Olfactory outcomes after resection of tuberculum sella and planum sphenoidale meningiomas via a transcranial approach

Objectives Controversy exists surrounding the optimal approaches to tuberculum sella meningioma (TSM) and planum meningioma (PM). Olfaction is infrequently considered within this context but is nonetheless an important quality of life measure. The evolution of olfactory outcomes following contemporary transcranial surgery remains unclear. This study reviews olfactory outcomes after supraorbital craniotomy for TSM or PM and defines temporal trends in its recovery. Study Design A prospective study of a patients who underwent a minimally invasive supraorbital craniotomy for TSM or PM was conducted at a single neurosurgical center. Participants & Main Outcome Measures All patients were questioned about olfaction at presentation 3 months postoperatively, 12 months postoperatively, and annually thereafter (median follow-up = 37 months). The olfactory status of patients was categorized as normosmia, anosmia, hyposmia, parosmia, (altered perception of odours), or phantosmia, (olfactory hallucinations). Results Twenty-two patients were included in the study analysis, (range = 27–76). Precisely, 3 months after surgery, seven patients had normal olfaction (32%). Six patients were anosmic, (27%) four hyposmic, (18%), three parosmic, (14%), and two were phantosmic (9%). At 1-year follow-up, almost half of patients (10; 48%) were normosmic, while two patients (9.5%) were anosmic. There were no further improvements in olfaction between 1 year and long-term follow-up. Conclusion Subfrontal transcranial approaches for TSM or PM appear to be associated with changes in olfaction that can improve with time; these improvements occur within the first year after surgery. Impacts upon olfaction should be considered when selecting a surgical approach and patients counseled appropriately

Acromegaly and the information gap: patient perceptions of the journey from primary to tertiary care

Objective Acromegaly is a rare condition and there is often a long path to diagnosis for many patients. We sought to explore patient’s perceptions and understanding of acromegaly, to examine the quality of communication and find gaps in the information provided at diagnosis. Design A prospective study using qualitative research methodology and grounded theory. A semi-structured interview was conducted with 18 patients treated for acromegaly in a single tertiary centre and verbatim transcripts were thematically analysed for overarching themes. Results Eighteen patients with acromegaly were interviewed. The mean age of participants was 52 (range 30–72). Four overarching themes emerged; (1) Patients rely on online resources to understand acromegaly in the time between diagnosis and tertiary care clinic; (2) There is not enough support available for patients; (3) Patients have a basic understanding of acromegaly and associated conditions, but the long-term impact is underestimated; and (4) Patients initially felt intimidated by the multidisciplinary team panel, but overall found it useful. Conclusion Acromegalic patients have a strong need for information at the point of initial diagnosis, in particular online resources and interaction with other experienced patients. Wider dissemination of patient educational resources into primary and secondary care settings may improve overall patient satisfaction, treatment adherence and subsequent health care provider–patient relationships

Diffuse low grade glioma after the 2016 WHO update, seizure characteristics, imaging correlates and outcomes

Objectives The majority of patients with supratentorial diffuse grade II glioma present with seizures, which adversely affect quality of life. The exact mechanism of epileptogenesis is unknown and the influence of tumour characteristics, radiological and histological, are not well studied, particularly following the introduction of molecular genetics in the 2016 WHO reclassification of gliomas. We sought to define predictors of seizure development and outcome in low grade glioma. Patients and Methods A retrospective review of patients who underwent resection of a supratentorial grade II glioma in a single institution. All patients underwent surgery at initial presentation with the aim of maximal safe resection. Presenting symptoms and radiological variables were recorded, including eloquent location, cortical involvement, tumour margins and tumour volume. Extent of resection (EOR), surgery type (awake vs asleep) and seizure outcome were analysed. Using molecular genetics data the original histology was reclassified according to the 2016 WHO update. Results 63 patients were included, 45 (71%) presented with seizures. 36 (57%) had oligodendroglioma and 27 astrocytoma. IDH-1 mutation was present in 53 (84%). 18 (29%) had tumour in an eloquent location. 33 (73%) were Engel class I following surgery at median follow up of 43 months. 6 patients were Engel II, 6 class III. Complete and near total resection were associated with improved Engel class compared to subtotal resection. No factors such as age, tumour location, tumour margins or tumour molecular genetics (including IDH-1 mutation) predicted better seizure outcome. Updated histological subtype did not predict the presence of seizures at initial diagnosis, only tumour heterogeneousity on initial MRI (p = 0.043). More patients who underwent awake craniotomy with intraoperative mapping were Engel class 1 post-operatively than those operated under general anaesthetic (84% vs 65%). Tumour volume at presentation did not correlate with seizure outcome but impacts on the EOR. Conclusion Seizure outcome is directly related to EOR in low grade glioma, which can be predicted by the initial tumour volume. Tumour histological subtype, including updated molecular genetic classification did not predict seizure development or outcome in this series. The use of awake craniotomy results in greater EOR and improved Engel Class following surgery

Pituitary xanthogranulomas: clinical features, radiological appearances and post-operative outcomes

Background Xanthogranulomas are inflammatory masses most commonly found at peripheral sites such as the skin. Sellar and parasellar xanthogranulomas are rare and present a diagnostic challenge as they are difficult to differentiate from other sellar lesions such as craniopharyngiomas and Rathke’s cleft cysts pre-operatively. Their radiological imaging features are yet to be clearly defined, and clinical outcomes after surgery are also uncertain. This study reviews clinical presentation, radiological appearances, and clinical outcomes in a cohort of patients with pituitary xanthogranulomas. Methods A prospectively maintained pituitary surgery database was screened for histologically confirmed pituitary xanthogranulomas between May 2011–December 2016. Retrospective case note assessments were then performed by three independent reviewers. Patient demographics, clinical presentations, imaging, and clinical outcomes were analysed. Results During the study period 295 endoscopic endonasal pituitary surgeries were performed. Six patients had confirmed pituitary xanthogranulomas (2%). Patients most commonly presented with visual field deficits and/or endocrine dysfunction. Common imaging features included: a cystic consistency, hyperintensity on T1-weighted MR images, and contrast enhancement either peripherally (n = 3) or homogenously (n = 3). The most common pre-operative endocrine deficits were hyperprolactinaemia and hypoadrenalism (at least one of which was identified in 4/6 patients; 66%). Thirty-three percent (2/6) of patients presented with diabetes insipidus. The most common post-operative endocrinological deficits were adrenocortical dysfunction (66%) and gonadotropin deficiency (66%). Visual assessments normalised in all six patients post-operatively. Gross total resection was achieved in all patients, and at median follow up of 33.5 months there were no cases of tumour recurrence. Conclusions The prevalence of pituitary xanthogranulomas in our series is higher than that suggested in the literature. Surgery restored normal vision to all cases, however four patients (67%) required long-term hormonal replacement post-operatively. Imaging features such peripheral rim enhancement, a suprasellar tumour epicentre, and the absence of both calcification or cavernous sinus invasion were identified as potential indicators that together should alert clinicians to the possibility of pituitary xanthogranuloma when assessing patients with cystic sellar and parasellar tumours

Cerebral salt wasting following traumatic brain injury

Hyponatraemia is the most commonly encountered electrolyte disturbance in neurological high dependency and intensive care units. Cerebral salt wasting (CSW) is the most elusive and challenging of the causes of hyponatraemia, and it is vital to distinguish it from the more familiar syndrome of inappropriate antidiuretic hormone (SIADH). Managing CSW requires correction of the intravascular volume depletion and hyponatraemia, as well as mitigation of on-going substantial sodium losses. Herein we describe a challenging case of CSW requiring large doses of hypertonic saline and the subsequent substantial benefit with the addition of fludrocortisone

Trends in peri-operative performance status following resection of high grade glioma and brain metastases: The impact on survival

Objectives: Maximal surgical resection of high grade brain tumours is associated with improved overall survival (OS). It carries the risk of neurological deterioration leading to worsening performance status (PS), which may affect overall survival and preclude patients from adjuvant therapy. We aim to review the changes in performance status of patients undergoing resection of high grade tumours and metastases and the impact of changes on overall survival. Patients and methods: A prospective study of the perioperative performance status of 75 patients who underwent primary resection of malignant primary brain tumour or solitary metastasis in a single centre. Data on patients’ demographics, tumour histology and overall survival were also collected. WHO performance status was recorded pre-operatively and at intervals following surgery. Results: Of the 75 patients (35 males, 40 females, median age 61 years at diagnosis), 50 had primary malignant brain tumours, 25 had metastasis. Although PS dropped at postoperative day 1 in 14 patients (18.7%), 28% improved by day 5 and there was significant improvement by day 14 (41%, p=0.02). The number of patients with PS 3 or worse changed from 4% pre-operatively (n=3) to 8% (n=6). Overall survival is better in those whose PS remained improved or unchanged at 2 weeks after surgery compared to those whose PS deteriorated; high grade glioma median survival 15.67 vs. 2.4 months (p=0.005) and metastasis median survival 8.53 vs.2.33 months (p=0.001). Conclusion: Our data demonstrates that although PS may deteriorate immediately after surgery, the majority of patients regain their baseline PS or improve by 2 weeks postoperatively; decisions on fitness for adjuvant treatment should therefore be delayed until then. In those patients whose PS declines following surgery overall survival is poor

Vitamin D deficiency is endemic in neurosurgical patients and is associated with a longer length of inpatient stay

Introduction Vitamin D deficiency is common in spinal surgery and critical care. Hypovitaminosis D may impact on outcomes in cranial neurosurgical care and play roles in underlying disease processes. Methods A prospective observational cohort study was performed. All emergency cranial neurosurgical ward admissions from 1st January to 10th May 2017 were screened for inclusion (n = 406). Patients already receiving vitamin D supplementation, spinal patients and elective admissions were excluded. Admission vitamin D levels were checked for all remaining patients (n = 95). Patients with vitamin D <30 nmol/L were defined as “deficient” and those 30‐50 nmol/L as “inadequate.” All patients with levels <50 nmol/L were replaced, as per local guidelines. Descriptive analyses of the cohorts were undertaken, with multivariate regression used to assess the effect of vitamin D on length of stay, inpatient morbidity and mortality. Results The median age of participants was 61 years (n = 95; 57% male, 43% female). The median vitamin D level was 23 nmol/L (deficient). 84% (n = 80) of patients had low vitamin D levels, with 61% (n = 58) classed as deficient (<30 nmol/L). Vitamin D deficiency rates were similar in those aged below 65 years (86%; n = 38/44) and those above 65 years (82%; n = 42/51). Deficient vitamin D level was associated with longer hospital stay (P = .03), and this relationship persisted after adjusting for potential confounders such as age, sex and preadmission Charlson co‐morbidity index. No statistically significant association was seen with vitamin D status and inpatient morbidity or mortality. Conclusions Vitamin D deficiency is common in cranial neurosurgical patients, even in predefined low‐risk groups (age <65). Lower vitamin D level was associated with longer length of stay. This study supports the need for: (a) further investigation into the roles of vitamin D in neurosurgical pathologies and management and (b) an appropriately powered, randomised investigation into the impact of vitamin D status upon neurosurgical diagnoses and complications

Evolution of design considerations in complex craniofacial reconstruction using patient-specific implants

Previously published evidence has established major clinical benefits from using Computer Aided Design (CAD), Computer Aided Manufacturing (CAM), and Additive Manufacturing (AM) to produce patient-specific devices. These include cutting guides, drilling guides, positioning guides, and implants. However, custom devices produced using these methods are still not in routine use – particularly by the UK National Health Service (NHS). Oft-cited reasons for this slow uptake include: a higher up-front cost than conventionally-fabricated devices, material-choice uncertainty, and a lack of long-term follow-up due to their relatively recent introduction. This paper identifies a further gap in current knowledge – that of design rules, or key specification considerations for complex CAD/CAM/AM devices. This research begins to address the gap by combining a detailed review of the literature with first-hand experience of interdisciplinary collaboration on five craniofacial patient case-studies. In each patient case, bony lesions in the orbito-temporal region were segmented, excised, and reconstructed in the virtual environment. Three cases translated these digital plans into theatre via polymer surgical guides. Four cases utilised AM to fabricate titanium implants. One implant was machined from PolyEther Ether Ketone (PEEK). From the literature, articles with relevant abstracts were analysed to extract design considerations. 19 frequently-recurring design considerations were extracted from previous publications. 9 new design considerations were extracted from the case studies – on the basis of subjective clinical evaluation. These were synthesised to produce a design considerations framework to assist clinicians with prescribing and design engineers with modelling. Promising avenues for further research are proposed

Components, impacts and costs of dementia home support: a research programme including the DESCANT RCT

BackgroundOver half of people with dementia live at home. We know little about what home support could be clinically effective or cost-effective in enabling them to live well.ObjectivesWe aimed to (1) review evidence for components of home support, identify their presence in the literature and in services in England, and develop an appropriate economic model; (2) develop and test a practical memory support package in early-stage dementia, test the clinical effectiveness and cost-effectiveness of routine home support in later-stage dementia and design a toolkit based on this evidence; and (3) elicit the preferences of staff, carers and people with dementia for home support inputs and packages, and evaluate the cost-effectiveness of these approaches in early- and later-stage dementia.DesignWe undertook (1) an evidence synthesis, national surveys on the NHS and social care and an economic review; (2) a multicentre pragmatic randomised trial [Dementia Early Stage Cognitive Aids New Trial (DESCANT)] to estimate the clinical effectiveness and cost-effectiveness of providing memory aids and guidance to people with early-stage dementia (the DESCANT intervention), alongside process evaluation and qualitative analysis, an observational study of existing care packages in later-stage dementia along with qualitative analysis, and toolkit development to summarise this evidence; and (3) consultation with experts, staff and carers to explore the balance between informal and paid home support using case vignettes, discrete choice experiments to explore the preferences of people with dementia and carers between home support packages in early- and later-stage dementia, and cost–utility analysis building on trial and observational study.SettingThe national surveys described Community Mental Health Teams, memory clinics and social care services across England. Recruitment to the trial was through memory services in nine NHS trusts in England and one health board in Wales. Recruitment to the observational study was through social services in 17 local authorities in England. Recruitment for the vignette and preference studies was through memory services, community centres and carers’ organisations.ParticipantsPeople aged > 50 years with dementia within 1 year of first attendance at a memory clinic were eligible for the trial. People aged > 60 years with later-stage dementia within 3 months of a review of care needs were eligible for the observational study. We recruited staff, carers and people with dementia for the vignette and preference studies. All participants had to give written informed consent.Main outcome measuresThe trial and observational study used the Bristol Activities of Daily Living Scale as the primary outcome and also measured quality of life, capability, cognition, general psychological health and carers’ sense of competence.MethodsOwing to the heterogeneity of interventions, methods and outcome measures, our evidence and economic reviews both used narrative synthesis. The main source of economic studies was the NHS Economic Evaluation Database. We analysed the trial and observational study by linear mixed models. We analysed the trial by ‘treatment allocated’ and used propensity scores to minimise confounding in the observational study.ResultsOur reviews and surveys identified several home support approaches of potential benefit. In early-stage dementia, the DESCANT trial had 468 randomised participants (234 intervention participants and 234 control participants), with 347 participants analysed. We found no significant effect at the primary end point of 6 months of the DESCANT intervention on any of several participant outcome measures. The primary outcome was the Bristol Activities of Daily Living Scale, for which scores range from 0 to 60, with higher scores showing greater dependence. After adjustment for differences at baseline, the mean difference was 0.38, slightly but not significantly favouring the comparator group receiving treatment as usual. The 95% confidence interval ran from –0.89 to 1.65 (p = 0.56). There was no evidence that more intensive care packages in later-stage dementia were more effective than basic care. However, formal home care appeared to help keep people at home. Staff recommended informal care that cost 88% of formal care, but for informal carers this ratio was only 62%. People with dementia preferred social and recreational activities, and carers preferred respite care and regular home care. The DESCANT intervention is probably not cost-effective in early-stage dementia, and intensive care packages are probably not cost-effective in later-stage dementia. From the perspective of the third sector, intermediate intensity packages were cheaper but less effective. Certain elements may be driving these results, notably reduced use of carers’ groups.LimitationsOur chosen outcome measures may not reflect subtle outcomes valued by people with dementia.ConclusionsSeveral approaches preferred by people with dementia and their carers have potential. However, memory aids aiming to affect daily living activities in early-stage dementia or intensive packages compared with basic care in later-stage dementia were not clinically effective or cost-effective.Future workFurther work needs to identify what people with dementia and their carers prefer and develop more sensitive outcome measures.Study registrationCurrent Controlled Trials ISRCTN12591717. The evidence synthesis is registered as PROSPERO CRD42014008890.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 6. See the NIHR Journals Library website for further project information

The transcriptional activity of hepatocyte nuclear factor 4 alpha is inhibited via phosphorylation by ERK1/2

Hepatocyte nuclear factor 4 alpha (HNF4alpha) nuclear receptor is a master regulator of hepatocyte development, nutrient transport and metabolism. HNF4alpha is regulated both at the transcriptional and post-transcriptional levels by different mechanisms. Several kinases (PKA, PKC, AMPK) were shown to phosphorylate and decrease the activity of HNF4alpha. Activation of the ERK1/2 signalling pathway, inducing proliferation and survival, inhibits the expression of HNF4alpha. However, based on our previous results we hypothesized that HNF4alpha is also regulated at the post-transcriptional level by ERK1/2. Here we show that ERK1/2 is capable of directly phosphorylating HNF4alpha in vitro at several phosphorylation sites including residues previously shown to be targeted by other kinases, as well. Furthermore, we also demonstrate that phosphorylation of HNF4alpha leads to a reduced trans-activational capacity of the nuclear receptor in luciferase reporter gene assay. We confirm the functional relevance of these findings by demonstrating with ChIP-qPCR experiments that 30-minute activation of ERK1/2 leads to reduced chromatin binding of HNF4alpha. Accordingly, we have observed decreasing but not disappearing binding of HNF4alpha to the target genes. In addition, 24-hour activation of the pathway further decreased HNF4alpha chromatin binding to specific loci in ChIP-qPCR experiments, which confirms the previous reports on the decreased expression of the HNF4a gene due to ERK1/2 activation. Our data suggest that the ERK1/2 pathway plays an important role in the regulation of HNF4alpha-dependent hepatic gene expression