Neuroprotection in post-stroke epilepsy: A realistic goal?

I read with great interest the study by van Tuijl et al. aimed to investigate the anti-epileptogenic effect of levetiracetam in stroke patients in order to prevent poststroke seizures and epilepsy. However, due to several problems encountered during execution of this trial, the authors concluded that this trial seems not feasible. On the basis of the similarity of the cascade of synaptic and intracellular events exhibited by epilepsy and brain ischemia, antiepileptic drugs (AEDs) have been tested as possible neuroprotective agents in animal models of stroke. Among the AEDs, levetiracetam may have a crucial role in the regulation of epileptogenesis and neuroprotection and some particular mechanisms of action of levetiracetam might be involved in neuroprotection after brain ischemia. There are different pathophysiological processes underlying early and late seizures after stroke, with a predominance of acute cellular biochemical disturbances in early seizures and epileptogenic gliotic scarring in late seizures. Interestingly, literature data support the view that patients with epilepsy exhibit an increased risk for stroke but the effect of late onset poststroke seizures on recurrent brain ischemia has not been investigated. Experimental observations have demonstrated that levetiracetam has a direct ability to protect against the neurotoxicity induced by several chemical compounds and levetiracetam’s neuroprotective properties have been investigated in the rat middle cerebral artery occlusion model (i.e. a condition of focal cerebral ischemia). Although the need for clinical studies to investigate the benefits of prophylactic treatment to prevent poststroke epilepsy is clear, the study by van Tuijl et al. concluded that the problems encountered during this prophylactic trial seem unavoidable. For these reasons, the conclusions of the work by van Tuijl et al. could suggest the need for a different clinical study aimed no to