Abstract
INTRODUCTION
Several studies suggest that exercise [1] and physical therapy [2–4] programmes improve the outcomes of Parkinson’s disease (PD) patients; however, detailed description of the treatment programmes used are not always provided. Moreover, the reported results are often different of magnitudes, possibly because of differences in the types of exercise or treatment programmes used. We searched the medical literature using the electronic databases Medline, Cinahl, Embase, PEDro, and the Cochrane Library and found several papers comparing two or more specific physiotherapy treatment regimens. Many of these trials focused on a physical therapy technique versus other interventions [4–8], while others concentrated on the importance of different forms of care delivery using combined exercises [9]. Two Cochrane reviews [10, 11] based on randomized controlled trials (RCTs) only reported that there was insufficient evidence to support or reject the efficacy of physical therapy in Parkinson’s disease. Another article [12] reviewing the current evidence for rehabilitation in Parkinson’s disease acknowledged that there has been little evidence to support the positive impact of physiotherapy on motor symptoms. Recently, a randomized trial [13] focusing on the effectiveness of physiotherapy and occupational therapy in mild to moderate Parkinson disease highlighted that the group receiving therapy showed a lack of clinically meaningful improvements in activities of daily living or quality of life in the immediate or medium term. Interestingly, the PDREHAB trial [13] was carried out based on the usual National Health Service (NHS) practices and following European guidelines. Earlier reviews did demonstrate that physiotherapy is effective in Parkinson’s disease [11], noting small significant effects on motor function but not on quality of life. A recent review by Lauzé [14] analysed 106 papers and concluded that physical activity interventions have a positive impact on physical and functional capacities in patients with Parkinson’s disease. This recent paper defined physical activity simply as a body movement produced by the action of skeletal muscles that increases energy expenditure. Hence, the evidence to support one specific form of physical therapy over another is uncertain. Furthermore, general exercise programmes are often proposed to PD patients to improve their performance and quality of life, but the evidence of the real efficacy of this approach is poor. The costs and resources needed for a physiotherapy programme are greater than those required for a general exercise programme; moreover, physiotherapy is often paid for by the health care system, while general exercise is more likely to be paid for by the patients.
The high prevalence of depression among Parkinson’s patients has been known for many years [15] and has been confirmed and characterized more recently [16]. Anecdotal communications of improvement in depressive symptoms after exercise programmes or failure to reach possible functional goals because of depressed mood in Parkinson’s patients are common; however, no formal report has been published to date, although improvements in “quality of life” after physiotherapy have been reported [4]. Assessing the difference between physical treatments in terms of autonomy and mood improvement in patients with Parkinson’s disease is clinically and socially relevant. Thus, we conducted a study of patients with stage II Parkinson’s disease according to Hoehn and Yahr’s classification to assess the efficacy of a standardized rehabilitation programme versus a generic physical exercise programme.
MATERIALS AND METHODS
The study complied with CONSORT guidelines (CONSORT flow diagram: see Fig. 1) and was approved by our hospital ethics committee (Protocol #002529/2007). The inclusion criteria were idiopathic Parkinson’s disease, as defined by Gelb et al. [17], time from diagnosis ≥24 months, Hoehn Yahr stage II, medical therapy unchanged for at least one month, and ability to follow the studyprotocol.
Exclusion criteria were contraindications for physical activity at the intensity level of the study protocol, age >85 years, Mini Mental State Examination [18] <24, score higher than three in one or more Cumulative Illness Rating Scale [19] categories, and physiotherapy treatment or supervised physical activity in the past six months.
We evaluated a sample of 297 patients selected from those followed at our movement disorders clinic; 257 were excluded because they did not meet the inclusion criteria or met one or more of the exclusion criteria. The main reasons for exclusion were the presence of comorbidity and the lack of transportation to and from the clinic throughout the study. Additionally, the lack of a stable drug regimen without on-off or frequent dosage adjustment and the presence of cognitive or mood alterations are more frequent in patients with Hoehn Yahr stage III and IV, leading to a potential major confounding.
The remaining 40 subjects gave their informed consent to participate in the experimental study, as required by the Declaration of Helsinki and the Institutional Research Ethics Committee, and were enrolled from November 2008 to October 2010. A power analysis based on FIM [20] scores indicated that an initial number of 40 subjects was necessary to have sufficient power (based on an evaluation of our clinic patients’ parameters obtained in a pilot study) to detect differences of at least three points between the two conditions with alpha set at 5% and beta set at 75%.
The study population consisted of 13 women and 27 men with an average age of 67 years (standard deviation 8.92, median 69, age range between 35 and 80 years) Table 1 summarizes the samplecharacteristics.
A randomized clinical trial design was used. The participants were randomly assigned to one of the two groups using bingo ballots extracted by a person not involved in the study; to have a balanced distribution between groups, the Urn method [21] was utilized (controlled randomization). By sheer luck, we ended up with two groups of twenty subjects each. Upon a participant’s enrolment in the study, the clinician conducting the first evaluation assessed eligibility and then sent a letter with the participant’s name to a person not involved in the other activities of the study, who performed the randomization. The participant’s group assignment was sent by mail to the clerk at the appointment desk. One group of patients participated in a physiotherapy programme based on the Royal Dutch Society for Physical Therapy guidelines (PT group) [22, 23]; the other group participated in unspecified general exercise (GE group). Both programmes were scheduled in the same manner in terms of time and therapist-to-patient ratio. A psychiatrist and two medical doctors from the Graduate School in Physical Medicine and Rehabilitation assessed the participants; they were unaware of which programme the patient was following and were instructed not to ask to the patient to describe what type of exercises he was doing, and the patients were kept blind to their group allocation. The patients were instructed to take their medications as usual, and treatment or data collection began at least one hour after the first morning dose. We planned an intention-to-treat analysis; however, all eligible patients accepted the randomization, and no one asked to be treated differently from their original allocation treatment.
We choose the Royal Dutch Society for Physical Therapy Guidelines because the Royal Dutch Society for Physical Therapy is one of the oldest scientific physiotherapy societies; furthermore, they developed a reproducible treatment that is detailed, easy for both the physiotherapist and the patient to understand and follow, and is based on a critical review of the published literature.
The experimental group followed the treatment based on the Royal Dutch Society for Physical Therapy guidelines, which aimed to improve functional independence, with an emphasis on transfers, body posture, reaching and grasping, balance and gait. We selected from the guidelines the interventions described for patients with Hoehn Yahr stage II PD.
The general exercise programme, similar to those usually proposed to Parkinson’s patients in our country, was conducted by an expert in physical education and consisted of exercises for the upper limbs, lower limbs, spine, balance and breathing.
Each patient underwent two weekly sessions of one hour each for four months (32 sessions, with a maximum of four absences for each patient). No adverse events were reported among the two groups. The patients were tested before the start of treatment, at the end of treatment and at follow-up an average of 135±20 days (range: 118–190 days) after the end of the treatment.
The Parkinson’s disease severity and progression were assessed using motor part three of the Unified Parkinson’s Disease Rating Scale [24]. The Timed Up and Go test [25] and the Functional Independence Measure [20, 26] scale were used to evaluate physical and cognitive abilities.
The Hamilton Rating Scale for Depression [27] rated the severity of observed depressive symptoms. It is presently one of the most commonly used scales for rating depression in medical research, and its use in Parkinson’s disease is included in the guidelines for depression assessment by the American Academy of Neurology [28]. All the assessments across all visits were standardized and administered at the same time of the day for each subject to avoid fluctuation due to medication cycles.
Descriptive statistics examined the distributions and ranges of scores for the individuals within the two groups, confirming that before the treatment, the groups had similar clinical characteristics. Only the FIM scores were slightly lower and the UPDRS III scores were slightly higher in the physiotherapy group. Although these differences were not statistically significant, an analysis of covariance was performed on these parameters to assess and control baseline imbalances.
Non-parametric data were analysed using the Mann Whitney test, whereas parametric testing was performed with ANOVA and Student’s t test for paired data.
RESULTS
Of the 40 recruited participants, 9 (25% PT group; 20% GE group – O.R. 1.3 I.C.95% 0.3–5.9 n.s.) dropped out after the first week of the study. The main reported reason for dropout was difficulty reaching the clinical facility on a regularbasis.
FIM
The baseline FIM scores did not show significant differences between groups (median test, p = 0.101). The physiotherapy group started with a slightly lower FIM median total score (122 vs 124 –p = 0.041) and improved after the treatment, with a median difference of 3 points. This improvement was maintained at follow-up. In comparison, the general exercise group’s median FIM was still 124 after treatment and was slightly lower at follow-up, with a median loss of 1 point. The median difference in the changes from baseline between the two groups was 3 points at the end of treatment and 4 points after the follow-up; thus, at the end of follow-up, the difference between the two groups was still significant: p = 0.015(Table 2).
UPDRS
The median trend the UPDRS III total scores for the physiotherapy group was towards a decrease. On the contrary, the general exercise group (which started with lower scores) showed a tendency towards an increase (Table 2).
The UPDRS III changes between baseline and follow-up were significantly different for both groups (Friedman test results: physiotherapy group X2 = 20.237, p = 0.001; general exercise X2 = 7.033, p = 0.030).
TUG and Walk test
The TUG results showed a significant improvement over time for the physiotherapy group, while the other group’s scores showed significant worsening (Friedman test results: physiotherapy group X2 = 24.4, p = 0.001; general exercise X2 = 6.5, p = 0.039) as reported in Table 2.
Mood evaluation
The Hamilton Rating Scale for Depression scores showed (Table 2) that the physiotherapy group patients had a slightly higher score for the pervasiveness of depressive symptoms at the baseline (p = 0.401).
In both groups, the pervasiveness of depressive symptoms showed a non-significant reduction trend (Friedman test results: physiotherapy group X2 = 3.964, p = 0.138; general exercise X2 = 3.796, p = 0.150). It should be emphasized that this reduction was mainly due to the sharp reduction in scores among the few patients with high scores.
Dropout causes were as follows: one patient died (cardiac arrest), seven patients could not continue because they were unable to reach the clinic on a regular basis for the scheduled treatment, and the last patient discontinued the programme for personal reasons unrelated to the clinical situation.
DISCUSSION
Our data suggest that the benefit of physiotherapy treatment is greater than that of general exercise. Both the FIM and UPDRS III demonstrated improvements from the baseline scores in the physiotherapy group at the end of the treatment and the maintenance of substantial benefits at follow-up (up to four months). The TUG test data also showed an improvement for the patients treated with the Royal Dutch Society for Physical Therapy protocol compared with the general exercise group.
In contrast to a study of 32 Parkinson’s disease patients [2], our exercise programme did not improve the performance on the TUG test. This may be due to our experimental design, which aimed to identify between the groups and not intragroup variations, or to the lack of Hoehn Yahr scale grade I patients in our study.
Our data show improvements in the UPDRS III, in agreement with Cholewska et al. [4]. Additionally, an inpatient study [7] reported improvements in the UPDRS III and the TUG after two weeks of intensive treatment with movement strategies by a physiotherapist but no variations when simple exercises were performed. On the contrary, we did not find a regression at follow-up.
The differences in UPDRS III scores between the patients treated with the Royal Dutch Society for Physical Therapy [23] protocol and those treated with non-specific exercises suggest that physiotherapy may help to reduce the worsening of clinical conditions, whereas the non-specific general exercise programme does not. Improvement in UPDRS III scores has been reported after many types of treatment other than physiotherapy [5], including dance [29] and whole-body vibration [6]; however, we were unable to confirm this finding in our general exercise group, which, in contrast to the physiotherapy one, showed a slight increase in UPDRS III scores from start to follow-up. Interestingly, the change in the UPDRS motor score in the physiotherapy group was greater than the minimal clinically important change (i.e., 5 points) according to Schrag A et al. [30] at the second follow-up. In addition, the FIM total score showed a slight improvement only in the experimental group. Although this result was statistically significant up to the second follow up, the improvement was too small to reach clinically detectable levels. These findings underscore the clinical relevance and the efficacy of the Royal Dutch Society for Physical Therapy guidelines for the motor outcomes assessed using the UPDRS III.
The dropout rate during the study was similar across both groups. Although the dropout group seemed to be older, the fact that the main reason for dropout was a lack of transportation to and from the clinic highlights the importance of caregivers’ contributions to decision making regarding the schedules of outpatient clinic physiotherapyprogrammes.
The effects of physical treatment on depression have not been specifically addressed; however, some papers have investigated the effects on quality of life [11, 31], which is obviously linked to mood. None of them found any difference between the compared treatments, and the reported improvements were limited to the questionnaires’ mobility subscales [4, 31]; although one study using the Schwab scale reported improved quality of life in Parkinson’s disease patients after 24 sessions of physiotherapy, no comments were made on mood variations. We utilized a tool specifically designed to assess depression and checked by a psychiatrist and found that the small difference between the two experimental groups was attributable to a few patients with high scores; therefore, no generalized conclusions can be drawn concerning the treatments’ effects on mood. In contrast to our expectations, given the reported prevalence of depression in Parkinson’s disease [15, 16], none of our patients could be clinically classified as requiring specific treatment (drugs or psychotherapy) for depression.
A Cochrane review [32] identifying 33 trials with 1518 participants assessing walk velocity, step length and clinician-rated UPDRS III concluded, in agreement with our findings, that physiotherapy was beneficial. No evidence was found to support the effects of physiotherapy on patient-rated quality of life, nor did the treatment effect differ across the physiotherapy intervention types. Similar conclusions were drawn in a review of 39 trials of 1827 participants [33]. All the reviews were based on data concerning single-activity measures, and the only measure of disability cited was the activity of daily living; similarly, the emotional aspects were considered only in terms of “quality of life”, which in some questionnaires (for instance, EuroQuol) is strongly influenced by mobility activities.
In our study, the benefit obtained at the end of the treatment seemed to be maintained at follow-up, contrary to the findings of other published studies [5, 7]. This may be due in some cases to a longer follow-up time, a short treatment time, or, for the studies with a shorter follow-up time, a different schedule of treatment duration and intensity. Because there was no comparison with patients who did not undergo treatment, the impact of nonspecific factors (for instance, the level and intensity of ordinary motor activities) on treatment outcome cannot be determined. However, it was not possible to establish whether the stability of the follow-up outcome was due to the intervention alone or to compliance with regular therapy or home exercises.
A limitation of this study is the small sample size, which may have made it impossible to detect significant differences for more outcomes. Due to our sample characteristics, the results can give clinical hints concerning the more appropriate physical treatment only for people with stage II PD and no or mild cognitive impairment who are in overall good clinical condition and able to be followed by a clinic. Our sample of only 40 subjects from a population of 297 shows that these patients are not common, and this finding could limit the generalizability of the study. Our work was carried out in an outpatient clinic, and patients needed to be able to reach the facility for treatment via public transportation or a caregiver’s car. Most patients in stages above Hoehn Yahr II did not have a driver’s license and were unable to safely use public transportation or did not have access to a driver.
Hence, further data are needed to investigate whether this benefit is limited to this population of patients or if similar results can be obtained in patients with more severe symptoms or other conditions, for instance, in patients with a low MMSE or with co-morbidities.
A methodological limit is linked to the practical impossibility of completely blinding the patients; we tried to overcome the problem using an identical schedule and location of the treatments hoping that none of the patients was able to distinguish a physiotherapy exercise from a general one. A further limitation is related to the variability in the timing of the follow-up visits. However, none of the participants who received the allocated intervention were lost to follow-up.
In summary, our data suggest that physiotherapy treatment is superior to general exercise in terms of the effectiveness of meeting specific aims for patients with Parkinson’s disease at stage II of the Hoehn Yahr scale.
CONCLUSIONS
Our study results may question the utility of proposing generic exercise programmes to Parkinson’s patients; however, our experimental design does not permit us to draw conclusions on the absolute effectiveness of each treatment. Therefore, we are not stating that general exercises are not useful but only that physiotherapy (carried out according to evidence-based guidelines) seems to be more effective in Hoehn Yahr stage II PD.
CONFLICT OF INTEREST
The authors have no conflicts of interest to report.
ETHICS
The study was approved by our hospital ethics committee (Protocol #002529/2007).