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Purpose Postoperative cerebrospinal fluid rhinorrhoea (CSFR) remains a frequent complication of endonasal approaches to pituitary and skull base tumours. Watertight skull base reconstruction is important in preventing CSFR. We sought to systematically review the current literature of available skull base repair techniques. Methods Pubmed and Embase databases were searched for studies (2000–2020) that (a) reported on the endonasal resection of pituitary and skull base tumours, (b) focussed on skull base repair techniques and/or postoperative CSFR risk factors, and (c) included CSFR data. Roles, advantages and disadvantages of each repair method were detailed. Random-effects meta-analyses were performed where possible. Results 193 studies were included. Repair methods were categorised based on function and anatomical level. There was absolute heterogeneity in repair methods used, with no independent studies sharing the same repair protocol. Techniques most commonly used for low CSFR risk cases were fat grafts, fascia lata grafts and synthetic grafts. For cases with higher CSFR risk, multilayer regimes were utilized with vascularized flaps, gasket sealing and lumbar drains. Lumbar drain use for high CSFR risk cases was supported by a randomised study (Oxford CEBM: Grade B recommendation), but otherwise there was limited high-level evidence. Pooled CSFR incidence by approach was 3.7% (CI 3–4.5%) for transsphenoidal, 9% (CI 7.2–11.3%) for expanded endonasal, and 5.3% (CI 3.4–7%) for studies describing both. Further meaningful meta-analyses of repair methods were not performed due to significant repair protocol heterogeneity. Conclusions Modern reconstructive protocols are heterogeneous and there is limited evidence to suggest the optimal repair technique after pituitary and skull base tumour resection. Further studies are needed to guide practice.

Background CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) is a prospective multicenter observational study seeking to determine 1) the scope of skull base repair methods used and 2) corresponding rates of postoperative cerebrospinal fluid (CSF) rhinorrhea in the endonasal transsphenoidal approach (TSA) and the expanded endonasal approach (EEA) for skull base tumors. We sought to pilot the project, assessing the feasibility and acceptability by gathering preliminary data. Methods A prospective observational cohort study was piloted at 12 tertiary neurosurgical units in the United Kingdom. Feedback regarding project positives and challenges were qualitatively analyzed. Results A total of 187 cases were included: 159 TSA (85%) and 28 EEA (15%). The most common diseases included pituitary adenomas (n = 142/187), craniopharyngiomas (n = 13/187). and skull base meningiomas (n = 4/187). The most common skull base repair techniques used were tissue glues (n = 132/187, most commonly Tisseel), grafts (n = 94/187, most commonly fat autograft or Spongostan) and vascularized flaps (n = 51/187, most commonly nasoseptal). These repairs were most frequently supported by nasal packs (n = 125/187) and lumbar drains (n = 20/187). Biochemically confirmed CSF rhinorrhea occurred in 6/159 patients undergoing TSA (3.8%) and 2/28 patients undergoing EEA (7.1%). Four patients undergoing TSA (2.5%) and 2 patients undergoing EEA (7.1%) required operative management for CSF rhinorrhea (CSF diversion or direct repair). Qualitative feedback was largely positive (themes included user-friendly and efficient data collection and strong support from senior team members), demonstrating acceptability. Conclusions Our pilot experience highlights the acceptability and feasibility of CRANIAL. There is a precedent for multicenter dissemination of this project, to establish a benchmark of contemporary practice in skull base neurosurgery, particularly with respect to patients undergoing EEA.

Objective The extended endoscopic approach provides unimpaired visualization and direct access to ventral skull base pathology, but is associated with cerebrospinal fluid (CSF) leak in up to 25% of patients. To evaluate the impact of improved surgical techniques and devices to better repair skull base defects, we assessed published surgical outcomes of the extended endoscopic endonasal approach in the last two decades for a well-defined homogenous group of tuberculum sellae and olfactory groove meningioma patients. Methods Random-effects meta-analyses were performed for studies published between 2004 (first publications) and April 2020. We evaluated CSF leak as primary outcome. Secondary outcomes were gross total resection, improvement in visual outcomes in those presenting with a deficit, intraoperative arterial injury, and 30-day mortality. For the main analyses, publications were pragmatically grouped based on publication year in three categories: 2004–2010, 2011–2015, and 2016–2020. Results We included 29 studies describing 540 patients with tuberculum sellae and 115 with olfactory groove meningioma. The percentage patients with CSF leak dropped over time from 22% (95% CI: 6–43%) in studies published between 2004 and 2010, to 16% (95% CI: 11–23%) between 2011 and 2015, and 4% (95% CI: 1–9%) between 2016 and 2020. Outcomes of gross total resection, visual improvement, intraoperative arterial injury, and 30-day mortality remained stable over time Conclusions We report a noticeable decrease in CSF leak over time, which might be attributed to the development and improvement of new closure techniques (e.g., Hadad-Bassagasteguy flap, and gasket seal), refined multilayer repair protocols, and lumbar drain usage.

Background: The optimal management of craniopharyngiomas remains controversial. Objectives: To examine temporal trends in the management of craniopharyngioma with a focus on endocrine outcomes. Methods: This was a cross‐sectional, multicentre study. Patients treated between 1951 and 2015 were identified and divided into four quartiles. Demographics, presentation, treatment and outcomes were collected. Results: In total, 142 patients with childhood‐onset craniopharyngioma (48/142; 34%) and adult‐onset disease (94/142; 66%) were included. The median follow‐up was 15 years (IQR 5‐23 years). Across quartiles, there was a significant trend towards using transsphenoidal surgery (P < .0001). The overall use of radiotherapy was not different among the four quartiles (P = .33). At the latest clinical review, the incidence of GH, ACTH, gonadotrophin deficiencies and anterior panhypopituitarism fell significantly across the duration of the study. Anterior panhypopituitarism was not affected by treatment modality (surgery vs surgery and radiotherapy) (P = .23). There was no difference in the incidence of high BMI (≥25 kg/m2) among the four quartiles (P = .14). BMI was higher in patients who treated with surgery and radiotherapy than those treated with surgery only (P = .006). Tumour regrowth occurred in 51 patients (51/142; 36%) with no difference in regrowth among quartiles over the time course of the study (P = .15). Conclusion: We demonstrate a significant reduction in panhypopituitarism in craniopharyngioma patients over time, most likely because of a trend towards more transsphenoidal surgery. However, long‐term endocrine sequelae remain common and lifelong follow‐up is required.

Introduction: Cytokines are important elements of the tumor microenvironment (TME) coordinating host responses against the tumor, promoting growth, invasion, angiogenesis and regulating non-tumoral cells in TME. Little is known regarding the cytokine network in pituitary adenomas (PAs) and its role in the TME. We aimed to characterise PA-derived cytokines to study their role in the TME of PAs. Methods: The cytokine secretome of culture supernatants from 27 human PAs (16 NFPAs, 9 GHomas, 1 TSHoma, 1 ACTHoma) was assessed using Millipore MILLIPLEX cytokine/chemokine 42-plex. IL-8 and CCL2 expression was further studied by RNAscope. Angiogenesis, macrophages and epithelial-to-mesenchymal transition were evaluated by immunohistochemistry for CD31, CD68, CD163, HLA-DR, E-cadherin and ZEB1. Macrophage infiltration in PAs and its phenotype was further assessed with the gene-signature based method xCELL. We have developed an in vitro model of pituitary cells (GH3) and macrophages (RAW264.7) and studied their interaction via assessing the effect of conditioned media. We documented cell morphology (ImageJ), migration and invasion (Boyden chambers), epithelial-to-mesenchymal transition pathway (RT-qPCR and immunocytochemistry) and secretome changes (cytokine array). Results: IL-8, CCL2, CCL3 and CCL4 are the main PA-derived cytokines, with CXCL1, CXCL10, CCL22 and CX3CL1 also secreted by most of these tumors. RNAscope data showed that CCL2 and IL-8 are mainly synthesised in the pituitary tumour cells. NFPAs secreted more cytokines than somatotropinomas, especially CCL2 (16x more), IL-8 (25x more) and CCL4 (27x more). PAs contained more macrophages than normal pituitary (4.9±0.7 vs 1.2±0.2%, p=0.007). Macrophage infiltration was associated with higher chemokine levels (CCL2, CCL3, CCL4, CXCL1 and IL-8). Macrophages in PAs belong to the CD163+ M2-subtype, while in normal pituitary M1-macrophages predominate, resulting in 3-fold increased M2:M1 ratio in PAs (p

OBJECTIVE: The results of recent high-profile delict and medical negligence cases now require doctors to take "reasonable care to ensure that the patient is aware of any material risks involved in any recommended treatment, and of any reasonable alternative or variant treatments." Thus, we report the development and evaluation of a procedure-specific online educational resource to support the informed consent process for patients undergoing transsphenoidal excision of pituitary adenomas. METHODS: An interactive educational multimedia website was developed using a combination of text, images, and videos. A telephone questionnaire was devised to evaluate patients' understanding that included 15 true/false questions. The questionnaire was administered to separate cohorts of patients on the waiting list for transsphenoidal excision of a pituitary adenoma before and after introduction of the website. The patients were also asked to rate the extent to which they found the website easy to understand and useful on a 10-point Likert scale. Data were compared using the χ2 and Mann-Whitney U test, with P < 0.05 considered to indicate statistical significance. RESULTS: Ten consecutive patients completed the questionnaire before the introduction of the website and nine afterward. The median questionnaire scores were significantly greater after the introduction of the website (14 of 15 vs. 12 of 15; P = 0.002), and all patients subjectively found the website easy to understand and useful (10 of 10 in both groups). CONCLUSIONS: An interactive educational multimedia website appears to be a helpful adjunct to the informed consent process for patients undergoing transsphenoidal excision of a pituitary adenoma.

A young man presented with neck pain following a fall. Neurological examination was normal. Computed tomography (CT) scanning showed a normal brain and an undisplaced fracture of the C5 lamina and wedge fracture of the T1 vertebra. He was managed conservatively at another hospital by cervical immobilisation with a halo device. Two months later he had two generalised seizures. Systemic and neurological …

Spinal cord injury, whether due to trauma, neoplasia or medical conditions, is devastating for the patient, affecting every aspect of physical, social and psychological life. No one who regularly treats such patients can fail to be moved by their struggle to adjust. Since most of the aetiologies are either traumatic or benign, the patient will have a near normal life expectancy if medical complications are avoided. The very existence of Lin's huge textbook testifies to the major advances in spinal cord medicine achieved over the past three decades. This is dramatically illustrated by mortality rates among traumatic paraplegics due to renal complications which stood at 80% for those injured in World War One, fell to 25% during the Korean war and reached very low percentages for the Vietnam conflict. Whereas renal complications formerly prevailed as the cause of death, the main reason for concern in the first six months after injury are now suicide and accidental self-harm. This highlights both the success of medical therapies and the importance of psychological support as an active component of rehabilitation. The manifold physical, medical and psychosocial aspects of spinal cord medicine require the attention of an experienced multidisciplinary team, and in the UK there are several spinal injury units with excellent facilities and experienced dedicated staff. Unfortunately, places are severely restricted and a large proportion of patients with spinal cord injury will never be offered inpatient treatment at such units. For the clinicians struggling to manage spinal cord conditions in a conventional hospital environment Lin's textbook provides an authoritative and contemporary source of knowledge. With seventy-four chapters by 128 authors (most of them from the USA), it proceeds logically from the basic sciences to clinical management including psychosocial issues. The introductory section includes the anatomy and physiology of the spinal cord, imaging and overviews of epidemiology and outcomes. These chapters are necessary for completeness but are rather general and superficial. The second section on acute management of cord injury deals well with the decision-making process and controversies of surgical decompression and stabilization in spinal cord injury, but naturally does not cover the detail of surgical procedures. The third section entitled ‘Medical Management’ addresses the wide range of medical complications that occur with great regularity in spinal cord injury, dealing with each in turn in good detail. This section includes chapters on frequently overlooked complications such as disordered thermoregulation and the immune system response as well as the commonly appreciated problems of respiratory dysfunction and thromboembolism. Section four deals with bladder, bowel and sexual dysfunction and provides comprehensive advice on all aspects of these difficult management issues. Section five, on the neurological aspects of spinal cord care, is a miscellaneous arrangement of items on physiology, investigations, management of spasticity, various myelopathies and autonomic dysfunction. Whilst some of these provide only an overview others offer in-depth insight into aspects of spinal cord injury that are otherwise not dealt with in detail elsewhere. Section six, on musculoskeletal care, provides an excellent set of chapters about this very important aspect of secondary prevention. Section seven, self-evidently vital, addresses rehabilitation from every angle. Section eight deals with recent advances in spinal cord research, providing analyses of progress in neural regeneration, cord repair and retraining among others. Section nine concerns special topics in spinal cord medicine and incorporates further miscellaneous chapters that demonstrate the comprehensive nature of this text. The final section, on psychosocial issues and support environment, is perhaps the most important and instructive part of the book and is done well. The breadth, detail and inclusiveness of this text is impressive. Whichever aspect of spinal cord medicine one is faced with, this text will offer management advice and clinical information. In my practice I regularly see patients with spinal cord injury secondary to trauma, neoplasia and inflammatory processes who have to be managed in the neurosurgical unit. With the advice of these experts readily to hand, I shall feel more confident in managing these patients during their lengthy stays.