Variability in spatiotemporal gait characteristics over the course of the L-dopa cycle in people with advanced Parkinson disease.Key Words: Gait gait (gat) the manner or style of walking. antalgic gait a limp adopted so as to avoid pain on weight-bearing structures, characterized by a very short stance phase. , Levodopa levodopa: see l-dopa. levodopa or L-dopa Organic compound (L-3,4-dihydroxyphenylalanine) from which the body makes dopamine, a neurotransmitter deficient in persons with parkinsonism. , Motor fluctuations, Parkinson disease Parkinson Disease Definition Parkinson disease (PD) is a progressive movement disorder marked by tremors, rigidity, slow movements (bradykinesia), and posture instability. . Parkinson disease (PD) generally becomes manifest with a degeneration degeneration /de·gen·er·a·tion/ (de-jen?er-a´shun) deterioration; change from a higher to a lower form, especially change of tissue to a lower or less functionally active form. of 60% to 80% of the dopaminergic neurons A dopaminergic neuron is a neuron that releases dopamine from its synapses. Dopaminergic neurons are present chiefly in the ventral tegmental area (VTA) of the midbrain, substantia nigra pars compacta, and arcuate nucleus of the hypothalamus. in the substantia nigra substantia ni·gra n. A layer of large pigmented nerve cells in the mesencephalon that produce dopamine and whose destruction is associated with Parkinson's disease. Also called nigra. or a loss of 90% of striatal dopamine dopamine (dōp`əmēn), one of the intermediate substances in the biosynthesis of epinephrine and norepinephrine. See catecholamine. dopamine One of the catecholamines, widely distributed in the central nervous system. .[1] Because it is not possible to deliver dopamine across the bloodbrain barrier and into the central nervous system, levorotary le·vo·ro·ta·to·ry also le·vo·ro·ta·ry adj. Symbol l- Of or relating to an optically active chemical that rotates the plane of polarized light to the left, or counterclockwise: dihydroxy phenylalinine (L-dopa), the precursor of dopamine, is given. The L-dopa cycle is the interval between 2 consecutive times of ingestion ingestion /in·ges·tion/ (-chun) the taking of food, drugs, etc., into the body by mouth. in·ges·tion n. 1. The act of taking food and drink into the body by the mouth. 2. of medication. Often, titration titration (tītrā`shən), gradual addition of an acidic solution to a basic solution or vice versa (see acids and bases); titrations are used to determine the concentration of acids or bases in solution. of anti-PD medications is difficult, with the therapeutic window being different for each individual and usually narrowing over time.[2] For the first 3 to 5 years, patients with PD generally have a stable clinical response to L-dopa therapy, with reduction in tremor tremor /trem·or/ (trem´er) an involuntary trembling or quivering. action tremor rhythmic, oscillatory, involuntary movements of the outstretched upper limb; it may also affect the voice and , rigidity, and bradykinesia.[3] Fluctuations in motor performance, however, become noticeable later. In advanced PD, dose-related dyskinesias during the "on" period and an end-of-dose wearing-off effect (ie, "off" period) can amplify the extent of these fluctuations. These fluctuations include changes in spatial and temporal variables of gait, such as speed, stride length stride length Biomechanics The distance between 2 successive placements of the same foot, consisting of 2 step lengths; SL measured between successive positions of the left foot is always the same as that measured by the right foot, unless the subject is walking in a curve (SL), and stride time (ST), over the L-dopa cycle.[4,5] An appreciation of the nature and extent of these fluctuations in performance is important in order for clinicians to accurately assess and manage patients and to assess the effectiveness of interventions. In preparation for a large-scale clinical trial of the effects of neural tissue transplantation involving patients with long-standing PD, it was essential to identify outcome measures that could be used to document the effectiveness of the intervention. Gait characteristics were chosen as potential outcome measures because they are functionally relevant and meaningful to both patients and clinicians and because they can be simple and inexpensive to measure and interpret. No studies have been reported that involved monitoring spatiotemporal spa·ti·o·tem·po·ral adj. 1. Of, relating to, or existing in both space and time. 2. Of or relating to space-time. [Latin spatium, space + temporal1. variables of gait over the complete L-dopa cycle in people with advanced PD. Therefore, this preliminary study, involving a small number of patients with long-standing PD, was conducted to determine whether gait variables would be sufficiently stable to be used as outcome variables in the proposed study. The objectives of the study were (1) to document spatiotemporal gait variables of people with advanced PD over the L-dopa cycle and (2) to determine whether there is a systematic pattern of fluctuations in gait variables within the L-dopa cycle and over time. Method Subjects Five individuals with the diagnosis of idiopathic idiopathic /id·io·path·ic/ (id?e-o-path´ik) self-originated; occurring without known cause. id·i·o·path·ic adj. 1. Of or relating to a disease having no known cause; agnogenic. PD were recruited with the assistance of neurologists This is a list of the most important neurologists, with their dates of birth and death and nationality.
A doctor who specializes in disorders of the brain and central nervous system. Mentioned in: Cervical Disk Disease neurologist a specialist in neurology. a minimum of 5 years before the start of the study; and to be classified as being at Hoehn and Yahr[6] stage 3 during the "on" phase of the L-dopa cycle, which meant that the subjects had bilateral involvement of the extremities ex·trem·i·ty n. pl. ex·trem·i·ties 1. The outermost or farthest point or portion. 2. The greatest or utmost degree: the extremity of despair. 3. a. and impairment of balance but were independent in ambulation am·bu·late intr.v. am·bu·lat·ed, am·bu·lat·ing, am·bu·lates To walk from place to place; move about. [Latin ambul . The subjects were also required to be able to walk 12 m without ambulatory aids or manual assistance during both the "on" and "off" phases of the L-dopa cycle and to be able to provide informed consent. The subjects had a mean age of 67.8 years (range=57.4-74.6) and a mean duration of PD of 15.0 years (range=9.2-21.2). All subjects claimed to be independent in household ambulation, but they required the assistance of another person, a walking aid, or a wheelchair for community ambulation during the "off" phase of the L-dopa cycle. None of the subjects participated in physical rehabilitation physical rehabilitation See Physical therapy. during the course of the study. Background characteristics of the 5 subjects are summarized in Table 1.
Table 1.
Background Characteristics of Subjects
Subject
No. Gender Age (y) Height (cm)
1 F 61.3 159
2 F 74.2 143
3 M 57.4 172
4 M 74.6 172
5 M 71.8 168
Duration of Hoehn and Yahr Stage
Subject Parkinson
No. Disease (y) "On" Phase "Off" Phase
1 9.2 3 4
2 16.3 3 3
3 17.8 3 4
4 10.3 3 4
5 21.2 3 4
Subject
No. Medication Daily Dosage (mg)
I Sinemet 200/20
Parlodel 12.50
Sinemet CR 1,200/300
Cogentin 2
2 Sinemet 200/20
Parlodel 15
3 Sinemet 700/175
Parlodel 25
Sinemet CR 800/200
4 Sinemet 500/125
5 Sinemet 1,500/150
Instrumentation The temporal and spatial kinematics kinematics: see dynamics. kinematics Branch of physics concerned with the geometrically possible motion of a body or system of bodies, without consideration of the forces involved. of the gait cycle were measured using a computerized resistive resistive /re·sis·tive/ (re-zis´tiv) pertaining to or characterized by resistance. walkway walkway Rehabilitation medicine An instrument used to measure the timing of foot contact and or position of the foot on the ground , as described by Grouse grouse, common name for a game bird of the colder parts of the Northern Hemisphere. There are about 18 species. Grouse are henlike terrestrial birds, protectively plumaged in shades of red, brown, and gray. et al.[7] The walkway consisted of a series of rubber mats into which 2 grids of copper-clad steel welding welding, process for joining separate pieces of metal in a continuous metallic bond. Cold-pressure welding is accomplished by the application of high pressure at room temperature; forge welding (forging) is done by means of hammering, with the addition of heat. rods were set. The walkway was 10.4 m long, with the central 7.2 m containing the rods. Dummy mats were placed at the beginning and at the end of the central area of the measurement system to eliminate the effects of accelerations and decelerations that occur at initiation and conclusion of each walking trial. Thus, there was an attempt to measure trials with subjects walking at a constant speed. A stabilized voltage source A voltage source is any device or system that produces an electromotive force between its terminals OR derives a secondary voltage from a primary source of the electromotive force. drives the walkway. A strip of self-adhesive aluminum tape was attached to the sole of each of the subjects' shoes. These strips of aluminum tape completed, when the feet were in contact with the mat, a current path to the otherwise electrically isolated rods. A linear voltageposition relationship was established in which the voltage was measured at the output of the current source and the position alternated between the most proximal and most distal parts of the foot in contact with the walkway. These signals were processed through a control box, and data were collected and stored in a microcomputer. Procedure The subjects were requested to arrive at the gait laboratory 30 minutes before taking their morning medications and to bring comfortable walking shoes walking shoes walk npl → chaussures fpl de marche walking shoes walk npl → Wanderschuhe pl walking shoes npl and clothing. Calibration of the walkway was done prior to each testing session, and aluminum tape was placed on the soles of the subjects' shoes. Walking speed (measured in centimeters per second), SL (the distance between 2 consecutive right heel-strikes, measured in centimeters), and ST (the time between 2 consecutive right heelstrikes, measured in seconds) were recorded as the subjects walked on the walkway at a self-selected speed. A practice trial preceded each test, and standby supervision was provided during all tests as a safety precaution. Several strategies were used in an attempt to minimize potential sources of variability. Standard instructions were used (eg, "Walk down the walkway at your normal, comfortable walking pace"), and all tests were administered by the same investigator at the same time of the day and in the same environment. The medication schedule for each subject was established by the referring neurologist, depending on the individual's responsiveness to L-dopa. This schedule was stable for 3 to 4 months prior to and over the course of the study, and subjects were requested to maintain their normal schedule on the day of the test. The duration of the L-dopa cycle was determined by the medication schedule of the individual and ranged between 4 and 6 hours. Therefore, in an effort to standardize gait analyses across all subjects, testing was repeated 11 times, at 10% intervals during each cycle. The 0% time test was the test done immediately after ingestion of the morning medication, and the 100% time test was the test done after the subsequent ingestion of medication. At the end of each test, the subjects were asked an open-ended question A closed-ended question is a form of question, which normally can be answered with a simple "yes/no" dichotomous question, a specific simple piece of information, or a selection from multiple choices (multiple-choice question), if one excludes such non-answer responses as dodging a about how they were feeling, and their responses were documented. Between tests, subjects were encouraged to rest, read, or watch television in the laboratory while refreshments were provided. Each subject was tested in the same time period on 3 separate occasions, with approximately 1 month between tests. This interval was chosen because the protocol for the clinical trials that are to follow this preliminary study involves conducting physical performance evaluations Performance evaluation The assessment of a manager's results, which involves, first, determining whether the money manager added value by outperforming the established benchmark (performance measurement) and, second, determining how the money manager achieved the calculated return at monthly intervals. Data Analysis Descriptive statistics descriptive statistics see statistics. , including means, standard deviations In statistics, the average amount a number varies from the average number in a series of numbers. (statistics) standard deviation - (SD) A measure of the range of values in a set of numbers. , and ranges, were calculated for each dependent variable. Two-way repeated-measures analyses of covariance Covariance A measure of the degree to which returns on two risky assets move in tandem. A positive covariance means that asset returns move together. A negative covariance means returns vary inversely. (ANCOVAs), with 2 within-subject factors (percentage of L-dopa cycle x day) and I non-time-varying covariate (height), were applied to determine the extent of change in speed, SL, and ST during free-speed walking over the L-dopa cycle and over the 3 days. Because of the small sample size and missing data for some tests, the BMDP BMDP - BioMeDical Package 5V Unbalanced Repeated Measures Models statistical program[8,(*)] was used. All statistical tests were performed with the alpha level set at .03. To assess the pattern and magnitude of variability in repeated measurements of the gait characteristics across the L-dopa cycle, coefficients of variation were calculated for speed, SL, and ST. The coefficient of variation Coefficient of Variation A measure of investment risk that defines risk as the standard deviation per unit of expected return. is a dimensionless number dimensionless number A number representing a property of a physical system, but not measured on a scale of physical units (as of time, mass, or distance). Drag coefficients and stress, for example, are measured as dimensionless numbers. expressing the standard deviation (SD) as a proportion of the mean (X), using the formula [(SD/[bar]X) x 100].[9] For comparative purposes, coefficients of variation were also calculated using published means and standard deviations of speed, SL, and ST for elderly subjects with no known neurologic impairments neurologic impairment Neurology Any damage to, or deficiency of, the nervous system .[10] The pattern of variability in walking speed was also examined by plotting the standardized residuals obtained in the ANCOVA ANCOVA Analysis of Covariance against the fitted values for speed.[11] Results All subjects were tested, as scheduled, on 3 separate days. The subjects tolerated the testing protocol well. There were no reports of feeling fatigued during or at the end of each testing session, but some subjects reported higher levels of fatigue on the day after testing. There were a total of 11 missing data points for each dependent variable. Three data points were missing due to technical problems during data collection, and 2 data points were missing due to excusing subjects 1 and 2 from a test to use the washroom. Although all subjects initially met the inclusion criteria
Inclusion criteria are a set of conditions that must be met in order to participate in a clinical trial. for this study, 2 subjects were unable to walk 12 m independently throughout the L-dopa cycle by the second or third testing session. Subject 3 missed 3 tests because he was unable to walk during the corresponding phases of the L-dopa cycle (at 0%, 80%, and 90% of the L-dopa cycle on day 3). Subject 2 also missed 3 tests due to inability to walk at 90% and 100% of the L-dopa cycle on day 2 and at 100% of the L-dopa cycle on day 3. Imputed Attributed vicariously. In the legal sense, the term imputed is used to describe an action, fact, or quality, the knowledge of which is charged to an individual based upon the actions of another for whom the individual is responsible rather than on the individual's (fitted) values or estimates of the missing values In statistics, missing values are a common occurrence. Several statistical methods have been developed to deal with this problem. Missing values mean that no data value is stored for the variable in the current observation. were generated by the BMDP 5V statistical program for all 11 missing data points for each of the 3 independent variables. Two of these values were used in graphing the data of subject 2 (Figs. 1-3). However, because observed values were missing for this subject in 2 of the 3 tests at 100% of the L-dopa cycle, the mean value for this data point was excluded from the graphs. Table 2 shows the walking speed, SL, and ST measures averaged over the complete L-dopa cycle and over the 3 test days for each subject. Comparisons with normative data from age-matched subjects without PD are also provided, based on a study by Ostrosky and colleagues[10] involving 30 subjects without PD (mean age=67.4 years, range=60-80). The overall mean walking speed of the 5 subjects in my study was approximately 55% of the reported mean walking speed for comparison subjects in the same age range. Corresponding values for SL and ST were 63% and 112% of normal, respectively. Thus, on average, decreases in SL contributed more to the below-normal walking speed values than did increases in ST. The relationships between walking speed and SL and between walking speed and ST are depicted in the scatter plots See scatter diagram. in Figure 4. [Figure 4 ILLUSTRATION OMITTED] Table 2. Spatiotemporal Gait Measurements of Individuals and Group Averaged Across the L-dopa Cycle Over the 3 Test Days Variable Subject 1 Speed (cm/s) [bar] X [+ or -] SD 70.61 [+ or -] 10.48 Percentage of normal values(a) 55.60 Stride length (cm) [bar] X [+ or -] SD 89.68 [+ or -] 9.83 Percentage of normal values(b) 63.20 Stride time(s) [bar] X [+ or -] SD 1.27 [+ or -] 0.12 Percentage of normal values(c) 112.4 Variable Subject 2 Speed (cm/s) [bar] X [+ or -] SD 56.36 [+ or -] 11.53 Percentage of normal values(a) 44.40 Stride length (cm) [bar] X [+ or -] SD 68.19 [+ or -] 13.88 Percentage of normal values(b) 48.00 Stride time(s) [bar] X [+ or -] SD 1.21 [+ or -] 0.09 Percentage of normal values(c) 107.1 Variable Subject 3 Speed (cm/s) [bar] X [+ or -] SD 84.38 [+ or -] 9.65 Percentage of normal values(a) 66.40 Stride length (cm) [bar] X [+ or -] SD 101.26 [+ or -] 13.82 Percentage of normal values(b) 71.30 Stride time(s) [bar] X [+ or -] SD 1.20 [+ or -] 0.15 Percentage of normal values(c) 106.2 Variable Subject 4 Speed (cm/s) [bar] X [+ or -] SD 58.62 [+ or -] 7.26 Percentage of normal values(a) 46.2 Stride length (cm) [bar] X [+ or -] SD 80.89 [+ or -] 5.20 Percentage of normal values(b) 57.0 Stride time(s) [bar] X [+ or -] SD 1.38 [+ or - ] 0.11 Percentage of normal values(c) 122.1 Variable Subject 5 Speed (cm/s) [bar] X [+ or -] SD 83.48 [+ or -] 11.58 Percentage of normal values(a) 65.7 Stride length (cm) [bar] X [+ or -] SD 106.86 [+ or -] 12.80 Percentage of normal values(b) 75.3 Stride time(s) [bar] X [+ or -] SD 1.28 [+ or -] 0.07 Percentage of normal values(c) 113.3 Variable Group Speed (cm/s) [bar] X [+ or -] SD 70.39 [+ or -] 15.70 Percentage of normal values(a) 55.4 Stride length (cm) [bar] X [+ or -] SD 89.61 [+ or -] 18.23 Percentage of normal values(b) 63.2 Stride time(s) [bar] X [+ or -] SD 1.27 [+ or -] 0.13 Percentage of normal values(c) 112.4 (a) Normative values= 127 [+ or -] 167 (b) Normative values = 142 [+ or -] 14. m (c) Normative values = 1.13 [+ or -] 0.11.10 The coefficient of variation calculated for the mean walking speeds of all subjects averaged across the L-dopa cycle and over the 3 test days was 22.3%, almost twice the value of 12.6% reported for the subjects in the study by Ostrosky et al.[10] The disparity in the coefficients of variation of the pooled data for SL between the 2 studies was even greater (20.3% versus 9.6%, respectively), whereas the coefficients of variation for ST were comparable (10.1% and 9.7%, respectively). The results of Wald tests The Wald test is a statistical test, typically used to test whether an effect exists or not. In other words, it tests whether an independent variable has a statistically significant relationship with a dependent variable. of significance of fixed effects (percentage of the L-dopa cycle, day, and interaction of percentage of the L-dopa cycle and day) and the single covariate (height) for each of the dependent variables are summarized in Table 3. The only statistically significant result was that of the covariate (height) on each of the dependent variables.
Table 3.
Wald Tests of Significance
Speed
Test df(a) [chi square] P
Day 2 1.68 .433
Percentage of L-dopa cycle 10 5.02 .890
Day x percentage of bdopa cycle 20 7.99 .992
Height 1 25.64 .000(a)
Stride Length
Test [chi square] P
Day 0.02 .992
Percentage of L-dopa cycle 4.33 .931
Day x percentage of L-dopa cycle 5.17 1.000
Height 45.92 .000(a)
Stride Time
Test [chi square] P
Day 4.75 .093
Percentage of L-dopa cycle 7.45 .682
Day x percentage of L-dopa cycle 18.97 .524
Height 8.13 .004(a)
(a) Statistically signiticank P <.05. In Figures 1A, 2A, and 3A, line graphs In graph theory, the line graph L(G) of an undirected graph G is a graph such that
[Figures 1-3 ILLUSTRATION OMITTED] The plot of the standardized residuals against the fitted values for walking shown in Figure 5 are grouped into 3 portions of the L-dopa cycle: 0% to 20% and 100% of the L-dopa cycle to approximate the period when plasma levels of L-dopa would be assumed to be lowest, 30% to 60% of the L-dopa cycle to represent the period when plasma levels would typically be at the highest level, and 70% to 90% of the L-dopa cycle to represent the time frame when plasma levels would be expected to decrease toward the lowest level.[12] These groupings were done to determine whether the spread of the residuals changed,. during these periods, that is, to ascertain whether there were periods in the L-dopa cycle when walking speed was relatively stable. Visual inspection of the plots would suggest that this was not the case. [Figure 5 ILLUSTRATION OMITTED] Discussion Speed of gait and SL have been reported to be useful outcome measures for patients with neurologic impairments because these variables can be measured reliably and are thought to relate to function.[13] 0strosky et al[10] found high test-retest reliability test-retest reliability Psychology A measure of the ability of a psychologic testing instrument to yield the same result for a single Pt at 2 different test periods, which are closely spaced so that any variation detected reflects reliability of the instrument of measurements of walking speed obtained from 30 individuals without neurologic impairments (15 male, 15 female) with a mean age of 28.2 years (range=20-40) and from 30 individuals without neurologic impairments (15 male, 15 female) with a mean age of 67.4 years (range=60-80) (intraclass correlation In statistics, the intraclass correlation (or the intraclass correlation coefficient[1]) is a measure of correlation, consistency or conformity for a data set when it has multiple groups. coefficients [ICC ICC See: International Chamber of Commerce (2,1)]=.97). Bohannon et al[14] found high test-retest reliability of measurements of walking speed obtained from 156 individuals without neurologic impairments (77 male, 79 female) aged 50 to 79 years (ICC[3,1]=.882). Test-retest reliability of measurements of walking speed also has been reported to be high in studies of people with hemiparesis hemiparesis /hemi·pa·re·sis/ (-pah-re´sis) paresis affecting one side of the body. hem·i·pa·re·sis n. Slight paralysis or weakness affecting one side of the body. (n=37, age range=21-40 years) and multiple sclerosis (n=24, age range=21-60 years) (r=.97).[13] Some authors,[2,4,5] however, have noted that the gait profile of patients with PD becomes increasingly unpredictable over the L-dopa cycle as the disease progresses, with variability in the same patient from hour to hour and between patients at similar stages of PD. These fluctuations in motor performance affect most patients who have been exposed to L-dopa therapy for longer than 5 years.[4] Blin v. t. & i. 1. To stop; to cease; to desist. n. 1. Cessation; end. 1. a thin buckwheat pancake made with yeast and usually filled with sour cream and folded over. See also blini. et al[15] reported greater variability in SL of 21 subjects with PD (mean age=69.6 years, disease duration= 1-17 years, Hoehn and Yahr stages 1-4) compared with an age-matched group of 58 subjects without PD. In my study, involving patients ranging from 9 to 21 years postdiagnosis, ST varied randomly over the L-dopa cycle but within the range reported for individuals without PD. In contrast, the variability in walking speed and SL over the course of the L-dopa cycle was extensive, exceeding the reported coefficients of variation for subjects without PD by 2 times or more, thus precluding a clear pattern of systematic variation. Nevertheless, the lowest variability in walking speed and SL, albeit excessive, coincided with the portion of the L-dopa cycle (ie, 60%) when the plasma levels of L-dopa purportedly are highest.[12] These results are consistent with the findings of Blin et al,16 who performed gait assessments on 20 patients with PD before and 1 hour after ingestion of L-dopa. Walking speed and SL were found to be "dopa-sensitive," whereas temporal variables such as ST and swing duration were characterized as "dopa-resistant."[16] Although no researchers have reported investigating gait characteristics over the entire L-dopa cycle, there have been reports of changes over part of the cycle.[15-19] Boudreau et al measured spatiotemporal gait characteristics of 11 patients with PD (mean age=65.7 years) every 5 minutes beginning 30 minutes before medication and ending 40 minutes after medication (unpublished research). They found variability in all of the variables measured. Recently, Schenkman et al[17] investigated the stability of several impairment and physical performance measures in 15 individuals in Hoehn and Yahr stages 2 to 3 of PD (mean age=74.5 years, mean of 6.2 years since diagnosis). Measurements were taken at a single, consistent point in the L-dopa cycle on 2 consecutive days, and they were repeated on 2 days a week later. Their findings suggested that many of the measures, including one distance measure and one speed measure of gait, are relatively stable in the early to middle stages of the disease. They identified a need for investigations of measurement stability with patients in the later stages of PD. The most comprehensive investigation of the stability of spatiotemporal gait variables in PD has been conducted by Morris et al.[18] A series of 4 substudies were done involving a total of 45 individuals with PD. In one of these studies, gait was measured over a distance of 12 m at 15-minute intervals for 165 minutes beginning 30 minutes after peak dose (ie, the "on" phase of the L-dopa cycle). The sample consisted of 16 patients with PD (mean age = 72.8 years, mean disease duration of 7.8 years), all of whom were capable of independent community ambulation. In addition, patients with severe lower-extremity dyskinesia dyskinesia /dys·ki·ne·sia/ (-ki-ne´zhah) distortion or impairment of voluntary movement, as in tic or spasm.dyskinet´ic biliary dyskinesia or dystonia dystonia /dys·to·nia/ (-to´ne-ah) dyskinetic movements due to disordered tonicity of muscle.dyston´ic dystonia musculo´rum defor´mans were excluded because these abnormal movements interfered with data collection using footswitches. In contrast to the results of my study, they found little change in performance for any of the variables during the "on" phase of medication. The disease of the patients in that study, however, appeared to be less advanced than that of the subjects in my study, making comparability of results questionable. Another substudy by the same investigators compared the test-retest reliability of gait measurements obtained at peak dose (ie, "on" phase) and at end of dose (ie, "off" phase) in 12 patients with a mean age of 70.1 years and a mean disease duration of 8.8 years. Morris and colleagues found a low degree of repeatability for all measures between the "on" and "off" phases (ICCs [2,1] of -.54 to -.07), and they hypothesized that the greater variability seen in the "off" phase is related to L-dopa concentrations in the plasma and brain. In discussing the findings of the 4 substudies, Morris et al[18] concluded that the parkinsonian gait pattern is reproducible across either 30-minute or 24-hour intervals during the "on" phase but that there is marked variability during the "off" phase. My study showed extensive variability throughout the entire L-dopa cycle. The most obvious explanation for the difference in results is the contrast in disease severity (mild in the study by Morris et al[18] versus moderate in my study), average disease chronicity (8.3 years versus 15.0 years, respectively), and functional limitations (independent community ambulators versus household ambulators, respectively) of the subjects under study. Sage and Mark[3] reported that the extent of variability in motor responses increases with length and severity of the disease, but they did not provide supporting evidence for this observation. Findings similar to those of Morris et al[18] were reported by Bowes et al[19] who investigated spatiotemporal variables of gait in a group of 14 people without PD and without overt fluctuations in motor performance, comparing the sensitivity and specificity of these variables for the L-dopa treatment effect. After omission of a morning dose of L-dopa, baseline measurements of free-speed gait over a 6-m distance, mobility (ie, time taken to rise from a chair, walk an individually set distance, return, and sit), and manual dexterity (ie, a buttoning task) were taken. Assessments were then repeated 2, 4, and 6 hours after administration of L-dopa or a placebo. The tests of mobility and dexterity were not affected by the treatment effect (ie, a lack of sensitivity), but walking speed, SL, and double-limb support time during free-speed walking were affected. The extent of the treatment effect (eg, improvement in walking speed with L-dopa versus placebo) was inversely related to the concentration of L-dopa in the plasma. The authors postulated pos·tu·late tr.v. pos·tu·lat·ed, pos·tu·lat·ing, pos·tu·lates 1. To make claim for; demand. 2. To assume or assert the truth, reality, or necessity of, especially as a basis of an argument. 3. that this seemingly paradoxical loss of sensitivity may reflect reduced uptake of L-dopa from the plasma into the brain or an adverse effect of the drug or a metabolite metabolite, organic compound that is a starting material in, an intermediate in, or an end product of metabolism. Starting materials are substances, usually small and of simple structure, absorbed by the organism as food. . Poewe[4] categorized cat·e·go·rize tr.v. cat·e·go·rized, cat·e·go·riz·ing, cat·e·go·riz·es To put into a category or categories; classify. cat fluctuations in motor performance in persons with advanced PD as being either predictable (ie, predictable "wearing-off" response) or random (ie, unpredictable "on-off" effects). No data were presented to support this impression. According to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. Poewe,[4] approximately 15% of patients treated with L-dopa eventually develop random fluctuations in motor performance. He stated, "Without apparent relation to the timing of their individual L-dopa doses, these patients experience abrupt and frequent oscillations oscillations See Cortical oscillations. between mobile and dyskinetic states on the one hand and severe immobility immobility standing still and disinclined to move, as in an animal suddenly blinded; responds to other stimuli unless immobility is part of a dummy syndrome when all stimuli are ignored. on the other."[4(ps7)] Unpredictable "freezing" also may occur.[4] In my study, 4 of the 5 subjects demonstrated fluctuations in gait that I describe as random. For example, the minimum and maximum walking speeds of subject 1 were at 0% and 70% of the L-dopa cycle, respectively, on day 1 and at 70% and 20% of the L-dopa cycle, respectively, on day 2. Subject 3 demonstrated an abrupt change in walking status, from independent ambulation at 90% of the L-dopa cycle to complete immobility at 100% of the L-dopa cycle. Twenty minutes later, he was able to walk independently again. In contrast, subject 4 showed little variability over the course of the L-dopa cycle. Fluctuations in motor performance are affected by anti-PD medications, time since taking medication, time of day, degree of fatigue, physical or emotional stress, extent of dyskinesia, diet, and changes in responsiveness to L-dopa therapy.[2-4,20] In my study, the effect of time since medication was the primary focus. All of the subjects were taking Sinemet. In addition, subjects 1 and 3 were taking a controlled-release preparation (Sinemet CR), which is used to reduce motor fluctuations by providing a more stable and constant L-dopa plasma level. Koller and Pahwa[20] noted that such preparations are more efficacious ef·fi·ca·cious adj. Producing or capable of producing a desired effect. See Synonyms at effective. [From Latin effic in patients who manifest mild to moderate disease with predictable "wearing-of" phenomena. The time of day was kept constant among subjects and test days. The degree of fatigue was monitored qualitatively but not quantitatively. The subjects did not report increased fatigue at the end of the testing sessions, and, in 4 of the 5 subjects, the walking speed at 100% of the L-dopa cycle was equal to or greater than their walking speed at 0% of the L-dopa cycle (even subject 2, who could not walk at 100% of the cycle, did not identify fatigue as the limiting factor A factor or condition that, either temporarily or permanently, impedes mission accomplishment. Illustrative examples are transportation network deficiencies, lack of in-place facilities, malpositioned forces or materiel, extreme climatic conditions, distance, transit or overflight rights, ). Physical and emotional stress and diet were not tracked over the course of the study. Dyskinesias were noted during the gait trials of subjects 1, 2, and 5. The direct relationship between walking speed and SL and the inverse relationship A inverse or negative relationship is a mathematical relationship in which one variable decreases as another increases. For example, there is an inverse relationship between education and unemployment — that is, as education increases, the rate of unemployment between walking speed and ST observed in individuals without PD were also seen in subjects with PD. This finding supports a previous report that the relationships between kinematic kin·e·mat·ics n. (used with a sing. verb) The branch of mechanics that studies the motion of a body or a system of bodies without consideration given to its mass or the forces acting on it. variables of gait remain unchanged in persons with PD.[16] Compared with data from a comparison group, a substantially slower walking speed (55% of normal), a shorter SL (63% of normal), and a somewhat longer ST (112% of normal) were observed for the subjects with PD. The observation that decreases in SL contributed substantially more to the below-normal walking speeds than did increases in ST is consistent with the finding that, in people without neurologic impairments, walking speed and SL decrease with age but ST does not change.[21] The finding of an effect of height on walking speed and SL during free-speed gait has been reported for elderly individuals without neurologic impairments.[14,21] The averages for gait measures in my study corroborate To support or enhance the believability of a fact or assertion by the presentation of additional information that confirms the truthfulness of the item. The testimony of a witness is corroborated if subsequent evidence, such as a coroner's report or the testimony of other the findings of the studies by Blin et al[15] and Morris et al.[18] Although percentages of normal values normal values pl.n. A set of laboratory test values used to characterize apparently healthy individuals, now replaced by reference values. for walking speed, SL, and ST were similar in the 3 studies, the absolute values for the same variables in the study by Blin et al[15] were considerably different those in my study and in the study by Morris et al.[18] For example, the mean walking speed (averaged over all patients with PD) in the study by Blin et al[15] was 44 cm/s, whereas the mean walking speed was 70.39 cm/s in my study and 79.79 cm/s in the study by Morris et al.[18] The subjects in the study by Blin et al[15] were comparable to the subjects in my study in terms of age and height, but they differed in terms of disease severity in that 7 subjects (33%) were in Hoehn and Yahr stage 4 of PD during the "on" cycle. This difference, together with the methodological difference (data from chart recorder traces measured by hand versus computerized resistive walkway) could well have contributed to the differences in the results. Evans and colleagues[22] investigated systematic and random error in spatiotemporal gait measurements taken on 3 consecutive days for 31 individuals with stroke (mean age of 69 years, mean of 46 days poststroke). They attributed variability in walking speed to variations in performance rather than to measurement error, and they contended that, although this error was small relative to individual differences in the subjects, it was large relative to the extent of change reported over the course of stroke rehabilitation rehabilitation: see physical therapy. . They recommended that the clinical relevance of potentially unstable measurements could be enhanced by conducting serial evaluations in order to examine variations within the trends of change over a longer time interval. Limitations The small sample size used in my study limits the generalizability of the findings. The study was designed to be exploratory in nature, prior to initiating a large-scale clinical trial. Direct comparison of the results with those of other investigations is hindered not only by the sample size but also by analytical differences. Another limitation is the potentially confounding confounding when the effects of two, or more, processes on results cannot be separated, the results are said to be confounded, a cause of bias in disease studies. confounding factor effect of different interpretations to the verbal instruction "Walk down the walkway at your normal, comfortable walking speed." In an attempt to control for this effect, the investigator and the instructions remained constant throughout the study. Finally, it was not feasible, within the confines of this study, to control for all of the multiple factors mentioned (eg, emotional stress, dyskinesia, diet, changes in responsiveness to L-dopa) that can influence the extent of fluctuations in motor performance. Conclusions Lindsey contended that "a [PD] patient's response during a 10:00 AM therapy session may be very different than at a 2:00 PM treatment time."[2(p33)] The findings of my study suggest that this observation could be extended to include "and the patient's gait profile on a given Tuesday may be very different from that on a Tuesday a month later." Fluctuations in spatiotemporal variables of patients with advanced PD may be extensive and may not follow a predictable pattern. Thus, caution must be exercised when interpreting the results of gait kinematic data from patients with PD, particularly if the disease is in an advanced stage. The conventional method of assessing gait as part of an overall 1-hour neurologic neurologic /neu·ro·log·ic/ (-loj´ik) pertaining to neurology or to the nervous system. Neurologic Having to do with the nervous system. assessment is unlikely to yield data that are representative of the patient's performance over the course of the L-dopa cycle. To obtain a more valid representation and to ascertain the extent of variability in the gait profile, periodic assessment over the full L-dopa cycle is recommended, especially if the patient has long-standing PD and if these data are to be used to assess the effectiveness of intervention. The use of spatiotemporal gait characteristics as robust outcome measures for the subgroup sub·group n. 1. A distinct group within a group; a subdivision of a group. 2. A subordinate group. 3. Mathematics A group that is a subset of a group. tr.v. of patients with random fluctuations in motor performance is highly questionable. Rather than emphasizing impairment variables such as the types of gait measures used in my study with this subgroup, it may be more prudent to address functional activities that involve gait. Functional behaviors, however, may also be subject to erratic fluctuations over the course of the L-dopa cycle. Further research on this issue is warranted. Acknowledgments Appreciation is extended to the patients for their eager participation in this study, to James Crouse for his technical support, and to Dr Bruce Smith This article is about the football player. For other uses, see Bruce Smith (disambiguation). Bruce Bernard Smith (born June 18, 1963 in Norfolk, Virginia) is a former NFL football player who currently holds the NFL record for most career quarterback sacks with 200. for his statistical consultation. (*) BMDP Statistical Software Inc, 1440 S Sepulveda Blvd, Los Angeles Los Angeles (lôs ăn`jələs, lŏs, ăn`jəlēz'), city (1990 pop. 3,485,398), seat of Los Angeles co., S Calif.; inc. 1850. , CA 90025. References [1] Leenders KL, Salmon EP, Tyrrell P, et al. The nigrostriatal dopaminergic dopaminergic /do·pa·min·er·gic/ (do?pah-men-er´jik) activated or transmitted by dopamine; pertaining to tissues or organs affected by dopamine. do·pa·mi·ner·gic adj. system assessed in vivo in vivo /in vi·vo/ (ve´vo) [L.] within the living body. in vi·vo adj. Within a living organism. in vivo adv. by positron emission tomography positron emission tomography: see PET scan. positron emission tomography (PET) Imaging technique used in diagnosis and biomedical research. in healthy volunteer subjects and patients with Parkinson's disease Parkinson's disease or Parkinsonism, degenerative brain disorder first described by the English surgeon James Parkinson in 1817. When there is no known cause, the disease usually appears after age 40 and is referred to as Parkinson's disease. . Arch Neurol. 1990;47:1290-1298. [2] Lindsey B. Hourly monitoring system for patients with Parkinson's disease. Neurology neurology (n  rŏl`əjē, ny–), study of the morphology, physiology, and pathology of the human nervous system. Report. 1995;19:30-33.[3] Sage JI, Mark MH. Basic mechanisms of motor fluctuations. Neurology. 1994;44(suppl 6):S10-S14. [4] Poewe WH. Clinical aspects of motor fluctuations in Parkinson's disease. Neurology. 1994;44(suppl 6):S6-S9. [5] Wall JC, Turnbull GI. The kinematics of gait. In: Turnbull GI, ed. Physical Therapy Management of Parkinson's Disease. New York New York, state, United States New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of , NY: Churchill Livingstone Imprint of a medical publishing company owned by Elsevier Ltd, but previously owned by Harcourt and Pearsons. Originally formed from Livingstone, Edinburgh, Scotland, and J & A Churchill, London, UK, and subsequently with an office in New York, but now integrated with the rest of Inc; 1992:57-63. [6] Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology. 1967;17:427-442. [7] Crouse J, Wall JC, Marble AE. Measurement of the temporal and spatial parameters of gait using a microcomputer based system. J Biomed Eng. 1987;9:64-68. [8] Schluchter MD. BMDP 5V.' Unbalanced Repeated-Measures Models With Structured Covariance Matrices. Los Angeles, Calif.' BMDP Statistical Software Inc; 1988. Technical Report No. 86. [9] Afifi AA, Azen SP. Statistical Analysis. New York, NY: Academic Press Inc; 1979:60. [10] Ostrosky KM, VanSwearingen JM, Burdett RG, Gee Z. A comparison of gait characteristics in young and old subjects. Phys Ther. 1994;74: 637-644. [11] Glantz SA, Slinker BK. Primer of Applied Regression and Analysis of Variance. New York, NY: McGraw-Hill Inc; 1990:123-129. [12] Eriksson T, Magnusson T, Carlsson A, et al. "On-off" phenomenon in Parkinson's disease: correlation to the concentration of dopa in plasma. J Neural Transm. 1984;59:229-240. [13] Holden MK, Gill KM, Magliozzi MR, et al. Clinical gait assessment in the neurologically impaired: reliability and meaningfulness. Phys Ther. 1984;64:35-40. [14] Bohannon RW, Andrews AW, Thomas MW. Walking speed: reference values ref·er·ence values pl.n. A set of laboratory test values obtained from an individual or from a group in a defined state of health. and correlates for older adults. J Orthop Sports Phys 7'her. 1996;24:86-90. [15] Blin O, Ferrandez AM, Serratrice G. Quantitative analysis Quantitative Analysis A security analysis that uses financial information derived from company annual reports and income statements to evaluate an investment decision. Notes: of gait in Parkinson patients: increased variability of stride length. J Neurol Sci. 1990;98:91-97. [16] Blin O, Ferrandez AM, Pailhous J, Serratrice G. Dopa-sensitive and dopa-resistant gait parameters in Parkinson's disease. J Neurol Sci. 1991;103:51-54. [17] Schenkman ML, Cutson TM, Kuchibhatla M, et al. Reliability of impairment and physical performance measures for persons with Parkinson's disease. Phys Ther. 1997;77:19-27. [18] Morris ME, Matyas TA, Iansek R, Summers ]J. Temporal stability of gait in Parkinson's disease. Phys Ther. 1996;76:763-777. [19] Bowes SG, Clark PK, Charlett A, et al. Objective outcome criteria in trials of anti-Parkinsonian therapy in the elderly: sensitivity, specificity, and reliability of measures of brady- and hypo-kinesia. Br J Clin Pharmacol. 1991;31:295-304. [20] Koller WC, Pahwa R. Treating motor fluctuations with controlled-release levodopa preparations. Neurology. 1994;44(suppl 6):S23-S28. [21] Hageman PA, Blanke DJ. Comparison of gait of young women and elderly women. Phys Ther. 1986;66:1382-1387. [22] Evans MD, Goldie PA, Hill KD. Systematic and random error in repeated measurements of temporal and distance parameters of gait after stroke. Arch Phys Med Rehabil. 1997;78:725-729. M MacKay-Lyons, MSc(PT), is a doctoral student in the Department of Physiology and Biophysics biophysics, application of various methods and principles of physical science to the study of biological problems. In physiological biophysics physical mechanisms have been used to explain such biological processes as the transmission of nerve impulses, the muscle , School of Medicine, Dalhousie University Dalhousie University (dălhou`zē), at Halifax, N.S., Canada; nonsectarian; coeducational; founded 1818 by the 9th earl of Dalhousie. Except for a few years between 1838 and 1845, Dalhousie did not function as a university until 1863. , Halifax, Nova Scotia For other uses, see Halifax. Halifax, Nova Scotia may refer to any of the following:
This study was approved by the Victoria General Hospital Research Review Committee. Funding for this study was provided by the Royal Canadian Legion The Royal Canadian Legion is a non-profit Canadian ex-service organization (veterans organization) founded in 1925, with more than 400,000 members worldwide. Membership includes people who have served as current and former military, Royal Canadian Mounted Police, provincial and and the Neurosciences Division of the Canadian Physiotherapy physiotherapy: see physical therapy. Association. This article was submitted December 18, 1997, and was accepted May 28, 1998. |
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