The purpose of this study was to investigate the efficacy of transcutaneous vagus nerve stimulation in pediatric patients with drug-resistant epileptic encephalopathy with spike-and-wave activation in sleep.
Methods
We prospectively investigate seven drug-resistant epileptic encephalopathy with spike-and-wave activation in sleep children who underwent transcutaneous vagus nerve stimulation for 12 weeks. The Chinese Revised Wechsler Intelligence Scale for Children (C-WISC) was used to assess cognitive changes before and after stimulation. Microstate parameters (mean duration, occurrence, and coverage) were obtained by quantifying each patient's electroencephalography (EEG) findings. Correlation analyses were used to assess the association between microstate parameters and cognitive scores. We analyzed the brain dynamics of the patients based on 4 categories of classical microstates using weighted phase lag index to construct a whole brain dynamic network. Finally, the brain network was quantitatively analyzed based on graph theory metrics (including global efficiency, local efficiency, and strength).
Results
A 12-week transcutaneous vagus nerve stimulation resulted in a significant increase in M/CIQ (Memory/Concentration Intelligence Quotient) and in seizure cessation in 57.14% of patients. The mean duration of microstate C was significantly reduced and enlarged the bidirectional predominance of microstate A and B, while weakening the directional predominance of microstates A, B, and D to C. The global efficiency, local efficiency, and strength of the microstate-based functional subnetwork were significantly reduced. And M/CIQ showed a strong correlation with the mean duration.
Significance
This study revealed the efficacy of transcutaneous vagus nerve stimulation in improving the cognitive state of drug-resistant epileptic encephalopathy with spike-and-wave activation in sleep pediatric patients.
SpecchioNWirrellECSchefferIE, et al.International league against epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63:1398–1442. https://doi.org/10.1111/epi.17241
2.
SeegmüllerCDeonnaTDuboisCM, et al.Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep. Epilepsia. 2012;53:1067–1076. https://doi.org/10.1111/j.1528-1167.2012.03465.x
3.
MaYKaminskiMKimA. Surgical treatment of epileptic encephalopathy with spike-and-wave activation in sleep: a systematic review and meta-analysis. Seizure. 2024;119:78–83. https://doi.org/10.1016/j.seizure.2024.05.008
4.
MorrisGL3rdGlossDBuchhalterJMackKJNickelsKHardenC. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;81:1453–1459. https://doi.org/10.1212/WNL.0b013e3182a393d1
5.
NomuraSMizunoN. Central distribution of primary afferent fibers in the Arnold's nerve (the auricular branch of the vagus nerve): a transganglionic HRP study in the cat. Brain Res.1984;292:199–205. https://doi.org/10.1016/0006-8993(84)90756-x
MarrosuFSerraAMaleciAPulighedduMBiggioGPigaM. Correlation between GABA(A) receptor density and vagus nerve stimulation in individuals with drug-resistant partial epilepsy. Epilepsy Res.2003;55:59–70. https://doi.org/10.1016/s0920-1211(03)00107-4
8.
Ben-MenachemEHambergerAHednerT, et al.Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res.1995;20:221–227. https://doi.org/10.1016/0920-1211(94)00083-9
9.
BadranBWBrownJCDowdleLT, et al.Tragus or cymba conchae? Investigating the anatomical foundation of transcutaneous auricular vagus nerve stimulation (TAVNS). Brain Stimul.2018;11:947–948. https://doi.org/10.1016/j.brs.2018.06.003
10.
RongPLiuAZhangJ, et al.Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial. Clin Sci (Lond). Published online April 1, 2014. https://doi.org/10.1042/cs20130518
11.
MertensAGadeyneSLescrauwaetE, et al.The potential of invasive and non-invasive vagus nerve stimulation to improve verbal memory performance in epilepsy patients. Sci Rep.2022;12:1984. https://doi.org/10.1038/s41598-022-05842-3
12.
YapJYYKeatchCLambertEWoodsWStoddartPRKamenevaT. Critical review of transcutaneous vagus nerve stimulation: challenges for translation to clinical practice. Front Neurosci.2020;14:284. https://doi.org/10.3389/fnins.2020.00284
13.
GiraudierMVentura-BortCWeymarM. Transcutaneous vagus nerve stimulation (TVNS) improves high-confidence recognition memory but not emotional word processing. Front Psychol.2020;11:1276. https://doi.org/10.3389/fpsyg.2020.01276
14.
LamprosMVlachosNZigourisA, et al.Transcutaneous vagus nerve stimulation (t-VNS) and epilepsy: a systematic review of the literature. Seizure. 2021;91:40–48. https://doi.org/10.1016/j.seizure.2021.05.017
15.
EnglotDJRolstonJDWrightCW, et al.Rates and predictors of seizure freedom with vagus nerve stimulation for intractable epilepsy. Neurosurgery. 2016;79(3):345–353. https://doi.org/10.1227/NEU.0000000000001165
GaoFJiaHWuXYuDFengY. Altered resting-state EEG microstate parameters and enhanced spatial complexity in male adolescent patients with mild spastic diplegia. Brain Topogr.2017;30:233–244. https://doi.org/10.1007/s10548-016-0520-4
18.
Van de VilleDBritzJMichelCM. EEG microstate sequences in healthy humans at rest reveal scale-free dynamics. Proc Natl Acad Sci U S A.2010;107:18179–18184. https://doi.org/10.1073/pnas.1007841107
ZhangSTangJHuangJ, et al.Whole-brain dynamic resting-state functional network analysis in benign epilepsy with centrotemporal spikes. IEEE J Biomed Health Inform.2022;26:3813–3821. https://doi.org/10.1109/jbhi.2022.3164907
22.
KhannaAPascual-LeoneAMichelCMFarzanF. Microstates in resting-state EEG: current status and future directions. Neurosci Biobehav Rev.2015;49:105–113. https://doi.org/10.1016/j.neubiorev.2014.12.010
DamborskáAPiguetCAubryJM, et al.Altered electroencephalographic resting-state largescale brain network dynamics in euthymic bipolar disorder patients. Front Psychiatry.2019;10:826. https://doi.org/10.3389/fpsyt.2019.00826
25.
CustoAVan De VilleDWellsWM, et al.Electroencephalographic resting-state networks: source localization of microstates. Brain Connect.2017;7(10):671–682. https://doi.org/10.1089/brain.2016.0476
26.
ChuCWangXCaiL, et al.Spatiotemporal EEG microstate analysis in drug-free patients with Parkinson's disease. NeuroImage: Clinical. 2020;25:102132. https://doi.org/10.1016/j.nicl.2019.102132
27.
BréchetLBrunetDBirotG, et al.Capturing the spatiotemporal dynamics of self-generated, task-initiated thoughts with EEG and fMRI. NeuroImage. 2019;194:82–92. https://doi.org/10.1016/j.neuroimage.2019.03.029
28.
TarailisPKoenigTMichelCM, et al.The functional aspects of resting EEG microstates: a systematic review. Brain Topogr.2024;37(2):181–217. https://doi.org/10.1007/s10548-023-00958-9
29.
JongkeesBJImminkMAFinisguerraAColzatoLS. Transcutaneous vagus nerve stimulation (TVNS) enhances response selection during sequential action. Front Psychol.2018;9:1159. https://doi.org/10.3389/fpsyg.2018.01159
30.
TrevizolAPShiozawaPTaiarI, et al.Transcutaneous vagus nerve stimulation (TAVNS) for major depressive disorder: an open label proof-of-concept trial. Brain Stimul.2016;9:453–454. https://doi.org/10.1016/j.brs.2016.02.001
GrovesDABrownVJ. Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci Biobehav Rev.2005;29:493–500. https://doi.org/10.1016/j.neubiorev.2005.01.004
FératVScheltienneMBrunetDRosTMichelCJJOOSS. Pycrostates: a python library to study EEG microstates. J Open Source Software. 2022;7:4564. https://doi.org/10.21105/joss.04564
35.
KoenigTPrichepLLehmannD, et al.Millisecond by millisecond, year by year: normative EEG microstates and developmental stages. NeuroImage. 2002;16:41–48. https://doi.org/10.1006/nimg.2002.1070
MevelKGrassiotBChételatGDeferGDesgrangesBEustacheF. [The default mode network: cognitive role and pathological disturbances]. Rev Neurol (Paris).2010;166:859–872. https://doi.org/10.1016/j.neurol.2010.01.008
39.
HardmeierMHatzFBousleimanHSchindlerCStamCJFuhrP. Reproducibility of functional connectivity and graph measures based on the phase lag index (PLI) and weighted phase lag index (wPLI) derived from high resolution EEG. PloS One. 2014. 9:e108648 https://doi.org/10.1371/journal.pone.0108648
NapadowVEdwardsRRCahalanCM, et al.Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation. Pain Medicine. 2012;13:777–789. https://doi.org/10.1111/j.1526-4637.2012.01385.x
42.
KrausTKiessOHöslKTerekhinPKornhuberJForsterC. CNS bold fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study. Brain Stimul.2013;6:798–804. https://doi.org/10.1016/j.brs.2013.01.011
43.
YakuninaNKimSSNamEC. Optimization of transcutaneous vagus nerve stimulation using functional MRI. Neuromodulation Technol Neural Interface. 2017;20:290–300. https://doi.org/10.1111/ner.12541
44.
KrausTHöslKKiessOSchanzeAKornhuberJForsterC. Bold fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation. J Neural Transm.2007;114:1485–1493. https://doi.org/10.1007/s00702-007-0755-z
45.
StraubeAEllrichJErenOBlumBRuscheweyhR. Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS): a randomized, monocentric clinical trial. J Headache Pain.2015;16:543. https://doi.org/10.1186/s10194-015-0543-3
46.
von WredeRRingsTSchachSHelmstaedterCLehnertzKJSR. Transcutaneous auricular vagus nerve stimulation induces stabilizing modifications in large-scale functional brain networks: towards understanding the effects of TAVNS in subjects with epilepsy. Sci Rep.2021;11:7906. https://doi.org/10.1038/s41598-021-87032-1
AihuaLLuSLipingL, et al.A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy. Epilepsy Behav. 2014;39:105–110. https://doi.org/10.1016/j.yebeh.2014.08.005
