Theta burst and quadripulse repetitive Transcranial Magnetic Stimulation (rTMS) may have therapeutic potentials in migraine prevention: a proof-of-concept study in healthy volunteers and a pilot-trial in migraine patients.

Background
Migraine is characterized interictally by a lack of habituation of evoked responses, possibly due to a decreased preactivation level of sensory cortices. During an attack and in chronic migraine, habituation normalizes (1). Theta-burst (TB) (2) and quadripulse (QP) rTMS (3) can durably modify the cortex activation level and thus have therapeutic potentials in migraine prevention. Consequently, we studied the effects of TB and QP rTMS on visual evoked potentials (VEP) in healthy volunteers and performed a pilot-trial of QP rTMS in chronic migraine.

Methods
Excitatory and inhibitory TB and QP protocols (respectively TBE, TBI, QPE, QPI) were applied on the visual cortex of healthy volunteers (HV; n=49) at a 80% output of phosphene threshold or 90% of motor threshold. Pattern-reversal VEP were recorded in 6 sequential blocks before (T0), immediately (T1) and 3 hours (T2) after rTMS. We measured changes in 1st block amplitudes and in habituation slopes for N1P1 and P1N2 components as outcome measures. Guided by the results in HV, we performed a pilot trial of the QI protocol over the visual cortex in patients suffering from chronic migraine (CM).

Results
In the TBE group (n=13), 1st block P1N2 amplitude and habituation of N1P1 increased after the stimulation, with partial recovery at T2. Interestingly, habituation of P1N2 increased with time after the stimulation and was more pronounced at T2 compared to T0 or T1. In the QPI group (n=11), we found a reduction of 1st block amplitude in T1, which increased at T2. Twice weekly occipital QPI rTMS decreased headache days in the majority of CM patients included, whether or not they also had medication overuse.

Conclusions
Excitatory TB and inhibitory QP rTMS are thus able to modify durably and differentially cortical activation level and VEP habituation. The former could be potentially useful in the preventive treatment of episodic migraine, a trial we are currently initiating. Inhibitory QP rTMS, on the contrary, may have have a beneficial effect in chronic migraine, a hypothesis our pilot-trial is supporting.