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Vagus nerve stimulation (VNS) is a neuromodulation therapy increasingly used for treating drug-resistant epilepsy. However, it remains to be determined which patients are best suited for the treatment, and it is difficult to predict the therapeutic effect before the implantation. Mutations in some genes could lead to epilepsy. Here we report two cases of pediatric patients with drug-resistant epilepsy treated by VNS therapy: Patient 1 with ARX mutation achieved good outcomes; Patient 2 with the CDKL5 mutation did not show improvement. Additionally, the therapeutic impact of VNS on brain networks was investigated, hoping to provide some empirical evidence for a better understanding of the mechanism of VNS treatment.


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Vagus nerve stimulation for pediatric patients with drug-resistant epilepsy caused by genetic mutations: Two cases

Show Author's information Xiaoya Qin1,2,§Sufang Lin3,4,§Yuan Yuan1,2Jialun Wen3,4Qian Chen5Xingguo Lu3,4Yang Sun4,5Fangping Wang3Xiaoqin Tian3Ning Jiang3Jianxiang Liao3,4( )Luming Li1,2,6,7( )
Precision Medicine & Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518071, China
National Engineering Laboratory for Neuromodulation, School of Aerospace Engineering, Tsinghua University, Beijing 100084, China
Department of Neurology, Shenzhen Children's Hospital, Shenzhen 518038, Guangdong, China
Epilepsy Center, Shenzhen Children's Hospital, Shenzhen 518038, Guangdong, China
Department of Neurosurgery, Shenzhen Children's Hospital, Shenzhen 518038, Guangdong, China
IDG/McGovern Institute for Brain Research at Tsinghua University, Beijing 100084, China
Institute of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100093, China

§ These authors contributed equally to this work.

Abstract

Vagus nerve stimulation (VNS) is a neuromodulation therapy increasingly used for treating drug-resistant epilepsy. However, it remains to be determined which patients are best suited for the treatment, and it is difficult to predict the therapeutic effect before the implantation. Mutations in some genes could lead to epilepsy. Here we report two cases of pediatric patients with drug-resistant epilepsy treated by VNS therapy: Patient 1 with ARX mutation achieved good outcomes; Patient 2 with the CDKL5 mutation did not show improvement. Additionally, the therapeutic impact of VNS on brain networks was investigated, hoping to provide some empirical evidence for a better understanding of the mechanism of VNS treatment.

Keywords: vagus nerve stimulation, drug-resistant epilepsy, genetic mutation, EEG brain network

References(22)

[1]
M Brázdil, I Doležalová, E Koritáková, et al. EEG reactivity predicts individual efficacy of vagal nerve stimulation in intractable epileptics. Front Neurol. 2019, 10: 392.
[2]
R Nabbout, C Depienne, M de Chipaux, et al. CDKL5 and ARX mutations are not responsible for early onset severe myoclonic epilepsy in infancy. Epilepsy Res. 2009, 87(1): 25-30.
[3]
TY Ji, Z Yang, QZ Liu, et al. Vagus nerve stimulation for pediatric patients with intractable epilepsy between 3 and 6 years of age: study protocol for a double-blind, randomized control trial. Trials. 2019, 20(1): 44.
[4]
A Delorme, S Makeig. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods. 2004, 134(1): 9-21.
[5]
L Dong, FL Li, Q Liu, et al. MATLAB toolboxes for reference electrode standardization technique (REST) of scalp EEG. Front Neurosci. 2017, 11: 601.
[6]
D Yao. A method to standardize a reference of scalp EEG recordings to a point at infinity. Physiol Meas. 2001, 22(4): 693-711.
[7]
SP Fulton, K Van Poppel, AL McGregor, et al. Vagus nerve stimulation in intractable epilepsy associated with SCN1A gene abnormalities. J Child Neurol. 2017, 32(5): 494-498.
[8]
S Baba, Y Sugawara, K Moriyama, et al. Amelioration of intractable epilepsy by adjunct vagus nerve stimulation therapy in a girl with a CDKL5 mutation. Brain Dev. 2017, 39(4): 341-344.
[9]
N Zamponi, C Passamonti, S Cappanera, et al. Clinical course of young patients with Dravet syndrome after vagal nerve stimulation. Eur J Paediatr Neurol. 2011, 15(1): 8-14.
[10]
DJ Englot, EF Chang, KI Auguste. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg. 2011, 115(6): 1248-1255.
[11]
Z Lim, K Wong, J Downs, et al. Vagus nerve stimulation for the treatment of refractory epilepsy in the CDKL5 Deficiency Disorder. Epilepsy Res. 2018, 146: 36-40.
[12]
I Orosz, D McCormick, N Zamponi, et al. Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children. Epilepsia. 2014, 55(10): 1576-1584.
[13]
E Bettella, G di Rosa, R Polli, et al. Early-onset epileptic encephalopathy in a girl carrying a truncating mutation of the ARX gene: rethinking the ARX phenotype in females. Clin Genet. 2013, 84(1): 82-85.
[14]
J Gécz, D Cloosterman, M Partington. ARX: a gene for all seasons. Curr Opin Genet Dev. 2006, 16(3): 308-316.
[15]
G Friocourt, K Poirier, S Rakić, et al. The role of ARX in cortical development. Eur J Neurosci. 2006, 23(4): 869-876.
[16]
F Marrosu, F Santoni, M Puligheddu, et al. Increase in 20-50 Hz (Gamma frequencies) power spectrum and synchronization after chronic vagal nerve stimulation. Clin Neurophysiol. 2005, 116(9): 2026-2036.
[17]
T Uchida, K Fujiwara, T Inoue, et al. Analysis of VNS effect on EEG connectivity with granger causality and graph theory. In 2018 Asia-Pacific Signal and Information Processing Association Annual Summit and Conference (APSIPA ASC), Honolulu, USA, 2018, pp 861-864.
DOI
[18]
M Fraschini, M Puligheddu, M Demuru, et al. VNS induced desynchronization in Gamma bands correlates with positive clinical outcome in temporal lobe pharmacoresistant epilepsy. Neurosci Lett. 2013, 536: 14-18.
[19]
M Fraschini, M Demuru, M Puligheddu, et al. The re-organization of functional brain networks in pharmaco-resistant epileptic patients who respond to VNS. Neurosci Lett. 2014, 580: 153-157.
[20]
F Bartolomei, F Bonini, E Vidal, et al. How does vagal nerve stimulation (VNS) change EEG brain functional connectivity? Epilepsy Res. 2016, 126: 141-146.
[21]
A Ilyas, E Toth, D Pizarro, et al. Modulation of neural oscillations by vagus nerve stimulation in posttraumatic multifocal epilepsy: case report. J Neurosurg. 2019, 131(4): 1079-1085.
[22]
ZJ Wang, ES Kim, BH Noh, et al. Alteration in brain connectivity in patients with Dravet syndrome after vagus nerve stimulation (VNS): exploration of its effectiveness using graph theory analysis with electroencephalography. J Neural Eng. 2020, 17(3): 036014.
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Publication history

Received: 15 May 2020
Revised: 05 July 2020
Accepted: 23 July 2020
Published: 19 October 2020
Issue date: September 2020

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© The authors 2020

Acknowledgements

We would like to thank the entire team of researchers for their rigorous attitudes, professional skills, enthusiasm for the patients and great efforts, including the nurses and staff at Shenzhen Children’s Hospital, Shenzhen, China.

This work was supported by the International Cooperation Project in Shenzhen (GJHZ 20180930110402104); Sanming Project of Medicine in Shenzhen (SZSM201812005).

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This article is published with open access at http://jnr.tsinghuajournals.com

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