Abstract
Objective: To document the intra/interrater reliability and the construct validity of the Muscular Impairment Rating Scale (MIRS) in assessing patients with myotonic dystrophy type 1 (DM1). The MIRS is a ordinal five-point rating scale, established in accordance with the clinically recognized distal to proximal progression of the muscular involvement in DM1, based partly on a manual muscle testing (MMT) of 11 muscle groups.
Methods: To assess the reliability of the MIRS, 55 patients with DM1 were examined by three different observers, one of them evaluating each patient twice. Intra- and interobserver reliability of the MIRS was measured using Cohen’s weighted κ. To assess the construct validity of the MIRS, correlations were made with the Functional Status Index (FSI) and eight timed functional tasks.
Results: The intraobserver reliability of the MIRS was excellent (weighted κ = 0.84), and the interobserver reliability was interpreted as a substantial agreement (weighted κ = 0.77 to 0.79). The correlation coefficients between MMT scores and MIRS grades were all highly significant (rs = −0.81 to −0.88, p < 0.001). The FSI showed a significant progressive increase of the total median dependence score in activities of daily living from 0 in MIRS grade 1 to 39 in MIRS grade 5 (p < 0.001). The time needed to perform the eight functional tasks was also found to significantly increase in relation with the progression of the MIRS grades.
Conclusion: The MIRS is a quick, simple, and reliable measurement of muscular impairment in DM1. The FSI questionnaire and the timed motor activities supported its construct validity. The MIRS is useful to monitor major stages of DM1 progression, to study the natural history of the disease, and to identify homogeneous groups of patients for clinical trials.
Myotonic dystrophy type 1 (DM1),1 an autosomal dominant disorder, is the most common adult form of muscular dystrophy. DM1 results from an unstable CTG repeat expansion in the 3′ untranslated region of a myotonin kinase gene at 19q13.3.2 The clinical picture of DM1 includes ptosis and weakness of facial, jaw, and anterior neck muscles, distal weakness of the limbs progressing to proximal weakness, myotonia, and involvement of other systems such as cataracts or cardiac conduction defects.3
To assess the progression of muscular impairment in DM1, we developed a ordinal five-point Muscular Disability Rating Scale (MDRS) based on clinical muscular evaluation without reference to the functional impact of the weakness ( table 1).4 This scale is in concordance with the well-recognized distal to proximal progression of the muscular involvement in DM1.3,5,6⇓⇓ Unfortunately, the “Muscular Disability Rating Scale” is a misnomer that does not reflect the terminology of the World Health Organization7: This rating scale was designed to rate impairment and not disability. Instead of MDRS, we now refer to it as the “Muscular Impairment Rating Scale” or MIRS.
Muscular Impairment Rating Scale (MIRS)
The main purpose of the present study was to assess the intra/interrater reliability of the MIRS. In the absence of any gold standards in assessing muscular impairment in patients with DM1, we also documented the construct validity of this rating measure, using correlations with the Functional Status Index (FSI) and timed functional tasks (TFT).
Methods.
Patients.
Patients were recruited from the Neuromuscular Clinic of the Complexe Hospitalier de la Sagamie (CHS). The study protocol was approved by the institutional review board of the CHS. From a pool of 525 individuals with noncongenital DM1, we selected a sample of 55 patients (28 men, 27 women), aged 16 to 67 years, to include approximately an equal number of subjects in each of the 10-year age groups. Molecular confirmation of the diagnosis was obtained for all patients. The DM1 phenotype, defined in 51 patients according to the age at onset of symptoms,8 was distributed as follows: 9.8% of infantile form, 49% of early adult form, 25.5% of the adult form, and 15.7% of mild or late form.
MIRS assessment.
To categorize patients on the five-point MIRS, the examination included the detection of myotonia, jaw or temporal wasting, facial weakness, ptosis, nasal speech, and the performance of a manual muscle testing (MMT) of 11 muscle groups bilaterally: the neck flexors, six proximal muscle groups (shoulder abductors, elbow flexors, elbow extensors, hip flexors, knee extensors, knee flexors), and four distal muscle groups (wrist extensors, digits flexors, ankle dorsiflexors, ankle plantar flexors). According to the Modified Medical Research Council Scale (MRC),9 we defined a mild to moderate weakness as a MRC score between 3/5 and +4/5 and a severe weakness as a MRC score of <3/5 (≤−3/5). At the stage of severe weakness, the muscle moves the joint against gravity but not through the full extent of the mechanical range of the joint or is weaker than that.
Reliability study.
To study the intra/interobserver reliability of the MIRS, patients with DM1 were scored by three observers: a physical therapist (observer 1), a neurologist (observer 2), and a general practitioner (observer 3). Patients were assessed during two different sessions 3 weeks apart. During the first session, they were evaluated by a physical therapist and a neurologist, and during the second session by the same physical therapist and a general practitioner.
Validity study.
To verify the construct validity of the MIRS, correlations between MIRS grades and the FSI and TFT scores were assessed. Correlations between MIRS grades and MMT scores were also recorded. As construct validity correlations are attenuated by unreliability of measurements, we also determined the reliability coefficients of the FSI, TFT, and MMT.
FSI.
The dependency dimension of the FSI of the Pilot Geriatric Arthritis Project10 was used to assess the functional status in activities of daily living (ADL). This measure consists of 44 ADL items grouped under three headings: mobility (12 items), personal care (17 items), and work (15 items). In the original FSI, three questions were asked for each activity, yielding separate ratings for dependency, difficulty, and pain. In the present study, we used only the dependency dimension. Pain rating was not appropriate for patients with DM1, and difficulty rating showed a lower degree of interobserver reliability than dependency.11 For each of the 44 items, scores were assigned as follows: 0 = independent, 1 = uses mechanical help, 2 = uses human help, 3 = uses both kinds of help, 4 = cannot perform the activity. The questionnaires were administered by a telephone interview. The FSI total score (from 0 to 176) and subscores for mobility (from 0 to 48), personal care (from 0 to 68), and work (from 0 to 60) were recorded for each patient. To determine the test-retest reliability of the FSI in patients with DM1, two interviews were done by the same research nurse 3 weeks apart. The average scores of the two interviews were used to assess the relationship with the MIRS grades .
Upper and lower extremities TFT.
To assess functions of upper and lower limb musculature, we used eight TFT originally used in the ALS rating scale of Appel et al.12 Lower extremity tasks were to stand erect from a sitting position in a standard chair, to arise from a supine position, to walk 20 feet with assistive devices if necessary, and to climb and descend four standard steps, again with assistive devices if necessary. In none of these timed activities is assistance by others allowed. For upper extremity function, the time required to perform the following tasks was recorded: to propel a wheelchair 20 feet, to cut a piece of ¼-inch-thick Theraplast with a plastic knife positioned in the dominant hand at the beginning of the test, to assemble peg units (consisting of a pin, followed by a washer, followed by a collar) on a Purdue pegboard during a period of 60 seconds, and, using one hand at a time, to turn round blocks, 2½inches in diameter and ¾inch high, on a board during a period of 60 seconds.
To determine the test-retest reliability of the TFT in patients with DM1, data were collected twice in two different sessions, 3 weeks apart, by the same research nurse. The average of the two evaluations was used to assess the relationship with the MIRS grades. The TFT and the FSI assessments were done in the same sessions as MIRS evaluations.
MMT.
The MMT total score (from 0 to 220 points) obtained for each patient and by each observer was recorded. The intra/interobserver reliability was assessed by the same observers and in the same sessions as for the MIRS and was calculated for the MMT total score.
Statistical analysis.
Intra/interobserver reliability of the MIRS was analyzed using Cohen’s κ with quadratic weights as weighting scheme. The intraclass correlation coefficient (ICC), estimated through an analysis-of-variance model,13 was used to summarize the intra- and interrater reliability of the MMT and the test-retest reliability of the FSI and TFT scores. The ICC contrasts intrasubject and intersubject variability and was preferred to Cohen’s κ in analyses of continuous variables. Correlations between MMT, FSI, and TFT scores and MIRS grades were assessed using Spearman rank correlation coefficients with one-tailed significance. A p value of <0.05 was considered significant. Statistical analysis were performed using the SPSS statistical software package.14
Results.
Reliability.
MIRS.
The intraobserver reliability of the MIRS was 0.84, and the interobserver reliability ranged as follows: observers 1 versus 2, weighted κ = 0.77; observers 1 versus 3, weighted κ = 0.78; and observers 2 versus 3, weighted κ = 0.79. The intrarater and interrater reliability was similar for men and women. A perfect agreement was observed between the three evaluators for 30 (54.6%) of the 55 cases. A score difference of one grade from one evaluator was observed for 23 (41.8%) patients. A score difference of two grades from one evaluator was observed for two (3.6%) patients.
MMT.
The intrarater and interrater reliabilities of the total MMT score were found to be quite high (ICC = 0.93 and 0.87). However, the mean MMT scores (175 versus 163 versus 155) were all different from one observer to another (F = 33.0, p < 0.001) ( table 2). This variability suggested that there may be some systematic difference among them.
Changes in manual muscle testing (MMT) scores with Muscular Impairment Rating Scale (MIRS) grades and mean MMT score for all patients obtained by each observer
FSI.
Test-retest ICC for the FSI total score and subscores were found to be 0.89 for total score, 0.84 for mobility, 0.82 for work, and 0.67 for personal care.
TFT.
Test-retest ICCs for the eight TFT were found to be 0.96 for turning blocks and for climbing and descending four standard steps, 0.91 for assembling peg units, 0.81 for propelling a wheelchair 20 feet, 0.79 for walking 20 feet, 0.77 for cutting Theraplast, 0.71 for standing from lying supine, and 0.67 for standing from chair.
Construct validity of the MIRS.
To establish the correlations between the MIRS grades and the FSI and TFT scores, we elected to use the MIRS grading of observer 2 who gave a median MMT score.
FSI.
The questionnaire recorded a significant progressive increase of the ADL dependency from a total median score of 0 in MIRS grade 1 to 39 in MIRS grade 5 (rs = 0.50, p < 0.001) ( table 3). MIRS grades correlated with mobility (rs = 0.54, p < 0.001) and work (rs = 0.36, p < 0.01) but not with personal care activities (rs = 0.20, p = 0.08).
Correlations between subscores and total dependence scores of Functional Status Index (FSI) and Muscular Impairment Rating Scale (MIRS) grades
TFT.
The eight timed functional activities documented progressive limitations in accordance with the MIRS grades ( table 4). The most discriminant activities were cutting Theraplast with dominant hand (rs = 0.67, p < 0.001), standing from lying supine (rs = 0.61, p < 0.001), turning blocks (rs = −0.51, p < 0.001), climbing and descending four standard steps (rs = 0.51, p < 0.001), and assembling peg units (rs = −0.50, p < 0.001). Significant correlations were also recorded for propelling a wheelchair 20 feet (rs = 0.44, p = 0.001), walking 20 feet (rs = 0.41, p = 0.002), and standing from chair (rs = 0.34, p = 0.012).
Median time to perform eight functional activities in relation with Muscular Impairment Rating Scale (MIRS) grades
MMT.
The correlation coefficients between MMT scores and MIRS grades were all highly significant (rs = −0.81 to −0.88, p < 0.001) (table 2).
Discussion.
Impairment and disability rating scales in DM1.
Few scales of disease progression have been developed for DM1. The impairment has been rated according to the reduction of working ability6,15⇓ or on the requirement of medical attention.16 In DM1, the working ability and the requirement of medical attention are complex features that may be influenced by muscular involvement as well as by other factors such as diurnal sleepiness, educational level, personality, and type of work. Thus, we constructed the MIRS, an ordinal rating scale based strictly on the clinical muscular involvement without reference to the functional impact of the weakness.
Originally, the MIRS was conceived as a rating scale sufficiently coarse to minimize interobserver differences while allowing registration of significant changes in the degree of muscular deficit. The MIRS is concordant with the usual distal to proximal progression of the muscular involvement in DM1.3,5,6⇓⇓ In the first stage of the disease (grade 1), patients are asymptomatic, and the diagnosis of DM1 is confirmed by myotonic discharges at EMG or DNA analysis, without any significant weakness on muscle examination. Clinical myotonia, facial weakness, temporal atrophy, ptosis, nasal speech, and weakness of neck flexors are early muscular features of DM1, and patients displaying these features without limb weakness are grouped in grade 2. As the disease progresses (grade 3), distal muscles of upper and lower limbs are involved, particularly the extensors and flexors of the digits and of the wrist and the dorsiflexors of the foot. A proximal weakness occurs in the upper limbs (shoulder abductors, elbow flexors and extensors) and/or in the lower limbs (hip flexors, knee extensors) along with a more severe distal weakness in patients classified in grade 4. Finally, patients included in grade 5 present a severe (MRC scale less than or equal to −3/5) proximal weakness, especially of hip flexors and knee extensors. Occasionally, a severe proximal weakness appears in the upper limbs (shoulder abductors, elbow flexors) before the lower limbs. Most patients with an MIRS of grade 5 need a wheelchair for short or long displacements and have considerable difficulty in carrying out daily living activities.
Based on our clinical experience with patients with DM1, two exceptions to the rule are included in the MIRS grading. First, weakness of the digit flexors occurs very early in the course of the disease, often without any other significant distal weakness; this feature remains included in grade 2. Similarly, weakness of the elbow extensors frequently occurs without other proximal weakness; therefore, patients presenting this isolated proximal weakness remain in grade 3.
Reliability of the MIRS.
Values of reliability coefficients have been characterized as follows: slight, (0 to 0.20), fair (0.21 to 0.40), moderate (0.41 to 0.60), substantial (0.61 to 0.80), and excellent (0.81 to 1.00).17 The present study documented that the MIRS is a reliable instrument with excellent intrarater reliability. However, the interrater reliabilities, interpreted as substantial agreement, suggested that the MIRS should be used in large population studies, tolerating lower standards of reliability, rather than in the clinical assessment of individual patients.
Validity of the MIRS.
Validity is the degree to which a scale actually assesses what it is intended to measure. The MIRS scores must reflect progressive muscular impairment in patients with DM1 to be useful in screening functional disability and in monitoring changes in muscle weakness. In DM1, there are no instruments or scales with established validity (gold standards) for the assessment of the muscular impairment or for the assessment of functional disability. In this context, construct validation with correlational evidence must be used to examine the validity of a new scoring method.18 In the current study, correlations were determined between grades derived from the MIRS and three other measures: the MMT for the assessment of the muscular weakness and the FSI and the TFT for the assessment of the functional disability. Most correlation coefficients between the MIRS and these other measurements may be interpreted as quite high, confirming the convergent validity between these scales. The ADL dependency questionnaire and timed motor activities confirmed the construct validity of the MIRS, illustrated by the progressive modifications of functional scores in accordance with the MIRS grades. High correlation coefficients between MMT total score and the MIRS (rs = −0.81 to −0.88) were to be expected because the MIRS rating system is based partly on muscular weakness as measured by the MMT. These latter correlations may then reflect the notions of equivalent forms and of internal consistency of an instrument as well as a convergent validation.
Even if MMT and MIRS strongly correlate and both appear to accurately rate the muscular impairment, MIRS presents several advantages over MMT. The MIRS is more representative of the different stages of the muscular impairment than the MMT scores. Indeed, the MIRS gradation reflects the usual distal to proximal muscular impairment of DM1, and this clinical progression may be overlooked by the MMT scores. Moreover, MMT scores would not discriminate very mildly affected patients who present any or minor muscular impairment on the MMT as those classified in grades 1 and 2. Facial weakness, temporal atrophy, ptosis, and nasal speech are clinical signs that may be observed alone or in combination in grade 2, and these features are not easily assessed by manual testing. With the more frequent detection of asymptomatic patients by DNA analysis, it is important to use a classification allowing accurate identification of these mildly affected patients.
The MIRS is a simple scale to use, easy to learn, and needs only 10 to 15 minutes to execute. This scale is now used routinely in some research settings, and its acceptability is expanding. The correlational validity of the MIRS has also been illustrated by other studies. The usefulness of the MIRS to assess the disease severity was demonstrated in a DM1 genotype-phenotype correlation study,19 and a significant correlation was found between the MIRS and the size of the trinucleotide repeat.20 A significant correlation between mortality rates and MIRS grades was reported,21 and this rating scale was found to be useful to identify patients with DM1 who are at risk of chronic respiratory failure.22 The MIRS was also used to characterize the clinical stage of the disease in a relationship study with the muscle surface mechanical and electrical activities, and the authors observed a good concurrence of clinical findings and their experimental results.23
We previously reported that a distal weakness (grade 3) is identified in patients with DM1 after 9 to 10 years’ duration of the illness, a proximal weakness (grade 4) is noticed after a progression of 18 years, and patients presented a severe proximal weakness (grade 5) after a course of 27 years.4 Therefore, the MIRS lacks sensitivity to detect subtle changes in muscular impairment and is not appropriate for efficacy measurements in short-term therapeutic trials. The MIRS is useful to monitor major stages of DM1 progression, to study the natural history of this disease, and to document correlations with the impairments of other systems. For clinical trials, the MIRS may be used to select a sample with a homogeneous muscular involvement.
Acknowledgments
Supported by the Fonds de la Recherche en Santé du Québec and by Alcan Smelters and Chemicals Ltd.
Footnotes
-
Presented at the 49th annual meeting of the American Academy of Neurology; Minneapolis, MN; April 1998.
- Received March 27, 2000.
- Accepted October 10, 2000.
References
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