Skip to main content
SpringerLink
Log in

Clinical phenotype and risk of levodopa-induced dyskinesia in Parkinson’s disease

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

It is unclear whether patients with different clinical phenotypes of Parkinson’s disease (PD) differ in their risk of developing levodopa-induced dyskinesia. We evaluated the possible association between clinical phenotypes and risk of levodopa-induced dyskinesia in PD patients using a case–control design. The FRAGAMP study is a large Italian multicenter study. Patients affected by PD diagnosed according to the Gelb’s criteria were enrolled and underwent a face-to-face interview. Clinical scales were used to evaluate motor and cognitive impairment. Presence of dyskinesia was assessed by the item 32 of the UPDRS section IV. On the basis of the most prominent motor symptoms at onset PD, patients were classified as tremor-dominant, akinetic-rigid, or mixed type. 485 PD patients (292 men; mean age 65.6 ± 9.8) were enrolled in the study of whom 128 (26.4 %) presented levodopa-induced dyskinesia. Of the 485 patients, 311 (64.1 %) were classified as tremor-dominant, 104 (21.4 %) as Akinetic-Rigid and 70 (14.4 %) as mixed type. Multivariate logistic regression analysis showed a significant negative association between tremor-dominant phenotype and levodopa-induced dyskinesia (adjusted OR 0.48; 95 % CI 0.23–1.00; p value 0.05). When analysis was stratified by age at onset a stronger negative association was found among the late onset (>50 years) PD patients (OR 0.28; 95 % CI 0.11–0.70; p value 0.007) while no association was found among patients with an early onset. Our findings support the hypothesis that the occurrence of resting tremor as an initial manifestation of PD may predict a lower probability of developing levodopa-induced dyskinesia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fahn S (2008) The history of dopamine and levodopa in the treatment of Parkinson’s disease. Mov Disord 23:S497–S508

    Article  PubMed  Google Scholar 

  2. Ahlskog JE, Muenter MD (2011) Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 16:448–458

    Article  Google Scholar 

  3. Calabresi P, Di Filippo M, Ghiglieri V, Tambasco N, Picconi B (2010) Levodopa-induced dyskinesias in patients with Parkinson’s disease: filling the bench-to-bedside gap. Lancet Neurol 9:1106–1117

    Article  CAS  PubMed  Google Scholar 

  4. Manson A, Stirpe P, Schrag A (2012) Levodopa-induced-dyskinesias clinical features, incidence, risk factors, management and impact on quality of life. J Parkinson Dis 21:189–198

    Google Scholar 

  5. Olanow CW, Kieburtz K, Rascol O et al (2013) Factors predictive of the development of levodopa-induced dyskinesia and wearing-off in Parkinson’s disease. Mov Disord 28:1064–1071

    Article  CAS  Google Scholar 

  6. Zhang YH, Tang BS, Song CY et al (2013) The relationship between the phenotype of Parkinson’s disease and levodopa-induced dyskinesia. Neurosci Lett 556:109–112

    Article  CAS  PubMed  Google Scholar 

  7. Nicoletti A, Pugliese P, Nicoletti G et al (2010) The FRAGAMP study: environmental and genetic factors in Parkinson’s disease, methods and clinical features. Neurol Sci 31:47–52

    Article  PubMed  Google Scholar 

  8. Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. Arch Neurol 56:33–39

    Article  CAS  PubMed  Google Scholar 

  9. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression, and mortality. Neurology 17:427–442

    Article  CAS  PubMed  Google Scholar 

  10. Fahn S, Elton RL, Members of the UPDRS Development Committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M (eds) Recent developments in Parkinson’s disease. Macmillan Healthcare Information, Florham Park, pp 153–163

    Google Scholar 

  11. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  CAS  PubMed  Google Scholar 

  12. Munetz MR, Benjamin S (1988) How to examine patients using the abnormal involuntary movement scale. Hosp Community Psychiatry 39:1172–1177

    CAS  PubMed  Google Scholar 

  13. Nicoletti A, Pugliese P, Nicoletti G et al (2010) Voluptuary habits and clinical subtypes of Parkinson’s disease: the FRAGAMP case–control study. Mov Disord 25:2387–2394

    Article  PubMed  Google Scholar 

  14. Stata corp. STATA statistical software: release 12.1 College station, STATA corporation, TX, USA

  15. Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 25:2649–2653

    Article  PubMed  Google Scholar 

  16. Jankovic J, McDermott M, Carter J et al (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology 40:1529–1534

    Article  CAS  PubMed  Google Scholar 

  17. Jankovic J, Kapadia AS (2001) Functional decline in Parkinson disease. Arch Neurol 58:1611–1615

    Article  CAS  PubMed  Google Scholar 

  18. Thenganatt MA, Jankovic J (2014) Parkinson disease subtypes. JAMA Neurol 71:499–504

    Article  PubMed  Google Scholar 

  19. Kipfer S, Stephan MA, Schüpbach WM, Ballinari P, Kaelin-Lang A (2011) Resting tremor in Parkinson disease: a negative predictor of levodopa-induced dyskinesia. Arch Neurol 68:1037–1039

    Article  PubMed  Google Scholar 

  20. Zappia M, Annesi G, Nicoletti G et al (2005) Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study. Arch Neurol 62:601–605

    Article  PubMed  Google Scholar 

  21. Scott NW, Macleod AD, Counsell CE (2015) Motor complications in an incident Parkinson’s disease cohort. Eur J Neurol. doi:10.1111/ene.12751

    PubMed  Google Scholar 

  22. Jellinger KA (2002) Recent developments in the pathology of Parkinson’s disease. J Neural Transm Suppl 62:347–376

    Article  CAS  PubMed  Google Scholar 

  23. Mehanna R, Moore S, Hou JG, Sarwar AI, Lai EC (2014) Comparing clinical features of young onset, middle onset and late onset Parkinson’s disease. Parkinsonism Relat Disord 20:530–534

    Article  PubMed  Google Scholar 

  24. Lücking CB, Dürr A, Bonifati V, French Parkinson’s Disease Genetics Study Group, European Consortium on Genetic Susceptibility in Parkinson’s Disease et al (2000) Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 342:1560–1567

    Article  PubMed  Google Scholar 

  25. Khan NL, Graham E, Critchley P et al (2003) Parkin disease: a phenotypic study of a large case series. Brain 126:1279–1292

    Article  PubMed  Google Scholar 

  26. Cerasa A, Salsone M, Morelli M et al (2013) Age at onset influences neurodegenerative processes underlying PD with levodopa-induced dyskinesias. Parkinsonism Relat Disord 19:883–888

    Article  PubMed  Google Scholar 

  27. van Nuenen BF, Weiss MM, Bloem BR et al (2009) Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype. Neurology 72:1041–1047

    Article  PubMed  PubMed Central  Google Scholar 

  28. Oliveri RL, Annesi G, Zappia M et al (1999) Dopamine D2 receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD. Neurology 53:1425–1430

    Article  CAS  PubMed  Google Scholar 

  29. Sharma JC, Bachmann CG, Linazasoro G (2010) Classifying risk factors for dyskinesia in Parkinson’s disease. Parkinsonism Relat Disord 16:490–497

    Article  CAS  PubMed  Google Scholar 

  30. Doherty KM, Silveira-Moriyama L, Parkkinen L et al (2013) Parkin disease: a clinicopathologic entity? JAMA Neurol 70:571–579

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wickremaratchi MM, Knipe MD, Sastry BS et al (2011) The motor phenotype of Parkinson’s disease in relation to age at onset. Mov Disord 26:457–463

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Neurosciences, Department G.F. Ingrassia, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy

    Alessandra Nicoletti, Giovanni Mostile & Mario Zappia

  2. Istituto di Bioimmagini e Fisiologia Molecolare, Consiglio Nazionale delle Ricerche, Catanzaro, Italy

    Giuseppe Nicoletti & Aldo Quattrone

  3. Clinica Neurologica, Università “Magna Græcia” di Catanzaro, Catanzaro, Italy

    Gennarina Arabia & Aldo Quattrone

  4. Dipartimento di Scienze mediche di base, neuroscienze e organi di senso, Università di Bari, Bari, Italy

    Giovanni Iliceto & Paolo Lamberti

  5. Divisione di Neurologia, Ospedale Misericordia, Grosseto, Italy

    Roberto Marconi

  6. Dipartimento di Neuroscienze, Università di Messina, Messina, Italy

    Letterio Morgante

  7. Dipartimento di Medicina e Chirurgia, Università degli Studi di Salerno, Salerno, Italy

    Paolo Barone

Authors
  1. Alessandra Nicoletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovanni Mostile
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giuseppe Nicoletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gennarina Arabia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giovanni Iliceto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paolo Lamberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Roberto Marconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Letterio Morgante
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Paolo Barone
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Aldo Quattrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mario Zappia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario Zappia.

Ethics declarations

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards

The study has been approved by the appropriate ethics committee and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

All persons gave their informed consent prior to their inclusion in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nicoletti, A., Mostile, G., Nicoletti, G. et al. Clinical phenotype and risk of levodopa-induced dyskinesia in Parkinson’s disease. J Neurol 263, 888–894 (2016). https://doi.org/10.1007/s00415-016-8075-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-016-8075-6

Keywords

Search

Navigation