vendex and Myopathies--Nemaline

Patients with nemaline myopathy, a muscle disorder primarily affecting the thin filaments, suffer from weakness which is poorly understood. As disturbed excitation-contraction coupling has been suggested as a possible mechanism, the present study was designed to investigate whether the contractile properties of the knee-extensor muscles in patients from a single family with nemaline myopathy were different from able-bodied individuals. To assess central neural as well as more peripheral intrinsic aspects of muscle activation, isometric voluntary and electrically elicited quadriceps contractions were evoked at different knee angles. Interestingly, across the range of 30-70 degrees of knee flexion, the capacity to achieve maximal voluntary activation of the muscles, assessed by a super-imposed stimulation technique, was significantly higher in patients compared with controls. Furthermore, the torque-frequency relation differed between groups, with the muscles of patients producing higher torques at low (twitch and 10 Hz) stimulation frequencies relative to maximal (150 Hz) stimulation than controls at both 30 degrees and 60 degrees of knee flexion. These results suggest that no impairment was present at relatively low activation frequencies. It may, however, be indicative for a reduced cross-bridge attachment as part of the excitation-contraction coupling specifically at high activation frequencies. In conclusion, the quadriceps weakness observed in this specific patient group cannot be explained by an impaired capacity to maximally activate these muscles. However, the data of relatively high torques produced at submaximal activation frequencies are compatible with the hypothesis that patients with nemaline myopathy may have an impaired acto-myosin interaction specifically at high levels of activation.

Topics: Adult; Aged; Analysis of Variance; Case-Control Studies; Electric Stimulation; Female; Humans; Isometric Contraction; Knee Joint; Male; Middle Aged; Muscle Contraction; Muscle Weakness; Muscle, Skeletal; Myopathies, Nemaline; Phenotype; Torque

All patients of a large family with nemaline myopathy complained of slowness in movement. We confirmed this clinical complaint physiologically by showing lower contractile speed in quadriceps muscle. Electrically evoked contractions of the quadriceps muscle elicited a lower rate of relaxation and a tendency for slower torque generation. Here, we demonstrate for the first time slow muscle characteristics as a physiological correlate for the clinical complaint of slowness.

Topics: Adult; Aged; Biopsy; Chromosomes, Human, Pair 15; Electric Stimulation; Female; Genetic Predisposition to Disease; Humans; Isometric Contraction; Male; Middle Aged; Muscle Contraction; Muscle, Skeletal; Myopathies, Nemaline; Neurologic Examination; Quadriceps Muscle; Reaction Time; Time Factors; Torque

Nemaline myopathy is a congenital neuromuscular disorder, which primarily affects the thin filaments. Clinically the most important feature is muscle weakness; however, this weakness is poorly understood. The present investigation aimed to determine the torque angle relationship of the knee extensor muscles during in vivo muscle contractions in a family with a novel phenotype of nemaline myopathy. The results of this study show that quadriceps weakness occurs predominantly at higher knee flexion angles, but relatively normal strength was found at angles closer to full knee extension. When the relative torque angle relationships were considered, torque loss at smaller than optimum knee flexion angle was greater in the patients compared with the controls. In addition, the optimum angle for maximal quadriceps torque production was shifted towards smaller knee flexion angles in the patients. This suggests that a weakness specifically at higher knee flexion angles probably occurs as a result of adaptations consequently to the disease. Furthermore, it is important to assess muscle function at different joint positions to allow adequate interpretation of muscle weakness.

Topics: Adult; Analysis of Variance; Case-Control Studies; Chromosome Mapping; Chromosomes, Human, Pair 15; Female; Humans; Isometric Contraction; Knee Joint; Male; Middle Aged; Muscle Weakness; Muscle, Skeletal; Myopathies, Nemaline; Torque