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See detailHabituation of evoked responses is greater in patients with familial hemiplegic migraine than in controls: a contrast with the common forms of migraine.
Hansen, Jacob Moller; Bolla, Monica; Magis, Delphine ULg et al

in European Journal of Neurology (2011)

Background: Familial hemiplegic migraine (FHM) is a rare, dominantly inherited subtype of migraine with transient hemiplegia during the aura phase. Mutations in at least three different genes can produce ... [more ▼]

Background: Familial hemiplegic migraine (FHM) is a rare, dominantly inherited subtype of migraine with transient hemiplegia during the aura phase. Mutations in at least three different genes can produce the FHM phenotype. The mutated FHM genes code for ion transport proteins that animal and cellular studies have associated with disturbed ion homeostasis, altered cellular excitability, neurotransmitter release, and decreased threshold for cortical spreading depression. The common forms of migraine are characterized interictally by a habituation deficit of cortical and subcortical evoked responses that has been attributed to neuronal dysexcitability. FHM and the common forms of migraine are thought to belong to a spectrum of migraine phenotypes with similar pathophysiology, and we therefore examined whether an abnormal habituation pattern would also be found in FHM patients. Methods: In a group of genotyped FHM patients (five FHM-1, four FHM-2), we measured habituation of visual evoked potentials (VEP), auditory evoked potentials including intensity dependence (IDAP), the nociception-specific blink reflex (nsBR) and compared the results to a group of healthy volunteers (HV). Results: FHM patients had a more pronounced habituation during VEP (P = 0.025) and nsBR recordings (P = 0.023) than HV. There was no difference for IDAP, but the slope tended to be steeper in FHM. Conclusion: Contrary to the common forms of migraine, FHM patients are not characterized by a deficient, but rather by an increased habituation in cortical/brain stem evoked activities. These results suggest differences between FHM and the common forms of migraine, as far as central neuronal processing is concerned. [less ▲]

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See detailNeurostimulation therapy in intractable headaches
Schoenen, Jean ULg; Allena, M; MAGIS, Delphine ULg

in Nappi; Moskowitz (Eds.) Handbook of Clinical Neurology (2011)

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See detailTreatment of migraine: update on new therapies.
MAGIS, Delphine ULg; Schoenen, Jean ULg

in Current Opinion in Neurology (2011)

PURPOSE OF REVIEW: This review provides a comprehensive selection of the latest clinical trial results in antimigraine treatment. RECENT FINDINGS: The oral calcitonine gene-related peptide antagonist ... [more ▼]

PURPOSE OF REVIEW: This review provides a comprehensive selection of the latest clinical trial results in antimigraine treatment. RECENT FINDINGS: The oral calcitonine gene-related peptide antagonist telcagepant is efficacious in acute treatment. Compared to triptans, its efficacy is almost comparable but its tolerance is superior. The same is true for the 5HT-1F agonist lasmiditan, another agent devoid of vascular effects. Triptans, as other drugs, are more efficient if taken early but nonsteroidal anti-inflammatory drugs and analgesics remain useful for acute treatment, according to several meta-analyses. Single-pulse transcranial magnetic stimulation during the aura rendered more patients pain-free (39%) than sham stimulation (22%) in one study. Topiramate could be effective for migrainous vertigo, but it did not prevent transformation to chronic migraine in patients with high attack frequency. Onabotulinumtoxin A was effective for chronic migraine and well tolerated, but the therapeutic gain over placebo was modest; the clinical profile of responders remains to be determined before widespread use. Occipital nerve stimulation was effective in intractable chronic migraine with 39% of responders compared to 6% after sham stimulation. This and other neuromodulation techniques, such as sphenopalatine ganglion stimulation, are promising treatments for medically refractory patients but large controlled trials are necessary. One study suggests that outcome of patent foramen ovale closure in migraine might depend on anatomic and functional characteristics. SUMMARY: Drugs with a better efficacy or side-effect profile than triptans may soon become available for acute treatment. The future may also look brighter for some of the very disabled chronic migraineurs thanks to novel drug and neuromodulation therapies. [less ▲]

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See detailLa neurostimulation : quelle place dans les céphalées réfractaires?
MAGIS, Delphine ULg; SCHOENEN, Jean ULg

in Revue Médicale de Liège (2011), 66(2), 85-90

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See detailPeripheral nerve stimulation in chronic cluster headache.
MAGIS, Delphine ULg; Schoenen, Jean ULg

in Progress in Neurological Surgery (2011), 24

Cluster headache is well known as one of the most painful primary neurovascular headache. Since 1% of chronic cluster headache patients become refractory to all existing pharmacological treatments ... [more ▼]

Cluster headache is well known as one of the most painful primary neurovascular headache. Since 1% of chronic cluster headache patients become refractory to all existing pharmacological treatments, various invasive and sometimes mutilating procedures have been tempted in the last decades. Recently, neurostimulation methods have raised new hope for drug-resistant chronic cluster headache patients. The main focus of this chapter is on stimulation of the great occipital nerve, which has been the best evaluated peripheral nerve stimulation technique in drug-resistant chronic cluster headache, providing the most convincing results so far. Other peripheral nerve stimulation approaches used for this indication are also reviewed in detail. Although available studies are limited to a relatively small number of patients and placebo-controlled trials are lacking, existent clinical data suggest that occipital nerve stimulation should nonetheless be recommended for intractable chronic cluster headache patients before more invasive deep brain stimulation surgery. More studies are needed to evaluate the usefulness of supraorbital nerve stimulation and of vagus nerve stimulation in management of cluster headaches. [less ▲]

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See detailThe California Verbal Learning Test and other standard clinical neuropsychological tests to predict conversion from mild memory impairment to dementia.
Lekeu, Françoise ULg; Magis, Delphine ULg; Marique, Patricia et al

in Journal of Clinical & Experimental Neuropsychology (2010), 20

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See detailSustained efficacy of occipital nerve stimulation in drug-resistant chronic cluster headache after up to 5 years treatment
Magis, Delphine ULg; Gérardy, Pierre-Yves; Remacle, Jean-Michel et al

in Journal of Headache & Pain (2010), 11(Suppl 1), 15

Background. Drug-resistant chronic cluster headache (drCCH) is a devastating condition for which various invasive procedures have been tempted without any satisfactory effect. Our prospective pilot study ... [more ▼]

Background. Drug-resistant chronic cluster headache (drCCH) is a devastating condition for which various invasive procedures have been tempted without any satisfactory effect. Our prospective pilot study of great occipital nerve stimulation (ONS) in 8 drCCH patients showed encouraging results at 15 months (1). Methods. We recruited 15 patients with drCCH according to the previously published criteria of intractability (2). They were implanted with suboccipital stimulators on the side of their headache. Long-term follow-up was achieved by questionnaires administered during a headache consultation and/or by telephone interviews. Results. One patient had an immediate post operative infection of the material. Mean time with ONS was 28.8 months (range 3-60 months). Nine of the 14 remaining patients were totally pain-free (64%), 2 patients had an improvement in frequency exceeding 90% and one patient a 89% amelioration. Two patients did not respond or described mild improvement. Intensity of residual attacks was not improved by ONS. Four patients (29%) were able to reduce their prophylaxis. Common technical problems were battery depletion (N=8/14, 57%) and material infection (N=3/15, 20%). Recurrent battery replacement (until 2/ year in one patient) is now avoided by the availability of rechargeable batteries. Clinical peculiarities associated with ONS were occurrence of infrequent contralateral attacks (N=5/14, 36%), and/or isolated ispilateral autonomic attacks (N=5/14, 36%). Rapid attack recurrence after stimulator switch off was reported by 7/12 improved patients (58%). Two patients found ONS-related paresthesias unbearable; one had his stimulator removed, the other switched it off though he was objectively ameliorated. Subjectively, nine patients are very satisfied by ONS and one patient moderately satisfied. Conclusions. Our long-term follow-up confirms the efficacy of ONS in drCCH, which remains a safe and well-tolerated technique. The occurrence of contralateral attacks and isolated autonomic attacks in nearly 50% of ONS responders may have therapeutic and pathophysiological implications. [less ▲]

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See detailCentral neuromodulation in cluster headache patients treated with occipital nerve stimulators: A PET study
Magis, Delphine ULg; Bruno, Marie-Aurélie ULg; Fumal, Arnaud ULg et al

in Acta Neurologica Belgica (2010), 110(Suppl 1), 17

OBJECTIVES: Use functional brain imaging to explore activity changes in centres involved in trigeminal pain processing and control before and after occipital neurostimulation in drug-resistant chronic ... [more ▼]

OBJECTIVES: Use functional brain imaging to explore activity changes in centres involved in trigeminal pain processing and control before and after occipital neurostimulation in drug-resistant chronic cluster headache patients. BACKGROUND: Occipital nerve stimulation (ONS) provides relief to about 60% of patients suffering from drug-resistant chronic cluster headache (drCCH). Its mode of action, however, remains elusive, but the long latency to meaningful effect suggests that ONS induces slow neuromodulation. METHODS: Ten drCCH patients underwent an 18FDG-PET scan after ONS durations varying between 0 and 30 months. All were scanned with ongoing ONS (ON) and with the stimulator switched OFF. RESULTS: After 6-30 months of ONS, 3 patients were pain free and 4 had a ≥ 90% reduction of attack frequency (responders). In patients overall compared to controls, several areas of the pain matrix were hypermetabolic: ipsilateral hypothalamus, midbrain and ipsilateral lower pons. All normalized after ONS, except the hypothalamus. Switching ON or OFF the stimulator had little influence on brain glucose metabolism. The perigenual anterior cingulate cortex (PACC) was hyperactive in ONS responders compared to non-responders. INTERPRETATION AND CONCLUSIONS: Metabolic normalization in the pain neuromatrix and lack of short-term changes induced by the stimulation support the hypothesis that ONS acts in drCCH through slow neuromodulatory processes. Selective activation in responders of PACC, a pivotal structure in the endogenous opioid system, suggests that ONS may restore balance within dysfunctioning pain control centres. That ONS is nothing but a symptomatic treatment might be illustrated by the persistent hypothalamic hypermetabolism which could explain why autonomic attacks may persist despite pain relief and why cluster attacks recur shortly after stimulator arrest. [less ▲]

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See detailNeurostimulation therapy in intractable headaches.
Schoenen, Jean ULg; Allena, Marta; Magis, Delphine ULg

in Handbook of clinical neurology / edited by P.J. Vinken and G.W. Bruyn (2010), 97

A proportion of chronic headache patients become refractory to medical treatment and severely disabled. In such patients various neurostimulation methods have been proposed, ranging from invasive ... [more ▼]

A proportion of chronic headache patients become refractory to medical treatment and severely disabled. In such patients various neurostimulation methods have been proposed, ranging from invasive procedures such as deep-brain stimulation to minimally invasive ones like occipital nerve stimulation. They have been applied in single cases or small series of patients affected with varying headache disorders: cervicogenic headache, hemicrania continua, posttraumatic headache, chronic migraine, and cluster headache. Although favorable results were reported overall, it is premature to consider neurostimulation as a treatment with established utility in refractory headaches. At present, the most detailed clinical studies have been performed in intractable chronic cluster headache (iCCH) patients, who represent about 1% of all chronic cluster headache (CCH) patients. Various lesional interventions have been attempted in these patients, none with lasting benefits. In recent years, non-destructive neurostimulation methods have raised new hope. Hypothalamic deep-brain stimulation (hDBS) acts rapidly and has lasting efficacy, but is not without risk. Occipital nerve stimulation (ONS) was studied in two trials on a total of 17 iCCH patients. Clinical efficacy was found to be very satisfactory by most patients and by the investigators. Although slightly less efficacious than hDBS, ONS has the advantage of being rather harmless and reversible. At this stage, it should be preferred as first-line invasive therapy for iCCH. Recent case reports mention the efficacy of supraorbital (SNS) and vagal (VNS) nerve stimulation. Whether these neurostimulation methods have a place in the management of iCCH patients remains to be determined. [less ▲]

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See detailMigraine - clinical neurophysiology.
Ambrosini, Anna; Magis, Delphine ULg; Schoenen, Jean ULg

in Nappi, G.; Moskowitz, M. (Eds.) Headache (2010)

Central nervous system (CNS) dysfunction is thought to be pivotal in migraine, and could occur at several levels: the brain (the cortex and its connections with subcortical nuclei), the brainstem, and ... [more ▼]

Central nervous system (CNS) dysfunction is thought to be pivotal in migraine, and could occur at several levels: the brain (the cortex and its connections with subcortical nuclei), the brainstem, and even peripheral structures (e.g., trigeminal ganglion and nerve). As it is particularly suited to functional evaluation of various components of the nervous system, neurophysiological testing has become a valuable tool for investigating migraine pathophysiology and the effects of pharmacological treatment. However it has limited value for migraine diagnosis because of a high interindividual variability. In this chapter, we critically review and summarize the available published literature on neurophysiological approaches in migraine, i.e., electroencephalography, evoked and event-related potentials, transcranial magnetic stimulation (TMS), electromyography, and cerebellar testing. The most relevant techniques for understanding migraine pathophysiological mechanisms are highlighted. [less ▲]

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See detailOccipital nerve stimulation for drug-resistant chronic cluster headache: long term follow-up up to 3 years
Gérardy, Pierre-Yves ULg; Magis, Delphine ULg; Allena, M. et al

in Cephalalgia : An International Journal of Headache (2009, January), 29(1),

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See detailMitochondrial DNA haplogroups influence response to Riboflavin in Migraineurs
Di Lorenzo, C.; Coppola, G.; Santorelli, F. et al

in Cephalalgia : An International Journal of Headache (2009, January), 29(1),

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See detailMitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs.
Di Lorenzo, C.; Pierelli, F.; Coppola, G. et al

in Neurology (2009), 72(18), 1588-94

OBJECTIVES: In migraine, an interictal reduction of mitochondrial energy metabolism and a preventive effect of high-dose riboflavin were reported. To explore the relation between the two, we tested if the ... [more ▼]

OBJECTIVES: In migraine, an interictal reduction of mitochondrial energy metabolism and a preventive effect of high-dose riboflavin were reported. To explore the relation between the two, we tested if the therapeutic response to riboflavin is associated with specific mitochondrial DNA (mtDNA) haplogroups. We focused our attention on haplogroup H, which is known to differ from others in terms of energy metabolism. METHODS: Sixty-four migraineurs completed a 4-month open trial with riboflavin (400 mg QD) and were genotyped blindly for mtDNA haplogroups. RESULTS: Forty patients responded to riboflavin treatment and 24 were nonresponders. The mtDNA haplogroup H was found in 29 subjects (20 migraine without aura, 9 migraine with aura). Riboflavin responders were more numerous in the non-H group (67.5%). Conversely, nonresponders were mostly H (66.7%). The difference between the two groups was significant (chi(2) = 7.07; p = 0.01). The presence of aura had no influence on riboflavin's effectiveness (chi(2) = 0.113; p = 0.74) and was not associated with a particular haplogroup (chi(2) = 0.55; p = 0.46). CONCLUSIONS: In this pharmacogenetic study, riboflavin appears to be more effective in patients with migraine with non-H mitochondrial DNA haplotypes. The underlying mechanisms are unknown, but could be related to the association of haplogroup H with increased activity in complex I, which is a major target for riboflavin. Our results may have ethnic implications, since haplogroup H is chiefly found in the European population. [less ▲]

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See detailNitroglycerin sensitises in healthy subjects CNS structures involved in migraine pathophysiology: evidence from a study of nociceptive blink reflexes and visual evoked potentials.
Di Clemente, Laura; Coppola, Gianluca; Magis, Delphine ULg et al

in Pain (2009), 144(1-2), 156-61

Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4-6 h after administration. The causative mechanisms are not known, but the long delay leaves room for a central ... [more ▼]

Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4-6 h after administration. The causative mechanisms are not known, but the long delay leaves room for a central effect, such as a change in neuronal excitability and synaptic transmission of various CNS areas involved in pain and behaviour including trigeminal nucleus caudalis and monoaminergic brain stem nuclei. To explore the central action of NTG, we have studied its effects on amplitude and habituation of the nociceptive blink reflex (nBR) and the visual evoked potential (VEP) before, 1 h and 4 h after administration of NTG (1.2 mg sublingual) or placebo (vehicle sublingual) in two groups of 10 healthy volunteers. We found a significant decrease in nBR pain and reflex thresholds both 1 and 4 h post-NTG. At the 4 h time point R2 latency was shorter (p=0.04) and R2 response area increased (p<0.01) after NTG but not after placebo. Habituation tended to become more pronounced after both NTG and placebo administration. There was a significant amplitude increase in the 5th VEP block (p=0.03) at 1h after NTG and in the 1st block (p=0.04) at 4 h. VEP habituation was replaced by potentiation at both delays after NTG; the change in habituation slope was significant at 1h (p=0.02). There were no significant VEP changes in subjects who received sublingual placebo. In conclusion, we found that in healthy subjects sublingual NTG, but not its vehicle, induces changes in a trigeminal nociceptive reflex and an evoked cortical response which are comparable to those found immediately before and during an attack of migraine. These changes could be relevant for the attack-triggering effect of NTG in migraineurs. [less ▲]

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See detailMetabolic correlates of clinical heterogeneity in questionable Alzheimer’s disease
Salmon, Eric ULg; Lekeu, Françoise ULg; Garraux, Gaëtan ULg et al

in Neurobiology of Aging (2008), 29

Thirty-four subjects with questionable Alzheimer's disease (QAD) were included in a 3-year prospective study and underwent neuropsychological testing and measurement of brain metabolism using FDG-PET at ... [more ▼]

Thirty-four subjects with questionable Alzheimer's disease (QAD) were included in a 3-year prospective study and underwent neuropsychological testing and measurement of brain metabolism using FDG-PET at entry. Seventeen patients (50%) did not convert to AD during the follow-up period. Compared to elderly controls of similar age, the cerebral activity of non-converters was reduced in the dorsolateral prefrontal cortex. Moreover, the variability of metabolism in the posterior cingulate cortex was related to their visuospatial memory performance, while disparity in parietal activity was related to their verbal memory performance. These results demonstrate the cerebral metabolic heterogeneity of patients with QAD. Initial functional images of converters showed that activity was already impaired in the posterior cingulate, lateral temporal cortex, anterior cingulate and orbitofrontal cortex. This metabolic pattern is consistent with a pre-dementia stage of AD, and highlights the fact that significant frontal metabolic involvement may be associated with impaired activity in posterior associative cortices in very early AD. [less ▲]

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See detailNeurostimulation in chronic cluster headache.
Magis, Delphine ULg; Schoenen, Jean ULg

in Current Pain and Headache Reports (2008), 12(2), 145-53

About 1% of all chronic cluster headache patients become intractable (iCCH; ie, they are refractory to adequate regimens of all established preventive drugs). Various lesional interventions have been ... [more ▼]

About 1% of all chronic cluster headache patients become intractable (iCCH; ie, they are refractory to adequate regimens of all established preventive drugs). Various lesional interventions have been attempted in these patients, none with lasting benefits. In recent years, nondestructive neurostimulation methods have raised new hope. Hypothalamic deep brain stimulation (hDBS) acts rather rapidly and has durable efficacy, but it is not without risk. Occipital nerve stimulation (ONS) was studied in two trials that included 17 iCCH patients. Clinical efficacy was found to be very satisfactory by most patients and investigators. Although slightly less efficacious than hDBS, ONS has the advantage of being harmless and reversible. At this stage, it should be the preferred first-line invasive therapy for iCCH. Recent case reports mention efficacy of supraorbital and vagus nerve stimulation. Whether these neurostimulation methods have a place in the management of iCCH patients remains to be determined. [less ▲]

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See detailInterictal abnormalities of gamma band activity in visual evoked responses in migraine: an indication of thalamocortical dysrhythmia?
Coppola, G.; Ambrosini, Anna; Di Clemente, L. et al

in Cephalalgia : An International Journal of Headache (2007), 27(12), 1360-1367

Between attacks, migraineurs lack habituation in standard visual evoked potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the gamma band range (GBOs, 20-35 Hz) assumed to be ... [more ▼]

Between attacks, migraineurs lack habituation in standard visual evoked potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the gamma band range (GBOs, 20-35 Hz) assumed to be generated both at subcortical (early GBOs) and cortical levels (late GBOs). The consecutive peaks of GBOs were analysed regarding amplitude and habituation in six successive blocks of 100 averaged pattern reversal (PR)-VEPs in healthy volunteers and interictally in migraine with (MA) or without aura patients. Amplitude of the two early GBO components in the first PR-VEP block was significantly increased in MA patients. There was a significant habituation deficit of the late GBO peaks in migraineurs. The increased amplitude of early GBOs could be related to the increased interictal visual discomfort reported by patients. We hypothesize that the hypofunctioning serotonergic pathways may cause, in line with the thalamocortical dysrhythmia theory, a functional disconnection of the thalamus leading to decreased intracortical lateral inhibition, which can induce dishabituation. [less ▲]

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See detailEvaluation and proposal for optimization of neurophysiological tests in migraine: Part 2 - neuroimaging and the nitroglycerin test
Magis, Delphine ULg; Bendtsen, L.; Goadsby, P. J. et al

in Cephalalgia : An International Journal of Headache (2007), 27(12), 1339-1359

Neuroimaging methods have been widely used in headache and migraine research. They have provided invaluable information on brain perfusion, metabolism and structure during and outside of migraine attacks ... [more ▼]

Neuroimaging methods have been widely used in headache and migraine research. They have provided invaluable information on brain perfusion, metabolism and structure during and outside of migraine attacks, contributing to an improved understanding of the pathophysiology of the disorder. Human models of migraine attacks are indispensable tools in pathophysiological and therapeutic research. This review of neuroimaging methods and the attack-provoking nitroglycerin test is part an initiative by a task force within the EUROHEAD project (EU Strep LSHM-CT-2004-5044837-Workpackage 9) with the objective of critically evaluating neurophysiological tests used in migraine. The first part, presented in a companion paper, is devoted to electrophysiological methods, this second part to neuroimaging methods such as functional magnetic resonance imaging, positron emission tomography and voxel-based morphometry, as well as the nitroglycerin test. For each of these methods, we summarize the results, analyse the methodological limitations and propose recommendations for improved methodology and standardization of research protocols. [less ▲]

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