|
| |
 |
|
| ORIGINAL ARTICLES |
|
| Year : 2021 | Volume
: 4
| Issue : 3 | Page : 143-148 |
|
Analysis of dysgraphia in advanced Parkinson’s disease patients following bilateral STN-DBS: a prospective study
Swapnil Kolpakwar1, Rajesh Alugolu1, Vijaya Saradhi Mudumba1, Rukmini Kandadai2, Rupam Borgohain2
1 Department of Neurosurgery, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Neurology, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
| Date of Submission | 04-Mar-2021 |
| Date of Decision | 01-Jun-2021 |
| Date of Acceptance | 18-Jun-2021 |
| Date of Web Publication | 22-Dec-2021 |
Correspondence Address:
Dr. Rajesh Alugolu
Department of Neurosurgery, Nizam’s Institute of Medical Sciences, Panjagutta, Hyderabad, Telangana 500082.
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/AOMD.AOMD_4_21
BACKGROUND: Parkinson’s disease (PD) is characterized by varying intensities of bradykinesia, rigidity, and tremor leading to disturbances in writing skills of the patient. We undertook this study to evaluate dysgraphia features in advanced PD cases and changes in these features after bilateral subthalamic nucleus deep brain stimulation (DBS). METHODS: All idiopathic PD cases who underwent DBS at our center were included in this study. Patients were assessed preoperatively for dysgraphia by analysis of handwriting in “off” phase by a single investigator on bedside testing. For quantification of micrographia, vertical length of first letter and width of the word written were calculated. An analysis of legibility of handwriting was also done for all patients using Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS). Patients were analyzed for dysgraphia at 6 months post-surgery in drug ‘off’ phase, and outcomes were correlated with baseline parameters. RESULTS: There were a total of 51 patients who were included in our study. Significant reduction was noted in postoperative Unified Parkinson’s Disease Rating Scale part III (UPDRS III) scores (P = 0.0001). Age more than 65 years was associated with less improvement in FTMTRS grades. Prevalence of micrographia reduced in the postoperative period, but the difference was not statistically significant. Median FTMTRS grade in preoperative and postoperative “off” phase was 3 and 2, respectively. Difference in pre- and postsurgery FTMTRS grades was found to be statistically significant (P = 0.00001). CONCLUSION: Subthalamic nucleus DBS results in substantial improvement in legibility of handwriting of patients, particularly in cases with age less than 65 years. Keywords: DBS, dysgraphia, handwriting, Parkinson’s disease
How to cite this article:
Kolpakwar S, Alugolu R, Mudumba VS, Kandadai R, Borgohain R. Analysis of dysgraphia in advanced Parkinson’s disease patients following bilateral STN-DBS: a prospective study. Ann Mov Disord 2021;4:143-8 |
How to cite this URL:
Kolpakwar S, Alugolu R, Mudumba VS, Kandadai R, Borgohain R. Analysis of dysgraphia in advanced Parkinson’s disease patients following bilateral STN-DBS: a prospective study. Ann Mov Disord [serial online] 2021 [cited 2023 May 30];4:143-8. Available from: https://www.aomd.in/text.asp?2021/4/3/143/333364 |
| Introduction | |  |
Parkinson’s disease (PD) is characterized by varying intensities of tremor, rigidity, and bradykinesia.[1] These primary features of the disease can have a significant secondary impact on family, social, and professional life of affected individuals. Tremors and bradykinesia can lead to disturbances in writing skills of the patient affecting the amplitude and the legibility of handwriting.[2] Micrographia is one of the prominent features of PD.[3] Apart from micrographia, tremor can cause the handwriting to be illegible. Hence, the term “dysgraphia” is more apt for PD-related features in handwriting.[4] These disturbances in handwriting skills can have serious implications in legal, financial, and banking affairs of the patient. Individuals may suffer from hindrances in professional work, especially the ones who are involved in tasks involving writing. Though the features of dysgraphia have been studied in PD, information related to changes in these skilled motor features following deep brain stimulation (DBS) has been lacking.
We undertook this study to analyze dysgraphia in cases of advanced PD and changes in these features after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) by subjective analysis of different features of handwriting along with objective quantification of metric parameters of handwriting.
| Materials and Methods | | |
Following approval from the Institutional Ethics Committee, all the patients of advanced PD who were operated for bilateral STN-DBS from December 2018 to December 2019 were included in our study. Patients were analyzed for changes in handwriting at 6 months postsurgery.
Inclusion criteria
All idiopathic PD cases found eligible by the CAPSIT-PD protocol, with advanced stages of the disease and severe motor manifestations, who underwent DBS at our center were included in this study.
Exclusion criteria
Cases that required removal of implants or who died within 6 months of surgery and could not complete the final follow-up at 6 months were not included for analysis.
Preoperative evaluation
Preoperative evaluation included a detailed history and examination to assess disease, co-morbidities, and ongoing medications. The quantum of the gross motor symptoms of disease was assessed by measuring the UPDRS III by a neurologist trained in administering UPDRS III in “off” phase after withholding the patient of his anti-parkinsonian drugs for at least 12 h. Quantification of dopaminergic treatment was done using levodopa equivalent daily dose (LEDD) using appropriate levodopa equivalent dose conversion factor for each drug.[5] Handedness of patient was assessed on the basis of history. All patients were assessed for dysgraphia by analysis of handwriting in the “off” phase by a single investigator on bedside testing (after withholding the patient of all his medications for at least 12 h), and hemicorporal UPDRS III of that side was derived. Patients were asked to write their name and place of stay on a paper in patient’s preferred language. Clinical details regarding the quantum of disease and other features were not revealed to the reviewer who was appointed for analysis of handwriting. Analysis of patient’s handwriting was done by the single investigator by comparing with the previous written records of the patient. Handwriting that became small in vertical and horizontal axes was considered as vertical and horizontal micrographia, respectively. Writing that fatigued and decreased in size with progress was considered as progressive micrographia. Different features of micrographia—(a) vertical, (b) horizontal, and (c) progressive—were noted in the “off” phase in the preoperative period. Quantification of micrographia was done by measuring the vertical length of the first letter and the width of the word written [Figure 1]. Single item handwriting score of Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) [Table 1] was used to assess the legibility of handwriting of all patients. Handwriting was rated from grade 0 to grade 4 as per the legibility of handwriting, where grade 0 stood for normal handwriting. Patients who were not able to hold pen and write were given FTMTRS grade 4. | Figure 1: Comparison of maximum vertical length and width of letter written by two different patients in preoperative (A1, A2) and postoperative periods (A3, A4). (B–D) Comparison of handwriting in the preoperative (B.1, C.1, D.1) and postoperative periods (B.2, C.2, D.2)
Click here to view |
Follow-up
Overall UPDRS III, hemicorporal UPDRS III score, and LEDD were recorded at 6 months postsurgery. Postoperative analysis of handwriting was done in the drug “off” phase after depriving the patient of his anti-parkinsonian drugs for at least 12 h with implantable pulse generator (IPG) in the “on” state. Patients were asked to write the same set of words in the “off” phase that were written by patients in the preoperative “off” period, and various features of micrographia such as vertical, horizontal, and progressive components were noted by the reviewer. For quantification of change in micrographia, vertical length of the first letter and width of the word written were calculated and were compared with preoperative dimensions [Figure 1].
Statistical analysis
Statistical analysis was done using IBM SPSS (Statistical Package for the Social Sciences) trial version. The paired t-test and Wilcoxon signed-rank test were applied to test for significance. A P-value less than 0.05 was considered significant.
| Results | | |
Demography
A total of 51 patients were included in our study. There were 36 (70.59%) males and 15 (29.41%) females. The mean age of patients was 57.21 ± 10.32 years (range 36–83 years). Mean disease duration of the present cohort was 7.91 ± 4.49 years. Mean age of onset was 49.27 ± 11.1 years. Only two patients were left-handed [Table 2].
UPDRS III and LEDD
Median UPDRS III in the preoperative and postoperative “off” periods were 58 (36–83) and 35 (17–75), respectively. Median hemicorporal UPDRS III in the preoperative and postoperative “off” periods were 20 (11–27) and 10 (4–24), respectively. Differences in preoperative and postoperative UPDRS III scores (P = 0.0001) and LEDD (P = 0.0004) were found to be statistically significant. Postoperatively, there was a significant reduction in upper limb resting tremors (P = 0.0001) as well as action tremors (P = 0.0001). Similar statistical difference was noted in bradykinesia and rigidity subscores (P = 0.0001) [Table 3].
Prevalence of micrographia
Preoperatively, 28 (54.90%) patients had vertical micrographia, 14 (27.45%) patients had horizontal micrographia, and 24 (47.06%) patients had progressive micrographia. After surgery, 14 (27.45%) patients had vertical micrographia, whereas 11 (21.15%) patients had horizontal micrographia and 15 (29.41%) patients had progressive micrographia [Table 4]. Three (5.88%) patients had new onset vertical micrographia and progressive in the postoperative period, and six (11.76%) patients had new onset horizontal micrographia which was not present preoperatively. The prevalence of micrographia was reduced in the postoperative period, but the difference was not statistically significant via paired t-test [Table 4]. | Table 4: Frequency distribution of patients with micrographia in the preoperative off phase and postoperative off phase
Click here to view |
Fahn-Tolosa-Marin Tremor Rating Scale
The tremor component of handwriting was assessed by FTMTRS grading. There were 8, 15, and 28 patients in grades 1, 2, and 3, respectively, with none in grade 0, in the preoperative period. Postoperatively, only 10 (19.61%) patients had FTMTRS grade 3 handwriting. Postoperatively, four patients (7.84%) had deterioration in FTMTRS grades. Maximum patients (n = 22, 43.14%) had improvement in FTMTRS grades by 1 [Table 5]. Median preoperative FTMTRS grade in the “off” phase was 3 [Figure 1]. Post-DBS FTMTRS grade median in the “off” phase was 2. Difference in pre- and postsurgery scores was found to be statistically significant via the Wilcoxon signed-rank test (P = 0.00001).
Correlation of dysgraphia with demographic and clinical parameters
Patients with age more than 65 years of age had less improvement in FTMTRS grades (P = 0.03). No correlation was noted between FTMTRS grades and hemicorporal UPDRS III scores (P = 0.40). A significant positive correlation was seen between postoperative LEDD and FTMTRS scores (P = 0.03). Metric parameters of words written were compared in 51 cases. Mean vertical upstroke was 5.19 ± 2.01 and 5.65 ± 2.42 mm in the preoperative and postoperative periods, respectively. Mean horizontal width of words was 3.31 ± 1.61 and 3.88 ± 1.58 cm in the preoperative and postoperative periods, respectively. The differences in these parameters were not statistically significant [Figure 2] and [Figure 3]. | Figure 2: Boxplot demonstrating maximum vertical length of words in the preoperative and postoperative periods
Click here to view |
 | Figure 3: Boxplot demonstrating horizontal width of words in the preoperative and postoperative periods
Click here to view |
| Discussion | | |
Micrographia has been more frequently associated with PD than other movement disorders.[4] Variable incidence of micrographia ranging from 10% to 75% has been noted in the literature.[2],[6],[7] Recent trend has been to use the digitizing tablet to evaluate the handwriting of patients. Possible limitations with the digital tablets can be higher cost, non-availability at all centers, and differences in hardware and software limiting generalization of the results.[8] Subjective analysis of handwriting has comparable specificity to objective methods in detecting and distinguishing micrographia in PD from other movement disorders.[4] Although objective kinematic analysis can avoid inter-rater variability and be more accurate,[9] subjective analysis can be better in terms of being easy to perform and have a follow-up. Subjective analysis can be performed by asking the patient to write a defined set of words or sentences and noting a change in dimensions of handwriting. One of the earliest attempts to analyze handwriting was done by McLennan et al.,[10] who asked the patients to submit the serial specimens of their writing samples, most of which would be cancelled or rejected bank cheques. Ondo and Satija[11] subjected the patient to write “Today is a nice day” with eyes open and closed and correlated the effects of visual feedback on handwriting. Collett et al.[12] evaluated handwriting parameters in patients by subjecting them to write the pangram “the quick brown fox jumps over the lazy dog.” First word in the sentence “the” was analyzed using a ruler to look for changes in amplitude. To study graphological characteristics of PD cases, Ziliotto et al.[13] subjected cases to write Spanish phrase “Respiro el dulce aroma de las flores” and correlated the highest vertical amplitude of phrase and width of phrase for changes after rehabilitation measures. However, it is equally tough to get long handwriting exercises evaluated. Patients come from different strata of society with different education and native language. Streamlining all patients to write a single set of words or sentences in a single language can thus result in a bias and may always not be possible. Even stress during testing has also been known to affect the quality of handwriting.[10] Hence, to get the best possible handwriting, we asked the patient to write their name and place of stay, which is the bare minimum an educated individual can write in their own native language and we compared the parameters in the same group in the preoperative and postoperative periods. For quantification of improvement in micrographia, we considered the usage of size metrics which was used in some similar studies in the past.[2],[11],[12],[13],[14] FTMTRS, which evaluates tremor activities during writing, has been found to have a better ability to predict efficacy of anti-parkinsonian treatments.[15]
In previous studies, outcomes of the DBS were correlated to changes in gross motor symptoms.[16],[17] Evaluation and follow-up of skilled motor movements have always been considered as secondary measures for evaluation. Deterioration in handwriting skills can lead to a change in the quality of life. Interventions for improvement in handwriting skills have been found to improve the quality of life of patients and to decrease the stress and frustration associated with the disease.[12] Various forms of treatment for PD have been evaluated for their role in changes in skilled motor movements, with most of the studies focussing on comparison of handwriting in PD patients with controls or after levodopa therapy.[18],[19] Information pertaining to changes in handwriting after interventions, particularly DBS, is however lacking.[3] Handwriting was found to be uninfluenced by stereotaxic thalamotomy.[10] Positive results of levodopa therapy have also been noted in handwriting.[20] Siebner et al[21] proved that continuous bilateral STN stimulation can lead to significant changes in handwriting. Ultimately, all these changes in handwriting pertain to improvement in cardinal manifestations of the disease. In cases with age more than 65 years, we noted a significantly less improvement in postoperative UPDRS III and handwriting scores. Handwriting improvement thus can be considered as part of a clinical response that can be seen after DBS. Inferior clinical benefits have been noted previously in patients older than 70 years of age undergoing DBS surgery.[22] Even though we noticed a significant change in tremors, rigidity, and bradykinesia after DBS, we did not notice any significant change in the micrographia component of handwriting. Though limitation of small size can be implicated as a contributory factor for not achieving significance, neural correlates pertaining to complex sequential movements can also not be neglected.[23] Bradykinesia and other symptoms are known to worsen when patients are asked to perform complex sequential movements than when asked to perform simple single events.[24],[25] New onset micrographia has also been noted after STN-DBS.[26] All these factors can contribute to partial restoration of parameters of handwriting and non-improvement of micrographia after surgery. Even though we did not notice any change in vertical and progressive micrographia, a significant change in postoperative FTMTRS grade after surgery was seen. Improvement in FTMTRS grades without change in micrographia can be expected as FTMTRS mainly assesses tremors and legibility of handwriting independent of size of letters. Beneficial effects of visual cues[27] and external auditory stimuli[28] are well known for their role in improvement of handwriting. Hence, patients with PD should also be subjected to handwriting rehabilitation measures along with pharmacological and surgical measures to achieve maximum improvement in dysgraphia.
| Conclusion | | |
STN-DBS results in substantial improvement in legibility of handwriting of patients, particularly in cases with age less than 65 years. Improvement in legibility of handwriting can be beneficial to patients and can lead to an increase in involvement in social and occupational activities.
Author Contributions
Swapnil Kolpakwar: Research project, Statistical analysis, Manuscript preparation
Rajesh Alugolu: Research project, Statistical analysis, Manuscript preparation
Vijaya Saradhi Mudumba: Research project, Review and Critique
Rukmini Kandadai: Conception, Design, Review and Critique
Rupam Borgohain: Conception, Design, Review and Critique
Ethical compliance statement
Study was conducted after approval from Institutional Ethics Committee. Written informed consent was taken from all participants included in the study. A statement on ethics committee permission and ethical practice is included under the ‘Materials and Methods’ section.
Acknowledgements
The authors are pleased to acknowledge Dr Sayali Chinnawar, Dr Kode Sashanka, Ms Syed Tazeem Fathima, and Mr Santosh Kumar for their invaluable support for conducting this study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Jankovic J. Parkinson’s disease: Clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008;79:368-76.  |
| 2. | Shukla AW, Ounpraseuth S, Okun MS, Gray V, Schwankhaus J, Metzer WS. Micrographia and related deficits in Parkinson’s disease: A cross-sectional study. BMJ Open 2012;2:e000628. |
| 3. | Letanneux A, Danna J, Velay JL, Viallet F, Pinto S. From micrographia to Parkinson’s disease dysgraphia. Mov Disord 2014;29:1467-75. |
| 4. | Bajaj NP, Wang L, Gontu V, Grosset DG, Bain PG. Accuracy of subjective and objective handwriting assessment for differentiating Parkinson’s disease from tremulous subjects without evidence of dopaminergic deficits (SWEDDs): An FP-CIT-validated study. J Neurol 2012;259:2335-40. |
| 5. | Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 2010;25:2649-53. |
| 6. | Jarzebska E. [Evaluation of effectiveness of the micrographia’s therapy in Parkinson’s disease patients]. Pol Merkur Lekarski 2006;20:688-90. |
| 7. | Ishihara LS, Khaw KT, Luben R, Bingham S, Welch A, Day N, et al. Self-reported parkinsonian symptoms in the EPIC-Norfolk cohort. BMC Neurol 2005;5:15. |
| 8. | Thomas M, Lenka A, Kumar Pal P. Handwriting analysis in Parkinson’s disease: Current status and future directions. Mov Disord Clin Pract 2017;4:806-18. |
| 9. | Miler Jerkovic V, Kojic V, Dragasevic Miskovic N, Djukic T, Kostic VS, Popovic MB. Analysis of on-surface and in-air movement in handwriting of subjects with Parkinson’s disease and atypical parkinsonism. Biomed Tech (Berl) 2019;64:187-94. |
| 10. | McLennan JE, Nakano K, Tyler HR, Schwab RS. Micrographia in Parkinson’s disease. J Neurol Sci 1972;15:141-52. |
| 11. | Ondo WG, Satija P. Withdrawal of visual feedback improves micrographia in Parkinson’s disease. Mov Disord 2007;22:2130-1. |
| 12. | Collett J, Franssen M, Winward C, Izadi H, Meaney A, Mahmoud W, et al. A long-term self-managed handwriting intervention for people with Parkinson’s disease: Results from the control group of a phase II randomized controlled trial. Clin Rehabil 2017;31:1636-45. |
| 13. | Ziliotto A, Cersosimo MG, Micheli FE. Handwriting rehabilitation in Parkinson disease: A pilot study. Ann Rehabil Med 2015;39:586-91. |
| 14. | Kim EJ, Lee BH, Park KC, Lee WY, Na DL. Micrographia on free writing versus copying tasks in idiopathic Parkinson’s disease. Parkinsonism Relat Disord 2005;11:57-63. |
| 15. | Pintér D, Forjaz MJ, Martinez-Martin P, Rodriguez-Blazquez C, Ayala A, Juhász A, et al. Which scale best detects treatment response of tremor in parkinsonism? J Parkinsons Dis 2020;10:275-82. |
| 16. | Lilleeng B, Gjerstad M, Baardsen R, Dalen I, Larsen JP. Motor symptoms after deep brain stimulation of the subthalamic nucleus. Acta Neurol Scand 2015;131:298-304. |
| 17. | Su XL, Luo XG, Lv H, Wang J, Ren Y, He ZY. Factors predicting the instant effect of motor function after subthalamic nucleus deep brain stimulation in Parkinson’s disease. Transl Neurodegener 2017;6:14. |
| 18. | Raudmann M, Taba P, Medijainen K. Handwriting speed and size in individuals with Parkinson’s disease compared to healthy controls: The possible effect of cueing. Acta Kinesiologiae Universitatis Tartuensis 2014;20:40. |
| 19. | Rosenblum S, Samuel M, Zlotnik S, Erikh I, Schlesinger I. Handwriting as an objective tool for Parkinson’s disease diagnosis. J Neurol 2013;260:2357-61. |
| 20. | Eichhorn TE, Gasser T, Mai N, Marquardt C, Arnold G, Schwarz J, et al. Computational analysis of open loop handwriting movements in Parkinson’s disease: A rapid method to detect dopamimetic effects. Mov Disord 1996;11:289-97. |
| 21. | Siebner HR, Ceballos-Baumann A, Standhardt H, Auer C, Conrad B, Alesch F. Changes in handwriting resulting from bilateral high-frequency stimulation of the subthalamic nucleus in Parkinson’s disease. Mov Disord 1999;14:964-71. |
| 22. | Chiou SM. Benefits of subthalamic stimulation for elderly parkinsonian patients aged 70 years or older. Clin Neurol Neurosurg 2016;149:81-6. |
| 23. | Wu T, Zhang J, Hallett M, Feng T, Hou Y, Chan P. Neural correlates underlying micrographia in Parkinson’s disease. Brain 2016;139:144-60. |
| 24. | Agostino R, Berardelli A, Formica A, Stocchi F, Accornero N, Manfredi M. Analysis of repetitive and nonrepetitive sequential arm movements in patients with Parkinson’s disease. Mov Disord 1994;9:311-4. |
| 25. | Marsden CD. Slowness of movement in Parkinson’s disease. Mov Disord 1989;4(Suppl. 1):S26-37. |
| 26. | Fearon C, Vijayashankar P, Olszewska DA, Goggin C, Magennis B, Quigley G, et al. Micrographia following bilateral subthalamic nucleus deep brain stimulation. Parkinsonism Relat Disord 2016;28:161-2. |
| 27. | Bryant MS, Rintala DH, Lai EC, Protas EJ. An investigation of two interventions for micrographia in individuals with Parkinson’s disease. Clin Rehabil 2010;24:1021-6. |
| 28. | Oliveira RM, Gurd JM, Nixon P, Marshall JC, Passingham RE. Micrographia in Parkinson’s disease: The effect of providing external cues. J Neurol Neurosurg Psychiatry 1997;63:429-33. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
|
Search Pubmed for