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VIEWS AND REVIEWS • Arq. Neuro-Psiquiatr. 76 (6) • Jun 2018 • https://doi.org/10.1590/0004-282X20180048 copiar

Decisões a respeito da terapia com estimulação cerebral profunda na doença de Parkinson

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

A doença de Parkinson pode ser tratada cirurgicamente em pacientes que desenvolveram complicações motoras, como flutuações e discinesias, ou tremores refratários ao uso de medicação. Nesta revisão, um grupo de especialistas formulou sugestões para um protocolo de avaliação pré-operatória, depois de revisar a literatura publicada até outubro de 2017. Neste protocolo, são sugeridos critérios de elegibilidade e inadmissibilidade para tratamento cirúrgico, bem como procedimentos que devem ser realizados antes das decisões terapêuticas multidisciplinares. A revisão enfatiza a necessidade de estabelecer “equipes de DBS”, com profissionais dedicados especialmente a esta área. Ao final, a seleção do alvo cirúrgico (núcleo subtalâmico ou globo pálido interno) é discutida brevemente, ponderando prós e contras de cada escolha.

doença de Parkinson; estimulação cerebral profunda; padrões de referência; gânglios da base; procedimentos neurocirúrgicos

Author, year	N	Follow-up	Target	Mean disease duration	Center	Clinical outcomes
Anderson et al.¹²12. Anderson VC, Burchiel KJ, Hogarth P, Favre J, Hammerstad JP. Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease. Arch Neurol. 2005 Apr;62(4):554-60. https://doi.org/10.1001/archneur.62.4.554 https://doi.org/10.1001/archneur.62.4.55...	23	12 m	STN or GPi	15.6 y (STN); 10.2 y (GPi)	USA	STN DBS patients tend to remain on lower levodopa dosage (-38%), but have shown more cognitive and behavioral side effects
Deuschl et al.¹³13. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K et al. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006 Aug;355(9):896-908. https://doi.org/10.1056/NEJMoa060281 https://doi.org/10.1056/NEJMoa060281...	156	6 m	Bilateral STN (n = 78) vs. best medical therapy	13.0 y	Germany and Austria	STN DBS: 9.5 pts improvement in PDQ-39 and 19.6 improvement in UPDRS-III. One fatal brain hemorrhage.
Schüpbach et al.¹⁴14. Schüpbach WM, Maltête D, Houeto JL, Montcel ST, Mallet L, Welter ML et al. Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology. 2007 Jan;68(4):267-71. https://doi.org/10.1212/01.wnl.0000250253.03919.fb https://doi.org/10.1212/01.wnl.000025025...	20	18 m	Bilateral STN (n = 10) vs. best medical therapy	6.8 y	France	24% improvement in QoL; -69% severity of motor symptoms in off time; -83% motor complications; -57% reduction in levodopa dosage
Weaver et al.¹⁵15. Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009 Jan;301(1):63-73. https://doi.org/10.1001/jama.2008.929 https://doi.org/10.1001/jama.2008.929...	255	6 m	STN (n = 60); GPi (n = 61); best medical therapy (n = 134)	12.4 y	USA	Longer ON time without dyskinesia (+4.6 hours a day); similar between GPi and STN DBS; worse verbal fluency in STN DBS
Williams et al.¹⁶16. Williams A, Gill S, Varma T, Jenkinson C, Quinn N, Mitchell R et al. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson’s disease (PD SURG trial): a randomised, open-label trial. Lancet Neurol. 2010 Jun;9(6):581-91. https://doi.org/10.1016/S1474-4422(10)70093-4 https://doi.org/10.1016/S1474-4422(10)70...	366	12 m	Bilateral STN (n = 183) vs. best medical therapy (n = 183)	11.4 y	United Kingdom	Improved dyskinesia and daily ON time; 5 pts improvement in PDQ-39-SI; 19% serious adverse effects
Follett et al.¹⁷17. Follett KA, Weaver FM, Stern M, Hur K, Harris CL, Luo P et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2010 Jun;362(22):2077-91. https://doi.org/10.1056/NEJMoa0907083 https://doi.org/10.1056/NEJMoa0907083...	299	24 m	STN (n = 147) or GPi (n = 152)	11.1y (STN); 11.4 y (GPi)	USA	GPi and STN DBS similar efficacy. STN DBS: lower dose of dopaminergic agents, higher risk of depression and reduced visuomotor processing speed;
Okun et al.¹⁸18. Okun MS, Gallo BV, Mandybur G, Jagid J, Foote KD, Revilla FJ et al. Subthalamic deep brain stimulation with a constant-current device in Parkinson’s disease: an open-label randomised controlled trial. Lancet Neurol. 2012 Feb;11(2):140-9. https://doi.org/10.1016/S1474-4422(11)70308-8 https://doi.org/10.1016/S1474-4422(11)70...	136	3 m	STN: immediate (n = 131) or delayed (n = 35) stimulation	12.0 y	USA	+2h50 daily ON time; UPDRS-III: improvement (39%);4% surgical site infection; 3% intracranial hemorrhage;
Schüpbach et al.¹⁹19. Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L et al. Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med. 2013 Feb;368(7):610-22. https://doi.org/10.1056/NEJMoa1205158 https://doi.org/10.1056/NEJMoa1205158...	251	24 m	Bilateral STN (n = 124) vs. medical therapy (n = 127)	7.5 y	Germany and France	Improved motor disability, motor complications, daily life activities and ON time without troublesome dyskinesia.

Authors, year	Number of studies included	Conclusions
Kleiner-Fisman et al.²⁰20. Kleiner-Fisman G, Herzog J, Fisman DN, Tamma F, Lyons KE, Pahwa R et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord. 2006 Jun;21(S14 Suppl 14):S290-304. https://doi.org/10.1002/mds.20962 https://doi.org/10.1002/mds.20962...	22 studies	UPDRS-II: 13.3 pts improvement;
		UPDRS-III: 27.55 pts improvement;
		Mean reduction of LED: 55.9%
		Mean dyskinesia improvement: 69%;
		Mean OFF time reduction: 68%;
		PDQ-39: 34.5% improvement;
		Most severe adverse effect: intracranial hemorrhage 3.9%
Andrade et al.²¹21. Andrade P, Carrillo-Ruiz JD, Jiménez F. A systematic review of the efficacy of globus pallidus stimulation in the treatment of Parkinson’s disease. J Clin Neurosci. 2009 Jul;16(7):877-81. https://doi.org/10.1016/j.jocn.2008.11.006 https://doi.org/10.1016/j.jocn.2008.11.0...	22 studies (n = 327)	GPi: 19 pts improvement in UPDRS-III;
	22 studies (n = 327)	Best programming parameters for 50% improvement in UPDRS-III: amplitude between 2.0-3.5V, pulse width between 70-300 µs and frequency: 100-190Hz.
Sharma et al.²²22. Sharma A, Szeto K, Desilets AR. Efficacy and safety of deep brain stimulation as an adjunct to pharmacotherapy for the treatment of Parkinson disease. Ann Pharmacother. 2012 Feb;46(2):248-54. https://doi.org/10.1345/aph.1Q508 https://doi.org/10.1345/aph.1Q508...	5 studies	Improved motor function and QoL. Higher incidence of side effects. Studies limited due to design and sample size. Surgery is an option after best medical therapy (individual risk/benefit ratio shall be addressed)
Volkmann et al.²³23. Volkmann J, Albanese A, Antonini A, Chaudhuri KR, Clarke CE, Bie RM et al. Selecting deep brain stimulation or infusion therapies in advanced Parkinson’s disease: an evidence-based review. J Neurol. 2013 Nov;260(11):2701-14. https://doi.org/10.1007/s00415-012-6798-6 https://doi.org/10.1007/s00415-012-6798-...	6 class I studies;	Consistent evidence of benefit for dyskinesias and motor fluctuations. Evidence was considered insufficient for apomorphine infusion and levodopa duodenal pump.
	4 class II studies;	Safe procedure in cognitively intact patients.
	comparison with best medical therapy	Dementia must be an exclusion criterion.
Perestelo-Pérez et al.²⁴24. Perestelo-Pérez L, Rivero-Santana A, Pérez-Ramos J, Serrano-Pérez P, Panetta J, Hilarion P. Deep brain stimulation in Parkinson’s disease: meta-analysis of randomized controlled trials. J Neurol. 2014 Nov;261(11):2051-60. https://doi.org/10.1007/s00415-014-7254-6 https://doi.org/10.1007/s00415-014-7254-...	6 randomized controlled trials (n = 1184)	DBS improved QoL, motor symptoms and disability. Strong effects for OFF motor signs and disability. Reduces levodopa daily dosing and motor complications. Moderate effect for ON motor signs, time without disability in ON.
Liu et al.²⁵25. Liu Y, Li W, Tan C, Liu X, Wang X, Gui Y et al. Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease. J Neurosurg. 2014 Sep;121(3):709-18. https://doi.org/10.3171/2014.4.JNS131711 https://doi.org/10.3171/2014.4.JNS131711...	6 trials (n = 563), comparing GPi and STN as targets	STN and GPi DBS equally improved UPDRS part II and III.
	6 trials (n = 563), comparing GPi and STN as targets	GPi DBS: greater improvement in depression scores.
Mansouri et al.²⁶26. Mansouri A, Taslimi S, Badhiwala JH, Witiw CD, Nassiri F, Odekerken VJJ et al. Deep brain stimulation for Parkinson’s disease: meta-analysis of results of randomized trials at varying lengths of follow-up. J Neurosurg. 2018 Apr;128(4):1199-213. https://doi.org/10.3171/2016.11.JNS16715 https://doi.org/10.3171/2016.11.JNS16715...	13 studies (6 original trial cohorts), with follow-up for 6, 12, 24 and 36 months	Motor scores and QoL: long-term benefits are similar between both targets (GPi or STN);
		STN DBS: lower medication dosage;
		GPi DBS: better outcomes in Beck Depression Inventory.

Authors, year	Institution	Country	Surgical eligibility	Ineligibility	Recommendations
Pahwa et al.²⁷27. Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H et al. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr;66(7):983-95. https://doi.org/10.1212/01.wnl.0000215250.82576.87 https://doi.org/10.1212/01.wnl.000021525...	American Academy of Neurology (AAN).	USA	Response in levodopa challenge test is an outcome predictor for STN DBS (Evidence level B).	Not addressed	STN DBS could be offered as a therapeutic option to improve motor function and reduce dyskinesia, motor fluctuations and medication dosage (level C).
Lang et al.²⁸28. Lang AE, Houeto JL, Krack P, Kubu C, Lyons KE, Moro E et al. Deep brain stimulation: preoperative issues. Mov Disord. 2006 Jun;21(S14 Suppl 14):S171-96. https://doi.org/10.1002/mds.20955 https://doi.org/10.1002/mds.20955...	International Parkinson and Movement Disorder Society (MDS);	Diverse	Defined PD diagnosis; levodopa responsive; significant functional impairment;	Age does not predict outcome.	Mandatory preoperative MRI.
	Congress of Neurological Surgeons		UPDRS-III > 30 in OFF time and UPDRS-III < 30 in ON time;	Trials have excluded patients with comorbidities.	STB DBS could impair verbal fluency, induce psychiatric side effects (depression, hypomania, dopaminergic dysregulation syndrome, suicide risk)
			Individualized decision; evaluate interpersonal relations, work situation, expectations;	Active depression, suicidal ideation history, psychosis, bipolar disorder, medication abuse history, unable to give informed consent.	Psychiatric and neuropsychological evaluation is mandatory before surgery.
			Disease progression for, at least, 5 years.		Vim thalamic DBS could be considered if tremor is more important than rigidity or bradykinesia.
Bronstein et al.²⁹29. Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A et al. Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Arch Neurol. 2011 Feb;68(2):165. https://doi.org/10.1001/archneurol.2010.260 https://doi.org/10.1001/archneurol.2010....	Multi-institutional	Diverse	PD diagnosis for, at least, 5 years;	Dementia;	-
			dyskinesia, tremor or fluctuations refractory to best medical therapy.	Active psychiatric disorder
			> 30% improvement in UPDRS-III in the levodopa test;
Fox et al.³⁰30. Fox SH, Katzenschlager R, Lim SY, Ravina B, Seppi K, Coelho M et al. The movement disorder society evidence-based medicine review update: treatments for the motor symptoms of Parkinson’s disease. Mov Disord. 2011 Oct;26(S3 Suppl 3):S2-41. https://doi.org/10.1002/mds.23829 https://doi.org/10.1002/mds.23829...	International Parkinson and Movement Disorders Society (MDS)	Diverse	Not addressed	Not addressed	STN DBS is effective for dyskinesia and motor fluctuation;
		Diverse	Not addressed	Not addressed	GPi DBS is effective for motor symptoms, as an adjunct to levodopa, and to treat dyskinesia and motor fluctuations.
Rieder et al.³¹31. Rieder CR, Silva DJ. Indicações de tratamento cirúrgico na doença de Parkinson. In: Dias-Tosta E, Rieder CRM, Borges V, Correa-Neto Y. Doença de Parkinson: recomendações. São Paulo: Omnifarma, 2010. p. 129-39.	Academia Brasileira de Neurologia (ABN)	Brazil	Defined PD diagnosis, lasting at least 5 years;	Dementia;	Class B recommendation
			Levodopa-responsive (> 25-50% improvement in UPDRS-III) (with the exception of tremor);	Active psychiatric disorder (depression and psychosis);
			Unsatisfactory symptom improvement with best medical therapy (dyskinesia, tremor or fluctuations)	Significant brain atrophy,
			Easy access to the medical centre;	Significant ventricle enlargement.
			Intolerance to dopaminergic therapy;
Ferreira et al.³²32. Ferreira JJ, Katzenschlager R, Bloem BR, Bonuccelli U, Burn D, Deuschl G et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease. Eur J Neurol. 2013 Jan;20(1):5-15. https://doi.org/10.1111/j.1468-1331.2012.03866.x https://doi.org/10.1111/j.1468-1331.2012...	European Federation of Neurological Societies (EFNS)	Europe	Defined PD; severe motor fluctuations, unpredictable ON-OFF, dyskinesia*;	Exclude patients with advanced age (>70 y);	STN DBS: level A for reducing dopaminergic drug dosage;
			* There was no reference to disease duration, levodopa response.	Major cognitive or psychiatric disorder.	GPi DBS: level A for reducing severe dyskinesias;
					STN or GPi DBS: level A for treating severe dyskinesia or motor fluctuations;
					Slight decline in executive functions may occur (Stroop test and verbal fluency).

GPi	STN
May be indicated in cases with mild cognitive impairment	Intact cognition
Severe dyskinesias induced by relatively low doses of levodopa	Severe motor fluctuations on high doses of levodopa
On-period dystonia	Off-period dystonia
Levodopa responsive non-motor signs, including mood and behavior (levodopa reduction is not desirable)	Side effects with dopaminergic medications requiring reduction of levodopa dose
Usually less laborious postoperative programming	Usually requires less energy usage, delaying implantable pulse generator replacement

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