Historically, the treatment of stroke has been viewed with nihilism. With the approval of intravenous tissue plasminogen activator (i.v.-rTPA) (Nat. Inst. Neurol. Disorders, 1995), the past attitudes of helplessness in the face of stroke are changing. Despite the efficacy of thrombolytic therapy, less than 3% of all ischemic stroke patients are actually treated with i.v.-rTPA. The major reason for this lack of treatment appears to be the short time window. Both human and animal studies suggest that the time window for therapy will remain at approximately 3–6 hours even with the development of successful neuroprotection (Fig. 81.1). For this reason, time is a critically important factor in the treatment of acute stroke.
The approach to acute stroke can be separated into five overlapping concepts. The first and, thus far, most successful is restoring flow through the occluded vessel. The second is altering the ischemic cascade. Third is maximizing collateral flow. Fourth is the prevention of complications and the final concept is the use of a multidisciplinary team and designated Stroke Units to maximize patient care. Recovery and its augmentation is a sixth concept that is beyond the scope of this chapter.
Restoration of flow
The normal perfusion to brain grey matter is 60–70 ml for every 100 grams of brain tissue every minute. When perfusion decreases to less than 25 ml/100 mg/min, the neuron is no longer able to maintain aerobic respiration. If perfusion is not restored, the ischemic tissue will reach a point of no return where cell death is inevitable. This process is very time dependent, with irreversibility occurring after 5–6 hours. However, if flow is restored, then the brain tissue can potentially be spared and neurological function preserved (Figs. 81.2 and 81.3) (Jones et al., 1981). This concept has led to the use of pharmacological and mechanical attempts to disrupt the occluding thrombus. To date, this remains the most efficacious treatment of acute stroke and represents the only Food and Drug Administration approved therapy.
There have been multiple recent trials of intravenous thrombolytics in the setting of acute ischemic stroke. Streptokinase was examined in three major trials enrolling 1192 patients (MAST-I, 1995; Donnan et al., 1996; Multicenter Acute Stroke Trial, 1996).