Muscle Fiber Conduction Slowing and Decreased Levels of Circulating Muscle Proteins after Short-Term Dexamethasone Administration in Healthy Subjects

Abstract

The demonstration that glucocorticoid-induced muscle impairments can be unraveled by means of blood sampling and noninvasive electrophysiological tests has clinical implications for the early identification of subclinical or preclinical forms of myopathy in treated patients.

Do muscle fiber conduction slowing and decreased levels of circulating muscle proteins represent sensitive markers of steroid myopathy? A pilot study in Cushing's disease

“…These muscles were selected because they present differences in fiber-type composition: the percentages of type 2 fibers are 50% for the vasti and 30% for the tibialis anterior (11). For each muscle, the following protocol was adopted: i) the subject's limb was placed in an isometric brace and the joint was fixed at 1208 (1808 being full extension of the knee/ankle); ii) the muscle motor point was identified, using a stimulation pen electrode, as the location generating the maximal mechanical response with the minimum injected current (5,12,13), and an adhesive stimulation electrode was placed over it; iii) an adhesive array of surface electrodes for detection of electrically elicited EMG signals (massed action potentials, M-waves) (5,12,13) was located between the motor point and the distal tendon; and iv) one 60 s long stimulation burst was delivered at the current intensity generating the maximal M-wave (see below) and at the stimulation frequency of 20 Hz.…”

“…An adhesive stimulation electrode (30!30 mm; Spes Medica, Battipaglia, Italy) was placed over the motor point and a larger electrode (50!80 mm) was placed over the antagonist muscle (monopolar stimulation) (5,12,13). For each stimulation burst, biphasic rectangular pulses (200 ms duration each) were delivered at the maximal current intensity identified as follows: M-waves were monitored as the muscle was stimulated at 2 Hz with current pulses of increasing intensity.…”

“…Physiological values of MFCV estimated from surface EMG signals detected during electrically elicited muscle contractions (i.e. the average conduction velocity of all the muscle fibers that are excited by the externally imposed electrical field) ranged from 4.0 to 6.0 m/s for the vastus lateralis and medialis muscles (5,13,18,19) and from 3.5 to 5.5 m/s for the tibialis anterior muscle (5,20,21).…”

“…Although the cause of steroid myopathy is not precisely known, it appears that the major effect of the chronic glucocorticoid excess is to blunt muscle protein synthesis and activate muscle proteolysis (4). In subjects under glucocorticoid therapy, the downregulation of muscle protein synthesis can be unraveled by decreased levels of circulating muscle proteins (5). However, it may be hypothesized that the circulating levels of muscle proteins could potentially also be reduced in endogenous hypercortisolism.…”

“…Apart from the preliminary observation of Khaleeli et al (1) who found a plasma creatine kinase (CK) activity at the lower end of the normal range in two out of three patients with Cushing's disease, no previous study investigated whether the levels of circulating proteins such as CK and myoglobin are reduced in patients with Cushing's disease compared with healthy controls. Furthermore, two in vivo studies also showed a slowing of the muscle fiber conduction following short-term glucocorticoid administration (5,6): it has been suggested that the decrease in muscle fiber conduction velocity (MFCV) was related to the suppressive effect of glucocorticoids on sarcolemmal excitability (5,6). Besides sarcolemmal excitability, the other factor influencing MFCV is muscle fiber diameter.…”