Table 1:

Clinical diagnostic utility of TMS in neurological diseases: Consensus opinion

Disease	Characteristic TMS findings	Potential Clinical Utility	Clinical aspects that may affect interpretation
Amyotrophic lateral sclerosis (ALS)	SICI ↓ SICF ↑ ICF ↑ ⟷ RMT⟷ ↓ ↑ MEP/CMAP amplitude↑ or ↓* CSP duration ↓ CMCT ↑	-SICI is a potential diagnostic biomarker in differentiating ALS from mimicking disorders -Useful in differentiating ALS from other neuromuscular mimicking disorders.	-Riluzole therapy may transiently increase SICI -Changes in cortical excitability according to disease progression
Parkinson’s disease (PD)	SICI ↓ SICF ↑ ICF ⟷ ↓ RMT ⟷ ↓ (PD subtype) I/O curve steeper at resting state SAI ↓ (disease progression) CSP duration ⟷ ↓ ISP duration ⟷ ↓ (PD subtype) Normal SICI on I3 waves	-SICI and SICF might be used as biomarkers of disease progression -SAI might be used to predict PD dementia and falls -Limited diagnostic utility	- ON or OFF-drug condition -Tremor-dominant or akinetic-rigid subtype --Disease duration or severity of symptoms
Parkinsonism (MSA, PSP)	CMCT ↑ (MSA, PSP) SICF⟷	-Prolonged CMCT might be used to differentiate MSA/PSP from PD --Limited diagnostic utility	-Parkinsonism or cerebellar ataxia predominant MSA subtypes
Lewy Body Disease	SICI ↓ ICF ↓ SAI ↓	-SAI may help differentiate LBD (SAI ↓) from Parkinsonian syndrome and FTD (SAI⟷) --Limited diagnostic utility
Huntington’s disease (HD)	SAI ↓ SICI ⟷ ↓ CSP duration ↑ (early stage)	-Limited diagnostic utility	-Different charges according to disease stage -HD patients are not able to be fully relaxed
Dystonia	SICI ↓ LICI ↓ CSP ↓ IHI ↓ (with mirror movements) Surround inhibition ↓	-Limited diagnostic utility	-Test on affected side or unaffected side -Homogeneity of dystonia presentation -No single parameter can be used to prove organic dystonia
Tics and Tourette’s syndrome	SICI ↓ CSP duration ↓	-Limited diagnostic utility	-Timing of assessment (before tics occur or when tics are suppressed)
Cervical spondylitic myelopathy	CMCT ↑ MEP amplitude ↓	-Prolonged CMCT is a major and objective criterion for the diagnosis of pyramidal tract lesion in the context of myelopathy	MEP of APB muscle is most sensitive
Spinal cord injury	RMT ↑ CMCT ↑ MEP amplitude ↓	-Prolonged CMCT is a major and objective criterion for the diagnosis of pyramidal tract lesion in the context of myelopathy	-No single measurement can predict gait and balance outcome after SCI
Alzheimer’s disease (AD)	RMT ↓ AMT ↓ CSP duration ⟷ SICI ⟷ ICF ⟷ LICI ⟷ SAI ↓	-Potential diagnostic utility -SICI-ICF/SAI ratio may help differentiate AD from FTD -SICI-ICF may help differentiate AD from LBD	-SAI may be increased by acetylcholinesterase inhibitors
Mild cognitive impairment due to Alzheimer’s disease	RMT ↓ SICI ⟷ ICF ⟷ LICI ⟷ SAI ↓	-Potential diagnostic utility -SICI-ICF/SAI ratio may help differentiate MCI-AD from MCI-FTD -SICI-ICF may help differentiate MCI-AD from MCI-LBD	-Interpretation may be hampered by the heterogeneity of MCI and the paucity of studies performed in patients with a biomarker supported diagnosis of MCI
Frontotemporal dementia (FTD)	RMT ⟷ CMCT ↑ SICI ↓ ICF ↓ SAI ⟷	-Potential diagnostic utility -SICI-ICF/SAI ratio may help differentiate FTD from AD -SAI may help differentiate FTD from LBD
Epilepsy	RMT ⟷ CSP duration ↑ SICI ↓ ICF ⟷ LICI ↓	↓ SICI and LICI may be useful in discriminating seizure from syncope Follow up clinical condition	-Antiepileptic medications cause ↑RMT, SICI & LICI
Myoclonus epilepsy	SICI ↓ SICI ↓ even on I3 waves RMT ↓	-Limited diagnostic utility	Anti-epileptic drugs affect the results
Migraine without aura	SICI ↓ (at ISI 4ms) SICF ⟷ SICF ↑ (suprathreshold conditioning stimulus; weak test stimulus) SICF ↓ (preictal phase) RMT⟷ ↓ ↑ LICI ⟷ (up to 120 ms ISI) LICI ↓ (150% test stimulus) LICI ↓ (250 ms ISI) SAI ⟷ SAI ↓ (preictal phase) CSP ⟷ (interictal) CSP duration ↓ (interictal, women)	-TMS changes vary according to the phase of migraine cycle -Limited diagnostic utility -	-RMT/PT, and SAI change with proximity of migraine attack -ICF changes with conditioning/test stimulus intensity and proximity of migraine attack -CSP duration decreases with focused sustained attention and sleep restriction
Migraine with aura	SICI ↓ SICF ↑ RMT⟷ Steeper I/O curve at rest CSP duration ↓ LICI 250ms ↑ CBI↓ SAI ↓ (when disease progressed)	- PT might be used to discriminate between transient ischemic attacks and aura without headache	- 1Hz rTMS reduces PT - deficits of cortical inhibition are related more to aura rather than headache mechanisms - CSP shortens also in facial muscles - topiramate modulates occipital cortex excitability
Chronic migraines	RMT↓ SICI absent	-Limited diagnostic utility -Potential biomarker of treatment effects	Botulinum toxin therapy partially normalizes SICI after 12-months treatment
Episodic cluster headaches	SICI ↓ (ictal) SICI ↓ (allodynia) SICF ↑ (preictal and ictal) SICF ↑ (allodynia) RMT ⟷ CSP duration ⟷	-Limited utility	Changes in paired-pulse TMS variables are ipsilateral to the pain side; inhibitory changes are ictal; facilitatory changes are both interictal and ictal.
Medication-overuse headache	CSP duration ⟷ (NSAIDs alone or in combination) CSP duration ↓ (triptans)	-Limited utility	- CSP changes reveal medication-induced neural adaptation in motor cortex
Multiple Sclerosis	CMCT ↑ TST ↓ MEP amplitude ↓ (or desynchronized) TST-MEP amplitude ↓	-CMCT increase or MEP amplitude decrease after fatiguing exercise -SICI ↓ -SICF ↓ -SAI ↓ -CSP duration ↑ -ISP ↑ -Limited diagnostic utility -Potential prognostic utility	-TMS measures may be affected by multiple sclerosis type (RRMS vs. SPMS/PPMS), and treatment (corticosteroids and immunomodulatory drugs) and the presence of fatigue
Neuropathic pain	SICI ↓ (contralateral to pain side)	-SICI might be a biomarker to select candidates for analgesic cortical neuromodulation -Limited diagnostic utility	-Defective SICI can be restored by therapeutic intervention producing analgesic effects
Stroke	RMT ↑ MEP latency ↑ MEP amplitude ↓ Shallower I/O curves SICI ↓	-Potential prognostic utility: Absent upper limb MEPs predicts worse motor recovery and outcomes	-Depending on post-stroke phase (acute, sub-acute, or chronic)
Cerebellar disease	CBI ↓	-Differentiate cerebellar ataxia due to cerebellar or cerebellar efferent pathways dysfunction from that due to cerebellar afferent pathways dysfunction, or from non-cerebellar ataxia	-CBI changes may be seen for compensation of basal ganglia dysfunction (movement disorders)
Facial nerve disorders	MEP ↓ or absent Prolonged transosseal conduction time	-May localize facial nerve dysfunction -Prognostication (if MEP present better prognosis) -Limited diagnostic utility
Brain Tumors	RMT ↑ or ↓ (tumor hemisphere compared to contralateral hemisphere) MEP latency ↑ MEP amplitude ↓	-Preoperative brain mapping -Seed regions for function-based tractography -Preoperative risk stratification -Postoperative transcallosal disinhibition -Limited diagnostic utility	-Edema -Patient cooperation
Functional neurological disorders (paretic disorders)	RMT, SICI, ICF ⟷ RMT, SICI ↑ MEP duration with voluntary contraction ⟷ MEP amplitude with movement imagination ↓	-Change in MEP amplitude with movement imagination -Elemental measures in functional dystonia are similar to other types of dystonia - Limited clinical utility
Dystonic functional neurological disorders	SICI ↓ LICI ↓ CSP duration ↓ Forearm reciprocal inhibition ↓ Cutaneous silent period ↑	- Limited clinical utility in differentiating functional from organic dystonia	Neurophysiological measures in functional dystonia are similar to other types of dystonia.

APB: Abductor pollicis brevis, CBI: Cerebellar inhibition of the motor cortex, CMCT: Central motor conduction time, CSP: Cortical silent period, GABA: Gamma-aminobutyric acid, LBD: Lewy body disease, IHI: Interhemispheric inhibition, I/O curve: Input-output curve, ISP: Ipsilateral silent period, LICI: Long-interval intracortical inhibition, MEP: Motor evoked potential, MSA: Multiple system atrophy, PPMS: Primary progressive multiple sclerosis, PSP: Progressive supranuclear palsy, RMT: Resting motor threshold, PT phosphene threshold; NSAID (nonsteroidal anti-inflammatory drugs): RRMS: Relapsing-remitting multiple sclerosis, SAI: Short latency afferent inhibition, SCI: Spinal cord injury, SICF: Short-interval intracortical facilitation, SICI: Short-interval intracortical inhibition, SPMS: Secondary progressive multiple sclerosis, TST: Triple-stimulation technique.

^⟷,no change or normal

^↓,reduced

^↑,increased.

^*,The MEP amplitude, expressed as a percentage of the compound muscle action potential response (MEP/CMAP), is increased in strong limbs without marked UMN signs, and also in the early stages of ALS. In most ALS patients, the MEP amplitude patients is decreased. It should be stressed that a Delphi consensus process was not possible.