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Eur Neurol 2013;69:281-288

Levodopa-Resistant Freezing of Gait and Executive Dysfunction in Parkinson's Disease

Ferraye M.U.a,b,d · Ardouin C.c · Lhommée E.c · Fraix V.a-c · Krack P.a-c · Chabardès S.a-c · Seigneuret E.b, c · Benabid A-L.a-c · Pollak P.a-c · Debû B.a,b

Author affiliations

aUniversité J. Fourier Grenoble 1, bINSERM, U836, Grenoble Institut des Neurosciences, cCentre Hospitalier Universitaire de Grenoble, Grenoble, France, and dCentre for Cognitive Neuroimaging, Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands

Corresponding Author

Murielle Ferraye

Université J. Fourier Grenoble 1, INSERM, U836

CHU de Grenoble, Pavillon de neurologie, BP 217

FR-38043 Grenoble Cedex 9 (France)

E-Mail murielle.ferraye@fcdonders.ru.nl

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We examined executive functioning in patients with Parkinson's disease exhibiting, or not, levodopa-resistant freezing of gait (L-FOG). 38 advanced-stage patients with L-FOG were identified in a consecutive series of 400 patients. They were matched with 38 patients without L-FOG. All patients underwent prospective evaluations of cognitive and motor functioning before subthalamic nucleus surgery, and 1 year after. A composite frontal score, a measure of executive functioning, was compared between the two groups. We also examined correlations between the frontal score and the score on the FOG item of the Unified Parkinson Disease Rating Scale II. Results show that after surgery, patients with L-FOG, as a group, were more impaired in executive functioning than control patients. However, individual data analysis showed preserved executive functions in 11 patients with L-FOG. In addition, there was no correlation between L-FOG severity and the degree of executive impairment. Therefore, frontal dysfunction may be one mechanism underlying L-FOG in a number of patients with Parkinson's disease. However, since some patients develop L-FOG despite the preservation of executive functions, lesions or dysfunction of other neuronal structures are likely to be involved.

© 2013 S. Karger AG, Basel


  1. Amboni M, Barone P, Picillo M, et al: A two-year follow-up study of executive dysfunctions in parkinsonian patients with freezing of gait at on-state. Mov Disord 2010;25:800-802.
  2. Amboni M, Cozzolino A, Longo K, Picillo M, Barone P: Freezing of gait and executive functions in patients with Parkinson's disease. Mov Disord 2008;23:395-400.
  3. Naismith SL, Shine JM, Lewis SJ: The specific contributions of set-shifting to freezing of gait in Parkinson's disease. Mov Disord 2010;25:1000-1004.
  4. Giladi N, Nieuwboer A: Understanding and treating freezing of gait in parkinsonism, proposed working definition, and setting the stage. Mov Disord 2008;23(suppl 2):S423-S425.
  5. Moore O, Peretz C, Giladi N: Freezing of gait affects quality of life of peoples with Parkinson's disease beyond its relationships with mobility and gait. Mov Disord 2007;22:2192-2195.
  6. Ferraye MU, Debu B, Fraix V, et al: Effects of subthalamic nucleus stimulation and levodopa on freezing of gait in Parkinson's disease. Neurology 2008;70:1431-1437.
  7. Krack P, Batir A, Van Blercom N, et al: Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 2003;349:1925-1934.
  8. Deep-Brain Stimulation for Parkinson's Disease Study Group: Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease. N Engl J Med 2001;345:956-963.
  9. Nelson HE: A modified card sorting test sensitive to frontal lobe defects. Cortex 1976;12:313-324.
    External Resources
  10. Cardebat D, Doyon B, Puel M, Goulet P, Joanette Y: Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level (in French). Acta Neurol Belg 1990;90:207-217.
    External Resources
  11. Ardouin C, Pillon B, Peiffer E, et al: Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: a consecutive series of 62 patients. Ann Neurol 1999;46:217-223.
  12. Luria AR: Higher Cortical Functions in Man. London, Tavistock Publications, 1966.
  13. Pillon B, Ardouin C, Damier P, et al: Neuropsychological changes between ‘off' and ‘on' STN or GPi stimulation in Parkinson's disease. Neurology 2000;55:411-418.
  14. Dubois B, Pillon B, Legault F, Agid Y, Lhermitte F: Slowing of cognitive processing in progressive supranuclear palsy. A comparison with Parkinson's disease. Arch Neurol 1988;45:1194-1199.
  15. Bonnet AM, Loria Y, Saint-Hilaire MH, Lhermitte F, Agid Y: Does long-term aggravation of Parkinson's disease result from non-dopaminergic lesions? Neurology 1987;37:1539-1542.
  16. Hashimoto T: Speculation on the responsible sites and pathophysiology of freezing of gait. Parkinsonism Relat Disord 2006;12:S55-S62.
    External Resources
  17. Factor SA: The clinical spectrum of freezing of gait in atypical parkinsonism. Mov Disord 2008;23(suppl 2):S431-S438.
  18. Giladi N, Huber-Mahlin V, Herman T, Hausdorff JM: Freezing of gait in older adults with high level gait disorders: association with impaired executive function. J Neural Transm 2007;114:1349-1353.
  19. Giladi N, McDermott MP, Fahn S, et al: Freezing of gait in PD: prospective assessment in the DATATOP cohort. Neurology 2001;56:1712-1721.
    External Resources
  20. Yogev-Seligmann G, Hausdorff JM, Giladi N: The role of executive function and attention in gait. Mov Disord 2008;23:329-342.
  21. Lees AJ, Smith E: Cognitive deficits in the early stages of Parkinson's disease. Brain 1983;106:257-270.
  22. Almeida QJ, Lebold CA: Freezing of gait in Parkinson's disease: a perceptual cause for a motor impairment? J Neurol Neurosurg Psychiatry 2010;81:513-518.
  23. Cowie D, Limousin P, Peters A, Day BL: Insights into the neural control of locomotion from walking through doorways in Parkinson's disease. Neuropsychologia 2010;48:2750-2757.
  24. Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A: Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol 2011;10:734-744.
  25. Nandi D, Aziz TZ, Giladi N, Winter J, Stein JF: Reversal of akinesia in experimental parkinsonism by GABA antagonist microinjections in the pedunculopontine nucleus. Brain 2002;125:2418-2430.
  26. Kuo SH, Kenney C, Jankovic J: Bilateral pedunculopontine nuclei strokes presenting as freezing of gait. Mov Disord 2008;23:616-619.
  27. Ferraye MU, Debu B, Fraix V, et al: Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease. Brain 2010;133:205-214.
  28. Moro E, Hamani C, Poon YY, et al: Unilateral pedunculopontine stimulation improves falls in Parkinson's disease. Brain 2010;133:215-224.
  29. Stefani A, Lozano AM, Peppe A, et al: Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease. Brain 2007;130:1596-1607.
  30. Jahn K, Deutschlander A, Stephan T, et al: Imaging human supraspinal locomotor centers in brainstem and cerebellum. Neuroimage 2008;39:786-792.
  31. Piallat B, Chabardes S, Torres N, et al: Gait is associated with an increase in tonic firing of the sub-cuneiform nucleus neurons. Neuroscience 2009;158:1201-1205.
  32. Snijders AH, Leunissen I, Bakker M, et al: Gait-related cerebral alterations in patients with Parkinson's disease with freezing of gait. Brain 2011;134:59-72.
  33. Bohnen NI, Muller ML, Koeppe RA, et al: History of falls in Parkinson's disease is associated with reduced cholinergic activity. Neurology 2009;73:1670-1676.
  34. Parsons TD, Rogers SA, Braaten AJ, Woods SP, Troster AI: Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson's disease: a meta-analysis. Lancet Neurol 2006;5:578-588.
  35. Witt K, Daniels C, Reiff J, et al: Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson's disease: a randomised, multicentre study. Lancet Neurol 2008;7:605-614.
  36. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG: The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord 2008;23:837-844.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 19, 2012
Accepted: December 05, 2012
Published online: February 27, 2013

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 1

ISSN: 0014-3022 (Print)
eISSN: 1421-9913 (Online)

For additional information: https://www.karger.com/ENE