Neurophysiological and Genetic Findings in Patients With Juvenile Myoclonic Epilepsy.

Autor:	Stefani S; Cyprus School of Molecular Medicine, Nicosia, Cyprus.; Neurology Clinic B, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Kousiappa I; Cyprus School of Molecular Medicine, Nicosia, Cyprus.; Neurology Clinic B, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Nicolaou N; Medical School, University of Nicosia, Nicosia, Cyprus.; Centre for Neuroscience and Integrative Brain Research (CENIBRE), University of Nicosia, Nicosia, Cyprus., Papathanasiou ES; Cyprus School of Molecular Medicine, Nicosia, Cyprus.; Neurology Clinic B, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Oulas A; Cyprus School of Molecular Medicine, Nicosia, Cyprus.; Bioinformatics Group, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Fanis P; Cyprus School of Molecular Medicine, Nicosia, Cyprus.; Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Neocleous V; Cyprus School of Molecular Medicine, Nicosia, Cyprus.; Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Phylactou LA; Cyprus School of Molecular Medicine, Nicosia, Cyprus.; Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Spyrou GM; Cyprus School of Molecular Medicine, Nicosia, Cyprus.; Bioinformatics Group, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Papacostas SS; Cyprus School of Molecular Medicine, Nicosia, Cyprus.; Neurology Clinic B, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.; Medical School, University of Nicosia, Nicosia, Cyprus.; Centre for Neuroscience and Integrative Brain Research (CENIBRE), University of Nicosia, Nicosia, Cyprus.
Jazyk:	angličtina
Zdroj:	Frontiers in integrative neuroscience [Front Integr Neurosci] 2020 Aug 20; Vol. 14, pp. 45. Date of Electronic Publication: 2020 Aug 20 (Print Publication: 2020).
DOI:	10.3389/fnint.2020.00045
Abstrakt:	Objective: Transcranial magnetic stimulation (TMS), a non-invasive procedure, stimulates the cortex evaluating the central motor pathways. The response is called motor evoked potential (MEP). Polyphasia results when the response crosses the baseline more than twice (zero crossing). Recent research shows MEP polyphasia in patients with generalized genetic epilepsy (GGE) and their first-degree relatives compared with controls. Juvenile Myoclonic Epilepsy (JME), a GGE type, is not well studied regarding polyphasia. In our study, we assessed polyphasia appearance probability with TMS in JME patients, their healthy first-degree relatives and controls. Two genetic approaches were applied to uncover genetic association with polyphasia. Methods: 20 JME patients, 23 first-degree relatives and 30 controls underwent TMS, obtaining 10-15 MEPs per participant. We evaluated MEP mean number of phases, proportion of MEP trials displaying polyphasia for each subject and variability between groups. Participants underwent whole exome sequencing (WES) via trio-based analysis and two-case scenario. Extensive bioinformatics analysis was applied. Results: We identified increased polyphasia in patients (85%) and relatives (70%) compared to controls (47%) and significantly higher mean number of zero crossings (i.e., occurrence of phases) (patients 1.49, relatives 1.46, controls 1.22; p < 0.05). Trio-based analysis revealed a candidate polymorphism, p.Glu270del,in SYT14 (Synaptotagmin 14) , in JME patients and their relatives presenting polyphasia. Sanger sequencing analysis in remaining participants showed no significant association. In two-case scenario, a machine learning approach was applied in variants identified from odds ratio analysis and risk prediction scores were obtained for polyphasia. The results revealed 61 variants of which none was associated with polyphasia. Risk prediction scores indeed showed lower probability for non-polyphasic subjects on having polyphasia and higher probability for polyphasic subjects on having polyphasia. Conclusion: Polyphasia was present in JME patients and relatives in contrast to controls. Although no known clinical symptoms are linked to polyphasia this neurophysiological phenomenon is likely due to common cerebral electrophysiological abnormality. We did not discover direct association between genetic variants obtained and polyphasia. It is likely these genetic traits alone cannot provoke polyphasia, however, this predisposition combined with disturbed brain-electrical activity and tendency to generate seizures may increase the risk of developing polyphasia, mainly in patients and relatives. (Copyright © 2020 Stefani, Kousiappa, Nicolaou, Papathanasiou, Oulas, Fanis, Neocleous, Phylactou, Spyrou and Papacostas.)
Databáze:	MEDLINE
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