Neurodevelopmental effects of antiepileptic drugs

Abstract

Although the vast majority of children born to women with epilepsy are normal, these children are at increased risk for both anatomic and cognitive impairments. Current evidence suggests that the defects are the result of in utero antiepileptic drug (AED) exposure combined with a genetic predispositon. However, the exact mechanisms underlying these effects remain to be delineated. AED polytherapy increases the risk, but it remains uncertain if specific AEDs pose an overall greater threat. Most women with epilepsy cannot avoid AEDs during pregnancy because of the greater risks posed by seizures to the mother and fetus. Therefore, current recommendations emphasize definitive diagnosis and the use of AED monotherapy at the lowest effective dose if treatment is indicated. Prenatal folate and multivitamins should also be given routinely to women of childbearing age who require AED therapy.

Attention impairment in temporal lobe epilepsy: A neurophysiological approach via analysis of the P300 wave

“…Antiepileptic drugs (AEDs) can be responsible for cognitive impairment, due to their negative influence on attention, vigilance, and information processing speed [Meador, 2002]. Triantafyllou [1992] showed that AEDs increased the P300 latency and that the effect was greater with multiple drug therapy.…”

“…This argues against the predominant involvement of mesiotemporal structures in P300 generation but does not exclude the combined involvement of mesiotemporal and neocortical sources [Linden, 2006]. Studies of P300's characteristics in epilepsy have mainly concerned changes in latencies and amplitudes, with increased latencies and a trend toward lower P300 amplitudes in epileptic subjects [Abubakr and Wambacq, 2003;Drake et al, 1986;Fukai et al, 1990;Mccarthy et al, 1987a;Meador, 2002;Naganuma et al, 1991;Puce and Bladin, 1991;Rodin et al, 1989;Triantafyllou et al, 1992;Tuunainen et al, 1995;Verma et al, 1993].…”

Pediatric epilepsy surgery: could age be a predictor of outcomes?

“…Better postoperative development outcomes have been noted in children under 3 years old, 30 and the likely explanations for these findings include greater neural plasticity of the brain at this age. 4,15,16,20,38,39 Furthermore, there is evidence that AEDs have an ominous role in cognitive development, 6,9,24,32 an effect that may add to the deleterious role of persistent seizures. 23 Despite recent publications on specific subpopulations of patients demonstrating that various procedures for refractory epilepsies are safe in very young patients, 7 the invasiveness of the procedure and potential complications of surgical interventions may discourage pediatricians and neuropediatricians from referring their patients for early surgery.…”

In utero antiepileptic drug exposure

“…3 In addition to anatomic defects, in utero AED exposure has been associated with behavioral/cognitive defects. [4][5][6] The risk of AED teratogenesis must be balanced against potentially grave risks posed by seizures to both the mother and the child. Maternal deaths during pregnancy in women with epilepsy are 10 times more common than in women without epilepsy; this increase appears to be due to seizures, which are often related to discontinuing AED therapy or poor compliance.…”