Abstract
Background Clinical intervention trials in people with Huntington disease (HD) have been limited by a lack of reliable and appropriate outcome measures.
Objective The purpose of this study was to determine the reliability and minimal detectable change (MDC) of various outcome measures that are potentially suitable for evaluating physical functioning in individuals with HD.
Design This was a multicenter, prospective, observational study.
Methods Participants with pre-manifest and manifest HD (early, middle, and late stages) were recruited from 8 international sites to complete a battery of physical performance and functional measures at 2 assessments, separated by 1 week. Test-retest reliability (using intraclass correlation coefficients) and MDC values were calculated for all measures.
Results Seventy-five individuals with HD (mean age=52.12 years, SD=11.82) participated in the study. Test-retest reliability was very high (>.90) for participants with manifest HD for the Six-Minute Walk Test (6MWT), 10-Meter Walk Test, Timed “Up & Go” Test (TUG), Berg Balance Scale (BBS), Physical Performance Test (PPT), Barthel Index, Rivermead Mobility Index, and Tinetti Mobility Test (TMT). Many MDC values suggested a relatively high degree of inherent variability, particularly in the middle stage of HD. Minimum detectable change values for participants with manifest HD that were relatively low across disease stages were found for the BBS (5), PPT (5), and TUG (2.98). For individuals with pre-manifest HD (n=11), the 6MWT and Four Square Step Test had high reliability and low MDC values.
Limitations The sample size for the pre-manifest HD group was small.
Conclusions The BBS, PPT, and TUG appear most appropriate for clinical trials aimed at improving physical functioning in people with manifest HD. Further research in people with pre-manifest HD is necessary.
Huntington disease (HD) is a neurodegenerative disease that causes progressive decline in cognitive, psychological, and motor functions. Characteristic motor symptoms of HD are hyperkinetic (ie, chorea and dystonia) and hypokinetic (ie, akinesia, hypokinesia, and bradykinesia) movements, motor impersistence, and rigidity. As the disease progresses, gait impairments1,2 and decreased postural stability3,4 lead to loss of balance and frequent falls.5–7 In comparison with age-matched adults who are healthy, individuals with HD walk with a slower speed, a shorter and more variable stride length, a wider base of support, decreased cadence, and increased trunk sway.2,5,8 Individuals with HD also have greater postural sway in standing and delayed motor responses to unexpected balance disturbances.3,4 These balance and gait impairments ultimately lead to loss of independent mobility and functional decline.
Huntington disease may be amenable to physical therapy interventions aimed at restoring or maintaining functional abilities and minimizing the effect of sensorimotor impairments, and studies that show potential for the use of exercise as a possible disease-modifying intervention in movement disorders such as PD are beginning to emerge, as well as some pilot studies in HD.9–12 However, there is limited published evidence to guide clinicians in determining appropriate, valid, and reliable outcome measures for use in clinical trials and for clinical reasoning. The Unified Huntington's Disease Rating Scale (UHDRS)13 is currently the standard assessment tool used in most HD clinical trials. However, only 3 items on the UHDRS motor section (ie, gait, tandem walking, and retropulsion pull test) specifically assess balance and mobility.
A number of balance and mobility measures, including the Timed “Up & Go” Test (TUG), Berg Balance Scale (BBS), and Tinetti Mobility Test (TMT), have been shown to relate to fall risk in people with HD.7,14 The TUG also has been shown to relate to spatiotemporal gait parameters.15 Although these measures show potential, no studies have reported reliability or minimal detectable change (MDC)16 data to support the use of these clinical balance and mobility outcome measures in people with HD, limiting their utility.
Knowledge of the reliability and MDC of outcome measures is imperative for clinicians to accurately assess the impact of physical therapy and exercise-based interventions on functional performance and quality of life in the HD population. Test-retest reliability17 can be considered as relative or absolute.18 Relative reliability, typically measured using intraclass correlation coefficients (ICCs), examines the relationship between 2 or more measurements and the consistency of an individual's position within the group. Absolute reliability examines variability in scores in repeated measurements.
The use of ICCs alone as a measure of reliability is limited because their values are not related to the actual scale of measurement and are dependent on the range of the individual's performances. If a sample contains a large range of scores, the ICC may be high despite large within-subject differences between repeated measurements.17 It is important, therefore, to also measure absolute reliability,18 which is determined by the standard error of measurement (SEM), or the standard deviation of the measurement errors. A clinically useful mechanism for looking at absolute reliability, which utilizes the SEM, is the MDC,17 defined as the minimal amount of change that is not due to natural variation in measurement or due to error. Minimum detectable change values can be important to aid clinical reasoning in the absence of controlled trials. Test scores obtained in intervention trials or in clinical evaluations that are at or above the MDC can be considered real change rather than the result of measurement error.
The purpose of this study was to determine the test-retest reliability and MDC of various physical performance outcomes measures that have potential in evaluating individuals with HD. The selection of measures used for this study was based on their established reliability or validity in Parkinson disease (PD) (for gait, balance, and falls) or other neurological populations and on their applicability to the HD population.
Method
Study Design
The study was a multicenter, prospective, observational study involving a total of 8 sites: 7 across Europe and 1 in the United States. The European centers were all part of the European Huntington's Disease Network REGISTRY study,19 which is an international observational study with more than 10,000 registrants. The present study required participants to undergo a battery of tests in 2 sessions, with a 1-week gap between sessions. Each battery took approximately 90 minutes to complete per participant. The order of assessments for each participant was randomized (between participants) but remained the same for repeated testing (within participants).
Recruitment and Governance
Participants were approached during routine clinical visits and asked if they were interested in enrolling in the study. Ethical approval was granted for 6 of the sites (Leiden, Manchester, Birmingham, Southampton, Lisbon, and Oxford) as a substudy to REGISTRY, version 3. For Ohio State University, the study was approved by the Institutional Review Board (2008H0109). For Cardiff University, the study was approved by the South East Wales Research Ethics Committee (09/WSE02/24). All participants provided informed consent.
Participants
Inclusion criteria were as follows: (1) diagnosis of HD (gene positive) and (2) age 21 years or older. Exclusion criteria were: (1) history of a prior neurological condition, such as stroke; (2) moderate to severe arthritis in the hips, knees, or ankles, or orthopedic condition that limits movement (eg, ankle fracture); (3) medical conditions preventing completion of the full battery of tests; and (4) change in medication regimen or physical activity in preceding 6 weeks and the week between testing sessions. We aimed to recruit a maximum of 80 participants who were representative of stages of disease: pre-manifest, early, middle, and late stages of HD. People with pre-manifest HD were defined as having no clinical signs of HD, with a UHDRS Total Motor Score (TMS) <5 and a total functional capacity (TFC) score of 13, but with a confirmed genetic test. Total functional capacity13 is a general measure of function specific to people with HD, encompassing workplace, finances, domestic chores, activities of daily living, and requirements for unskilled or skilled care. Participants in the early stage of HD were defined as having a TFC score of 10 to 13, those in the middle stage were defined as having a TFC score of 7 to 9, and those in the late stage were defined as having a TFC score of 0 to 6. A list of each of the sites, including the number of participants recruited at each site, is provided in Appendix 2.
Data Collection
Cross-sectional demographic and disease-specific scores from the UHDRS13 were obtained from clinical records for each participant. In addition to TFC scores, UHDRS TMS and UHDRS function, independence, and cognitive (Verbal Fluency for Letters, Symbol Digit Modalities Test, Stroop Word Reading Test, Stroop Color Naming Test, and Stroop Interference Test) scores were collected. All UHDRS data were obtained within 1 month of the first assessment visit by certified raters at each of the sites.
Participants were permitted to use assistive devices for the Six-Minute Walk Test (6MWT), 10-Meter Walk Test, TUG, and TMT, but were excluded from performance if they were unable to ambulate without physical assistance. Detailed assessment protocols for the 6MWT, 10-Meter Walk Test, TUG, FSST, and Romberg and Sharpened Romberg tests are presented in Appendix 3. Scoring methods were the same with or without assistive devices, and participants who did use assistive devices were required to use them for both test sessions. Following completion of the test battery, all participants were asked several questions about their experience and level of fatigue.
Measures of Activities
6MWT.
In the 6MWT,20 participants walked around the perimeter of a set circuit for a total of 6 minutes. The distance (in meters) covered at 1, 3, and 6 minutes was recorded. Heart rate before and after completion of the walk also was recorded.
10-Meter Walk Test.
In the 10-Meter Walk Test,21 participants walked at a comfortable pace across a 14-m walking area that was marked with 10 m in the middle and an additional 2 m on either side to allow for starting and stopping of walking (acceleration and deceleration). The total time and numbers of steps taken to complete the 10-m walk was recorded. The test was repeated twice, and the average gait speed (distance/time) from both tests was calculated.
TUG.
In the TUG,22 participants stood up from a chair, walked 3 m, turned around, and returned to the chair while being timed. The test was repeated twice, and the average score for both tests was documented.
TMT.
The TMT23 includes balance and gait subscales that measure static and dynamic balance, and the test quantitatively ranks gait deviations. Each item of the TMT was scored using a scale of 0 to 1 or 2, with a total possible score of 28 points, where higher scores indicate better performance. The maximum score was 16 for the gait subscale and 12 for the balance subscale.
Physical Performance Test.
In the Physical Performance Test (PPT),24 participants were timed while performing a series of 9 standardized tasks mimicking basic and complex activities of daily living. Times for completion of tasks then were related to a categorical score of 0 to 4, where 0 represents inability to complete the task. The maximum score on the 9-item PPT is 36. A higher score indicates better performance. The full version of the PPT (9-item) was used because we felt it could better reflect the range of impairments in people with HD.
Rivermead Mobility Index.
The Rivermead Mobility Index (RMI)25 consists of 14 questions about a person's ability to perform a wide range of activities, from turning over in bed to running, and 1 observation (standing for 10 seconds without any aid). Scores were reported as either unable or able (0–1) and added to produce a total score (0–15). A higher score reflects better mobility.
Barthel Index.
The Barthel Index26 is a 10-category rating scale that evaluates the level of assistance needed by a person to perform the following tasks: feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfer, mobility, and stairs. Each subtest item was rated 0, 5, or 10 (or 15 for 2 of the test items) and added for a total possible score of 100, with higher scores indicating better performance.
International Physical Activity Questionnaire.
The International Physical Activity Questionnaire (IPAQ)27 was developed to measure health-related physical activity. The short version of the IPAQ has been tested extensively and is now used in many international studies. This questionnaire asks the individuals to rate how often and how much they have done vigorous activity and moderate activity in the last 7 days, as well as how much time they spent sitting. The scores for sitting are reported as minutes per week. Scores for physical activity are reported as metabolic equivalent (MET) minutes per week, and individuals can subsequently be categorized as having low, moderate, or high levels of physical activity (procedures for scoring the IPAQ were obtained from the IPAQ website28).
Measures of Impairments in Body Function
BBS.
The BBS29 entails 14 subtests of various activities related to balance control. Subtests include static postures (eg, sitting, standing), transitions (eg, sitting to standing, transferring between chairs), and challenging positions (eg, standing with eyes closed). Quality of performance for each item was scored using a 4-point scale, with higher scores indicating better balance, and a maximum score of 56.
Romberg and Sharpened Romberg tests.
Romberg and Sharpened Romberg tests were performed with and without cognitive loading and eyes closed.30 Participants performed the Romberg test, with feet positioned close together, with both eyes open and eyes closed, for a maximum of 30 seconds under each condition. Participants then performed the Sharpened Romberg test by standing with one foot placed directly in front of the other, with the front heel touching the toes of the back foot (tandem standing), again with eyes open and eyes closed. Both conditions of the Sharpened Romberg test also were performed as a dual task, with the addition of a secondary cognitive task (counting backward by 3's from 100). The amount of time the participant maintained the position without loss of balance for all 6 conditions was recorded (maximum score=180 seconds, with higher scores indicating better balance).
Four Square Step Test.
The Four Square Step Test (FSST)31 is a test of dynamic standing balance that requires participants to step over 4 canes as fast as possible in a predetermined sequence. Participants were timed as they stepped forward, right, backward, and left and then repeated this sequence in reverse. Participants performed 2 trials: 1 as a practice trial and 1 as a timed trial. Trials were repeated if the participant failed to complete the sequence successfully, lost balance, or made contact with a cane.
Site Coordination and Training
A site coordinator was appointed at each of the sites, and each coordinator liaised with the study team based in Cardiff to ensure that recruitment criteria and study procedures were followed. The study team at each site was responsible for recruiting participants and conducting the assessments in accordance with the study protocol.
Due to the number of sites involved, site training was critical to ensure consistency among sites in adhering to the study protocol. Once a site was recruited into the study, a site visit, lasting approximately 5 hours, was made to all European sites to review the protocol with the local team and conduct specific training of each of the assessments. The training entailed detailed review of the study protocol, review of equipment needed, assessment of location for testing, and demonstration of testing procedures for all tests. For the Ohio site, training was done remotely, which included reviewing and providing feedback on a videotaped assessment of a pilot participant. In addition to this training, each site was required to videotape a proportion of the testing sessions to confirm fidelity of the assessment protocol. Assessors at each site were clinically experienced, state-registered physical therapists. Each site utilized 1 or 2 assessors, with a total of 10 assessors across all sites. At each site, the same assessor conducted all tests for the first and second assessments for each participant.
Data Analysis
Data from all measures were analyzed using the Statistical Package for the Social Sciences version 18 (SPSS Inc, Chicago, Illinois).
Intraclass correlation coefficients were calculated to assess the relative test-retest reliability. The ICC (2,k) was used (the 2-way random model of consistency), either a type 2,1 or a type 2,2.32 The ICC (2,1) was used for the 6MWT, PPT, BBS, Barthel Index, TMT, IPAQ, FSST, and Romberg test. The ICC (2,2) was used for the 10-Meter Walk Test and TUG because final scores for these outcomes were based on an average of 2 trials.
Measures of absolute reliability were expressed as the MDC.17 The MDC at the 95% confidence level (MDC95) was calculated as:
The SEM was estimated from the square root of the mean error term from a repeated-measures analysis of variance.33,34
Role of the Funding Source
This study was funded by the European Huntington's Disease Network, Ulm, Germany. The authors gratefully acknowledge the support of the National Institute for Social Care and Health Research Clinical Research Centre and the Dementias & Neurodegenerative Diseases Research Network (DenDRoN), England. Dr Andrea H. Nemeth received support from Thames Valley DeNDRoN.
Results
A total of 81 people with HD were recruited and consented to participate in the study. Three individuals did not attend their first session and withdrew from the study. Three additional individuals participated in the first test session but did not attend the second session (1 participant withdrew due to personal constraints, and 2 participants felt that they had done too much at the first testing session). Seventy-five people (33 male, 42 female; mean age=52.12 years, SD=11.82) with pre-manifest or manifest HD completed both test sessions: 11 pre-manifest (TFC 13 and TMS <5), 20 early stage (TFC 10–13), 20 middle stage (TFC 7–9), and 24 late stage (TFC 0–6). Table 1 provides mean (SD) ages and UHDRS scores for all participants, grouped by pre-manifest and manifest HD, with the manifest group further delineated according to disease stage. The UHDRS TMS, independence, and function scores were not available for 1 participant (late stage). The UHDRS cognitive test scores were not available for 8 participants (3 pre-manifest, 2 early stage, 3 late stage). The group of participants in this study is comparable in age and disease severity to a larger sample of REGISTRY participants.19
Mean (SD) Age and Scores on Disease-Specific Measures for All Participants With Pre-manifest and Manifest Huntington Disease (HD)a
Table 2 provides means (SD), 95% confidence intervals, and sample sizes for the first test session on all outcome measures, delineated by stage of disease. Differences in participant numbers across tests are accounted for by several factors. One participant (late stage) was excluded from performing the 6MWT, 10-Meter Walk Test, TUG, and TMT because he was unable to ambulate without physical assistance. One participant (late stage) was too fatigued to complete the FSST, BBS, TMT, and TUG. One participant (middle stage) was unable to complete the 6MWT, 10-Meter Walk Test, PPT, and FSST because of personal time constraints. Three participants (1 middle stage, 2 late stage) were unable to complete the FSST during one or both of the test sessions. All other participants were able to complete the entire battery of assessments.
Mean (SD), 95% Confidence Interval [Range], and Sample Size (n) for Participants With Pre-manifest and Manifest Huntington Disease (HD) at the First Test Sessiona
The data presented in Table 2 show that there was a general progression across disease stage for most measures, with pre-manifest and early-stage HD participants performing better, on average, than those in the middle and late stages of the disease. The Figure shows a box plot diagram of the scores at the first test session across disease stage for the PPT, BBS, TMT, and TUG. The progressive nature of the disease is evident across all tests; however, there is greater variability in the measures for participants in the middle stage of the disease. The data also demonstrated that for several of the walking measures, including the 6MWT, TUG, and 10-Meter Walk Test, participants in the late stage of HD performed, on average, as well as, and sometimes better than, participants in the middle stage (Tab. 2; Figure, graph D).
Box plots representing median, 25th and 75th percentiles, and ranges of scores for (A) Physical Performance Test, (B) Berg Balance Scale, (C) Tinetti Mobility Test, and (D) Timed “Up & Go” Test (D) for participants with pre-manifest, early-stage, middle-stage, and late-stage Huntington disease (HD). Circles represent outliers 1.5 times greater than interquartile range. Asterisks represent outliers 3 times greater than interquartile range. Associated numbers refer to individual cases.
The ICC values for test-retest reliability for each of the tests are shown in Table 3. For individuals with manifest HD, the ICC values were excellent (>.90) for the 6MWT, 10-Meter Walk Test, TUG, PPT, RMI, Barthel Index, BBS, and TMT total score and balance subscale. Reliability for several of the measures was lower when assessing participants in the middle stage of HD; however, the TUG, 10-Meter Walk Test, PPT, and BBS had consistently high ICC values (good–excellent) across all stages of manifest HD. For participants with pre-manifest HD, the ICC values were considerably more variable, which may reflect the relatively small sample size for this group. Tests that had excellent (>.90) ICC values for this group included the 6MWT, 10-Meter Walk Test, TUG, TMT, and FSST.
Intraclass Correlation Coefficients for All Tests for Participants With Pre-manifest and Manifest Huntington Disease (HD)a
Table 4 shows the MDC values for all groups. Interestingly, the MDC values for several of the measures were considerably higher for participants in the middle stage of HD than in the early and late stages (most notably for the 6MWT, 10-Meter Walk Test, TUG, FSST, and Romberg and Sharpened Romberg tests). Minimal detectable change values for participants with manifest HD that were relatively low and stable across the disease stages were found for the BBS (5), PPT (5), and TUG (2.98). In the pre-manifest group, MDC values were relatively low for all measures tested except for the Romberg and Sharpened Romberg tests and the IPAQ.
Minimum Detectable Change Values for All Tests for Participants With Pre-manifest and Manifest Huntington Disease (HD)a
Discussion
This study presents reliability and MDC values for a range of physical performance measures in people with pre-manifest and manifest HD across sites in Europe and the United States. The test-retest reliability was excellent (>.90) for participants with manifest HD for most of the measures, including the 6MWT, 10-Meter Walk Test, TUG, PPT, RMI, Barthel Index, BBS, and TMT total score. The MDC values revealed some degree of variability, particularly for individuals in the middle stage of the disease. Minimal detectable change values for participants with manifest HD that were relatively low and stable across the disease stages were found for the BBS, PPT, and TUG. For the pre-manifest group, the measures with excellent reliability and low MDCs were the FSST and the 6MWT.
The disease-specific scores obtained for the UHDRS suggest that the cohort of patients in this study represented a broad range of people with HD. Although differences among participants based on stage of disease were not assessed, there was a general trend indicating progression across disease stage. For the physical performance measures, this trend also was apparent; however, participants in the late stage, on average, performed as well as, if not better than, those in the middle stage for walking measures such as the 6MWT, 10-Meter Walk Test, TUG, and FSST. This finding may partially be explained by the fact that 50% of the participants with late-stage HD came from a center where the participants engage in a regular walking program. Given the fact that most other measures, such as the UHDRS motor and cognitive measures, as well as other tests of general mobility and balance, did not show a similar trend suggests that there is something specifically related to walking that may have been different for the late-stage participants in this study. Although anecdotal, the possibility that the regular walking program may delay progression of walking limitations in people with HD warrants further investigation.
The test-retest reliability of many of the tests in this study was found to be excellent. This finding is in line with previous research in people with PD.35 We chose to group participants according to stage of disease in order to provide some insight as to which tests may be appropriate at different stages of the disease progression. In general, test-retest reliability was higher for individuals with manifest HD than those with pre-manifest HD. Within the manifest HD group, the ICCs were lower for those in the middle stage of the disease for many of the tests.
The MDC values for the BBS and the 6MWT were comparable to those values found in people with PD.35 However, the MDC for gait speed was considerably higher (0.18 in people with PD). This finding may be related to variability of motor performance as a feature of HD and is consistent with previous observations that variability in walking is a greater impairment in people with HD compared with people with PD.8 A recent study in people with Alzheimer disease also demonstrated considerably lower MDC values for the 6MWT (33.5 m) and for gait speed (0.094 m/s)36 compared with the findings presented here. Minimal detectable change values for the TUG have been found to be higher in both people with Alzheimer disease (4.09)36 and people with dementia (3.96 for people with mild cognitive impairment, 8.07 for people with moderate cognitive impairment).37 Despite the fact that many participants in the present study had varying degrees of cognitive impairments, their performance on the TUG suggests this variance does not affect reliability. Minimal detectable change values in this study for the TMT also were found to be lower than those found in a group of elderly people (4–5).38 These differences highlight the importance of disease-specific assessment of reliability and MDC.
In this study, we examined a combination of performance-based and self-report measures. The RMI and Barthel Index, both self-report measures, had excellent reliability and relatively narrow ranges of scores across all stages of HD. Interestingly, the MDC was low for these measures for participants in the middle and late stages of the disease. Future investigation of these self-report measures examining validity through comparison with objective measures by clinicians and caregiver reports is recommended. The usefulness of these scores across the stages of HD may be better examined through these studies. The IPAQ, which also is a self-report measure, showed a much higher degree of variability and lower test-retest reliability than many of the other measures. Differences between test sessions on this test, in part, may reflect limitations in participant recall or may highlight actual differences in activity levels from week to week. It is possible that impaired cognition in individuals in the middle and late stages of the disease could have influenced recall, which is required for self-report measures such as the IPAQ. Thus, limited recall secondary to impaired cognition may have affected the reliability of this measure.
We hypothesize that higher MDCs in the middle stage of HD may be due to higher variability in motor disability in this stage of the disease. The TFC is a function-based scale; therefore, an individual may be functionally impaired due to cognitive declines while having relatively low motor disability. Alternatively, individuals may receive higher functional scores due to support systems and have higher cognitive functioning while demonstrating higher motor disability. These factors would have more of an impact on TFC for individuals in the middle stage of the disease. Another factor leading to greater variability in the middle stage of the disease in gait and balance measures may be chorea. In general, individuals with HD can exhibit greater amounts of chorea in the middle stage of the disease compared with early and sometimes later stages.39 Because chorea can be variable across time and situations, it could lead to more variability in gait and balance measures across testing sessions.
The limited number of pre-manifest HD participants recruited for this study limits the ability to interpret and generalize the findings presented here. Several of the measures appeared to have low ICC values; this finding may reflect the relatively low variability among the participants, thus lowering the ICC artificially. People with pre-manifest HD did show ceiling effects on some, but not all, measures. There was a good range of scores for the 6MWT, 10-Meter Walk Test, Romberg and Sharpened Romberg tests, and FSST. Although the Romberg and Sharpened Romberg tests had a high MDC for pre-manifest HD participants (almost 30 seconds), the 6MWT, 10-Meter Walk Test, and FSST had a relatively low MDC and excellent reliability. The FSST requires a high degree of cognitive-motor planning, as the participant needs to follow a set sequence of moving through a series of boxes, and as such may be particularly challenging for participants in the later stages of the disease. Three participants could not complete the FSST; thus, this test may not be appropriate for all individuals. This test may rather prove to be a useful tool for clinical assessment of high-level balance and motor planning in people with pre-manifest and early-stage HD.
The BBS, PPT, and TUG, and to a lesser extent the TMT, demonstrated excellent reliability and low MDC across disease stages for people with manifest HD, suggesting these tests may be appropriate for clinical trials aimed at improving physical functioning. Many of the tests utilized in this study have common tasks, including walking, turning in place, and tandem stance. Although several of the measures presented here may be useful for clinical trials, further analysis of the individual component scores of each of these tests may provide important information as to the specific nature of some of the impairments in people with HD, particularly at different stages of the disease. It is evident from this study that participants with pre-manifest and early-stage HD have relatively few limitations in functional skills (reflected in scores on the UHDRS function and independence scales, Barthel Index, and RMI) but do have impairments in balance (BBS and Romberg and Sharpened Romberg tests) and coordination (FSST). It is unknown which specific components of these impairments may be sensitive to disease progression.
Individuals with pre-manifest and early-stage HD had walking speeds that, on average, were slower than reported for individuals of similar age who were healthy.40 However, gait speed had a higher MDC value than found in other populations (stroke41 and PD35), especially in participants in the middle stage of HD, which suggests that it may have limited utility as an outcome measure in this disease stage. The 6MWT, which is a measure of walking endurance, had a low MDC and excellent ICC in the early and middle stages of the disease and may be an effective tool for measuring gait impairments in these stages of the disease. Similar to gait speed, the high MDC seen in participants in the middle and late stages of HD, would suggest that the 6MWT may have limited utility in the later stages.
Limitations
Although we recruited a good spread of participants across the disease stages, the sample size in the pre-manifest group was relatively small. This fact likely reflects the high level of functioning of this group, many of whom continue to work and could find it difficult to take off time for 2 separate testing sessions within a 1-week interval. The low number of participants in this group limits the interpretability of the reliability and MDC values. Forthcoming intervention trials may likely be aimed at this patient group; therefore, it is critical that further work be done to ascertain which physical performance measures may be sensitive and reliable.
Conclusion
This study presents reliability and MDC values for various measures of functional abilities and physical impairments in people with pre-manifest and manifest HD. The BBS, PPT, and TUG demonstrated excellent reliability and low MDC across disease stages, suggesting that these tests may be appropriate for clinical trials aimed at improving physical functioning in people with HD. Our preliminary findings suggest that the 6MWT and FSST may be useful tools for assessing individuals with pre-manifest HD. Future research is needed to further identify tests that can be sensitive to interventions aimed at specific disease stages.
Appendix 1.
Participating Sites and Members
Appendix 2.
Participating Sites and Number of Participants Recruited per Site
Appendix 3.
Protocols and Instructions for Mobility Assessments
Footnotes
Dr Quinn, Dr Khalil, Dr Dawes, Dr Kegelmeyer, Dr Gillard, and Dr Busse provided concept/idea/research design. Dr Quinn, Dr Khalil, Dr Dawes, Dr Fritz, Dr Kegelmeyer, Dr Kloos, and Dr Busse provided writing. Dr Khalil, Dr Dawes, Dr Fritz, Dr Kegelmeyer, Dr Kloos, and Dr Busse provided data collection. Dr Quinn, Dr Khalil, Dr Kegelmeyer, Dr Kloos, Dr Gillard, and Dr Busse provided data analysis. Dr Quinn and Dr Busse provided project management and fund procurement. Dr Fritz, Dr Kegelmeyer, and Dr Kloos provided study participants. Dr Kegelmeyer and Dr Busse provided institutional liaisons. Dr Kegelmeyer provided clerical support. Dr Dawes, Dr Fritz, Dr Kegelmeyer, and Dr Kloos provided consultation (including review of manuscript before submission). The authors gratefully acknowledge the time and support of each of the participants and the caregivers in this study. They also acknowledge all members of the European Huntington's Disease Network Physiotherapy Working Group for their contribution at annual meetings and Dr Sheila Simpson for her insightful review of the study protocol.
Members of the Outcome Measures Study Subgroup, European Huntington's Disease Network: Wilco Achterberg, Veena Agarwal, Reineke Bos, Karen Bunnnig, Monica Busse, Johnny Collett, Leonor Correia Guedes, Helen Dawes, Josefa Domingos, Joaquim Ferreira, Nora Fritz, Kerry Gibson, Olivia Handley, Claire Hannam, Elizabeth Howard, Deb Kegelmeyer, Hanan Khalil, Anne Kloos, Christopher Kipps, Sara Minster, Andrea H. Nemeth, Lori Quinn, Hugh Rickards, Dawn Rogers, Anne Rosser, Bryony Sheridan, Jo Teal, Jenny Townhill, Jessie van der Bent.
This study was funded by the European Huntington's Disease Network, Ulm, Germany. The authors gratefully acknowledge the support of the National Institute for Social Care and Health Research Clinical Research Centre and the Dementias & Neurodegenerative Diseases Research Network (DenDRoN), England. Dr Andrea H Nemeth received support from Thames Valley DeNDRoN.
- Received February 1, 2013.
- Accepted March 18, 2013.
- © 2013 American Physical Therapy Association
References
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