Role of mechanical damage in pathogenesis of proximal myopathy in man

No adequate explanation has as yet been provided for the predominant proximal and symmetrical distribution of skeletal muscle weakness and wasting in human myopathies. One obvious difference between proximal and distal muscles is that in their postural antigravity role the former are involved in eccentric contractions to a much greater extent than are the latter. Recent physiological studies have shown that eccentric contractions produce considerable muscle damage in normal healthy subjects. The damage starts in individual sarcomeres but becomes more extensive over 1-2 days, the progression probably being due to the stronger sarcomeres stretching the weaker, damaged sarcomeres during normal activity and/or to the enzyme degradation of myofibrillar proteins when muscle damage results in Ca++ inflow. As a muscle becomes weaker and unable to meet the functional demands made upon it the likelihood of accidental stretch becomes greater. The vicious circle of weakness, stretch, damage, and further weakness may be the reason why the proximal muscles, which normally function eccentrically to some degree, are the most severely affected in a wide range of myopathic disorders.