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April 08, 2014; 82 (14) Article

rTMS in fibromyalgia

A randomized trial evaluating QoL and its brain metabolic substrate

Laurent Boyer, Alix Dousset, Philippe Roussel, Nathalie Dossetto, Serge Cammilleri, Virginie Piano, Stéphanie Khalfa, Olivier Mundler, Anne Donnet, Eric Guedj
First published March 26, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000280
Laurent Boyer
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Alix Dousset
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Philippe Roussel
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Nathalie Dossetto
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Serge Cammilleri
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Virginie Piano
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Stéphanie Khalfa
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Olivier Mundler
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Anne Donnet
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Eric Guedj
From EA 3279–Self-perceived Health Assessment Research Unit (L.B.), School of Medicine, La Timone University, Marseille; Centre d'Evaluation et de Traitement de la Douleur (A. Dousset, P.R., N.D., V.P., A. Donnet) and Service Central de Biophysique et Médecine Nucléaire (S.C., O.M., E.G.), APHM, Hôpital de la Timone, Marseille; CERIMED (S.C., O.M., E.G.) and Institut de Neurosciences de la Timone, CNRS UMR 7289 (S.K., E.G.), Aix-Marseille Université, Marseille, France.
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Citation
rTMS in fibromyalgia
A randomized trial evaluating QoL and its brain metabolic substrate
Laurent Boyer, Alix Dousset, Philippe Roussel, Nathalie Dossetto, Serge Cammilleri, Virginie Piano, Stéphanie Khalfa, Olivier Mundler, Anne Donnet, Eric Guedj
Neurology Apr 2014, 82 (14) 1231-1238; DOI: 10.1212/WNL.0000000000000280

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Abstract

Objective: This double-blind, randomized, placebo-controlled study investigated the impact of repetitive transcranial magnetic stimulation (rTMS) on quality of life (QoL) of patients with fibromyalgia, and its possible brain metabolic substrate.

Methods: Thirty-eight patients were randomly assigned to receive high-frequency rTMS (n = 19) or sham stimulation (n = 19), applied to left primary motor cortex in 14 sessions over 10 weeks. Primary clinical outcomes were QoL changes at the end of week 11, measured using the Fibromyalgia Impact Questionnaire (FIQ). Secondary clinical outcomes were mental and physical QoL component measured using the 36-Item Short Form Health Survey (SF-36), but also pain, mood, and anxiety. Resting-state [18F]-fluorodeoxyglucose-PET metabolism was assessed at baseline, week 2, and week 11. Whole-brain voxel-based analysis was performed to study between-group metabolic changes over time.

Results: At week 11, patients of the active rTMS group had greater QoL improvement in the FIQ (p = 0.032) and in the mental component of the SF-36 (p = 0.019) than the sham stimulation group. No significant impact was found for other clinical outcomes. Compared with the sham stimulation group, patients of the active rTMS group presented an increase in right medial temporal metabolism between baseline and week 11 (p < 0.001), which was correlated with FIQ and mental component SF-36 concomitant changes (r = −0.38, p = 0.043; r = 0.51, p = 0.009, respectively). QoL improvement involved mainly affective, emotional, and social dimensions.

Conclusion: Our study shows that rTMS improves QoL of patients with fibromyalgia. This improvement is associated with a concomitant increase in right limbic metabolism, arguing for a neural substrate to the impact of rTMS on emotional dimensions involved in QoL.

Classification of evidence: This study provides Class II evidence that rTMS compared with sham rTMS improves QoL in patients with fibromyalgia.

GLOSSARY

BDI=
Beck Depression Inventory;
DSM-IV-R=
Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised;
FDG=
[18F]-fluorodeoxyglucose;
FIQ=
Fibromyalgia Impact Questionnaire;
MCS=
Mental Composite Score;
PCS=
Physical Composite Score;
QoL=
quality of life;
rTMS=
repetitive transcranial magnetic stimulation;
SF-36=
36-Item Short Form Health Survey

Footnotes

  • ↵* These authors contributed equally to this work.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received March 1, 2013.
  • Accepted in final form January 6, 2014.
  • © 2014 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Response of the authors
    • Eric Guedj, Prof., APHMeric.guedj@ap-hm.fr
    • Laurent Boyer, Marseille, France
    Submitted July 08, 2014
  • rTMS for fibromyalgia: protocol departures and interpretive issues
    • Luke Parkitny, Postdoctoral Research Fellow, Stanford University, Department of Anesthesialukeparkitny@interleuk.in
    • Luke Parkitny, Palo Alto, CA; Neil Edward O'Connell, London, UK.
    Submitted June 27, 2014
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