La Neuromodulazione non invasiva nel trattamento dell’emicrania: stato dell’arte e prospettive future Dr. Tommaso Bocci ASST Santi Paolo e Carlo, Dipartimento di Scienze della Salute Università di Milano

L’elettromagnetismo nella storia della medicina

tDCS or rTMS? This is the question … - polarity-dependent effects (anodal tDCS decreases GABA, cathodal tDCS reduces Glu; Stagg et al., 2009); Non synaptic short-term effects, by modulating the intrinsic neuronal «firing rate»; tDCS interferes with superficial cortical layers; rTMS - frequency-dependent effects (> 5 Hz excitatory rTMS, < 1 Hz inhibitory rTMS); «trans-synaptic» activation of Betz cells, by modulating the activity of excitatory interneurons; deeper action than tDCS;

NIBS for the treatment of migraine “Low or very low quality of evidence suggests that our primary outcome evaluation failed to find support forthe superiority of NIBS over sham treatment. Although, subgroup analysis reveals that tDCS have moderate to high effects and could be a promising non pharmacological alternative to pain control, mainly for painkiller intake reduction”

NIBS for the treatment of migraine: state of the art “rTMS is most promising with moderate evidence that it contributes to reductions in headache frequency, duration, intensity, abortive medication use, depression, and functional impairment. However, only few studies reported changes greater than sham treatment.“

NIBS for the treatment of migraine: A position statement “ … any neurostimulation device should only be used in patients with medically intractable syndromes from tertiary headache centers either as part of a valid study or have shown to be effective in such controlled studies withan acceptable side effect profile ... “

NIBS for the treatment of migraine: which targets? Cathodal tDCS / LF rTMS over Primary Visual Area (V1: Antal et al., 2011; Rocha et al., 2015; Wickmann et al., 2015) Cathodal tDCS / LF rTMS over the Dorsolateral Prefrontal Cortex (DLPFC) Anodal tDCS / HF rTMS over Primary Motor Area (M1: Przeklasa-Muszyńska et al., 2017)

tDCS for the treatment of migraine Antal et al., Cephalalgia 2011 (N = 26) Rocha et al., J Neurol Sci 2015 (N = 23) NO CHANGE BETWEEN ACTIVE AND SHAM tDCS!

NIBS for the treatment of migraine: potential biases Differences in sham protocols Variability of electrodes’ position (especially, the return electrode for tDCS) Small series

A key role for metaplasticity in migraine? Brighina e collaboratori hanno successivamente dimostrato un’alterazione dei fenomeni inibitori intracorticali anche a livello delle aree visive extrastriate; in particolare, PT is paradoxically decreased after 1 Hz rTMS in migraineurs Anodal tDCS, followed by high-frequency rTMS, induces a persistent facilitation of MEPs in patients compared to controls 11

Evidence for metaplasticity in the intact human visual cortex

New frontiers Kangoroo Island, AUS, 35°50′S 137°15′E