Journal of Neurology

, Volume 266, Issue 6, pp 1376–1382 | Cite as

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

  • Poonam Zham
  • Dinesh KumarEmail author
  • Rekha Viswanthan
  • Kit Wong
  • Kanae J. Nagao
  • Sridhar Poosapadi Arjunan
  • Sanjay Raghav
  • Peter Kempster
Original Communication


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.


Parkinson’s disease Levodopa Kinematic Dysgraphia 



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

Compliance with ethical standards

Conflicts of Interest

The authors declare that they have no conflict of interest.


  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:1–10Google Scholar
  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–e000628Google 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. 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):e0162799Google 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 171–176Google Scholar
  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. 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 8:435Google 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 414–418Google Scholar
  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):289–297Google 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):609–623Google 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):71–84Google 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. 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):181–184Google 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):1755–1762Google 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):2129–2170Google 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):695–699Google 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):2649–2653Google 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):1648–1652Google 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):307–318Google Scholar
  20. 20.
    Thomassen AJ, Teulings H-L (1983) Constancy in stationary and progressive handwriting. Acta Physiol (Oxf) 54(1–3):179–196Google 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):169–174Google 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):343Google Scholar
  23. 23.
    Fritz CO, Morris PE, Richler JJ (2012) Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen 141(1):2Google Scholar
  24. 24.
    American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Association, ArlingtonGoogle Scholar
  25. 25.
    Lewis FM, Lapointe LL, Murdoch BE, Chenery HJ (1998) Language impairment in Parkinson’s disease. Aphasiology 12(3):193–206Google 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):1648–1652Google 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):2357–2361Google Scholar
  28. 28.
    Marsden C (1982) The mysterious motor function of the basal ganglia: the Robert Wartenberg Lecture. Neurology 32(5):514–539Google Scholar
  29. 29.
    Schwab RS, England AC, Peterson E (1959) Akinesia in Parkinson’s disease. Neurology 9(1):65–65Google 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):760Google 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):e46541Google 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):131–137Google 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):1951–1952Google 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):187–196Google 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):824–829Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of EngineeringRMIT UniversityMelbourneAustralia
  2. 2.Monash Medical CentreMelbourneAustralia

Personalised recommendations