Ischaemic stroke

E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas R Randomised double-blind placebo-controlled trial of thrombol3ffic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998 352 1245-1251. 

Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial-Italy (MAST-I)... 

Wardlaw JM, Zoppo G, Yamaguchi T, Berge E. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2003 CD000213. 

Dimagl U, ladecola C, Moskowitz MA. Pathobiology of ischaemic stroke an integrated view. Trends Neurosci 1999 22 391-397. 

Catalase, the antioxidant enzyme that converts hydrogen peroxide to water, has been evaluated in combination with SOD in a model of focal ischaemic stroke in the rat. Both enzymes were eonjugated with polyethylene glycol to increase the circulatory half-life. They significantly reduced inferct volume (Liu et al., 1989). 

Further support for the hypothesis that NO may play a mediatory role in focal ischaemic stroke was provided by a study in which N -nitro-L-argine was given intraperitoneally (i.p.) to 6-day-old rat pups. The drug protected against hypoxic-ischaemic injury (Trifiletti, 1992). 

Feigin VL, Doronin BM, Popova TF, Gribatcheva EV and Tchervov DV (2001). Vinpocetine treatment in acute ischaemic stroke A pilot single-blind randomized clinical trial. 

Ischaemic stroke is the third leading cause of death in industrialized countries. The debilitating or lethal consequences of transient or temporary reductions in cerebral blood flow are not only caused by necrosis in the infarct zone itself, but also by pathophysiological events in the peri-infarct zone [14]. Apparently, the release of inflammatory mediators such as cytokines and NO contributes to tissue inflammatory injury. There is also evidence for apoptosis in the peri-infarct zone. These processes offer novel targets for therapeutic strategies. In this respect, the potential of neurotrophic factor treatment is described in Section 2.4.2.6. 

Mursu J, Voutilainen S, Nurmi T, Tuomainen TP, Kurl S, Salonen JT. 2008. Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men The Kuopio Ischaemic Heart Disease Risk Factor Study. Br J Nutr 100 890-895. 

Elwood, P. C., Pickering, J. E., Fehily, A. M., Hughes, J., and Ness, A. R. (2004a). Milk drinking, ischaemic heart disease and ischaemic stroke I. Evidence from the Caerphilly cohort. Eur. ]. Clin. Nutr. 58, 711-717. 

Ischaemic stroke commonly occurs due to the occlusion of blood vessels which perfuse the brain by the occurrence of a blood clot that originates from the heart or an atherosclerotic arterial plaque. To date, most therapeutic strategies have failed to prevent cerebral infarction but currently a number of experimental studies in animal models of stroke have led to the development of potential agents that can reduce infarct size. Some of these experimental approaches will now be considered. 

Adams, M. P. Treating ischaemic stroke as an emergency. Arch. Neurol. 55 (1998) 457-461. 

Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH) randomised, double-blind, placebo-controlled trial. Lancet 2004 364 331-337. 

Dawson, V. L. (1995). Nitric oxide Role in neurotoxicity. Clin. Exp. Pharmacol. Physiol. 22, 305-308. Dirnagl, U., Iadecola, C., and Moskowitz, M. A. (1999). Pathobiology of ischaemic stroke An integrated view. Trends Neurosci. 22, 391—397. 

Fallon UB, Elwood P, Ben Shiomo Y, Ubbink JB, Greenwood R, Smith GD. 2001. Homocysteine and ischaemic stroke in men the Caerphilly study. J Epidemiol Community Health 55 91-96. 

AMPA receptor antagonist treatment in ischaemic stroke (Artist-MRI) No No Yes... 

Although ongoing trials may modify the following treatment algorithm, a possible role of combined PI and DWI as part of a multimodal MRI protocol in the near future for the selection of acute ischaemic stroke patient for thrombolysis is presented below. Indeed, many centres do use stroke MRI to select patients for thrombolysis beyond 3 h (Schellinger et al. 2003). At present, as the evidence is not conclusive, we prefer to randomise post-3-h patients to thrombolytic trials. 

Castillo J., Davalos A., and Noya M. (1997) Progression of ischaemic stroke and excitotoxic aminoacids. Lancet 349,79-83. 

Mrs SL, aged 75, is admitted to hospital unable to speak, swallow or move her right arm and leg, having collapsed when out to dinner with her son. She has an urgent CT scan which reveals an ischaemic stroke of the partial anterior circulation (PAC) type. She had a transient ischaemic attack (TIA) two weeks ago and her son says she has had them infrequently for the last year. She has been treated for hypertension and high cholesterol for the past 2 years and has been taking aspirin. 

Ischaemic and haemorrhagic strokes are identified by CT scan within 24—48 hours of a stroke, not by clinical signs and symptoms. However, seizures, nausea, vomiting and headache may increase the clinical likehood of haemorrhagic stroke. Haemorrhagic strokes must not be treated with any anticoagulants (e.g. aspirin) in the acute phase, whereas this is recommended for patients with ischaemic stroke. 

Thrombolysis can be considered for ischaemic stroke but ideally needs to be given within 3 hours of the stroke. There are strict guidelines which must be adhered to to maximise benefit and minimise harm from this intervention (e.g. haemorrhagic stroke must be excluded). Aspirin 300 mg orally or rectally should be given as soon as possible after the diagnosis of ischaemic stroke has been made. Many centres reduce this dose to 75 mg daily after two weeks. However, aspirin treatment should be not be initiated until 24 hours after thrombolysis (Royal College of Physicians, 2004). 

Mrs SL should be given aspirin 300 mg rectally daily from admission, once ischaemic stroke has been diagnosed. Dipyridamole SR 200 mg b.d. may be added when Mrs SL can swallow, following recommendations for secondary prevention of stroke (ESPRIT Study Group, 2006). 

Previous ischaemic stroke/ transient ischaemic attack or thromboembolic event Age > 75 years with hypertension, diabetes, or vascular disease (coronary artery disease or peripheral artery disease) Age > 65 years with no high risk factors Age < 75 years with hypertension, diabetes, or vascular disease (coronary artery disease or peripheral artery disease) Age less than 65 years with no moderate or high risk factors... 

Gill SS, Rochon PA, Herrmann N, Lee PE, Sykora K, Gunraj N, Normand SLT, Gurwitz JH, Marras C, Wodchis WP, Mamdani M. Atypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study. BMJ 2005 330 445. 

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