Ischemic strokes

Homocysteine arises from dietary methionine. High levels of homocysteiae (hyperhomocysteinemia) are a risk factor for occlusive vascular diseases including atherosclerosis and thrombosis (81—84). In a controlled study, semm folate concentrations of <9.2 nmol/L were linked with elevated levels of plasma homocysteiae. Elevated homocysteine levels have beea associated also with ischemic stroke (9). The mechanism by which high levels of homocysteine produce vascular damage are, as of yet, aot completely uaderstood. lateractioa of homocysteiae with platelets or eadothehal cells has beea proposed as a possible mechanism. Clinically, homocysteine levels can be lowered by administration of vitamin B, vitamin B 2> foHc acid. 

S-0139 Shionogi/GSK, Japan ETA receptor Hemorrhagic and ischemic stroke (phase II, Japan)... 

BKCa The diversity of BKCa channels can be attributed to the assembly of pore-forming a subunit together with four different auxiliary subunits ((31 -(34). BMS-204352 has been identified as a BKCa channel opener for the treatment of acute ischemic stroke although it has also been shown as an M-channel activator. Therapeutic applications for channel openers include epilepsy, bladder overactivity, asthma, hypertension, and psychosis. Other known BKCa channel openers include NS-8, NS-1619, NS-4, and certain aminoazaindole analogs. 

Acute Ischemic Stroke An Evidence-based Approach, Edited by David M. Greer. Copyright 2007 John Wiley Sons, Inc. 

Recent years have seen the emergence of successful treatment strategies for ischemic stroke, but these are most effective only when initiated within several hours after stroke onset. Therefore, extremely rapid diagnosis and initiation of treatment are critical in avoiding death or severe disability. 

Besides establishing the diagnosis of ischemic stroke, DWI also offers the capability of measuring the approximate age of infarcts. The apparent diffusion coefficient (ADC) of water, a measure of diffusion that can be derived easily from DWI images, follows a typical sequence of changes in evolving infarcts. °" ADC... 

However, several important studies have shown that intravenous thrombolysis may be beneficial more than 3 hours after stroke onset, provided that only patients with a significant diffusion-perfusion mismatch are treated. In one such smdy, Ribo et al. found that patients with a significant diffusion-perfusion mismatch could be treated safely and effectively in the 3-6-hour time period. In phase II of the desmo-teplase in acute stroke (DIAS) trial, patients with diffusion-perfusion mismatch were treated with desmoteplase up to 9 hours after stroke onset, and showed better outcomes than patients given placebo, with only a minimal incidence of symptomatic hemorrhage. Similar success was achieved in the same time window by the dose escalation study of desmoteplase in acute ischemic stroke (DEDAS). ... 

NfNDS rt-PA Study Group. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N EnglJMed 1995 333 1581-1587. 

Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR, Soehngen M, Warach S, Group DS. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS) a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke 2005 36 66-73. 

Lutsep TIL, Albers GW, de Crespigny A, Kamat GN, Marks MP, Moseley ME. Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke. Ann Neurol 1997 41 574-580. 

Nagesh V, Welch KM, Windham JP, Patel S, Levine SR, Hearshen D, Peck D, Robbins K, D OIhaberriague L, Soltanian-Zadeh H, Boska MD. Time course of ADCw changes in ischemic stroke beyond the human eye. Stroke 1998 29 1778-1782. 

Copen WA, Schwamm LH, Gonzalez RG, Wu O, Harmath CB, Schaefer PW, Koroshetz WJ, Sorensen AG. Ischemic stroke effects of etiology and patient age on the time course of the core apparent diffusion coefficient. Radiology 2001 221 27-34. 

Pomerantz SR, Harris GJ, Desai HJ, Lev MH. Computed tomography angiograph and computed tomography perfusion in ischemic stroke a step-hy-step approach to image acquisition and three-dimensional postprocessing. Semin Ultrasound CT MR 2006 27 243-270. 

Tong DC, Yenari MA, Albers GW, O Brien M, Marks MP, Moseley ME. Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute (<6.5 hour) ischemic stroke. Neurology 1998 50 864-870. 

Karonen JO, Vanninen RL, Liu Y, 0stergaard L, Kuikka JT, Nuutinen J, Vanninen EJ, Partanen PL, Vainio PA, Korbonen K, Perkio J, Roivainen R, Sivenius J, Aronen HJ. Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke. Ischemic penumbra predicts infarct growth. Stroke 1999 30 1583-1590. 

Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999 282 2019-2026 [see comment]. 

Eurlan AJ, Eyding D, Albers GW, Al-Rawi Y, Lees KR, Rowley HA, Sachara C, Soehngen M, Warach S, Hacke W, Investigators D. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS) evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke 2006 37 1227-1231. 

Katzan IL, Eurlan AJ, Lloyd EE, Erank JI, Harper DL, Hinchey JA, Hammel JP, Qu A, Sila CA. Use of tissue-t)fpe plasminogen activator for acute ischemic stroke the Cleveland area experience. JAMA 2000 283 1151-1158. 

O Connor RE, McGraw P, Edelsohn L. Thrombolytic therapy for acute ischemic stroke why the majority of patients remain ineligible for treatment. Ann Emerg Med 1999 33 9-14. 

Anonymous. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NBSfDS t-PA Stroke Study Group. Stroke 1997 28 2109-2118. 

Kassner A, Roberts T, Taylor K, Silver F, Mikulis D. Prediction of hemorrhage in acute ischemic stroke using permeability MR imaging. Am J Neuroradiol 2005 26 2213-2217. 

Stroke is the leading cause of major long-term disability in adults and the third leading cause of death in the United States. On average, a new stroke occurs every 45 seconds. Thrombolytic therapy with intravenous recombinant tissue-plasminogen activator (IV rt-PA) is the most effective treatment for acute ischemic stroke. In this chapter, we review the rationale for thrombolysis in acute ischemic stroke, clinical evidence supporting the use of thrombolytics, and the application of thrombolysis in practice. 

Ischemic stroke has numerous causes. Cerebral infarction may result from large artery atherosclerosis, cardiac embolism, small artery lipohyalinosis, cryptogenic embolism, or, more rarely, from other diverse conditions such as arterial dissection, infective endocarditis, and sickle cell disease. Arterial occlusion is the cause of at least 80% of acute cerebral infarctions. " ... 

---