Response to high-intensity eccentric muscle contractions in persons with myopathic disease.

Although the response to intense eccentric muscle contractions is well described in normal subjects, concern exists about possible untoward effects in persons with myopathic diseases. We investigated 14 subjects with slowly progressive muscular dystrophies including myotonic muscular dystrophy (n = 9), facioscapulohumeral dystrophy (n = 2), limb-girdle syndrome (n = 2), and Becker muscular dystrophy (n = 1). Control subjects consisted of 18 able-bodied persons. Subjects performed two sets of eight maximal-effort eccentric repetitions of the elbow flexors, with measurement of maximal concentric strength, serum creatine kinase, resting and flexed arm angle, arm circumference, and soreness at days 0, 3, and 7. Although the myopathic group had less initial strength, both groups demonstrated a similar response to the protocol over 7 days. Both groups had a significant rise in serum creatine kinase, which was still elevated at 7 days (P < 0.05). The control group demonstrated a slightly greater injury response in terms of soreness, resting and flexed arm angles, and arm swelling. Both groups of subjects appeared to respond similarly to an acute bout of eccentric contractions. However, the potential long-term effects of this type of exercise in persons with myopathic diseases remains unknown.

Simulated work performance tasks in persons with neuropathic and myopathic weakness.

OBJECTIVES: To determine the test-retest reliability of selected simulated work performance tasks in persons with neuropathic and myopathic weakness and control subjects, and the association between muscular performance during these work tasks and conventional isolated muscle group testing. DESIGN: Measurement of three tasks performed on a work simulation device on two different days separated by 1 week. Associations between work task performance and previously reported strength measures in six muscle groups by hand-held dynamometry (HHD) were examined. SETTING: Human performance laboratory of a university. PARTICIPANTS: Convenience sample of ambulatory outpatients with hereditary motor and sensory neuropathy, type I (n = 9), myotonic muscular dystrophy (n = 10), and able-bodied controls (n = 11). MAIN OUTCOME MEASURES: For work simulation, isokinetic peak torque and total work; and for HHD, maximal isometric torque. RESULTS: Mean between-session differences for work simulation tasks ranged from -11% to +4% for peak torque and from -12% to +12% for total work; test sessions did not differ significantly for either patient or control groups. All groups had between-session intraclass correlation coefficients usually >.80, indicating good consistency. In general, correlations between peak torque during work simulation and HHD were strongest in the control group. CONCLUSION: Persons with neuromuscular weakness reliably performed the simulated work tasks examined in this investigation. Work simulation tasks may be a useful tool to assess muscular performance in persons with neuromuscular weakness.

Energy expenditure, physical activity, and body composition of ambulatory adults with hereditary neuromuscular disease.

Persons with neuromuscular disease (NMD) have progressive weakness and wasting of skeletal muscle, reduced fat-free mass, and increased fat mass relative to healthy control subjects. To test the hypothesis that resting energy expenditure (REE), estimated total daily energy expenditure (TEE), and physical activity patterns are altered in ambulatory adults with NMD, 26 adult men and women with slowly progressive NMD and 19 able-bodied control subjects similar in age and weight were evaluated. REE was measured after an overnight fast by indirect calorimetry, TEE by heart rate monitoring, and body composition by air-displacement plethysmography. REE was not significantly different between NMD and control subjects; however, TEE was significantly reduced in NMD subjects compared with control subjects, respectively (women: 7.8 +/- 1.5 compared with 10.5 +/- 2.8; men: 10.2 +/- 3.6 compared with 12.7 +/- 2.6 MJ/d; P < or = 0.01), indicating that NMD subjects expended less energy in physical activity than did control subjects. NMD subjects also tended toward an increased energy cost of physical activity, particularly at higher activity levels (P = 0.06). Multiple regression analysis indicated that for all subjects combined, adiposity was positively associated with age and TEE and negatively associated with time spent in the active heart rate range and fat-free mass (P < or = 0.0001). This relation did not differ between NMD and control subjects, nor did it differ between men and women. We hypothesize that because of their reduced physical activity and increased adiposity, persons with NMD may be at risk for developing secondary conditions such as cardiovascular disease, hypertension, and diabetes.

Hand-held dynamometry reliability in persons with neuropathic weakness.

OBJECTIVE: To determine test-retest reliability of hand-held dynamometry (HHD) in measuring strength of persons with neuropathic weakness. DESIGN: Intratester and intertester reliability of HHD-measured strength over a 7- to 10-day period. In addition, HHD knee strength was compared with criterion standard of fixed dynamometry (FD). SETTING: Human performance laboratory of a university. PARTICIPANTS: Convenience sample of ambulatory outpatients with Hereditary Motor and Sensory Neuropathy, Type I (HMSN) (n = 10) and able-bodied controls (CTL) (n = 11). MAIN OUTCOME MEASURE: Maximal isometric torque. RESULTS: Intratester intraclass correlation coefficients (ICCs) were high, generally ranging from .82 to .96 for HHD- and FD-measured strength for both HMSN and CTL groups. There were no significant differences between sessions for HHD-measured strength, while FD-measured strength was only significantly different for knee extension (p < .01). Intertester reliability was generally good for both HHD- and FD-measured strength, with ICCs ranging from .72 to .97 for HMSN and CTL groups. Exceptions were knee extensors and ankle dorsiflexors for the CTL group. Knee extensor strength was significantly lower measured by HHD compared with FD (p < .01), but knee flexor strength was similar for the two methods. CONCLUSION: HHD appears to be a reliable method to measure maximal isometric strength in persons with neurogenic weakness, and may be useful to quickly and objectively evaluate strength in the clinical setting.

Aerobic walking in slowly progressive neuromuscular disease: effect of a 12-week program.

OBJECTIVE: Poor cardiorespiratory endurance is a common finding in neuromuscular disease (NMD), and the capacity of such patients to respond to aerobic training is unclear. This study was conducted to determine if a 12-week walking program results in increased aerobic capacity in slowly progressive NMD subjects, whether such a program is safely tolerated, and whether such patients can adhere to a self-monitored, home-based training program. DESIGN: Before-after trial. SETTING: Subjects' homes. PATIENTS: A cohort of 8 slowly progressive NMD subjects (4 men, 4 women) followed in the neuromuscular disease clinic participated (age, 36.6 +/- 8.0 yrs; ht, 170 +/- 11 cm; wt, 74.3 +/- 19.0 kg) (Mean +/- SD). INTERVENTION: Subjects walked 15 to 30 min 3 to 4 days a week at 50% to 60% of their heart rate reserve. MAIN OUTCOME MEASURES: Resting, submaximal, and peak heart rates, systolic and diastolic blood pressures, oxygen uptake, and peak power output. RESULTS: Graded exercise testing to volitional fatigue using a semirecumbent cycle ergometer before and after the training program found significant decreases in submaximal heart rate by 7 +/- 3 beats/min (Mean +/- SEM) (95% CI = -23 to 9) (p = .046) and submaximal systolic blood pressure by 11 +/- 4 mmHg (95% CI = -31 to 9) (p = .019), and nonsignificant increases in peak power output and VO2. CONCLUSIONS: These results suggest that moderate-intensity aerobic exercise training is well tolerated and may provide modest improvement in aerobic capacity in slowly progressive NMD subjects.

A new air displacement method for the determination of human body composition.

A new device based on the plethysmographic measurement of body volume has been developed for the purpose of estimating human body composition. The device, the BOD POD Body Composition System, uses the relationship between pressure and volume to derive the body volume of a subject seated inside a fiberglass chamber. Derivation of body volume, together with measurement of body mass, permits calculation of body density and subsequent estimation of percent fat and fat-free mass. Critical issues which have hampered prior plethysmographic approaches are discussed. The present system's ability to measure the volume of inanimate objects was evaluated for accuracy, reliability, and linearity. Twenty successive tests of a known volume (50,039 ml) on two separate days produced values of 50,037 +/- 12.7 ml and 50,030 +/- 13.5 ml (mean +/- SD) for each day, respectively. The CV for these series were 0.025% and 0.027%. Further testing across a wide range of volumes approximating human size (25-150 1) produced the following regression equation where y = measured volume (1) and x = actual volume (1): y = 0.9998x - 0.0274, r2 = 1.0, SEE = 0.004 1. The resultant device is likely to enhance opportunities for the quick, simple and noninvasive measurement of body composition for both research and clinical applications.

Profiles of neuromuscular diseases. Design of the protocol.

The purpose of this 10-yr investigation was to develop comprehensive impairment and disability profiles of the clinical characteristics of seven neuromuscular diseases: spinal muscular atrophy, hereditary motor sensory neuropathy, Duchenne muscular dystrophy, Becker's muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle syndrome, and myotonic dystrophy. Based on the World Health Organization's classification of disablement, as applied to neuromuscular diseases, impairment was evaluated by measurements of strength, range of motion, spine deformity, cardiac and pulmonary function, and intellectual capacity. Disability was evaluated by measures of mobility and upper extremity function, cardiopulmonary adaptations, cardiac and pulmonary complications, and psychosocial adjustment.

The effect of a high resistance exercise program in slowly progressive neuromuscular disease.

A 12-week high resistance home exercise program was completed by 10 subjects with slowly progressive neuromuscular diseases (NMD) and 6 normal control subjects (CTL). After evaluating baseline maximal isometric and isokinetic strength of the elbow flexors and knee extensors, subjects completed the home program using adjustable ankle and wrist cuff weights. One side of the body was randomly chosen for exercise. Subjects initially performed 1 set of 10 repetitions on 3 days a week and gradually increased to 5 sets of 10 repetitions on 4 days a week. The NMD group demonstrated significant (p < 0.05) gains in several knee extension isokinetic strength measures but loss of elbow flexion eccentric peak torque and work per degree. The CTL group demonstrated significant gains in all measures of knee extension strength, with improvement of elbow isokinetic eccentric work per degree as well. There was evidence of cross training to the nonexercised limbs for both groups. A high resistance training program, although well tolerated in NMD subjects with mild to moderate weakness, may cause some deleterious effects to diseased skeletal muscle. A high resistance training program appears to offer no advantage over a moderate resistance training program in this population.

Moderate resistance exercise program: its effect in slowly progressive neuromuscular disease.

A 12-week moderate resistance exercise program was performed by 27 patients with slowly progressive neuromuscular diseases (NMD) and 14 control subjects (CTL) in order to determine safety and efficacy of a strengthening program. A 3-day per week submaximal regimen of home exercise using ankle and wrist weights and hand grip exerciser was prescribed. One side of the body was randomly chosen for exercise. Subjects were tested for maximal isokinetic and isometric strength at baseline and after weeks 4 and 12 of the training protocol, and the prescribed amount of work was gradually increased throughout the program. Both the NMD and CTL groups demonstrated significant (p < .05) increases in most strength measures. Both groups responded similarly to the exercise program, and strength gains did not significantly differ between the exercised and nonexercised limbs in either group. This study provides evidence that a 12-week submaximal strength training program is practical and safe in slowly progressive NMD and produces moderate improvement in measured strength.

Isometric and isokinetic measurement of hamstring and quadriceps strength.

This study evaluates quadriceps strength at varying movement velocities in a group of healthy subjects. Specific objectives included (1) investigating the effect of angular velocity on peak torque (PT) (2) investigating the effect of angular velocity on joint angle at peak torque (JAPT) and (3) evaluating whether the use of a relatively new isokinetic testing device yields new insights to previously accepted relationships between angular velocity and PT or JAPT. Twenty healthy subjects were tested for isometric and isokinetic knee extension and flexion strength on a LIDO Active Isokinetic Rehabilitation System at velocities of 0 degrees, 60 degrees, 120 degrees, and 180 degrees/sec. Isometric PT (0 degrees/sec) was found to be highly correlated with isokinetic PT for both extensors and flexors at all velocities (r = .88-.93, p less than .01). PT declined significantly as angular velocity increased for both extension (p less than .01) and flexion (p less than .05). A relationship between isometric and isokinetic JAPT was significant for extension only at 60 degrees and 180 degrees/sec (r = .48-.52, p less than .05). These results indicate that knee isometric and isokinetic PT as measured on the LIDO Active system are highly related for both extension and flexion. PT declined as isokinetic angular velocity increased. Isometric and isokinetic JAPT are significantly related only for extension.

Relationship of manual muscle testing to objective strength measurements.

This study investigates the relationship between manual muscle test scores (MMT) and quantitative isometric strength measurements (QIS). It also evaluates the implications of that relationship for design of therapeutic trials. Extension and flexion strength at the elbows, hips, and knees of 21 neuromuscular disease patients were tested a total of 26 times utilizing both MMT and QIS testing. Paired data were evaluated with Spearman ranked correlation coefficients, and then QIS was predicted from MMT using Lowess, a consistent form of nonparametric regression. Finally, the implications of the Lowess analysis for designing a therapeutic trial were evaluated. MMT and QIS measurements were significantly correlated in all movements tested. Lowess analysis yielded prediction errors ranging from 16 to 24% of QIS range. Analysis of the sample size needed for a therapeutic trial suggested that a protocol measuring MMT would require more subjects for the same level of statistical significance as a protocol measuring QIS. Since it was not possible to reliably predict QIS values from MMT scores, such conversions are not appropriate for clinical use. This inconsistent relationship between MMT and QIS carries major implications for the design of therapeutic trials. Since therapeutic trials are time consuming, expensive, and most centers do not have large numbers of individuals available, using QIS as an outcome measure is a preferable research design.

Cisplatin plus cytosine arabinoside in adults with malignant gliomas.

A combination of cisplatin and cytosine arabinoside was used to treat 21 patients with glioblastomas and 5 patients with recurrent grade II gliomas. Cisplatin 60-100 mg/m2 was given I.V. in 250 ml 0.45% saline and preceded by 500 ml dextrose 5% in 0.45% saline. Mannitol 50 g was given I.V. concurrently with the cisplatin. Cytosine arabinoside 500-1000 mg/m2 was given by rapid I.V. infusion immediately after the cisplatin. Of 25 evaluable patients, 10 (40%) experienced objective tumor shrinkage on CT scan, and 6 (24%) stabilized. There were 2 complete remissions. Patients who had had no prior treatment had a higher response rate (58%) than those previously treated (23%). Myelosuppression occurred in some patients 2-3 weeks after treatment. Gastrointestinal toxicity (vomiting and diarrhea) was dose-limiting. Two patients had possible neurological toxicity. Recommended doses for further studies are cisplatin 90 mg/m2 and cytosine arabinoside 900 mg/m2.