Can the Long-Term Outcome after Status Epilepticus be Modified?
Authors: Sankar Raman 
Published: December 2022

Phenobarbital and MK-801, but Not Phenytoin, Improve the Long-Term Outcome of Status Epilepticus

Prasad A, Williamson JM, Bertram EH

Ann Neurol 2002;51:175–181

To examine the effect of therapy on status epilepticus (SE) acutely and on long-term outcome, we compared three drugs with three different mechanisms. Phenobarbital, MK-801, and phenytoin were administered at 1, 2, and 4 hours after initiation of limbic status epilepticus by “continuous” hippocampal stimulation in rats. We evaluated the effects of these drugs on the course of SE and the subsequent development of chronic epilepsy. Phenobarbital and MK-801 were superior to phenytoin in suppressing SE and in preventing chronic epilepsy. There was no benefit if treatment was given 2 hours after the initiation of SE. Phenobarbital was most effective in suppressing electrographic seizure activity, but MK-801 had a slightly wider window for the prevention of chronic epilepsy. Early treatment, rather than electrographic suppression of SE, correlated with prevention of chronic epilepsy. This study shows that the drugs administered, which have different mechanisms of action, have clear differences in altering the outcomes. The findings suggest that studies of SE treatment should examine the effect of therapy on SE itself, as well as the long-term benefits of each treatment. The use of N-methyl-D-aspartate receptor antagonists should be considered early in the treatment of SE.

Seizure-Induced Memory Impairment is Reduced by Choline Supplementation Before or After Status Epilepticus

Holmes GL, Yang Y, Liu Z, Cermak JM, Sarkisian MR, Stafstrom CE, Neill JC, Blusztajn JK

Epilepsy Res 2002;48:3–13

Prenatal choline supplementation can protect rats against cognitive deficits induced by status epilepticus induced by the cholinergic agent pilocarpine [J. Neurosci. 20 (2000) 1]. In the present day, we have extended this novel finding by investigating the effects of pre- and postnatal choline supplementation in memory deficits associated with status epilepticus induced with kainic acid (KA). In the first experiment pregnant rats received a normal, choline-supplemented, or choline deficient diet starting on the 11th day of gestation and continuing until postnatal (P) 7. At P42, rats were given a convulsant dosage of KA. Two weeks following the KA-induced status epilepticus rats underwent testing of visual-spatial memory using the Morris water maze test. Rats receiving supplemental choline performed better in the water maze than the deficient and control groups. Moreover, the activity of hippocampal choline acetyltransferase was 18% lower in the choline deficient animals as compared with the other two groups. In the second experiment we administered KA to P35 rats that had been given a normal diet. Following the status epilepticus the rats were given a choline-supplemented or control diet for 4 weeks and then tested in the water maze. Rats receiving choline supplementation performed far better than rats receiving a regular diet. This study demonstrates that choline supplementation prior to or following KA-induced status epilepticus can protect rats from memory deficits induced by status epilepticus.