Dataset Information

Functional Electrical Stimulation: A Possible Strategy to Improve Muscle Function in Central Core Disease?

ABSTRACT: Central Core Disease (CCD) is a congenital myopathy characterized by presence of amorphous central areas (or cores) lacking glycolytic/oxidative enzymes and mitochondria in skeletal muscle fibers. Most CCD families are linked to mutations in ryanodine receptor type-1 (RYR1), the gene encoding for the sarcoplasmic reticulum (SR) Ca2+ release channel of skeletal muscle. As no treatments are available for CCD, currently management of patients is essentially based on a physiotherapic approaches. Functional electrical stimulation (FES) is a technique used to deliver low energy electrical impulses to artificially stimulate selected skeletal muscle groups. Here we tested the efficacy of FES in counteracting muscle loss and improve function in the lower extremities of a 55-year-old female patient which was diagnosed with CCD at the age of 44. Genetic screening of the RyR1 gene identified a missense mutation (c.7354C>T) in exon 46 resulting in an amino acid substitution (p.R2452W) and a duplication (c.12853_12864dup12) in exon 91. The patient was treated with FES for 26 months and subjected before, during, and after training to a series of functional and structural assessments: measurement of maximum isometric force of leg extensor muscles, magnetic resonance imaging, a complete set of functional tests to assess mobility in activities of daily living, and analysis of muscle biopsies by histology and electron microscopy. All results point to an improvement in muscle structure and function induced by FES suggesting that this approach could be considered as an additional supportive measure to maintain/improve muscle function (and possibly reduce muscle loss) in CCD patients.

SUBMITTER: Iodice P

PROVIDER: S-EPMC6548841 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional Electrical Stimulation: A Possible Strategy to Improve Muscle Function in Central Core Disease?

Iodice Pierpaolo P Boncompagni Simona S Pietrangelo Laura L Galli Lucia L Pierantozzi Enrico E Rossi Daniela D Fusella Aurora A Caulo Massimo M Kern Helmut H Sorrentino Vincenzo V Protasi Feliciano F

Frontiers in neurology 20190529

Central Core Disease (CCD) is a congenital myopathy characterized by presence of amorphous central areas (or <i>cores</i>) lacking glycolytic/oxidative enzymes and mitochondria in skeletal muscle fibers. Most CCD families are linked to mutations in ryanodine receptor type-1 (RYR1), the gene encoding for the sarcoplasmic reticulum (SR) Ca<sup>2+</sup> release channel of skeletal muscle. As no treatments are available for CCD, currently management of patients is essentially based on a physiotherap ...[more]

PMID: 31191425

Similar Datasets

Project description:Stimulation of the mouse hindlimb via the sciatic nerve was used to induce contractions for 4 hours to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 + 0.1 g/g body weight) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon completion of the study. An immediate-early growth response was present in the EDL (FOS, JUN, ATF3, MAFK) with a similar but attenuated pattern in the soleus. Transcript profiles showed decreased fast fiber specific mRNA (myosin heavy chains 2A, 2B; troponins T3, I; -tropomyosin, m-creatine kinase) and increased slow transcripts (myosin heavy chain slow/1, troponin C, tropomyosin 3) in the EDL. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration or myofiber damage in stimulated vs. control muscles. Several fiber type specific transcription factors (EYA1, TEAD1, NFATc1 and c4, PPARG, PPARGC1 and β, BHLHB2) increased in the EDL along with transcription factors characteristic of embryogenesis (KLF4, SOX17, TCF15, PKNOX1, ELAV). No established in vivo satellite cell markers or the genes activated during our parallel studies of satellite cell proliferation in vitro (CYCLINS A2, B2, C, E1, MyoD) increased in the stimulated muscles. These data indicated that onset of fast to slow phenotype conversion occurred in the EDL within 4 hours of stimulation without satellite cell recruitment or muscle injury but was driven by phenotype specific transcription factors from resident fiber myonuclei including activation of nascent developmental transcriptional programs. Adult male Swiss Webster mice (30-35 g) were anesthetized, a bipolar electrode was implanted adjacent to the sciatic nerve and the hindlimb immobilized. The voltage-force relation was determined to establish supramaximal stimulation conditions and the length-tension relation was determined to set the resting length for maximum twitch tension. Contractions were induced by sciatic nerve stimulation (0.5 msec duration, 2-5 volts). The muscles were allowed to rest 15 minutes for full metabolic recovery at physiologic temperatures. Supramaximal stimulation was applied at a rate of 10 Hz for 4 hours. At the end of each experiment the soleus muscles were carefully dissected and flash frozen in liquid nitrogen for analysis of mRNA expression via microarray analysis. The contralateral, unstimulated Soleus provided a genetically matched, paired control for each specimen.

Project description:Spinal cord injury (SCI) causes severe bone loss and disrupts connections between higher centers in the central nervous system (CNS) and bone. Muscle contraction elicited by functional electrical stimulation (FES) partially protects against loss of bone but cellular and molecular events by which this occurs are unknown. Here, using a rat model, we characterized effects of 7 days of contraction-induced loading of tibia and fibula due to FES when begun 16 weeks after SCI. SCI reduced tibial and femoral BMD by 12-17% and promoted bone resorption, as indicated by increased serum CTX; SCI-related changes in CTX were reversed by FES. In cultures of bone marrow cell-derived cells, SCI increased the number of osteoclasts and mRNA levels of the several osteoclast differentiation markers; these changes were significantly reversed by FES. The number of osteoblasts was also reduced by SCI as was the ratio of OPG/RANKL mRNAs therein; the unfavorable change in OPG/RANKL ratio was partially reversed by FES. cDNA microarray analysis revealed that alterations in genes involved in signaling through Wnt, FSH/LH, PTH and calcineurin/NFAT pathways may be linked to the favorable action of FES on SCI-induced bone resorption. In particular, SCI increased levels of the Wnt inhibitors DKK1, sFRP2 and SOST in osteoblasts, These effects were completely or partially reversed by FES. Our results demonstrate an anti-bone resorptive activity of acute FES in bone loss after SCI and suggest potential underlying mechanisms, among them involving increased Wnt signaling to cause more favorable ratios of OPG and RANKL for the inhibition of osteoclastogenesis. The present study indicates that the effects of bone reloading on SCI- related bone remodeling occurred independently of the effects of higher CNS centers on bone. Implantation of the FES microstimulators was performed 14 weeks after SCI. The FES was begun during the 16th week following spinal cord transection. Stimulation was provided for 60 minutes on each training day and consisted of brief periods of contraction (2 seconds) at 40 Hz at 1.5 V with longer periods of rest (18 seconds). Animals received FES on 7 consecutive days; collection of blood and tissues occurred at day at after initiating FES, as described below. The SCI-Sham FES animals received the implant surgery and gastrocnemius ablation during the 14th week after the spinal cord transection, but did not have a stimulator unit inserted; samples were collected from these animals at week 17. To provide age-matched non-SCI controls, additional animals underwent a sham-SCI surgery identical to that for the SCI animals, except that the spinal cord was not transected. Tissues were collected from these animals at 12-14 weeks after surgery. Of note, at this age, animals were sexually mature and their growth minimal. To collect blood and tissues, animals were anesthetized by inhalation of isofluorane followed by removal of the soleus and plantaris muscles after careful dissection and collection of blood by ventricular puncture and aspiration. Animals were euthanized by aortic transaction and tibia and femur were removed as a single piece, leaving the knee joint intact, and placed in a-MEM for isolation of bone marrow cells. Muscles were weighed; weights are expressed after being normalized to body weight before SCI or sham-SCI surgeries to control for individual variations in size.

Dataset Information

Functional Electrical Stimulation: A Possible Strategy to Improve Muscle Function in Central Core Disease?

Publications

Functional Electrical Stimulation: A Possible Strategy to Improve Muscle Function in Central Core Disease?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets