Validation of manual muscle testing and a subset of eight muscles for adult and juvenile idiopathic inflammatory myopathies.

OBJECTIVE: To validate manual muscle testing (MMT) for strength assessment in juvenile and adult dermatomyositis (DM) and polymyositis (PM). METHODS: Patients with PM/DM (73 children and 45 adults) were assessed at baseline and reevaluated 6-9 months later. We compared Total MMT (a group of 24 proximal, distal, and axial muscles) and Proximal MMT (7 proximal muscle groups) tested bilaterally on a 0-10 scale with 144 subsets of 6 and 96 subsets of 8 muscle groups tested unilaterally. Expert consensus was used to rank the best abbreviated MMT subsets for face validity and ease of assessment. RESULTS: The Total, Proximal, and best MMT subsets had excellent internal reliability (Total MMT r(s) = 0.91-0.98), and consistency (Cronbach's alpha = 0.78-0.97). Inter- and intrarater reliability were acceptable (Kendall's W 0.68-0.76, r(s) = 0.84-0.95). MMT subset scores correlated highly with Total and Proximal MMT scores and with the Childhood Myositis Assessment Scale, and correlated moderately with physician global activity, functional disability, magnetic resonance imaging, and axial and distal MMT scores, and, in adults, with creatine kinase level. The standardized response mean for Total MMT was 0.56 in juveniles and 0.75 in adults. Consensus was reached to use a subset of 8 muscles (neck flexors, deltoids, biceps, wrist extensors, gluteus maximus and medius, quadriceps, and ankle dorsiflexors) that performed as well as the Total and Proximal MMT, and had good face validity and ease of assessment. CONCLUSION: These findings aid in standardizing the use of MMT for assessing strength as an outcome measure for myositis.

Intra-rater and inter-rater reliability of the 10-point Manual Muscle Test (MMT) of strength in children with juvenile idiopathic inflammatory myopathies (JIIM).

OBJECTIVE: Children with juvenile idiopathic inflammatory myopathies (JIIM) present with muscle inflammation and decreased strength that may affect their functional abilities. The purpose of this study was to determine the intra-rater and inter-rater reliability of the 0 to 10-point manual muscle testing method for children with JIIM. METHODS: For the intra-rater and inter-rater reliability studies, 10 and 9 children with JIIM participated, respectively. For intra-rater reliability, one pediatric therapist completed two assessments in one day with a one-hour break. For inter-rater reliability, four therapists assessed the same child within a single morning. RESULTS: Spearman correlations for intra-rater reliability ranged from 0.70 to 1.00. Kendall's W coefficient for inter-rater reliability of groups of muscles (total, proximal, distal, and peripheral) ranged from 0.51 to 0.76. CONCLUSIONS: The total, proximal, and peripheral Manual Muscle Test (MMT) score, using the 0-10 point scale, has acceptable reliability in JIIM patients.

Pentoxifylline in the treatment of radiation-induced fibrosis.

PURPOSE: Fibrotic sequelae remain the most important dose-limiting toxicity of radiation therapy to soft tissue. Functionally, this is reflected in loss of range of motion and muscle strength and the development of limb edema and pain. Tumor necrosis factor alpha and fibroblast growth factor 2 (FGF2), which are abnormally elevated in irradiated tissues, may mediate radiation fibrovascular injury. PATIENTS AND METHODS: In an open label drug trial, we studied the effects of pentoxifylline (400 mg orally tid for 8 weeks) on 30 patients who displayed late, radiation-induced fibrosis at 1 to 29 years posttreatment (40 to 84 Gy). The primary outcome measurement was change in physical impairments thought to be secondary to radiation, including active and passive range of motion (AROM and PROM), muscle strength, limb edema, and pain. Plasma levels of cytokines (tumor necrosis factor alpha and FGF2) also were measured. Twenty-seven patients completed baseline and 8-week assessments, and 24 patients completed baseline, 8-week, and 16-week assessments. RESULTS: After 8 weeks of pentoxifylline intervention, 20 of 23 patients with impaired AROM and 19 of 22 with impaired PROM improved; 11 of 19 patients with muscle weakness showed improved motor strength; five of seven patients with edema had decreased limb girth; and nine of 20 patients had decreased pain. Pretreatment FGF2 levels dropped from an average of 44.9 pg/mL to 24.0 pg/mL after 8 weeks of treatment. CONCLUSION: Patients receiving pentoxifylline demonstrated improved AROM, PROM, and muscle strength and decreased limb edema and pain. Reversal of these delayed radiation effects was associated with a decrease in circulating FGF2.

Ultrasound imaging distinguishes between normal and weak muscle.

OBJECTIVE: To determine whether real-time ultrasound imaging can provide quantitative data that distinguish pathologic from healthy muscle and that correlate with strength measures. DESIGN: Nonrandomized matched-pair, repeated-measures design. SETTING: Ultrasound imaging laboratory, rehabilitation medicine department, government research hospital. PARTICIPANTS: Nine patients with stable active or inactive myositis, stratified into 3 groups based on their 10-point manual muscle test (MMT) scores, and 9 age- and gender-matched controls. INTERVENTIONS: Maximal isometric contraction of the rectus femoris muscle in 2 knee-flexion positions (60 degrees, 90 degrees ) during simultaneous ultrasound imaging and muscle force dynamometry. MAIN OUTCOME MEASURES: Changes of the rectus femoris muscle in horizontal (X) and vertical (Y) diameters between relaxed and contracted states, and muscle force measurements. RESULTS: The X diameters decreased and the Y diameters increased during isometric contraction in all participants. For each group, average changes in cross-sectional diameters were consistently higher in controls than in patients. Patients with MMT less than 8 differed significantly from controls in both X and Y dimensions. A moderately strong correlation was found between muscle force and the Y diameter during contraction at 60 degrees (r =.78) and 90 degrees (r =.67) knee-flexion angles. CONCLUSIONS: Ultrasonography provided a quantitative measure of change between relaxed and contracted state of muscle, which correlated with muscle force. Ultrasound identified significant differences in cross-sectional diameters between the myopathic and normal muscles sampled and may be useful for measuring muscle response to drug and exercise therapy.

Normal scores for nine maneuvers of the Childhood Myositis Assessment Scale.

OBJECTIVE: To document and evaluate the scores that normal, healthy children achieve when performing 9 maneuvers of the Childhood Myositis Assessment Scale (CMAS). METHODS: A total of 303 healthy children, 4-9 years of age, were scored as they performed 9 CMAS maneuvers. The data were then evaluated to determine whether normal scores for some maneuvers are age and sex dependent. RESULTS: All children were able to achieve maximum possible scores for the supine to prone, supine to sit, floor sit, floor rise, and chair rise maneuvers. All but 2 4-year-olds achieved a maximum possible score for the arm raise/duration maneuver. Performance of the head lift and sit-up maneuvers varied significantly, depending primarily on age. Children in all age groups had less difficulty performing the leg lift than the head lift or sit-up. CONCLUSION: The normative data generated by this study are of value for interpreting the serial CMAS scores of children with idiopathic inflammatory myopathies.

Validation and clinical significance of the Childhood Myositis Assessment Scale for assessment of muscle function in the juvenile idiopathic inflammatory myopathies.

OBJECTIVE: To examine the measurement characteristics of the Childhood Myositis Assessment Scale (CMAS) in children with juvenile idiopathic inflammatory myopathy (juvenile IIM), and to obtain preliminary data on the clinical significance of CMAS scores. METHODS: One hundred eight children with juvenile IIM were evaluated on 2 occasions, 7-9 months apart, using various measures of physical function, strength, and disease activity. Interrater reliability, construct validity, and responsiveness of the CMAS were examined. The minimum clinically important difference (MID) and CMAS scores corresponding to various degrees of physical disability were estimated. RESULTS: The intraclass correlation coefficient for 26 patients assessed by 2 examiners was 0.89, indicating very good interrater reliability. The CMAS score correlated highly with the Childhood Health Assessment Questionnaire (C-HAQ) score and with findings on manual muscle testing (MMT) (r(s) = -0.73 and 0.73, respectively) and moderately with physician-assessed global disease activity and skin activity, parent-assessed global disease severity, and muscle magnetic resonance imaging (r(s) = -0.44 to -0.61), thereby demonstrating good construct validity. The standardized response mean was 0.81 (95% confidence interval 0.53, 1.09) in patients with at least 0.8 cm improvement on a 10-cm visual analog scale for physician-assessed global disease activity, indicating strong responsiveness. In bivariate regression models predicting physician-assessed global disease activity, MMT remained significant in models containing the CMAS (P = 0.03) while the C-HAQ did not (P = 0.4). Estimates of the MID ranged from 1.5 to 3.0 points on a 0-52-point scale. CMAS scores corresponding to no, mild, mild-to-moderate, and moderate physical disability, respectively, were 48, 45, 39, and 30. CONCLUSION: The CMAS exhibits good reliability, construct validity, and responsiveness, and is therefore a valid instrument for the assessment of physical function, muscle strength, and endurance in children with juvenile IIM. Preliminary data on MID and corresponding levels of disability should aid in the clinical interpretation of CMAS scores when assessing patients with juvenile IIM.

Walking ability and its relationship to lower-extremity muscle strength in children with idiopathic inflammatory myopathies.

OBJECTIVE: To describe gait deficits and their association with lower-extremity muscle strength in children with juvenile idiopathic inflammatory myopathies (IIM). DESIGN: Cross-sectional, descriptive study. SETTING: Clinical research center. PARTICIPANTS: Consecutive sample of 25 ambulatory children diagnosed with juvenile IIM. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Manual muscle test (MMT) of bilateral hip flexor, extensor, and abductor; knee extensor; and ankle plantarflexor strength, all measured on a 0- to 10-point scale and summary strength measures. Video-based movement analysis to determine walking speed; gait cycle time; right and left step time; stride length; right and left step length; and stance, swing, and double-limb support phase durations. RESULTS: Walking speed (1.03+/-0.27 m/s) was reduced because of shortened stride lengths (1.03+/-0.21 m) more than prolonged gait cycle times (1.05+/-0.22s). Walking speed highly correlated with the number of muscle groups weaker than grade 7 out of 10 (r=-.89) and the strength of the hip flexors (r=.85). CONCLUSIONS: Lower-extremity strength measures, including MMT scores of individual muscle groups and the number of weak muscle groups, were predictive of gait limitations in children with juvenile IIM.

Fitness as a determinant of the oxygen uptake/work rate slope in healthy children and children with inflammatory myopathy.

UNLABELLED: There is evidence that the slope of the change in oxygen uptake accompanying changes in work rate (delta VO2/delta W). during moderate incremental exercise is influenced by fitness (peak VO2). We set out to determine whether delta VO2/delta W was related to fitness in a group of healthy children and in children with juvenile dermatomyositis (JDM), a condition associated with decreased peak VO2. We also hypothesized that delta VO2/delta would be significantly decreased in children with JDM compared to healthy children. METHODS: Twelve children (2 boys) with JDM, mean age 11.6 +/- 3.6 yrs, and 20 healthy children (4 boys), mean age 11.3 +/- 2.9 years, performed an incremental exercise test using a cycle ergometer. delta VO2/delta W below the anaerobic threshold was analyzed using linear regression. Correlations between peak VO2 and delta VO2/delta W were calculated, and differences between the JDM and healthy groups were analyzed using independent t-tests. RESULTS: The delta VO2/delta W was significantly correlated with peak VO2 for children with JDM (r = 0.71, p < 0.01), healthy children (r = 0.53, p < 0.01), and all children combined (r = 0.78, p < 0.001). The delta VO2/delta W (7.4 +/- 1.4 vs. 10.8 +/- 1.2 ml O2.min-1.watt-1) and peak oxygen uptake (VO2peak) (19.2 +/- 5.0 vs. 31.4 +/- 7.2 ml O2.kg-1, min-1) were significantly lower in children with JDM than in healthy children, respectively (all p < or = 0.001). CONCLUSION: Fitness is significantly related to delta VO2/delta W in healthy children and those with JDM. Children with JDM have a significantly lower delta VO2/delta W than healthy children. Further study is needed to identify specific factors influencing delta VO2/delta W.

Neopterin and quinolinic acid are surrogate measures of disease activity in the juvenile idiopathic inflammatory myopathies.

OBJECTIVE: We evaluated the utility of neopterin and quinolinic acid (QUIN) as surrogate measures of disease activity in juvenile idiopathic inflammatory myopathies (IIMs). METHODS: Plasma and first morning void urine samples were measured for neopterin and QUIN using commercial ELISA, HPLC, or gas chromatography-mass spectrometry in 45 juvenile IIM patients and 79 healthy controls. Myositis disease activity assessments were obtained. RESULTS: Plasma and urine neopterin and QUIN concentrations were increased in juvenile IIM patients compared with healthy controls (P <0.017). Urine neopterin and QUIN highly correlated with each other (r(s) = 0.73; P <0.0001). Urine neopterin and QUIN correlated moderately with myositis disease activity assessments, including physician and parent global activity assessments, muscle strength testing, functional assessments (Childhood Myositis Assessment Scale, Childhood Health Assessment Questionnaire), skin global activity, and edema on magnetic resonance imaging (r(s) = 0.42-0.62; P <0.05), but generally not with muscle-associated enzymes in serum. Urine neopterin or QUIN, in combination with either serum lactate dehydrogenase (LD) or aspartate aminotransferase (AST), significantly predicted global disease activity (R(2) =0.40-0.56; P <0.002), and both were more sensitive to change than these serum enzymes (standardized response means, -0.41 to -0.48). CONCLUSIONS: Urinary neopterin and QUIN are candidate measures of disease activity in juvenile IIM patients and add significantly to the prediction of global disease activity in combination with serum LD or AST values. Measurement of these markers in first morning void urine specimens appears to be as good as, or possibly better than, measurements of their concentrations in plasma.

Decreased aerobic capacity in children with juvenile dermatomyositis.

OBJECTIVE: To determine whether patients with juvenile dermatomyositis (DM) have limited aerobic capacity compared with healthy controls. METHODS: Fourteen juvenile DM patients with inactive to moderately active, stable disease (age range 7-17 years) and 14 age- and sex-matched controls performed a maximal exercise test using a cycle ergometer. Oxygen uptake and power were measured at peak exercise (VO(2peak) and W(peak), respectively) and at anaerobic threshold (AT and W(AT)). Juvenile DM disease activity and damage were also assessed. RESULTS: Patients with juvenile DM had significantly reduced VO(2peak) (19.6 ml O(2)/kg/minute in juvenile DM versus 31.1 ml O(2)/kg/minute in controls), peak heart rate (166 versus 184 beats per minute), W(peak) (1.6 versus 2.7 watts/kg), AT (11.1 versus 18.0 ml O(2)/kg/minute) and W(AT) (0.6 versus 1.4 watts/kg), compared to controls (P