Publications of Jean Schoenen
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See detailAge related metabolic modifications in the migraine brain
Lisicki, M.; D'Ostilio, K.; Coppola, G. et al

in Cephalalgia (2019), 39(8), 978-987

Purpose: The aim of this study was to evaluate the possibility that migraine patients exhibit specific age-related metabolic changes in the brain, which occur regardless of disease duration or the ... [more ▼]

Purpose: The aim of this study was to evaluate the possibility that migraine patients exhibit specific age-related metabolic changes in the brain, which occur regardless of disease duration or the frequency of attacks. Methods: We analysed the relation between brain glucose (18F-fluorodeoxyglucose) uptake and age in healthy volunteers (n = 20) and episodic migraine patients (n = 19). In the latter, we additionally compared the correlation between 18F-fluorodeoxyglucose uptake and disease duration and monthly migraine days. Results: In contrast to controls, in migraine patients advancing age was positively correlated to increased metabolism in the brainstem (especially the posterior pons), hippocampus, fusiform gyrus and parahippocampus. Conversely, no significant correlations between cerebral metabolism and disease duration or migraine days were observed. Conclusions: Findings of this cross-sectional study show that episodic migraine patients exhibit specific metabolic brain modifications while ageing. As such, age is correlated with metabolic changes in key regions of the brain previously associated with migraine's pathophysiology to a better extent than disease duration or the number of monthly migraine days. More than the repeated headache attacks, the continuous interaction with the environment seemingly models the brain of migraine sufferers in an adaptive manner. A positive control (e.g. chronic pain) is missing in this study and therefore findings cannot be proven to be migraine-specific. © International Headache Society 2019. [less ▲]

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See detailPotential Protective Mechanisms of Ketone Bodies in Migraine Prevention
Gross, E. C.; Klement, R. J.; Schoenen, Jean ULiege et al

in Nutrients (2019), 11(4),

An increasing amount of evidence suggests that migraines are a response to a cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity. The ketogenic diet (KD), a diet ... [more ▼]

An increasing amount of evidence suggests that migraines are a response to a cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity. The ketogenic diet (KD), a diet mimicking fasting that leads to the elevation of ketone bodies (KBs), is a therapeutic intervention targeting cerebral metabolism that has recently shown great promise in the prevention of migraines. KBs are an alternative fuel source for the brain, and are thus likely able to circumvent some of the abnormalities in glucose metabolism and transport found in migraines. Recent research has shown that KBs-D-β-hydroxybutyrate in particular-are more than metabolites. As signalling molecules, they have the potential to positively influence other pathways commonly believed to be part of migraine pathophysiology, namely: mitochondrial functioning, oxidative stress, cerebral excitability, inflammation and the gut microbiome. This review will describe the mechanisms by which the presence of KBs, D-BHB in particular, could influence those migraine pathophysiological mechanisms. To this end, common abnormalities in migraines are summarised with a particular focus on clinical data, including phenotypic, biochemical, genetic and therapeutic studies. Experimental animal data will be discussed to elaborate on the potential therapeutic mechanisms of elevated KBs in migraine pathophysiology, with a particular focus on the actions of D-BHB. In complex diseases such as migraines, a therapy that can target multiple possible pathogenic pathways seems advantageous. Further research is needed to establish whether the absence/restriction of dietary carbohydrates, the presence of KBs, or both, are of primary importance for the migraine protective effects of the KD. [less ▲]

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See detailAcute migraine therapy with external trigeminal neurostimulation (ACME): A randomized controlled trial
Chou, D. E.; Shnayderman Yugrakh, M.; Winegarner, D. et al

in Cephalalgia (2019), 39(1), 3-14

Objective: To assess the safety and efficacy of external trigeminal nerve stimulation for acute pain relief during migraine attacks with or without aura via a sham-controlled trial. Methods: This was a ... [more ▼]

Objective: To assess the safety and efficacy of external trigeminal nerve stimulation for acute pain relief during migraine attacks with or without aura via a sham-controlled trial. Methods: This was a double-blind, randomized, sham-controlled study conducted across three headache centers in the United States. Adult patients who were experiencing an acute migraine attack with or without aura were recruited on site and randomly assigned 1:1 to receive either verum or sham external trigeminal nerve stimulation treatment (CEFALY Technology) for 1 hour. Pain intensity was scored using a visual analogue scale (0 = no pain to 10 = maximum pain). The primary outcome measure was the mean change in pain intensity at 1 hour compared to baseline. Results: A total of 109 participants were screened between February 1, 2016 and March 31, 2017. Of these, 106 patients were randomized and included in the intention-to-treat analysis (verum: n = 52; sham: n = 54). The primary outcome measure was significantly more reduced in the verum group than in the sham group: −3.46 ± 2.32 versus −1.78 ± 1.89 (p < 0.0001), or −59% versus −30% (p < 0.0001). With regards to migraine subgroups, there was a significant difference in pain reduction between verum and sham for ‘migraine without aura’ attacks: mean visual analogue scale reduction at 1 hour was −3.3 ± 2.4 for the verum group versus −1.7 ± 1.9 for the sham group (p = 0.0006). For ‘migraine with aura’ attacks, pain reduction was numerically greater for verum versus sham, but did not reach significance: mean visual analogue scale reduction at 1 hour was −4.3 ± 1.8 for the verum group versus −2.6 ± 1.9 for the sham group (p = 0.060). No serious adverse events were reported and five minor adverse events occurred in the verum group. Conclusion: One-hour treatment with external trigeminal nerve stimulation resulted in significant headache pain relief compared to sham stimulation and was well tolerated, suggesting it may be a safe and effective acute treatment for migraine attacks. Study protocol: ClinicalTrials.gov Identifier: NCT02590939. © International Headache Society 2018. [less ▲]

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See detailThe metabolic face of migraine — from pathophysiology to treatment
Gross, Elena C.; Lisicki, Marco; Fischer, Dirk et al

in Nature Reviews. Neurology (2019), 15(11), 627-643

Migraine can be regarded as a conserved, adaptive response that occurs in genetically predisposed individuals with a mismatch between the brain’s energy reserve and workload. Given the high prevalence of ... [more ▼]

Migraine can be regarded as a conserved, adaptive response that occurs in genetically predisposed individuals with a mismatch between the brain’s energy reserve and workload. Given the high prevalence of migraine, genotypes associated with the condition seem likely to have conferred an evolutionary advantage. Technological advances have enabled the examination of different aspects of cerebral metabolism in patients with migraine, and complementary animal research has highlighted possible metabolic mechanisms in migraine pathophysiology. An increasing amount of evidence — much of it clinical — suggests that migraine is a response to cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity and that the attack itself helps to restore brain energy homeostasis and reduces harmful oxidative stress levels. Greater understanding of metabolism in migraine offers novel therapeutic opportunities. In this Review, we describe the evidence for abnormalities in energy metabolism and mitochondrial function in migraine, with a focus on clinical data (including neuroimaging, biochemical, genetic and therapeutic studies), and consider the relationship of these abnormalities with the abnormal sensory processing and cerebral hyper-responsivity observed in migraine. We discuss experimental data to consider potential mechanisms by which metabolic abnormalities could generate attacks. Finally, we highlight potential treatments that target cerebral metabolism, such as nutraceuticals, ketone bodies and dietary interventions. © 2019, Springer Nature Limited. [less ▲]

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See detailIncreased cerebral responses to salient transitions between alternating stimuli in chronic migraine with medication overuse headache and during migraine attacks
Bogdanov, V.B.; Bogdanov, O.V.; Vigano, A. et al

in Cephalalgia (2019), 39(8), 988-999

Introduction In a previous study exploring central pain modulation with heterotopic stimuli in healthy volunteers, we found that transitions between sustained noxious and innocuous thermal stimulations on ... [more ▼]

Introduction In a previous study exploring central pain modulation with heterotopic stimuli in healthy volunteers, we found that transitions between sustained noxious and innocuous thermal stimulations on the foot activated the “salience matrix”. Knowing that central sensory processing is abnormal in migraine, we searched in the present study for possible abnormalities of these salient transitional responses in different forms of migraine and at different time points of the migraine cycle. Methods Participants of both sexes, mostly females, took part in a conditioned pain modulation experiment: Migraineurs between (n = 14) and during attacks (n = 5), chronic migraine patients with medication overuse headache (n = 7) and healthy volunteers (n = 24). To evoke the salience response, continuous noxious cold or innocuous warm stimulations were alternatively applied on the right foot. Cerebral blood oxygenation level dependent responses were recorded with fMRI. Results Switching between the two stimulations caused a significant transition response in the “salience matrix” in all subject groups (effect of the condition). Moreover, some group effects appeared on subsequent post-hoc analyses. Augmented transitional blood oxygenation level dependent responses in the motor cortex and superior temporal sulcus were found in two patient groups compared to healthy controls: chronic migraine with medication overuse headache patients and migraineurs recorded during an attack. In chronic migraine with medication overuse headache patients, salience-related responses were moreover greater in the premotor cortex, supplementary motor area, lingual gyrus and dorso-medial prefrontal cortex and other “salience matrix” areas, such as the anterior cingulate and primary somatosensory cortices. Conclusion This study shows salience-related hyperactivation of affective and motor control areas in chronic migraine with medication overuse headache patients and, to a lesser extent, in episodic migraine patients during an attack. The greater extension of exaggerated blood oxygenation level dependent responses to unspecific salient stimuli in chronic migraine with medication overuse headache than during a migraine attack could be relevant for headache chronification. [less ▲]

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See detailA randomized double-blind, cross-over trial of very low-calorie diet in overweight migraine patients: A possible role for ketones?
Di Lorenzo, C.; Pinto, A.; Ienca, R. et al

in Nutrients (2019), 11(8),

Here we aimed at determining the therapeutic effect of a very low-calorie diet in overweight episodic migraine patients during a weight-loss intervention in which subjects alternated randomly between a ... [more ▼]

Here we aimed at determining the therapeutic effect of a very low-calorie diet in overweight episodic migraine patients during a weight-loss intervention in which subjects alternated randomly between a very low-calorie ketogenic diet (VLCKD) and a very low-calorie non-ketogenic diet (VLCnKD) each for one month. In a nutritional program, 35 overweight obese migraine sufferers were allocated blindly to 1-month successive VLCKD or VLCnKD in random order (VLCKD-VLCnKD or VLCnKD-VLCD). The primary outcome measure was the reduction of migraine days each month compared to a 1-month pre-diet baseline. Secondary outcome measures were 50% responder rate for migraine days, reduction of monthly migraine attacks, abortive drug intake and body mass index (BMI) change. Only data from the intention-to-treat cohort (n = 35) will be presented. Patients who dropped out (n = 6) were considered as treatment failures. Regarding the primary outcome, during the VLCKD patients experienced −3.73 (95% CI: −5.31, −2.15) migraine days respect to VLCnKD (p < 0.0001). The 50% responder rate for migraine days was 74.28% (26/35 patients) during the VLCKD period, but only 8.57% (3/35 patients) during VLCnKD. Migraine attacks decreased by −3.02 (95% CI: −4.15, −1.88) during VLCKD respect to VLCnKD (p < 0.00001). There were no differences in the change of acute anti-migraine drug consumption (p = 0.112) and BMI (p = 0.354) between the 2 diets. A VLCKD has a preventive effect in overweight episodic migraine patients that appears within 1 month, suggesting that ketogenesis may be a useful therapeutic strategy for migraines. © 2019 by the authors. Licensee MDPI, Basel, Switzerland. [less ▲]

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See detailEvidence of an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients: a study comparing 18FDG-PET and visual evoked potentials
Lisicki Martinez, Marco ULiege; D'Ostilio, Kevin; Coppola, Gianluca et al

in Journal of Headache and Pain (2018)

Background: Migraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but ... [more ▼]

Background: Migraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves. The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (18fluorodeoxyglucose-PET)), and visual cortex activation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers. Methods: Twenty episodic migraine without aura patients and twenty healthy volunteers were studied. 18FDG-PET and VEP recordings were performed on separate days. The overall glucose uptake in the visual cortex-to-VEP response ratio was calculated and compared between the groups. Additionally, PET scan comparisons adding area under the VEP curve as a covariate were performed. For case-wise analysis, eigenvalues from a specific region exhibiting significantly different FDG-PET signal in the visual cortex were extracted. Standardized glucose uptake values from this region and VEP values from each subject were then coupled and compared between the groups. Results: The mean area under the curve of VEP was greater in migraine patients compared to healthy controls. In the same line, patients had an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex. Statistical parametric mapping analysis revealed that cortical FDG-PET signal in relation to VEP area under the curve was significantly reduced in migraineurs in a cluster extending throughout the left visual cortex, from Brodmann’s areas 19 and 18 to area 7. Within this region, case-wise analyses showed that a visual neuronal activation exceeding glucose uptake was present in 90% of migraine patients, but in only 15% of healthy volunteers. Conclusion: This study identifies an area of increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients between attacks. Such observation supports the concept that an activity-induced rupture of cerebral metabolic homeostasis may be a cornerstone of migraine pathophysiology. This article has been selected as the winner of the 2018 Enrico Greppi Award. The Enrico Greppi Award is made to an unpublished paper dealing with clinical, epidemiological, genetic, pathophysiological or therapeutic aspects of headache. Italian Society for the Study of Headaches (SISC) sponsors this award, and the award is supported through an educational grant from Teva Neuroscience. This article did not undergo the standard peer review process for The Journal of Headache and Pain. The members of the 2018 Enrico Greppi Award Selection Committee were: Francesco Pierelli, Paolo Martelletti, Lyn Griffiths, Simona Sacco, Andreas Straube and Cenk Ayata. [less ▲]

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See detailBrain correlates of single trial visual evoked potentials in migraine: more than meets the eye.
Lisicki Martinez, Marco ULiege; D’Ostilio, Kevin; Coppola, Gianluca et al

in Frontiers in Neurology (2018)

Background: Using conventional visual evoked potentials (VEPs), migraine patients were found to be hyperresponsive to visual stimulus. Considering that a significant portion of neuronal activity is lost ... [more ▼]

Background: Using conventional visual evoked potentials (VEPs), migraine patients were found to be hyperresponsive to visual stimulus. Considering that a significant portion of neuronal activity is lost for analysis in the averaging process of conventional VEPs, in this study we investigated visual evoked responses of migraine patients and healthy volunteers using a different approach: single trial analysis. This method permits to preserve all stimulus-induced neuronal activations, whether they are synchronized or not. In addition, we used MRI voxel-based morphometry to search for cortical regions where gray matter volume correlated with single trial (st) VEP amplitude. Finally, using resting-state functional MRI, we explored the connectivity between these regions. Results: stVEP amplitude was greater in episodic migraine patients than in healthy volunteers. Moreover, in migraine patients it correlated positively with gray matter volume of several brain areas likely involved in visual processing, mostly belonging to the ventral attention network. Finally, resting state functional connectivity corroborated the existence of functional interactions between these areas and helped delineating their directions. Conclusions: st-VEPs appear to be a reliable measure of cerebral responsiveness to visual stimuli. Mean st-VEP amplitude is higher in episodic migraine patients compared to controls. Visual hyper-responsiveness in migraine involves several functionally-interconnected brain regions, suggesting that it is the result of a complex multi-regional process coupled to stimulus driven attention systems rather than a localized alteration. [less ▲]

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See detailHeterogeneous incidence and propagation of spreading depolarizations
Kaufmann, D; SCHOENEN, Jean ULiege

in Journal of Cerebral Blood Flow and Metabolism (2018)

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See detailEfficacy and mode of action of external trigeminal neurostimulation in migraine
Schoenen, Jean ULiege; Coppola, G.

in Expert Review of Neurotherapeutics (2018), 18(7), 545-555

Introduction: Available preventive drug treatments for migraine lack complete efficacy and often have unpleasant adverse effects. Hence, their clinical utility and therapeutic adherence are limited ... [more ▼]

Introduction: Available preventive drug treatments for migraine lack complete efficacy and often have unpleasant adverse effects. Hence, their clinical utility and therapeutic adherence are limited. Noninvasive neurostimulation methods applied over various peripheral sites (forehead, mastoid, upper arm, cervical vagus nerve) have raised great interest because of their excellent efficacy/tolerance profile. Among them external trigeminal nerve stimulation (eTNS) was first to obtain FDA approval for migraine therapy. Areas covered: All clinical trials of eTNS as preventive or acute migraine treatment published in extenso or presented at congresses are reviewed. The paper analyzes neuroimaging and neurophysiological studies on mechanisms of action of eTNS. As many of these studies point toward the anterior cingulate cortex (ACC) as a likely eTNS target, the paper scrutinizes the available literature on the ACC implication in migraine pathophysiology. Expert commentary: eTNS is a viable alternative to standard pharmacological antimigraine strategies both for prevention and abortive therapy. eTNS could chiefly exert its action by modulating the perigenual ACC, which might also be of interest for treating other disorders like fibromyalgia or depression. It remains to be determined if this might be a common mechanism to other peripheral noninvasive neurostimulation methods. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. [less ▲]

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See detailVisually induced analgesia during face or limb stimulation in healthy and migraine subjects
SAVA, Simona Liliana ULiege; DE PASQUA, Victor ULiege; MAERTENS DE NOORDHOUT, Alain ULiege et al

in Journal of Pain Research (2018), 11

Background: Visually induced analgesia (VIA) defines a phenomenon in which viewing one’s own body part during its painful stimulation decreases the perception of pain. VIA occurs during direct vision of ... [more ▼]

Background: Visually induced analgesia (VIA) defines a phenomenon in which viewing one’s own body part during its painful stimulation decreases the perception of pain. VIA occurs during direct vision of the stimulated body part and also when seeing it reflected in a mirror. To the best of our knowledge, VIA has not been studied in the trigeminal area, where it could be relevant for the control of headache. Subjects and methods: We used heat stimuli (53°C) to induce pain in the right forehead or wrist in 11 healthy subjects (HSs) and 14 female migraine without aura (MO) patients between attacks. The subjects rated pain on a visual analog scale (VAS) and underwent contact heat-evoked potential (CHEP) recordings (five sequential blocks of four responses) with or without observation of their face/wrist in a mirror. Results: During wrist stimulation, amplitude of the first block of P1–P2 components of CHEPs decreased compared to that in the control recording when HSs were seeing their wrist reflected in the mirror (p = 0.036; Z = 2.08); however, this was not found in MO patients. In the latter, the VAS pain score increased viewing the reflected wrist (p = 0.049; Z = 1.96). Seeing their forehead reflected in the mirror induced a significant increase in N2 latency of CHEPs in HSs, as well as an amplitude reduction in the first block of P1–P2 components of CHEPs both in HSs (p = 0.007; Z = 2.69) and MO patients (p = 0.035; Z = 2.10). Visualizing the body part did not modify habituation of CHEP amplitudes over the five blocks of averaged responses, neither during wrist nor during forehead stimulation. Conclusion: This study adds to the available knowledge on VIA and demonstrates this phenomenon for painful stimuli in the trigeminal area, as long as CHEPs are used as indices of central pain processing. In migraine patients during interictal periods, VIA assessed with CHEPs is within normal limits in the face but absent at the wrist, possibly reflecting dysfunctioning of extracephalic pain control. © 2018 Sava et al. [less ▲]

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See detailMigraine triggers and habituation of visual evoked potentials
Lisicki Martinez, Marco ULiege; Ruiz-Romagnoli, Emiliano; Piedrabuena, Raul et al

in Cephalalgia (2018)

Background: Identifying specific subsets of patients within the clinical spectrum of migraine could help in personalizing migraine treatment. Profiling patients by combining clinical characteristics and ... [more ▼]

Background: Identifying specific subsets of patients within the clinical spectrum of migraine could help in personalizing migraine treatment. Profiling patients by combining clinical characteristics and neurophysiological biomarkers is largely unexplored. We studied the association between migraine attack triggers and habituation of visual evoked potentials. Methods: We personally interviewed 25 patients about their migraine triggers following a structured list, and measured the N1-P1 habituation slope over six blocks of 100 averaged pattern-reversal VEP afterwards. Results: The mean number of triggers per patient was 4.52 1.42. Habituation slopes differed significantly between subjects who reported stress as a migraine trigger (deficient VEP habituation) and subjects who did not (preserved VEP habituation). For the remaining categories, the mean amplitude slope was always positive, indicating deficient habituation, and was not significantly different between subgroups. Conclusions: Migraine patients not reporting perceived stress as a trigger for their attacks might constitute a distinct clinic-physiological subset within the migraine spectrum. [less ▲]

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See detailIncreased functional connectivity between the right temporo-parietal junction and the temporal poles in migraine without aura
Lisicki Martinez, Marco ULiege; D'Ostilio, Kevin; Coppola, Gianluca et al

in Cephalalgia Reports (2018)

Rather than a localized alteration, increased visual reactivity in migraine patients seems to result from a complex interaction between several brain structures, mostly involving the ventral attention ... [more ▼]

Rather than a localized alteration, increased visual reactivity in migraine patients seems to result from a complex interaction between several brain structures, mostly involving the ventral attention network. The hub of this network is the right temporo-parietal junction. In this report, complementing our previous findings, we describe the differences in seed to-voxel resting-state functional connectivity seeded in the right temporo-parietal junction (right angular gyrus) between migraine patients and healthy controls. Resting-state functional MRIs of episodic migraine without aura patients in the interictal period (n ¼ 19) and matched healthy controls (n ¼ 19) were analysed. With the seed placed in the right temporo-parietal junction (right angular gyrus), seed-to-voxel connectivity was compared between groups. Electrophysiological, voxel-based morphometry (both groups) and specific region of interest (ROI)-to-ROI functional connectivity (migraine patients) data have already been published. Migraine patients showed a higher positive interaction between the right temporo-parietal junction and both temporal poles and a higher negative interaction between this same region and bilateral areas of the visual cortex. On the basis of our results, and because of their established properties as multisensory integration hubs, it is likely that the right temporo-parietal junction and both temporal poles are involved in the altered processing of sensory stimulus commonly observed in migraine patients. Therefore, more attention should be paid to these regions for migraine research in the future. [less ▲]

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See detailResting state connectivity between default mode network and insula encodes acute migraine headache
Coppola, Gianluca; Di Renzo, Antonio; Tinelli, Emanuele et al

in Cephalalgia (2018), 38(5), 846-854

Background: Previous functional MRI studies have revealed that ongoing clinical pain in different chronic pain syndromes is directly correlated to the connectivity strength of the resting default mode ... [more ▼]

Background: Previous functional MRI studies have revealed that ongoing clinical pain in different chronic pain syndromes is directly correlated to the connectivity strength of the resting default mode network (DMN) with the insula. Here, we investigated seed-based resting state DMN-insula connectivity during acute migraine headaches. Methods: Thirteen migraine without aura patients (MI) underwent 3 T MRI scans during the initial six hours of a spontaneous migraine attack, and were compared to a group of 19 healthy volunteers (HV). We evaluated headache intensity with a visual analogue scale and collected seed-based MRI resting state data in the four core regions of the DMN: Medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and left and right inferior parietal lobules (IPLs), as well as in bilateral insula. Results: Compared to HV, MI patients showed stronger functional connectivity between MPFC and PCC, and between MPFC and bilateral insula. During migraine attacks, the strength of MPFC-to-insula connectivity was negatively correlated with pain intensity. Conclusion:We show that greater subjective intensity of pain during a migraine attack is associated with proportionally weaker DMN-insula connectivity. This is at variance with other chronic extra-cephalic pain disorders where the opposite was found, and may thus be a hallmark of acute migraine head pain. [less ▲]

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See detailExploring insulin resistance in migraine: a population-based study
Streel, Sylvie ULiege; Donneau, Anne-Françoise ULiege; Schoenen, Jean ULiege et al

Poster (2017, September 09)

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See detailSunlight irradiance and habituation of visual evoked potentials in migraine: The environment makes its mark
Lisicki Martinez, Marco ULiege; D'Ostilio, Kevin; Erpicum, Michel ULiege et al

in Cephalalgia (2017)

Background Migraine is a complex multifactorial disease that arises from the interaction between a genetic predisposition and an enabling environment. Habituation is considered as a fundamental adaptive ... [more ▼]

Background Migraine is a complex multifactorial disease that arises from the interaction between a genetic predisposition and an enabling environment. Habituation is considered as a fundamental adaptive behaviour of the nervous system that is often impaired in migraine populations. Given that migraineurs are hypersensitive to light, and that light deprivation is able to induce functional changes in the visual cortex recognizable through visual evoked potentials habituation testing, we hypothesized that regional sunlight irradiance levels could influence the results of visual evoked potentials habituation studies performed in different locations worldwide. Methods We searched the literature for visual evoked potentials habituation studies comparing healthy volunteers and episodic migraine patients and correlated their results with levels of local solar radiation. Results After reviewing the literature, 26 studies involving 1291 participants matched our inclusion criteria. Deficient visual evoked potentials habituation in episodic migraine patients was reported in 19 studies. Mean yearly sunlight irradiance was significantly higher in locations of studies reporting deficient habituation. Correlation analyses suggested that visual evoked potentials habituation decreases with increasing sunlight irradiance in migraine without aura patients. Conclusion Results from this hypothesis generating analysis suggest that variations in sunlight irradiance may induce adaptive modifications in visual processing systems that could be reflected in visual evoked potentials habituation, and thus partially account for the difference in results between studies performed in geographically distant centers. Other causal factors such as genetic differences could also play a role, and therefore well-designed prospective trials are warranted. [less ▲]

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See detailEstrogen-dependent effects of 5-hydroxytryptophan on cortical spreading depression in rat: Modelling the serotonin-ovarian hormone interaction in migraine aura.
Chauvel, Virginie; Multon, Sylvie ULiege; Schoenen, Jean ULiege

in Cephalalgia (2017)

Background: Cortical spreading depression (CSD) is the likely culprit of the migraine aura. Migraine is sexually dimorphic and thought to be a ‘‘low 5-HT’’ condition. We sought to decipher the ... [more ▼]

Background: Cortical spreading depression (CSD) is the likely culprit of the migraine aura. Migraine is sexually dimorphic and thought to be a ‘‘low 5-HT’’ condition. We sought to decipher the interrelation between serotonin, ovarian hormones and cortical excitability in a model of migraine aura. Methods: Occipital KCl-induced CSDs were recorded for one hour at parieto-occipital and frontal levels in adult male (n 1⁄4 16) and female rats (n 1⁄4 64) one hour after intraperitoneal (i.p.) injection of 5-hydroxytryptophan (5-HTP) or NaCl. Sixty-five oophorectomized females were treated with estradiol- (E2) or cholesterol- (Chol) filled capsules. Two weeks later we recorded CSDs after 5-HTP/NaCl injections before or 20 hours after capsule removal. Results: 5-HTP had no effect in males, but decreased CSD frequency in cycling females, significantly so during estrus, at parieto-occipital (􏰀3.5CSD/h, p<0.001) and frontal levels (􏰀2.5CSD/h, p1⁄40.014). In oophorectomized rats, CSD susceptibility increased during E2 treatment at both recording sites (þ5CSD/h, p1⁄40.001 and þ3CSD/h, p<0.01), but decreased promptly after E2 withdrawal (􏰀4.7CSD/h, p < 0.001 and 􏰀1.7CSD/h, p 1⁄4 0.094). The CSD inhibitory effect of 5-HTP was significant only in E2-treated rats (􏰀3.4CSD/h, p 1⁄4 0.006 and 􏰀1.8CSD/h, p 1⁄4 0.029). Neither the estrous cycle phase, nor E2 or 5-HTP treatments significantly modified CSD propagation velocity. Conclusion: 5-HTP decreases CSD occurrence in the presence of ovarian hormones, suggesting its potential efficacy in migraine with aura prophylaxis in females. Elevated E2 levels increase CSD susceptibility, while estrogen withdrawal decreases CSD. In a translational perspective, these findings may explain why migraine auras can appear during pregnancy and why menstrual-related migraine attacks are rarely associated with an aura. [less ▲]

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See detailMigraine treatment with external trigeminal nerve stimulation: current knowledge on mechanisms.
Schoenen, Jean ULiege

in Internal Medicine Reviews (2017)

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See detailFunctional changes of the pain processing network after external trigeminal neurostimulation in migraine patients
Russo, Antonio; SCHOENEN, Jean ULiege

in Frontiers in Neurology (2017)

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