INTRAARTERIAL THROMBOLYSIS FOR ACUTE ISCHEMIC STROKE

ABSTRACT

Stroke affects more than 700,000 people each year in the United States and is the third leading cause of death behind heart disease and cancer. It is the leading cause of health care dollar expenditure and the most common cause of disability resulting in rehabilitation and nursing home admissions.[1] Despite a decline in stroke mortality in some countries,[1] there is little evidence for a decline in incidence.[2] Due to anticipated demographic changes from an aging population, the incidence of stroke is expected to increase, causing an even greater need to find effective treatments.[3]

Stroke is a clinical event defined as an acute onset of neurologic deficit in which maximal dysfunction is reached rapidly and in which delayed neurologic deterioration does not occur unless additional complications arise. Cerebrovascular occlusion due to embolus or thrombosis accounts for 75% of strokes.[4] The vascular occlusion causes tissue oligemia with ischemia resulting in neuronal dysfunction and clinical stroke.

Twenty percent of patients with thromboembolic stroke die in the first month after the event.[5] Outcome for survivors can be devastating. About two-thirds have decreased vocational and social function, half have peripheral motor weakness, one-third have marked inability to perform activities of daily living, and one-sixth require institutional care.[6] Patients with proven occlusions of the main trunk of the middle cerebral artery have initial mortality rates as high as 25 to 40%.[7] [8] [9] Patients with less severe middle cerebral artery (MCA) branch occlusions have been shown to have 3-month mortality as high as 14.3%.[10] Even more devastating, basilar occlusions are generally thought to have an 80-90% mortality rate without treatment.

Prior to the United States (U.S.) Food and Drug Administation's (FDA) approval of intravenous tissue plasminogen activator (tPA) for acute stroke in 1995, no approved direct therapeutic intervention was available for acute stroke in the U.S. Care was predominately supportive, with a prevailing attitude among health care providers that the damage was completed. Indirect strategies to treat thromboembolic stroke targeted the management of potential complications and attempted to reverse or stabilize neurologic impairment. Management of concurrent medical conditions was undertaken in an attempt to minimize brain injury. Anticoagulation agents were used to reverse or prevent progression of thrombus formation. Neuroprotective agents have been postulated to protect viable neurons from ongoing damage by toxic metabolites formed by ischemia. Although these approaches have begun to unravel the complexities of treating acute stroke by managing various aspects of stroke evolution, none has proven particularly effective and none have directly approached the inciting vascular occlusion.

The development of and experience with thrombolytic agents has recently created great interest in directing stroke therapy at the site of thromboembolic vascular occlusion. Success of peripherally administered intravenous thrombolytic trials have culminated in the FDA approval of recombinant-tPA as the first effective treatment of stroke.[11] Concurrently, advances in catheter technology for endovascular navigation have enabled direct access to the site of cerebrovascular occlusion and have the potential to provide the next step for effective treatment of thromboembolic stroke. Intra-arterial delivery of thrombolytic agents has been used for several years for acute ischemic stroke with some initial success, and has become the standard for selected patients at many institutions. Our purpose is to examine newer clinical and technical aspects of this promising neurointerventional treatment, to review past experience with intra-arterial thrombolysis, and to discuss current treatment protocols and future developments.

KEYWORD

Brain ischemia - thrombolytic therapy - fibrinolytic agents

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