迷走神經刺激術治療兒童難治性癲癇的研究進展_Journal of Epilepsy

Authors：

曹藝耀 ¹ , 熊金彪 ¹ ,  楊衛東 ¹ , 毓青 ² ,  陳旨娟 ¹

1. ;
2. ;

Corresponding?author：

楊衛東, Email: yangweidongshine@sina.com; 陳旨娟, Email: hapzhijuan0217@126.com

Keywords：

迷走神經刺激術; 兒童; 癲癇; 藥物難治性癲癇

DOI：

10.7507/2096-0247.20190061

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自 1997 年美國食物藥物管理局批準迷走神經刺激術（Vagus nerve stimulation，VNS）作為≥12 歲難治局灶性癲癇患者的輔助治療以來，VNS 因其有效性、相對安全性被廣泛應用。但大部分研究主要針對成年藥物難治性癲癇（Drug refractory epilepsy，DRE）患者，兒童是 DRE 的高發人群，癲癇發作對患兒生長發育、社會適應甚至家庭情況等有很大影響，隨著 VNS 治療 DRE 患兒的研究不斷增多，已有研究證實 VNS 能有效控制患兒癲癇發作。為了解近年來 VNS 治療 DRE 患兒的進展，現主要從 VNS 控制 DRE 患兒的發作機制、手術方式、術后評估等方面進行綜述。

Citation： 曹藝耀, 熊金彪, 楊衛東, 毓青, 陳旨娟. 迷走神經刺激術治療兒童難治性癲癇的研究進展. Journal of Epilepsy, 2019, 5(5): 376-381. doi: 10.7507/2096-0247.20190061 Copy

1.	Wheless JW, Gienapp AJ, Ryvlin P. Vagus nerve stimulation (VNS) therapy update. Epilepsy &Behavior, 2018, 88(6): 2-10.
2.	Eriksson KJ, Koivikko MJ. Prevalence, classification, and severity of epilepsy and epileptic syndromes in children. Epilepsia, 1997, 38(12): 1275-1282.
3.	Holmes GL, Lenck-Santim PP. Role of interictal epileptiform abnormalities in cognitive impairment. Epilepsy&Behavior, 2006, 8(3): 504-515.
4.	Ibrahim GM, Morgan BR, Lee W, et al. Impaired development of intrinsic connectivity networks in children with medically intractable localization-related epilepsy. Hum Brain Mapp, 2015, 35(11): 5686-5700.
5.	Berg AT, Zelko FA, Levy SR, et al. Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes a prospective cohort study. Neurology, 2012, 79(3): 1384-1391.
6.	Orosz I, McCormick D, Zamponi N, 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.
7.	Fan HC, Hsu TR, Chang KP, et al. Vagus nerve stimulation for 6- to 12-year-old children with refractory epilepsy: impact on seizure frequency and parenting stress index. Epilepsy &Behavior, 2018, 83(6): 119-123.
8.	The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology, 1995, 45(2): 224-230.
9.	Fornai F, Ruffoli R, Giorgi FS, et al. The role of locus coeruleus in the antiepileptic activity induced by vagus nerve stimulation. Eur J Neurosci, 2011, 33(7): 2169-2178.
10.	Schevernels H, van Bochove ME, De Taeye L, et al. The effect of vagus nerve stimulation on response inhibition. Epilepsy Behav, 2016, 64(Pt A): 171-179.
11.	Klinkenberg S, van den Borne CJ, Aalbers MW, et al. The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy. Epilepsy Behav, 2014, 37(8): 133-138.
12.	Hachem LD, Wong SM, Ibrahim GM. The vagus afferent network: emerging role in translational connectomics. Neurosurg Focus, 2018, 45(8): E2.
13.	Yu R, Verschuure P, Kessels AG, et al. Interregional metabolic connectivity of 2-deoxy-2[(18) F]fluoro-D-glucose positron emission tomography in vagus nerve stimulation for pediatric patients with epilepsy: a retrospective cross-sectional study. Epilepsia, 2018, 59(4): 2249-2259.
14.	De Herdt V, Leenen L, Rijkers K, et al. Effects of vagus nerve stimulation on pro- and anti-inflammatory cytokine induction in patients with refractory epilepsy. J Neuroimmunol, 2009, 214(6): 104-108.
15.	Majoie HJ, Rijkers K, Berfelo MW, et al. Vagus nerve stimulation in refractory epilepsy: effects on pro- and anti-inflammatory cytokines in peripheral blood. Neuroimmunomodulation, 2011, 18(1): 52-56.
16.	Koopman FA, Chavan SS, Miljko S, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci USA, 2016, 113(7): 8284-8289.
17.	McGregor A, Wheless T, Baumgartner J, et al. Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans. Epilepsia, 2005, 46(3): 91-96.
18.	Amar AP, Marotta G, Visani E, et al. An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome. Neurosurgery, 1998, 43(6): 1265-1276.
19.	Kirse DJ, Rolston JD, Harward SC, et al. Vagus nerve stimulator implantation in children. Arch Otolaryngol, 2002, 128(7): 1263-1268.
20.	Vaiman M, Heyman E, Lotan G. Neurological results of the modified treatment of epilepsy by stimulation of the vagus nerve. Childs Nerv Syst, 2017, 33(2): 2017-2022.
21.	Hauptman JS, Mathern GW. Vagal nerve stimulation for pharmacoresistant epilepsy in children. Surg Neurol Int, 2012, 3(suppl): 269-274.
22.	Lotan G, Vaiman M. Treatment of epilepsy by stimulation of the vagus nerve from head-and-neck surgical point of view. The Laryngoscope, 2015, 125(3): 1352-1355.
23.	Bodin E, Le Moing AG, Bourel-Ponchel E, et al. Vagus nerve stimulation in the treatment of drug-resistant epilepsy in 29 children. Eur J Paediatr Neurol, 2016, 20(3): 346-351.
24.	Yowtak J, Jenkins P, Giller C. Transection of omohyoid muscle as an aid during vagus nerve stimulator implantation. World Neurosurgery, 2017, 99(3): 118-121.
25.	Kawai K, Tanaka T, Baba H, et al. Outcome of vagus nerve stimulation for drug-resistant epilepsy: the first three years of a prospective Japanese registry. Epileptic Disord, 2017, 19(3): 327-338.
26.	Barbella G, Cocco I, Freri E, et al. Transcutaneous vagal nerve stimulatio (t-VNS): an adjunctive treatment option for refractory epilepsy. Seizure, 2018, 60(8): 115-119.
27.	Chambers A, Bowen JM. Electrical stimulation for drug-resistant epilepsy: an evidence-based analysis. Ont Health Technol Assess Ser, 2013, 13(8): 1-37.
28.	Frost M, Forster CR, Baise C, et al. Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome. Epilepsia, 2001, 42(5): 1148-1152.
29.	Cukiert A, Cukiert CM, Burattini JA, et al. A prospective long-term study on the outcome after vagus nerve stimulation at maximally tolerated current intensity in a cohort of children with refractory secondary generalized epilepsy. Neuromodulation, 2013, 16(6): 30-31.
30.	Klinkenberg S, Watemberg N, Boxer M, et al. Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial. Dev Med Child Neurol, 2012, 54(5): 855-861.
31.	Menascu S, Kremer U, Schiller Y, et al. The Israeli retrospective multicenter open-label study evaluating vagus nerve stimulation efficacy in children and adults. Israel Medical Association Journal, 2013, 15(11): 673-677.
32.	Colicchio G, Mangano FT, Gonsalves C, et al. Vagal nerve stimulation for drug-resistant epilepsies in different age, aetiology and duration. Child Nerv Syst, 2010, 26(7): 811-819.
33.	Arya R, Greiner HM, Lewis A, et al. Predictors of response to vagus nerve stimulation in childhood-onset medically refractory epilepsy. Journal of Child Neurology, 2014, 29(12): 1652-1659.
34.	Tomei KL, Mau CY, GhaliM, et al. Vagal nerve stimulation for medically refractory epilepsy in Angelman syndrome: a series of three cases. Childs Nerv Syst, 2018, 34(6): 395-400.
35.	Serdaroglu A, Connolly MB, French J, et al. Long term effect of vagus nerve stimulation in pediatric intractable epilepsy: an extended follow-up. Childs Nerv Syst, 2016, 32(2): 641-646.
36.	Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521.
37.	Englot DJ, Chang EF, AugusteKI. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response A review. Journal of Neurosurgery, 2011, 115(8): 1248-1255.
38.	Morris GL, Bouthiller A, Scavarda D, et al. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the guideline development subcommittee of the american academy of neurology. Epilepsy Curr, 2013, 13(4): 297-303.
39.	Dravet C, Oguni H. Dravet syndrome (severe myoclonic epilepsy in infancy). Handbook of Clinical Neurology, 2013, 111: 627-633.
40.	Zamponi N, Passamonti C, Cappanera S, et al. Clinical course of young patients with Dravet syndrome after vagal nerve stimulation. Eur J Paediatr Neurol, 2011, 15(1): 8-14.
41.	Rossignol E, Lortie A, Thomas T, et al. Vagus nerve stimulation in pediatric epileptic syndromes. Seizure, 2009, 18(1): 34-37.
42.	Shahwan A, Bailey C, Maxiner W, et al. Vagus nerve stimulation for refractory epilepsy in children: more to VNS than seizure frequency reduction. Epilepsia, 2009, 50(5): 1220-1228.
43.	Cerminara C, Marciano S, Bombardieri R, et al. Epilepsy in tuberous sclerosis complex. Journal of Pediatric Epilepsy, 2015, 5(1): 64-69.
44.	Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. The Lancet, 2008, 372(4): 657-668.
45.	Lagae L, Verstrepen A, Nada A, et al. Vagus nerve stimulation in children with drug-resistant epilepsy: age at implantation and shorter duration of epilepsy as predictors of better efficacy? Epileptic Disorders, 2015, 17(3): 308-314.
46.	Zamponi N, Petrelli C, Passamonti C, et al. Vagus nerve stimulation for refractory epilepsy in tuberous sclerosis. Pediatric Neurology, 2009, 43(3): 29-34.
47.	Elliott RE, Carlson C, Kalhorn SP, et al. Refractory epilepsy in tuberous sclerosis: vagus nerve stimulation with or without subsequent resective surgery. Epilepsy & Behavior, 2009, 16(3): 454-460.
48.	Hunter RM, Van Roost D, Thiery E, et al. The health, education, and social care costs of school-aged children with active epilepsy: a population-based study. Epilepsia, 2015, 56(4): 1056-1064.
49.	Laxer KD, Trinka E, Hirsch LJ, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav, 2014, 37(1): 59-70.
50.	Patel A, Wang L, Gedela S. Health care utilization following vagus nerve stimulation therapy in pediatric epilepsy patients from a pediatric accountable care organization. Journal of Child Neurology, 2018, 33(3): 136-139.
51.	Aburahma SK, Alzoubi FQ, Hammouri HM, et al. Vagus nerve stimulation therapy in a developing country: a long term follow up study and cost utility analysis. Seizure, 2015, 25(6): 167-172.
52.	Helmers SL, Duh MS, Guérin A, et al. Clinical outcomes, quality of life, and costs associated with implantation of vagus nerve stimulation therapy in pediatric patients with drug-resistant epilepsy. Eur J Paediatr Neurol, 2016, 16(5): 449-458.
53.	Jette N, Engel JJr. Refractory epilepsy is a life-threatening disease: lest we forget. Neurology, 2016, 86(3): 1932-1933.
54.	Sherman EM, Connolly MB, Slick DJ, et al. Quality of life and seizure outcome after vagus nerve stimulation in children with intractable epilepsy. J Child Neurol, 2008, 23(9): 991-998.
55.	Terra VC, Furlanetti LL, Nunes AA, et al. Vagus nerve stimulation in pediatric patients: is it really worthwhile? Epilepsy Behav, 2014, 31(2): 329-333.
56.	Ryzi M, Brázdil M, Novák Z, et al. Long-term vagus nerve stimulation in children with focal epilepsy. Acta neurologica Scandinavica, 2013, 127(5): 316-322.
57.	Thompson EM, Wozniak SE, Roberts CM, et al. Vagus nerve stimulation for partial and generalized epilepsy from infancy to adolescence. J Neurosurg Pediatr, 2012, 10(3): 200-205.
58.	Majkowska-Zwolinska B, Zwolinski P, Roszkowski M, et al. Long-term results of vagus nerve stimulation in children and adolescents with drug-resistant epilepsy. Childs Nerv Syst, 2012, 28(3): 621-628.
59.	Elliott RE, Rodgers SD, Bassani L, et al. Vagus nerve stimulation for children with treatment-resistant epilepsy: a consecutive series of 141 cases. J Neurosurg Pediatr, 2011, 7(5): 491-500.
60.	Van Wagoner ZD, Evans DC, Askegard-Giesmann JR, et al. Perforated peptic ulcer in a child with a vagus nerve stimulator for seizure control. Brain Stimul, 2013, 6(1): 972-973.
61.	Sheck L, Meyer HD. Episodic monocular vision loss after implantation of a vagal nerve stimulator. Ann Intern Med, 2011, 155(8): 648-649.
62.	Rychlicki F, Zamponi N, Cesaroni E, et al. Complications of vagal nerve stimulation for epilepsy in children. Neurosurg Rev, 2006, 29(2): 103-107.
63.	Cantarin-Extremera V, Ruíz-Falcó-Rojas ML, Tamaríz-Martel-Moreno A, et al. Late-onset periodic bradycardia during vagus nerve stimulation in a pediatric patient: a new case and review of the literature. Eur J Paediatr Neurol, 2016, 20(4): 678-683.
64.	Clark AJ, Kuperman RA, Auguste KI, et al. Intractable episodic bradycardia resulting from progressive lead traction in an epileptic child with a vagus nerve stimulator: a delayed complication. J Neurosurg Pediatr, 2012, 9(2): 389-393.
65.	Borusiak P, Zilbauer M, Cagnoli S, et al. Late-onset cardiac arrhythmia associated with vagus nerve stimulation. J Neurol, 2009, 256(10): 1578-1580.
66.	Amark P, Stodberg T, Wallstedt L. Late onset bradyarrhythmia during vagus nerve stimulation. Epilepsia, 2007, 48(5): 1023-1024.
67.	Fernandez L, Gedela S, Tamber M, et al. Vagus nerve stimulation in children less tran 3 years with medically intractable epilepsy. Epilepsy Res, 2015, 112(5): 37-42.

1. Wheless JW, Gienapp AJ, Ryvlin P. Vagus nerve stimulation (VNS) therapy update. Epilepsy &Behavior, 2018, 88(6): 2-10.
2. Eriksson KJ, Koivikko MJ. Prevalence, classification, and severity of epilepsy and epileptic syndromes in children. Epilepsia, 1997, 38(12): 1275-1282.
3. Holmes GL, Lenck-Santim PP. Role of interictal epileptiform abnormalities in cognitive impairment. Epilepsy&Behavior, 2006, 8(3): 504-515.
4. Ibrahim GM, Morgan BR, Lee W, et al. Impaired development of intrinsic connectivity networks in children with medically intractable localization-related epilepsy. Hum Brain Mapp, 2015, 35(11): 5686-5700.
5. Berg AT, Zelko FA, Levy SR, et al. Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes a prospective cohort study. Neurology, 2012, 79(3): 1384-1391.
6. Orosz I, McCormick D, Zamponi N, 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.
7. Fan HC, Hsu TR, Chang KP, et al. Vagus nerve stimulation for 6- to 12-year-old children with refractory epilepsy: impact on seizure frequency and parenting stress index. Epilepsy &Behavior, 2018, 83(6): 119-123.
8. The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology, 1995, 45(2): 224-230.
9. Fornai F, Ruffoli R, Giorgi FS, et al. The role of locus coeruleus in the antiepileptic activity induced by vagus nerve stimulation. Eur J Neurosci, 2011, 33(7): 2169-2178.
10. Schevernels H, van Bochove ME, De Taeye L, et al. The effect of vagus nerve stimulation on response inhibition. Epilepsy Behav, 2016, 64(Pt A): 171-179.
11. Klinkenberg S, van den Borne CJ, Aalbers MW, et al. The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy. Epilepsy Behav, 2014, 37(8): 133-138.
12. Hachem LD, Wong SM, Ibrahim GM. The vagus afferent network: emerging role in translational connectomics. Neurosurg Focus, 2018, 45(8): E2.
13. Yu R, Verschuure P, Kessels AG, et al. Interregional metabolic connectivity of 2-deoxy-2[(18) F]fluoro-D-glucose positron emission tomography in vagus nerve stimulation for pediatric patients with epilepsy: a retrospective cross-sectional study. Epilepsia, 2018, 59(4): 2249-2259.
14. De Herdt V, Leenen L, Rijkers K, et al. Effects of vagus nerve stimulation on pro- and anti-inflammatory cytokine induction in patients with refractory epilepsy. J Neuroimmunol, 2009, 214(6): 104-108.
15. Majoie HJ, Rijkers K, Berfelo MW, et al. Vagus nerve stimulation in refractory epilepsy: effects on pro- and anti-inflammatory cytokines in peripheral blood. Neuroimmunomodulation, 2011, 18(1): 52-56.
16. Koopman FA, Chavan SS, Miljko S, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci USA, 2016, 113(7): 8284-8289.
17. McGregor A, Wheless T, Baumgartner J, et al. Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans. Epilepsia, 2005, 46(3): 91-96.
18. Amar AP, Marotta G, Visani E, et al. An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome. Neurosurgery, 1998, 43(6): 1265-1276.
19. Kirse DJ, Rolston JD, Harward SC, et al. Vagus nerve stimulator implantation in children. Arch Otolaryngol, 2002, 128(7): 1263-1268.
20. Vaiman M, Heyman E, Lotan G. Neurological results of the modified treatment of epilepsy by stimulation of the vagus nerve. Childs Nerv Syst, 2017, 33(2): 2017-2022.
21. Hauptman JS, Mathern GW. Vagal nerve stimulation for pharmacoresistant epilepsy in children. Surg Neurol Int, 2012, 3(suppl): 269-274.
22. Lotan G, Vaiman M. Treatment of epilepsy by stimulation of the vagus nerve from head-and-neck surgical point of view. The Laryngoscope, 2015, 125(3): 1352-1355.
23. Bodin E, Le Moing AG, Bourel-Ponchel E, et al. Vagus nerve stimulation in the treatment of drug-resistant epilepsy in 29 children. Eur J Paediatr Neurol, 2016, 20(3): 346-351.
24. Yowtak J, Jenkins P, Giller C. Transection of omohyoid muscle as an aid during vagus nerve stimulator implantation. World Neurosurgery, 2017, 99(3): 118-121.
25. Kawai K, Tanaka T, Baba H, et al. Outcome of vagus nerve stimulation for drug-resistant epilepsy: the first three years of a prospective Japanese registry. Epileptic Disord, 2017, 19(3): 327-338.
26. Barbella G, Cocco I, Freri E, et al. Transcutaneous vagal nerve stimulatio (t-VNS): an adjunctive treatment option for refractory epilepsy. Seizure, 2018, 60(8): 115-119.
27. Chambers A, Bowen JM. Electrical stimulation for drug-resistant epilepsy: an evidence-based analysis. Ont Health Technol Assess Ser, 2013, 13(8): 1-37.
28. Frost M, Forster CR, Baise C, et al. Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome. Epilepsia, 2001, 42(5): 1148-1152.
29. Cukiert A, Cukiert CM, Burattini JA, et al. A prospective long-term study on the outcome after vagus nerve stimulation at maximally tolerated current intensity in a cohort of children with refractory secondary generalized epilepsy. Neuromodulation, 2013, 16(6): 30-31.
30. Klinkenberg S, Watemberg N, Boxer M, et al. Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial. Dev Med Child Neurol, 2012, 54(5): 855-861.
31. Menascu S, Kremer U, Schiller Y, et al. The Israeli retrospective multicenter open-label study evaluating vagus nerve stimulation efficacy in children and adults. Israel Medical Association Journal, 2013, 15(11): 673-677.
32. Colicchio G, Mangano FT, Gonsalves C, et al. Vagal nerve stimulation for drug-resistant epilepsies in different age, aetiology and duration. Child Nerv Syst, 2010, 26(7): 811-819.
33. Arya R, Greiner HM, Lewis A, et al. Predictors of response to vagus nerve stimulation in childhood-onset medically refractory epilepsy. Journal of Child Neurology, 2014, 29(12): 1652-1659.
34. Tomei KL, Mau CY, GhaliM, et al. Vagal nerve stimulation for medically refractory epilepsy in Angelman syndrome: a series of three cases. Childs Nerv Syst, 2018, 34(6): 395-400.
35. Serdaroglu A, Connolly MB, French J, et al. Long term effect of vagus nerve stimulation in pediatric intractable epilepsy: an extended follow-up. Childs Nerv Syst, 2016, 32(2): 641-646.
36. Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521.
37. Englot DJ, Chang EF, AugusteKI. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response A review. Journal of Neurosurgery, 2011, 115(8): 1248-1255.
38. Morris GL, Bouthiller A, Scavarda D, et al. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the guideline development subcommittee of the american academy of neurology. Epilepsy Curr, 2013, 13(4): 297-303.
39. Dravet C, Oguni H. Dravet syndrome (severe myoclonic epilepsy in infancy). Handbook of Clinical Neurology, 2013, 111: 627-633.
40. Zamponi N, Passamonti C, Cappanera S, et al. Clinical course of young patients with Dravet syndrome after vagal nerve stimulation. Eur J Paediatr Neurol, 2011, 15(1): 8-14.
41. Rossignol E, Lortie A, Thomas T, et al. Vagus nerve stimulation in pediatric epileptic syndromes. Seizure, 2009, 18(1): 34-37.
42. Shahwan A, Bailey C, Maxiner W, et al. Vagus nerve stimulation for refractory epilepsy in children: more to VNS than seizure frequency reduction. Epilepsia, 2009, 50(5): 1220-1228.
43. Cerminara C, Marciano S, Bombardieri R, et al. Epilepsy in tuberous sclerosis complex. Journal of Pediatric Epilepsy, 2015, 5(1): 64-69.
44. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. The Lancet, 2008, 372(4): 657-668.
45. Lagae L, Verstrepen A, Nada A, et al. Vagus nerve stimulation in children with drug-resistant epilepsy: age at implantation and shorter duration of epilepsy as predictors of better efficacy? Epileptic Disorders, 2015, 17(3): 308-314.
46. Zamponi N, Petrelli C, Passamonti C, et al. Vagus nerve stimulation for refractory epilepsy in tuberous sclerosis. Pediatric Neurology, 2009, 43(3): 29-34.
47. Elliott RE, Carlson C, Kalhorn SP, et al. Refractory epilepsy in tuberous sclerosis: vagus nerve stimulation with or without subsequent resective surgery. Epilepsy & Behavior, 2009, 16(3): 454-460.
48. Hunter RM, Van Roost D, Thiery E, et al. The health, education, and social care costs of school-aged children with active epilepsy: a population-based study. Epilepsia, 2015, 56(4): 1056-1064.
49. Laxer KD, Trinka E, Hirsch LJ, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav, 2014, 37(1): 59-70.
50. Patel A, Wang L, Gedela S. Health care utilization following vagus nerve stimulation therapy in pediatric epilepsy patients from a pediatric accountable care organization. Journal of Child Neurology, 2018, 33(3): 136-139.
51. Aburahma SK, Alzoubi FQ, Hammouri HM, et al. Vagus nerve stimulation therapy in a developing country: a long term follow up study and cost utility analysis. Seizure, 2015, 25(6): 167-172.
52. Helmers SL, Duh MS, Guérin A, et al. Clinical outcomes, quality of life, and costs associated with implantation of vagus nerve stimulation therapy in pediatric patients with drug-resistant epilepsy. Eur J Paediatr Neurol, 2016, 16(5): 449-458.
53. Jette N, Engel JJr. Refractory epilepsy is a life-threatening disease: lest we forget. Neurology, 2016, 86(3): 1932-1933.
54. Sherman EM, Connolly MB, Slick DJ, et al. Quality of life and seizure outcome after vagus nerve stimulation in children with intractable epilepsy. J Child Neurol, 2008, 23(9): 991-998.
55. Terra VC, Furlanetti LL, Nunes AA, et al. Vagus nerve stimulation in pediatric patients: is it really worthwhile? Epilepsy Behav, 2014, 31(2): 329-333.
56. Ryzi M, Brázdil M, Novák Z, et al. Long-term vagus nerve stimulation in children with focal epilepsy. Acta neurologica Scandinavica, 2013, 127(5): 316-322.
57. Thompson EM, Wozniak SE, Roberts CM, et al. Vagus nerve stimulation for partial and generalized epilepsy from infancy to adolescence. J Neurosurg Pediatr, 2012, 10(3): 200-205.
58. Majkowska-Zwolinska B, Zwolinski P, Roszkowski M, et al. Long-term results of vagus nerve stimulation in children and adolescents with drug-resistant epilepsy. Childs Nerv Syst, 2012, 28(3): 621-628.
59. Elliott RE, Rodgers SD, Bassani L, et al. Vagus nerve stimulation for children with treatment-resistant epilepsy: a consecutive series of 141 cases. J Neurosurg Pediatr, 2011, 7(5): 491-500.
60. Van Wagoner ZD, Evans DC, Askegard-Giesmann JR, et al. Perforated peptic ulcer in a child with a vagus nerve stimulator for seizure control. Brain Stimul, 2013, 6(1): 972-973.
61. Sheck L, Meyer HD. Episodic monocular vision loss after implantation of a vagal nerve stimulator. Ann Intern Med, 2011, 155(8): 648-649.
62. Rychlicki F, Zamponi N, Cesaroni E, et al. Complications of vagal nerve stimulation for epilepsy in children. Neurosurg Rev, 2006, 29(2): 103-107.
63. Cantarin-Extremera V, Ruíz-Falcó-Rojas ML, Tamaríz-Martel-Moreno A, et al. Late-onset periodic bradycardia during vagus nerve stimulation in a pediatric patient: a new case and review of the literature. Eur J Paediatr Neurol, 2016, 20(4): 678-683.
64. Clark AJ, Kuperman RA, Auguste KI, et al. Intractable episodic bradycardia resulting from progressive lead traction in an epileptic child with a vagus nerve stimulator: a delayed complication. J Neurosurg Pediatr, 2012, 9(2): 389-393.
65. Borusiak P, Zilbauer M, Cagnoli S, et al. Late-onset cardiac arrhythmia associated with vagus nerve stimulation. J Neurol, 2009, 256(10): 1578-1580.
66. Amark P, Stodberg T, Wallstedt L. Late onset bradyarrhythmia during vagus nerve stimulation. Epilepsia, 2007, 48(5): 1023-1024.
67. Fernandez L, Gedela S, Tamber M, et al. Vagus nerve stimulation in children less tran 3 years with medically intractable epilepsy. Epilepsy Res, 2015, 112(5): 37-42.

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腦損傷生物標記物研究進展

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迷走神經刺激術治療兒童難治性癲癇的研究進展

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