Impaired Intracortical Inhibition in EPM1 and Association with Genotype
Abstract number :
2.037
Submission category :
3. Neurophysiology / 3E. Brain Stimulation
Year :
2022
Submission ID :
2204631
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Katri Silvennoinen, MD – Neurocenter, Kuopio University Hospital; Laura Säisänen, PhD – Department of Clinical Neurophysiology, Kuopio Epilepsy Center – Kuopio University Hospital; Jelena Hyppönen, MD,PhD – Department of Clinical Neurophysiology, Kuopio Epilepsy Center – Kuopio University Hospital; Saara Rissanen, PhD – Department of Applied Physics – University of Eastern Finland; Pasi Karjalainen, PhD – Department of Applied Physics – University of Eastern Finland; Sasha D’Ambrosio, PhD – Department of Clinical and Experimental Epilepsy – UCL Queen Square Institute of Neurology; Diego Jimenez-Jimenez, MD,PhD – Department of Clinical and Experimental Epilepsy – UCL Queen Square Institute of Neurology; Sara Zagaglia, MD – Department of Clinical and Experimental Epilepsy – UCL Queen Square Institute of Neurology; Simona Balestrini, MD,PhD – Department of Clinical and Experimental Epilepsy – UCL Queen Square Institute of Neurology; Sanjay Sisodiya, FRCP,PhD – Department of Clinical and Experimental Epilepsy – UCL Queen Square Institute of Neurology; Petro Julkunen, PhD – Department of Clinical Neurophysiology, Kuopio Epilepsy Center – Kuopio University Hospital, Kuopio; Esa Mervaala, MD,PhD – Department of Clinical Neurophysiology, Kuopio Epilepsy Center – Kuopio University Hospital; Reetta Kälviäinen, MD, PhD – Kuopio Epilepsy Center, Neurocenter – Kuopio University Hospital
Rationale: Progressive myoclonic epilepsy type 1 (EPM1) is caused by biallelic alterations in the CSTB gene. Disease mechanisms and underpinnings of interindividual phenotypic variability are poorly understood. Pathological changes in EPM1 include impaired GABAergic inhibition (Neurobiol Dis. 2012;47:216-224). Transcranial magnetic stimulation (TMS)-induced short-interval intracortical inhibition (SICI), a measure of GABAAergic inhibition (Clin Neurophysiol. 2015;126:1847-1868), was shown to be reduced in individuals with EPM1, whilst long-interval intracortical inhibition was preserved (Epilepsy Res. 2010;89:232-237). We explored the association between these measures and clinical and genetic features in a group of patients with EPM1.
Methods: TMS combined with EMG was performed under neuronavigation. LICI with inter-stimulus interval (ISI) of 100ms, and SICI with ISIs 2 and 3ms and their mean (mSICI) were expressed as the ratio of conditioned to unconditioned stimulus. LICI and mSICI and their average (combined ICI, cICI) were compared between patients and controls. A receiver operator characteristic (ROC) analysis was performed to assess the ability of cICI to differentiate between patients and controls. Non-parametric correlation was used to study the association between cICI and parameters of clinical severity, including Unified Myoclonus Rating Scale (UMRS) and disease duration. Among patients with EPM1 due to biallelic expansion repeats, the association between cICI and the number of repeats in the more affected allele (greater repeat number, GRN) was assessed.
Results: The study protocol was completed in 19 patients (15 with biallelic expansion repeats and 4 compound heterozygotes), and 7 healthy control participants. Compared to controls, patients demonstrated significantly less SICI (median mSICI, 1.18 vs. 0.38; p< 0.001). Whilst on group level, no statistically significant difference in LICI was seen between patients and controls, LICI was clearly impaired in some patients. cICI was robust in differentiating between patients and controls (Figure 1). cICI was not associated with parameters of clinical severity. In those with biallelic repeat expansions, GRN significantly correlated with cICI (Figure 2).
Neurophysiology