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See detailAnodal transcranial direct stimulation (tDCS) targeting the anterior cingulate gyrus for the preventive treatment of chronic cluster headache: a proof of concept trial.
MAGIS, Delphine ULiege; D'Ostilio, Kevin ULiege; Cosseddu, Anna et al

Poster (2016, April)

Background There is a need for better treatments in chronic cluster headache (CCH). In responders to percutaneous occipital nerve stimulation, the subgenual anterior cingulate gyrus (sACG) was found ... [more ▼]

Background There is a need for better treatments in chronic cluster headache (CCH). In responders to percutaneous occipital nerve stimulation, the subgenual anterior cingulate gyrus (sACG) was found hypermetabolic (Magis et al. 2011). We reasoned that activation of this area by transcranial neurostimulation could be effective in CCH. Aim To explore the preventive effect of anodal (i.e. activating) transcranial direct current stimulation (tDCS) targeting the anterior cingulate gyrus in CCH patients. Method & subjects Difficult-to-treat CCH patients with a stable preventive drug regimen applied tDCS (2mA) interictally in 20-minute daily sessions for 4 weeks with the anode positioned over the forehead (FpZ), the cathode over the C7 spinous process. Therapeutic effects were monitored with paper diaries. Results Nineteen patients were enrolled up to now. In 13 patients who completed the trial, mean weekly attack frequency decreased by 38% after 4 weeks of daily stimulation (W-test: p = 0.002). The 50% responder rate was 54%. Patients (n=12) reported an improvement in headache impact, as shown by 5-point decrease in the mean HIT-6 score (from 67 to 62, p = 0.02). In 10 patients who were followed up after the treatment period, the benefit remained stable up to 4 weeks after the last stimulation. The first 3 enrolled patients had superficial skin burns under the adhesive cathode electrode. Sponge electrodes were therefore used in all subsequent patients without any adverse effect. Conclusion Anodal tDCS targeting the anterior cingulate gyrus seems promising for the preventive treatment of chronic cluster headache as suggested by this ongoing proof-of-concept trial. Use of adhesive electrodes is not recommended. [less ▲]

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See detailNon-invasive vagus nerve stimulation with the gammaCore® in healthy subjects: is there electrophysiological evidence for activation of vagal afferents ?
Schoenen, Jean ULiege; NONIS, Romain ULiege; D'Ostilio, Kevin ULiege et al

Poster (2016, April)

Abstract: Background Non-invasive vagus nerve stimulation (nVNS) with the gammaCore® improves migraine and cluster headache. Animal experiments suggest that nVNS acts via stimulation of vagal afferents ... [more ▼]

Abstract: Background Non-invasive vagus nerve stimulation (nVNS) with the gammaCore® improves migraine and cluster headache. Animal experiments suggest that nVNS acts via stimulation of vagal afferents, but proof in humans is lacking. Vagal somatosensory evoked potentials (vSEP) are identified after invasive VNS or transcutaneous stimulation of auricular vagal branches, but late components could be muscle artifacts. Objective To search in healthy volunteers for reliable vSEP during nVNS with the gammaCore® Methods In 12 healthy subjects (7males) evoked potentials were recorded at A1/A2 (ref Cz) and C3/C4 (ref F3/F4) during 2-minute stimulation over left/right cervical vagus nerve with the gammaCore® (25Hz, 6-24V) and during stimulation over the inner tragus with a monopolar stimulator (2Hz, 50 stimuli, mean intensity 8mA). Results We identified 3 reproducible peaks P1, N1, P2 in 10 patients on the side of the gammaCore® stimulation at mean latencies of 2.05ms, 5.20ms and 9.13ms. P1-N1 amplitude increased significantly (p<0.01) with increasing voltage from 0.04μV to 0.52μV (C3/C4) and from 0.13µV to 2.04μV (A1/A2) respectively at 10V and 30V. Inner tragus stimulation elicited P1, N1, P2 peaks with shorter mean latencies (2.21ms, 3.72ms, 5.71ms) and a mean P1-N1 amplitude (A1/A2) of 5.0µV. When the gammaCore® was placed over the sternocleidomastoid muscle, there were no reproducible evoked potentials. Conclusion Non-invasive transcutaneous stimulation of the cervical vagus nerve with the gammaCore® elicits evoked potentials similar to those found with implanted electrodes or stimulation of Arnold’s nerve in the outer ear. The gammaCore®-evoked potentials increase in amplitude with stimulation intensity and disappear when the stimulator is positioned over neck muscles, suggesting that they are not muscle artifacts. Their short latency is compatible with their generation at the level of the foramen jugulare. The therapeutic effects reported with the gammaCore® in primary headaches can thus be mediated by genuine activation of vagus nerve afferents. [less ▲]

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See detailMETABOLIC CHANGES IN THE MIGRAINE BRAIN IN RELATION TO AGEING AND DISEASE LOAD
D'Ostilio, Kevin ULiege; Lisicki Martinez, Marco ULiege; NONIS, Romain ULiege et al

in Cephalalgia (2016), 36(1S), 59

Introduction: Migraine prevalence tends to decrease with advancing age. Morphological and functional brain changes occuring in migraine could be secondary to repeated attacks and/or to abnormal sensory ... [more ▼]

Introduction: Migraine prevalence tends to decrease with advancing age. Morphological and functional brain changes occuring in migraine could be secondary to repeated attacks and/or to abnormal sensory processing. In normal ageing, brain modifications could traduce a progressive refinement to cope with the environment, associated with a reduction in the complexity of brain connections. We hypothesized that metabolism in various brain regions might be differentially modified by age in migraine patients. Materials and methods: Forty-one subjects underwent a FDG-PET scan: 21 patients with interictal episodic migraine without aura (MO, age range: 20–63 years, 5M) and 20 healthy controls (HV, 21–59 years, 5 M). Results: In MO vs. HV, the overall FDG uptake was reduced in the left visual cortex, left medial frontal gyrus and bilaterally in the insula, somatosensory and motor cortices. Metabolisms of the posterior thalamus, brainstem including the periaqueductal gray (PAG), visual cortex, and (para)hippocampus, strongly increased with age in MO patients but not in HV. Disease duration positively correlated with PAG, (para)hippocampus and rostral anterior cingulate cortex (rACC) metabolisms in MO. Conclusion: Migraine patients, compared to HV, have a decreased resting metabolism in several areas belonging to the ‘‘pain/salience matrix’’, which is in line with previous neuroimaging studies. Metabolism of the rACC is specifically related to disease load whereas metabolism of other sensory processing regions is more affected by age. Whether these functional changes are due to repeated stereotyped attack-related stimulations and to a learning process with complexity reduction of neuronal connections and/or compensatory age-related hyperactivity, remains to be demonstrated [less ▲]

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See detailTRANSCUTANEOUS OCCIPITAL NERVE STIMULATION AND TRANSCRANIAL DIRECT CURRENT STIMULATION IN CHRONIC MIGRAINE: A PILOT COMPARISON OF THERAPEUTIC AND ELECTROPHYSIOLOGICAL EFFECTS
MAGIS, Delphine ULiege; D'Ostilio, Kevin ULiege; Baschi et al

in Cephalalgia (2016), 36(1S), 31

Background: Management of chronic migraine (CM) is often challenging. There is a need for more effective and better-tolerated preventive therapies. Among non-invasive neurostimulation procedures ... [more ▼]

Background: Management of chronic migraine (CM) is often challenging. There is a need for more effective and better-tolerated preventive therapies. Among non-invasive neurostimulation procedures, transcutaneous occipital nerve stimulation (tONS) would act via central pain modulation, while transcranial direct current stimulation (tDCS) would modify cortical excitability that is abnormal in CM. Objectives: In this pilot trial we compared the clinical effects of tDCS and tONS in refractory CM and their ability to modify nociception and cortical responsiveness. Methods: Forty-three CM patients (17 with history of drug overuse) applied either 2mA tDCS during 2 months (N¼20, cathode over visual cortex, anode over left DLPFC), or tONS during 3 months (N¼23, Cefaly Kit ArnoldTM), both in daily 20 min-sessions. Visual evoked potentials (VEP), nociceptive blink reflexes (nBR) and quantitative sensory testing were recorded before and after treatment. Results: During the last stimulation month, total headache days decreased in both groups ( 16.4% for tDCS, 17% for tONS, p<0.05). Migraine days were reduced by 21.4% (p¼0.06) and 22% (p<0.05) respectively, while 30% responder rates were 47% and 42%. Medication intake was significantly reduced after tONS ( 43%). There was no significant change of nBR in either group. VEP habituation reversed to an episodic migraine pattern, i.e. a deficit, after tONS but not after tDCS. Conclusion: tONS and inhibitory tDCS of the visual cortex are interesting non-invasive options for the treatment of CM, but these results have to be confirmed in a randomized controlled trial. tONS was able to induce recordable changes in visual cortex responsiveness [less ▲]

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