Ischemic stroke, treatment

There have been three large randomized trials of streptokinase in acute ischemic stroke treatment, all of which were terminated early because of increased sICH and mortality in the treatment group (Table 3.1)." " " ... 

Martinez-Vila E, Mmia P. Challenges of neuroprotection and neurorestoration in ischemic stroke treatment. Cerebrovasc Dis. 2005 20 Suppl 2 148-158. 

Diener HC, Cortens M, Eord G, Grotta J, Hacke W, Kaste M, Koudstaal PJ. Lubeluzole in acute ischemic stroke treatment a double-bhnd study with an 8-hour inclusion window comparing a 10-mg daily dose of lubeluzole with placebo. Stroke 2000 31 2543-2551. 

In 2004, the abciximab and rt-PA in Acute Ischemic Stroke Treatment trial treated hve patients with abciximab and half dose of rt-PA within 3 hours of symptom onset. The primary aim was to examine the frequency of SICH at 24 hours. This occurred in one of the five patients. The median NIHSS improvement was 6. 

Abciximab and rt-PA in acute ischemic stroke treatment. Presented at the 28th International Stroke Conference February 2003. Acad Emerg Med 2003 10(12) 1396-1399. 

Streptokinase is not indicated for use in acute ischemic stroke treatment. Three large randomized controlled trials evaluating streptokinase were stopped early due to a high incidence of hemorrhage in the streptokinase-treated patients.14-16 At the present time, there is no indication for the use of streptokinase or thrombolytics other than alteplase in the acute treatment of ischemic stroke. 

Many of the trials of therapy in acute stroke did not distinguish between stroke subtypes other than by division into hemorrhagic and ischemic stroke. Therefore, there is little evidence for different effectiveness for most acute ischemic stroke treatments according to stroke subtype and location. However, stroke subtype determines patient selection for specific secondary preventive strategies. Therefore, better characterization of stroke will aid overall patient management (Ch. 6). 

Hypoglycemia drug-induced Hypothalamic hormones Immunization agents used in Immunosuppressive medications In vitro fertilization drugs for Insomnia treatment with benzodiazepines Insulin preparations Iodine-containing products Ischemic stroke treatment of Laxatives... 

Evidence-Based Recommendations for Acute Ischemic Stroke Treatment with IV Fibrinolysis... 

Shah, Q.A., et al. Preliminary experience with the use of intra-arterial tenecteplase for acute ischemic stroke treatment. 

Lapchak, P.A. and Araujo, D.M. (2007) Advances in ischemic stroke treatment Neuroprotective and combination therapies. Expert Opin. Emerg. Drugs, 12 97-112. 

The intermolecular Mitsunobu alkylation can be followed by a number of other reactions to make larger cyclic structures. The example below shows a phenol alkylation to make a chiral precursor for the synthesis of repintonan (BAY-3702), a high affinity 5-HTia receptor agonist in clinical trials as an ischemic stroke treatment.After the initial Mitsunobu reaction, the alkylated intermediate 99 is converted into the chromene 100 according to a protocol initially developed by Grubbs and Chang. 

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. 

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. 

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. 

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. 

The NINDS rt-PA smdy was divided into two parts. NINDS part I included 291 patients and NINDS part II included 333 patients. In both parts, acute ischemic stroke patients presenting within 3 hours of symptom onset were randomized to placebo versus treatment with the human rt-PA Alteplase (Activase). The dose was 0.9 mg/kg (maximum dose 90 mg), with 10% of the total dose given as a bolus and the remaining 90% infused over 60 minutes. Inclusion and exclusion criteria for both parts are listed in Table 3.2. These criteria are now the standard clinical criteria used to determine IV rt-PA eligibility in acute stroke patients. 

Three large randomized trials, the European Cooperative Acute Stroke Study (ECASS) parts I and II, and the Alteplase Thrombolysis for Acute Noninterven-tional Therapy in Ischemic Stroke (ATLANTIS), have investigated the efficacy of IV rt-PA in acute stroke beyond the 3-hour window. All three studies showed high rates of sICH complicating rt-PA treatment, and no overall efficacy of rt-PA. 

The authors concluded that campaigns to educate patients to seek treatment sooner should be major components of system-wide interventions to increase the rate of thrombolysis for acute ischemic stroke. There is some evidence that public education may help to increase the rate of rt-PA utilization by encouraging earlier presentation when stroke symptoms occur. ... 

Adams HP, Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE, 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993 24 35 1. 

Sherman DG, Atkinson RR Chippendale T, Levin KA, Ng K, Futrell N, Hsu CY, Levy DE. Intravenous ancrod fortreatment of acute ischemic stroke The STAT study A randomized controlled trial. Stroke Treatment with Ancrod Trial. JAMA. 2000 283 2395-2403. 

Reed SD, Cramer SC, Blough DK, Meyer K, Jarvik JG. Treatment with tissue plasminogen activator and inpatient mortality rates for patients with ischemic stroke treated in community hospitals. Stroke. 2001 32 1832-1840. 

OR 1.81, 95% Cl 1.46-2.24), most of which were related to symptomatic intracranial hemorrhage (OR 3.37, 95% Cl 2.68. 22). In addition, a pooled analysis of six major randomized placebo-controlled IV rt-PA stroke trials (Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) I and II, European Cooperative Acute Stroke Study (ECASS) I and II, and NINDS I and II), including 2775 patients who were treated with IV rt-PA or placebo within 360 minutes of stroke onset, confirmed the beneht up to 3 hours and suggested a potential beneht beyond 3 hours for some patients. The pattern of a decreasing chance of a favorable 3-month outcome as the time interval from stroke onset to start of treatment increased was consistent with the findings of the original NINDS study. ... 

Acute ischemic stroke s3miptoms with onset or last known well, clearly defined. Treatment within 6 h of established, nonfluctuating deficits due to Anterior Circulation (carotid/MCA) stroke, between 6 and 8 h mechanical treatment (e.g.. Concentric Retriever) should be considered. The window of opportunity for treatment is less well defined in posterior circulation (vertebral/basilar) ischemia, and patients may have fluctuating, reversible ischemic symptoms over many hours or even days and stiU be appropriate candidates for therapy. 

No direct comparison trials have been reported between the different thrombolytic agents in acute ischemic stroke. In a retrospective review of the results for acute stroke lAT performed at our center, we have found significantly higher rates of recanalization and good clinical outcome in the era in which lA UK was used versus the era in which UK was not available and lAT with rt-PA was the primary treatment. Conversely, in another retrospective study, Eckert et al. found no major difference between the recanalization rates of UK and rt-PA. 

Hacke W. The results of the joint analysis of two phase II trials on desmoteplase in acute ischemic stroke with treatment 3 to 9 hours after stroke onset. 14th European Stroke Conference. Bologna, Italy, May 2005. 

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