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1.
Cureus ; 16(5): e59703, 2024 May.
Article in English | MEDLINE | ID: mdl-38841049

ABSTRACT

BACKGROUND: Tandem occlusions are intracranial large vessel occlusions (LVOs) with a concomitant ipsilateral extracranial internal carotid artery occlusion and can cause more severe stroke symptoms. AIM: To develop a simple, rigorously cross-validated novel tool to predict clinical outcomes following tandem occlusion in patients with acute LVO stroke, based on data that are easily available to clinicians. To have used machine learning approaches to utilize the available information from clinical and angiographic data to make predictive models able to distinguish between mortality versus survival and good (modified Rankin Scale (mRS) ≤ 2) versus unfavorable neurological outcomes (mRs ≥ 3) Materials and methods: Retrospective data from 87 consecutive patients with anterior circulation stroke and tandem occlusions who underwent mechanical thrombectomy and stenting between December 2009 and January 2020 were analyzed. Patients were stratified into three groups based on the location of their LVO, and these groups were compared using statistical tests. Predictive models were built and cross-validated 1000 times to estimate their predictive power, measured by accuracy and area under the receiver operating curve (AUROC). RESULTS: For distinguishing good outcome (mRS ≤ 2) versus poor outcome (mRS ≥ 3), the model comprised age, initial National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT Score (ASPECTS), NIHSS at 24 hours, NIHSS at discharge and intracranial haemorrhage and yielded an accuracy of 83% and the AUROC of 0.91. For mortality prediction, the model comprised age, initial NIHSS, intravenous thrombolysis, NIHSS at 24 hours and NIHSS at discharge and yielded an accuracy of 91% and an AUROC of 0.94. CONCLUSIONS: Models developed exhibit strong predictive performance and can distinguish between both the instances of survival versus mortality and good versus poor outcome with an aim to support clinicians in deciding on optimal management for these complex patients. The developed model will help identify those at risk of poorer outcomes and the prospective better selection of patients with acute ischaemic large vessel stroke secondary to tandem occlusions.

3.
J Clin Med ; 12(23)2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38068341

ABSTRACT

Endovascular therapy (EVT) is the standard treatment for ischemic stroke caused by a large vessel occlusion (LVO). The effectiveness of EVT for distal medium vessel occlusions (MDVOs) is still uncertain, but newer, smaller devices show potential for EVT in MDVOs. The new Solitaire X 3 mm device offers a treatment option for MDVOs. Our study encompassed consecutive cases of primary and secondary MDVOs treated with the Solitaire X 3 mm stent-retriever as first-line EVT device between January and December 2022 at 12 European stroke centers. The primary endpoint was a first-pass near-complete or complete reperfusion, defined as a modified treatment in cerebral infarction (mTICI) score of 2c/3. Additionally, we examined reperfusion results, National Institutes of Health Stroke Scale (NIHSS) scores at 24 h and discharge, device malfunctions, complications and procedural technical parameters. Sixty-eight patients (38 women, mean age 72 ± 14 years) were included in our study. Median NIHSS at admission was 11 (IQR 6-16). In 53 (78%) cases, a primary combined approach was used as the frontline technique. Among all enrolled patients, first-pass mTICI 2c/3 was achieved in 22 (32%) and final mTICI 2c/3 in 46 (67.6%) patients after a median of 1.5 (IQR 1-2) passes. Final reperfusion mTICI 2b/3 was observed in 89.7% of our cases. We observed no device malfunctions. Median NIHSS at discharge was 2 (IQR 0-4), and no symptomatic intracranial hemorrhages were reported. Based on our analysis, the utilization of the Solitaire X 3 mm device appears to be both effective and safe for performing EVT in cases of MDVO stroke.

4.
Stroke Vasc Neurol ; 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37788913

ABSTRACT

BACKGROUND: Intraoperative antiplatelet therapy is recommended for emergent stenting during mechanical thrombectomy (MT). Most patients undergoing MT are also given thrombolysis. Antiplatelet agents are contraindicated within 24 hours of thrombolysis. We evaluated outcomes and complications of patients stented with and without intravenous aspirin during MT. METHODS: All patients who underwent emergent extracranial stenting during MT at the Royal Stoke University Hospital, UK between 2010 and 2020, were included. Patients were thrombolysed before MT, unless contraindicated. Aspirin 500 mg intravenously was given intraoperatively at the discretion of the operator. Symptomatic intracranial haemorrhage (sICH) and the National Institutes for Health Stroke Scale score (NIHSS) were recorded at 7 days, and mortality and functional recovery (modified Rankin Scale: mRS ≤2) at 90 days. RESULTS: Out of 565 patients treated by MT 102 patients (median age 67 IQR 57-72 years, baseline median NIHSS 18 IQR 13-23, 76 (75%) thrombolysed) had a stent placed. Of these 49 (48%) were given aspirin and 53 (52%) were not. Patients treated with aspirin had greater NIHSS improvement (median 8 IQR 1-16 vs median 3 IQR -9-8 points, p=0.003), but there were no significant differences in sICH (2/49 (4%) vs 9/53 (17%)), mRS ≤2 (25/49 (51%) vs 19/53 (36%)) and mortality (10/49 (20%) vs 12/53 (23%)) with and without aspirin. NIHSS improvement (median 12 IQR 4-18 vs median 7 IQR -7-10, p=0.01) was greater, and mortality was lower (4/33 (12%) vs 6/15 (40%), p=0.05) when aspirin was combined with thrombolysis, than for aspirin alone, with no increase in bleeding. CONCLUSION: Our findings based on registry data derived from routine clinical care suggest that intraprocedural intravenous aspirin in patients undergoing emergent stenting during MT does not increase sICH and is associated with good clinical outcomes, even when combined with intravenous thrombolysis.

5.
Interv Neuroradiol ; : 15910199231201518, 2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37769320

ABSTRACT

INTRODUCTION: Endovascular mechanical thrombectomy for ischaemic stroke is one of the most effective treatments. Despite the devices and techniques that have been developed, thrombi are not always successfully retrieved. The incidence of futile reperfusion after successful clot retrieval also remains a major concern. We hypothesise that simply placing an aspiration catheter in the system compromises collateral flow which may have an impact on functional outcomes. METHODS: An in vitro study was conducted using a physical pulsatile flow model designed in glass to mimic the anterior cerebral circulation with middle cerebral artery M1 segment occlusion. A 5Fr aspiration catheter was positioned at the supra-clinoid internal carotid (SC-ICA), carotid terminus (T-ICA) and M1. For each catheter position, the flow rate through the model's anterior cerebral (ACA) and posterior communicating (PCOM) arteries was measured (no aspiration applied). RESULTS: Our results showed significant mean percentage flow reductions in the ACA and PCOM with the catheter positioned at the SC-ICA (PCOM 59.14% ± 0.93, ACA 59.52% ± 0.82, p < 0.001), T-ICA (PCOM 81.54% ± 0.55, ACA 85.65% ± 1.54) and M1 (PCOM 75.79% ± 0.98, ACA 84.20% ± 0.43) (Mann-Whitney U Test, p < 0.001). CONCLUSION: These results indicate a significant reduction in collateral flow following the insertion of a wide bore catheter in an in vitro model. In a clinical setting, this could have an impact on patient outcome, particularly in prolonged procedures and those requiring several passes to achieve recanalisation.

6.
Interv Neuroradiol ; 29(4): 386-392, 2023 Aug.
Article in English | MEDLINE | ID: mdl-35404161

ABSTRACT

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is emerging as an important biomarker of acute physiologic stress in a myriad of medical conditions, and is a confirmed poor prognostic indicator in COVID-19. OBJECTIVE: We sought to describe the role of NLR in predicting poor outcome in COVID-19 patients undergoing mechanical thrombectomy for acute ischemic stroke. METHODS: We analyzed NLR in COVID-19 patients with large vessel occlusion (LVO) strokes enrolled into an international 12-center retrospective study of laboratory-confirmed COVID-19, consecutively admitted between March 1, 2020 and May 1, 2020. Increased NLR was defined as ≥7.2. Logistic regression models were generated. RESULTS: Incidence of LVO stroke was 38/6698 (.57%). Mean age of patients was 62 years (range 27-87), and mortality rate was 30%. Age, sex, and ethnicity were not predictive of mortality. Elevated NLR and poor vessel recanalization (Thrombolysis in Cerebral Infarction (TICI) score of 1 or 2a) synergistically predicted poor outcome (likelihood ratio 11.65, p = .003). Patients with NLR > 7.2 were 6.8 times more likely to die (OR 6.8, CI95% 1.2-38.6, p = .03) and almost 8 times more likely to require prolonged invasive mechanical ventilation (OR 7.8, CI95% 1.2-52.4, p = .03). In a multivariate analysis, NLR > 7.2 predicted poor outcome even when controlling for the effect of low TICI score on poor outcome (NLR p = .043, TICI p = .070). CONCLUSIONS: We show elevated NLR in LVO patients with COVID-19 portends significantly worse outcomes and increased mortality regardless of recanalization status. Severe neuro-inflammatory stress response related to COVID-19 may negate the potential benefits of successful thrombectomy.


Subject(s)
Arterial Occlusive Diseases , Brain Ischemia , COVID-19 , Ischemic Stroke , Stroke , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Arterial Occlusive Diseases/complications , Brain Ischemia/surgery , Cerebral Infarction/etiology , COVID-19/complications , Ischemic Stroke/etiology , Lymphocytes , Neutrophils , Retrospective Studies , Stroke/etiology , Thrombectomy/methods , Treatment Outcome , Male , Female
7.
Methods Mol Biol ; 2557: 101-111, 2023.
Article in English | MEDLINE | ID: mdl-36512212

ABSTRACT

Immunofluorescence is a technique that uses antibodies and fluorophores to label structures inside cells. The cells are normally fixed and permeabilized, and then structures are labelled using primary antibodies directly conjugated to fluorophores, or, more commonly, first with an antibody against an antigen of interest followed by a secondary antibody conjugated to a fluorophore that binds to the primary antibody. Fluorescence can be visualized using widefield, confocal, or super-resolution microscopy. Here we focus on labelling of the Golgi apparatus and show that different fixation and permeabilization conditions can significantly affect labelling of Golgi proteins and describe how to optimize fluorescent detection of Golgi proteins.


Subject(s)
Fluorescent Dyes , Golgi Apparatus , Animals , Golgi Apparatus/metabolism , Microscopy, Fluorescence/methods , Fluorescent Antibody Technique , Fluorescent Dyes/metabolism , Antibodies/metabolism , Microscopy, Confocal , Mammals
8.
Cureus ; 14(10): e30562, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36415419

ABSTRACT

Acute disseminated encephalomyelitis (ADEM) is a central nervous system demyelinating condition. The postulated etiology is an autoimmune reaction, however, the mechanistic details are yet unknown. While infection and immunization are the most prevalent precipitating causes of ADEM, we postulate that radiopaque contrast material might have played a role as an immunological trigger. This presentation is unusual and has not been recorded so far. This case also emphasizes the challenges involved in evaluating emerging neurological problems following a period of intubation/sedation among these patients. We present a patient who passed away due to the manifestations of ADEM following admission to the intensive care unit after thoracic endovascular aortic repair for type B aortic dissection. Magnetic resonance imaging (MRI) performed following multiple attempts at sedation weaning demonstrated typical features of this condition. Clinicians and radiologists should be diligent and consider ADEM as a differential diagnosis when treating patients who present with neurological symptoms following radiological interventional procedures and have a high index suspicion to reduce mortality and achieve satisfactory clinical outcomes.

9.
Cureus ; 14(10): e30345, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36407243

ABSTRACT

Malignant pleural mesothelioma (MPM) typically has a short median survival of only a few months from diagnosis, with death usually due to thoracic disease. This has led to the belief in the past that mesothelioma rarely has distant metastasis, with cerebral metastasis accounting for only 3%. The multiple cases of brain metastasis from MPM recorded so far were discovered after death at autopsy. This report describes a rare case of known malignant mesothelioma with distant haemorrhagic metastasis to the brain, reviews current literature about its metastatic potential to the brain and discusses prognosis and management. We also review the imaging evaluation in known MPM patients with suspected intracranial involvement and describe typical imaging findings of parenchymal brain metastasis on computed tomography (CT) and magnetic resonance imaging (MRI).

10.
Cureus ; 14(10): e30328, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36407248

ABSTRACT

Conventional magnetic resonance imaging (MRI) and computed tomography (CT) are used to diagnose central pontine myelinolysis (CPM), which is seen in the setting of osmotic changes, typically with the rapid correction of hyponatremia. However, they typically follow clinical symptoms and fail to detect myelinolytic lesions within the first two weeks, limiting their efficacy in early diagnosis. CPM can mimic brainstem ischaemic changes on CT head and a glioma on MRI. This case reviews the relationship between radiological changes seen with clinical symptoms and serum sodium levels, combined with reviewing pioneering advances in radiomic analysis, including diffusion-weighted MRI, CT brain perfusion and MR spectroscopy.

11.
Neurosurgery ; 89(1): E35-E41, 2021 06 15.
Article in English | MEDLINE | ID: mdl-33734404

ABSTRACT

BACKGROUND: While there are reports of acute ischemic stroke (AIS) in coronavirus disease 2019 (COVID-19) patients, the overall incidence of AIS and clinical characteristics of large vessel occlusion (LVO) remain unclear. OBJECTIVE: To attempt to establish incidence of AIS in COVID-19 patients in an international cohort. METHODS: A cross-sectional retrospective, multicenter study of consecutive patients admitted with AIS and COVID-19 was undertaken from March 1 to May 1, 2020 at 12 stroke centers from 4 countries. Out of those 12 centers, 9 centers admitted all types of strokes and data from those were used to calculate the incidence rate of AIS. Three centers exclusively transferred LVO stroke (LVOs) patients and were excluded only for the purposes of calculating the incidence of AIS. Detailed data were collected on consecutive LVOs in hospitalized patients who underwent mechanical thrombectomy (MT) across all 12 centers. RESULTS: Out of 6698 COVID-19 patients admitted to 9 stroke centers, the incidence of stroke was found to be 1.3% (interquartile range [IQR] 0.75%-1.7%). The median age of LVOs patients was 51 yr (IQR 50-75 yr), and in the US centers, African Americans comprised 28% of patients. Out of 66 LVOs, 10 patients (16%) were less than 50 yr of age. Among the LVOs eligible for MT, the average time from symptom onset to presentation was 558 min (IQR 82-695 min). A total of 21 (50%) patients were either discharged to home or discharged to acute rehabilitation facilities. CONCLUSION: LVO was predominant in patients with AIS and COVID-19 across 2 continents, occurring at a significantly younger age and affecting African Americans disproportionately in the USA.


Subject(s)
Brain Ischemia/diagnostic imaging , Brain Ischemia/epidemiology , COVID-19/diagnostic imaging , COVID-19/epidemiology , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/epidemiology , Adult , Aged , Aged, 80 and over , Brain Ischemia/therapy , COVID-19/therapy , Cerebrovascular Disorders/diagnostic imaging , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/therapy , Cohort Studies , Cross-Sectional Studies , Female , Humans , Incidence , Internationality , Ischemic Stroke/therapy , Male , Middle Aged , Retrospective Studies , Thrombectomy/adverse effects , Treatment Outcome
12.
Stem Cell Rev Rep ; 17(4): 1465-1477, 2021 08.
Article in English | MEDLINE | ID: mdl-33624208

ABSTRACT

C3G (RAPGEF1), engaged in multiple signaling pathways, is essential for the early development of the mouse. In this study, we have examined its role in mouse embryonic stem cell self-renewal and differentiation. C3G null cells generated by CRISPR mediated knock-in of a targeting vector exhibited enhanced clonogenicity and long-term self-renewal. They did not differentiate in response to LIF withdrawal when compared to the wild type ES cells and were defective for lineage commitment upon teratoma formation in vivo. Gene expression analysis of C3G KO cells showed misregulated expression of a large number of genes compared with WT cells. They express higher levels of self-renewal factors like KLF4 and ESRRB and show high STAT3 activity, and very low ERK activity compared to WT cells. Reintroduction of C3G expression in a KO line partially reverted expression of ESRRB, and KLF4, and ERK activity similar to that seen in WT cells. The expression of self-renewal factors was persistent for a longer time, and induction of lineage-specific markers was not seen when C3G KO cells were induced to form embryoid bodies. C3G KO cells showed poor adhesion and significantly reduced levels of pFAK, pPaxillin, and Integrin-ß1, in addition to downregulation of the cluster of genes involved in cell adhesion, compared to WT cells. Our results show that C3G is essential for the regulation of STAT3, ERK, and adhesion signaling, to maintain pluripotency of mouse embryonic stem cells and enable their lineage commitment for differentiation.


Subject(s)
Cell Differentiation , Guanine Nucleotide-Releasing Factor 2/genetics , Mouse Embryonic Stem Cells , Signal Transduction , Animals , Cell Differentiation/genetics , Extracellular Signal-Regulated MAP Kinases , Leukemia Inhibitory Factor , Mice , Mouse Embryonic Stem Cells/cytology , STAT3 Transcription Factor , Signal Transduction/genetics
13.
Sci Rep ; 10(1): 18838, 2020 11 02.
Article in English | MEDLINE | ID: mdl-33139841

ABSTRACT

Mice lacking C3G (RapGEF1), a ubiquitously expressed protein essential for neuronal differentiation, show multiple defects in brain development. Function of C3G in neurogenesis is poorly defined. Here, we identify brain specific expression of a novel C3G isoform in mice and humans. This isoform has an insert in the Crk-binding region, generating a polypeptide of 175 kDa, unlike the previously known 140 kDa form expressed in all other tissues. In the adult mouse brain, C3G expression is seen in neurons, but was not detectable in GFAP-positive cells. C3G levels were high in the CA3 region of hippocampus and in mitral cells of olfactory bulb. Neural progenitor cells positive for Doublecortin and Nestin, show expression of C3G. During development, C3G is expressed in precursor cells prior to their differentiation into mature neurons or astrocytes. The 175 kDa as well as 140 kDa forms are seen in embryonic mouse brain, while only the 175 kDa variant is seen in post-natal brain. Human cerebral organoids generated from induced pluripotent stem cells predominantly expressed the 140 kDa polypeptides, and the 175 kDa isoform appeared upon maturation. This study describes developmental regulation and neuronal expression of a brain specific isoform of C3G, a molecule essential for normal development of the mammalian brain.


Subject(s)
Brain/growth & development , Brain/metabolism , Gene Expression Regulation, Developmental , Gene Expression , Guanine Nucleotide-Releasing Factor 2/genetics , Guanine Nucleotide-Releasing Factor 2/metabolism , Animals , Brain/embryology , Hippocampus/metabolism , Humans , Mice , Olfactory Bulb/metabolism , Organoids/metabolism , Peptides/metabolism , Protein Isoforms/metabolism
14.
J Neuroimaging ; 30(6): 754-761, 2020 11.
Article in English | MEDLINE | ID: mdl-33142040

ABSTRACT

BACKGROUND AND PURPOSE: Mechanical Thrombectomy (MT) using modern devices has proved to be efficacious in re-establishing intracranial circulation and reduced procedural times. We outline a number of endovascular techniques utilizing the distal access catheter, the circumstances where they are applicable, and the outcomes achieved. METHODS: In this review, we describe a variety of endovascular techniques with distal access catheter, deployed with and without the stent retriever device gained from our experience of performing over 700 procedures in 10 years of providing a 24/7 service within the national framework of a hyperacute stroke centre. RESULTS: We used distal access catheter techniques for intracranial support during a stent-retriever thrombectomy or thrombo-suction on its own. When used as a sole suction device, or combined with a stent-retriever, we have been able to provide a rapid route to successful reperfusion, with minimal complications related to our endovascular procedures. We can report distal access catheter techniques works well when access to thrombi involves navigation through tortuous vessel anatomy, notably when convoluted loops in the cervical internal carotid artery are encountered. We suggest use of the distal access catheter techniques in thrombectomy procedures for steep-angle Middle Cerebral Artery occlusions, M2/M3 occlusion, and for basilar occlusion, where thrombectomy via suction alone proved to be adequate. CONCLUSION: In this pictorial review, we have demonstrated techniques where distal access catheter when used as a sole suction device, or combined with a stent-retriever, has been able to provide a rapid route to successful reperfusion, with minimal complications related to our endovascular procedures.


Subject(s)
Catheters , Endovascular Procedures/methods , Infarction, Middle Cerebral Artery/surgery , Stroke/surgery , Thrombectomy/methods , Humans , Retrospective Studies , Stents , Treatment Outcome
15.
BMC Neurol ; 20(1): 326, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32873250

ABSTRACT

BACKGROUND: Mechanical thrombectomy was approved by NICE as a treatment for stroke in 2016. However, most of the evidence is from studies conducted during working hours. Only few centres in the UK perform thrombectomies out-of-hours. The Royal Stoke University Hospital (RSUH) has offered thrombectomies over 24 h (24/7) since 2010. The aim of this service review is to compare the outcomes for patients treated in regular working hours to those treated outside normal working hours within this unit. METHODS: This retrospective service analysis includes all patients treated with mechanical thrombectomy at RSUH since the start of the service in January 2010 to June 2019. Data on key demographics, timings, procedural complications, and long-term outcomes including death and disability at 90 days were collected. In-hours was defined as the time between 8:00-17:00 h, Monday to Friday; out-of-hours was defined as any time outside this period. RESULTS: In total, 516 mechanical thrombectomies were performed in this time period; data were available on 501 of these. Successful recanalization (TICI 2b/3) was achieved in 86% of patients. By 90 days 96 (19%) had died and 234 (47%) were functionally independent (modified Rankin Scale score ≤ 2). 211 (42%) of the procedures were performed in-hours and 290 (58%) out-of-hours. Door-to-CT and door-to-groin times were significantly longer out-of-hours than in-hours, but thrombectomy duration was significantly shorter. There were no significant differences in complications and short- and long-term outcomes. CONCLUSION: Mechanical thrombectomy was delivered safely and effectively 24/7 in this UK hospital, with no difference in clinical outcomes.


Subject(s)
After-Hours Care , Stroke/therapy , Thrombectomy/methods , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Stroke/etiology , Treatment Outcome , United Kingdom
16.
Clin Med (Lond) ; 20(3): e40-e45, 2020 05.
Article in English | MEDLINE | ID: mdl-32414740

ABSTRACT

INTRODUCTION: The clinical efficacy and cost-effectiveness of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke is well established, but uncertainty remains around the true cost of delivering this treatment within the NHS. The aim of this study was to establish the cost of providing MT within the hyperacute phase of care and to explore differences in resources used and costs across different neuroscience centres in the UK. METHOD: This was a multicentre retrospective study using micro-costing methods to enable a precise assessment of the costs of MT from an NHS perspective. Data on resources used and their costs were collected from five UK neuroscience centres between 2015 and 2018. RESULTS: Data were collected on 310 patients with acute ischaemic stroke treated with MT. The mean total cost of providing MT and inpatient care within 24 hours was £10,846 (95% confidence interval (CI) 10,527-11,165) per patient. The main driver of cost was MT procedure costs, accounting for 73% (£7,943; 95% CI 7,649-8,237) of the total 24-hour cost. Costs were higher for patients treated under general anaesthesia (£11,048; standard deviation (SD) 2,654) than for local anaesthesia (£9,978; SD 2,654), mean difference £1,070 (95% CI 381-1,759; p=0.003); admission to an intensive care unit (ICU; £12,212; SD 3,028) against for admission elsewhere (£10,179; SD 2,415), mean difference £2,032 (95% CI 1,345-2,719; p<0001).The mean cost within 72 hours was £12,440 (95% CI 10,628-14,252). The total costs for the duration of inpatient care before discharge from a thrombectomy centre was £14,362 (95% CI 13,603-15,122). CONCLUSIONS: Major factors contributing to costs of MT for stroke include consumables and staff for intervention, use of general anaesthesia and ICU admissions. These findings can inform the reimbursement, provision and strategic planning of stroke services and aid future economic evaluations.


Subject(s)
Brain Ischemia , Stroke , Brain Ischemia/surgery , Humans , Retrospective Studies , State Medicine , Stroke/therapy , Thrombectomy , United Kingdom
17.
J Cell Sci ; 133(11)2020 06 08.
Article in English | MEDLINE | ID: mdl-32371504

ABSTRACT

C3G (also known as RAPGEF1) plays a role in cell differentiation and is essential for early embryonic development in mice. In this study, we identify C3G as a centrosomal protein that colocalizes with cenexin (also known as ODF2) at the mother centriole in interphase cells. C3G interacts with cenexin through its catalytic domain, and the two proteins show interdependence for localization to the centrosome. C3G depletion causes a decrease in cellular cenexin levels. Centrosomal localization of C3G is lost as myocytes differentiate to form myotubes. Depletion of C3G by CRISPR/Cas9 results in the formation of supernumerary centrioles, whereas overexpression of C3G, or expression of a catalytically active C3G deletion construct, inhibits centrosome duplication. Cilium length is increased in C3G knockout cells, and this phenotype is reverted upon reintroduction of C3G or its catalytic domain alone. Association of C3G with the basal body is dynamic, decreasing upon serum starvation and increasing upon re-entry into the cell cycle. C3G inhibits cilium formation and length, and this inhibition is dependent on C3G catalytic activity. We conclude that C3G regulates centrosome duplication and maintains ciliary homeostasis, properties that could be important for its role in embryonic development.


Subject(s)
Centrioles , Cilia , Animals , Cell Cycle , Centrosome , Female , Guanine Nucleotide-Releasing Factor 2 , Heat-Shock Proteins , Humans , Mice , Mothers
19.
Neuroradiology ; 61(4): 443-449, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30770963

ABSTRACT

PURPOSE: There is overwhelming evidence for the clinical benefits that are derived following mechanical thrombectomy in large-vessel acute ischaemic stroke. The risk of stroke is elevated in pregnancy due to many factors. To date, there have been two reports, totalling five patients, who have undergone mechanical thrombectomy in pregnancy, thus demonstrating the feasibility of the procedure; however, there is no data on the radiation exposure to the mother or foetus related to this therapy. METHODS: We highlight the important technical considerations to minimise the risk of the procedure and report the estimated dose received by mother and foetus. We also compare these doses with those received during whole-body CT in trauma and CT pulmonary angiogram (CTPA) examinations. RESULTS: Three cases of mechanical thrombectomy were performed at separate tertiary referral neuroscience centres in the UK. Following diagnostic CT and mechanical thrombectomy, the total whole-body effective dose to the pregnant patient was significantly higher than in patients undergoing CTPA (p < 0.05), but not significant different compared to whole-body CT imaging in trauma patients. The estimated dose received by the foetus following diagnostic CT and mechanical thrombectomy was significantly lower than in whole-body imaging in trauma patients at p < 0.05, with no difference in estimated foetal dose compared to CTPA imaging. CONCLUSION: The estimated doses received by the foetus during diagnostic stroke imaging and mechanical thrombectomy are equivalent to, or less than, purely diagnostic imaging in emergency situations.


Subject(s)
Brain Ischemia/diagnostic imaging , Brain Ischemia/surgery , Computed Tomography Angiography/methods , Fetus/radiation effects , Pregnancy Complications, Cardiovascular/diagnostic imaging , Pregnancy Complications, Cardiovascular/surgery , Stroke/diagnostic imaging , Stroke/surgery , Thrombectomy/methods , Adult , England , Female , Humans , Pregnancy , Radiation Dosage , Whole Body Imaging
20.
Interv Neuroradiol ; 25(2): 187-193, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30290720

ABSTRACT

BACKGROUND AND PURPOSE: A direct aspiration first pass technique involves first-line aspiration to remove the thrombus through a large-bore aspiration catheter in large vessel strokes. The aim of this study was to assess safety and clinical outcomes with a direct aspiration first pass technique using the new ARC catheter. METHODS: A retrospective analysis of prospectively collected data from three university hospitals was performed between June 2016 and May 2018. The following parameters of all acute ischemic stroke interventions using the ARC catheter were analyzed: use of intravenous thrombolysis, National Institutes of Health Stroke Scale scores at presentation and discharge, successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3), procedure duration, procedure-related complications and 90-day clinical outcome (modified Rankin Scale score). RESULTS: In total, 41 patients were included in the study and anterior circulation occlusion was noted in 35 (85%). The median National Institutes of Health Stroke Scale at admission was 18 and prior intravenous thrombolysis was administered in 35 patients (85%). Only six (15%) patients required the use of a rescue stent retriever. Successful reperfusion was achieved in 40 patients (98%) with a median procedure time of 32 minutes. No catheter-related complications were observed. Symptomatic intracerebral hemorrhage occurred in one patient (2%). Median National Institutes of Health Stroke Scale at discharge was 3; 49% were independent and 10% died at 90 days. CONCLUSIONS: In the present study, the ARC catheter allowed a 98% successful reperfusion rate. The complication rate was in line with those of previous a direct aspiration first pass technique publications.


Subject(s)
Arterial Occlusive Diseases/surgery , Stroke/surgery , Thrombectomy/instrumentation , Aged , Female , Humans , Male , Retrospective Studies , Suction , Treatment Outcome
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