RECENTLY DEVELOPED NEUROPROTECTIVE THERAPIES FOR ACUTE STROKE - A QUALITATIVE SYSTEMATIC REVIEW OF CLINICAL-TRIALS

An increased understanding of the pathophysiological consequences of s troke and, in particular, the notion of an ischaemic penumbra in acute cerebral infarction has led to the development of novel neuroprotecti ve treatments. These act at different stages of the pathophysiological cascade that lends to ischaemic neuronal damage. A bewildering number of potentially neuroprotective treatments are currently in preclinica l and clinical development. This article systematically reviews all th e completed and ongoing randomised controlled trials evaluating the ef fect of the mon recently developed neuroprotective agents on clinical outcomes in patients with acute stroke. These agents are focused on be cause more detailed quantitative meta-analyses are available for many of the earlier neuroprotective agents. A simple classification of all the current neuroprotective agents on the basis of common potential me chanisms of action is presented. The agents are classified into 8 majo r groups: modulators of excitatory amino acids, modulators of calcium influx, metabolic activators, antioedema agents, inhibitors of leucocy te adhesion, free radical scavengers, promoters of membrane repair and these with an unknown mechanism of action. The data emerging from cli nical trials of currently available neuroprotective therapies have not provided clear evidence of the benefit of this type of treatment. Fur ther large randomised trials involving patients with both ischaemic an d haemorrhagic stroke are required before the routine use of neuroprot ective therapy in clinical practice can be recommended.