Startle Response in Progressive Myoclonic Epilepsy

Abstract

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.

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

“…Thus, cholinergic nuclei were supposed to be structurally normal. Additionally, the rate of ASR suppression in patients using VPA in our study was milder relative to the patients with PME reported in the previous study 7 who supposedly had lesions of cholinergic nuclei. Overall, VPA does not affect cholinergic signal transmitting and there are suggestions about protective effect of VPA on cholinergic system.…”

“…12 In humans, we previously investigated patients with JME or PME, some of whom were using VPA. 6,7 Indirectly, we did not show any abnormal ASR findings in the former group whereas PME patients had suppressed ASR which was supposedly related to the brainstem involvement or AED use. Similarly, findings in this study supported VPA was related to lower ASR probability and longer latencies.…”

“…[3][4][5] Previously, we found that ASR was normal in juvenile myoclonic epilepsy (JME) 6 ; however, ASR probability was decreased and response latencies were longer in progressive myoclonic epilepsy (PME). 7 In the case of ASR suppression in PME, we hypothesized that the degeneration of pontine reticular nuclei which is seen in PME or functional inhibition by antiepileptic drugs (AEDs), especially by VPA may be responsible.…”

In depth behavioral phenotyping unravels complex motor disturbances in Cstb−/− mouse, a model for progressive myoclonus epilepsy type 1

“… 1 Lehesjoki and Kälviäinen (2020) , 2 Kälviäinen (2015) , 3 Kiziltan et al (2017) , and 4 Julkunen et al (2018) . …”

Long‐term follow‐up of two siblings with adult‐onset neuronal ceroid lipofuscinosis, Kufs type A

“…Here, we aimed to present detailed temporal evolution of clinical findings, drug responses, and electrophysiological features of two siblings with adult-onset NCL (homozygous mutation in the CLN6 gene; CLN6 disease) after a long follow-up by the same clinician. These patients were previously included in a multicentre genetic study (Muona et al, 2015) and in two electrophysiological analysis studies at our centre (Cos ¸kun et al, 2015;Kızıltan et al, 2016), however, their clinical details were not reported in detail.…”