Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines

Simone Rossi¹, Andrea Antal², Sven Bestmann³, Marom Bikson⁴, Carmen Brewer⁵, Jürgen Brockmöller⁶, Linda L Carpenter⁷, Massimo Cincotta⁸, Robert Chen⁹, Jeff D Daskalakis¹⁰, Vincenzo Di Lazzaro¹¹, Michael D Fox¹², Mark S George¹³, Donald Gilbert¹⁴, Vasilios K Kimiskidis¹⁵, Giacomo Koch¹⁶, Risto J Ilmoniemi¹⁷, Jean Pascal Lefaucheur¹⁸, Letizia Leocani¹⁹, Sarah H Lisanby²⁰, Carlo Miniussi²¹, Frank Padberg²², Alvaro Pascual-Leone²³, Walter Paulus²⁴, Angel V Peterchev²⁵, Angelo Quartarone²⁶, Alexander Rotenberg²⁷, John Rothwell³, Paolo M Rossini²⁸, Emiliano Santarnecchi²⁹, Mouhsin M Shafi²⁹, Hartwig R Siebner³⁰, Yoshikatzu Ugawa³¹, Eric M Wassermann³², Abraham Zangen³³, Ulf Ziemann³⁴, Mark Hallett³⁵; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020

Affiliations

¹ Department of Scienze Mediche, Chirurgiche e Neuroscienze, Unit of Neurology and Clinical Neurophysiology, Brain Investigation and Neuromodulation Lab (SI-BIN Lab), University of Siena, Italy. Electronic address: Simone.rossi@unisi.it.
² Department of Clinical Neurophysiology, University Medical Center, Georg-August University of Goettingen, Germany; Institue of Medical Psychology, Otto-Guericke University Magdeburg, Germany.
³ Department of Movement and Clinical Neurosciences, UCL Queen Square Institute of Neurology, London, UK and Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, London, UK.
⁴ Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
⁵ National Institute on Deafness and Other Communication Disorders, National Institutes of Health (NIH), Bethesda, MD, USA.
⁶ Department of Clinical Pharmacology, University Medical Center, Georg-August University of Goettingen, Germany.
⁷ Butler Hospital, Brown University Department of Psychiatry and Human Behavior, Providence, RI, USA.
⁸ Unit of Neurology of Florence - Central Tuscany Local Health Authority, Florence, Italy.
⁹ Krembil Research Institute and Division of Neurology, Department of Medicine, University of Toronto, Canada.
¹⁰ Center for Addiction and Mental Health (CAMH), University of Toronto, Canada.
¹¹ Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico, Roma, Italy.
¹² Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
¹³ Medical University of South Carolina, Charleston, SC, USA.
¹⁴ Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹⁵ Laboratory of Clinical Neurophysiology, Aristotle University of Thessaloniki, AHEPA University Hospital, Greece.
¹⁶ IRCCS Santa Lucia, Roma, Italy.
¹⁷ Department of Neuroscience and Biomedical Engineering (NBE), Aalto University School of Science, Aalto, Finland.
¹⁸ EA 4391, ENT Team, Faculty of Medicine, Paris Est Creteil University (UPEC), Créteil, France; Clinical Neurophysiology Unit, Henri Mondor Hospital, Assistance Publique Hôpitaux de Paris, (APHP), Créteil, France.
¹⁹ Department of Neurology, Institute of Experimental Neurology (INSPE), IRCCS-San Raffaele Hospital, Vita-Salute San Raffaele University, Milano, Italy.
²⁰ National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
²¹ Center for Mind/Brain Sciences - CIMeC, University of Trento, Rovereto, Italy.
²² Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
²³ Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Guttmann Brain Health Institut, Institut Guttmann, Universitat Autonoma Barcelona, Spain.
²⁴ Department of Clinical Neurophysiology, University Medical Center, Georg-August University of Goettingen, Germany.
²⁵ Departments of Psychiatry & Behavioral Sciences, Biomedical Engineering, Electrical & Computer Engineering, and Neurosurgery, Duke University, Durham, NC, USA.
²⁶ Department of Biomedical, Dental Sciences and Morphological and Functional Images, University of Messina, Messina, Italy.
²⁷ Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
²⁸ Department of Neuroscience and Rehabilitation, IRCCS San Raffaele-Pisana, Roma, Italy.
²⁹ Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA.
³⁰ Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark; Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; Institute for Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
³¹ Department of Human Neurophysiology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
³² National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
³³ Zlotowski Center of Neuroscience, Ben Gurion University, Beer Sheva, Israel.
³⁴ Department of Neurology & Stroke, and Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany.
³⁵ Human Motor Control Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, USA. Electronic address: hallettm@ninds.nih.gov.

PMID: 33243615
PMCID: PMC9094636
DOI: 10.1016/j.clinph.2020.10.003

Review

Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines

Simone Rossi et al. Clin Neurophysiol. 2021 Jan.

. 2021 Jan;132(1):269-306.

doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.

Authors

Affiliations

¹ Department of Scienze Mediche, Chirurgiche e Neuroscienze, Unit of Neurology and Clinical Neurophysiology, Brain Investigation and Neuromodulation Lab (SI-BIN Lab), University of Siena, Italy. Electronic address: Simone.rossi@unisi.it.
² Department of Clinical Neurophysiology, University Medical Center, Georg-August University of Goettingen, Germany; Institue of Medical Psychology, Otto-Guericke University Magdeburg, Germany.
³ Department of Movement and Clinical Neurosciences, UCL Queen Square Institute of Neurology, London, UK and Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, London, UK.
⁴ Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
⁵ National Institute on Deafness and Other Communication Disorders, National Institutes of Health (NIH), Bethesda, MD, USA.
⁶ Department of Clinical Pharmacology, University Medical Center, Georg-August University of Goettingen, Germany.
⁷ Butler Hospital, Brown University Department of Psychiatry and Human Behavior, Providence, RI, USA.
⁸ Unit of Neurology of Florence - Central Tuscany Local Health Authority, Florence, Italy.
⁹ Krembil Research Institute and Division of Neurology, Department of Medicine, University of Toronto, Canada.
¹⁰ Center for Addiction and Mental Health (CAMH), University of Toronto, Canada.
¹¹ Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico, Roma, Italy.
¹² Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
¹³ Medical University of South Carolina, Charleston, SC, USA.
¹⁴ Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹⁵ Laboratory of Clinical Neurophysiology, Aristotle University of Thessaloniki, AHEPA University Hospital, Greece.
¹⁶ IRCCS Santa Lucia, Roma, Italy.
¹⁷ Department of Neuroscience and Biomedical Engineering (NBE), Aalto University School of Science, Aalto, Finland.
¹⁸ EA 4391, ENT Team, Faculty of Medicine, Paris Est Creteil University (UPEC), Créteil, France; Clinical Neurophysiology Unit, Henri Mondor Hospital, Assistance Publique Hôpitaux de Paris, (APHP), Créteil, France.
¹⁹ Department of Neurology, Institute of Experimental Neurology (INSPE), IRCCS-San Raffaele Hospital, Vita-Salute San Raffaele University, Milano, Italy.
²⁰ National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
²¹ Center for Mind/Brain Sciences - CIMeC, University of Trento, Rovereto, Italy.
²² Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
²³ Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Guttmann Brain Health Institut, Institut Guttmann, Universitat Autonoma Barcelona, Spain.
²⁴ Department of Clinical Neurophysiology, University Medical Center, Georg-August University of Goettingen, Germany.
²⁵ Departments of Psychiatry & Behavioral Sciences, Biomedical Engineering, Electrical & Computer Engineering, and Neurosurgery, Duke University, Durham, NC, USA.
²⁶ Department of Biomedical, Dental Sciences and Morphological and Functional Images, University of Messina, Messina, Italy.
²⁷ Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
²⁸ Department of Neuroscience and Rehabilitation, IRCCS San Raffaele-Pisana, Roma, Italy.
²⁹ Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA.
³⁰ Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark; Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; Institute for Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
³¹ Department of Human Neurophysiology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
³² National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
³³ Zlotowski Center of Neuroscience, Ben Gurion University, Beer Sheva, Israel.
³⁴ Department of Neurology & Stroke, and Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany.
³⁵ Human Motor Control Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, USA. Electronic address: hallettm@ninds.nih.gov.

PMID: 33243615
PMCID: PMC9094636
DOI: 10.1016/j.clinph.2020.10.003

Abstract

This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings (Rossi et al., 2009). Therefore, only emerging and new issues are covered in detail, leaving still valid the 2009 recommendations regarding the description of conventional or patterned TMS protocols, the screening of subjects/patients, the need of neurophysiological monitoring for new protocols, the utilization of reference thresholds of stimulation, the managing of seizures and the list of minor side effects. New issues discussed in detail from the meeting up to April 2020 are safety issues of recently developed stimulation devices and pulse configurations; duties and responsibility of device makers; novel scenarios of TMS applications such as in the neuroimaging context or imaging-guided and robot-guided TMS; TMS interleaved with transcranial electrical stimulation; safety during paired associative stimulation interventions; and risks of using TMS to induce therapeutic seizures (magnetic seizure therapy). An update on the possible induction of seizures, theoretically the most serious risk of TMS, is provided. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. Finally, new operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.

Keywords: Neurology; Neuromodulation; Psychiatry; QPS; Safety; TBS; TMS; rTMS.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Comment in

Updated safety standards for TMS: A must-read in brain stimulation.
Krieg SM, Gerloff C. Krieg SM, et al. Clin Neurophysiol. 2021 Jan;132(1):214-215. doi: 10.1016/j.clinph.2020.11.015. Epub 2020 Dec 2. Clin Neurophysiol. 2021. PMID: 33317994 No abstract available.

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Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines

Affiliations

Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous