Richard K. Shields, PhD, Janet L. Ruhland, PT, Mark A. Ross, MD, Margaret M. Saehler, PT, Kent B. Smith, PT, Marta L. Heffner, RN

Transcription

1 855 Analysis of Health-Related Quality of Life and Muscle Impairment in Individuals With Amyotrophic Lateral Sclerosis Using the Medical Outcome Survey and the Tufts Quantitative Neuromuscular Exam Richard K. Shields, PhD, Janet L. Ruhland, PT, Mark A. Ross, MD, Margaret M. Saehler, PT, Kent B. Smith, PT, Marta L. Heffner, RN ABSTRACT. Shields RK, Ruhland JL, Ross MA, Saehler MM, Smith KB, Heffner ML. Analysis of health-related quality of life and muscle impairment in individuals with amyotrophic lateral sclerosis using the Medical Outcome Survey and the Tufts Quantitative Neuromuscular Exam. Arch Phys Med Rehabil 1998;79: Objective: The Tufts Quantitative Neuromuscular Exam (TQNE) is commonly used to assess the rate of disease progression in individuals with amyotrophic lateral sclerosis (ALS). The Medical Outcome Study Short Form (SF-36) is a general method to assess health-related quality of life (HRQL). This study examined the relationship between the TQNE and SF-36, established the reliability and responsiveness of each, and contrasted the HRQL between individuals with ALS and the general population. Design: Subjects (31) completed the SF-36 and TQNE within 1 week to determine reliability. Subjects (17) also completed both the TQNE and SF-36 each month for 1 year after diagnosis of ALS to establish the relationship between the two assessment tools. Setting: A primary care university teaching hospital. Patients: Thirty-one subjects with an age range of 27 to 76 years (mean 59.1, SD 1.32), recently diagnosed with ALS. Results: Each test was highly reliable and responsive. The intraclass correlations (2, 1) were consistently higher for the TQNE (.93 to.98) than for the SF-36 (.57 to.9). Changes in physical function were correlated to changes in lower extremity force megascores (.48). Conclusion: Both the TQNE and the SF-36 are reliable and responsive and appear important in characterization of patient status after ALS is diagnosed by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation A MYOTROPHIC LATERAL sclerosis (ALS) is a devastating disease not only to the individuals afflicted but to their From the Physical Therapy Department, University of Iowa Hospitals and Clinics, Iowa City, IA. Submitted for publication October 29, Accepted in revised form January 13, Supported in part by the University of Iowa Physical Therapy Clinical Research Center, which was originally funded by the Foundation for Physical Therapy, Inc., and by a Geriatric Center grant from the National Institutes of Health. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Reprint requests to Richard K. Shields, PhD, PT, Physical Therapy Graduate Program, The University of Iowa, 26 Steindler Building, Iowa City, IA by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation /98/ / families and to society as well. In the United States, ALS has an incidence rate of 1 to 3 per 1,.1 Approximately 6 new cases of ALS are diagnosed each year. 2 ALS is a disease of the nervous system in which there is degeneration of both upper and lower motor neurons. Degeneration of motor neurons causes decreased motor control, paralysis, muscle atrophy, spasticity, speech loss, swallowing difficulties, respiratory compromise, and eventually death. 3 The psychosocial impact of ALS is profound. Life roles, including work, family, and social roles, change. Persons become physically dependent and can become socially isolated. 3 Families take on increased responsibility for long-term care, leading to the eventual loss of a loved one. Society endures a decreased workforce, decreased productivity at work, and increased health care use. Traditionally, natural history studies and therapeutic drug trials for ALS use mortality, days of survival, and clinical measures of strength to monitor disease progression and evaluate the efficacy of interventions. 4-8 One scale, the Tufts Quantitative Neuromuscular Exam (TQNE), 6 assesses five areas of muscle function: btflbar, respiratory, timed hand function, upper extremity isometric muscle force, and lower extremity isometric muscle force. The developers of the TQNE believe the upper and lower extremity force measurements accurately reflect motor unit function. 9 The course of motor unit loss is the most important factor to document the progression of ALS.1 A recent study reported an increased survival (3 months) or slowed progression of muscle weakness 11 in individuals with ALS who took a glutamate inhibitor (riluzole). It is remarkable that individuals' perceptions of their quality of life was not measured. Indeed, the changes observed in results of neuromuscular tests (such as the TQNE) during efficacy trials may be below an individual's threshold of perception. For example, we may consider an intervention efficacious if the TQNE improves, but there is little information on the relationship between changes in muscle force and an individual's perceived healthrelated quality of life (HRQL). Some investigators studying individuals with ALS emphasize that in the absence of a cure we should treat the person rather than the disease. 2,3,12 Bocker and associates 12 and Hunter and coworkers 3 studied the relation between functional and psychologic status in patients with ALS. They both concluded that severity of functional impairment relates to psychologic distress but that function explains only a small part of the overall variability associated with psychologic distress. McDonald and colleagues 2 concluded that psychologic status relates to survival time in ALS. These studies generally limit the scope of their investigation to clinical psychologic assessment scales. Hence, although these studies provide an important first step in investigation of broader aspects of the impact of a disease like ALS, they do not encompass the full variety of health concepts needed to describe a person's HRQL.

2 m 856 QUALITY OF LIFE FOR INDIVIDUALS WITH ALS, Shields HRQL includes areas of physical function, psychologic well-being, and social functioning. 13 The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) 14 is an HRQL measure that covers eight health status concepts including physical functioning, role functioning because of physical problems, role functioning because of emotional problems, general health, bodily pain, vitality, social function, and mental health. The SF-36 is valid, reliable, and responsive to change in a variety of patient groups The reliability and responsiveness of the SF-36 and TQNE for individuals with ALS has not been studied extensively. Furthermore, we do not know how volitional muscle force (TQNE) relates to HRQL (SF-36) for individuals with ALS. Accordingly, the purposes of this study are to establish the reliability and responsiveness of the TQNE and SF-36 in patients with ALS, examine the relationship between isometric measures of muscle force and HRQL for 1 year after diagnosis of ALS, and contrast the perceived HRQL of individuals with ALS to that of the general population. PATIENTS AND METHODS Subjects Thirty-one right-handed individuals with newly diagnosed unequivocal ALS, as defined by the World Federation of Neurology Subcommittee on Motor Neuron Disease, 22 participated in the study. In the majority of subjects, onset began with weakness of the limbs; patients with severe bulbar dysfunction or with severely impaired pulmonary function (forced vital capacity [FVC] <5% predicted) were excluded from the study because of the rapid rate of disease progression associated with these complications. All 31 subjects (aged 27 to 76 years, mean 59.1, SD 1.3) were initially evaluated by TQNE and SF-36. We evaluated 3 subjects with the TQNE and SF-36 a second time within 1 week (one subject was disqualified because his FVC was below the 5% acceptable level). These 3 subjects provided the sample for the reliability study. We evaluated 17 subjects (aged 41 to 69 years, mean 57.7, SD 8.5) every month using the TQNE and SF-36 for 1 year to establish responsiveness and the relation between the two measurements. We lost 13 individuals to follow-up because they either died (n = 11) or were unable to return for reassessment because of the severity of their disease (n = 3). This study protocol was approved by our university's Human Subjects Review Board. Subjects reviewed and signed informed consent forms before agreeing to participate in the study. All subjects were recruited from our university hospital's Department of Neurology. Instruments We obtained quantitative isometric muscle force impairment data for this study using the TQNE. 6,23 Investigators received 2 days of training in administering the TQNE. The TQNE test battery consists of five categories of items that assess motor neuron function at different levels of the neuraxis. These categories include pulmonary function, bulbar function, timed hand activities, maximal isometric muscle force of the upper extremities, and maximal isometric muscle force of the lower extremities. Specific items included in each category vary somewhat in different studies. 6,9,24 In this study, pulmonary function consisted of two items, FVC (best of two trials) and forced expiratory volume (FEV). Timed hand activities included the Purdue Peg Board test with the right and left hands. We recorded the number of pegs inserted in a board in 3 seconds (best of two trials). Isometric force measurements for the upper extremity were carried out in the supine position and included bilateral shoulder flexion and extension, bilateral elbow flexion and extension, and right- and left-hand grip strength (1 muscle groups). Lower extremity isometric muscle forces were tested in the seated position and included bilateral hip flexion and bilateral knee flexion and extension. We determined all forces from the best of two trials. We excluded a fifth category, bulbar function, because of the rapid progression typically associated with this dysfunction in ALS. We administered the TQNE as recommended using a bed instrumented with a strain gauge. 6 Each TQNE test took approximately 1 hour to administer. The analog to digital board housed in an expansion slot of a microcomputer sampled the force signal at 1 samples per second. We calibrated the force transducer weekly. The transducer had a nonlinearity of less than 1.4% of full scale. The transducer was accurate to _+2% of full scale. As previously indicated, we determined the forces produced by each muscle group as well as calculating extremity scores. We calculated the extremity scores, or megascores, for both the upper and lower extremity muscles according to the methodology described by Andres and associates. 23 Z scores were calculated for each muscle group tested. Z Score = Muscle Force Megascore for Upper Extremities ALS Population Mean for That Muscle Force ALS Population Standard Deviation for That Muscle Force 23 Sum of Z Scores for Each Muscle Group of Upper Extremities Number of Upper Extremity Muscle Group Z Scores The developers of the TQNE emphasize the upper and lower extremity isometric force measurements because they believe they reflect motor unit loss more accurately than do the timed tests used to assess bulbar and hand function. 9 Others used the TQNE to examine the natural history of ALS 9,1 and in drug intervention studies.24-3 The reliability of the TQNE in individuals with ALS was found to be excellent (Pearson correlations varied from.92 to.99).6,3 The HRQL measure used for this study was the Medical Outcomes Study (MOS) 36-Item Short Form Health Survey (SF-36). Each of the eight health concepts--physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social function (SF), role emotional (RE), and mental health (MH)--is measured on a scale from to 1, with a higher score indicating better health. 14 A physical component summary (PCS) and a mental component summary (MCS), which represents a weighted aggregate of the other health concepts, can also be calculated. 14 The usefulness, validity, and reliability of the SF-36 have been examined extensively in the general population and in groups of persons with other chronic conditions This questionnaire takes between 5 and 15 minutes to complete. Procedure The individuals who administered the SF-36 questionnaire and TQNE assessments were physical therapists. Patients completed the SF-36 questionnaire on their own. One of three physical therapists, trained in administering the TQNE, evaluated each subject. We repeated both the TQNE and SF-36 within 1 week of the initial assessment to determine the

3 QUALITY OF LIFE FOR INDIVIDUALS WITH ALS, Shields 857 reliability of these measurements (n = 3). We generally had the same therapist administer the TQNE and SF-36 for a given patient. However, on six occasions we were unable to have the same therapist administer both tests to the same subject. After we completed the reliability study, we evaluated 17 of the subjects on a monthly basis for 1 year to determine disease progression and to establish the responsiveness of both the TQNE and SF-36. Data Analyses We performed our statistical analysis using the Statistical Analysis Systems (SAS) a software procedures. We calculated descriptive statistics for the 31 patients evaluated initially and the subset of 17 patients evaluated at baseline and each month for 1 year. We used an intraclass correlation coefficient (ICC) (2, 1) to estimate the level of agreement between the repeated tests performed in the first week after diagnosis, sl We computed scores for each SF-36 health concept and component scores as well as values of individual muscle force measurements, upper and lower extremity megascores, and percentage change for all muscle test scores. We estimated the responsiveness by using the formula originally described by Guyatt and coworkers, 32 which is equivalent to the clinical change/square root (2x mean square error). We expressed the number of subjects needed to detect the changed score at, 3, 6, and 12 months (n = 17) according to Guyatt, 32 using an alpha level of.5 and a beta level of.2. The sample size was less than 3; therefore, we used a correction factor as described by Lachin. 33 We used paired t tests to determine whether scores at months were different from scores at 12 months. We used a one-way ANOVA to determine if the percentage change in the physical function health concept was different from the percentage change in lower extremity or upper extremity muscle force scores. We used a p value that was less than or equal to.5 as our level of significance for all tests. RESULTS Descriptive statistics and SF-36 scores are reported for 31 individuals with ALS at baseline and for the subsample of 17 patients at baseline and 12 months after diagnosis (table 1). Of the 31 subjects assessed at baseline, floor effects were present for PF (6%), RP (65%), and RE (32%). Of the 17 subjects assessed at 12 months, floor effects were present for PF (63%), RP (69%), and RE (19%). None of the health concepts showed ceiling effects. Muscle forces, number of pegs placed, and TQNE megascores for the 31 individuals with ALS at baseline and for the 17 patients at baseline and at 12 months after diagnosis are presented in table 2. For TQNE muscle force measurements, only three muscle groups (two persons) had a floor effect on initial assessment out of 221 muscles tested (1.3%). At 12 months, 17 muscle groups (three subjects) showed floor effects (8%). Reliability Overall, the muscle force measurements from the TQNE showed higher test-retest correlations than the various health concepts that make up the SF-36. Correlation coefficients (ICC 2, 1) for the health concepts of the SF-36 varied from.74 to.9, except for RE, which was.57 (table 3). Correlation coefficients (ICC 2,1) for the force measurements of the TQNE varied from.93 to.98 (table 3). FVC and FEV showed the lowest correlations for tests performed as part of the TQNE (ICC.61). Although most correlations were high, indicating good reliability for both HRQL and muscle force impairment measures, muscle force impairment measures consistently showed greater reproducibility. Responsiveness The various health concepts of the SF-36 are responsive if it takes few subjects to detect a clinically meaningful change in the patient's health status. Three and 6 months after the diagnosis of ALS, the most responsive health concept was MH, which required 36 subjects to detect a 9-point change (table 4). Interestingly, the MH score increased at 3 and 6 months, indicating that patients' perception of their MH was poorest at the time of diagnosis but, on average, improved over the next 6 months. By 12 months, the MH concept was no longer responsive, indicating that individuals' perceptions of their MH declined over months 9 to 12. Twelve months after the diagnosis of ALS, the most responsive health concept was PE We needed only 19 subjects to detect an 18-point decrease in PF, whereas we needed 82 and 197 subjects at 6 months and 3 months, respectively (table 4). The increase in responsiveness of the PF health concept over the year indicates that individuals perceived that their PF was progressively declining. The PCS, an aggregate of several of the health concepts, was equally responsive at 1 year, requiring 19 subjects to detect an average change of The mean values for the mental component aggregate, physical component aggregate, and PF health concept are depicted every 3 months for 1 year in figure 1. Three months after diagnosis of ALS, the most responsive Table 1: Descriptive Statistics (Mean -+ SD) and SF-36 Scores for All Subjects and the Subset of Subjects Followed for 12 Months n = 31 (Baseline) n = 17 (Baseline) n = 17 (at 12 Months) pvalue Age (yrs) 59.1 _ (27-76) 57.7 ± 8.51 (41-71) 58.7 _ (42-72) Height (cm) 66.7 ± ± ± 3,95 Weight (kg) 77.9 ± _ _ Women (n) Physical function _ ± ± * Role physical ± 25, ± ± Bodily pain ± ± ± General health ± _ ,63 ± Vitality 48.6 ± ± ± Social function ± ± ± Role emotional _ ± ,54 ± Mental health 71,22 ± ± ± Physical component 32,96 ± ± ± * Mental component _ _ _ * Significant difference between 17 subjects at baseline and at 12 months (p -<.5).

4 858 QUALITY OF LIFE FOR INDIVIDUALS WITH ALS, Shields Table 2: Muscle Forces (N), Number of Pegs, and the Megascores (Mean -+ SD) at the Time of Diagnosis for All Subjects and the Subjects (n = 17) Followed Up for 12 Months Subset of n = 31 (Baseline) n = 17 (Baseline) n = 17 (at 12 Months) pvalue Left grip _ Right grip ± 159. Left shoulder extension ± 12.5 Right shoulder extension ± 127. Left shoulder flexion _ 85.7 Right shoulder flexion 152. ± 86.3 Left elbow extension 132. ± 72.4 Right elbow extension ± 65.3 Left elbow flexion ± 92.7 Right elbow flexion _ Left knee extension _ Right knee extension 257,6 ± Left knee flexion Right knee flexion _ Left hip flexion _ Right hip flexion ± Left peg t 7.97 ± 5.13 Right peg t 9.55 ± 5.4 FVC (% normal) ± 2.89 FEV (% normal) ± 19.3 Upper extremity megascore (z score) 1.44 ± 1.46 Lower extremity megascore (zscore) _ _ * 37.2 ± " ± _ " ± _ " ± ± " _+ 94, ± " _ " ± ± " ± _ " 29.8 ± _ " 3.9 ± _+ 144.,1" ± _ " _ * ± ± " ± _ " 356. _ * _ ± _ * ± _ ± _ ,99 ± _ ".93 _ _ " * Significant difference between 17 subjects at baseline and t Number of pegs completed. at 12 months (p -<.5). muscle force measurements of the TQNE were shoulder flexion and hip flexion and required between 25 and 37 patients to detect a change between 14 and 37N of force (table 5). Six months after diagnosis, all muscle groups tested were similarly responsive to the changes in muscle force, but changes in shoulder flexion continued to be the most responsive (six to eight subjects). Twelve months after diagnosis, there were large changes in all muscle groups. Only two to nine subjects were needed to detect the change in muscle force measured for any of the muscle groups tested. Interestingly, the Purdue pegboard functional task and the FVC were consistently the least responsive measures to change at all three times during the year after the diagnosis of ALS. Relationships and Comparative Analysis of SF-36 and TONE On average, only one of the eight health concepts (PF) and the PCS of the SF-36 decreased (p =.5 and.6, respec- Table 3: Reliability of the Various Health Concepts of the SF-36 and the Muscle Force Variables of the TQNE ICC ICC ICC PF.86 Left grip.97 Left knee extension.95 RP.76 Right grip.98 Right knee extension.96 BP.74 Left shoulder extension.93 Left knee flexion.93 GH.75 Right shoulder extension.93 Right knee flexion.97 VT.9 Left shoulder flexion.97 Left hip flexion.96 SF.82 Right shoulder flexion.98 Right hip flexion.95 RE.57 Left elbow extension.96 Left peg.96 MH.81 Right elbow extension.94 Rightpeg.91 PCS.82 Left elbow flexion.95 FVC.61 MCS.81 Right elbow flexion.95 FEV.61 Abbreviations: ICC, intraclass correlation coefficient (2, 1)31; PF, physical function; RP, role physical; BP, bodily pain; GH, general health; VT, vitality; SF, social function; RE, role emotional; MH, mental health; PCS, physical component score; MCS, mental component score; FVC, force vital capacity; FEV, forced expiratory volume. tively) in the 12 months after diagnosis (table 1). However, all impairment measures for muscle force declined 12 months after the diagnosis of ALS (table 2). The lower extremity muscle forces decreased between 46.2 and 14.8N, whereas upper extremity muscle forces decreased between 55.2 and 99.4N. The upper and lower extremity megascores also changed after 12 months (p =.1). The pegboard test changed on the right side (p =.8) but not the left side (p =.13), although both grip strengths decreased (p =.1). The FVC and FEV were not changed over 12 months. The average percentage change in muscle force for all upper and lower extremity muscle groups was 44.7% (+26.2) and 39.9% (_+22.4), respectively. The mean percentage change in the PF health concept score was 6.5% (+ 28.1). There was no Table 4: Responsiveness of Various Health Concepts of the SF-36 in Patients With ALS: Overall Change From Mean Baseline Score/Sample Size Requirements 3Mo 6Mo 12Mo P F 5.29/ / /19 RP 4.41/ / /154 BP 8.76/ / /114 G H -.47/ / /53 VT -7.35/ -2.65/ /65 SF 2.94/ / /3988 RE / / /251 M H / / /3419 PCS 4.26/ / /19 MCS -5.55/5-7.2/ /12 Assumptions: o~ =,5 (2-tailed); 13 =.2; independent groups. The n has been increased according to the method of Lachin when sample size was less than 3. A negative number indicates an increase in score. Abbreviations: PF, physical function; RP, role physical; BP, bodily pain; GH, general health; VT, vitality; SF, social function; RE, role emotional; MH, mental health; PCS, physical component score; MCS, mental component score.

5 QUALITY OF LIFE FOR INDIVIDUALS WITH ALS, Shields Physical Function I/) o to I.u ~O ; i 4 ; ; ; 1' O o o 25 (D 3 II= 2. if) Elbow Flexion x n - Z.i o 14. o Time (months) Fig 1. Mean mental component score (MCS), physical component score (PCS), and physical function score (PF) of the SF-36 every 3 months for 1 year after diagnosis of ALS. Note that the perception of physical function decreases while the perception of mental health improves slightly. difference between percentage change in the PF health concept and percentage change in the upper or lower extremity muscle forces (p =. 18). The mean decrease in individuals' perceptions of their PF was consistent with the mean decline in muscle force scores (fig 2). The individual Pearson product moment correlations between the change in PF scores and the change in individual muscle force measurements were highest for the lower extremities (table 6). Hence, on average, the change in perceived PF from the SF-36 better matched the change in measured muscle force from the lower extremities. The lower extremity muscle force (megascore) was moderately correlated to the PF score at diagnosis (Pearson correlation r =.55) and remained moderately correlated after 12 months (.65) (table 6). As evident in figure 3, the three subjects Table 5: Responsiveness of Muscle Force Impairment Variables of TQNE in Patients With ALS: Change (N)/Sample Size Requirements 3Mo 6Mo 12Mo Left grip 13.63/173 3./ /5 Right grip 14.94/ / /5 Left shoulder extension 12.2/ / /7 Right shoulder extension 12.6/ /24 98,9/7 Left elbow extension 9.7/85 21,4/2 58.1/5 Right elbow extension 7/ / /6 Left shou Ider flexion 15/3 45.1/6 88.6/2 Right shoulder flexio n 14.8/ /8 89.1/3 Left elbow flexion 26.8/ /1 93.7/3 Right elbow flexion 12.3/132 36/ /5 Left knee extension 2.7/ / /6 Right knee extension 2.9/ / /7 Left knee flexion 3.1/1, / /7 Right knee flexion 14.7/ /11 5.3/6 Left hip flexion 35.3/25 45/ /8 Right hip flexion 37/31 6.6/13 8.5/9 Right peg.1/729.6/ /17 Forced vital capacity -3.8/ / ,41/46 Assumptions: c~ =.5 (2-tailed); 13 =.2; independent groups. The n has been increased according to the method of Lachin when sample size was less than 3. A negative number indicates an increase in score '2 14 Time (months) Fig 2. Mean physical function score, knee extension force, and elbow flexion force every 3 months for I year after diagnosis of ALS (n = 17). who had the highest megascore, indicating greater muscle force after 12 months, also maintained the highest perception of PE After normalization of the lower extremity muscle forces to subject body weight, the correlation between PF and the lower extremity muscle scores at diagnosis and at 12 months increased from.55 to.64 and from.65 to.68, respectively. Conversely, the upper extremity megascore was poorly correlated to PF both at diagnosis (Pearson correlation r =.5) and at 12 months (.14) (fig 3). The subjects generating higher muscle forces did not report a higher perception of their physical health. This general pattern of a poor correlation between PF and upper extremity forces held true for most of the individual muscles tested in the upper extremity (table 6). After normalization of upper extremity muscle forces to subject body weight, the correlations at diagnosis and at 12 months increased to only.11 and.23, respectively. The perceived physical disability at the time of ALS diagnosis was severe compared with the general population (fig 4). At Table 6: Pearson Product Moment Correlation Between Physical Function and Extremity Forces at Months, 12 Months, and the Change Between and 12 Months Change in Physical Physical Physical Function Function Function at OMo at 12Mo Over 12Mo Left/right grip,7/ /-,1.18/.14 Left/right shoulder extension.7/ /.23.11/.11 Left/right shoulder flexion.6/-.6."/.26.21/.18 Left/right elbow extension.2/-.7.3*/.32*.2/.12 Left/right elbow flexion.5/-.2.5/-,5.1/.3 Left/right knee extension,54*/.36*.7*/.55*.62*/.48* Left/right knee flexion.65*/.66*,67*/.69*.41"/.31 * Left/right hip flexion,39*/,35*.59*/.*.37*/.22 Upper extremity megascore -.5,14.8 Lower extremity megascore.55*.63*.48* * p -<.5 based on the null hypothesis: r = O.

6 86 QUALITY OF LIFE FOR INDIVIDUALS WITH ALS, Shields 12 - = 1 - "~ so = 6 "~ ;~ ,. 1 - "~ 8- = = 6 2 r =.55 Upon Diagnosis 11 I I I I I r = -.5 i i i / At 12 Months r =.~ Lower Extremity Mega Score i i i i J i r =.14 Upper Extremity Mega Score i i i Fig 3. Scatterplot ofthe physical function scores plotted against the TQNE megascore upon diagnosis (upper left) and at 12 months (upper right) for the lower extremities and upon diagnosis (lower left) and at 12 months (lower right) for the upper extremities. the time of diagnosis, PF and RP were less than 5% of the values in the general US population (p <.5). Individuals' perceptions of GH, SF, and RE in society were significantly less than those of the general population (p <.5). As depicted in figure 4, the greatest change after diagnosis occurred in the PF domain. Indeed, the PF health concept 12 months after diagnosis of ALS is less than 25% of the general population's PE DISCUSSION There were several major findings in this study. First, the TQNE and the SF-36 provide reliable measurements when monitoring outcomes of individuals with ALS. However, the muscle force measurements were consistently more reliable than the individual health concepts of the self-administered SF-36 questionnaire. Second, all muscle force measurement values were significantly reduced 12 months after diagnosis of ALS, but only the PF health concept changed significantly over the same time. Accordingly, muscle force measurements were more responsive to changes over 12 months after the diagnosis of ALS than were changes in the various domains of the SF-36. Third, the changes that occurred in muscle force measurements were closely associated with changes in individuals' perceptions of their physical health 1 year after diagnosis of ALS. The lower extremity forces were moderately correlated to PF of the SF-36 at diagnosis and after 12 months, but the upper extremity muscle forces were poorly correlated to the PF health concept at these same times. Finally, compared with the general population, individuals with ALS have a significant depression in their perception of PE even at the time of diagnosis. Reliability Issues The high correlation coefficients for repeated muscle forces and the repeated Purdue pegboard test are significant given that the ICC statistic is more conservative than the Pearson correlation. 31 Andres and coworkers 6 reported Pearson product moment correlations between.92 and.99 for interrater and intrarater reliability of the TQNE of patients with ALS. Hence our study confirmed that the TQNE is highly reproducible in individuals with ALS. We also found high correlation coefficients (table 4) for repeated SF-36 tests administered 1 week apart. No previous study reported the reliability of the SF-36 in individuals with ALS for comparison. However, Jette and Downing 34 recently reported the reliability of the SF-36 for a large sample of patients entering a cardiac rehabilitation program. The ICCs varied from.7 to.84 for the various health concepts of the SF-36, with the exception of RE, which was.37. Interestingly, the RE health concept also showed the poorest reliability in our study. The ICC for the RE health concept was significantly lower than for other health concepts. One possible explanation for this lower correlation is that patients' perceptions of their emotional roles in society may change during the week that separates repeated administrations of the questionnaire. Responsive Issues The muscle force measurements were not only most reliable, but also were most responsive to change during the 12 months after diagnosis. Indeed, fewer than 1 subjects were required to detect the mean change in any muscle group tested over the 12 months after diagnosis of ALS. In contrast, only the PF and the PCS of the SF-36 approached the responsiveness of the muscle force measurements. If we assume that SF-36 was detecting what individuals perceive about their physical health, then the greater responsiveness for the muscle force measurements Physical Role Bodily General 1 Functioning Physical Pain Health Vitality Social Role Mental Function Emotional Health Physical Component Score ++~ +++ }l; Mental Component Score Fig 4. Mean SF-36 scores upon diagnosis ([]) and after 12 months (E~) for individuals with ALS (n = 17) and for the general population (R, n = 2,474). Error bars represent SE.

7 QUALITY OF LIFE FOR INDIVIDUALS WITH ALS, Shields 861 suggests that early changes in muscle force may not be perceptible to the individual. Hence, interventions based on a minimal improvement in muscle force may not be recognized by the individual as improving physical health. No previous study has contrasted the responsiveness of the TQNE and SF-36 in patients with ALS using Guyatt's statistic32; hence, we are unable to compare our findings with those of previous reports. Accordingly, additional studies, with even larger sample sizes, are needed to clearly delineate the definitive relationship between changes in muscle force and perception of physical health after the diagnosis of ALS. The duration of symptoms before diagnosis of ALS and the cohort of subjects studied for 1 year are factors that could influence the magnitude of change found in the SF-36 and TQNE. We were not able to accurately characterize the duration of symptoms for subjects in our study, but Haverkamp and associates, ~ using similar diagnostic criteria, reported that patients, on average, had symptoms for 14.4 ± 9.9 months before diagnosis. This lengthy time before diagnosis may explain why individuals' perceptions of PF was only 5% of those of the general population at the time of diagnosis. Andres 23 calculated megascores for 176 randomly chosen subjects with ALS diagnosed using criteria similar to those used in this study. Upon diagnosis, our upper extremity megascores were approximately two times those reported by Andres. 23 The average megascore of 1.99 for the upper extremities indicates that the mean of our sample was 2 SD above the "standard" ALS population established from a larger database. 23 The mean megascore of.93 for the lower extremities indicates that our sample was 1 SD greater than the "standard" ALS population. 23 At 12 months, the upper extremity and lower extremity megascores were.58 and.47, respectively, indicating that the muscle forces were still.5 SD above the "standard" ALS sample. ~3 Hence, in all likelihood our sample had significantly less muscle weakness at the time of diagnosis and at 12 months than Andres'.23 These differences in disease severity no doubt influence the relative disease progression and ultimately the responsiveness of impairment measurements. Accordingly, the findings from our subset of individuals with ALS cannot be generalized to the population of individuals with ALS. Relationship Between Muscle Force and SF-36 Although upper extremity strength, lower extremity strength, and perceived PF changed similarly over the course of the 12 months (fig 2), these changes do not support the idea that PF questions from the SF-36 are sensitive to both upper and lower extremity strength differences. Support for this notion emerged when we discovered a moderate correlation between the perception of PF and the lower extremity megascores upon diagnosis (r =.64) and after 12 months (r =.68) (fig 3) but a poor association between PF and the upper extremity megascores for the same times (.5 and.14). Individuals with high upper extremity megascores did not demonstrate a high perception of PF, and individuals with low upper extremity megascores did not demonstrate a low perception of PF at and 12 months after diagnosis. Closer scrutiny of the 1 questions that make up the PF health concept of the SF-36 indicates that most of the questions address lower extremity function and therefore may not be the ideal tool to assess health status in individuals with primarily upper extremity dysfunction. For example, six of the 1 questions address whether the individual's health affects climbing several flights of stairs, climbing one flight of stairs, bending and kneeling, walking more than a mile, walking several blocks, and walking one block. The remaining four questions address whether the individual's health limits vigor- ous activities (running, lifting heavy objects, strenuous sports), moderate activities (moving a table, pushing a vacuum, bowling, golf), lifting or carrying groceries, or bathing or dressing oneself. Thus the higher correlations between perceived PF and lower extremity knee extension strength may reflect that the 1 questions regarding PF in the SF-36 emphasize activities that relate primarily to the lower extremities. HRQL Comparison to General Population When we analyzed the 17 subjects at the time of diagnosis, we found that the PF and the RP scores were 5% and 3% of those of the general population, respectively (fig 4). GH, VT, SF, and RE were all slightly lower than those of the general population. The MH concept was no different from that of the general population and actually increased over the first 9 months of the study then began to decline by 12 months. The MH concept of the SF-36 measures feelings of depression and anxiety. 14 Bocker 12 found three of four patients with advanced ALS to be moderately to severely depressed. Hunter, 3 after assessing 181 patients with ALS who were on average 2.4 years postdiagnosis, reported General Health Questionnaire scores indicative of possible psychiatric disturbance. Perhaps the subjects in our study would have continued to show a decrease in MH concept if they were followed up more than 1 year. In any event, the improved perception of MH while the perceived PF was declining underscores the importance of understanding the various health concepts that contribute to disability. CONCLUSIONS The SF-36 and TQNE are reliable and responsive methods of assessing outcomes in clinical trials involving individuals with ALS. The muscle force measurements of the TQNE were more reliable and more responsive than the various health concepts of the SF-36. The most responsive domain of the SF-36 was the PF health concept, which also changed according to changes in muscle force measurements. The greater responsiveness in muscle force measurements suggests that changes in muscle force may be detected before changes in perceived physical health based on the SF-36. Accordingly, medical interventions may be considered efficacious because muscle force measurements improve even if the individual receiving the treatment cannot perceive this improvement. This finding suggests that minimal improvements in strength may not necessarily translate into improvements in perceived function. Alternatively, our methods of assessing perceived health quality may lack sensitivity so that real change in perceived health is not detected. Hence, it does not appear reasonable at this time to conclude that either measurement (strength or HRQL) by itself can capture the various dimensions contributing to disease progression and functional disability. Therefore, we recommend use of both impairment (strength) and HRQL (SF-36) measures to best characterize the status of patients with ALS. References 1. Haverkamp LJ, Appel V, Appel SH. Natural history of amyotrophic lateral sclerosis in a database population. Brain 1995;118: McDonald ER, Wiedenfeld SA, HilM A, Carpenter CL, Walker RA. Survival in amyotrophic lateral sclerosis. The role of psychological factors. Arch Neurol 1994;51: Hunter MD, Robinson IC, Nei]son S. The functional and psychological status of patients with amyotrophic lateral sclerosis: some implications for rehabilitation. Disabil Rehabi11993; 15: Norris FH, Calanchini PR, Fallat RJ, Panchari S, Jewett B. The administration of guanidine in amyotrophic lateral sclerosis. Neurology 1974;244: Arch Phys Med RehabU Vol 79, July 1998

8 862 QUALITY OF LIFE FOR INDIVIDUALS WITH ALS, Shields 5. Olarte MR. Therapeutic trials in amyotrophic lateral sclerosis. Adv Neurol 1982; Andres PL, Hedlund W, Finison L, Conlon T, Felmus M, Munsat TL. Quantitative motor assessment in amyotrophic lateral sclerosis. Neurology 1986;36: Appel V, Stewart SS, Smith G, Appel SH. A rating scale for amyotrophic lateral sclerosis: description and preliminary experience. Ann Neurol 1987;22: Eisen A, Schulzer M, MacNeil M, Pant B, Mak E. Duration of amyotrophic lateral sclerosis is age dependent. Muscle Nerve 1993;16: Pradas J, Finison L, Andres PL, Thornell B, Hollander D, Munsat TL. The natural history of amyotrophic lateral sclerosis and the use of natural history controls in therapeutic trials. Neurology 1993;43: Munsat TL, Andres PL, Finison L, Conlon T, Thibodeau L. The natural history of motoneuron loss in amyotrophic lateral sclerosis. Neurology 1988;38: Bensimon G, Lacombley L, Meininger V. A controlled trial of Riluzole in amyotrophic lateral sclerosis. N Engl J Med 1994;33: Bocker FM, Seibold 1, Neundorfer B. Physical disability and depression in patients with advanced amyotrophic lateral sclerosis (ALS). Fortsch Neurol Psychiatr 199;58: Rubenstein LV, Calkins DR, Greenfield S, Jette AM, Meenan RF, Nevins MA, et al. Health status assessment for elderly patients: report of the Society of General Internal Medicine Task Force on Health Assessment. J Am Geriatr Soc 1988;37: Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 health survey manual and interpretation guide. Boston (MA): The Health Institute, New England Medical Center; Stewart AL, Greenfield S, Hays RD, Wells K, Rogers WH, Berry SD, et al. Functional status and well being of patients with chronic conditions. JAMA 1989;262: McHorney CA, Ware JE, Rogers W, Raczek AE, Lu JR The validity and relative precision of MOS short- and long-form health status scales and Dartmouth COOP charts. Med Care 1992;3: MS McHorney CA, Ware JE, Raczek AE. The MOS 36-item shortform health survey (SF-36): 1I: psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 1993;31: McHorney CA, Ware JE, Rachel Lu JF, Sherbourne CD. The MOS 36-item short form health survey (SF-36): III: tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care 1994;32: Enloe LJ, Shields RK. Evaluation of health related quality of life in individuals with vestibular disease using a disease specific and general outcome measure. Phys Ther 1997;77: Ruhland JL, Shields RK. The efficacy of a home exercise program on impairment and health related quality of life in persons with chronic peripheral neuropathy. Phys Ther 1997;77:12 I Shields RK, Ruhland JL, Ross M. A descriptive study of patients with amyotrophic lateral sclerosis (ALS) using the Tufts Quantitative Neuromuscular Exam (TQNE) and the Medical Outcomes Study Short Form Health Survey (SF-36) [abstract]. Phys Ther 1996;76 Suppl:S World Federation of Neurology Research Committee on Neuromuscular Disease. Classification of neuromuscular diseases. J Neurol Sci 1988;86: Andres PL, Finison LJ, Conlon T, Thibodeau LM, Munsat TL. Use of composite scores (megascores) to measure deficit in amyotrofic lateral sclerosis. Neurology 1988;38: Bradley WG, Hedlund W, Cooper C, Desousa GJ, Gabbai A, Mora JS, et al. A double-blind controlled trial of bovine brain gangliosides (cronassial). Neurology 1984;34: Smith RA, Melmed S, Sherman B, Frane J, Munsat TL, Festoff BW. Recombinant growth hormone treatment of amyolateral sclerosis. Muscle Nerve 1993; 16: Kelemau J, Hedlund W, Murray-Douglas P, Munsat TL. Lecithin is not effective in amyotrophic lateral sclerosis. Neurology 1982;32: Munsat TL, Easterday CS, Levy S, Wolff SM, Hiatt R. Amantadine and quanedine are ineffective in ALS. Neurology 1981 ;31: Munsat TL, Taft J, Kasdon D. Intrathecal infusion of thyrotropinreleasing hormone (TRH) in amyotrophic lateral sclerosis. Neurol Clin 1987;5: Festoff RA, Smith S, Melmed J, Frane B, Sherman B, Finson R, et al. Tufts Quantitative Neuromuscular Examination and amyotrophic lateral sclerosis trials in the recombinant age. Ann Neurol 1988;24: Munsat TL, Taft J, Jackson 1M, Andres PL, Hollander D, Skerry L, et al. Intrathecal thyrotropin releasing hormone does not alter the progressive course of ALS: experience with an intrathecal drug delivery system. Neurology 1992;42: Shrout PE, Fleiss JL. Intraclass correlation: uses in assessing rate reliability. Psychol Bull 1979;86: Guyatt G, Walter S, Norman G. Measuring change over time: assessing the usefulness of evaluative instruments. J Chron Dis 1987;: Lachin JM. Introduction to sample size determination and power analysis for clinical trials. Control Clin Trials 1981 ;2: Jette DU, Downing J. Health status of individuals entering a cardiac rehabilitation program as measured by the Medical Outcomes Study 36-Item Short Form Survey (SF-36). Phys Ther 1994;74: Supplier a. SAS Institute Inc., Box 8, Cary, NC