Reverse Denervated Muscle Atrophy - Clinical Evidence

[Christopher]

This clinical paper and discussion following it is, I believe, of extreme importance to new and old BPI sufferers. It's the first medical document that I've come across that gets into the reversing of long term denervated muscle atrophy.

When I had my first surgery 3 years ago (4/15/03) this info wasn't available and I asked my neurosurgeon his thoughts on Electrical Stimulation and what course of treatment he would recommend. Unfortunately when asked "personally, if this was your injury what would you do" he replied, "It works on rats, but I wouldn't waste my time". When asked a bit further as to why, he explained that the nerve, not the muscle, is what receives the majority of the electrical impulse and that that could do damage to the newly grafted nerves.

I have to admit this is one of the few BPI subjects that I haven't done extensive research on, a fair bit, but not staying up night and day reading and learning medical jargon in hopes of helping my, and the rest of our, situation out.

I neglected to fully utilize Functional Electrical Stimulation (FES) for a couple of reasons. One, it was depressing as hell and I was depressed and angry. Watching my arm, shoulder, chest and hand, get smaller by the week as I prodded it daily gave me a feeling of ever growing hopelessness. The more I focussed my attention on my arm, the more depressed and angry I'd get. Not believing it was working, because my muscles were getting smaller, and also of what my Dr. had said he'd do if it was his arm (let it be known that I have the utmost respect and appreciation for my neurosurgeon, especially for answering my 'personal' question honestly). Now there are E-Stim machines that have biofeedback indicators that let the user know if the muscle is receiving current and how it much it is receiving (which I think is great for motivation and confirmation when E-Stim "dead" muscles for weeks and months on end).

The second reason was that I believed the new nerve grafts (two intercostals to biceps, two intercostals to transfered gracilis, and half of uninjured side's C7 to injured side's deltoid) that would be reinnervating my once large and substantial muscles, would never be able to provide enough "juice" to sustain any real "staying" power for my muscles. The new nerves were simply smaller and provided less stimulation. In my mind I compared it to, trying to put out a burning house thru a drinking straw instead of using a fire hose.

Anyway, I believe this "logic" was tainted by my depression and increasing apathy for my situation as doomed and hopeless. As I continue to research and learn (and stay off mind numbing pain killers) I find my hope and enthusiasm for the future for BPI sufferers increases! I truly believe that within 5-10 years I will get some important and much missed return of function back into my arm, chest, shoulder and hand. The science is being researched and perfected all across the globe. Stem cells holding the biggest promise.

Okay the point... below is a paper published in a medical journal that gets into the specifics of what kind of exact FES works on reversing atrophy on long term, and of course short term, denervated muscle. And below that is a discussion from a Spinal Cord Injury site/forum about this paper. The discussion offers very understandable insights into the do's and don'ts of FES by one of the Spinal Cord Injury Community's most preeminent researchers and advocates, Dr. Wise Young. That's why I think this information is essential, especially for those freshly injured! If I was newly injured I'd print out a couple of both of these links and take them to my neurosurgeon (to help educate) and to my physical therapist (to help facilitate the best possible replication during therapy of what has been proven to work by the researchers)

Sorry for the long winded onslaught. I just don't want anyone making the same mistakes I've made and I'd like to spread the hope.

Cheers
Christopher


Journal of Rehabilitation Research & Development-
http://www.vard.org/jour/05/42/3%20suppl%201/kern.html

CareCure Community-
Dr. Young: Rebuilding Denervated Degenerated Muscles (Please Comment)
http://sci.rutgers.edu/forum/showthread.php?t=63004


Beginning of Article from Journal of Rehabilitation Research & Development

Supplement Number 1
Volume 42 Number 3, May/June 2005
Pages 43 — 54

Muscle biopsies show that FES of denervated muscles reverses human muscle degeneration from permanent spinal motoneuron lesion



Abstract — This paper presents biopsy analyses in support of the clinical evidence of muscle recovery induced by a new system of life-long functional-electrical-stimulation (FES) training in permanent spinal-motoneuron-denervated human muscle. Not earlier than 1 year after subjects experienced complete conus cauda lesion, their thigh muscles were electrically stimulated at home for several years with large skin surface electrodes and an expressly designed stimulator that delivered much longer impulses than those presently available for clinical use. The poor excitability of long-term denervated muscles was first improved by several months of twitch-contraction training. Then, the muscles were tetanically stimulated against progressively increased loads. Needle biopsies of vastus lateralis from long-term denervated subjects showed severe myofiber atrophy or lipodystrophy beginning 2 years after spinal cord injury (SCI). Muscle biopsies from a group of 3.6- to 13.5-year denervated subjects, who underwent 2.4 to 9.3 years of FES, show that this progressive training almost reverted long-term muscle atrophy/degeneration.

INTRODUCTION
Spinal cord injury (SCI) causes a rapid loss of muscle mass, which is especially severe when the injury involves spinal motoneurons. While much interest has been shown in the use of functional electrical stimulation (FES) to restore movement of the limbs of subjects paralyzed by upper motoneuron lesions [1-2], very few clinicians hope to recover permanent spinal-motoneuron-denervated muscles by means of electrical stimulation training. Indeed, atrophy is especially severe when the injury involves spinal motoneurons, in which long-term irreversible denervation results in fat substitution and muscle fibrosis. Although early denervation has been widely studied both in animal models and humans, the long-term effects of denervation have attracted much less attention since the general belief is that all myofibers disappear within several months of denervation [3-5]. In rats, myofibers exhibit a net loss of nuclear domains for 7 months, followed by nuclear groupings, a specific morphologic marker of long-term severe muscle atrophy [6]. Furthermore, permanent spinal motoneuron denervation has also demonstrated to be accompanied by a continuous production of new myofibers [7-12]. Activated satellite cells, myotubes, and regenerated myofibers are consistently present in atrophic rat muscles, even after year-long permanent denervation in both hemidiaphragm and leg muscles [7-9]. Interestingly, we have recently extended these observations to human muscle [13]. All these events can prolong the period during which denervated tissue may be recovered through reinnervation or FES training.

In permanent, complete conus cauda lesions, SCI results in irreversible loss of the nerve supply to some or all the muscles of the affected limbs, making the marked atrophy of the denervated muscle and the severe secondary medical problems of skin and bone more difficult to treat successfully (e.g., pressure sores and bone demineralization and fracture). Without functional motor nerve fibers, activating a sufficient population of myofibers is more problematic when electric currents are provided by surface electrodes; 6 months after SCI, long-term spinal-motoneuron-denervated muscle is poorly excitable by standard clinically approved electrodes and stimulation devices. Despite these difficulties, pilot studies on FES of long-term human denervated and degenerated muscles (DDM) have been published [5]. Especially encouraging are some of our previous results, which have shown that a new electrical-stimulation training strategy is effective in restoring a certain degree of muscle mass and force production even after long-standing complete spinal-motoneuron lesions [14-17]. These clinical works strongly supported the idea that FES training of denervated muscles could restore DDM, a fact that had not previously been recognized, principally because of the lack of customized technology that can meet demands completely different from those required for motor-nerve stimulation. On the other hand, a stimulator delivering biphasic long-duration impulses with a pulse width between 10 ms and 200 ms and amplitudes of up to ±80 V and ±200 mA is able to elicit DDM twitch contractions via surface electrodes [16-17]. Within a few months, such training increases myofiber excitability of the quadriceps muscle to a level that allows tetanic contractions. Finally, the structural and metabolic characteristics of the tetanically stimulated muscles are restored to values that allow electrically supported standing up and standing. Recently, clinical results by computerized tomography (CT) scan and force measurements during tetanic stimulation of the thigh muscles were promising enough to convince ethical committees and funding agencies to accept our proposal for a European Union (EU) Trial ("RISE") for restoration of DDM in conus cauda syndrome by FES training. With the support of the EU RISE project, we are using light and electron microscopy to analyze in detail biopsies of human long-term DDM before and after FES.

We present the preliminary results of morphometric analyses of DDM in a group of subjects enrolled in the RISE Trial, who were biopsied before FES. We compare these subjects with a previous group of subjects who had undergone FES training of denervated muscles and were biopsied after 2.4 to 9.3 years of FES training that was initiated between 1.2 and 8.7 years after SCI. Our purpose was to present biopsy analyses in support of the clinical evidence of muscle recovery induced by the new life-long FES training in permanent spinal-motoneuron-denervated human muscle. Microscopic muscle analyses from these two independent groups of subjects support our previous clinical observations [14-15,18]. Besides recovery of the atrophic muscle fibers, sustained regeneration of new myofibers may explain the observations that in the FES-treated muscle, the fibers are larger than the fibers in untreated muscles of the group of DDM subjects from the EU RISE Trial [19].