title: Atrophy, ultra-structural disorders, severe atrophy and degeneration of denervated human muscle in SCI and Aging. Implications for their recovery by Functional Electrical Stimulation, updated 2017.
abstract: OBJECTIVE
  Long-term lower motor neuron denervation of skeletal muscle is known to result in degeneration of muscle with replacement by adipose and fibrotic tissues. However, long-term survival of a subset of skeletal myofibers also occurs.
  
  
  METHODS
  We performed transverse and longitudinal studies of patients with spinal cord injury (SCI), patients specifically complete Conus and Cauda Equina Syndrome and also of active and sedentary seniors which included analyses of muscle biopsies from the quadriceps m.
  
  
  RESULTS
  Surprisingly, we discovered that human denervated myofibers survive years of denervation after full and irreversible disconnection from their motor neurons. We found that atrophic myofibers could be rescued by home-based Functional Electrical Stimulation (h-bFES), using purpose developed stimulators and electrodes. Although denervated myofibers quickly lose the ability to sustain high-frequency contractions, they respond to very long impulses that are able to allow for re-emergence of tetanic contractions. A description of the early muscle changes in humans are hampered by a paucity of patients suffering complete Conus and Cauda Equina Syndrome, but the cohort enrolled in the EU RISE Project has shown that even five years after SCI, severe atrophic myofibers with a peculiar cluster reorganization of myonuclei are present in human muscles and respond to h-bFES.
  
  
  CONCLUSIONS
  Human myofibers survive permanent denervation longer than generally accepted and they respond to h-bFES beyond the stage of simple atrophy. Furthermore, long-term denervation/reinnervation events occur in elderly people and are part of the mechanisms responsible for muscle aging and again h-bFES was beneficial in delaying aging decay.
authors.affiliation: a Physiko- und Rheumatherapie , St. Poelten , Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Kern
authors.affiliation: b Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation , Vienna , Austria.
authors.forename: Cristian
authors.initials: C
authors.lastname: Hofer
authors.affiliation: a Physiko- und Rheumatherapie , St. Poelten , Austria.
authors.forename: Stefan
authors.identifier: http://orcid.org/0000-0002-6592-0663
authors.initials: S
authors.lastname: Loefler
authors.affiliation: a Physiko- und Rheumatherapie , St. Poelten , Austria.|c Department of Biomedical Sciences , University of Padova , Padova , Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zampieri
authors.affiliation: d Instutute for Biomedical and Neural Engineering/Biomedical Technology Centre , Reykjavik University and Landspitali , Reykjavik , Iceland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gargiulo
authors.affiliation: e IRCCS Fondazione Ospedale San Camillo , Venice , Italy.
authors.forename: Alfonc
authors.initials: A
authors.lastname: Baba
authors.affiliation: e IRCCS Fondazione Ospedale San Camillo , Venice , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marcante
authors.affiliation: e IRCCS Fondazione Ospedale San Camillo , Venice , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piccione
authors.affiliation: f Anatomy Department , Southern Illinois University School of Medicine , Carbondale , IL , USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Pond
authors.affiliation: e IRCCS Fondazione Ospedale San Camillo , Venice , Italy.
authors.forename: Ugo
authors.identifier: http://orcid.org/0000-0002-0924-4998
authors.initials: U
authors.lastname: Carraro
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology; D000818:Animals; D001284:Atrophy; D004599:Electric Stimulation Therapy; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology / Q000534:rehabilitation
keywords: Human skeletal muscle; home-based FES; longstanding denervation; reversible and irreversible changes; structure and ultrastructure