Severe muscle atrophy due to spinal cord injury can be reversed in complete absence of peripheral nerves

In the last years, a new efficient treatment has been developed to treat paralyzed skeletal muscle of patients affected by spinal cord injury (SCI). The capability of the functional electrical stimulation (FES) to improve trophism and in some cases muscle function, are now well documented both in animals after experimental cord lesion, and in humans, generally after traumatic cord lesion. This new findings makes FES an important tool for the rehabilitation of SCI patients. FES stimulation has been proven to be an effective method used to retard muscle atrophy and improve recovery after reinnervation. Sophisticated FES devices have been developed for restoring function in the upper and lower extremities, the bladder and bowel, and the respiratory system of SCI patients. However, there are SCI cases, such as those affected by flaccid paralysis, in which the musculature is not treated with FES rehabilitation therapy. This is because conventional FES apparatuses are designed for direct stimulation of peripheral nerves that need small currents to be depolarized, and are not effective in patients that have lost their peripheral nerves, and, therefore, require higher currents for the direct depolarization of the muscle fibers. Lack of muscle treatment generates, as a secondary problem, a long series of alterations to tissues other than muscle, such as bones (osteoporosis), skin (pressure sores, decubital ulcers), etc., that are a direct consequence of inactivity and poor blood supply to the denervated areas. These complications represent an extremely serious problem for the general health of the injured individuals, who usually have a shorter than normal life span. In the hopes of changing this common belief, an innovative rehabilitation procedure, based on FES, has been developed with the aim of reversing long-lasting muscle atrophy in the muscles of the lower extremities of SCI patients affected by complete lesion of the conus cauda, i.e. that have no peripheral nerves. Experimental and clinical results have shown that electrical stimulation training by long impulses can restore muscle mass, force production and movements even after long lasting complete denervation. Measurements by CT-scans revealed a substantial increase of tight muscle cross sectional area during the first years of FES and muscle function of the lower extremities was restored in some patients sufficiently to allow for supported standing, standing, and even for a few steps to be taken. We have described the ultrastructural changes accompanying the recovery of skeletal muscle in the total absence of either sensory or motor innervation. The results showed a striking structural recovery of muscle fiber ultrastructure in all FES treated patients: the 90% (or more) of the studied fibers recovery from a very profound atrophy under the influence of the electrical stimulation. Restoration of ultrastructure involves all the major apparatuses of muscle fibers, such as the one deputed to muscle activation and Ca2+ handling (ECC apparatus), to contractility (myofibrils), and to metabolic and energy generation tasks (mitochondria). This structural recovery occurs in complete absence of nerve endings, under the influence of muscle activity, and follows pattern that mimics in many aspects normal muscle differentiation as well as recovery after short-term disuse and/or denervation. The present ultra-structural studies are important because they show that, despite the apparent complete loss of specific structure, the long-term denervated fibers maintain their full differentiation program. Reversal of the damages from long-standing denervation in humans may be of significant importance also for the rehabilitation and the general health of SCI patients.