Summary.
Treatment-related motor fluctuations (MFs) and dyskinesias are considered one of the most important problems in the long-term management of Parkinson’s disease (PD). However, only a few studies have focused on their characteristics during advanced and end stages of the disease. We therefore assessed MFs and dyskinesias in a cohort of 61 late/end stage patients with a clinical and pathological diagnosis of PD and investigated the influence of disease- and treatment-related variables on their occurrence. A total of 62.3% of our patients experienced “wearing-off” phenomena, 68.9% “on-off” motor fluctuations and 60.7% dyskinesias at advanced/end stage disease. Age at disease onset and disease duration were significantly associated with dyskinesias. A substantial number of patients experienced spontaneous resolution of their motor complications during the last two years of their disease without treatment modifications.
The clinical heterogeneity of treatment-related motor complications in PD points towards a complex mechanism for their etiopathogenesis. Although advanced disease and L-dopa administration are closely tied to their development, other mechanisms involving synaptic aging, altered neuronal plasticity and post-synaptic degeneration may be involved.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
JE Ahlskog MD Muenter (2001) ArticleTitleFrequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature Mov Disord 16 448–458 Occurrence Handle11391738 Occurrence Handle10.1002/mds.1090 Occurrence Handle1:STN:280:DC%2BD3MzitVCmtg%3D%3D
B Bokobza M Ruberg B Scatton F Javoy-Agid Y Agid (1984) ArticleTitle[3H]spiperone binding, dopamine and HVA concentrations in Parkinson’s disease and supranuclear palsy Eur J Pharmacol 99 167–175 Occurrence Handle6734727 Occurrence Handle10.1016/0014-2999(84)90238-3 Occurrence Handle1:STN:280:BiuB3snksVw%3D
T Brannan MD Yahr (1995) ArticleTitleComparative study of selegiline plus L-dopa-carbidopa vs L-dopa-carbidopa alone in the treatment of Parkinson’s disease Ann Neurol 37 95–98 Occurrence Handle7818264 Occurrence Handle10.1002/ana.410370117 Occurrence Handle1:STN:280:ByqC3MfgsVA%3D
JM Cedarbaum SE Gandy FH McDowell (1991) ArticleTitle“Early” initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias, or dementia in Parkinson’s disease Neurology 41 622–629 Occurrence Handle2027475 Occurrence Handle1:STN:280:By6B38nmsFc%3D
R Cortes M Camps B Gueye A Probst JM Palacios (1989) ArticleTitleDopamine receptors in human brain: autoradiographic distribution of D1 and D2 sites in Parkinson syndrome of different etiology Brain Res 483 30–38 Occurrence Handle2650806 Occurrence Handle10.1016/0006-8993(89)90031-0 Occurrence Handle1:CAS:528:DyaL1MXhvFSgtLo%3D
F Grandas ML Galiano C Tabernero (1999) ArticleTitleRisk factors for levodopa-induced dyskinesias in Parkinson’s disease J Neurol 246 1127–1133 Occurrence Handle10653303 Occurrence Handle10.1007/s004150050530 Occurrence Handle1:STN:280:DC%2BD3c7hslShug%3D%3D
MM Hoehn MD Yahr (1967) ArticleTitleParkinsonism: onset, progression and mortality Neurology 17 427–442 Occurrence Handle6067254 Occurrence Handle1:STN:280:CCiC3sbgtlQ%3D Occurrence Handle10.1159/000137111
AJ Hughes SE Daniel L Kilford AJ Lees (1992) ArticleTitleAccuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases J Neurol Neurosurg Psychiatry 55 181–184 Occurrence Handle1564476 Occurrence Handle1:STN:280:By2B38nnsFQ%3D Occurrence Handle10.1136/jnnp.55.3.181
MJ Hurley DC Mash P Jenner (2001) ArticleTitleDopamine D(1) receptor expression in human basal ganglia and changes in Parkinson’s disease Brain Res Mol Brain Res 87 271–279 Occurrence Handle11245931 Occurrence Handle10.1016/S0169-328X(01)00022-5 Occurrence Handle1:CAS:528:DC%2BD3MXhs1eisLg%3D
J Jankovic (2005) ArticleTitleMotor fluctuations and dyskinesias in Parkinson’s disease: clinical manifestations Mov Disord 20 Suppl 11 S11–S16 Occurrence Handle10.1002/mds.20458
G Linazasoro (2005) ArticleTitleNew ideas on the origin of L-dopa-induced dyskinesias: age, genes and neural plasticity Trends Pharmacol Sci 26 391–397 Occurrence Handle16009432 Occurrence Handle10.1016/j.tips.2005.06.007 Occurrence Handle1:CAS:528:DC%2BD2MXmvVCqtL4%3D
MM Maier Hoehn (1983) ArticleTitleParkinsonism treated with levodopa: progression and mortality J Neural Transm Suppl 19 253–264 Occurrence Handle6583311 Occurrence Handle1:STN:280:BiuC3sjmtlI%3D
CD Marsden JD Parkes (1977) ArticleTitleSuccess and problems of long-term levodopa therapy in Parkinson’s disease Lancet 1 345–349 Occurrence Handle64868 Occurrence Handle10.1016/S0140-6736(77)91146-1 Occurrence Handle1:STN:280:CSiD1MbhtVU%3D
SS Mirra A Heyman D McKeel SM Sumi BJ Crain LM Brownlee et al. (1991) ArticleTitleThe Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease Neurology 41 479–486 Occurrence Handle2011243 Occurrence Handle1:STN:280:By6C1cjitVc%3D
JG Nutt (2001) ArticleTitleMotor fluctuations and dyskinesia in Parkinson’s disease Parkinsonism Relat Disord 8 101–108 Occurrence Handle11489675 Occurrence Handle10.1016/S1353-8020(01)00024-4 Occurrence Handle1:STN:280:DC%2BD383ovFWrtg%3D%3D
S Papapetropoulos AA Argyriou J Ellul E Chroni (2004) ArticleTitleComparison of motor fluctuations and L-dopa-induced dyskinesias in patients with familial and sporadic Parkinson’s disease Eur J Neurol 11 115–119 Occurrence Handle14748772 Occurrence Handle10.1046/j.1351-5101.2003.00727.x Occurrence Handle1:STN:280:DC%2BD2c%2FkvVCguw%3D%3D
S Papapetropoulos A Lieberman J Gonzalez DC Mash (2005) ArticleTitleCan Alzheimer’s type pathology influence the clinical phenotype of Parkinson’s disease? Acta Neurol Scand 111 353–359 Occurrence Handle15876335 Occurrence Handle10.1111/j.1600-0404.2005.00411.x Occurrence Handle1:STN:280:DC%2BD2M3jvFSjsA%3D%3D
WH Poewe AJ Lees GM Stern (1986) ArticleTitleTreatment of motor fluctuations in Parkinson’s disease with an oral sustained-release preparation of L-dopa: clinical and pharmacokinetic observations Clin Neuropharmacol 9 430–439 Occurrence Handle3768865 Occurrence Handle10.1097/00002826-198610000-00003 Occurrence Handle1:STN:280:BiiD38fgt1Q%3D
JC Pressley MX Tang K Marder LJ Cote R Mayeux (2005) ArticleTitleDisparities in the recording of Parkinson’s disease on death certificates Mov Disord 20 315–321 Occurrence Handle15580618 Occurrence Handle10.1002/mds.20339
JO Rinne JK Rinne K Laakso P Lonnberg UK Rinne (1985) ArticleTitleDopamine D-1 receptors in the parkinsonian brain Brain Res 359 306–310 Occurrence Handle2934111 Occurrence Handle10.1016/0006-8993(85)91441-6 Occurrence Handle1:CAS:528:DyaL28Xjt1KnsQ%3D%3D
A Schrag N Quinn (2000) ArticleTitleDyskinesias and motor fluctuations in Parkinson’s disease. A community-based study Brain 123 IssueIDPt 11 2297–2305 Occurrence Handle11050029 Occurrence Handle10.1093/brain/123.11.2297
RD Sweet FH McDowell (1975) ArticleTitleFive years’ treatment of Parkinson’s disease with levodopa. Therapeutic results and survival of 100 patients Ann Intern Med 83 456–463 Occurrence Handle1166978 Occurrence Handle1:STN:280:CSmD3sfhslM%3D
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Papapetropoulos, S., Mash, D. Motor fluctuations and dyskinesias in advanced/end stage Parkinson’s disease: a study from a population of brain donors. J Neural Transm 114, 341–345 (2007). https://doi.org/10.1007/s00702-006-0603-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-006-0603-6