Development of an Activity Scale for Individuals With Advanced Parkinson Disease: Reliability and "On-Off" Variability.

For people affected with Parkinson disease (PD), motor performance is likely to fluctuate under the influence of pharmacological therapy.[1-3] The most benign type of L-dopa-induced fluctuations is "wearing off" or "end-of-dose" deterioration. At a later stage, more severe, abrupt, and unpredictable "on" and "off" phases may occur, during which there may be a swing from well-controlled symptoms to severe akinesia. Other treatment-related effects may be dyskinesias comprising a mix of choreatic movement and dystonia.[4,6] Dyskinesias usually occur at "peak dose," when the medication dose is most effective, during the "on" phase. However, these involuntary movements can also occur during the transition between the "on" and "off" phases--the so-called "diphasic dyskinesias." The mechanisms responsible for these fluctuations in symptoms are complex and may depend on many factors, including the rise and fall of plasma L-dopa levels and pharmacokinetic factors as well as the variability in responsiveness of dopaminergic receptors (pharmacodynamic factors).[1,3,5]

Currently available clinical scales used for the evaluation of people with PD, such as the Unified Parkinson's Disease Rating Scale (UPDRS)[6] and the Hoehn and Yahr Scale[7] designed for people in all stages of the disease, appear to us to be essentially global measures covering components of disability as well as impairment. Although the reliability and validity of measurements obtained with the UPDRS are well-established, the scale includes several items that we believe are not very relevant to physical therapy (eg, items on speech, facial expression, salivation, swallowing).[8-10] Moreover, the relatively long time it takes to obtain the measurements (the motor examination part alone includes 27 ratings), in our view, makes the UPDRS impractical for patients who are prone to sudden fluctuations of dopaminergic status. Therefore, we developed a 10-item scale to characterize the functional problems of people who are in the middle and advanced stages of PD.

Reliability of measurements of motor performance in people with PD has been studied mainly in patients in the early and middle Hoehn and Yahr stages.[11-13] In these people, measurements of musculoskeletal impairments as well as timed functional tests such as turning 360 degrees and walking and rising from a supine position to a standing position were found to be sufficiently repeatable for retesting after several days.[11] Similarly, reliability was evaluated for a number of balance tests during the peak-dose period in patients with and without a history of falls.[12] Both immediate test repetitions of spatiotemporal gait measures (conducted every 15 minutes) and delayed test repetitions of spatiotemporal gait measures (conducted after a 24-hour interval) resulted in stable measurements of walking speed, cadence, stride length, and double support duration, provided that patients were tested in the "on" phase and had a relatively short disease duration (mean=8.3 years).[13] However, O'Sullivan et al[14] and MacKay-Lyons[15] found that measurements of gait-related variables obtained in people with chronic PD (mean disease durations of 13 and 15 years, respectively) differed in major ways when comparing "on," "wearing off," and "off" conditions. The intrasubject variability, in our opinion, illustrates a dramatic and inconsistent effect of medication on gait performance.

In summary, it seems that measuring outside of the periods in which medication is working optimally leads to greater variability in measurements. This is not considering the confounding influence of "peak-dose" dyskinesias, which are most likely to occur at the time of a presumed stable effect of medication on functional or motor performance (or mobility). As most researchers have addressed either impairment variables or isolated measures of motor performance, the question for us remains whether the performance of functional activities can be measured reliably in the context of L-dopa-induced variability. Therefore, we conducted 2 related studies. In study 1, we examined the intertester reliability and internal consistency of measurements obtained with a newly developed activity scale. In study 2, we examined whether randomly occurring fluctuations ("on-off" and dyskinesias), as rated by the patients themselves, led to differences in functional performance. Functional performance refers to motor activities such as basic transfer movements and walking. We also investigated the test-retest stability of 6 consecutive measurements during one day within the self-rated "on" and "off" phases.

Method

Subjects

Twenty-nine patients attending a weekly outpatient clinic for movement disorders volunteered to participate in both studies. They were selected over a period of 6 months from a cohort of 275 patients with PD and had motor problems warranting rehabilitation in the areas of gait, moving from a sitting position to a standing position, and bed mobility. The suitable candidates were recruited consecutively as they presented themselves in the outpatient clinic. None of the participants, however, were receiving rehabilitation at the time of study. Subjects also had to have a diagnosis of idiopathic PD confirmed by a consultant neurologist and had to be medically stable (ie, not likely to require an adaptation of their medication regimen). Subjects were excluded if they had: (1) cognitive deficits (a score of less than 23 on the Mini Mental State Examination[16]), (2) other acute medical problems influencing mobility, (3) severe dyskinesia (a score greater than 2 on item 33 of the UPDRS[6]), and (4) unpredictable "off" periods (a score of 0 on item 37 of the UPDRS). Screening took place during a pretrial interview, after which the subjects were asked to sign a consent form. The subjects were categorized in the Hoehn and Yahr stages for the "on" and "off" phases. Table 1 contains a summary of the characteristics of the subjects.

Table 1. Clinical Characteristics of Patients (N=29)

                           N       [bar]X    SD      Range

Age (y)                              64.1    6.2    49-76

Duration of Parkinson
disease (y)                          11.7    4.9     6-22

Sex
  Male                  18 (62%)
  Female                11 (38%)

Hoehn and Yahr
stage ("on")(a)
  II                     3 (10%)
  II.5                  14 (48%)
  III                   12 (42%)
  IV                     0 (0%)

Hoehn and Yahr
stage ("off")(b)
  II                     0 (0%)
  II.5                   2 (7%)
  III                    9 (31%)
  IV                    18 (62%)

Medication used
  during study (mg)
  L-dopa substitutes    29          625.9    239   200-1,000
  Pergolide             10           2.45   0.78     1-3
  Bromocriptine          7           22.1    7.6    15-30
  Amantadine            12          162.5   48.3   100-200
  Selegeline             8            7.5    2.7     5-10

(a) "On" phase is when the action of medication is considered optimal.

(b) "Off" phase is when the action of medication is strongly decreased or absent.

Parkinson Activity Scale

Ten test items concerning key areas of disability in PD were constructed based on physical therapy goals relevant to the middle and later stages of the disease. As described in the literature, such practice would consist of using cues, cognitive planning, and biomechanically efficient strategies to aid functional motor performance.[17-21] The scale contents reflected the following movement problems in PD: (1) difficulties with controlling the center of body mass when rising from a chair and vice versa as a result of impaired balance and insufficient velocity of forward flexion of the trunk,[22] (2) hesitation, festination, and freezing when turning and starting to walk,[23] (3) impaired axial mobility, particularly prominent when rotating and positioning the trunk in bed,[17,24,25] and (4) difficulties with executing complex movements such as carrying out 2 tasks at once (eg, moving bedcovers and transferring in and out of bed).[26,27]

The items of the Parkinson Activity Scale (PAS) are described in the Appendix and are divided into 4 categories: chair transfers, gait akinesia, bed mobility, and bed mobility with cover. A 5-point scoring system (0-4) was devised, corresponding to that used in the UPDRS. The maximum score indicated test performance without difficulties. Carrying out the overall task more slowly than people without health problems was seen by us as without difficulty in the context of chronic disease. A minimum score implied that the subject required physical help. In-between scores (1-3), usually expressed in nonexplicit terminology such as "mild," "moderate," and "severe," were defined according to the degree of movement efficiency and to the extent to which an adequate end position was reached. In the case of bed movements, grades represented the number of problems occurring in these areas.

Procedure

Study 1. Two physical therapists, one (aged 23 years) with 1 year of experience in neurology and one (aged 38 years) with 10 years of experience in neurology, participated in the interrater reliability study. The subjects carried out the test items of the PAS while being videotaped. Following completion of testing, the 2 raters scored the videotapes independently of each other (initial reliability test). Six weeks after improving the definitions of the scoring criteria, the procedure was repeated (final reliability test). The subjects performed the tests mostly during the "on" phase and in 3 cases during the "off" phase.

Study 2. In this study, "on-off" variability and test-retest repeatability of the scale were examined. The junior therapist involved in study 1 tested the same subjects at their home on 6 occasions dispersed over 2 medication cycles within one day. The first test was carried out 90 minutes after the subject took the first morning dose of medication. This test was followed by 2 additional evaluations repeated at 1-hour intervals. The hour between repetitions was timed from the beginning of the previous test. The same test sequence was used in the afternoon starting 90 minutes after the midday dose. The subjects took their medication as normal. In an effort to minimize variability, we used the PAS in a standardized fashion adapted to each home situation. For chair rise (item 1), an armchair with a seat height of between 40 and 45 cm was chosen. The order of test categories was randomized so that fatigue or stiffness would not influence performance. On average, 20 minutes (range= 15-28) was needed to obtain the measurement. Missing values were generated on 2 occasions during the sixth test due to fatigue.

Additional scores were given to record the occurrence of "on-off" fluctuations of motor performance during the 6 measurements. Because the "on" and "off" phases are acknowledged to be highly individual and sometimes occur randomly, describing a variety of conditions for different patients, a self-rating procedure was used in agreement with the Core Assessment Program for Surgical Interventional Therapies (CAPSIT) recommendations.[28] Our purpose in adopting a self-monitoring method was our belief that it would allow discriminating between "on" and "off" phases and thus controlling for the confounding effects of medication independent of time. Therefore, the "on-off" score (0-2) represented the subjects' own evaluation of their response to medication, in agreement with the researcher, using their normally experienced fluctuations as a point of reference.

Before recording the occurrence of "on-off" fluctuations of motor performance, we explained the operational definitions of the "on-off" phenomena to the subjects. We defined the "on" phase (2) as the typical stable level of motor performance present at peak dose, when the action of medication was considered optimal. We defined the "off" phase (0) as the typical stable level of motor performance at the end of dose, when the action of medication was strongly decreased or absent. We defined "wearing off" (1) as the unstable period in which a patient changes from the "on" phase to the "off" phase. Similarly, the subjects monitored the presence and severity of dyskinesias as absent (2), mild, without interference with the motor tasks involved (1), or moderate, interfering with the efficiency of performance (0). In our descending scoring scale, the highest score (2) indicates the best condition for the patient, and the lowest score (0) indicates the worst condition for the patient. These variables were scored after the measurement of the PAS items so as not to bias the observer.

Data Analysis

Study 1. Interrater reliability for each item was calculated using the weighted Kappa coefficient[29] (Kw), which is appropriate for ordinal data. A Cronbach alpha and item total correlations were used to assess the internal consistency of the PAS total score (range= 0-40) and the 4 subscale scores: chair transfers (range=0-8), gait akinesia (range=0-8), bed mobility (range=0-12), and bed mobility with cover (range= 0-12).

Study 2. Subsequent to the analysis of internal consistency, our statistical analysis considered the 4 summed subscale scores and the total score as continuous data, requiring the use of parametric statistics. The gait akinesia subscale scores were not normally distributed, which led us to perform a logarithmic transformation. To explore the test-retest reliability of the 6 measurements obtained during one day, a linear mixed model[30] was used, enabling correction for missing values and confounding variables such as age, sex, and disease duration. The separate estimation of regression lines for each subject's "on" and "off" phases allowed for the random occurrence of fluctuations within the subjects (also for having dyskinesia). The "wearing-off" phase was not included in the analysis because of its very infrequent occurrence. The significance and size of the difference between "on" and "off" phase performance and having dyskinesias were analyzed. We then calculated separate test-retest reliability values for the "on" and "off" phase status. We used an intraclass correlation coefficient (ICC), the ratio of the between-subject variability over the total variability. Total variability was the sum of the within-subject variability (the variability between the subject-specific intercepts in the "on" or "off" phase) and the between-subject variability (the measurement error in the "on" or "off" phase).[32] The formula for the ICC is comparable to the one described by Shrout and Fleiss,[31] but it differs in that it is based on PROC MIXED,[32] an SAS procedure that can incorporate unequal numbers of repetitions by fitting a regression model for each subject and combining the results of all subjects. As a measure of the size of variation within the "on" or "off" phase, the square root of the within-subject variability was computed as a percentage of the range of scores.

We examined the possibility of a fatiguing effect (systematically descending slope) or a training effect (systematically ascending slope) over the 6 occasions for the "on" phase status. Using the linear mixed method, we tested whether the slopes differed significantly from zero.

Results

Study 1: Interrater Reliability and Internal Consistency

Results for interrater reliability of the PAS measurements of the initial trial showed that 6 items had Kappa values greater than .70, which is considered the acceptable standard of agreement[33] (Tab. 2). Analyzing the weaker results in more detail revealed systematic interpretation differences between the 2 raters. Scoring criteria were adapted as follows. For item 4, compensatory behavior such as slowing down before turning was determined as normal; mild difficulties pertained to actual interruptions. For items 5 through 7, the pelvis was regarded as part of the trunk. Concerning items 8 through 10, 3 or more corrections of the blanket were defined as abnormal. After improving the scoring criteria, intertester reliability had Kappa values ranging from .86 to .98 (weighted Kappa final trial).

Table 2. Interrater Reliability and Internal Consistency for the Parkinson Activity Scale: Weighted Kappa Values of Agreement Between 2 Raters (Kw), and Item Total Correlations (ITC) (N=29)

                                 Kw        Kw
                              (Initial   (Final
Item                           Trial)    Trial)   ITC

 1. Getting up from a chair      .97      .97     .29
 2. Sitting down                 .84      .86     .35
 3. Gait initiation             1.00      .92     .77
 4. Turning 360 [degrees]        .62      .95     .63
 5. Lying down on the bed        .59      .93     .67
 6. Rolling onto the side        .94      .96     .73
 7. Rising from the bed          .36      .98     .76
 8. Lying down on the bed
    with cover                   .66      .98     .74
 9. Rolling onto the side
    with cover                   .84      .97     .69
10. Rising from the bed
    with cover                  1.00      .98     .87

The Cronbach alpha for the PAS as a whole was .85. Values for the 4 subscale scores were .76 for chair transfers, .75 for gait akinesia, .79 for bed mobility, and .89 for bed mobility with covers. The item total correlations are displayed in Table 2. This statistic, expressing the strength of the relationship between each item on the scale and the sum score, varied between .29 and .87.

Study 2

Descriptive data. Thirteen subjects (44.8%) were without "on-off" fluctuations of motor performance during the home assessments. Three subjects (10.3%) who reported having predictable fluctuations at the onset of the study experienced unexpected "off" phases. Of all the evaluations carried out, 78.2% (136) were within an "on" phase, 17.2% (30) were within an "off" phase, and 4.6% (8) were within a "wearing-off" phase. Dyskinesias were absent in 75.9% (132) of the assessments, mild to moderate in 20.1% (35) of the assessment, and functionally significant (ie, having a score of 0, indicating moderate dyskinesias interfering with movement) in 4% (7) of the assessments. In one subject, mild dyskinesias were observed during an "off" phase.

Impact of fluctuations on movements. Analyzing the effects of "on-off" variation and dyskinesias on the data, we found that movements were different during the perceived "on" and "off" phases (Tab. 3). Mean differences, expressed as a percentage of the range of scores, varied from 48.2% for bed mobility with handling the cover and 29.6% for transfers from the chair. In contrast, dyskinesias did not have an effect on the movements, except for bed mobility with cover where a mean difference of -10.8% was found (P=.05). The negativity of the figure illustrated the fact that experiencing dyskinesias was associated with improved performance.

Table 3. Estimated Results From the Linear Mixed Model of the Mean, 95% Confidence Interval (CI), and Mean Percentage of the Maximum Range (Mean %) of the Difference in Measurements Between "On" and "Off" Phases and Their Significance for the 4 Movement Categories and Parkinson Activity Scale Total Score

                      Mean                     Mean %
                   Difference     95% CI     Difference     P

Chair transfers       2.37      1.41, 3.33      29.6      .0001
Gait akinesia(a)       0.4      0.20, 0.59      37.1      .0006
Bed mobility
  without cover       4.19      2.66, 5.17      34.9      .0001
Bed mobility
  with cover          5.78      4.61, 6.95      48.2      .0001
PAS total score       14.9      10.7, 19.1      37.3      .0001

(a) Results represent exponentially transformed values.

Repeatability of movements. Because of the results, separate test-retest reliability was calculated of the 6 repeated measurements for the self-rated "on" and "off" phases, which are given in Table 4. Intraclass correlation coefficients varied between .41 and .93. Stability was found for bed mobility without cover (ICC=.70 and .91) and with cover (ICC= .80 and .77) and for the total score (ICC=.81 and .93) during both "on" and "off" phases. Test-retest reliability was measured for transfers in and out of the chair in the "on" and "off" phases and was considered moderate when taking the lower confidence limits of the ICCs (.62 and .63) into account. There was a low ICC value of .41 for gait akinesia during the "on" phase. Stability was demonstrated for gait akinesia during the "off" phase (ICC=.78).

Table 4. Between- and Within-Subject Variability of 6 Repeated Measurements Within the "On" and "Off" Phases, the Square Root of the Within-Subject Variability Expressed as a Percentage of Range of Scores (% Within), Intraclass Correlation Coefficients (ICC), and 95% Confidence Intervals (95% CI)

                     Between-Subject   Within-Subject
                       Variability      Variability

Chair transfers
  "On"                     2.1              1.14
  "Off"                    3.0              1.47

Gait akinesia(a)
  "On"                    0.01              0.02
  "Off"                   0.12              0.03

Bed mobility
without cover
  "On"                    3.12              1.34
  "Off"                   10.3              1.03

Bed mobility
with cover
  "On"                    4.83              1.23
  "Off"                   3.93              1.16

PAS(b) total score
  "On"                    28.8               6.6
  "Off"                   67.3               5.4

                     % Within   ICC     95% CI

Chair transfers
  "On"                13.35     .65   0.63, 0.66
  "Off"               15.16     .67   0.62, 0.72

Gait akinesia(a)
  "On"                14.29     .41   0.39, 0.42
  "Off"               14.86     .78   0.75, 0.80

Bed mobility
without cover
  "On"                 9.65     .70   0.69, 0.71
  "Off"                8.46     .91   0.90, 0.91

Bed mobility
with cover
  "On"                 9.24     .80   0.79, 0.80
  "Off"                8.98     .77   0.75, 0.79

PAS(b) total score
  "On"                 6.42     .81   0.80, 0.81
  "Off"                5.81     .93   0.92, 0.93

(a) Results represent exponentially transformed values.

(b) PAS=Parkinson Activity Scale.

The square root of the within-subject variability, expressed as a percentage of the total range of scores, indicated the magnitude of error within each "on" and "off" phase. The PAS total score varied between 5.8% for the "off" phase and 6.4% for the "on" phase. For the subscale scores, greater variability was found, ranging from 8.5% to 15.2%. Graphic exploration of the functional scores exhibited no systematic trend upward or downward pointing to a learning effect or fatigue, which was confirmed by the linear mixed model (P [is greater than] .05).

Discussion

We examined the reliability of measurements obtained with a scale designed to assess the ability to do activities of people with PD who had a mean disease duration of 12 years and who from time to time experienced drug-induced fluctuations of motor performance. Interrater reliability of measurements obtained for the videotaped items of the PAS was established after setting specific scoring criteria and refining definitions. Whether this result generalized to real-life situations and to using a variety of different testers from various disciplines was not investigated and needs to be studied. The level of internal consistency of measurements obtained with the instrument allowed summing of total and separate category scores.

We believe that the most important finding of our study was that, when measuring repeatedly within either the self-reported "on" or "off" phase, all but one aspect of the movements studied provided relatively consistent results. High temporal repeatability was previously ascertained on measures of gait, balance, musculoskeletal impairment, and timed tests in patients with mild to moderate PD in the "on" phase.[11-13] We add to these findings that acceptable reproducibility also could be achieved in patients with considerable disease duration when measuring transfer movements and walking in the home several times. Test-retest reliability was similar within the "off" and "on" phases. There was a large difference in the number of evaluations performed in the "off" phase (30) compared with the "on" phase (136). Although this difference did not pose a statistical problem, it implied that the reliability estimates calculated for the "off" phase were less accurate than for the "on" phase. The large between-subject variability observed for the total PAS score and bed mobility in the "off" phase was probably responsible for the fact that in these cases the consistency in the "off" phase exceeded that in the "on" phase. More variable results might have been obtained by inclusion of the "wearing-off" phase. The poor result (ICC=.41) for gait initiation and turning (gait akinesia) during the "on" phase may be explained by the skewed distribution of scores not fully ameliorated with transformation. This raises the question of whether it is relevant to test this area of mobility during an "on" phase. Despite the fact that 75.9% of subjects reported having regular "freezing" or starting difficulties, these problems were difficult to provoke consistently in a standardized test situation even within a familiar environment. Earlier work emphasized the susceptibility of freezing to psychological factors, in that the higher levels of arousal and attention inherent to a test situation might prevent it from occurring.[23,34]

Having demonstrated overall satisfactory standards of test-retest reliability, the magnitude of within-subject variability remained considerable within "on" and "off" phases, especially for the subcategory scores (8.5%-15.2%). The fact that this variation was smaller for the total scores might be explained by the fact that fluctuations occurred randomly in one area of function and were cancelled out by stability in other areas. Recently, high degrees of variability in gait measurements within each "on" and "off" phase were reported in patients with longer disease duration than in our study, leading to the suggestion that measures of general functional performance might produce more stable results.[15] Our results would favor this contention.

Our results showed differences in performance of activities between self-reported "on" and "off" phases. A recent study by O'Sullivan et al[14] demonstrated similar swings of "on-off" responses in relation to gait variables, timed tests, and tapping counts following overnight withdrawal of antiparkinson medication in patients with established motor fluctuations. Mean "on-off" changes demonstrated in O'Sullivan and colleagues' study varied between 29.3% and 35.4%, percentages that overlap the range of between 30% and 48% in our study. We found that the occurrence of mild to moderate dyskinesias did not have an effect on performance of activities except on double task performance (bed mobility with cover), illustrating the activating effect of medication. Our results, however, were obtained while we excluded patients with severe dyskinesias.

Our results highlight the importance of implementing strategies to deal with the problem of confounding drug effects in clinical trials. Such methods might include (1) adopting rigorous inclusion criteria, (2) testing patients at the same time of day within the therapeutic window, and (3) carrying out repeated measurements within the same day as well as over several days to gain a valid picture of mean performance. Yet, all of these measures have a number of practical and validity problems.

Excluding patients with dyskinesias and "on-off" fluctuations of motor performance not only may seriously reduce the number of patients available for study but also may introduce selection bias, diminishing the clinical relevance of results. Notwithstanding its feasibility, measuring patients at the same time of day requires rigorous control of patients living in the community. Lack of adherence to the drug regimen as well as daily variations in response to medication make this method far from ideal. Disappointing results on adherence were recently published on a group of individuals with moderate depression but no other health problems, a large proportion (57%) of whom adhered only 50% of the time to a once-a-day drug regimen at home.[35] These findings may be extrapolated to people with advanced PD, who are characterized by a high incidence of depression[36] and a long-term requirement of multiple doses. Finally, carrying out repeated measurements may create an intolerable burden on elderly people with disabilities, who often experience problems of transportation, despondency, and fatigue.

Although we found that the most likely source of variation is due to L-dopa status, other reasons for within-subject variability were also explored in this study. Even though no evidence of fatigue was apparent, 2 subjects were not able to complete the sixth test due to exhaustion. Fatigue is a common complaint in almost 50% of people with PD,[37] a factor that needs to be managed carefully when planning repeated measurements. We found no training effect in our study, which is not surprising given that the test items consisted of well-learned daily activities.

Our results point to an additional strategy to control for fluctuations of motor performance. Subjects' self-perceptions of being in an "on" or "off" phase were used as a tool to document and thus control for their changing L-dopa status at regular intervals during the test procedure. Subjects evaluated their responses to medication using their normal fluctuations as a point of reference, a method also recommended in the CAPSIT.[28]

We believe that it makes sense to ask people with long-standing disease, who are sensitive and aware of fluctuations as part of their daily experience, to distinguish between their "on" and "off" phases. We believe that the validity of measurements obtained with this method was verified by the fact that similar levels of "on-off" differences, imposed by withdrawal of medication, were established on a comparable population, but on different variables.[14] Other researchers[38] have suggested that self-reports of disability from patients with PD can be accurate when compared with reports from their spouses, even in the presence of depression and mild cognitive decline. Furthermore, in the CAPSIT recommendations,[28] an "off" phase was operationally defined as the standardized condition observed after 12 hours after withdrawal of medication. Interfering with medication regimens was not feasible in the context of a home-based study and, more importantly, did not concur with our aim of testing for reliability against the background of naturally rather than artificially occurring fluctuations of motor performance. Further study is needed to confirm the validity of self-determinations of "on-off" status as a tool for improving reliability.

Our results not only illustrate that fluctuations have implications for measurement but also underscore the impact of these side effects for patients and clinical practice. The estimated "on-off" swings of function ranged between 30% and 48%, results that cannot be generalized to all patients with middle- and late-stage PD because patients with severe dyskinesias and unpredictable "on" and "off" phases were excluded. However, the participants represented a clinically relevant population of "possible candidates" for rehabilitation taking medication regimens that are common in advanced disease. The largest size of "off" phase deterioration was found for bed mobility with a blanket, often indicating total dependence on physical assistance.

Conclusion

Our results suggest that studies of the effectiveness of physical therapy for people with PD should occur within well-defined "on" or "off" phases to obtain comparable results. Distinguishing between possible effects of medication and rehabilitation requires adequate documentation of the pattern of fluctuations. We recommend obtaining evaluations on the basis of patients' own accounts of their L-dopa status at regular intervals throughout the test procedure.

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Appendix Parkinson Activity Scale

I. Chair Transfers

1. Getting up (From arm     --normal, without apparent
   chair; first trial         difficulties                  [] 4
   without using arms;      --without arms, mild
   then second trial          difficulties (toes
   with using arms)           dorsiflex to maintain
                              balance)                      [] 3
                            --without arms, impossible
                              or several attempts needed,
                              with arms normal              [] 2
                            --with arms, difficult
                              (several attempts,
                              hesitation)                   [] 1
                            --dependent on physical
                              assistance                    [] 0

2. Sitting down (First      --normal, without apparent
   trial without hands,       difficulties                  [] 4
   second trial with        --without arms, mild
   hands when necessary)      difficulties (uncontrolled
                              landing)                      [] 3
                            --without arms, abrupt
                              landing or ending in an
                              uncomfortable position,
                              with arms normal              [] 2
                            --with arms, abrupt landing
                              or ending in an
                              uncomfortable position        [] 1
                            --dependent on physical
                              assistance                    [] 0

II. Gait Akinesia

3. Gait initiation          --normal, without apparent
   (Tested after rising       difficulties                  [] 4
   from a chair)            --hesitation or short
                              festination                   [] 3
                            --unwanted arrest of movement
                              with or without festination
                              lasting 5 s or less           [] 2
                            --unwanted arrest of movement
                              with or without festination
                              lasting more than 5 s         [] 1
                            --dependent on physical
                              assistance to start walking   [] 0

4. Turning 360 [degrees]    --normal, without apparent
   (Testing in a              difficulties                  [] 4
   situation provoking      --hesitation or short
   difficulties in daily      festination                   [] 3
   life)                    --unwanted arrest of
                              movement with or without
                              festination lasting 5 s or
                              less                          [] 2
                            --unwanted arrest of movement
                              with or without festination
                              lasting more than 5 s         [] 1
                            --dependent on physical
                              assistance to start walking   [] 0

III. Bed Mobility

5. Lying down (The          --normal, without apparent
   patient is asked to        difficulties                  [] 4
   lie down on his or       --1 difficulty, with lifting
   her back)                  legs, moving trunk, or
                              reaching adequate end
                              position                      [] 3
                            --2 difficulties, with
                              lifting legs, moving trunk,
                              or reaching adequate end
                              position                      [] 2
                            --3 difficulties, with
                              lifting legs, moving trunk,
                              and reaching adequate end
                              position                      [] 1
                            --dependent on physical
                              assistance                    [] 0

6. Rolling onto the side    --normal, without apparent
   (The patient is asked      difficulties                  [] 4
   to roll over to the      --1 difficulty, with
   side)                      turning, shifting trunk, or
                              reaching adequate end
                              position                      [] 3
                            --2 difficulties, with
                              turning, or shifting trunk,
                              or reaching adequate end
                              position                      [] 2
                            --3 difficulties, with
                              turning, shifting trunk,
                              and reaching adequate end
                              position                      [] 1
                            --dependent on physical
                              assistance                    [] 0

7. Rising (The patient is   --normal, without apparent
   asked to get up and        difficulties                  [] 4
   sit on the edge of       --1 difficulty, with moving
   the bed)                   legs or trunk or reaching
                              adequate end position         [] 3
                            --2 difficulties, with moving
                              legs or trunk or reaching
                              adequate end position         [] 2
                            --3 difficulties, with moving
                              legs and trunk and reaching
                              adequate end position         [] 1
                            --dependent on physical
                              assistance                    [] 0

IV. Bed Mobility With
    Cover

8. Lying down with cover    --normal, without apparent
   (The patient is asked      difficulties                  [] 4
   to lie down on his or    --1 difficulty, with either
   her back under the         moving body, adjusting
   covers)                    cover, or reaching adequate
                              end position                  [] 3
                            --2 difficulties, with moving
                              body, adjusting cover, or
                              reaching adequate end
                              position                      [] 2
                            --3 difficulties, with
                              moving body, adjusting
                              cover, and reaching
                              adequate end position         [] 1
                            --dependent on physical
                              assistance                    [] 0

9. Rolling onto the side    --normal, without apparent
   with cover (The            difficulties                  [] 4
   patient is asked to      --1 difficulty, with turning
   roll onto his or her       body, adjusting cover, or
   side under the covers)     reaching adequate end
                              position                      [] 3
                            --2 difficulties, with
                              turning body, adjusting
                              cover, or reaching adequate
                              end position                  [] 2
                            --3 difficulties, with
                              turning body, adjusting
                              cover, and reaching
                              adequate end position         [] 1
                            --dependent on physical
                              assistance                    [] 0

10. Rising with cover       --normal, without apparent
    (The patient is asked     difficulties                  [] 4
    to get up and sit on    --1 difficulty, with moving
    the edge of the bed)      body, adjusting cover, or
                              reaching adequate end
                              position                      [] 3
                            --2 difficulties, with moving
                              body, adjusting cover, or
                              reaching adequate end
                              position                      [] 2
                            --3 difficulties, with
                              moving body, adjusting
                              cover, and reaching
                              adequate end position         [] 1
                            --dependent on physical
                              assistance                    [] 0

A Nieuwboer, PT, PhD, is Researcher, Neuromotor Unit, Department of Rehabilitation Science, Faculty of Physical Education and Physiotherapy, University of Leuven, Tervuursevest 101, 3001 Heverlee, Belgium ([e-mail]). Address all correspondence to Dr Nieuwboer.

W De Weerdt, PT, PhD, Professor, Department of Rehabilitation Science, Faculty of Physical Education and Physiotherapy, University of Leuven.

R Dom, MD, is Neurologist and Professor, Department of Neuroscience and Psychiatry, Faculty of Medicine, University of Leuven.

K Bogaerts, MSc, is Statistical Consultant, Biostatistical Centre of Clinical Trials, Faculty of Medicine, University of Leuven.

G Nuyens, PT, PhD, is Research Assistant, Neuromotor Unit, Department of Rehabilitation Science, Faculty of Physical Education and Physiotherapy, University of Leuven.

Dr Nieuwboer, Dr De Weerdt, Dr Dom, Dr Nuyens, and Liesbeth De Craen provided concept/research design. Dr Nieuwboer and Dr Nuyens provided writing. Dr Nieuwboer and Ms De Craen provided data collection, and Dr Nieuwboer and Mr Bogaerts provided data analysis. Dr De Weerdt and Dr Dom provided fund procurement. Dr De Weerdt provided project management and facilities/equipment. Dr Dom provided subjects and institutional liaisons. Dr De Weerdt, Dr Dom, Mr Bogaerts, and Dr Nuyens provided consultation (including review of manuscript before submission). The authors thank the patients who welcomed them into their homes and participated in the study.

This work was supported by the Research Council of the Katholieke Universiteit Leuven and the Fund of Scientific Research-Flanders.

This article was submitted April 20, 2000, and was accepted July 11, 2000.