Does Valproic Acid/Na Valproate Suppress Auditory Startle Reflex in Patients With Epilepsy?

BACKGROUND AND OBJECTIVE: Auditory startle response (ASR) was normal in juvenile myoclonic epilepsy whereas it was suppressed in progressive myoclonic epilepsy. However, both groups were using valproic acid/Na valproate (VPA) in different doses. Therefore, we aimed to analyze whether VPA has an impact on ASR in a cohort of epilepsy. For this purpose, we included patients with epilepsy and analyzed ASR in patients who were using VPA. PATIENTS AND METHOD: We included 51 consecutive patients who had epilepsy and were using VPA between January 2014 and January 2016. Two control groups of 37 epilepsy patients using other antiepileptic drugs (AEDs) and of 25 healthy subjects were also constituted. All participants underwent investigations of ASR and startle response to somatosensory inputs (SSS) under similar conditions. RESULTS: An analysis of patients using VPA, not using VPA and healthy subjects revealed significantly longer latency and lower probability of orbicularis oculi (O.oc) and sternocleidomastoid responses after auditory stimulation, decreased total ASR probability and longer latency of O.oc response after somatosensory stimulation in patient groups compared with healthy subjects. Multivariate analysis showed type of AED had a role in the generation of abnormalities. VPA, carbamazepine, and multiple AED use caused suppression of ASR. Total ASR probability was decreased or O.oc latency got longer with longer duration of VPA use whereas serum VPA level at the time of investigation did not correlate with total ASR probability. DISCUSSION: Both ASR and SSS are suppressed by the effect of VPA, especially in patients using for a long period and in patients using other AEDs with VPA. Given the fact that VPA leads to long-standing synaptic changes of dopaminergic transmission, abnormalities of this network may be the more likely cause.

Startle Response in Progressive Myoclonic Epilepsy.

Cortical reflex myoclonus is a typical feature of progressive myoclonic epilepsy (PME) in which it is accompanied by other types of mostly drug-resistant seizures and progressive neurological signs. Although PME is characterized by cortical hyperexcitability, studies have demonstrated atrophy and degenerative changes in the brainstem in various types of PME. Thus, we have questioned whether any stimuli may trigger a hyperactive response of brainstem reticular formation in PME and investigated the startle reflex in individuals with PME. We recorded the auditory startle response (ASR) and the startle response to somatosensory inputs (SSS) in patients with PME, and compared the results with healthy volunteers and patients with other types of drug-resistant epilepsy. All patients were using antiepileptic drugs (AEDs), 12 were on multiple AEDs. The probability of ASR was significantly lower and mean onset latency was longer in patients with PME compared with other groups. SSS responses over all muscles were low in both the PME and drug-resistant epilepsy groups; however, the differences were not statistically significant. The presence of a response over the biceps brachii muscle was zero in the PME group and showed a borderline difference compared with the other groups. Decreased probability and prolonged latencies of ASR in PME indicate inhibition of reflex circuit. A trend for decreased responses of SSS suggests hypoactive SSS in both PME and other epilepsy groups. Hypoactive ASR in PME and hypoactive SSS in both PME and other epilepsies may be attributed to the degeneration of pontine reticular nuclei in PME and functional inhibition by AEDs in both disorders.