Abstract
In Parkinson’s disease (PD), slow gait speed is significantly related to clinical ratings of disease severity, impaired performance of daily activities, as well as increased overall disability. Conducting a meta-analysis on gait speed is an objective and quantitative technique to summarize the effectiveness of DBS and to determine the effect sizes for future studies. We conducted a systematic review and meta-analysis that analyzed the effects of deep brain stimulation (DBS) surgery on gait speed in patients with PD to gain fundamental insight into the nature of therapeutic effectiveness. A random effects model meta-analysis on 27 studies revealed a significant overall standardized mean difference medium effect size equal to 0.60 (SE = 0.06; p < 0.0001; Z = 10.58). Based on our synthesis of the 27 studies, we determined the following: (1) a significant and medium effect size indicating DBS improves gait speed; (2) DBS improved gait speed regardless of whether the patients were tested in the on or off medication state; (3) both bilateral and unilateral DBS led to gait speed improvement; (4) the effects of DBS on gait speed in the data collection sessions after surgery (DBS on vs. off) were comparable with data collection before surgery (before surgery vs. DBS after surgery); and (5) when evaluating the effects of DBS and medication on gait speed suprathreshold doses were comparable to normal dosages of medication and DBS. The current analysis provides objective evidence that both unilateral and bilateral DBS provide a therapeutic benefit on gait speed in persons with PD.
Similar content being viewed by others
References
Hass CJ, Malczak P, Nocera J, Stegemöller EL, Wagle Shukla A, Malaty I, Jacobson IV CE, Okun MS, McFarland N (2012) Quantitative normative gait data in a large cohort of ambulatory persons with Parkinson’s disease. PLoS One. doi:10.1371/journal.pone.0042337
Plummer-D’Amato P, Altmann LJ, Reilly K (2011) Dual-task effects of spontaneous speech and executive function on gait in aging: exaggerated effects in slow walkers. Gait Posture. doi:10.1016/j.gaitpost.2010.11.011
Hollman JH, McDade EM, Petersen RC (2011) Normative spatiotemporal gait parameters in older adults. Gait Posture. doi:10.1016/j.gaitpost.2011.03.024
Brusse KJ, Zimdars S, Zalewski KR, Steffen TM (2005) Testing functional performance in people with Parkinson disease. Phys Ther 85:134–141
Himann JE, Cunningham DA, Rechnitzer PA, Paterson DH (1988) Age-related changes in speed of walking. Med Sci Sports Exerc 20:161–166
White DK, Neogi T, Nevitt MC, Peloquin CE, Zhu Y, Boudreau RM, Cauley JA, Ferrucci L, Harris TB, Satterfield SM, Simonsick EM, Strotmeyer ES, Zhang Y (2013) Trajectories of gait speed predict mortality in well-functioning older adults: the Health Aging and Body Composition study. J Gerontol A Biol Sci Med Sci. doi:10.1093/gerona/gls197
Lim LI, van Wegen EE, de Goede CJ, Jones D, Rochester L, Hetherington V, Nieuwboer A, Willems AM, Kwakkel G (2005) Measuring gait and gait-related activities in Parkinson’s patients own home environment: a reliability, responsiveness and feasibility study. Parkinsonism Relat Disord 11:19–24
Morris ME, Matyas TA, Iansek R, Summers JJ (1996) Temporal stability of gait in Parkinson’s disease. Phys Ther 76:763–777
Studenski S, Perera S, Wallace D, Chandler JM, Duncan PW, Rooney E, Fox M, Guralnik JM (2003) Physical performance measures in the clinical setting. J Am Geriatr Soc 51:314–322
Elbers RG, van Wegen EE, Verhoef J, Kwakkel G (2013) Is gait speed a valid measure to predict community ambulation in patients with Parkinson’s disease? J Rehabil Med. doi:10.2340/16501977-1123
Ellis TD, Cavanaugh JT, Earhart GM, Ford MP, Foreman KB, Thackeray A, Thiese MS, Dibble LE (2016) Identifying clinical measures that most accurately reflect the progression of disability in Parkinson disease. Parkinsonism Relat Disord 25:65–71
Tan D, Danoudis M, McGinley J, Morris ME (2012) Relationships between motor aspects of gait impairments and activity limitations in people with Parkinson’s disease: a systematic review. Parkinsonism Relat Disord. doi:10.1016/j.parkreldis.2011.07.014
Nisenzon AN, Robinson ME, Bowers D, Banou E, Malaty I, Okun MS (2011) Measurement of patient-centered outcomes in Parkinson’s disease: what do patients really want from their treatment? Parkinsonism Relat Disord. doi:10.1016/j.parkreldis.2010.09.005
Borenstein M (2009) Introduction to meta-analysis. Wiley, Chichester
Rosenthal R (1995) Writing meta-analytic reviews. Psychol Bull 118:183–192
Rosenthal R, DiMatteo MR (2001) Meta-analysis: recent developments in quantitative methods for literature reviews. Annu Rev Psychol. doi:10.1146/annurev.psych.52.1.59
Rosenthal R, Hiller JB, Bornstein RF, Berry DT, Brunell-Neuleib S (2001) Meta-analytic methods, the Rorschach, and the MMPI. Psychol Assess 13:449–451
Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. doi:10.1002/jrsm.12
Hedges LV, Olkin I (1985) Statistical methods for meta-analysis. Academic Press, Orlando
Sutton AJ (2000) Methods for meta-analysis in medical research. Wiley, Chichester
Cumming G, Fidler F, Kalinowski P, Lai J (2012) The statistical recommendations of the american psychological association publication manual: effect sizes, confidence intervals, and meta-analysis. Aust J Psychol 64:138–146. doi:10.1111/j.1742-9536.2011.00037.x
Cohen J (1988) Statistical power analysis for the behavioral sciences. L. Erlbaum Associates, Hillsdale
Kelly VE, Israel SM, Samii A, Slimp JC, Goodkin R, Shumway-Cook A (2010) Assessing the effects of subthalamic nucleus stimulation on gait and mobility in people with Parkinson disease. Disabil Rehabil. doi:10.3109/09638280903374139
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. doi:10.1016/j.gaitpost.2010.07.012
Krystkowiak P, Blatt JL, Bourriez JL, Duhamel A, Perina M, Blond S, Guieu JD, Destee A, Defebvre L (2003) Effects of subthalamic nucleus stimulation and levodopa treatment on gait abnormalities in Parkinson disease. Arch Neurol 60:80–84
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ. doi:10.1136/bmj.327.7414.557
Higgins JP, Green S (2008) Cochrane handbook for systematic reviews of interventions. Wiley, New Jersey
Fanelli D (2009) How many scientists fabricate and falsify research? A systematic review and meta-analysis of survey data. PLoS ONE. doi:10.1371/journal.pone.0005738
Sterne JA, Egger M, Smith GD (2001) Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ 323:101–105
Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56:455–463
Rothstein H, Sutton AJ, Borenstein M (2005) Publication bias in meta-analysis: prevention, assessment and adjustments. Wiley, Hoboken, NJ
Piper M, Abrams GM, Marks Jr WJ (2005) Deep brain stimulation for the treatment of Parkinson’s disease: overview and impact on gait and mobility. NeuroRehabilitation
Liu W, McIntire K, Kim SH, Zhang J, Dascalos S, Lyons KE, Pahwa R (2005) Quantitative assessments of the effect of bilateral subthalamic stimulation on multiple aspects of sensorimotor function for patients with Parkinson’s disease. Parkinsonism Relat Disord 11:503–508
Faist M, Xie J, Kurz D, Berger W, Maurer C, Pollak P, Lucking CH (2001) Effect of bilateral subthalamic nucleus stimulation on gait in Parkinson’s disease. Brain 124:1590–1600
Xie J, Krack P, Benabid AL, Pollak P (2001) Effect of bilateral subthalamic nucleus stimulation on parkinsonian gait. J Neurol 248:1068–1072
Okun MS (2012) Deep-brain stimulation for Parkinson’s disease. N Engl J Med. doi:10.1056/NEJMct1208070
Alberts JL, Hass CJ, Vitek JL, Okun MS (2008) Are two leads always better than one: an emerging case for unilateral subthalamic deep brain stimulation in Parkinson’s disease. Exp Neurol. doi:10.1016/j.expneurol.2008.07.019
Taba HA, Wu SS, Foote KD, Hass CJ, Fernandez HH, Malaty IA, Rodriguez RL, Dai Y, Zeilman PR, Jacobson CE, Okun MS (2010) A closer look at unilateral versus bilateral deep brain stimulation: results of the National Institutes of Health COMPARE cohort. J Neurosurg. doi:10.3171/2010.8.JNS10312
Okun MS, Foote KD (2010) Parkinson’s disease DBS: what, when, who and why? The time has come to tailor DBS targets. Expert Rev Neurother 10:1847–1857
Bastian AJ, Kelly VE, Revilla FJ, Perlmutter JS, Mink JW (2003) Different effects of unilateral versus bilateral subthalamic nucleus stimulation on walking and reaching in Parkinson’s disease. Mov Disord. doi:10.1002/mds.10493
Chung SJ, Jeon SR, Kim SR, Sung YH, Lee MC (2006) Bilateral effects of unilateral subthalamic nucleus deep brain stimulation in advanced Parkinson’s disease. Eur Neurol 56:127–132
Germano IM, Gracies JM, Weisz DJ, Tse W, Koller WC, Olanow CW (2004) Unilateral stimulation of the subthalamic nucleus in Parkinson disease: a double-blind 12-month evaluation study. J Neurosurg. doi:10.3171/jns.2004.101.1.0036
Kumar R, Lozano AM, Sime E, Halket E, Lang AE (1999) Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation. Neurology 53:561–566
Tabbal SD, Ushe M, Mink JW, Revilla FJ, Wernle AR, Hong M, Karimi M, Perlmutter JS (2008) Unilateral subthalamic nucleus stimulation has a measurable ipsilateral effect on rigidity and bradykinesia in Parkinson disease. Exp Neurol. doi:10.1016/j.expneurol.2008.01.024
Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:1436–1438
Benabid AL, Chabardes S, Mitrofanis J, Pollak P (2009) Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol. doi:10.1016/S1474-4422(08)70291-6
Allert N, Volkmann J, Dotse S, Hefter H, Sturm V, Freund HJ (2001) Effects of bilateral pallidal or subthalamic stimulation on gait in advanced Parkinson’s disease. Mov Disord. doi:10.1002/mds.1222
Goff LK, Jouve L, Melon C, Salin P (2009) Rationale for targeting the thalamic centre-median parafascicular complex in the surgical treatment of Parkinson’s disease. Parkinsonism Relat Disord. doi:10.1016/S1353-8020(09)70807-7
Plaha P, Khan S, Gill SS (2008) Bilateral stimulation of the caudal zona incerta nucleus for tremor control. J Neurol Neurosurg Psychiatry. (jnnp.2006.112334 [pii])
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. doi:10.1016/j.gaitpost.2014.05.002
References marked with an asterisk indicate studies included in the meta-analysis. Asterisks do not precede the in-text citations to studies
*Carpinella I, Crenna P, Marzegan A, Rabuffetti M, Rizzone M, Lopiano L, Ferrarin M (2007) Effect of L-dopa and subthalamic nucleus stimulation on arm and leg swing during gait in Parkinson’s Disease. Conf Proc IEEE Eng Med Biol Soc. doi:10.1109/IEMBS.2007.4353888
*Fasano A, Herzog J, Seifert E, Stolze H, Falk D, Reese R, Volkmann J, Deuschl G (2011) Modulation of gait coordination by subthalamic stimulation improves freezing of gait. Mov Disord. doi:10.1002/mds.23583
*Ferrarin M, Rizzone M, Lopiano L, Recalcati M, Pedotti A (2004) Effects of subthalamic nucleus stimulation and L-dopa in trunk kinematics of patients with Parkinson’s disease. Gait Posture. doi:10.1016/S0966-6362(03)00058-4
*Ferrarin M, Rizzone M, Bergamasco B, Lanotte M, Recalcati M, Pedotti A, Lopiano L (2005) Effects of bilateral subthalamic stimulation on gait kinematics and kinetics in Parkinson’s disease. Exp Brain Res. doi:10.1007/s00221-004-2036-5
*Ferrarin M, Carpinella I, Rabuffetti M, Rizzone M, Lopiano L, Crenna P (2007) Unilateral and bilateral subthalamic nucleus stimulation in Parkinson’s disease: effects on EMG signals of lower limb muscles during walking. IEEE Trans Neural Syst Rehabil Eng. doi:10.1109/TNSRE.2007.897000
*Hausdorff JM, Gruendlinger L, Scollins L, O’Herron S, Tarsy D (2009) Deep brain stimulation effects on gait variability in Parkinson’s disease. Mov Disord. doi:10.1002/mds.22554
*Hill KK, Campbell MC, McNeely ME, Karimi M, Ushe M, Tabbal SD, Hershey T, Flores HP, Hartlein JM, Lugar HM, Revilla FJ, Videen TO, Earhart GM, Perlmutter JS (2013) Cerebral blood flow responses to dorsal and ventral STN DBS correlate with gait and balance responses in Parkinson’s disease. Exp Neurol. doi:10.1016/j.expneurol.2012.12.003
* Iansek R, Rosenfeld JV, Huxham FE (2002) Deep brain stimulation of the subthalamic nucleus in Parkinson’s disease. Med J Aust. (ian10553_fm [pii])
*Johnsen EL, Mogensen PH, Sunde NA, Ostergaard K (2009) Improved asymmetry of gait in Parkinson’s disease with DBS: gait and postural instability in Parkinson’s disease treated with bilateral deep brain stimulation in the subthalamic nucleus. Mov Disord. doi:10.1002/mds.22419
*Johnsen EL, Sunde N, Mogensen PH, Ostergaard K (2010) MRI verified STN stimulation site–gait improvement and clinical outcome. Eur J Neurol. doi:10.1111/j.1468-1331.2010.02962.x
*Lohnes CA, Earhart GM (2012) Effect of subthalamic deep brain stimulation on turning kinematics and related saccadic eye movements in Parkinson disease. Exp Neurol. doi:10.1016/j.expneurol.2012.05.001
*Lubik S, Fogel W, Tronnier V, Krause M, Konig J, Jost WH (2006) Gait analysis in patients with advanced Parkinson disease: different or additive effects on gait induced by levodopa and chronic STN stimulation. J Neural Transm. doi:10.1007/s00702-005-0310-8
*McNeely ME, Hershey T, Campbell MC, Tabbal SD, Karimi M, Hartlein JM, Lugar HM, Revilla FJ, Perlmutter JS, Earhart GM (2011) Effects of deep brain stimulation of dorsal versus ventral subthalamic nucleus regions on gait and balance in Parkinson’s disease. J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp.2010.232900
*Muniz AM, Liu H, Lyons KE, Pahwa R, Liu W, Nadal J (2010) Quantitative evaluation of the effects of subthalamic stimulation on gait in Parkinson’s disease patients using principal component analysis. Int J Neurosci. doi:10.3109/00207454.2010.504904
*Rocchi L, Carlson-Kuhta P, Chiari L, Burchiel KJ, Hogarth P, Horak FB (2012) Effects of deep brain stimulation in the subthalamic nucleus or globus pallidus internus on step initiation in Parkinson disease: laboratory investigation. J Neurosurg. doi:10.3171/2012.8.JNS112006
*Rochester L, Chastin SF, Lord S, Baker K, Burn DJ (2012) Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson’s disease. J Neurol. doi:10.1007/s00415-011-6301-9
*Seri-Fainshtat E, Israel Z, Weiss A, Hausdorff JM (2013) Impact of sub-thalamic nucleus deep brain stimulation on dual tasking gait in Parkinson’s disease. J Neuroeng Rehabil. doi:10.1186/1743-0003-10-38
*Stolze H, Klebe S, Poepping M, Lorenz D, Herzog J, Hamel W, Schrader B, Raethjen J, Wenzelburger R, Mehdorn HM, Deuschl G, Krack P (2001) Effects of bilateral subthalamic nucleus stimulation on parkinsonian gait. Neurology
Vallabhajosula S, Haq IU, Hwynn N, Oyama G, Okun M, Tillman MD, Hass CJ (2015) Low-frequency versus high-frequency subthalamic nucleus deep brain stimulation on postural control and gait in Parkinson’s disease: a quantitative study. Brain Stimul 8:64–75. doi:10.1016/j.brs.2014.10.011
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Full financial disclosure for the past 12 months: JAR, NK, JB, JHC, and CJH do not have any disclosures. MSO serves as a consultant for the National Parkinson Foundation, and has received research Grants from NIH, NPF, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. Dr. Okun has previously received honoraria, but in the past >60 months has received no support from industry. Dr. Okun has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, and Cambridge (movement disorders books). Dr. Okun is an associate editor for New England Journal of Medicine Journal Watch Neurology. Dr. Okun has participated in CME and educational activities on movement disorders (in the last 36) months sponsored by PeerView, Prime, Quantia, Henry Stewart, and by Vanderbilt University. The institution and not Dr. Okun receives grants from Medtronic, Abbvie, and ANS/St. Jude, and the PI has no financial interest in these grants. Dr. Okun has participated as a site PI and/or co-I for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria.
Ethical standards
The manuscript does not contain clinical studies or patient data.
Rights and permissions
About this article
Cite this article
Roper, J.A., Kang, N., Ben, J. et al. Deep brain stimulation improves gait velocity in Parkinson’s disease: a systematic review and meta-analysis. J Neurol 263, 1195–1203 (2016). https://doi.org/10.1007/s00415-016-8129-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-016-8129-9