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DOI: 10.1055/s-0037-1602423
Motor Complications of Dopaminergic Medications in Parkinson's Disease
Publikationsverlauf
Publikationsdatum:
16. Mai 2017 (online)
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Abstract
Motor complications are a consequence of the chronic treatment of Parkinson's disease (PD) and include motor fluctuations (wearing-off phenomenon) and levodopa-induced dyskinesia. Both can have a significant impact on functionality and quality of life; thus, proper recognition and management is essential. The phenomenology and temporal relationship of motor complications to the schedule of levodopa dosing can be helpful in characterizing them. There are several therapeutic approaches to motor complications, including pharmacological and surgical options. The authors summarize the different types of motor complications according to phenomenology and the currently available medical treatments, including ongoing trials for the management of this condition.
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References
- 1 Hornykiewicz O. A brief history of levodopa. J Neurol 2010; 257 (Suppl. 02) S249-S252
- 2 Aquino CC, Fox SH. Clinical spectrum of levodopa-induced complications. Mov Disord 2015; 30 (01) 80-89
- 3 Anderson E, Nutt J. The long-duration response to levodopa: phenomenology, potential mechanisms and clinical implications. Parkinsonism Relat Disord 2011; 17 (08) 587-592
- 4 Contin M, Martinelli P. Pharmacokinetics of levodopa. J Neurol 2010; 257 (Suppl. 02) S253-S261
- 5 Widnell K. Pathophysiology of motor fluctuations in Parkinson's disease. Mov Disord 2005; 20 (Suppl. 11) S17-S22
- 6 Marsden CD, Parkes JD. Success and problems of long-term levodopa therapy in Parkinson's disease. Lancet 1977; 1 (8007): 345-349
- 7 Pahwa R, Lyons KE. Levodopa-related wearing-off in Parkinson's disease: identification and management. Curr Med Res Opin 2009; 25 (04) 841-849
- 8 Yoritaka A, Shimo Y, Takanashi M. , et al. Motor and non-motor symptoms of 1453 patients with Parkinson's disease: prevalence and risks. Parkinsonism Relat Disord 2013; 19 (08) 725-731
- 9 Thenganatt MA, Jankovic J. Parkinson disease subtypes. JAMA Neurol 2014; 71 (04) 499-504
- 10 Warren Olanow C, Kieburtz K, Rascol O. , et al; Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) Investigators. Factors predictive of the development of Levodopa-induced dyskinesia and wearing-off in Parkinson's disease. Mov Disord 2013; 28 (08) 1064-1071
- 11 Fox SH, Lang AE. Levodopa-related motor complications--phenomenology. Mov Disord 2008; 23 (Suppl. 03) S509-S514
- 12 Stocchi F, Rascol O, Kieburtz K. , et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann Neurol 2010; 68 (01) 18-27
- 13 Chen H, Fang J, Li F, Gao L, Feng T. Risk factors and safe dosage of levodopa for wearing-off phenomenon in Chinese patients with Parkinson's disease. Neurol Sci 2015; 36 (07) 1217-1223
- 14 Cilia R, Akpalu A, Sarfo FS. , et al. The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa. Brain 2014; 137 (Pt 10): 2731-2742
- 15 Virmani T, Tazan S, Mazzoni P, Ford B, Greene PE. Motor fluctuations due to interaction between dietary protein and levodopa in Parkinson's disease. J Clin Mov Disord 2016; 3 (01) 8 . doi: 10.1186/s40734-016-0036-9
- 16 Rahne K-E, Tagesson C, Nyholm D. Motor fluctuations and Helicobacter pylori in Parkinson's disease. J Neurol 2013; 260 (12) 2974-2980
- 17 Hashim H, Azmin S, Razlan H. , et al. Eradication of Helicobacter pylori infection improves levodopa action, clinical symptoms and quality of life in patients with Parkinson's disease. PLoS One 2014; 9 (11) e112330
- 18 Çamcı G, Oğuz S. Association between Parkinson's disease and Helicobacter pylori . J Clin Neurol 2016; 12 (02) 147-150
- 19 Niccolini F, Rocchi L, Politis M. Molecular imaging of levodopa-induced dyskinesias. Cell Mol Life Sci 2015; 72 (11) 2107-2117
- 20 Kostic V, Przedborski S, Flaster E, Sternic N. Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease. Neurology 1991; 41 (2 ( Pt 1)): 202-205
- 21 Bjornestad A, Forsaa EB, Pedersen KF, Tysnes O-B, Larsen JP, Alves G. Risk and course of motor complications in a population-based incident Parkinson's disease cohort. Parkinsonism Relat Disord 2016; 22: 48-53
- 22 Scott NW, Macleod AD, Counsell CE. Motor complications in an incident Parkinson's disease cohort. Eur J Neurol 2016; 23 (02) 304-312
- 23 Colombo D, Abbruzzese G, Antonini A. , et al. The “gender factor” in wearing-off among patients with Parkinson's disease: a post hoc analysis of DEEP study. Sci World J 2015; 2015: 787451
- 24 Kumagai T, Nagayama H, Ota T, Nishiyama Y, Mishina M, Ueda M. Sex differences in the pharmacokinetics of levodopa in elderly patients with Parkinson disease. Clin Neuropharmacol 2014; 37 (06) 173-176
- 25 Nicoletti A, Arabia G, Pugliese P. , et al. Hormonal replacement therapy in women with Parkinson disease and levodopa-induced dyskinesia: a crossover trial. Clin Neuropharmacol 2007; 30 (05) 276-280
- 26 Sharma JC, Ross IN, Rascol O, Brooks D. Relationship between weight, levodopa and dyskinesia: the significance of levodopa dose per kilogram body weight. Eur J Neurol 2008; 15 (05) 493-496
- 27 Müller T, Woitalla D, Saft C, Kuhn W. Levodopa in plasma correlates with body weight of parkinsonian patients. Parkinsonism Relat Disord 2000; 6 (03) 171-173
- 28 Strong JA, Dalvi A, Revilla FJ. , et al. Genotype and smoking history affect risk of levodopa-induced dyskinesias in Parkinson's disease. Mov Disord 2006; 21 (05) 654-659
- 29 Lee J-Y, Cho J, Lee E-K, Park S-S, Jeon BS. Differential genetic susceptibility in diphasic and peak-dose dyskinesias in Parkinson's disease. Mov Disord 2011; 26 (01) 73-79
- 30 Kaplan N, Vituri A, Korczyn AD. , et al. Sequence variants in SLC6A3, DRD2, and BDNF genes and time to levodopa-induced dyskinesias in Parkinson's disease. J Mol Neurosci 2014; 53 (02) 183-188
- 31 Lee JY, Beom BJ. Risk factors for levodopa-induced dyskinesia. In: Fox SH, Brotchie JM. , eds. Levodopa-Induced Dyskinesia in Parkinson's Disease . London: Springer; 2014: 51-68
- 32 Dekker MCJ, Bonifati V, van Duijn CM. Parkinson's disease: piecing together a genetic jigsaw. Brain 2003; 126 (Pt 8): 1722-1733
- 33 Oliveri RL, Annesi G, Zappia M. , et al. Dopamine D2 receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD. Neurology 1999; 53 (07) 1425-1430
- 34 Cheshire P, Bertram K, Ling H. , et al. Influence of single nucleotide polymorphisms in COMT, MAO-A and BDNF genes on dyskinesias and levodopa use in Parkinson's disease. Neurodegener Dis 2014; 13 (01) 24-28
- 35 Huot P, Johnston TH, Koprich JB, Fox SH, Brotchie JM. The pharmacology of L-DOPA-induced dyskinesia in Parkinson's disease. Pharmacol Rev 2013; 65 (01) 171-222
- 36 Bateman DE, Levett K, Marsden CD. Sleep benefit in Parkinson's disease. J Neurol Neurosurg Psychiatry 1999; 67 (03) 384-385
- 37 van Gilst MM, Bloem BR, Overeem S. “Sleep benefit” in Parkinson's disease: a systematic review. Parkinsonism Relat Disord 2013; 19 (07) 654-659
- 38 Hutton JT, Morris JL. Long-term evaluation of Sinemet CR in parkinsonian patients with motor fluctuations. Can J Neurol Sci 1991; 18 (04) 467-471
- 39 Yeh KC, August TF, Bush DF. , et al. Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. Neurology 1989; 39 (11) (Suppl. 02) 25-38
- 40 DeMaagd G, Philip A. Parkinson's disease and its management: part 4: treatment of motor complications. P&T 2015; 40 (11) 747-773
- 41 Gottwald MD, Aminoff MJ. Therapies for dopaminergic-induced dyskinesias in Parkinson disease. Ann Neurol 2011; 69 (06) 919-927
- 42 Okuma Y, Yanagisawa N. The clinical spectrum of freezing of gait in Parkinson's disease. Mov Disord 2008; 23 (02) (Suppl. 02) S426-S430
- 43 Espay AJ, Fasano A, van Nuenen BFL, Payne MM, Snijders AH, Bloem BR. “On” state freezing of gait in Parkinson disease: a paradoxical levodopa-induced complication. Neurology 2012; 78 (07) 454-457
- 44 Gazibara T, Pekmezovic T, Kisic-Tepavcevic D. , et al. Incidence and prediction of falls in Parkinson's disease: a prospective cohort study. Eur J Epidemiol 2015; 30 (04) 349-352
- 45 Malkani R, Zadikoff C, Melen O, Videnovic A, Borushko E, Simuni T. Amantadine for freezing of gait in patients with Parkinson disease. Clin Neuropharmacol 2012; 35 (06) 266-268
- 46 Kim YE, Yun JY, Yang HJ. , et al. Intravenous amantadine for freezing of gait resistant to dopaminergic therapy: a randomized, double-blind, placebo-controlled, cross-over clinical trial. PLoS One 2012; 7 (11) e48890
- 47 Lee J-Y, Oh S, Kim J-M. , et al. Intravenous amantadine on freezing of gait in Parkinson's disease: a randomized controlled trial. J Neurol 2013; 260 (12) 3030-3038
- 48 Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 2005; 62 (02) 241-248
- 49 Rascol O, Brooks DJ, Melamed E. , et al; LARGO study group. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, lasting effect in adjunct therapy with rasagiline given once daily, study): a randomised, double-blind, parallel-group trial. Lancet 2005; 365 (9463): 947-954
- 50 Rahimi F, Roberts AC, Jog M. Patterns and predictors of freezing of gait improvement following rasagiline therapy: A pilot study. Clin Neurol Neurosurg 2016; 150: 117-124
- 51 Espay AJ, Dwivedi AK, Payne M. , et al. Methylphenidate for gait impairment in Parkinson disease: a randomized clinical trial. Neurology 2011; 76 (14) 1256-1262
- 52 Devos D, Moreau C, Delval A, Dujardin K, Defebvre L, Bordet R. Methylphenidate: a treatment for Parkinson's disease?. CNS Drugs 2013; 27 (01) 1-14
- 53 Moreau C, Delval A, Defebvre L. , et al; Parkgait-II study group. Methylphenidate for gait hypokinesia and freezing in patients with Parkinson's disease undergoing subthalamic stimulation: a multicentre, parallel, randomised, placebo-controlled trial. Lancet Neurol 2012; 11 (07) 589-596
- 54 Bastide MF, Meissner WG, Picconi B. , et al. Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease. Prog Neurobiol 2015; 132: 96-168
- 55 Guridi J, González-Redondo R, Obeso JA. Clinical features, pathophysiology, and treatment of levodopa-induced dyskinesias in Parkinson's disease. Parkinsons Dis 2012; 2012: 943159
- 56 Poewe WH, Lees AJ, Stern GM. Dystonia in Parkinson's disease: clinical and pharmacological features. Ann Neurol 1988; 23 (01) 73-78
- 57 Tolosa E, Compta Y. Dystonia in Parkinson's disease. J Neurol 2006; 253 (Suppl. 07) VII7-VII13
- 58 Luquin MR, Scipioni O, Vaamonde J, Gershanik O, Obeso JA. Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification. Mov Disord 1992; 7 (02) 117-124
- 59 Chen R, Ashby P, Lang AE. Stimulus-sensitive myoclonus in akinetic-rigid syndromes. Brain 1992; 115 (Pt 6): 1875-1888
- 60 Grötzsch H, Sztajzel R, Burkhard PR. Levodopa-induced ocular dyskinesia in Parkinson's disease. Eur J Neurol 2007; 14 (10) 1124-1128
- 61 LeWitt PA. Conjugate eye deviations as dyskinesias induced by levodopa in Parkinson's disease. Mov Disord 1998; 13 (04) 731-734
- 62 Linazasoro G, Van Blercom N, Lasa A, Indakoetxea B, Ruiz J. Levodopa-induced ocular dyskinesias in Parkinson's disease. Mov Disord 2002; 17 (01) 186-187
- 63 Rich MW, Radwany SM. Respiratory dyskinesia. An underrecognized phenomenon. Chest 1994; 105 (06) 1826-1832
- 64 Rice JE, Antic R, Thompson PD. Disordered respiration as a levodopa-induced dyskinesia in Parkinson's disease. Mov Disord 2002; 17 (03) 524-527
- 65 Pietracupa S, Fasano A, Fabbrini G. , et al. Poor self-awareness of levodopa-induced dyskinesias in Parkinson's disease: clinical features and mechanisms. Parkinsonism Relat Disord 2013; 19 (11) 1004-1008
- 66 Amanzio M, Palermo S, Zibetti M. , et al. Self-unawareness of levodopa induced dyskinesias in patients with Parkinson's disease. Brain Cogn 2014; 90: 135-141
- 67 Marconi R, Lefebvre-Caparros D, Bonnet AM, Vidailhet M, Dubois B, Agid Y. Levodopa-induced dyskinesias in Parkinson's disease phenomenology and pathophysiology. Mov Disord 1994; 9 (01) 2-12
- 68 Wirdefeldt K, Odin P, Nyholm D. Levodopa-carbidopa intestinal gel in patients with Parkinson's disease: a systematic review. CNS Drugs 2016; 30 (05) 381-404
- 69 Krack P, Pollak P, Limousin P, Benazzouz A, Deuschl G, Benabid AL. From off-period dystonia to peak-dose chorea. The clinical spectrum of varying subthalamic nucleus activity. Brain 1999; 122 (Pt 6): 1133-1146
- 70 Jankovic J. Motor fluctuations and dyskinesias in Parkinson's disease: clinical manifestations. Mov Disord 2005; 20 (Suppl. 11) S11-S16
- 71 Vijayakumar D, Jankovic J. Drug-Induced Dyskinesia, Part 1: Treatment of Levodopa-Induced Dyskinesia. Drugs 2016; 76 (07) 759-777
- 72 Stowe R, Ives N, Clarke CE. , et al; van Hilten. Evaluation of the efficacy and safety of adjuvant treatment to levodopa therapy in Parkinson's disease patients with motor complications. Cochrane Database Syst Rev 2010; (07) CD007166
- 73 Morgan JC, Fox SH. Treating the Motor Symptoms of Parkinson Disease. Continuum (Minneap Minn) 2016; 22 (4 Movement Disorders): 1064-1085
- 74 Mokhles MM, Trifirò G, Dieleman JP. , et al. The risk of new onset heart failure associated with dopamine agonist use in Parkinson's disease. Pharmacol Res 2012; 65 (03) 358-364
- 75 Perez-Lloret S, Rey MV, Crispo J. , et al. Risk of heart failure following treatment with dopamine agonists in Parkinson's disease patients. Expert Opin Drug Saf 2014; 13 (03) 351-360
- 76 Cannas A, Solla P, Floris G. , et al. Reversible Pisa syndrome in patients with Parkinson's disease on dopaminergic therapy. J Neurol 2009; 256 (03) 390-395
- 77 Katzenschlager R, Head J, Schrag A, Ben-Shlomo Y, Evans A, Lees AJ. ; Parkinson's Disease Research Group of the United Kingdom. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology 2008; 71 (07) 474-480
- 78 Dewey Jr RB, Hutton JT, LeWitt PA, Factor SA. A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events. Arch Neurol 2001; 58 (09) 1385-1392
- 79 Trosch RM, Silver D, Bottini PB. Intermittent subcutaneous apomorphine therapy for ‘off’ episodes in Parkinson's disease: a 6-month open-label study. CNS Drugs 2008; 22 (06) 519-527
- 80 Haasio K. Toxicology and safety of COMT inhibitors. Int Rev Neurobiol 2010; 95: 163-189
- 81 Fox SH, Katzenschlager R, Lim S-Y. , et al. The Movement Disorder Society evidence-based medicine review update: treatments for the motor symptoms of Parkinson's disease. Mov Disord 2011; 26 (Suppl. 03) S2-S41
- 82 Smith KM, Eyal E, Weintraub D. ; ADAGIO Investigators. Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability. JAMA Neurol 2015; 72 (01) 88-95
- 83 Hauser RA, Hsu A, Kell S. , et al; IPX066 ADVANCE-PD investigators. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial. Lancet Neurol 2013; 12 (04) 346-356
- 84 Stocchi F, Hsu A, Khanna S. , et al. Comparison of IPX066 with carbidopa-levodopa plus entacapone in advanced PD patients. Parkinsonism Relat Disord 2014; 20 (12) 1335-1340
- 85 Pahwa R, Lyons KE, Hauser RA. , et al; APEX-PD Investigators. Randomized trial of IPX066, carbidopa/levodopa extended release, in early Parkinson's disease. Parkinsonism Relat Disord 2014; 20 (02) 142-148
- 86 Olanow CW, Kieburtz K, Odin P. , et al; LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol 2014; 13 (02) 141-149
- 87 Seeberger LC, Hauser RA. Carbidopa levodopa enteral suspension. Expert Opin Pharmacother 2015; 16 (18) 2807-2817
- 88 Freitas ME, Ruiz-Lopez M, Fox SH. Novel levodopa formulations for Parkinson's disease. CNS Drugs 2016; 30 (11) 1079-1095
- 89 LeWitt PA, Hauser RA, Grosset DG. , et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson's disease. Mov Disord 2016; 31 (09) 1356-1365
- 90 Hauser RA, Olanow CW, Dzyngel B. , et al. Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson's disease. Mov Disord 2016; 31 (09) 1366-1372
- 91 Freitas ME, Fox SH. Nondopaminergic treatments for Parkinson's disease: current and future prospects. Neurodegener Dis Manag 2016; 6 (03) 249-268
- 92 Vorovenci RJ, Antonini A. The efficacy of oral adenosine A(2A) antagonist istradefylline for the treatment of moderate to severe Parkinson's disease. Expert Rev Neurother 2015; 15 (12) 1383-1390
- 93 Mizuno Y, Kondo T. ; Japanese Istradefylline Study Group. Adenosine A2A receptor antagonist istradefylline reduces daily OFF time in Parkinson's disease. Mov Disord 2013; 28 (08) 1138-1141
- 94 Hauser RA, Olanow CW, Kieburtz KD. , et al. Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol 2014; 13 (08) 767-776
- 95 Borgohain R, Szasz J, Stanzione P. , et al; Study 016 Investigators. Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations. Mov Disord 2014; 29 (02) 229-237
- 96 Borgohain R, Szasz J, Stanzione P. , et al; Study 018 Investigators. Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease. Mov Disord 2014; 29 (10) 1273-1280
- 97 Cattaneo C, Ferla RL, Bonizzoni E, Sardina M. Long-term effects of safinamide on dyskinesia in mid- to late-stage Parkinson's disease: a post-hoc analysis. J Parkinsons Dis 2015; 5 (03) 475-481
- 98 Pahwa R, Tanner CM, Hauser RA. , et al. Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study). Mov Disord 2015; 30 (06) 788-795
- 99 Eskow KL, Gupta V, Alam S, Park JY, Bishop C. The partial 5-HT(1A) agonist buspirone reduces the expression and development of l-DOPA-induced dyskinesia in rats and improves l-DOPA efficacy. Pharmacol Biochem Behav 2007; 87 (03) 306-314
- 100 Svenningsson P, Rosenblad C, Af Edholm Arvidsson K. , et al. Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson's disease: a dose-finding study. Brain 2015; 138 (Pt 4): 963-973