The management of patients with asymptomatic carotid artery stenosis is one of the most controversial topics in the cerebrovascular disease literature. The results of the Asymptomatic Carotid Atherosclerosis Study (ACAS)¹ showed a reduction of the risk of stroke in patients undergoing endarterectomy compared with those treated medically. However, the actual benefit of carotid endarterectomy in asymptomatic patients, in terms of prevention of annual disabling stroke vs the risk of angiography and surgery, may not justify its introduction into routine clinical practice.² The benefit of surgery could be significantly increased in a subgroup of patients with a high predisposition to develop cerebrovascular events. However, defining a high-risk patient with severe asymptomatic carotid stenosis remains difficult. Selecting patients for surgery based on their age, progression of lesion, morphologic characteristics, and degree of carotid stenosis and concomitant risk factors is apparently acceptable,³(pp1506-1507) but to date, there is no evidence of any factor that may influence the prognosis of patients with asymptomatic carotid stenosis.⁴

Repetitive transcranial magnetic stimulation (rTMS) of human motor cortex can produce long-lasting changes in the excitability of excitatory and inhibitory neuronal networks. The effects of rTMS depend critically on stimulus frequency. The aim of our present study was to compare the effects of different rTMS protocols. We compared the aftereffects of 6 different rTMS protocols [paired associative stimulation at interstimulus intervals of 25 (PAS₂₅) and 10 ms (PAS₁₀); theta burst stimulation delivered as continuous (cTBS) or intermittent delivery pattern (iTBS); 1- and 5-Hz rTMS] on the excitability of stimulated and contralateral motor cortex in 10 healthy subjects. A pronounced increase of cortical excitability, evaluated by measuring the amplitude of motor evoked potentials (MEPs), was produced by iTBS (+56%) and PAS₂₅ (+45%). Five-hertz rTMS did not produce a significant increase of MEPs. A pronounced decrease of cortical excitability was produced by PAS₁₀ (−31%), cTBS (−29%), and 1-Hz rTMS (−20%). Short-interval intracortical inhibition was suppressed by PAS₁₀. Cortical silent period duration was increased by 1-Hz stimulation. No significant effect was observed in the contralateral hemisphere. Head-to-head comparison of the different protocols enabled us to identify the most effective paradigms for modulating the excitatory and inhibitory circuits activated by TMS.