Treatment of Ischemic Stroke

Race—African-American Genetic Modifiable Hypertension Diabetes Smoking Atrial fibrillation Coronary artery disease Prior stroke 

Prior transient ischemic attack Metabolic syndrome Illicit drug use 

Post-menopausal hormone replacement therapy Periodontal disease 

Elevated lipoprotein associated phosphohpase Aj Elevated IL-6 (precursor of CRP) 

Elevated hpoprotem associated phospholipase A Elevated IL-6 (precmsor of CRP) 

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A major goal in the long-term treatment of ischemic stroke involves the prevention of a recurrent stroke through the reduction and modification of risk factors. 

Assessment of risk factors for ischemic stroke as well as for hemorrhagic stroke is an important component of the diagnosis and treatment of patients. A major goal in the long-term treatment of ischemic stroke involves the prevention of a recurrent stroke through the reduction and modification of risk factors. The major focus of primary prevention (prevention of the first stroke) is also reduction and modification of risk factors. Risk factors for ischemic stroke can be divided into modifiable and non-modifiable factors. Every patient should have risk factors assessed and treated, if possible, as management of risk factors can decrease the occurrence and/or recurrence of stroke.4... 

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. 

The effectiveness of intravenous (IV) tPA in the treatment of ischemic stroke was demonstrated in the National Institutes of Neurologic Disorders and Stroke (NINDS) rt-PA Stroke Trial, published in 1995. ... 

Hirsch J, Yoo AJ, Nogueira RG, Verduzco LA, Schwamm LH, Pryor JC, Rabinov JD, Gonzalez RG (2009) Case volumes of intra-arterial and intravenous treatment of ischemic stroke in the U.S. J Neurointerv Surg 1 27-31... 

Liebig T, Reinartz J, Guethe T et al. Early clinical experiences with a new thrombectomy device for the treatment of ischemic stroke. Stroke. 2008 39 608... 

Recanalization remains the most important step in the treatment of ischemic stroke. In fact, without recanalization further treatment is very limited. However, recanalization alone does not restore all the function especially when ischemia has been allowed to last for several hours. Restoration of normal CBF to an ischemic brain region is beneficial only within the first 3-6 h. In very rare situations and mostly in the brain stem ischemias, recanaUzation procedures are undertaken beyond the 6-h limit. Recanalization into a severely ischanic tissue generates a cascade of untoward processes. Reperfusion injury leads to further deterioration of tissue that is already compromised. In general, shorter and less severe ischemia leads to fewer reperfusion injury consequences. In clinical practice the most significant and most visible complication of reperfusion into a severely injured brain parenchyma is hanonhage. It is mostly the increased risk of hemorrhagic transformation that limits the administration of thrombolytic therapy beyond 3 h. The key to success in thrombolysis remains a shorter duration of ischemia. 

In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

Reperfusion of Stroke Safety Study Imaging Evaluation-2 Adjunctive Treatment to Standard Alteplase Therapy of Ischemic Stroke. Presented at the 29th International Stroke Conference Fehmary 2004. 

Alteplase (rt-PA Activase) is an IV thrombolytic (fibrinolytic) that was approved for acute stroke treatment in 1996 based on the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial.10 The current American Stroke Association guidelines include alteplase as the only Food and Drug Administration (FDA) approved acute treatment for ischemic stroke and strongly encourage early diagnosis and treatment of appropriate patients.11... 

Although MRI is promising in that it provides specific information which could improve treatment in ischemic stroke, there is no scientific proof that it actually does improve patients clinical outcome. Consequently, based on current knowledge, the recommendation to base acute stroke management solely on MRI means a big investment without a guaranteed return in the form of reduced health care costs. 

Therapeutic uses Currently alteplase is approved for the treatment of myocardial infarction, massive pulmonary embolism, and acute ischemic stroke. Alteplase seems to be superior to streptokinase and urokinase in dissolving older clots, and may ultimately be approved for other applications. Alteplase administered within 3 hours of the onset of ischemic stroke significantly improves clinical outcome, that is, the patients ability to perform activites of daily living. 

So far predictive models only apply to a small proportion of patients and are not sufficiently accurate to inform treatment decisions in routine clinical practice. The various subtypes of ischemic stroke have very different outcomes patients with total anterior circulation infarction (TACI) have just as poor an outcome as those with primary intracerebral hemorrhage (Table 16.1). The best single predictor of early death is impaired consciousness, but many other predictors of survival have been identified (Table 16.2). Many of these variables are inter-related, but prognostic models based on independent variables do not provide much more information than an experienced clinician s estimate (Counsell and Dennis 2001 Counsell et al. 2002). 

There is no clear evidence that any particular dose of aspirin is more effective than others. However, the symptoms of aspirin toxicity, such as dyspepsia and constipation, are dose related, so the smallest effective dose should be used. A starting dosage of 150-300 mg per day is advised for the acute phase of ischemic stroke followed by longterm treatment with 75-150 mg per day. Patients intolerant of aspirin should be treated with clopidogrel if available, or if not with dipyridamole. These newer agents cost significantly more than aspirin. The use of combination antiplatelet therapy is discussed further in Ch. 24. 

Fig. 27.6. A model derived from the data from the Furopean Carotid Surgery Trial (ESCT) for the five-year risk of ipsilateral risk of ischemic stroke on medical treatment tested on data from the North American Symptomatic Carotid Endartereaomy Trial (NASCET). The closed squares show the risk of stroke in the medical treatment group in NASCET, stratified into quintiles on the basis of predicted risk. The open diamonds show the operative risk of stroke and death in the surgical group in NASCET stratified by their predicted medical risk.

Simard JM, Yurovsky V, Tsymbalyuk N, Melnichenko L, Ivanova S, Gerzanich V (2009a) Protective effect of delayed treatment with low-dose gjibenclamide in three models of ischemic stroke. Stroke 40 604-609... 

In the absence of effective neuroprotective treatment for ischemic stroke, a double-blind, randomized, placebo-controUed trial has been performed in 454 patients in primary care (1). Nimodipine 30 mg/day or placebo was started within 6 hours after the onset of the stroke and continued for 10 days. Nimodipine had no effect on all-cause mortality or dependency in daily life. In patients with ischemic stroke documented by CT scan, nimodipine had a borderline significant adverse effect on outcome. Nimodipine was tolerated as well as placebo (7 versus 8 treatment withdrawals respectively), but the lack of benefit does not support the use of any voltage-sensitive calcium channel blocker in ischemic stroke. 

The underlying cause of this benefit differential from CEA between men and women, aside from the higher perioperative risk in women, is probably the more favorable natural history of asymptomatic CAS in women who are treated conservatively (27). The lower rate of ischemic stroke in women versus men with asymptomatic CAS was also apparent in the medical treatment arms of both the ACAS and ACST trials. The 5-year risk of ipsilateral ischemic stroke was lower for women than men in ACAS (8.7% versus 12.1%) (5) and ACST (7.5% versus 10.6%) (6). 

The concept of the ischemic penumbra has proven to be an extremely valuable construct for both experimental studies of ischemic stroke and for the development of tools for the management of patients with this disorder. Indeed, a major driver in the development of treatments for ischemic stroke is the belief that in many acute stroke patients, there is a region of salvageable brain that is threatened with permanent injury. This region of brain corresponds to the ischemic penumbra originally described in experimental stroke studies. The clinical condition does not strictly meet the criteria as originally defined by experimentalists. Nonetheless, the concept is clinically valuable, and a suitable modification of its definition applicable to the clinical condition is appropriate. 

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