Oliveira, Tatiana Von Hertwig Fernandes de; Francisco, Alexandre Novicki; Demartini, Zeferino; Stebel, Sergio Leandro

doi:10.1590/0004-282X20170113

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Arquivos de Neuro-Psiquiatria

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VIEWS AND REVIEWS • Arq. Neuro-Psiquiatr. 75 (9) • Set 2017 • https://doi.org/10.1590/0004-282X20170113 copiar

O papel da estimulação do nervo vago na epilepsia refratária

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

A estimulação vagal é uma terapia paliativa utilizada no tratamento de pacientes com epilepsia refratária que não são candidatos à cirurgia ressectiva ou naqueles com evolução insatisfatória após o procedimento cirúrgico. Seu mecanismo de ação ainda não foi completamente elucidado mas possivelmente envolve a modulação do locus coeruleus, tálamo e circuito límbico através de projeções noradrenérgicas e serotoninérgicas. Atualmente há evidência suficiente para corroborar o uso desta terapia em pacientes com epilepsia focal e outros tipos de crise, com resultados que, apesar de não imediatos, melhoram progressivamente no longo prazo. Os eventos adversos são, em sua maioria, relacionados à estimulação e auto-limitados. Perspectivas futuras para aumentar a eficácia e reduzir os efeitos colaterais como a utilização de baterias com maior durabilidade, estimulação transcutânea e identificação de fatores prognósticos devem ser investigadas.

estimulação do nervo vago; epilepsia

Variable	1	2	3	4	5	6	7	8
Output current (mA)	0.25	0.5	0.75	1	1.25	1.5	1.5	1.5
Frequency (Hz)	20/30	20/30	20/30	20/30	20/30	20/30	20/30	20/30
Pulse width (µs)	250/500	250/500	250/500	250/500	250/500	250/500	250/500	250/500
ON time (sec)	30	30	30	30	30	30	30	30
OFF time (min)	5	5	5	5	5	5	3	1.8
Magnet current (mA)	0.5	0.75	1	1.25	1.5	1.75	1.75	1.75
Magnet ON time (sec)	60	60	60	60	60	60	60	60

Duty cycle (% ON time)

OFF time (min)	ON time (sec)

	7	14	21	30	60
0.2	58*	69*	76*	81*	89*
0.3	44	56*	64*	71*	82*
0.5	30	41	49	57*	71*
0.8	20	29	36	44	59*
1.1	15	23	29	35	51*
1.8	10	15	19	25	38
3	6	9	12	16	27
5	4	6	8	10	18
10	2	3	4	5	10

Authors and year	Class of evidence	No. of patients	Follow-up (mos)	> 50% reduction (%)	Mean or median % reduction (%)
Ben-Menachem et al., 1994⁹9. Ben-Menachem E, Mañon-Espaillat R, Ristanovic R, Wilder BJ, Stefan H, Mirza W et al.; First International Vagus Nerve Stimulation Study Group. Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. Epilepsia. 1994;35(3):616-26. https://doi.org/10.1111/j.1528-1157.1994.tb02482.x https://doi.org/10.1111/j.1528-1157.1994...	I	67	3.5	38.7	30.9
George et al., 1994⁴⁷47. George R, Salinsky M, Kuzniecky R, Rosenfeld W, Bergen D, Tarver WB et al.Vagus nerve stimulation for treatment of partial seizures:3. Long-term follow-up on first 67 patients exiting a controlled study. Epilepsia. 1994;35(3):637-43. https://doi.org/10.1111/j.1528-1157.1994.tb02484.x https://doi.org/10.1111/j.1528-1157.1994...	II	24	16–18	NR	52
Salinski et al., 1996¹¹11. Salinsky MC, Uthman BM, Ristanovic RK, Wernicke JF, Tarver WB.Vagus nerve stimulation for the treatment of medically intractable seizures. Results of a 1-year open-extension trial. Arch Neurol. 1996;53(11):1176-80. https://doi.org/10.1001/archneur.1996.00550110128021 https://doi.org/10.1001/archneur.1996.00...	II	100	12	18,40	32
Handforth et al., 1998¹²12. Handforth A, DeGiorgio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES et al.Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 1998;51(1):48-55. https://doi.org/10.1212/WNL.51.1.48 https://doi.org/10.1212/WNL.51.1.48...	I	94	3	NR	28
Ben-Menachem et al., 1999⁴⁸48. Ben-Menachem E, Hellström K, Waldton C, Augustinsson LE.Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 yers. Neurology. 1999;52(6):1265-7. https://doi.org/10.1212/WNL.52.6.1265 https://doi.org/10.1212/WNL.52.6.1265...	II	64	20 (3–64)	NR	45
Amar et al., 1999⁴⁹49. Amar AP, DeGiorgio CM, Tarver WB, Apuzzo ML.Long-term multicenter experience with vagus nerve stimulation for intractable partial seizures. Stereotact Funct Neurosurg. 1999;73(1-4):104-8. https://doi.org/10.1159/000029764 https://doi.org/10.1159/000029764...	I	164	15	39	37 and 45*
Labar et al., 1999⁵⁰50. Labar D, J Murphy, E Tecoma.Vagus nerve stimulation for medication-resistant feneralized epilepsy. Neurology. 1999;52(7):1510-2. https://doi.org/10.1212/WNL.52.7.1510 https://doi.org/10.1212/WNL.52.7.1510...	II	24	3	45.8	46
Vonck et al., 1999³⁴34. Vonck K, Boon P, D’Havé M, Vandekerckhove T, O’Connor S, DeReuck J. Long-term results of vagus nerve stimulation in refractory epilepsy. Seizure. 1999;8(6):328-34. https://doi.org/10.1053/seiz.1999.0299 https://doi.org/10.1053/seiz.1999.0299...	II	15	29 (12–48)	66.6	57.1
Parker et al., 1999⁵¹51. Parker AP, Polkey CE, Binnie CD, Madigan C, Ferrie CD, Robinson RO.Vagal nerve stimulation in epileptic encephalopathies. Pediatrics. 1999;103(4):778-82. https://doi.org/10.1542/peds.103.4.778 https://doi.org/10.1542/peds.103.4.778...	III	15	12	26.6	17
Murphy et al., 1999⁵²52. Murphy JV.Left vagal nerve stimulation in children with medically refractory epilepsy. J Pediatr. 1999;134(5):563-6. https://doi.org/10.1016/S0022-3476(99)70241-6 https://doi.org/10.1016/S0022-3476(99)70...	III	51	18	NR	42
DeGiorgio et al., 2000¹³13. DeGiorgio CM, Schachter SC, Handforth A, Salinsky M, Thompson J, Uthman B et al.Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia. 2000;41(9):1195-200. https://doi.org/10.1111/j.1528-1157.2000.tb00325.x https://doi.org/10.1111/j.1528-1157.2000...	II	195	12	35	45
Kawai et al., 2002³¹31. Kawai K, Shimizu H, Maehara T, Murakami H.Outcome of long-term vagus nerve stimulation for intractable epilepsy. Neurol Med Chir (Tokyo). 2002;42(11):481-90. https://doi.org/10.2176/nmc.42.481 https://doi.org/10.2176/nmc.42.481...	III	13	56 (48–91)	69	63
Chavel et al., 2003⁵³53. Chavel SM, Westerveld M, Spencer S.Long-term outcome of vagus nerve stimulation for refractory partial epilepsy. Epilepsy Behav. 2003;4(3):302-9. https://doi.org/10.1016/S1525-5050(03)00109-4 https://doi.org/10.1016/S1525-5050(03)00...	III	23	24	61	54
Murphy et al., 2003⁵⁴54. Murphy JV, Torkelson R, Dowler I, Simon S, Hudson S.Vagal nerve stimulation in refractory epilepsy: the first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy center. Arch Pediatr Adolesc Med. 2003;157(6):560-4. https://doi.org/10.1001/archpedi.157.6.560 https://doi.org/10.1001/archpedi.157.6.5...	III	96	32 (12–108)	45	NR
Uthman et al., 2004⁵⁵55. Uthman BM, Reichl AM, Dean JC, Eisenschenk S, Gilmore R, Reid S et al.Effectiveness of vagus nerve stimulation in epilepsy patients: a 12-year observation. Neurology. 2004;63(6):1124-6. https://doi.org/10.1212/01.WNL.0000138499.87068.C0 https://doi.org/10.1212/01.WNL.000013849...	III	25	6–144	60	52**
Saneto et al., 2006⁵⁶56. Saneto RP, Menezes MAS, Ojemann JG, Bournival BD, Murphy PJ, Cook WB et al.Vagus nerve stimulation for intractable seizures in children. Pediatr Neurol. 2006;35(5):323-6. https://doi.org/10.1016/j.pediatrneurol.2006.06.005 https://doi.org/10.1016/j.pediatrneurol....	III	43	18 (7–40)	51	51
De Herdt et al., 2007⁵⁷57. De Herdt V, Boon P, Ceulemans B, Hauman H, Lagae L, Legros B et al.Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. Eur J Paediatr Neurol. 2007;11(5):261-9. https://doi.org/10.1016/j.ejpn.2007.01.008 https://doi.org/10.1016/j.ejpn.2007.01.0...	III	138	44 (12–120)	59	51
Ghaemi et al., 2010⁴³43. Ghaemi K, Elsharkawy AE, Schulz R, Hoppe M, Polster T, Pannek H et al.Vagus nerve stimulation: outcome and predictors of seizure freedom in long-term follow-up. Seizure. 2010;19(5):264-8. https://doi.org/10.1016/j.seizure.2010.03.002 https://doi.org/10.1016/j.seizure.2010.0...	III	144	36 (24–71)	62	NR
Englot et al., 2011³⁰30. Englot DJ, Chang EF, Auguste KI.Efficacy of vagus nerve stimulation for epilepsy by patient age, epilepsy duration, and seizure type, Neurosurg Clin N Am. 2011;22(4):443-8. https://doi.org/10.1016/j.nec.2011.07.002 https://doi.org/10.1016/j.nec.2011.07.00...	III	1104	24	56	62
Elliot et al., 2011⁵⁸58. Elliott RE, Morsi A, Tanweer O, Grobelny B, Geller E, Carlson C et al.Efficacy of vagus nerve stimulation over time: review of 65 consecutive patients with treatment-resistant epilepsy treated with VNS>10 years. Epilepsy Behav. 2011;20(3):478-83. https://doi.org/10.1016/j.yebeh.2010.12.042 https://doi.org/10.1016/j.yebeh.2010.12....	III	65	124	NR	76.3 and 80*
Elliot et al., 2011⁴⁴44. Elliott RE, Morsi A, Kalhorn SP, Marcus J, Sellin J, Kang M et al.Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response. Epilepsy Behav. 2011;20(1):57-63. https://doi.org/10.1016/j.yebeh.2010.10.017 https://doi.org/10.1016/j.yebeh.2010.10....	III	400	59 (3–136)	64	55.8 and 59.2*
Ching et al., 2013³³33. Ching J, Khan S, White P, Reed J, Ramnarine D, Sieradzan K et al.Long-term effectiveness and tolerability of vagal nerve stimulation in adults with intractable epilepsy: a retrospective analysis of 100 patients. Br J Neurosurg. 2013;27(2):228-34. https://doi.org/10.3109/02688697.2012.732716 https://doi.org/10.3109/02688697.2012.73...	III	100	6–144	51	49
Yu et al., 2014⁵⁹59. Yu C, Ramgopal S, Libenson M, Abdelmoumen I, Powell C, Remy K et al.Outcomes of vagal nerve stimulation in a pediatric population: a single center experience. Seizure. 2014;23(2):105-11. https://doi.org/10.1016/j.seizure.2013.10.002 https://doi.org/10.1016/j.seizure.2013.1...	III	69	12	41	40
Orosz et al., 2014⁸8. Orosz I, McCormick D, Zamponi N, Varadkar S, Feucht M, Parain D 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):1576-84. https://doi.org/10.1111/epi.12762 https://doi.org/10.1111/epi.12762...	II	347	12	38	NR
Serdaroglu et al., 2016⁶⁰60. Serdaroglu A, Arhan E, Kurt G, Erdem A, Hirfanoglu T, Aydin K et al.Long term effect of vagus nerve stimulation in pediatric intractable epilepsy: an extended follow-up. Childs Nerv Syst. 2016;32(4):641-6. https://doi.org/10.1007/s00381-015-3004-z https://doi.org/10.1007/s00381-015-3004-...	III	56	87	62.5	NR
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[1] Correspondence: Tatiana Von Hertwig Fernandes de Oliveira; Av. Sete de Setembro, 3165; 80230-901 Curitiba PR, Brasil; E-mail: tatiana.hertwig@gmail.com