Abstracts

Several studies carried out in epileptic patients treated with common AEDs suggest that the drugs could cause BAEPs alterations. Although, only in a couple of case report studies hearing deficits have been directly linked to the antiepileptic medication. BAEPs are far field-evoked potentials that consist of several waves that occur within 10 ms post-stimulus. Determination of BAEPs threshold is an objective measure of the hearing sensitivity. In the guinea pig, changes in the amplitude or the latency of P1, the first wave of BAEPs, reflects cochlear nerve alterations, whereas changes in the parameters of P3 and P4, express alterations in the activity of the medial and the lateral superior olivary nuclei of the brainstem, respectively. Previously we have shown that the BAEPs alterations and the hearing decline induced by amikacin and by the convulsing agents, pentylenetetrazole and 4-aminopyridine in the guinea pig [italic]in vivo[/italic] are prevented by VPC (ethyl apovincamine-22-oate), a nootropic drug with anticonvulsant capabilities. Since the few studies directed to investigate the effects of CBZ, PHT and VPA on BAEP parameters in animals, have only tested their acute effects at extremely high doses, their chronic effects at relevant doses on BAEP parameters and threshold were investigated here in the guinea pig in vivo, and compared with the effects of VPC in parallel., The latency and amplitude of each BAEP wave elicited by a stimulus of high intensity (100 dB) and the auditory thresholds at two tone frequencies (8 and 4 kHz) before the start of treatment (control recordings), 2 hours after the start of treatment (i.e. first injection of 20 mg/kg CBZ, 6 mg/kg PHT, 30 mg/kg VPA or 2 mg/kg VPC), and 28 days after a daily injection of the above drugs at the indicated doses, were measured following the methods described previously [italic](Epilepsy Res.[/italic] 2004; 60: 63-71 ; [italic]Clin. Neurophysiol[/italic]. 2004; 115: 2711-17)., P1 and P2 parameters are unchanged by the drugs tested either after the start of treatment or following 28 days of injection. Also, P3 and P4 are unchanged after the start of treatment. However, marked changes are observed after the long term (28 days) treatments; CBZ and PHT increase and VPC reduces P3 and P4 latencies, PHT reduces P3 amplitude, and CBZ and PHT reduce P4 amplitude.
Following the 28 days of CBZ, PHT or VPA injection the BAEP thresholds increase, whereas they decrease following the 28 days of VPC injection., The long term treatment with the most commonly used AEDs at therapeutic relevant doses could reduce the hearing sensitivity through physiological changes in specific nuclei of the superior olivary complex. The long term treatment with VPC, in contrast, ameliorates audition., (Supported by: This work was financially supported by Psicofarma S.A. de C.V. and by project P-48695 from SEP-CONACYT.)