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July 21, 1993, Vol 270, No. 3 >
ARTICLE | July 21, 1993

Evolving Toward Effective Therapy for Acute Ischemic Stroke FREE

Marc Fisher, MD; Julien Bogousslavsky, MD
[+] Author Affiliations

Reprint requests to The Medical Center of Central Massachusetts, 119 Belmont St, Worcester, MA 01605 (Dr Fisher).


JAMA. 1993;270(3):360-364. doi:10.1001/jama.1993.03510030084039
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Article
References

Acute ischemic stroke is a common, devastating disorder without beneficial therapy. Recent advances concerning the pathophysiology of ischemic brain injury have led to the development of rational pharmacological interventions. Thrombolytic and cytoprotective therapies may be useful and are being evaluated in clinical trials. The design of adequate clinical trials to evaluate these promising therapies has also evolved based on experience. Potential therapy for acute ischemic stroke must be assessed in a large number of patients who are given the intervention within hours of onset using a neurological scoring scale and a disability scale. Several new magnetic resonance imaging technologies are emerging that should allow the clinician to rapidly and accurately identify ischemic brain lesions and to evaluate cerebral perfusion. The availability of potentially efficacious therapies for ischemic stroke evaluated in well-designed clinical trials with magnetic resonance imaging technology, which can also assess therapeutic effects in vivo, should lead to the emergence of therapy to improve the outcome of patients with ischemic stroke in the near future.

(JAMA. 1993;270:360-364)

REFERENCES

1 +
Albers GW, Sherman DG, Gress DR, Paulseth JE, Petersen PE.  Stroke prevention in nonvalvular atrial fibrillation: a review of prospective randomized trials. Ann Neurol . 1991;;30:511-518.
2 +
North American Symptomatic Carotid Endarterectomy Trial Collaborators.  Beneficial effects of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med . 1991;;325:445-453.
3 +
Whisnant JP.  Changing incidence and mortality rates for stroke. J Stroke Cerebrovasc Dis . 1992;; 2:42-44.
4 +
Levine SR.  Acute cerebral ischemia in a critical care unit: a review of diagnosis and management. Arch Intern Med . 1989;;149:90-98.
5 +
Pulsinelli W.  Pathophysiology of acute ischaemic stroke. Lancet . 1992;;339:533-536.
6 +
Fieschi C, Argentino C, Lenzi GL, Sacchetti ML, Toni D, Bozzao L.  Clinical and instrumental evaluation of patients with ischemic stroke within the first six hours. J Neurol Sci . 1989;;91:311-322.
7 +
del Zoppo GJ, Poeck K, Pessin MS, et al.  Recombinant tissue plasminogen activator for acute thrombotic and embolic stroke. Ann Neurol . 1992;; 32:78-86.
8 +
Loscalzo J, Braunwald E.  Tissue plasminogen activator. N Engl J Med . 1988;;319:925-931.
9 +
Sloan MA, Gore JM.  Ischemic stroke and intracranial hemorrhage following thrombolytic therapy for acute myocardial infarction: a risk benefit analysis. Am J Cardiol . 1992;;69:21A-38A.
10 +
Overgaard K, Sereghy T, Boysen G, Pedersen H, Diemer NH.  Reduction of infarct volume and mortality by thrombolysis in a rat embolic stroke model. Stroke . 1992;;23:1167-1174.
11 +
Brott TG, Haley EC, Levy DE, et al.  Urgent therapy for stroke, I: pilot study of tissue plasminogen activator administered within 90 minutes. Stroke . 1992;;23:632-640.
12 +
Mori E, Yoneda Y, Tabuchi M, et al.  Intravenous recombinant tissue plasminogen activator in acute carotid territory stroke. Neurology . 1992;;42:976-982.
13 +
Von Kummer R, Hacke W.  Safety and efficacy of intravenous tissue plasminogen activator and heparin in acute middle cerebral artery stroke. Stroke . 1992;;23:646-652.
14 +
Ringelstein EB, Biniek R, Weiller C, Ammeling B, Nolte PN, Throw A.  Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization. Neurology . 1992;;42:289-298.
15 +
Choi D.  Methods for antagonizing glutamate neurotoxicity. Cerebrovasc Brain Metab Rev . 1990;; 2:105-147.
16 +
Astrup J, Siesjo BK, Symon L.  Thresholds in cerebral ischemia: the ischemic penumbra. Stroke . 1981;;12:723-725.
17 +
Memzawa H, Smith ML, Siesso BK.  Penumbral salvage by reperfusion following middle cerebral artery occlusion in rats. Stroke . 1992;;23:552-559.
18 +
Jones T, Morawetz R, Crowell R, et al.  Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg . 1981;;54:773-782.
19 +
Grotta JC.  Clinical aspects of the use of calcium antagonists in cerebrovascular disease. Clin Neuropharmacol . 1991;;14:373-390.
20 +
Gelmers HJ, Gorter K, de Weerdt CJ, Wiezer JHA.  A controlled trial of nimodipine in acute ischemic stroke. N Engl J Med . 1988;;318:203-207.
21 +
Scatton B, Carter C, Benavides J, Giroux C.  N-methyl-D-aspartate receptor antagonists: a novel therapeutic perspective for the treatment of ischemic brain injury. Cerebrovasc Dis . 1991;;1:121-135.
22 +
Olney JW, Labruyere J, Price MT.  Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science . 1989;;244:1360-1362.
23 +
Buchan A, Xue D, Huang ZG, Smith KH, Lesiuk H.  Delayed AMPA receptor blockade reduces cerebral infarction induced by focal ischemia. Neurol Rep . 1991;;2:473-476.
24 +
Smith SE, Meldrum BS.  Cerebroprotective effect of a non-N-methyl-D-aspartate antagonist, GYKI52466, after focal ischemia in the rat. Stroke . 1992;;23:861-864.
25 +
Kusomoto K, MacKay KB, McCulloch J.  The effect of the kappa-opioid receptor agonist CI-977 in a rat model of focal cerebral ischemia. Brain Res . 1992;;576:147-151.
26 +
Xue D, Sliuka A, Buchan AM.  Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats. Stroke . 1992;; 23:894-899.
27 +
Kochawek PM, Hallenback JM.  Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke . 1992;;23:1367-1379.
28 +
Sackett DL.  Rational therapy in the neurosciences: the role of the randomized trial. Stroke . 1983;;17:1325-1329.
29 +
The International Nimodipine Study Group.  Meta-analysis of nimodipine trials in acute ischemic stroke. Stroke . 1992;;23:148.
30 +
Rocca WA, Dorsey FC, Grigoletto F, et al.  Design and baseline results of the monosialoganglioside early stroke trial. Stroke . 1992;;23:519-526.
31 +
Barsan W, Brott T, Broderick J, Haley EC, Levy D, Marles J.  Factors associated with early hospital arrival after acute stroke. Stroke . 1992;;23: 149.
32 +
The American Nimodipine Study Group.  Clinical trial of nimodipine in acute ischemic stroke. Stroke . 1992;;23:3-8.
33 +
Orgogozo JM, Dartigues JF. Methodology of  clinical trials in acute cerebral ischemia. Cerebrovasc Dis . 1991;;1( (suppl 1) ):100-111.
34 +
Lyden PD, Lau GT.  A critical appraisal of stroke evaluation and rating scales. Stroke . 1991;;22:1345-1352.
35 +
Granger CV, Hamilton BB, Gresham GE, Kramer AA.  The Stroke Rehabilitation Outcome Study, II: relative merits of the total Barthel Index score and a four-item subscore in predicting patient outcome. Arch Phys Med Rehabil . 1989;;70:100-103.
36 +
Van Gijn J, Warlow C.  Down with stroke scales. Cerebrovasc Dis . 1992;;2:244-246.
37 +
Bryan RL, Levy LM, Whitlow WD, et al.  Diagnosis of acute cerebral infarction: comparison of CT and MRI imaging. AJR Am J Roentgenol . 1991;; 157:585-597.
38 +
Lebihan D.  Molecular diffusion nuclear magnetic resonance imaging. Magn Reson Q . 1991;;7:1-30.
39 +
Minematsu K, Li L, Fisher M, Sotak CH, Davis MA, Fiandaca MS.  Diffusion-weighted magnetic resonance imaging: rapid and quantitative detection of focal brain ischemia. Neurology . 1992;;42:235-240.
40 +
Warach S, Chien D, Li W, Ronthal M, Edelman RR.  Fast magnetic resonance diffusion-weighted imaging of acute human stroke. Neurology . 1992;; 42:1717-1723.
41 +
Minematsu K, Li L, Sotak CH, Davis MA, Fisher M.  Reversible focal ischemic injury demonstrated by diffusion-weighted magnetic resonance imaging. Stroke . 1992;;23:1304-1311.
42 +
Minematsu K, Fisher M, Li L, et al.  Effects of a novel NMDA antagonist on experimental stroke rapidly and quantitatively assessed by diffusion-weighted MRI. Neurology . 1993;;43:397-403.
43 +
Minematsu K, Fisher M, Li L, et al.  Combined therapy with a non-competitive NMDA antagonist CNS-1102 and reperfusion in a rat stroke model evaluated by diffusion weighted MRI. J Stroke Cerebrovasc Dis . 1992;;2( (suppl 1) ):138.
44 +
Wendland MF, White DL, Aicher KP, Ka AA, Moseley ME.  Detection with echoplanar imaging of transit of susceptibility contrast medium in a rat model of regional brain ischemia. J MRI . 1991;;1: 285-292.
45 +
Belliveau JW, Kennedy DW, Mekinstry RC, et al.  Functional mapping of the human visual cortex by magnetic resonance imaging. Science . 1991;;254: 716-718.
46 +
Warach S, Li W, Ronthal M, Edelman RR.  Evaluation of acute cerebral ischemia using dynamic contrast-enhanced MR and MR angiography. Radiology . 1992;;182:41-47.
47 +
Stehling MK, Turner R, Mansfield P.  Echo planar imaging: magnetic resonance imaging in a fraction of a second. Science . 1991;;254:43-50.

Figures

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Albers GW, Sherman DG, Gress DR, Paulseth JE, Petersen PE.  Stroke prevention in nonvalvular atrial fibrillation: a review of prospective randomized trials. Ann Neurol . 1991;;30:511-518.
2 +
North American Symptomatic Carotid Endarterectomy Trial Collaborators.  Beneficial effects of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med . 1991;;325:445-453.
3 +
Whisnant JP.  Changing incidence and mortality rates for stroke. J Stroke Cerebrovasc Dis . 1992;; 2:42-44.
4 +
Levine SR.  Acute cerebral ischemia in a critical care unit: a review of diagnosis and management. Arch Intern Med . 1989;;149:90-98.
5 +
Pulsinelli W.  Pathophysiology of acute ischaemic stroke. Lancet . 1992;;339:533-536.
6 +
Fieschi C, Argentino C, Lenzi GL, Sacchetti ML, Toni D, Bozzao L.  Clinical and instrumental evaluation of patients with ischemic stroke within the first six hours. J Neurol Sci . 1989;;91:311-322.
7 +
del Zoppo GJ, Poeck K, Pessin MS, et al.  Recombinant tissue plasminogen activator for acute thrombotic and embolic stroke. Ann Neurol . 1992;; 32:78-86.
8 +
Loscalzo J, Braunwald E.  Tissue plasminogen activator. N Engl J Med . 1988;;319:925-931.
9 +
Sloan MA, Gore JM.  Ischemic stroke and intracranial hemorrhage following thrombolytic therapy for acute myocardial infarction: a risk benefit analysis. Am J Cardiol . 1992;;69:21A-38A.
10 +
Overgaard K, Sereghy T, Boysen G, Pedersen H, Diemer NH.  Reduction of infarct volume and mortality by thrombolysis in a rat embolic stroke model. Stroke . 1992;;23:1167-1174.
11 +
Brott TG, Haley EC, Levy DE, et al.  Urgent therapy for stroke, I: pilot study of tissue plasminogen activator administered within 90 minutes. Stroke . 1992;;23:632-640.
12 +
Mori E, Yoneda Y, Tabuchi M, et al.  Intravenous recombinant tissue plasminogen activator in acute carotid territory stroke. Neurology . 1992;;42:976-982.
13 +
Von Kummer R, Hacke W.  Safety and efficacy of intravenous tissue plasminogen activator and heparin in acute middle cerebral artery stroke. Stroke . 1992;;23:646-652.
14 +
Ringelstein EB, Biniek R, Weiller C, Ammeling B, Nolte PN, Throw A.  Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization. Neurology . 1992;;42:289-298.
15 +
Choi D.  Methods for antagonizing glutamate neurotoxicity. Cerebrovasc Brain Metab Rev . 1990;; 2:105-147.
16 +
Astrup J, Siesjo BK, Symon L.  Thresholds in cerebral ischemia: the ischemic penumbra. Stroke . 1981;;12:723-725.
17 +
Memzawa H, Smith ML, Siesso BK.  Penumbral salvage by reperfusion following middle cerebral artery occlusion in rats. Stroke . 1992;;23:552-559.
18 +
Jones T, Morawetz R, Crowell R, et al.  Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg . 1981;;54:773-782.
19 +
Grotta JC.  Clinical aspects of the use of calcium antagonists in cerebrovascular disease. Clin Neuropharmacol . 1991;;14:373-390.
20 +
Gelmers HJ, Gorter K, de Weerdt CJ, Wiezer JHA.  A controlled trial of nimodipine in acute ischemic stroke. N Engl J Med . 1988;;318:203-207.
21 +
Scatton B, Carter C, Benavides J, Giroux C.  N-methyl-D-aspartate receptor antagonists: a novel therapeutic perspective for the treatment of ischemic brain injury. Cerebrovasc Dis . 1991;;1:121-135.
22 +
Olney JW, Labruyere J, Price MT.  Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science . 1989;;244:1360-1362.
23 +
Buchan A, Xue D, Huang ZG, Smith KH, Lesiuk H.  Delayed AMPA receptor blockade reduces cerebral infarction induced by focal ischemia. Neurol Rep . 1991;;2:473-476.
24 +
Smith SE, Meldrum BS.  Cerebroprotective effect of a non-N-methyl-D-aspartate antagonist, GYKI52466, after focal ischemia in the rat. Stroke . 1992;;23:861-864.
25 +
Kusomoto K, MacKay KB, McCulloch J.  The effect of the kappa-opioid receptor agonist CI-977 in a rat model of focal cerebral ischemia. Brain Res . 1992;;576:147-151.
26 +
Xue D, Sliuka A, Buchan AM.  Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats. Stroke . 1992;; 23:894-899.
27 +
Kochawek PM, Hallenback JM.  Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke . 1992;;23:1367-1379.
28 +
Sackett DL.  Rational therapy in the neurosciences: the role of the randomized trial. Stroke . 1983;;17:1325-1329.
29 +
The International Nimodipine Study Group.  Meta-analysis of nimodipine trials in acute ischemic stroke. Stroke . 1992;;23:148.
30 +
Rocca WA, Dorsey FC, Grigoletto F, et al.  Design and baseline results of the monosialoganglioside early stroke trial. Stroke . 1992;;23:519-526.
31 +
Barsan W, Brott T, Broderick J, Haley EC, Levy D, Marles J.  Factors associated with early hospital arrival after acute stroke. Stroke . 1992;;23: 149.
32 +
The American Nimodipine Study Group.  Clinical trial of nimodipine in acute ischemic stroke. Stroke . 1992;;23:3-8.
33 +
Orgogozo JM, Dartigues JF. Methodology of  clinical trials in acute cerebral ischemia. Cerebrovasc Dis . 1991;;1( (suppl 1) ):100-111.
34 +
Lyden PD, Lau GT.  A critical appraisal of stroke evaluation and rating scales. Stroke . 1991;;22:1345-1352.
35 +
Granger CV, Hamilton BB, Gresham GE, Kramer AA.  The Stroke Rehabilitation Outcome Study, II: relative merits of the total Barthel Index score and a four-item subscore in predicting patient outcome. Arch Phys Med Rehabil . 1989;;70:100-103.
36 +
Van Gijn J, Warlow C.  Down with stroke scales. Cerebrovasc Dis . 1992;;2:244-246.
37 +
Bryan RL, Levy LM, Whitlow WD, et al.  Diagnosis of acute cerebral infarction: comparison of CT and MRI imaging. AJR Am J Roentgenol . 1991;; 157:585-597.
38 +
Lebihan D.  Molecular diffusion nuclear magnetic resonance imaging. Magn Reson Q . 1991;;7:1-30.
39 +
Minematsu K, Li L, Fisher M, Sotak CH, Davis MA, Fiandaca MS.  Diffusion-weighted magnetic resonance imaging: rapid and quantitative detection of focal brain ischemia. Neurology . 1992;;42:235-240.
40 +
Warach S, Chien D, Li W, Ronthal M, Edelman RR.  Fast magnetic resonance diffusion-weighted imaging of acute human stroke. Neurology . 1992;; 42:1717-1723.
41 +
Minematsu K, Li L, Sotak CH, Davis MA, Fisher M.  Reversible focal ischemic injury demonstrated by diffusion-weighted magnetic resonance imaging. Stroke . 1992;;23:1304-1311.
42 +
Minematsu K, Fisher M, Li L, et al.  Effects of a novel NMDA antagonist on experimental stroke rapidly and quantitatively assessed by diffusion-weighted MRI. Neurology . 1993;;43:397-403.
43 +
Minematsu K, Fisher M, Li L, et al.  Combined therapy with a non-competitive NMDA antagonist CNS-1102 and reperfusion in a rat stroke model evaluated by diffusion weighted MRI. J Stroke Cerebrovasc Dis . 1992;;2( (suppl 1) ):138.
44 +
Wendland MF, White DL, Aicher KP, Ka AA, Moseley ME.  Detection with echoplanar imaging of transit of susceptibility contrast medium in a rat model of regional brain ischemia. J MRI . 1991;;1: 285-292.
45 +
Belliveau JW, Kennedy DW, Mekinstry RC, et al.  Functional mapping of the human visual cortex by magnetic resonance imaging. Science . 1991;;254: 716-718.
46 +
Warach S, Li W, Ronthal M, Edelman RR.  Evaluation of acute cerebral ischemia using dynamic contrast-enhanced MR and MR angiography. Radiology . 1992;;182:41-47.
47 +
Stehling MK, Turner R, Mansfield P.  Echo planar imaging: magnetic resonance imaging in a fraction of a second. Science . 1991;;254:43-50.

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