We studied 60 PD patients who were included in the Parkinson Disease and Movement Disorders Program in the Hospital de Clinicas "Jose de San Martin" at the University of Buenos Aires. The study was approved by the local Ethics Committee and written informed consent was obtained from all subjects. Inclusion criteria were diagnosis of idiopathic PD and difficulties with handwriting and signing. The diagnosis of PD was made according to the United Kingdom Brain Bank criteria [13]. The presence of handwriting problems was specifically assessed by a neurologist from the Parkinson Disease and Movement Disorders Program. Exclusion criteria included: Mini-Mental State Examination score ≤26; severe dominant hand tremor or dyskinesia; history of other neurological diseases, such as peripheral neuropathies, stroke, or dystonia; osteoarticular diseases affecting the hand; and any other medical condition that could diminish the dominant hand skills. Hand tremor was considered to be severe when the score for items 20 and 21 of the Unified Parkinson's Disease Rating Scale (UPDRS) part-III was ≥2 points. Dyskinesia affecting the dominant hand was considered to be severe when the score for item 33 of the UPDRS part-IV was ≥2 points [14]. All patients were specifically asked not to make changes either in their pharmacological or non-pharmacological therapies during the study period.

The study design was prospective, longitudinal, and comparative. Duration of the study was 10 weeks, and all patients were evaluated at the beginning (basal evaluation) and at the end of the study (final evaluation). After the basal assessment, 30 PD patients were included in a HR program. The assignment of patients to this program was not randomized.

The group of patients assigned to HR participated in training sessions, once a week, for 9 weeks. After this period, both groups of PD patients (with and without HR) were evaluated and results between basal and final evaluations were compared.

In order to analyze the graphological characteristics, participants were asked to write a phrase (in Spanish) "Respiro el dulce aroma de las flores" with their dominant hand on a blank, 40×50 cm², white sheet of paper. The following features were measured:

1) Letter size: characterized by vertical amplitude (highest vertical stroke of the phrase in millimeters) and width (phrase length in centimeters).

2) Decreasing size of letters: vertical amplitude (millimeters) of the first and the last 'e' in the phrase.

3) Direction of handwriting (number of cases and percentage): ascending, horizontal, or descending (nominal variable) direction of handwriting with respect to the horizontal.

4) Surface area of the signature (cm²): was calculated by framing the signature within a quadrilateral with horizontal and vertical lines parallel to the sides of the sheet.

5) Superior margin (millimeters): distance from the highest vertical stroke of the phrase to the upper end of the sheet.

6) Force exerted was measured by employing the Calligraphy 2.7 software. This program classifies force from 1 (minimal) to 7 (maximal force), where 4 is considered normal.

7) Velocity or speed: number of letters written in one minute.

HR training was conducted by a graphologist and each training session lasted 90 minutes.

The purpose of HR exercises was that the patient should be able to perform the handwriting task in a less automatic manner by using different external stimuli. Visual external stimuli were provided by asking the patients to write with multiple colored inks, and by using markers with broad nibs in order to produce thick strokes and spontaneous large letter size. Patients were asked to draw freely making large strokes across the whole area of the 40×50 cm² sheet of paper. Patients were also encouraged to include shoulder strength in the act of handwriting in order to minimize arm oscillations. Execution of calligrammes was part of the training and it was aimed at improving the control of writing direction. Auditory external cues consisted of rhythmic clapping of hands by the instructors and rhythmic music in the background during the training session.

Descriptive statistics were used to show the characteristics of the sample. Student t-test for paired samples was used to compare graphological changes before and after HR. The prevalence of the direction of writing (qualitative variable) at basal and final evaluations was compared using two by two tables and the chi-square test. A p-value ≤0.05 was considered statistically significant. Statistical analyses were performed with the SPSS software ver. 20 (IBM SPSS, Armonk, NY, USA).

Sixty right-handed PD patients (33 females), with a mean age of 65.5±9.1 years (range, 41 to 84 years) participated in this study. Forty-five cases showed the wearing-off phenomenon, and in these cases, all evaluations were performed during the 'On' motor condition. After the assignment of PD patients to the groups with (n=30) and without HR (n=30), socio-demographic characteristics were similar in both groups (Table 1).

The severity of handwriting impairment was similar in both groups for all the graphological variables assessed except for force, which was higher in the group not assigned to HR (Table 2). Most of the patients in the two groups exhibited handwriting with progressively decreasing size of letters and ascending direction with respect to the horizontal (Table 2).

The most relevant changes in the group that underwent HR were higher amplitude of the first 'e' in the phrase, a larger signature surface area (Fig. 1), and a larger superior margin. There was a trend of increase in letter size (Fig. 2). Both the decreasing letter size and the ascending direction of handwriting did not change after HR. A significant increase in force was observed in the group not assigned to HR at final evaluation (Tables 3, 4).