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See detailInvasive and Non-invasive Electrical Pericranial Nerve Stimulation for the Treatment of Chronic Primary Headaches
D'Ostilio, Kevin ULg; MAGIS, Delphine ULg

in Current Pain and Headache Reports (2016), 20

Chronic primary headaches are widespread disorders which cause significant quality of life and socioprofessional impairment. Available pharmacological treatments have often a limited efficacy and/or can ... [more ▼]

Chronic primary headaches are widespread disorders which cause significant quality of life and socioprofessional impairment. Available pharmacological treatments have often a limited efficacy and/or can generate unbearable side effects. Electrical nerve stimulation is a well known non-destructive method of pain modulation which has been recently applied to headache management. In this review, we summarise recent advances in invasive and non-invasive neurostimulation techniques targeting pericranial structures for the treatment of chronic primary headaches, chiefly migraine and cluster headache: occipital nerve, supraorbital nerve, vagus nerve, and sphenopalatineganglion stimulations. Invasive neurostimulation therapies have offered a new hope to drug-refractory headache sufferers but are not riskless and should be proposed only to chronic patients who failed to respond to most existing preventives. Non-invasive neurostimulation devices are user-friendly, safe and well tolerated and are thus taking an increasing place in the multidisciplinary therapeutical armamentarium of primary headaches. [less ▲]

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See detailVisual and auditory cortical evoked potentials in interictal episodic migraine: An audit on 624 patients from three centres.
Ambrosini, Anna; Kisialou, A; Coppola, Gianluca et al

in Cephalalgia : An International Journal of Headache (2016)

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See detailDistinct cerebral metabolic patterns related to high pain sensitivity in episodic or chronic migraine patients and healthy volunteers
D'Ostilio, Kevin ULg; Lisicki Martinez, Marco ULg; Schoenen, Jean ULg et al

in Frontiers in Aging Neuroscience (2016, July)

Introduction Allodynia, i.e. pain evoked by a non-painful stimulus, is prevalent in chronic pain and in migraine where it augments with disease severity and chronicity [1]. Central sensitization is ... [more ▼]

Introduction Allodynia, i.e. pain evoked by a non-painful stimulus, is prevalent in chronic pain and in migraine where it augments with disease severity and chronicity [1]. Central sensitization is thought to be the culprit [2]. It is not known, however, which central areas are involved. The aim of the present study was to evaluate whether brain metabolism in subjects that are more sensitive to pain is different between migraine patients and healthy controls. Subjects and methods Quantitative heat sensory testing on the forehead and 18FDG-PET were performed in 55 subjects: 20 healthy volunteers (HV, 21-59 years, 5M), 21 patients with episodic migraine in the interictal phase (MO, age range: 20-63 years, 5M) and 14 patients with chronic migraine (CM, age range: 22-62 years, 1M). The 3 cohorts were subdivided according to the median heat pain threshold into subgroups with low and high pain thresholds. PET results were compared between these subgroups in each cohort. Data analyses were restricted to areas of the pain/salience matrix. Results There was no significant difference in heat pain thresholds between HV (median: 43.7 °C), MO median: 44.2°C) and CM (median: 43.3°C) (p=0.64). In an SPM-ANOVA, a contrast modelling the potential gradual effect of increased differences in pain sensitivity in relation to disease severity showed significant metabolic changes in bilateral thalamus and midbrain (p < 0.001). Additional analyses revealed that hypometabolic areas in subgroups with a low heat pain threshold differed between HV (anterior cingulate and somatosensory cortices), MO (lower pons and somatosensory cortex) and CM (midbrain and thalamus) (Figure 1). Conclusion Overall migraine patients do not have reduced heat pain thresholds. However, hypometabolic areas related to high thermal pain sensitivity are strictly cortical in HV, but comprise the pons in episodic migraine and are restricted to midbrain and thalamus in chronic migraine. The distinct central correlates of heat pain sensitivity in migraine patients might therefore represent a biomarker of migraine and its chronification. Legend to figure Figure 1. Hypometabolic areas in low pain threshold subgroups in HV (green), MO (orange) and CM (red). p < 0.01 for display purpose. Résumé en Français: Titre: Métabolisme cérébral distinct en relation avec la sensibilité à la douleur entre sujets sains, migraine épisodique et migraine chronique. Les migraineux ont une sensibilité anormale à la douleur. Les mécanismes cérébraux en sont inconnus. Nous avons comparé le métabolisme cérébral chez des sujets sains et chez des migraineux épisodiques ou chroniques et correlé les résultats avec le seuil douloureux. Les aires cérébrales hypométaboliques liées à un seuil douloureux bas diffèrent entre groupes: régions corticales chez les sujets sains, aires corticales et sous-corticales dans la migraine épisodique, régions sous-corticales dans la migraine chronique .Le contrôle central de la douleur semble modifié distinctement dans les formes de migraine, ce qui pourrait en constituer un biomarqueur et avoir des implications thérapeutiques. [less ▲]

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See detailCerebral metabolism before and after external trigeminal nerve stimulation in episodic migraine
MAGIS, Delphine ULg; D'Ostilio, Kevin ULg; Thibaut, Aurore ULg et al

in Cephalalgia : An International Journal of Headache (2016)

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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 ULg; D'Ostilio, Kevin ULg; 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 ULg; NONIS, Romain ULg; D'Ostilio, Kevin ULg 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 detailNoninvasive neurostimulation methods for migraine therapy: The available evidence
SCHOENEN, Jean ULg; Baschi, Roberta; MAGIS, Delphine ULg et al

in Cephalalgia : An International Journal of Headache (2016)

Abstract Background: Migraine is one of the most disabling neurological disorders. The current pharmacological armamentarium is not satisfying for a large proportion of patients because the responder rate ... [more ▼]

Abstract Background: Migraine is one of the most disabling neurological disorders. The current pharmacological armamentarium is not satisfying for a large proportion of patients because the responder rate does not exceed 50% on average and the most effective drugs often induce intolerable side effects. During recent years, noninvasive central and peripheral neuromodulation methods have been explored for migraine treatment. Overview: A review of the available evidence suggests that noninvasive neuromodulation techniques could be beneficial for migraine patients. The transcranial stimulation methods allow modulating selectively cortical activity and can thus be curtailed to the patient’s pathophysiological profile, while transcutaneous stimulation of pericranial nerves likely modulates central pain control centers. Occipital single-pulse transcranial magnetic stimulation and transcutaneous supraorbital stimulation have the strongest evidence respectively for acute and preventive treatment. Transcranial direct current stimulation and repetitive magnetic stimulation are promising in pilot studies, but large sham-controlled trials are not yet available. Conclusions: The noninvasive neurostimulation methods are promising for migraine treatment and devoid of serious adverse effects allowing their combination with drug therapies. Their application in clinical practice will depend on the industry’s capacity to develop portable and user-friendly devices, and on the scientists’ capacity to prove their efficacy in randomized sham-controlled trials. [less ▲]

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See detailInvasive occipital nerve stimulation for refractory chronic cluster headache: what evolution at long-term? Strengths and weaknesses of the method.
MAGIS, Delphine ULg; Gerard, Pascale; Schoenen, Jean ULg

in Journal of Headache & Pain (2016)

BACKGROUND: Invasive Occipital Nerve Stimulation (iONS) is a costly technique which appears effective in drug-refractory chronic cluster headache (drCCH) management. Available data on long-term ... [more ▼]

BACKGROUND: Invasive Occipital Nerve Stimulation (iONS) is a costly technique which appears effective in drug-refractory chronic cluster headache (drCCH) management. Available data on long-term effectiveness and safety of iONS in this indication are scarce, though they could be useful to neurologists and patients in daily practice. The purpose of this short report is to discuss the very long-term outcome of a drCCH cohort, including adverse events. FINDINGS: Previously, favourable results were obtained with iONS in 15 drCCH patients: 80 % were significantly improved and 60 % were pain free. We report here the very long-term follow-up (up to nine years) of 10 patients belonging to this cohort. Meanwhile 5 patients had to be definitively explanted because of device infection (3) or paresthesia intolerance (2). Four patients (40 %) evolved to an episodic form of CH. Six remained chronic but their attack frequency was decreased by 70 % on average. Intake of preventive drugs is still necessary in 80 % of patients. All patients needed at least one battery replacement. CONCLUSIONS: Up to nine years after implantation, iONS is still effective in most patients with drCCH. Concomitant preventive drugs remain often necessary. Forty percent of patients reverse to episodic CH, possibly by natural history. iONS is not a benign procedure but device-related complications appear similar to those reported with other invasive neurostimulators. [less ▲]

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See detailMETABOLIC CORRELATES OF VISUAL EVOKED POTENTIALS HABITUATION IN MIGRAINEURS AND CONTROLS
D'Ostilio, Kevin ULg; Lisicki Martinez, Marco ULg; SCHOENEN, Jean ULg et al

in Cephalalgia : An International Journal of Headache (2016), 36(1S), 60

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

in Cephalalgia : An International Journal of Headache (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 detailDOES NON-INVASIVE VAGUS NERVE STIMULATION NORMALIZE HABITUATION OF EVOKED POTENTIALS IN PATIENTS WITH EPISODIC MIGRAINE
NONIS, Romain ULg; D'Ostilio, Kevin ULg; Lisicki Martinez, Marco ULg et al

in Cephalalgia : An International Journal of Headache (2016), 36(1S), 58

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See detailNON-INVASIVE CERVICAL VAGUS NERVE STIMULATION: IS THERE ELECTROPHYSIOLOGICAL EVIDENCE FOR GENUINE VAGAL AFFERENTS ACTIVATION?
NONIS, Romain ULg; D'Ostilio, Kevin ULg; Lisicki Martinez, Marco ULg et al

in Cephalalgia : An International Journal of Headache (2016), 36(1S), 56

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See detailA MACHINE-LEARNING CLASSIFIER FOR EPISODIC MIGRAINE BASED ON VISUAL EVOKED GAMMA BAND ACTIVITY
D'Ostilio, Kevin ULg; Lisicki Martinez, Marco ULg; SCHOENEN, Jean ULg et al

in Cephalalgia : An International Journal of Headache (2016), 36(1S), 56

Introduction: Objective and reliable biomarkers of migraine may be of interest for diagnosis and research purposes. Neuroimaging-based machine-learning classifiers are promising but hampered by ... [more ▼]

Introduction: Objective and reliable biomarkers of migraine may be of interest for diagnosis and research purposes. Neuroimaging-based machine-learning classifiers are promising but hampered by availability and cost issues. Conversely, evoked potential are of easy access and affordable. They have provided increasing evidence that sensory information processing is impaired in migraine. We have used gamma band oscillations (GBOs) of visual evoked potentials (VEPs) to compute a machine-learning neural network classifier in episodic migraine. Materials and methods: We analyzed GBOs from VEPs (6x100 responses). Recordings were performed in two matched samples: a training sample composed of 43 migraine patients (EM) and 20 healthy volunteers (HV) and a validating sample of 18 EM and 10 HV. A logistic regression model of the training sample was performed to evaluate the relevance of the predictor variables. Ten neural networks were automatically generated based on late component frequency, n3-p4 and p4-n4 slopes, 1st block n1-p2 amplitude and age. Results: The logistic regression model of the training sample reached a significant classification rate of 79% (EM: 88%; HV: 60%, p¼0.002). The best neural network was able to classify the groups with an accuracy of 73% in the training phase and 89% in the subsequent validation (success rate HV: 90%; EM: 88%). The mean global accuracy within the training and validating samples were 69% (63–78%) and 84% (82–89%). Conclusions: This machine-learning neural network classifier based on visual GBOs provides an accurate and costefficient tool for objective migraine diagnosis. Further training and validation studies with new cohorts are warranted [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 ULg; D'Ostilio, Kevin ULg; Baschi et al

in Cephalalgia : An International Journal of Headache (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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See detailHighlights in migraine electrophysiology: are controversies just reflecting disease heterogeneity?
MAGIS, Delphine ULg; Lisicki Martinez, Marco ULg; Coppola, Gianluca

in Current Opinion in Neurology (2016), 29(3)

PURPOSE OF REVIEW: In migraine, the brain is 'hyperresponsive', which refers to a deficit of habituation to repeated sensory stimuli between attacks. This deficit normalizes in peri-ictal and ictal phases ... [more ▼]

PURPOSE OF REVIEW: In migraine, the brain is 'hyperresponsive', which refers to a deficit of habituation to repeated sensory stimuli between attacks. This deficit normalizes in peri-ictal and ictal phases. A decreased cortical preactivation of thalamo-cortical origin and an impaired intracortical inhibition are probably involved in its pathophysiology. RECENT FINDINGS: The reality of a habituation deficit of visual evoked potentials, a neurophysiological 'hallmark' of interictal migraine, has been questioned. Blinding may be an issue, but some genetic, environmental, or behavioural differences could also exist between populations. A habituation deficit is found interictally in other sensory modalities, and strongly depends on the time of the recordings within the migraine cycle. An impaired thalamocortical drive is demonstrated in interictal phase, and normalizes in ictal phase as well as in chronic migraine, where a strength enhancement of primary cortical activation is observed. An interictal dysexcitability, of subcortical or primary cortical origin, is suggested by magnetic stimulation. These phenomena could occur in varying degrees depending on patients and on the migraine cycle, and account for the heterogeneity of electrophysiological results. SUMMARY: Finding a reliable electrophysiological biomarker for such a multifaceted and cycling disease as migraine is still a challenge. A better standardization of protocols would be worthwhile. [less ▲]

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See detailNon-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study.
Gaul, Charly; Diener, Hans-Christoph; Silver, Nicholas et al

in Cephalalgia : An International Journal of Headache (2015)

Background: Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was ... [more ▼]

Background: Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH. Methods: PREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS (n=48) with standard of care (SoC) alone (control (n=49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety tolerability were also assessed. Results: During the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS (n=45) had a significantly greater reduction in the number of attacks per week vs controls (n=48) (-5.9 vs -2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p=0.02). Higher #50% response rates were also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p<0.001). No serious treatment-related adverse events occurred. Conclusion: Adjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC. [less ▲]

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See detailCerebral FDG uptake changes with supraorbital transcutaneous electrical stimulation for episodic migraine prevention
D'Ostilio, Kevin ULg; Thibaut, Aurore ULg; Laureys, Steven ULg et al

Conference (2015, May)

Background: A recent multicentre RCT has shown that supraorbital transcutaneous stimulation (STS) targeting branches of the ophtalmic nerve with the Cefaly® device is effective as a preventive therapy for ... [more ▼]

Background: A recent multicentre RCT has shown that supraorbital transcutaneous stimulation (STS) targeting branches of the ophtalmic nerve with the Cefaly® device is effective as a preventive therapy for migraine (Schoenen et al., Neurology 2013). However, the mechanisms of action in the central nervous system remain unknown. Here, we conducted voxel-based analyses of [18]FDG-PET to evaluate metabolic changes immediately after the first STS session and after 3 months of treatment in patients with migraine. Methods: Twenty-eight subjects participated in the experiment: 14 patients with episodic migraine (ICHD3 beta criteria) and 14 age-matched controls. Healthy volunteers underwent only one [18]FDG-PET scan whereas patients were scanned at baseline, directly after a first session of STS and after 3 months of daily treatment. Results: Compliant patients showed a significant decrease in the number of attacks (p = 0.03). When compared to controls, patients (n = 14) at baseline were hypometabolic in the fronto-temporal regions (p < 0.001), especially in the orbitofrontal (OFC) and perigenual anterior cingulate cortex. OFC hypometabolism was not correlated with medication intake. In compliant patients, daily STS for 3 months was followed by a normalization of the fronto-temporal hypometabolism (p< 0.001; OFC: pFWE<0.01). Conclusion: Our study suggests that the OFC is hypoactive in episodic migraine. STS with the Cefaly° device is able to normalize this hypoactivity. This indicates that STS exerts its beneficial effect via slow neuromodulatory mechanisms, as also previously shown for percutaneous occipital nerve stimulation in refractory cluster headache (Magis et al., BMC Neurology 2011). [less ▲]

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