73 research outputs found
Persistent CSF Rhinorrhoea, Pneumocephalus, and Recurrent Meningitis Following Misdiagnosis of Olfactory Neuroblastoma
A 41-year-old female patient was admitted with streptococcal meningitis on a background of 5-month history of CSF rhinorrhoea. Imaging revealed an extensive skull base lesion involving the sphenoid and ethmoid sinuses, the pituitary fossa with suprasellar extension and bony destruction. Histological examination of an endonasal transethmoidal biopsy suggested a diagnosis of olfactory neuroblastoma. A profuse CSF leak occurred and the patient developed coliform meningitis. A second endonasal endoscopic biopsy was undertaken which demonstrated the tumour to be a prolactinoma. Following endonasal repair of the CSF leak and lumbar drainage, she developed profound pneumocephalus. The patient underwent three further unsuccessful CSF leak repairs. Definitive control of the CSF leak was finally achieved through a transcranial approach with prolonged lumbar drainage. This case illustrates some of the potentially devastating complications which can occur as a consequence of complex skull base lesions. A multidisciplinary approach may be required to successfully manage such cases
Non-pharmacological fatigue interventions for patients with a primary brain tumour: A scoping review protocol
Introduction Fatigue is the most prevalent symptom for patients with a primary brain tumour (PBT), significantly reducing quality of life and limiting daily activities. Currently, there are limited options for managing cancer-related fatigue (CRF) in patients with a PBT, using non-pharmacological methods. The objective of this scoping review is to identify current and emerging evidence in relation to non-pharmacological CRF interventions for patients with a PBT. Methods and analysis Electronic databases OVID and EBSCO platforms: MEDLINE, EMBASE and CINAHL will be searched. In addition, PROSPERO, The Cochrane Library and ISI Web of Science will be searched. Trials registries CENTRAL and the International Clinical Trials Registry platform will also be searched for ongoing research. Inclusion criteria: studies from 2006 onwards, primary research on non-pharmacological interventions in patients with a PBT (>18 years). A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram will be utilised to summarise the screening process and results. Quantitative data will be analysed descriptively, while content analysis will be used for qualitative data. Findings will map the existing and emerging evidence on non-pharmacological interventions for CRF in patients with PBTs. This will provide insights into the extent and nature of the evidence in this evolving field, identifying gaps in knowledge and research priorities, and guide further investigations in this area. Ethics and dissemination Ethical approval is not required for this scoping review. Findings will be disseminated via relevant peer-reviewed journals, PhD thesis, conference presentations, and shared with relevant charities and health professionals
Intrastriatal convection-enhanced delivery results in widespread perivascular distribution in a pre-clinical model
Combined use of CDK4/6 and mTOR inhibitors induce synergistic growth arrest of diffuse intrinsic pontine glioma cells via mutual downregulation of mTORC1 activity
The 2019 and 2021 International Workshops on Alport Syndrome
In 1927 Arthur Cecil Alport, a South African physician, described a British family with an inherited form of kidney disease that affected males more severely than females and was sometimes associated with hearing loss. In 1961, the eponymous name Alport syndrome was adopted. In the late twentieth century three genes responsible for the disease were discovered: COL4A3, COL4A4, and COL4A5 encoding for the α3, α4, α5 polypeptide chains of type IV collagen, respectively. These chains assemble to form heterotrimers of type IV collagen in the glomerular basement membrane. Scientists, clinicians, patient representatives and their families, and pharma companies attended the 2019 International Workshop on Alport Syndrome, held in Siena, Italy, from October 22 to 26, and the 2021 online Workshop from November 30 to December 4. The main topics included: disease re-naming, acknowledging the need to identify an appropriate term able to reflect considerable clinical variability; a strategy for increasing the molecular diagnostic rate; genotype-phenotype correlation from monogenic to digenic forms; new therapeutics and new therapeutic approaches; and gene therapy using gene editing. The exceptional collaborative climate that was established in the magical medieval setting of Siena continued in the online workshop of 2021. Conditions were established for collaborations between leading experts in the sector, including patients and drug companies, with the aim of identifying a cure for Alport syndrome
Impact of COVID-19 pandemic on surgical neuro-oncology multi-disciplinary team decision making: a national survey (COVID-CNSMDT Study).
OBJECTIVES: Pressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making. DESIGN: A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020. SETTING: Regional neurosurgical units outside London (as the pandemic was more advanced at time of study). PARTICIPANTS: Representatives from all units were invited to collect data on new patients discussed at their MDT meetings during the study period. Each unit decided if management decision for each patient had changed due to COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures included number of patients where the decision to undergo surgery changed compared with standard management usually offered by that MDT. Secondary outcome measures included changes in surgical extent, numbers referred to MDT, number of patients denied surgery not receiving any treatment and reasons for any variation across the UK. RESULTS: 18 units (75%) provided information from 80 MDT meetings that discussed 1221 patients. 10.7% of patients had their management changed-the majority (68%) did not undergo surgery and more than half of this group not undergoing surgery had no active treatment. There was marked variation across the UK (0%-28% change in management). Units that did not change management could maintain capacity with dedicated oncology lists. Low volume units were less affected. CONCLUSION: COVID-19 has had an impact on patients requiring surgery for malignant brain tumours, with patients receiving different treatments-most commonly not receiving surgery or any treatment at all. The variations show dedicated cancer operating lists may mitigate these pressures. STUDY REGISTRATION: This study was registered with the Royal College of Surgeons of England's COVID-19 Research Group (https://www.rcseng.ac.uk/coronavirus/rcs-covid-research-group/)
Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson's disease
We investigated the effects of glial cell line-derived neurotrophic factor (GDNF) in Parkinson’s disease, using intermittent intraputamenal convection-enhanced delivery via a skull-mounted transcutaneous port as a novel administration paradigm to potentially afford putamen-wide therapeutic delivery. This was a single-centre, randomized, double-blind, placebo-controlled trial. Patients were 35–75 years old, had motor symptoms for 5 or more years, and presented with moderate disease severity in the OFF state [Hoehn and Yahr stage 2–3 and Unified Parkinson’s Disease Rating Scale motor score (part III) (UPDRS-III) between 25 and 45] and motor fluctuations. Drug delivery devices were implanted and putamenal volume coverage was required to exceed a predefined threshold at a test infusion prior to randomization. Six pilot stage patients (randomization 2:1) and 35 primary stage patients (randomization 1:1) received bilateral intraputamenal infusions of GDNF (120 mg per putamen) or placebo every 4 weeks for 40 weeks. Efficacy analyses were based on the intention-to-treat principle and included all patients randomized. The primary outcome was the percentage change from baseline to Week 40 in the OFF state (UPDRS-III). The primary analysis was limited to primary stage patients, while further analyses included all patients from both study stages. The mean OFF state UPDRS motor score decreased by 17.3 17.6% in the active group and 11.8 15.8% in the placebo group (least squares mean difference: 4.9%, 95% CI: 16.9, 7.1, P = 0.41). Secondary endpoints did not show significant differences between the groups either. A post hoc analysis found nine (43%) patients in the active group but no placebo patients with a large clinically important motor improvement (510 points) in the OFF state (P = 0.0008). 18F-DOPA PET imaging demonstrated a significantly increased uptake throughout the putamen only in the active group, ranging from 25% (left anterior putamen; P = 0.0009) to 100% (both posterior putamina; P50.0001). GDNF appeared to be well tolerated and safe, and no drug-related serious adverse events were reported. The study did not meet its primary endpoint. 18F-DOPA imaging, however, suggested that intermittent convection-enhanced delivery of GDNF produced a putamen-wide tissue engagement effect, overcoming prior delivery limitations. Potential reasons for not proving clinical benefit at 40 weeks are discussed
Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson's Disease
Background:
Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson’s disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [18F]DOPA uptake throughout the entire putamen.
Objective:
This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks.
Methods:
Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo). The primary outcome was the percentage change from baseline to Week 80 in the OFF state Unified Parkinson’s Disease Rating Scale (UPDRS) motor score.
Results:
All 41 parent study participants were enrolled. The primary outcome decreased by 26.7±20.7% in patients on GDNF for 80 weeks (GDNF/GDNF; N = 21) and 27.6±23.6% in patients on placebo for 40 weeks followed by GDNF for 40 weeks (placebo/GDNF, N = 20; least squares mean difference: 0.4%, 95% CI: –13.9, 14.6, p = 0.96). Secondary endpoints did not show significant differences between the groups at Week 80 either. Prespecified comparisons between GDNF/GDNF at Week 80 and placebo/GDNF at Week 40 showed significant differences for mean OFF state UPDRS motor (–9.6±6.7 vs. –3.8±4.2 points, p = 0.0108) and activities of daily living score (–6.9±5.5 vs. –1.0±3.7 points, p = 0.0003). No treatment-emergent safety concerns were identified.
Conclusions:
The aggregate study results, from the parent and open-label extension suggest that future testing with GDNF will likely require an 80- rather than a 40-week randomized treatment period and/or a higher dose
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