine surgery. However, post-operative instructions are heterogeneous. The purpose of this report is to assess, by survey, the perioperative care practices of Australasian neurosurgeons in the minimally invasive era., Methods: A survey was conducted by email invitation sent to all full members of the Neurosurgical Society of Australasia (NSA). This consisted of 11 multi-choice questions relating to operative indications, technique, and post-operative instructions for lumbar microdiscectomy answered by an electronically distributed anonymized online survey., Results: The survey was sent to all Australasian Neurosurgeons. In total, 68 complete responses were received (28.9%). Most surgeons reported they would consider a period of either 4 to 8 weeks (42.7%) or 8 to 12 weeks (32.4%) as the minimum duration of radicular pain adequate to offer surgery. Unilateral muscle dissection with unilateral discectomy was practiced by 76.5%. Operative microscopy was the most commonly employed method of magnification (76.5%). The majority (55.9%) always refer patients to undergo inpatient physiotherapy. Sitting restrictions were advised by 38.3%. Lifting restrictions were advised by 83.8%., Conclusions: Australasian neurosurgical lumbar microdiscectomy perioperative care practices are generally consistent with international practices and demonstrate a similar degree of heterogeneity. Recommendation of post-operative activity restrictions by Australasian neurosurgeons is still common. This suggests a role for the investigation of the necessity of such restrictions in the era of minimally invasive spine surgery., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: The pharmaceutical agent pentosan polysulfate (PPS) is known to induce proliferation and chondrogenesis of mesenchymal progenitor cells (MPCs) in vitro and in vivo. However, the mechanism(s) of action of PPS in mediating these effects remains unresolved. In the present report we address this issue by investigating the binding and uptake of PPS by MPCs and monitoring gene expression and proteoglycan biosynthesis before and after the cells had been exposed to limited concentrations of PPS and then re-established in culture in the absence of the drug (MPC priming)., Methods: Immuno-selected STRO-1 + mesenchymal progenitor stem cells (MPCs) were prepared from human bone marrow aspirates and established in culture. The kinetics of uptake, shedding, and internalization of PPS by MPCs was determined by monitoring the concentration-dependent loss of PPS media concentrations using an enzyme-linked immunosorbent assay (ELISA) and the uptake of fluorescein isothiocyanate (FITC)-labelled PPS by MPCs. The proliferation of MPCs, following pre-incubation and removal of PPS (priming), was assessed using the Wst-8 assay method, and proteoglycan synthesis was determined by the incorporation of 35 SO 4 into their sulphated glycosaminoglycans. The changes in expression of MPC-related cell surface antigens of non-primed and PPS-primed MPCs from three donors was determined using flow cytometry. RNA sequencing of RNA isolated from non-primed and PPS-primed MPCs from the same donors was undertaken to identify the genes altered by the PPS priming protocol., Results: The kinetic studies indicated that, in culture, PPS rapidly binds to MPC surface receptors, followed by internalisation and localization within the nucleus of the cells. Following PPS-priming of MPCs and a further 48 h of culture, both cell proliferation and proteoglycan synthesis were enhanced. Reduced expression of MPC-related cell surface antigen expression was promoted by the PPS priming, and RNA sequencing analysis revealed changes in the expression of 42 genes., Conclusion: This study has shown that priming of MPCs with low concentrations of PPS enhanced chondrogenesis and MPC proliferation by modifying their characteristic basal gene and protein expression. These findings offer a novel approach to re-programming mesenchymal stem cells for clinical indications which require the repair or regeneration of cartilaginous tissues such as in osteoarthritis and degenerative disc disease.

Intra-operative blood loss remains a major cause of perioperative morbidity for patients with hypervascular spinal metastasis undergoing surgery. Pre-operative embolization is used to reduce intraoperative blood loss and operative time. This is commonly performed under general anesthesia via a trans-arterial approach, which carries a risk of spinal stroke. We propose an alternative technique for embolization of hypervascular metastases using the Onyx embolic agent via a percutaneous direct intra-tumoural injection under local anesthesia and sedation to reduce embolization risks and procedure time, as well as operative blood loss and operative time. A 74-year-old man presented with thoracic myelopathy with back and radicular pain on background of metastatic renal cell carcinoma. Magnetic resonance imaging (MRI) revealed a 3cm mass centered on the right lamina of T10 with extension into the spinal canal. The patient underwent a percutaneous imaging-guided direct intra-tumoural contrast parenchymogram, and Onyx embolization via a single needle. Initial needle placement and tumour assessment was completed in 30min; embolization time was 15min. Complete devascularization was achieved with no complications. Surgical resection was performed with lower than expected operative blood loss (150ml) and operative time (90min). His pre-operative symptoms improved, and he was discharged home the following day. At 6-month follow-up there was no recurrence of his symptoms. Further evaluation of direct percutaneous intra-tumoural Onyx embolization for hypervascular spinal tumours is warranted., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: The occurrence of bone metastases is common in patients with advanced cancer. The literature supports percutaneous vertebroplasty and kyphoplasty as minimally invasive procedures to relieve pain and improve quality of life for selected patients with disabling pain from pathological vertebral fractures secondary to bone metastases., Case: We describe a case of a 71-year-old patient with castrate-resistant metastatic prostate cancer who underwent sacroplasty for painful sacral metastases. The patient had previously been treated with maximally tolerated analgesics and anticancer therapies including systemic anticancer treatments and local radiotherapy. After sacroplasty, he experienced significant pain reduction and improvement in mobility and function., Conclusion: This case and recent literature demonstrate positive outcomes of sacroplasty in terms of pain reduction and improved mobility. Further research is warranted to establish the role of such minimally invasive percutaneous procedures for pain management in cancer patients., (© 2016 World Institute of Pain.)