Review Article

Transcranial Magnetic Stimulation as a Potential Biomarker in Multiple Sclerosis: A Systematic Review with Recommendations for Future Research

Table 2

Key confounding variables evaluated in risk of bias assessment [40, 5461, 78, 113].

Key confounding variable description

(i) Age of participants.
(ii) Sex of participants.
(iii) Handedness of participants.
(iv) Participants prescribed medication.
(v) Use of CNS active drugs (e.g., anticonvulsants).
(vi) Presence of neurological/psychiatric disorders when studying healthy participants.
(vii) Any medical conditions.
(viii) History of specific repetitive motor activity.
(ix) Position and contact of EMG electrodes.
(x) Amount of relaxation/contraction of target muscles.
(xi) Prior motor activity of the muscle to be tested.
(xii) Level of relaxation of muscles other than those being tested.
(xiii) Coil type (i.e., size and geometry).
(xiv) Coil orientation.
(xv) Direction of induced current in the brain.
(xvi) Coil location and stability (with or without a neuronavigation system).
(xvii) Type of a stimulator used (e.g., brand).
(xviii) Stimulation intensity.
(xix) Pulse shape (i.e., monophasic or biphasic).
(xx) Determination of optimal hotspot.
(xxi) The time between MEP trials.
(xxii) Time between days of testing.
(xxiii) Participant attention (i.e., level of arousal) during testing.
(xxiv) Method for determining threshold (i.e., active/resting).
(xxv) Number of MEP measures made.
(xxvi) Paired-pulse only: intensity of test pulse.ǂ
(xxvii) Paired-pulse only: intensity of conditioning pulse.ǂ
(xxviii) Paired-pulse only: interstimulus interval.ǂ
(xxix) Method for determining MEP size during analysis.
(xxx) Size of unconditioned MEP.
(xxxi) Disease duration in MS.
(xxxii) Disease severity in MS.
(xxxiii) MS subtype (i.e., relapsing-remitting and progressive).
(xxxiv) Participants experiencing a relapse in MS.
(xxxv) Participants receiving corticosteroid treatment for MS.
(xxxvi) Participants undergoing immunomodulatory treatment for MS.
(xxxvii) Participants taking nonprescription or recreational drugs (e.g., caffeine and nicotine).
(xxxviii) Room or skin temperature reported.

CNS: central nervous system; EMG: electromyography; MEP: motor-evoked potential; MS: multiple sclerosis. Criterion (xxii) was disregarded because we did not examine longitudinal studies. ǂCriteria (xxvi), (xxvii), and (xxviii) were marked NA, when studies did not utilize paired-pulse TMS measures.