Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study

Abstract The aim of the study was to verify whether neuromuscular magnetic stimulation (NMMS) improves muscle function in spinal-onset amyotrophic lateral sclerosis (ALS) patients. Twenty-two ALS patients were randomized in two groups to receive, daily for two weeks, NMMS in right or left arm (refer...

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Autores principales:	Antonio Musarò, Gabriella Dobrowolny, Chiara Cambieri, Emanuela Onesti, Marco Ceccanti, Vittorio Frasca, Annalinda Pisano, Bruna Cerbelli, Elisa Lepore, Gabriele Ruffolo, Pierangelo Cifelli, Cristina Roseti, Carla Giordano, Maria Cristina Gori, Eleonora Palma, Maurizio Inghilleri
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ee91cdfe2d3748f786491fa8b3a64c99
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spelling	oai:doaj.org-article:ee91cdfe2d3748f786491fa8b3a64c992021-12-02T15:08:30ZNeuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study10.1038/s41598-019-39313-z2045-2322https://doaj.org/article/ee91cdfe2d3748f786491fa8b3a64c992019-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-39313-zhttps://doaj.org/toc/2045-2322Abstract The aim of the study was to verify whether neuromuscular magnetic stimulation (NMMS) improves muscle function in spinal-onset amyotrophic lateral sclerosis (ALS) patients. Twenty-two ALS patients were randomized in two groups to receive, daily for two weeks, NMMS in right or left arm (referred to as real-NMMS, rNMMS), and sham NMMS (sNMMS) in the opposite arm. All the patients underwent a median nerve conduction (compound muscle action potential, CMAP) study and a clinical examination that included a handgrip strength test and an evaluation of upper limb muscle strength by means of the Medical Research Council Muscle Scale (MRC). Muscle biopsy was then performed bilaterally on the flexor carpi radialis muscle to monitor morpho-functional parameters and molecular changes. Patients and physicians who performed examinations were blinded to the side of real intervention. The primary outcome was the change in the muscle strength in upper arms. The secondary outcomes were the change from baseline in the CMAP amplitudes, in the nicotinic ACh currents, in the expression levels of a selected panel of genes involved in muscle growth and atrophy, and in histomorphometric parameters of ALS muscle fibers. The Repeated Measures (RM) ANOVA with a Greenhouse-Geisser correction (sphericity not assumed) showed a significant effect [F(3, 63) = 5.907, p < 0.01] of rNMMS on MRC scale at the flexor carpi radialis muscle, thus demonstrating that the rNMMS significantly improves muscle strength in flexor muscles in the forearm. Secondary outcomes showed that the improvement observed in rNMMS-treated muscles was associated to counteracting muscle atrophy, down-modulating the proteolysis, and increasing the efficacy of nicotinic ACh receptors (AChRs). We did not observe any significant difference in pre- and post-stimulation CMAP amplitudes, evoked by median nerve stimulation. This suggests that the improvement in muscle strength observed in the stimulated arm is unlikely related to reinnervation. The real and sham treatments were well tolerated without evident side effects. Although promising, this is a proof of concept study, without an immediate clinical translation, that requires further clinical validation.Antonio MusaròGabriella DobrowolnyChiara CambieriEmanuela OnestiMarco CeccantiVittorio FrascaAnnalinda PisanoBruna CerbelliElisa LeporeGabriele RuffoloPierangelo CifelliCristina RosetiCarla GiordanoMaria Cristina GoriEleonora PalmaMaurizio InghilleriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Antonio Musarò Gabriella Dobrowolny Chiara Cambieri Emanuela Onesti Marco Ceccanti Vittorio Frasca Annalinda Pisano Bruna Cerbelli Elisa Lepore Gabriele Ruffolo Pierangelo Cifelli Cristina Roseti Carla Giordano Maria Cristina Gori Eleonora Palma Maurizio Inghilleri Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study
description	Abstract The aim of the study was to verify whether neuromuscular magnetic stimulation (NMMS) improves muscle function in spinal-onset amyotrophic lateral sclerosis (ALS) patients. Twenty-two ALS patients were randomized in two groups to receive, daily for two weeks, NMMS in right or left arm (referred to as real-NMMS, rNMMS), and sham NMMS (sNMMS) in the opposite arm. All the patients underwent a median nerve conduction (compound muscle action potential, CMAP) study and a clinical examination that included a handgrip strength test and an evaluation of upper limb muscle strength by means of the Medical Research Council Muscle Scale (MRC). Muscle biopsy was then performed bilaterally on the flexor carpi radialis muscle to monitor morpho-functional parameters and molecular changes. Patients and physicians who performed examinations were blinded to the side of real intervention. The primary outcome was the change in the muscle strength in upper arms. The secondary outcomes were the change from baseline in the CMAP amplitudes, in the nicotinic ACh currents, in the expression levels of a selected panel of genes involved in muscle growth and atrophy, and in histomorphometric parameters of ALS muscle fibers. The Repeated Measures (RM) ANOVA with a Greenhouse-Geisser correction (sphericity not assumed) showed a significant effect [F(3, 63) = 5.907, p < 0.01] of rNMMS on MRC scale at the flexor carpi radialis muscle, thus demonstrating that the rNMMS significantly improves muscle strength in flexor muscles in the forearm. Secondary outcomes showed that the improvement observed in rNMMS-treated muscles was associated to counteracting muscle atrophy, down-modulating the proteolysis, and increasing the efficacy of nicotinic ACh receptors (AChRs). We did not observe any significant difference in pre- and post-stimulation CMAP amplitudes, evoked by median nerve stimulation. This suggests that the improvement in muscle strength observed in the stimulated arm is unlikely related to reinnervation. The real and sham treatments were well tolerated without evident side effects. Although promising, this is a proof of concept study, without an immediate clinical translation, that requires further clinical validation.
format	article
author	Antonio Musarò Gabriella Dobrowolny Chiara Cambieri Emanuela Onesti Marco Ceccanti Vittorio Frasca Annalinda Pisano Bruna Cerbelli Elisa Lepore Gabriele Ruffolo Pierangelo Cifelli Cristina Roseti Carla Giordano Maria Cristina Gori Eleonora Palma Maurizio Inghilleri
author_facet	Antonio Musarò Gabriella Dobrowolny Chiara Cambieri Emanuela Onesti Marco Ceccanti Vittorio Frasca Annalinda Pisano Bruna Cerbelli Elisa Lepore Gabriele Ruffolo Pierangelo Cifelli Cristina Roseti Carla Giordano Maria Cristina Gori Eleonora Palma Maurizio Inghilleri
author_sort	Antonio Musarò
title	Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study
title_short	Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study
title_full	Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study
title_fullStr	Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study
title_full_unstemmed	Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study
title_sort	neuromuscular magnetic stimulation counteracts muscle decline in als patients: results of a randomized, double-blind, controlled study
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/ee91cdfe2d3748f786491fa8b3a64c99
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Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study

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