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An unusual cause of cranial dural thickeningWe describe an unusual cause of cranial dural thickening in an elderly female with a chronic meningeal inflammatory process. A 70-year-old ethnically Chinese, Singaporean female presented with a history of chronic daily headache with no other meningeal signs. Serial MRI brains showed progressive pachymeningeal and leptomeningeal enhancement in the left frontal region with underlying vasogenic oedema, similar appearances in the right frontal region to a lesser extent, and persistent inflammatory changes in her bilateral paranasal sinuses. Investigative work-up showed a chronically raised ESR with a normal CRP, negative ANCA, and a chronically raised serum IgA kappa paraprotein. Bone marrow trephine biopsy was suggestive of a low level plasma cell disorder. Olfactory cleft biopsy showed no evidence of IgG4-related disease or vasculitis and no significant plasma cell infiltrate. Histopathological examination from a meningeal biopsy revealed a diagnosis of an en-plaque meningioma (the WHO, 2016; Grade I) causing an unusual granulomatous reaction. We discuss the radiological and histological relations of this rare form of meningioma. Clinicians can consider en-plaque meningioma in the differential diagnosis of linear dural thickening and enhancement. Copyright © 2020 Jing Ming Yeo et al.
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Evaluating the efficacy and safety of single-agent etoposide intra-CSF chemotherapy in children and young people with relapsed/refractory central nervous system tumoursPurpose: The aim of the project was to evaluate intra-CSF etoposide administration in a palliative setting for children and young people with relapsed/refractory central nervous system (CNS) tumours, with the primary endpoints being overall survival and progression-free survival time. A safety endpoint was to assess the side effect profile and complications of intra-CSF etoposide. Method(s): Thirty-five patients under the age of 30 years (median age: 5.33 years) were enrolled onto the project. The cross-centre study was a service evaluation, with a data collection spreadsheet designed in Nottingham and completed by both Nottingham and Oxford centres. Data was analysed using SPSS, assessing the overall survival and progression-free survival times, as well as the 6-month and 1-year survival rates. Result(s): The median overall survival and progression-free survival times were 10.97 and 5.91 months, respectively. The 6-month and 1-year overall survival rates were 67% and 48%, and the progression-free survival rates were 50% and 22%. Age at the start of intra-CSF therapy was significantly associated with overall survival (P = 0.046), with the 6 + age group having improved overall survival. Treatment type was significantly associated with overall survival (P = 0.012), with etoposide intra-CSF treatment being associated with improved overall survival. Treatment duration was significantly associated with both overall survival (P < 0.001) and progression-free survival (P < 0.001). Conclusion(s): Intra-CSF etoposide treatment has shown to increase both overall and progression-free survival significantly, whilst having few side effects and maintaining a good quality of life for patients, reflecting it as a beneficial therapy in the palliative setting.Copyright © 2023, Crown.
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Phase II study of intravenous etoposide in patients with relapsed ependymoma (CNS 2001 04)Background: Relapsed ependymoma has a dismal prognosis, and the role of chemotherapy at relapse remains unclear. This study prospectively evaluated the efficacy of intensive intravenous (IV) etoposide in patients less than 21 years of age with relapsed intracranial ependymoma (NCT00278252). Method(s): This was a single-arm, open-label, phase II trial using Gehan's two-stage design. Patients received IV etoposide 100 mg/m2 on days 1-3, 8-10, and 15-17 of each 28-day cycle, up to maximum of 6 cycles. Primary outcome was radiological response after 3 cycles. Pharmacokinetic analysis was performed in 10 patients. Result(s): Twenty-five patients were enrolled and included in the intention-to-treat (ITT) analysis. Three patients were excluded in per-protocol (PP) analysis. After 3 cycles of etoposide, 5 patients (ITT 20%/PP 23%) had a complete response (CR), partial response (PR), or objective response (OR). Nine patients (ITT 36%/PP 41%,) had a best overall response of CR, PR, or OR. 1-year PFS was 24% in ITT and 23% in PP populations. 1-year OS was 56% and 59%, 5-year OS was 20% and 18%, respectively, in ITT and PP populations. Toxicity was predominantly hematological, with 20/25 patients experiencing a grade 3 or higher hematological adverse event. Conclusion(s): This study confirms the activity of IV etoposide against relapsed ependymoma, however, this is modest, not sustained, and similar to that with oral etoposide, albeit with increased toxicity. These results confirm the dismal prognosis of this disease, provide a rationale to include etoposide within drug combinations, and highlight the need to develop novel treatments for recurrent ependymoma.Copyright © 2022 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
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EPEN-24. SIOP ependymoma II: Central ependymoma management advisory group - The UK experiencePaediatric Ependymoma is the second most common malignant brain tumour of childhood with approximately 50% of cases recurring. It has been described as a "surgical" disease since patients who have undergone a gross total surgical resection (GTR) have a better prognosis than those who have a subtotal resection (STR). Analysis of the UKCCSG/SIOP 1992 04 clinical trial has shown that only 49% of cases had a GTR, with 5-year survival rates for STR of 22-47% and GTR of 67-80%. As part of the SIOP II Ependymoma trial the UK established a panel of experts in the treatment of Ependymoma from Neuro-oncology, Neuro-radiology and Neuro-surgery. Meeting weekly, cases are discussed to provide a consensus on radiological review, ensuring central pathological review, trial stratification and whether further surgery should be advocated on any particular case. Evaluation of the first 68 UK patients has shown a GTR in 47/68 (69%) of patients and STR in 21/68 (31%) of patients. Following discussion at EMAG it was felt that 9/21 (43%) STR patients could be offered early second look surgery. Following this 2nd look surgery the number of cases with a GTR increased to 56/68 (82%). There has been a clear increase in the number of patients for whom a GTR has been achieved following discussion at EMAG and prior to them moving forwards with their oncological treatment. This can only have beneficial effects in decreasing their risk of tumour recurrence or CSF dissemination and also in reducing the target volume for radiotherapy.
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EPEN-05. Surgery for childhood ependymoma: The ependymoma multidisciplinary advisory group (EMAG) clinical trial experienceINTRODUCTION: The National Ependymoma Multidisciplinary Advisory Group (EMAG) is the central review mechanism for the SIOP Ependymoma II clinical trial in the UK. EMAG is a multiprofessional group which meets weekly to support decision making. We report detailed surgical outcomes for children with confirmed intracranial ependymoma, discussed through EMAG between January 2020 and November 2022. METHOD(S): Data was collected on resection status, surgical outcomes, reasons for not achieving Gross Total Resection (GTR), number of surgeries and adjuvant therapies. Data was analysed descriptively. RESULT(S): After first surgery, GTR or near total resection (NTR) rate was 69/105 (66%) rising to 83/105 (79%) following repeated surgeries. 17 patients underwent second-look surgery prior to further therapy, whilst 9 underwent second-look surgery after chemotherapy but before radiotherapy. Eight (17%) posterior fossa (PF) surgeries were not completed due to factors including patient instability and tumour attachments. Most post-operative problems were seen in PF tumours with 26/60 (43%) bulbar palsy, 13/60 (22%) focal weakness and 12/60 (20%) cerebellar mutism. Incomplete PF resections were associated with increased bulbar palsy risk (p=0.02, Chi-Square test). 73% of PF patients required hydrocephalus management with external ventricular drainage, endoscopic third ventriculostomy (ETV) or shunt. Longer term hydrocephalus management with ETV or shunt was required in 29% and was more common in those with subtotal resection (R3-RX, 8/16, 50%) compared to GTR or NTR (R0-R2, 9/43, 21%, p=0.03). 27/60 (45%) received post-op NG feeding and 2/60 (3%) needed tracheostomies. Second surgery was associated with lower complication rates. DISCUSSION(S): Our National MDT approach supports collaborative surgical decision making without a need for centralisation of the surgery itself. There was no evidence of increased complication rates compared to historical trials despite a more aggressive surgical approach. We argue for continued centralisation of EPN evaluation to support optimal care for children with this devastating disease.
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Extracellular vesicles potentiate medulloblastoma metastasis in an EMMPRIN and MMP-2 dependent mannerExtracellular vesicles (EVs) have emerged as pivotal mediators of communication in the tumour microenvironment. More specifically, nanosized extracellular vesicles termed exosomes have been shown to contribute to the establishment of a premetastatic niche. Here, we sought to determine what role exosomes play in medulloblastoma (MB) progression and elucidate the underlying mechanisms. Metastatic MB cells (D458 and CHLA-01R) were found to secrete markedly more exosomes compared to their nonmetastatic, primary counterparts (D425 and CHLA-01). In addition, metastatic cell-derived exosomes significantly enhanced the migration and invasiveness of primary MB cells in transwell migration assays. Protease microarray analysis identified that matrix metalloproteinase-2 (MMP-2) was enriched in metastatic cells, and zymography and flow cytometry assays of metastatic exosomes demonstrated higher levels of functionally active MMP-2 on their external surface. Stable genetic knockdown of MMP-2 or extracellular matrix metalloproteinase inducer (EMMPRIN) in metastatic MB cells resulted in the loss of this promigratory effect. Analysis of serial patient cerebrospinal fluid (CSF) samples showed an increase in MMP-2 activity in three out of four patients as the tumour progressed. This study demonstrates the importance of EMMPRIN and MMP-2-associated exosomes in creating a favourable environment to drive medulloblastoma metastasis via extracellular matrix signalling.Copyright © 2023 by the authors.
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Impact of the SARS-CoV-2/COVID-19 pandemic on the patient journeys of those with a newly diagnosed paediatric brain tumour in the UK: A qualitative studyObjectives To explore the impact of the SARS-CoV-2/COVID-19 pandemic on the diagnosis, management and patient journey for children and young people with a newly diagnosed brain tumour in the UK. Design Exploratory qualitative study focused on patient journeys from multiple perspectives, conducted as part of a wider mixed-methods study. Setting Three paediatric oncology tertiary centres in the UK. Participants 10 children and young people with brain tumours (n=6 females, n=4 males), 20 caregivers (n=16 females, n=4 males) and 16 stakeholders (specialist nurses, consultant neurosurgeons and oncologists, and representatives from brain tumour charities) were interviewed between January 2022 and June 2023. Results The paper incorporates multiple perspectives, including those of children and young people, parents/caregivers, clinical staff and charity representatives, to explore the patient journey. Five themes describe the journey for new patients with paediatric brain tumour during the pandemic, focusing on (1) challenges getting into the healthcare system, (2) managing as a family during restrictions imposed by the pandemic, (3) complexities of building a cohesive and supportive healthcare team, (4) difficulties caregivers experienced in accessing practical and emotional support in hospital and (5) ongoing difficulties experienced by families in the community. Conclusions Findings from this study offer practical insights from children, parents/caregivers and relevant stakeholders to improve the healthcare system during future disruptions. Overall, this study not only sheds light on the challenges faced by families during the pandemic but also provides suggestions for improving healthcare services to ensure a more comprehensive and effective response in times of crisis.Copyright © Author(s) (or their employer(s)) 2025.
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EPEN-43. Targeting intra-tumour heterogeneity in paediatric ependymoma: An integrated omics study towards patient-tailored therapyEpendymoma (EPN) is the second most common malignant paediatric brain tumour, which despite extensive genomic sequencing, no novel therapeutic options have been discovered. Multi-omics are anticipated to reveal dysregulated pathways that may be predictive of patient-specific biomarkers. Given the close association between gene expression, active biochemical signaling and metabolism, there is an unmet scientific challenge to determine whether EPN gene expression correlates with aberrant metabolic pathways, thus presenting therapeutic vulnerabilities. We first compared two distinct subgroups of EPN, PF-A and ST-RELA, identifying 115 metabolites and 1580 upregulated genes between the two subgroups, therefore validating previously reported genetic clustering of these two subtypes. We next integrated transcriptomics and metabolomics, comparing 28 intra-tumour tissue regions from eight primary PF-A EPN patients. Polar metabolites and RNA were simultaneously extracted from the same population of cells. RNAseq identified dysregulated genes and liquid chromatography-mass spectrometry (LC-MS) detected 98 significantly altered metabolites between 18 multi-regions, the majority mapping onto the arginine and proline pathways. Integration of genes and metabolites using pathway-based network analysis revealed 124 aberrant gene-metabolite interactions between intra-tumour regions, with large numbers occurring in the glucogenesis and glycine metabolic pathways in 6/8 patients. These may represent ubiquitous and therapeutically relevant metabolic pathways critical for EPN survival. Additionally, patients presented at least one unique intra-tumour genomic-metabolomic interaction, applicable for patient-tailored therapy. This is the first exploration of EPN multi-omic integration and intra-tumour heterogeneity. Selected drug targets predicated on aberrant gene-metabolite networks will be validated in multi-region patient-derived cell lines and orthotopic models using repurposed therapeutics.
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EPEN-15. Transcriptomic and metabolic integration reveal intra-tumour heterogeneity and identify disulfiram and copper as a synergistic therapy in paediatric ependymomaBACKGROUND: Ependymoma (EPN) is the second most malignant paediatric brain tumour. The PF-A subgroup, associated with a hypoxic microenvironment, has a dismal survival rate of 50% with clinical trials failing to demonstrate a significant survival advantage from chemotherapy to date. As the lack of genomic alterations makes it difficult to uncover novel therapeutic targets, we present a multi-omic integration investigating whether spatially-distinct tumour microenvironments represent targetable metabolic niches in PF-A EPN. METHOD(S): Surgical sampling of spatiallydistinct regions was performed on eight PF-A EPN patients. Metabolites and RNA were simultaneously extracted from the same cellular population and analysed using liquid chromatography-mass spectrometry (LC-MS) and RNAseq. Multi-omic integration was performed using Metscape3 and functional assays evaluating proliferation, invasion and siRNA-mediated knockdown were performed in 2D and 3D models of intra-tumour region patient-derived cell lines. Selected single and drug combination therapy was performed in normoxia and hypoxia, and synergy assessed using the Chou-Talalay method. RESULT(S): Multi-omic integration revealed 124 dysregulated metabolic pathways, encompassing 156 genes and 49 metabolites with the largest number of interactions occurring in the gluconeogenesis pathway. Each anatomical region also presented at least one unique genemetabolite interaction demonstrating heterogeneity within and across PF-A EPN tumours. Four selected drug targets (Disulfiram, Vandetanib, Mildronate and FBP1 inhibitor) based on metabolically relevant genes (ALDH3A1, FMO3, BBOX1, FBP1) showed impairment of metabolic viability in vitro, with limited chemosensitivity observed in control human cerebellar astrocytes. The addition of Cu2+ significantly sensitised cells to Disulfiram, particularly under hypoxic conditions. This synergistic combination significantly impaired invasion in both normoxia and hypoxia. CONCLUSION(S): This is the first instance where multi-omic data integration and intra-tumour heterogeneity has been investigated for paediatric EPN revealing novel therapeutic targets in the context of gene-metabolite correlations. Drug tolerability will be further assessed in vivo using the previously characterised PF-A EPN orthotopic mouse xenograft MAF-928.
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A reappraisal of the pathophysiology of cushing ulcer: A narrative reviewIn 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
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An explanation for Terson syndrome at last: The glymphatic reflux theoryTerson Syndrome (TS) describes the presence of intraocular hemorrhage in patients with intracranial hemorrhage, typically subarachnoid hemorrhage. Despite TS being a well-defined and frequently occurring phenomenon, its pathophysiology remains controversial. This review will present the current understanding of TS, with view to describing a contemporary and more plausible pathomechanism of TS, given recent advances in ophthalmic science and neurobiology. Previously proposed theories include a sudden rise in intracranial pressure (ICP) transmitted to the optic nerve sheath leading to rupture of retinal vessels; or intracranial blood extending to the orbit via the optic nerve sheath. The origin of blood in TS is uncertain, but retinal vessels appear to be an unlikely source. In addition, an anatomical pathway for blood to enter the eye from the intracranial space remains poorly defined. An ocular glymphatic system has recently been described, drainage of which from the globe into intracranial glymphatics is reliant on the pressure gradient between intraocular pressure and intracranial pressure. The glymphatic pathway is the only extravascular anatomical conduit between the subarachnoid space and the retina. We propose that subarachnoid blood in skull base cisterns near the optic nerve is the substrate of blood in TS. Raised ICP causes it to be refluxed through glymphatic channels into the globe, resulting in intraocular hemorrhage. We herewith present glymphatic reflux as an alternative theory to explain the phenomenon of Terson Syndrome.Copyright © 2021, Springer-Verlag GmbH Germany, part of Springer Nature.
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Evaluating neurosurgical training: A national survey examining the British trainee experiencePurpose: Neurosurgery training in the UK has undergone significant changes over the past few years, including the new competency-based curriculum and a reduction of elective operating due to the pandemic. We conducted a comprehensive survey to assess UK neurosurgical trainees' experiences and perceptions to develop targeted action plans. Method(s): An online anonymised survey was developed and distributed amongst the BNTA mailing list. Question types included 10-point Likert scales and free text options. Descriptive statistics, non-parametric testing of Likert scores, and Spearman's rank correlation were used to analyse responses. Pearson's chi-squared test was used for subgroup analysis of categorical data. Result(s): A total of 75 trainees with a National Training Number (NTN) responded. Overall trainees feel they are well trained, well supported, and have caught up with training emerging out of COVID. Funding for training varied between deaneries. There is significant concern amongst trainees regarding the workforce crisis. This, as well as financial concerns are leading to more than a quarter of trainees considering quitting. Half of the trainees are considering going OOP. More than one third of the trainees and more than half of the female trainees are considering working Less Than Full Time (LTFT). Most important supportive mechanisms towards completion of training were social support, along with personal satisfaction from work. An independent mentoring scheme is a preferred additional support mechanism. Conclusion(s): Overall training experience for neurosurgery trainees in UK and Ireland was positive. There are significant concerns regarding the workforce crisis and costs of training, with a large proportion of neurosurgery trainees considering resigning. OOP and LTFT are popular means of becoming more competitive for consultant posts and to spend time with their families. Deanery experience, senior and peer support does, and will improve trainee experience and protect against attrition.Copyright © 2024 The Neurosurgical Foundation.
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Magnetic resonance imaging of inner ear and internal auditory canal structures in the presence of a cochlear implantOBJECTIVE: To determine whether the internal auditory canal (IAC) can be visualized using magnetic resonance imaging (MRI) in users of a cochlear implant (CI) model that can safely undergo MRI at 3 T. PATIENTS: Four normally hearing controls and three individuals unilaterally implanted with a HiRes Ultra 3D (Advanced Bionics LLC, California, USA). INTERVENTIONS: Participants underwent 3 T MRI using sequences appropriate for the postoperative surveillance of the IAC. Images in normally hearing individuals were acquired after placing a fully functional, unpowered, CI underneath a swimming cap at each of eight candidate scalp positions, four on each side of the head. Images were compared to a control condition without a CI present. and CI users were imaged with similar sequences. MAIN OUTCOME MEASURES: In normally hearing controls, the likely impact of the artifact on detection of pathology for multiple neuroradiological locations as rated by two independent radiologists. In CI users, a qualitative assessment of the diagnostic usability of images. RESULT(S): Visibility of the ipsilateral IAC and cochlea varied among the three CI users, with images from one participant deemed largely usable, while those from the other two participants exhibited less diagnostic certainty, likely due to differences in implant locations and cranial/neuroanatomical variations. Ratings of images in normally hearing participants showed that more middle-to-anterior CI locations were associated with reduced likelihood of overlooking gross abnormalities. CONCLUSION(S): Through meticulous surgical placement, bilateral IAC visualization may be achievable for monitoring chronic health conditions such as tumor surveillance in high-risk patients, and as a safety monitoring outcome measure in clinical trials.Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.
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Disproportionate expression of ATM in cerebellar cortex during human neurodevelopmentCerebellar neurodegenerationis a classical feature of ataxia telangiectasia (A-T), an autosomal recessive condition caused by loss-of-function mutation of the ATM gene, a gene with multiple regulatory functions. The increased vulnerability of cerebellar neurones to degeneration compared to cerebral neuronal populations in individuals with ataxia telangiectasia implies a specific importance of intact ATM function in the cerebellum. We hypothesised that there would be elevated transcription of ATM in the cerebellar cortex relative to ATM expression in other grey matter regions during neurodevelopment in individuals without A-T. Using ATM transcription data from the BrainSpan Atlas of the Developing Human Brain, we demonstrate a rapid increase in cerebellar ATM expression relative to expression in other brain regions during gestation and remaining elevated during early childhood, a period corresponding to the emergence of cerebellar neurodegeneration in ataxia telangiectasia patients. We then used gene ontology analysis to identify the biological processes represented in the genes correlated with cerebellar ATM expression. This analysis demonstrated that multiple processes are associated with expression of ATM in the cerebellum, including cellular respiration, mitochondrial function, histone methylation, and cell-cycle regulation, alongside its canonical role in DNA double-strand break repair. Thus, the enhanced expression of ATM in the cerebellum during early development may be related to the specific energetic demands of the cerebellum and its role as a regulator of these processes.Copyright © The Author(s) 2023.
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Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): A UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trialBackground: The risk of death from spontaneous intracerebral haemorrhage is increased for people taking antiplatelet drugs. We aimed to assess the feasibility of randomising patients on antiplatelet drug therapy with spontaneous intracerebral haemorrhage to desmopressin or placebo to reduce the antiplatelet drug effect. Method(s): DASH was a phase 2, randomised, placebo-controlled, multicentre feasibility trial. Patients were recruited from ten acute stroke centres in the UK and were eligible if they had an intracerebral haemorrhage with stroke symptom onset within 24 h of randomisation, were aged 18 years or older, and were taking an antiplatelet drug. Participants were randomly assigned (1:1) to a single dose of intravenous desmopressin 20 mug or matching placebo. Treatment allocation was concealed from all staff and patients involved in the trial. The primary outcome was feasibility, which was measured as the number of eligible patients randomised and the proportion of eligible patients approached, and analysis was by intention to treat. The trial was prospectively registered with ISRCTN (reference ISRCTN67038373), and it is closed to recruitment. Finding(s): Between April 1, 2019, and March 31, 2022, 1380 potential participants were screened for eligibility. 176 (13%) participants were potentially eligible, of whom 57 (32%) were approached, and 54 (31%) consented and were subsequently recruited and randomly assigned to receive desmopressin (n=27) or placebo (n=27). The main reason for eligible patients not being recruited was the patient arriving out of hours (74 61%] of 122 participants). The recruitment rate increased after the enrolment period was extended from 12 h to 24 h, but it was then impaired due to the COVID-19 pandemic. Of the 54 participants included in the analysis (mean age 76.4 years SD 11.3]), most were male (36 67%]) and White (50 93%]). 53 (98%) of 54 participants received all of their allocated treatment (one participant assigned desmopressin only received part of the infusion). No participants were lost to follow-up or withdrew from the trial. Death or dependency on others for daily activities at day 90 (modified Rankin Scale score >4) occurred in six (22%) of 27 participants in the desmopressin group and ten (37%) of 27 participants in the placebo group. Serious adverse events occurred in 12 (44%) participants in the desmopressin group and 13 (48%) participants in the placebo group. The most common adverse events were expansion of the haemorrhagic stroke (four 15%] of 27 participants in the desmopressin group and six 22%] of 27 participants in the placebo group) and pneumonia (one 4%] of 27 participants in the desmopressin group and six 22%] of 27 participants in the placebo group). Interpretation(s): Our results show it is feasible to randomise patients with spontaneous intracerebral haemorrhage who are taking antiplatelet drugs to desmopressin or placebo. Our findings support the need for a definitive trial to determine if desmopressin improves outcomes in patients with intracerebral haemorrhage on antiplatelet drug therapy. Funding(s): National Institute for Health Research.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license
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Effect of proximal blood flow arrest during endovascular thrombectomy (ProFATE): Study protocol for a multicentre randomised controlled trialBackground: Observational studies have demonstrated improved outcomes with the adjunctive use of balloon guide catheters (BGC) during endovascular thrombectomy (EVT) for anterior circulation acute ischaemic stroke (AIS). However, the lack of high-level evidence and global practice heterogeneity justifies a randomised controlled trial (RCT) to investigate the effect of transient proximal blood flow arrest on the procedural and clinical outcomes of patients with AIS following EVT. Hypothesis: Proximal blood flow arrest in the cervical internal carotid artery during EVT for proximal large vessel occlusion is superior to no flow arrest in achieving complete vessel recanalisation. Method(s): ProFATE is an investigator-initiated, pragmatic, multicentre RCT with blinding of participants and outcome assessment. An estimated 124 participants with an anterior circulation AIS due to large vessel occlusion, an NIHSS of 2, ASPECTS 5 and eligible for EVT using a first-line combined technique (contact aspiration and stent retriever) or contact aspiration only will be randomised (1:1) to receive BGC balloon inflation or no inflation during EVT. Outcome(s): The primary outcome is the proportion of patients achieving near-complete/complete vessel recanalisation (eTICI 2c-3) at the end of the EVT procedure. Secondary outcomes include the functional outcome (modified Rankin Scale at 90 days), new or distal vascular territory clot embolisation rate, near-complete/complete recanalisation after the first pass, symptomatic intracranial haemorrhage, procedure-related complications and death at 90 days. Discussion(s): This is the first RCT to investigate the effect of proximal blood flow arrest during EVT using a BGC on the procedural and clinical outcomes of patients with AIS due to large vessel occlusion.Copyright © European Stroke Organisation 2023.
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Effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: A secondary analysis of a large randomised controlled trialBackground Tranexamic acid reduced haematoma expansion and early death, but did not improve functional outcome in the tranexamic acid for hyperacute spontaneous intracerebral haemorrhage-2 (TICH-2) trial. In a predefined subgroup, there was a statistically significant interaction between prerandomisation baseline systolic blood pressure (SBP) and the effect of tranexamic acid on functional outcome (p=0.019). Methods TICH-2 was an international prospective double-blind placebo-controlled randomised trial evaluating intravenous tranexamic acid in patients with acute spontaneous intracerebral haemorrhage (ICH). Prerandomisation baseline SBP was split into predefined 170 mm Hg groups. The primary outcome at day 90 was the modified Rankin Scale (mRS), a measure of dependency, analysed using ordinal logistic regression. Haematoma expansion was defined as an increase in haematoma volume of >33% or >6 mL from baseline to 24 hours. Data are OR or common OR (cOR) with 95% CIs, with significance at p170 mm Hg groups. The primary outcome at day 90 was the modified Rankin Scale (mRS), a measure of dependency, analysed using ordinal logistic regression. Haematoma expansion was defined as an increase in haematoma volume of >33% or >6 mL from baseline to 24 hours. Data are OR or common OR (cOR) with 95% CIs, with significance at p170 mm Hg. Tranexamic acid was associated with a favourable shift in mRS at day 90 in those with baseline SBP170 mm Hg (cOR 1.05, 95% CI 0.85 to 1.30, p=0.63). In those with baseline SBP170 mm Hg (OR 1.02, 95% CI 0.77 to 1.35, p=0.90). Conclusions Tranexamic acid was associated with improved clinical and radiological outcomes in ICH patients with baseline SBP170 mm Hg (OR 1.02, 95% CI 0.77 to 1.35, p=0.90). Conclusions Tranexamic acid was associated with improved clinical and radiological outcomes in ICH patients with baseline SBPCopyright © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.
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Endovascular thrombectomy vs best medical management for late presentation acute ischaemic stroke with large vessel occlusion without CT perfusion or MR imaging selection: A systematic review and meta-analysisBackground: The efficacy and safety of endovascular thrombectomy (EVT) beyond 6 hours from stroke onset for patients with large vessel occlusion (LVO) selected without CT perfusion(CTP) or MR imaging(MRI) is undetermined. We conducted a systematic review and meta-analysis of the current literature comparing outcomes for late presenting patients with LVO treated by best medical management (BMM) with those selected for EVT based only on non-contrast CT(NCCT)/CT angiography(CTA) (without CTP or MRI). Method(s): PRISMA guidelines were employed. The primary outcome was functional independence (modified Rankin Scale 0-2) at 3 months. Secondary outcomes were symptomatic intracranial haemorrhage (sICH) and mortality at 3 months. Data were analysed using the random-effects model. Result(s): Six studies of 2083 patients, including three randomised controlled trials, were included; 1271 patients were treated with EVT and 812 patients with BMM. Compared to BMM, patients treated with EVT demonstrated higher odds of achieving functional independence (39.0 % EVT vs 22.0 % BMM; OR = 2.55, 95 %CI 1.61-4.05,p Result(s): Six studies of 2083 patients, including three randomised controlled trials, were included; 1271 patients were treated with EVT and 812 patients with BMM. Compared to BMM, patients treated with EVT demonstrated higher odds of achieving functional independence (39.0 % EVT vs 22.0 % BMM; OR = 2.55, 95 %CI 1.61-4.05,p 2 = 74 %). The rates of sICH (OR = 2.09, 95 %CI 0.86-5.04,p = 0.10) and mortality (OR = 0.62, 95 %CI 0.35-1.10,p = 0.10) were not significantly different between each cohort. Conclusion(s): Compared to BMM, late presenting stroke patients selected for EVT eligibility with NCCT/CTA only and treated with EVT achieved significantly higher rates of functional independence at 90 days, without increasing the incidence of sICH or mortality. Whilst these findings indicate that NCCT/CTA only may be used for EVT eligibility selection for patients who present beyond 6 hours from stroke onset, the results should be interpreted with caution due to the substantial heterogeneity between studies.Copyright © 2024 The Authors
