History, mechanisms and clinical value of fibrillation analyses in muscle denervation and reinnervation by Single Fiber Electromyography and Dynamic Echomyography

News on skeletal muscle fibrillation analyses Eur J Trans Myol - Basic Appl Myol 2014; 24 (1): 41-54 History, mechanisms and clinical value of fibrillation analyses in muscle denervation and reinnervation by Single Fiber Electromyography and Dynamic Echomyography (1) Amber Pond, (2) Andrea Marcante, (3) Riccardo Zanato, (3) Leonora Martino, (3) Roberto Stramare, (4) Vincenzo Vindigni, (5,6) Sandra Zampieri, (6) Christian Hofer, (6,7) Helmut Kern, (2) Stefano Masiero, (8) Francesco Piccione (1) Anatomy Department, Southern Illinois University School of Medicine, Carbondale, IL USA; (2) CIR-Myo, Rehabilitation and Physical Medicine Unit, Department of Neurosciences, University of Padova, (3) CIR-Myo, Radiology, Department of Medicine, University of Padova, (4) CIR-Myo, Plastic Surgery, Department of Neuroscience, University of Padova, Italy; (5) CIR-Myo, Department of Biomedical Sciences, University of Padova, Italy; (6) Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation, Vienna, Austria; (7) Department of Physical Medicine and Rehabilitation, Wilhelminenspital, Vienna, Austria; (8) Clinical Neurophysiology, San Camillo Hospital I.R.C.C.S., Venezia-Lido, Italy Abstract This work reviews history, current clinical relevance and future of fibrillation, a functional marker of skeletal muscle denervated fibers. Fibrillations, i.e., spontaneous contraction, in denervated muscle were first described during the nineteenth century. It is known that alterations in membrane potential are responsible for the phenomenon and that they are related to changes in electrophysiological factors, cellular metabolism, cell turnover and gene expression. They are known to inhibit muscle atrophy to some degree and are used to diagnose neural injury and reinnervation that are occurring in patients. Electromyography (EMG) is useful in determining progress, prognosis and efficacy of therapeutic interventions and their eventual change. For patients with peripheral nerve injury, and thus without the option of volitional contractions, electrical muscle stimulation may be helpful in preserving the contractility and extensibility of denervated muscle tissue and in retarding/counteracting muscle atrophy. It is obvious from the paucity of recent literature that research in this area has declined over the years. This is likely a consequence of the decrease in funding available for research and the fact that the fibrillations do not appear to cause serious health issues. Nonetheless, further exploration of them as diagnostic tools in long-term denervation is merited, in particular if Single Fiber EMG (SFEMG) is combined with Dynamic Echomyography (DyEM), an Ultra Sound muscle approach we recently designed and developed to explore denervated and reinnervating muscles. Key Words: skeletal muscle, denervation, atrophy, fibrillation, clinical electromyography, Single Fiber EMG (SFEMG), dynamic echomyography (DyEM) Eur J Trans Myol - Basic Appl Myol 2014; 24 (1): 41-54 sclerosis,2,7 conditions in which muscle fiber regeneration and /or denervation are often or very often present.8,9 However, they are considered to be a defining characteristic of motor nerve disruption to the skeletal muscle fiber in humans 10-15 and in animal models of spinal cord injury (SCI) and peripheral denervation.1,3,16-18 These spontaneous fibrillations are often used clinically to determine the severity and magnitude of neural injury 19-21 and nerve regeneration status.22 It also has been proposed that these fibrillations could be useful in assessing the muscle Skeletal muscle fibrillation refers to small, local muscular contractions that occur in response to spontaneous activation of single muscle fibers which then contract independently of surrounding fibers. This activity contrasts with muscle fasciculations which occur when muscle fibers of a motor unit are stimulated and contract in a synchronous manner.1-3 Spontaneous fibrillations have been described in cases of certain muscle disorders such as muscular dystrophy,4 polymyositis 5,6 and amyotrophic lateral - 41 - News on skeletal muscle fibrillation analyses Eur J Trans Myol - Basic Appl Myol 2014; 24 (1): 41-54 atrophy occurring subsequent to denervation.11,23 We would like to add the mechanism of pre-neural stages of muscle fiber development that are mandatory events of muscle fiber regeneration.24 most active two to four weeks following nerve lesion.” The often cited Eaton and Lambert paper32 “Electromyography and Electric Stimulation of Nerves in Diseases of Motor Unit” from 1957 summarized fibrillation potential timing as: “They are observed regularly in denervated muscle, beginning 2 to 3 weeks after interruption of the axon and persisting for a variable time up to many years thereafter.” To determine the length dependent nature of the onset of fibrillation potentials, Luco and Eyzaguirre29 experimentally sectioned the sciatic nerve of two groups of animals: 1) the sciatic nerves of one group were sectioned high in the pelvis, while 2) the sciatic nerves of the animals in the second group were sectioned at the nerve twig to the tenuissimus muscle; the result was that there was a difference in residual nerve length of 25–35 mm between the two groups. In the former group, fibrillation potentials were first detectable at 140 h, whereas in the latter, fibrillation potentials were present in all by 120 h. From this work, the investigators concluded: “…if the cut portion of a nerve is short the above phenomena [fibrillation potentials] appear earlier than when a greater length of nerve is left to degenerate.” Salafsky et al.30 published similar findings in 1968 based on experiments designed to determine if there was a difference between the onset of fibrillation potentials in fast versus slow twitch muscle and to investigate length dependency of onset. As with Luco and Eyzaguirre,29 they had demonstrated length dependency, however, only in muscles presumed to be slow twitch. The significance of this result is unclear, as neither the sampling interval nor the number of data points was detailed in the article. With the onset timing of fibrillation potentials issue thought to be relatively settled, scientific study in the late 1940s and early 1950s shifted more toward study of the underlying mechanism of fibrillation potentials and their origin. History The first recorded observations of muscle fibrillations after denervation have been attributed to Schiff25 who reported, in his 1851 article entitled “Ubermotorische Lahmung der Zunge,” visual observations of fibrillations in the tongue muscles of dogs after bilateral hypoglossal nerve section. In 1915, experiments by Langley and Kato26,27 were the first to show explicitly that fibrillations followed denervation. Interestingly, three years later Langley and Hashimoto,28 in continued experiments along the same vein, arguably may have come close to observing length dependency (that is, the curren (...truncated)