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Stroke, alteplase, brain

Magd Fouad Zakaria, Hany Aref, Azza Abd ElNasser, Nagia Fahmy, Mohamed Amir Tork, Mohamed Mahmoud Fouad, Ahmed ElBokl, Tamer Roushdy, Sara ElFaramawy, Mohammad Abdullah El-Shiekh, Ramez Reda Moustafa
Background The rate of alteplase (tPA) thrombolysis utilization in acute stroke in Egypt is <1%. We report on the causes of this low rate of reperfusion therapies and take corrective action to improve it. Methods Two prospective observational studies were conducted at Ain Shams University hospitals. The first included 269 acute stroke patients admitted to the hospital over a six-month period. Obstacles to reperfusion therapy were identified, and based on the results, a corrective action plan was implemented including making alteplase(tPA) available, training, and establishing a standardized local protocol for reperfusion therapy...
January 1, 2017: International Journal of Stroke: Official Journal of the International Stroke Society
Sheng Zhang, Ying Zhou, Ruiting Zhang, Meixia Zhang, Bruce Campbell, Longting Lin, Fu-Dong Shi, Min Lou
Rationale In acute ischemic stroke patients with large vessel occlusion, although reperfusion within 6 h after stroke onset using combined intravenous alteplase and mechanical thrombectomy (bridging therapy) can improve functional outcome, still approximately 50% patients suffer disability which may result from reperfusion injury. Proof-of-concept clinical trials have indicated that the sphingosine-1-phosphate receptor modulator fingolimod may be efficacious in attenuating brain inflammation and improving clinical outcomes in acute ischemic stroke patients as a single therapy beyond 4...
January 1, 2017: International Journal of Stroke: Official Journal of the International Stroke Society
Daniel F Hanley, Richard E Thompson, John Muschelli, Michael Rosenblum, Nichol McBee, Karen Lane, Amanda J Bistran-Hall, Steven W Mayo, Penelope Keyl, Dheeraj Gandhi, Tim C Morgan, Natalie Ullman, W Andrew Mould, J Ricardo Carhuapoma, Carlos Kase, Wendy Ziai, Carol B Thompson, Gayane Yenokyan, Emily Huang, William C Broaddus, R Scott Graham, E Francois Aldrich, Robert Dodd, Cristanne Wijman, Jean-Louis Caron, Judy Huang, Paul Camarata, A David Mendelow, Barbara Gregson, Scott Janis, Paul Vespa, Neil Martin, Issam Awad, Mario Zuccarello
BACKGROUND: Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. METHODS: MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany...
November 2016: Lancet Neurology
Graeme J Hankey
In the past decade, the definition of stroke has been revised and major advances have been made for its treatment and prevention. For acute ischaemic stroke, the addition of endovascular thrombectomy of proximal large artery occlusion to intravenous alteplase increases functional independence for a further fifth of patients. The benefits of aspirin in preventing early recurrent ischaemic stroke are greater than previously recognised. Other strategies to prevent recurrent stroke now include direct oral anticoagulants as an alternative to warfarin for atrial fibrillation, and carotid stenting as an alternative to endarterectomy for symptomatic carotid stenosis...
February 11, 2017: Lancet
Darren Fernandes, Udayaraj Umasankar
Ischaemic stroke can result in approximately 2 million brain neurones being damaged for each minute that it is left untreated. Various trials and studies such as the National Institute of Neurologic Disorders (NINDS) trial, the European Cooperative Acute Stroke Study (ECASS), ECASS II, and the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study have clearly demonstrated the beneficial effects of intravenous tissue plasminogen activator (tPA) for treatment of acute stroke...
2016: BMJ Quality Improvement Reports
Gilad Rosenberg, Israel Steiner
The fear that alteplase may aggravate primary intracerebral hemorrhages has led to the mandatory prerequisite for prealteplase imaging in all acute stroke patients in order to exclude such hemorrhages. Consequently, in a situation in which "time is brain," administration of alteplase is delayed until the patients are transferred to a hospital where such imaging is available, at the cost of additional ischemic damage to the brain parenchyma. Yet, theoretical considerations and empirical data suggest that alteplase's effects on primary intracerebral hemorrhages may not be that detrimental...
July 12, 2016: Neurology
Ángel Chamorro, Ulrich Dirnagl, Xabier Urra, Anna M Planas
Treatments for acute ischaemic stroke continue to evolve after the superior value of endovascular thrombectomy was confirmed over systemic thrombolysis. Unfortunately, numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischaemic stroke, making the search for new treatments imperative. Increased awareness of the relevance of rigorous preclinical testing, and appropriate selection of study participants, might overcome the barriers to progress in stroke research. Relevant areas of interest include the search for safe and effective treatment strategies that combine neuroprotection reperfusion, better use of advanced brain imaging for patient selection, and wider implementation of prehospital conducted clinical trials...
July 2016: Lancet Neurology
Toshimasa Ikeda, Masahiro Oomura, Chikako Sato, Chise Anan, Kentaro Yamada, Kaoru Kamimoto
A 74-year-old man lost consciousness immediately after defecation. The loss of consciousness lasted for several minutes, and he experienced difficulty in walking when he regained consciousness. He was transferred to our hospital via an ambulance. Upon neurological examination, nystagmus and ataxia in the left arm and leg were noted. An MRI of the brain revealed multiple acute infarcts mainly in the bilateral cerebellum. Intravenous thrombolytic therapy with alteplase was initiated 3 h and 20 min after the onset of symptoms, and an improvement in neurological symptoms was observed...
May 31, 2016: Rinshō Shinkeigaku, Clinical Neurology
Janet M Gutiérrez, Robert J Emery, Stephanie A Parker, Kamilah Jackson, James C Grotta
When a blood clot blocks the blood supply to the brain or when a blood vessel bursts, resulting in brain cell death, the medical condition is referred to as a "stroke." Stroke is a main cause of death worldwide and is a common cause of disability. A common form of stroke, called ischemic stroke, is when blood flow to the brain is decreased. Clinical research has revealed that treatment within the very first hours of symptom onset is key for ischemic stroke with recanalization of occluded arteries by thrombolysis with alteplase...
May 2016: Health Physics
Anka Aleksic-Shihabi, Eni Jadrijevic, Nina Milekic, Ana Repic Bulicic, Marina Titlic, Enra Suljic
INTRODUCTION: Stroke is a medical emergency in neurology, and is one of the leading causes of death nowadays. At a recent time, a therapeutic method used in adequate conditions is thrombolysis, a treatment of an emerging clot in the brain vascular system by alteplase. The application of alteplase also has a high risk of life threatening conditions. CASE REPORT: This is a brief report of a case with thrombolysis complication which manifested as a spleen rupture.
February 2016: Medical Archives
Fahad S Al-Ajlan, Mayank Goyal, Andrew M Demchuk, Priyanka Minhas, Farahna Sabiq, Zarina Assis, Robert Willinsky, Walter J Montanera, Jeremy L Rempel, Ashfaq Shuaib, John Thornton, David Williams, Daniel Roy, Alexandre Y Poppe, Tudor G Jovin, Biggya L Sapkota, Blaise W Baxter, Timo Krings, Frank L Silver, Donald F Frei, Christopher Fanale, Donatella Tampieri, Jeanne Teitelbaum, Cheemun Lum, Dar Dowlatshahi, Jai J Shankar, Philip A Barber, Michael D Hill, Bijoy K Menon
BACKGROUND AND PURPOSE: The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume. METHODS: The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation...
March 2016: Stroke; a Journal of Cerebral Circulation
Jingrui Pan, Xiangpen Li, Ying Peng
Stroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning...
July 1, 2016: Reviews in the Neurosciences
Francesco Arba, Vanessa Palumbo, Jean-Martin Boulanger, Giovanni Pracucci, Domenico Inzitari, Alastair M Buchan, Michael D Hill
BACKGROUND: The effect of preexisting small vessel disease on outcomes of patients with ischemic stroke treated with i.v. thrombolysis is not fully understood. AIM: We aim to investigate the effect of combined leukoaraiosis and lacunes as detected on unenhanced brain computer tomography at baseline on clinical outcomes after i.v. thrombolysis. METHODS: We analyzed data from the Canadian Alteplase for Stroke Effectiveness Study. Small vessel disease was assessed on baseline computer tomography rating for leukoaraiosis and lacunes...
January 2016: International Journal of Stroke: Official Journal of the International Stroke Society
Laura Llull, Sergio Amaro, Ángel Chamorro
Oxidative stress is one of the main mechanisms implicated in the pathophysiology of inflammatory and neurodegenerative diseases of the central nervous system (CNS). Uric acid (UA) is the end product of purine catabolism in humans, and it is the main endogenous antioxidant in blood. Low circulating UA levels have been associated with an increased prevalence and worse clinical course of several neurodegenerative and inflammatory diseases of the CNS, including Parkinson's disease and multiple sclerosis. Moreover, the exogenous administration of UA exerts robust neuroprotective properties in experimental models of CNS disease, including brain ischemia, spinal cord injury, meningitis, and experimental allergic encephalitis...
January 2016: Current Neurology and Neuroscience Reports
Grant Mair, Rüdiger von Kummer, Zoe Morris, Anders von Heijne, Nick Bradey, Lesley Cala, André Peeters, Andrew J Farrall, Alessandro Adami, Gillian Potter, Geoff Cohen, Peter A G Sandercock, Richard I Lindley, Joanna M Wardlaw
OBJECTIVE: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3). METHODS: All prerandomization and follow-up (24-48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase...
January 12, 2016: Neurology
Jan Paweł Bembenek, Marta Bilik, Anna Członkowska
A 79-year-old woman with hypertension was evaluated 3 hours and 20 minutes after the sudden onset of left-sided weakness which lasted about 15 minutes and was followed by involuntary, coarse, flinging movements of the left extremities (hemiballistic), occurring every few minutes, and facial asymmetry. Brain computed tomography revealed no abnormalities. The patient received intravenous thrombolysis with 0.9 mg/kg of alteplase 4 hours after the symptom onset. Involuntary movements and central facial nerve paresis subsided within 48 hours of the thrombolysis...
January 2015: Functional Neurology
Zilong Zhu, Ying Fu, Decai Tian, Na Sun, Wei Han, Guoqiang Chang, Yinhua Dong, Xiaolin Xu, Qiang Liu, Deren Huang, Fu-Dong Shi
BACKGROUND: Inflammatory and immune responses triggered by brain ischemia worsen clinical outcomes of stroke and contribute to hemorrhagic transformation, massive edema, and reperfusion injury associated with intravenous alteplase. We assessed whether a combination of the immune-modulator fingolimod and alteplase is safe and effective in attenuating reperfusion injury in patients with acute ischemic stroke treated within the first 4.5 hours of symptom onset. METHODS AND RESULTS: In this multicenter trial, we randomly assigned 25 eligible patients with hemispheric ischemic stroke stemming from anterior or middle cerebral arterial occlusion to receive alteplase alone and 22 patients to receive alteplase plus oral fingolimod 0...
September 22, 2015: Circulation
Bruce C V Campbell, Geoffrey A Donnan, Kennedy R Lees, Werner Hacke, Pooja Khatri, Michael D Hill, Mayank Goyal, Peter J Mitchell, Jeffrey L Saver, Hans-Christoph Diener, Stephen M Davis
BACKGROUND: Results of initial randomised trials of endovascular treatment for ischaemic stroke, published in 2013, were neutral but limited by the selection criteria used, early-generation devices with modest efficacy, non-consecutive enrollment, and treatment delays. RECENT DEVELOPMENTS: In the past year, six positive trials of endovascular thrombectomy for ischaemic stroke have provided level 1 evidence for improved patient outcome compared with standard care...
August 2015: Lancet Neurology
Stavros Panagiotou, Sikha Saha
Stroke represents one of the major causes of death and disability worldwide, for which no effective treatments are available. The thrombolytic drug alteplase (tissue plasminogen activator or tPA) is the only treatment for acute ischemic stroke but its use is limited by several factors including short therapeutic window, selective efficacy, and subsequent haemorrhagic complications. Numerous preclinical studies have reported very promising results using neuroprotective agents but they have failed at clinical trials because of either safety issues or lack of efficacy...
2015: Frontiers in Neuroscience
(no author information available yet)
BACKGROUND: Brain scans are essential to exclude haemorrhage in patients with suspected acute ischaemic stroke before treatment with alteplase. However, patients with early ischaemic signs could be at increased risk of haemorrhage after alteplase treatment, and little information is available about whether pre-existing structural signs, which are common in older patients, affect response to alteplase. We aimed to investigate the association between imaging signs on brain CT and outcomes after alteplase...
May 2015: Lancet Neurology
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