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Weekly UpdatesLimitations and Further Recommendations
Timed tests do not reflect all aspets of the movement disorder of PD, but mainly bradykinesia. To provide a more complete picture of the motor impairment, it is useful to add the motor examination section of the UPDRS, or at least tremor and rigidity ratings according to the UPDRS, to each test occasion. Such ratings are easy to perform, and detailed instructions, including a video teaching tape, are available. (11)
One problem with the original timed tests according to CAPIT, as well as the walking test as it appears in CAPSIT-PD, is that no time limits have been set for their completion. In patients with, for example, severely impaired gait, this can result in unreasonable situations in which the patient may take up to 5 minutes to complete the test. Furthermore, there is no rational way to treat data from patients who are unable to perform or complete tasks when these data are analyzed together with those from patients who completed tests.
For these reasons, the hand/arm movement was modified in the CAPSIT-PD. Originally, in CAPIT the time taken to complete 10 movement cycles was recorded, (19) whereas CAPSIT-PD recommends the number of movements completed in 20 seconds be recorded. (6) No such set time limits have been suggested for the other tests, including the walking test in CAPSIT-PD. Instead, it is recommended that an a priori maximum time limit for the walking test be defined by each investigator. (6) Hence, different centers may apply different standards, prohibiting valid comparisons of results from different investigators, because the change score will be dependent not only on patients' performances before and after intervention but also on the predefined maximum value assigned to failed tests. Similarly, the lack of a time limit will influence the effect size (i.e., the responsiveness to change) of the test, which in turn has implications for the validity of the test.
Until this issue has been more thoroughly addressed, a time limit of 90 seconds (although not rigorously evaluated but based on clinical experience) is suggested for the walking test in order to circumvent this problem. Hence, when a patient fails to complete the whole walking distance or cannot walk at all, 90 seconds should be recorded as the test result. In addition, the distance and number of steps completed at 90 seconds should be recorded. This will enable researchers to use both the required time to walk 2 x 7 meters and the speed of gait, expressed as meters per second (calculated also from incomplete test performances), as outcome measures of this test.
In contrast to the hand/arm movement between two points and the walking test, (4,5,15,21) formal evaluations of the finger dexterity and pronation/supination tests are sparse. One concern about the finger dexterity and pronation/supination tests is that they do not necessarily reflect the level of bradykinesia, because the time taken to complete them is influenced not only by the speed but also by the quality of movements. For example, a severely hypokinetic patient may perform finger dexterity relatively fast but virtually without any movement amplitude at all, which renders the outcome measure for bradykinesia (i.e., the time taken to perform the test) inconclusive. Therefore, the value of these tests has been questioned, (18) and this is the main reason they were omitted in the revised CAPSIT-PD protocol.
According to the experience of our own and other research groups, these tests can, however, be useful; they have been shown to broadly agree with other valid and quantitative measures of parkinsonian impairments and to correlate with the level of striatal dopaminergic deficiency. (13,14,23) Furthermore, in clinical trials, the omission of pronation/suppination of the hands and finger dexterity should be adopted cautiously. In clinical transplantation trials in PD, for example, virtually all investigators so far have used the pronation/supination test as the quantitative measure of bradykinesia, while only a minority have reported results from the other timed tests. To allow for comparisons with results from clinical trials performed to date, it is recommended that this test also be used in future transplantation trials. (20)
Clinical Value of Timed Tests
We have used timed tests for well over a decade for scientific as well as clinical purposes. In our experience these tests are valuable and sometimes a more reliable complement to clinical rating scales for quantification of motor function. The timed tests may, for example, be used as a tool for assessment and determination of dopaminergic responsiveness in the differential diagnosis of idiopathic PD and other atypical forms of parkinsonism. To exemplify this, the results from two single-dose levodopa challenges are depicted in Fig 1 and Fig 2.
[FIGURES 1-2 OMITTED]
The patient in Fig 1 was diagnosed with idiopathic PD and had been on a combination of different anti-parkinsonian medications for 7 years. He received a test dose of 150 mg standard oral levodopa (given together with a peripheral dopadecarboxylase inhibitor, pDDI). As illustrated in the figure, there is a significant levodopa response that begins after 30-45 minutes and has a duration of about 100 minutes, with clear improvements in all three test parameters. By 45 minutes after levodopa intake, rigidity decreased markedly and diminished 15 minutes later; walking speed and stride (as measured by the number of steps required to walk 2 x 7 meters) both improved by about 50%; and upper limb bradykinesia (as measured using the pronation/supination test) improved by about 30%. By 150 minutes after levodopa intake, all test measures had returned to baseline.
The patient illustrated in Fig 2 also was diagnosed with idiopathic PD and had been on a combination of different anti-parkinsonian drugs for several years. He was reported to have a moderate anti-parkinsonian drug response when referred to us for optimization of treatment. As clearly shown in the figure, the tests did not detect any improvements after a test dose of 200 mg standard oral levodopa (+pDDI). Subsequently, following further investigations, this patient was re-diagnosed with striatonigral degeneration, a multiple system atrophy.
When timed tests are used as means of evaluating dopaminergic responsiveness, an important issue is the magnitude of improvement required for the response to be considered positive. The hand/arm movement between two points is the timed test that has been applied most widely and evaluated best for use in determining dopaminergic responsiveness. This test has demonstrated a 100% sensitivity and specificity in detecting modifications of velocity when a threshold between 10% and 20% improvement is used, (4) and a 15% threshold has been confirmed to be adequate in assessment of dopaminergic responsiveness of bradykinesia. (15) Although the other tests have not been formally evaluated in the same way, it seems reasonable to presume a similar cut-off threshold would be adequate for them as well. Timed walking tests have, for example, been shown to exhibit good correlations with the motor examination score of the UPDRS, (21) which in turn has high sensitivity and specificity for dopaminergic responsiveness when a cut-off value between 15% and 20% improvement compared with the drug-free condition is used. (10,24) Both the hand/arm movement and walking tests also improve significantly following dopaminergic stimulation in idiopathic PD. (5) CAPIT and CAPSIT-PD advocate a 33% improvement in the UPDRS motor score as a criterion for dopaminergic responsiveness. This recommendation has, however, been advanced to avoid inclusion of patients with non-idiopathic PD in clinical trials of new, experimental, invasive therapeutic interventions.
Discussion
Timed motor tests are valuable for scientific as well as clinical assessment of motor function in parkinsonian patients. Timed tests offer a quantitative complement to other clinical rating scales, and a combination of the two is, thus, advantageous. In addition to the use recommended in the CAPIT and CAPSIT-PD protocols (i.e., for evaluation of novel therapeutic interventions), timed tests are also useful in other, non-interventional clinical research. These tests provide simple and reliable measures of motor function that easily can be implemented in studies exploring, for example, relationships between motor function and other phenomena in PD. In clinical practice, they may be helpful in assessing dopaminergic responsiveness as part of the often difficult task of distinguishing between idiopathic PD and atypical forms of parkinsonism. Attention must be paid to the methodology in order to achieve reliable and valuable results. These tests are associated with minimal costs, are easy to use, and can be applied clinically by anyone experienced with parkinsonian patients.
Summary
To maximize the value of timed motor tests, attention must be paid to methodological issues of consistency in test procedures between examiners, as well as external conditions, such as where and when tests are performed. When these requirements are fulfilled, timed tests are a valuable quantitative complement to other, more qualitative, assessment tools for PD in clinical research and practice. Although all timed tests suggested in CAPIT appear useful, only the ones recommended in CAPSIT-PD have been formally evaluated. The choice of tests should be guided by the possibility for comparing results from different studies, as well as the validity of the tests. By applying valid response criteria, the timed tests can be useful when dopaminergic responsiveness is assessed, and thereby contribute to solving the often difficult diagnostic enigma of parkinsonian syndromes. For optimal use of the timed motor tasks, anyone involved with clinical assessment of motor function in PD patients should be aware of both their strengths and weaknesses, as well as of how to best circumvent threats to their usefulness and validity. With these considerations in mind, timed motor tests are easy to use, yield quantitative measures of motor function, and can be applied clinically by anyone working with parkinsonian patients.
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