Effect of levodopa on handwriting tasks of different complexity in Parkinson’s disease: a kinematic study

Abstract

Levodopa treatment does improve Parkinson’s disease (PD) dysgraphia, but previous research is not in agreement about which aspects are most responsive. This study investigated the effect of levodopa on the kinematics of writing. Twenty-four patients with PD of less than 10 years duration and 25 age-matched controls were recruited. A practically defined off state method was used to assess the levodopa motor response, measured on the Unified Parkinson’s Disease Rating Scale Part III. The kinematic features for six handwriting tasks involving different levels of complexity were recorded from PD patients in off and on states and from the control group. Levodopa is effective for simple writing activities involving repetition of letters, denoting improved fine motor control. But the same benefit was not seen for copying a sentence and a written category fluency test, tasks that carry memory and cognitive loads. We also found significant differences in kinematic features between control participants and PD patients, for all tasks and in both on and off states. Serial testing of handwriting in patients known to be at risk for developing PD might prove to be an effective biomarker for cell loss in the substantia nigra and the associated dopamine deficiency. We recommend using a panel of writing tasks including sentence copying and memory dependence. Dual-task effects may make these activities more sensitive to early motor deficits, while their weaker levodopa responsiveness would cause them to be more stable indicators of motor progression once symptomatic treatment has been commenced.

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

Fig. 1
Fig. 2

References

  1. 1.

    Kinnier Wilson S (1925) The Croonian Lecutures on some disorders of mortility and of muscle tone, with special reference to the corpus striatum. Lancet ii:1–10

  2. 2.

    Shukla AW, Ounpraseuth S, Okun MS, Gray V, Schwankhaus J, Metzer WS (2012) Micrographia and related deficits in Parkinson’s disease: a cross-sectional study. BMJ Open 2(3):e000628–e000628

    Article  Google Scholar 

  3. 3.

    Letanneux A, Danna J, Velay JL, Viallet F, Pinto S (2014) From micrographia to Parkinson’s disease dysgraphia. Mov Disord 29(12):1467–1475. https://doi.org/10.1002/mds.25990

    Article  PubMed  Google Scholar 

  4. 4.

    San Luciano M, Wang C, Ortega RA, Yu Q, Boschung S, Soto-Valencia J, Bressman SB, Lipton RB, Pullman S, Saunders-Pullman R (2016) Digitized spiral drawing: a possible biomarker for early Parkinson’s disease. PloS One 11(10):e0162799

    Article  Google Scholar 

  5. 5.

    Pereira CR, Pereira DR, da Silva FA, Hook C, Weber SA, Pereira LA, Papa JP (2015) A step towards the automated diagnosis of Parkinson’s disease: analyzing handwriting movements. In: 2015 IEEE 28th international symposium on computer-based medical systems. pp 171–176

  6. 6.

    Drotar P, Mekyska J, Rektorova I, Masarova L, Smekal Z, Faundez-Zanuy M (2015) Decision support framework for Parkinson’s disease based on novel handwriting markers. IEEE Trans Neural Syst Rehabil Eng 23(3):508–516. https://doi.org/10.1109/TNSRE.2014.2359997

    Article  PubMed  Google Scholar 

  7. 7.

    Zham PZ, Kumar DK, Dabnichki P, Arjunan S, Raghav S (2017) Distinguishing different stages of Parkinson’s disease using composite index of speed and pen-pressure of sketching a spiral. Front Neurol 8:435

    Article  Google Scholar 

  8. 8.

    Cobbah W, Fairhurst MC (2000) Computer analysis of handwriting dynamics during dopamimetic tests in Parkinson’s disease. In: Euromicro Conference, 2000. Proceedings of the 26th IEEE, pp 414–418

  9. 9.

    Eichhorn T, Gasser T, Mai N, Marquardt C, Arnold G, Schwarz J, Oertel W (1996) Computational analysis of open loop handwriting movements in Parkinson’s disease: a rapid method to detect dopamimetic effects. Mov Disord 11(3):289–297

    CAS  Article  Google Scholar 

  10. 10.

    Tucha O, Mecklinger L, Thome J, Reiter A, Alders G, Sartor H, Naumann M, Lange K (2006) Kinematic analysis of dopaminergic effects on skilled handwriting movements in Parkinson’s disease. J Neural Transm 113(5):609–623

    CAS  Article  Google Scholar 

  11. 11.

    Poluha P, Teulings H-L, Brookshire R (1998) Handwriting and speech changes across the levodopa cycle in Parkinson’s disease. Acta Psychol 100(1):71–84

    CAS  Article  Google Scholar 

  12. 12.

    Broeder S, Nackaerts E, Nieuwboer A, Smits-Engelsman BC, Swinnen SP, Heremans E (2014) The effects of dual tasking on handwriting in patients with Parkinson’s disease. Neuroscience 263:193–202. https://doi.org/10.1016/j.neuroscience.2014.01.019

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184

    CAS  Article  Google Scholar 

  14. 14.

    Kempster PA, O’Sullivan SS, Holton JL, Revesz T, Lees AJ (2010) Relationships between age and late progression of Parkinson’s disease: a clinico-pathological study. Brain 133(6):1755–1762

    Article  Google Scholar 

  15. 15.

    Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results. Mov Disord 23(15):2129–2170

    Article  Google Scholar 

  16. 16.

    Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53(4):695–699

    Article  Google Scholar 

  17. 17.

    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(15):2649–2653

    Article  Google Scholar 

  18. 18.

    Zham P, Arjunan S, Raghav S, Kumar DK (2017) Efficacy of guided spiral drawing in the classification of Parkinson’s Disease. IEEE J Biomed Health Inform 22(5):1648–1652

    Article  Google Scholar 

  19. 19.

    Pfeiffer HCV, Løkkegaard A, Zoetmulder M, Friberg L, Werdelin L (2014) Cognitive impairment in early-stage non-demented Parkinson’s disease patients. Acta Neurol Scand 129(5):307–318

    CAS  Article  Google Scholar 

  20. 20.

    Thomassen AJ, Teulings H-L (1983) Constancy in stationary and progressive handwriting. Acta Physiol (Oxf) 54(1–3):179–196

    Google Scholar 

  21. 21.

    Ma H-I, Hwang W-J, Chang S-H, Wang T-Y (2013) Progressive micrographia shown in horizontal, but not vertical, writing in Parkinson’s disease. Behav Neurol 27(2):169–174

    Article  Google Scholar 

  22. 22.

    du Prel J-B, Röhrig B, Hommel G, Blettner M (2010) Choosing statistical tests: part 12 of a series on evaluation of scientific publications. Dtsch Ärztebl Int 107(19):343

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Fritz CO, Morris PE, Richler JJ (2012) Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen 141(1):2

    Article  Google Scholar 

  24. 24.

    American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Association, Arlington

    Google Scholar 

  25. 25.

    Lewis FM, Lapointe LL, Murdoch BE, Chenery HJ (1998) Language impairment in Parkinson’s disease. Aphasiology 12(3):193–206

    Article  Google Scholar 

  26. 26.

    Zham P, Arjunan S, Raghav S, Kumar DK (2017) Efficacy of guided spiral drawing in the classification of Parkinson’s Disease. IEEE J Biomed Health Inform 22(5):1648–1652

    Article  Google Scholar 

  27. 27.

    Rosenblum S, Samuel M, Zlotnik S, Erikh I, Schlesinger I (2013) Handwriting as an objective tool for Parkinson’s disease diagnosis. J Neurol 260(9):2357–2361

    Article  Google Scholar 

  28. 28.

    Marsden C (1982) The mysterious motor function of the basal ganglia: the Robert Wartenberg Lecture. Neurology 32(5):514–539

    CAS  Article  Google Scholar 

  29. 29.

    Schwab RS, England AC, Peterson E (1959) Akinesia in Parkinson’s disease. Neurology 9(1):65–65

    CAS  Article  Google Scholar 

  30. 30.

    Redgrave P, Rodriguez M, Smith Y, Rodriguez-Oroz MC, Lehericy S, Bergman H, Agid Y, DeLong MR, Obeso JA (2010) Goal-directed and habitual control in the basal ganglia: implications for Parkinson’s disease. Nat Rev Neurosci 11(11):760

    CAS  Article  Google Scholar 

  31. 31.

    Maillet A, Krainik A, Debû B, Troprès I, Lagrange C, Thobois S, Pollak P, Pinto S (2012) Levodopa effects on hand and speech movements in patients with Parkinson’s disease: a FMRI study. PLoS One 7(10):e46541

    CAS  Article  Google Scholar 

  32. 32.

    Ho AK, Iansek R, Marigliani C, Bradshaw JL, Gates S (1999) Speech impairment in a large sample of patients with Parkinson’s disease. Behav Neurol 11(3):131–137

    CAS  Article  Google Scholar 

  33. 33.

    Rusz J, Čmejla R, Růžičková H, Klempíř J, Majerová V, Picmausová J, Roth J, Růžička E (2011) Acoustic assessment of voice and speech disorders in Parkinson’s disease through quick vocal test. Mov Disord 26(10):1951–1952

    Article  Google Scholar 

  34. 34.

    De Letter M, Santens P, Van Borsel J (2005) The effects of levodopa on word intelligibility in Parkinson’s disease. J Commun Disord 38(3):187–196

    Article  Google Scholar 

  35. 35.

    Ricciardi L, Bloem BR, Snijders AH, Daniele A, Quaranta D, Bentivoglio AR, Fasano A (2014) Freezing of gait in Parkinson’s disease: the paradoxical interplay between gait and cognition. Parkinsonism Relat Disord 20(8):824–829

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge the funding supported by RMIT University scholarship and clinical support from Monash Medical Centre, Melbourne, Australia.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Dinesh Kumar.

Ethics declarations

Conflicts of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zham, P., Kumar, D., Viswanthan, R. et al. Effect of levodopa on handwriting tasks of different complexity in Parkinson’s disease: a kinematic study. J Neurol 266, 1376–1382 (2019). https://doi.org/10.1007/s00415-019-09268-2

Download citation

Keywords

  • Parkinson’s disease
  • Levodopa
  • Kinematic
  • Dysgraphia