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

Helmut Kern, Cristian Hofer, Stefan Loefler, Sandra Zampieri, Paolo Gargiulo, Alfonc Baba, Andrea Marcante, Francesco Piccione, Amber Pond, Ugo Carraro

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Objectives: 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.

Original languageEnglish
Pages (from-to)660-666
Number of pages7
JournalNeurological Research
Volume39
Issue number7
DOIs
Publication statusPublished - Jul 3 2017

Fingerprint

Denervation
Spinal Cord Injuries
Electric Stimulation
Atrophy
Polyradiculopathy
Muscles
Motor Neurons
Quadriceps Muscle
Longitudinal Studies
Adipose Tissue
Electrodes
Skeletal Muscle
Biopsy
Survival

Keywords

  • home-based FES
  • Human skeletal muscle
  • longstanding denervation
  • reversible and irreversible changes
  • structure and ultrastructure

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

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. / Kern, Helmut; Hofer, Cristian; Loefler, Stefan; Zampieri, Sandra; Gargiulo, Paolo; Baba, Alfonc; Marcante, Andrea; Piccione, Francesco; Pond, Amber; Carraro, Ugo.

In: Neurological Research, Vol. 39, No. 7, 03.07.2017, p. 660-666.

Research output: Contribution to journalReview article

Kern, Helmut ; Hofer, Cristian ; Loefler, Stefan ; Zampieri, Sandra ; Gargiulo, Paolo ; Baba, Alfonc ; Marcante, Andrea ; Piccione, Francesco ; Pond, Amber ; Carraro, Ugo. / 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. In: Neurological Research. 2017 ; Vol. 39, No. 7. pp. 660-666.
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abstract = "Objectives: 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.",
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AU - Hofer, Cristian

AU - Loefler, Stefan

AU - Zampieri, Sandra

AU - Gargiulo, Paolo

AU - Baba, Alfonc

AU - Marcante, Andrea

AU - Piccione, Francesco

AU - Pond, Amber

AU - Carraro, Ugo

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N2 - Objectives: 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.

AB - Objectives: 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.

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