Author: Klein MM1, Treister R, Raij T, Pascual-Leone A, Park L, Nurmikko T, Lenz F, Lefaucheur JP, Lang M, Hallett M, Fox M, Cudkowicz M, Costello A, Carr DB, Ayache SS, Oaklander AL.
Affiliation: 1aDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA bAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA cBerenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA dU.S. Food and Drug Administration, Center for Devices and Radiological Health, Division of Neurological and Physical Medicine Devices, Office of Device Evaluation, Bethesda, MD eU.S. National Institutes of Health, National Institute on Mental Health, Bethesda, MD fNeuroscience Research Centre, The Walton Centre NHS Foundation Trust, United Kingdom gDepartment of Neurosurgery, Johns Hopkins Medical Institutions, Baltimore, MD hExplorations Fonctionnelles, Hôpital Henri Mondor, Faculté de Médecine de Créteil, Université Paris Est Créteil, Créteil, France iHuman Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD jDepartments of Anesthesiology, Medicine, and Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA kDepartment of Pathology (Neuropathology), Massachusetts General Hospital, Boston, MA.
Date published: 2015 Apr 25
Other: Word Count: 259
Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of non-invasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multi-day repetitive TMS (rTMS) can induce long-lasting, potentially therapeutic, brain plasticity. Nearby ferromagnetic or electronic implants are contraindications, and adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. TMS devices are marketed for depression and migraine in the U.S. and for multiple indications elsewhere. Although multiple studies report that high-frequency rTMS of motor cortex reduces neuropathic pain, their quality has been insufficient to support FDA application. Harvard's Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters, and improve strategies for sham and double-blinding. Subjects should have common, well-characterized pain conditions amenable to motor-cortex rTMS and samples should be adequately powered. They recommended standardized assessment tools (e.g., NIH's PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (e.g. IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion/exclusion criteria, baseline and post-treatment means and standard deviations, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months post-initiation with pre-specified statistical analyses. Multi-group collaborations or registry studies may be needed for pivotal trials.