Efficacy of caudal pedunculopontine nucleus stimulation on postural instability and gait disorders in Parkinson's disease.

Kaijia Yu, Zhiwei Ren, Yongsheng Hu, Song Guo, Xiaofan Ye, Jianyu Li, Yongjie Li
Author Information
  1. Kaijia Yu: Beijing Institute of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.
  2. Zhiwei Ren: Beijing Institute of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.
  3. Yongsheng Hu: Beijing Institute of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.
  4. Song Guo: Beijing Institute of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.
  5. Xiaofan Ye: Department of Neurosurgery, The University of Hong Kong - Shenzhen Hospital, Shenzhen, 518040, China.
  6. Jianyu Li: Beijing Institute of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China. ljy83198671@163.com.
  7. Yongjie Li: Beijing Institute of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.

Abstract

OBJECTIVES: Gait-related symptoms like postural instability and gait disorders (PIGD) inexorably worsen with Parkinson's disease (PD) deterioration and become refractory to current available medical treatment and deep brain stimulation (DBS) of conventional targets. Pedunculopontine nucleus (PPN) deep brain stimulation (DBS) is a promising method to treat PIGD. This prospective study aimed to clarify the clinical application of PPN-DBS and to explore effects of caudal PPN stimulation on PIGD.
METHODS: Five consecutive PD patients with severe medication-resistant postural instability and gait disorders accepted caudal PPN-DBS. LEAD-DBS toolbox was used to reconstruct and visualize the electrodes based on pre- and postoperative images. Outcomes were assessed with Movement Disorder Society (MDS)-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), gait-specific questionnaires, and objective gait analysis with GAITRite system.
RESULTS: MDS-UPDRS subitems 35-38 scores were improved at postoperative 6 months (mean, 4.40 vs 11.00; p = 0.0006) and 12 months (mean, 5.60 vs 11.00; p = 0.0013) compared with baseline, and scores at 6 months were slightly lower than scores at 12 months (mean, 4.40 vs 5.60; p = 0.0116). Gait and Falls Questionnaire, New Freezing of Gait Questionnaire, and Falls Questionnaire scores also significantly improved at postoperative 6 months and 12 months compared with baseline. In addition, cadence, bilateral step length, and bilateral stride length significantly increased when PPN On-stimulation compared with Off-stimulation.
CONCLUSIONS: This study suggested that caudal PPN low-frequency stimulation improved PIGD for PD patients at the 6- and 12-month period.

Keywords

References

  1. Bekkers EMJ, Dijkstra BW, Dockx K, Heremans E, Verschueren SMP, Nieuwboer A (2017) Clinical balance scales indicate worse postural control in people with Parkinson’s disease who exhibit freezing of gait compared to those who do not: a meta-analysis. Gait Posture 56:134–140. https://doi.org/10.1016/j.gaitpost.2017.05.009 [DOI: 10.1016/j.gaitpost.2017.05.009]
  2. Bilney B, Morris M, Webster K (2003) Concurrent related validity of the GAITRite walkway system for quantification of the spatial and temporal parameters of gait. Gait Posture 17:68–74. https://doi.org/10.1016/s0966-6362(02)00053-x [DOI: 10.1016/s0966-6362(02)00053-x]
  3. Bloem BR, Hausdorff JM, Visser JE, Giladi N (2004) Falls and freezing of gait in Parkinson’s disease: a review of two interconnected, episodic phenomena. Mov Disord 19:871–884. https://doi.org/10.1002/mds.20115 [DOI: 10.1002/mds.20115]
  4. Bohnen NI, Muller ML, Koeppe RA, Studenski SA, Kilbourn MA, Frey KA, Albin RL (2009) History of falls in Parkinson disease is associated with reduced cholinergic activity. Neurology 73:1670–1676. https://doi.org/10.1212/WNL.0b013e3181c1ded6 [DOI: 10.1212/WNL.0b013e3181c1ded6]
  5. Brudzynski SM, Houghton PE, Brownlee RD, Mogenson GJ (1986) Involvement of neuronal cell bodies of the mesencephalic locomotor region in the initiation of locomotor activity of freely behaving rats. Brain Res Bull 16:377–381. https://doi.org/10.1016/0361-9230(86)90059-6 [DOI: 10.1016/0361-9230(86)90059-6]
  6. Caliandro P, Insola A, Scarnati E, Padua L, Russo G, Granieri E, Mazzone P (2011) Effects of unilateral pedunculopontine stimulation on electromyographic activation patterns during gait in individual patients with Parkinson’s disease. J Neural Transm (Vienna) 118:1477–1486. https://doi.org/10.1007/s00702-011-0705-7 [DOI: 10.1007/s00702-011-0705-7]
  7. de Lima-Pardini AC, de Azevedo Neto RM, Coelho DB, Boffino CC, Shergill SS, de Oliveira SC, Brant R, Barbosa ER, Cardoso EF, Teixeira LA, Cohen RG, Horak FB, Amaro E Jr (2017) An fMRI-compatible force measurement system for the evaluation of the neural correlates of step initiation. Sci Rep 7:43088. https://doi.org/10.1038/srep43088 [DOI: 10.1038/srep43088]
  8. Ferraye MU, Debu B, Fraix V, Goetz L, Ardouin C, Yelnik J, Henry-Lagrange C, Seigneuret E, Piallat B, Krack P, Le Bas JF, Benabid AL, Chabardes S, Pollak P (2010) Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson’s disease. Brain 133:205–214. https://doi.org/10.1093/brain/awp229 [DOI: 10.1093/brain/awp229]
  9. Fonoff ET, de Lima-Pardini AC, Coelho DB, Monaco BA, Machado B, Pinto de Souza C, Dos Santos Ghilardi MG, Hamani C (2019) Spinal cord stimulation for freezing of gait: from bench to bedside. Front Neurol 10:905. https://doi.org/10.3389/fneur.2019.00905 [DOI: 10.3389/fneur.2019.00905]
  10. Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA (2009) Spinal cord stimulation restores locomotion in animal models of Parkinson’s disease. Science 323:1578–1582. https://doi.org/10.1126/science.1164901 [DOI: 10.1126/science.1164901]
  11. Giladi N, Nieuwboer A (2008) Understanding and treating freezing of gait in parkinsonism, proposed working definition, and setting the stage. Mov Disord 23(Suppl 2):S423-425. https://doi.org/10.1002/mds.21927 [DOI: 10.1002/mds.21927]
  12. Hamani C, Stone S, Laxton A, Lozano AM (2007) The pedunculopontine nucleus and movement disorders: anatomy and the role for deep brain stimulation. Parkinsonism Relat Disord 13(Suppl 3):S276-280. https://doi.org/10.1016/S1353-8020(08)70016-6 [DOI: 10.1016/S1353-8020(08)70016-6]
  13. Horn A, Li N, Dembek TA, Kappel A, Boulay C, Ewert S, Tietze A, Husch A, Perera T, Neumann WJ, Reisert M, Si H, Oostenveld R, Rorden C, Yeh FC, Fang Q, Herrington TM, Vorwerk J, Kuhn AA (2019) Lead-DBS v2: towards a comprehensive pipeline for deep brain stimulation imaging. Neuroimage 184:293–316. https://doi.org/10.1016/j.neuroimage.2018.08.068 [DOI: 10.1016/j.neuroimage.2018.08.068]
  14. Hwang YI, An DH, Yoo WG (2012) Effects of the Dual AFO on gait parameters in stroke patients. NeuroRehabilitation 31:387–393. https://doi.org/10.3233/NRE-2012-00808 [DOI: 10.3233/NRE-2012-00808]
  15. Karachi C, Grabli D, Bernard FA, Tande D, Wattiez N, Belaid H, Bardinet E, Prigent A, Nothacker HP, Hunot S, Hartmann A, Lehericy S, Hirsch EC, Francois C (2010) Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease. J Clin Invest 120:2745–2754. https://doi.org/10.1172/JCI42642 [DOI: 10.1172/JCI42642]
  16. Lavoie B, Parent A (1994) Pedunculopontine nucleus in the squirrel monkey: projections to the basal ganglia as revealed by anterograde tract-tracing methods. J Comp Neurol 344:210–231. https://doi.org/10.1002/cne.903440204 [DOI: 10.1002/cne.903440204]
  17. Lee SM, Cynn HS, Yi CH, Yoon TL, Lee JH (2017) Wearable tubing assistive walking device immediately enhances gait parameters in subjects with stroke: a randomized controlled study. NeuroRehabilitation 40:99–107. https://doi.org/10.3233/NRE-161394 [DOI: 10.3233/NRE-161394]
  18. Mazzone P, Paoloni M, Mangone M, Santilli V, Insola A, Fini M, Scarnati E (2014) Unilateral deep brain stimulation of the pedunculopontine tegmental nucleus in idiopathic Parkinson’s disease: effects on gait initiation and performance. Gait Posture 40:357–362. https://doi.org/10.1016/j.gaitpost.2014.05.002 [DOI: 10.1016/j.gaitpost.2014.05.002]
  19. Mazzone P, Sposato S, Insola A, Scarnati E (2013) The clinical effects of deep brain stimulation of the pedunculopontine tegmental nucleus in movement disorders may not be related to the anatomical target, leads location, and setup of electrical stimulation. Neurosurgery 73:894–906. https://doi.org/10.1227/NEU.0000000000000108 (discussion 905-896) [DOI: 10.1227/NEU.0000000000000108]
  20. Mestre TA, Sidiropoulos C, Hamani C, Poon YY, Lozano AM, Lang AE, Moro E (2016) Long-term double-blinded unilateral pedunculopontine area stimulation in Parkinson’s disease. Mov Disord 31:1570–1574. https://doi.org/10.1002/mds.26710 [DOI: 10.1002/mds.26710]
  21. Milner KL, Mogenson GJ (1988) Electrical and chemical activation of the mesencephalic and subthalamic locomotor regions in freely moving rats. Brain Res 452:273–285. https://doi.org/10.1016/0006-8993(88)90031-5 [DOI: 10.1016/0006-8993(88)90031-5]
  22. Moore O, Peretz C, Giladi N (2007) Freezing of gait affects quality of life of peoples with Parkinson’s disease beyond its relationships with mobility and gait. Mov Disord 22:2192–2195. https://doi.org/10.1002/mds.21659 [DOI: 10.1002/mds.21659]
  23. Munhoz RP, Li JY, Kurtinecz M, Piboolnurak P, Constantino A, Fahn S, Lang AE (2004) Evaluation of the pull test technique in assessing postural instability in Parkinson’s disease. Neurology 62:125–127. https://doi.org/10.1212/wnl.62.1.125 [DOI: 10.1212/wnl.62.1.125]
  24. Nieuwboer A, Rochester L, Herman T, Vandenberghe W, Emil GE, Thomaes T, Giladi N (2009) Reliability of the New Freezing Of Gait Questionnaire: agreement between patients with Parkinson’s disease and their carers. Gait Posture 30:459–463. https://doi.org/10.1016/j.gaitpost.2009.07.108 [DOI: 10.1016/j.gaitpost.2009.07.108]
  25. Nowacki A, Galati S, Ai-Schlaeppi J, Bassetti C, Kaelin A, Pollo C (2019) Pedunculopontine nucleus: an integrative view with implications on deep brain stimulation. Neurobiol Dis 128:75–85. https://doi.org/10.1016/j.nbd.2018.08.015 [DOI: 10.1016/j.nbd.2018.08.015]
  26. Peppe A, Pierantozzi M, Chiavalon C, Marchetti F, Caltagirone C, Musicco M, Stanzione P, Stefani A (2010) Deep brain stimulation of the pedunculopontine tegmentum and subthalamic nucleus: effects on gait in Parkinson’s disease. Gait Posture 32:512–518. https://doi.org/10.1016/j.gaitpost.2010.07.012 [DOI: 10.1016/j.gaitpost.2010.07.012]
  27. Pienaar IS, Harrison IF, Elson JL, Bury A, Woll P, Simon AK, Dexter DT (2015) An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson’s disease. Brain Struct Funct 220:479–500. https://doi.org/10.1007/s00429-013-0669-5 [DOI: 10.1007/s00429-013-0669-5]
  28. Rinne JO, Ma SY, Lee MS, Collan Y, Roytta M (2008) Loss of cholinergic neurons in the pedunculopontine nucleus in Parkinson’s disease is related to disability of the patients. Parkinsonism Relat Disord 14:553–557. https://doi.org/10.1016/j.parkreldis.2008.01.006 [DOI: 10.1016/j.parkreldis.2008.01.006]
  29. Scelzo E, Lozano AM, Hamani C, Poon YY, Aldakheel A, Zadikoff C, Lang AE, Moro E (2017) Peduncolopontine nucleus stimulation in progressive supranuclear palsy: a randomised trial. J Neurol Neurosurg Psychiatry 88:613–616. https://doi.org/10.1136/jnnp-2016-315192 [DOI: 10.1136/jnnp-2016-315192]
  30. Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ (2009) A clinico-pathological study of subtypes in Parkinson’s disease. Brain 132:2947–2957. https://doi.org/10.1093/brain/awp234 [DOI: 10.1093/brain/awp234]
  31. Shinotoh H, Namba H, Yamaguchi M, Fukushi K, Nagatsuka S, Iyo M, Asahina M, Hattori T, Tanada S, Irie T (1999) Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson’s disease and progressive supranuclear palsy. Ann Neurol 46:62–69 [DOI: 10.1002/1531-8249(199907)46]
  32. Thevathasan W, Cole MH, Graepel CL, Hyam JA, Jenkinson N, Brittain JS, Coyne TJ, Silburn PA, Aziz TZ, Kerr G, Brown P (2012) A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation. Brain 135:1446–1454. https://doi.org/10.1093/brain/aws039 [DOI: 10.1093/brain/aws039]
  33. Thevathasan W, Coyne TJ, Hyam JA, Kerr G, Jenkinson N, Aziz TZ, Silburn PA (2011) Pedunculopontine nucleus stimulation improves gait freezing in Parkinson disease. Neurosurgery 69:1248–1253. https://doi.org/10.1227/NEU.0b013e31822b6f71 (discussion 1254) [DOI: 10.1227/NEU.0b013e31822b6f71]
  34. Thevathasan W, Debu B, Aziz T, Bloem BR, Blahak C, Butson C, Czernecki V, Foltynie T, Fraix V, Grabli D, Joint C, Lozano AM, Okun MS, Ostrem J, Pavese N, Schrader C, Tai CH, Krauss JK, Moro E, Movement Disorders Society PPNDBSWGcwtWSfS, Functional N (2018) Pedunculopontine nucleus deep brain stimulation in Parkinson’s disease: a clinical review. Mov Disord 33:10–20. https://doi.org/10.1002/mds.27098 [DOI: 10.1002/mds.27098]
  35. Welter ML, Demain A, Ewenczyk C, Czernecki V, Lau B, El Helou A, Belaid H, Yelnik J, Francois C, Bardinet E, Karachi C, Grabli D (2015) PPNa-DBS for gait and balance disorders in Parkinson’s disease: a double-blind, randomised study. J Neurol 262:1515–1525. https://doi.org/10.1007/s00415-015-7744-1 [DOI: 10.1007/s00415-015-7744-1]
  36. Yu K, Ren Z, Guo S, Li J, Li Y (2020) Effects of pedunculopontine nucleus deep brain stimulation on gait disorders in Parkinson’s disease: a meta-analysis of the literature. Clin Neurol Neurosurg 198:106108. https://doi.org/10.1016/j.clineuro.2020.106108 [DOI: 10.1016/j.clineuro.2020.106108]
  37. Zrinzo L, Zrinzo LV, Hariz M (2007) The pedunculopontine and peripeduncular nuclei: a tale of two structures. Brain 130. https://doi.org/10.1093/brain/awm079 (author reply e74) [DOI: 10.1093/brain/awm079]
  38. Zrinzo L, Zrinzo LV, Tisch S, Limousin PD, Yousry TA, Afshar F, Hariz MI (2008) Stereotactic localization of the human pedunculopontine nucleus: atlas-based coordinates and validation of a magnetic resonance imaging protocol for direct localization. Brain 131:1588–1598. https://doi.org/10.1093/brain/awn075 [DOI: 10.1093/brain/awn075]

MeSH Term

Deep Brain Stimulation
Gait
Gait Disorders, Neurologic
Humans
Parkinson Disease
Pedunculopontine Tegmental Nucleus
Prospective Studies

Word Cloud

Created with Highcharts 10.0.0stimulationgaitPIGDPPNcaudalscoresposturalinstabilitydisordersParkinson'sdiseasePDbrainnucleuspostoperativeimproved6 monthsmeanvsp = 012 monthscomparedGaitQuestionnairedeepDBSPedunculopontinestudyPPN-DBSpatientsLEAD-DBSMDS-UPDRS4401100560baselineFallssignificantlybilaterallengthOBJECTIVES:Gait-relatedsymptomslikeinexorablyworsendeteriorationbecomerefractorycurrentavailablemedicaltreatmentconventionaltargetspromisingmethodtreatprospectiveaimedclarifyclinicalapplicationexploreeffectsMETHODS:Fiveconsecutiveseveremedication-resistantacceptedtoolboxusedreconstructvisualizeelectrodesbasedpre-imagesOutcomesassessedMovementDisorderSocietyMDS-SponsoredRevisionUnifiedDiseaseRatingScalegait-specificquestionnairesobjectiveanalysisGAITRitesystemRESULTS:subitems35-3800060013slightlylower0116NewFreezingalsoadditioncadencestepstrideincreasedOn-stimulationOff-stimulationCONCLUSIONS:suggestedlow-frequency6-12-monthperiodEfficacypedunculopontineDeepParkinson’s

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