http://www.thejournalofheadacheandpain.com/content/15/1/2André Pradalier (internal medicine)migraine chez l'adulte et chez l'enfant. Rev Neurol (Paris) 2013;169:14-29.
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L'orientation diagnostique devant une cephalee est un probleme frequent en medecine generale. Le plus souvent, il s'agit d'une cephalee chronique deja connue, et le patient consulte pour sa prise en charge plus que pour son... more
L'orientation diagnostique devant une cephalee est un probleme frequent en medecine generale. Le plus souvent, il s'agit d'une cephalee chronique deja connue, et le patient consulte pour sa prise en charge plus que pour son identification. Mais parfois, il s'agit d'une cephalee aigue ou d'une cephalee recemment apparue: un bilan s'impose pour ne pas laisser passer une cause curable. L'examen d'un patient cephalalgique passe d'abord et avant tout par un interrogatoire minutieux, semi-structure, qui va permettre de definir semiologiquement la cephalee, ce qui suffit souvent a en determiner la cause. Au terme de cet interrogatoire et de l'examen clinique, si un doute persiste, des examens complementaires s'imposent.
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Resume La migraine est une maladie tres frequente concernant 17 % de la population francaise adulte et 5 a 10 % des enfants et des adolescents. Les propositions therapeutiques, medicamenteuses ou non medicamenteuses, sont tres nombreuses... more
Resume La migraine est une maladie tres frequente concernant 17 % de la population francaise adulte et 5 a 10 % des enfants et des adolescents. Les propositions therapeutiques, medicamenteuses ou non medicamenteuses, sont tres nombreuses tant pour le traitement des crises que pour le traitement preventif, dit traitement de fond. Il n’existait jusqu’a maintenant aucune regle precise, aucun consensus professionnel pour la prise en charge therapeutique des migraineux, tant et si bien que chaque praticien agissait a sa guise, en fonction de ses habitudes et de sa propre experience. Ceci a contribue a creer autour de cette affection un sentiment d’impuissance et de fatalisme encore present de nos jours, malgre les progres therapeutiques realises. Les enquetes realisees en France montrent que 30 % des migraineux n’ont jamais consulte pour leur migraine, que 50 % ont cesse de le faire, que la moitie des migraineux s’automediquent. Les raisons invoquees sont : « je suis capable de me debrouiller tout seul » ou « la migraine ce n’est pas vraiment une maladie, la migraine ca ne se soigne pas ». Devant cette insuffisance de prise en charge la Societe francaise d’etudes des migraines et cephalees (SFEMC) a demande a l’Agence nationale d’accreditation et d’evaluation de la sante (ANAES) d’elaborer des Recommandations pour la pratique clinique (RPC) concernant la migraine de l’adulte et de l’enfant. Ces recommandations ont ete publiees en 2003. Le texte de ces recommandations apparait en italique dans cet article. Une prise en charge adaptee du migraineux repose d’abord et avant tout sur une evaluation du handicap social, professionnel et familial genere par ses crises. Nous envisageons donc ce point avant d’aborder les recommandations therapeutiques proprement dites.
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In patients suffering from headaches, diagnosis is a common dilemma in general practice. Patients mostly present with chronic headaches which have already been identified and consult their physician for headache management rather than for... more
In patients suffering from headaches, diagnosis is a common dilemma in general practice. Patients mostly present with chronic headaches which have already been identified and consult their physician for headache management rather than for identification. However, acute headaches or recent-onset headaches are sometimes observed; in that case, an examination is required to screen for a potential curable cause. The examination of headache patients consists first and foremost of an exhaustive, semi-structured history taking, which will enable the physician to characterize the headaches in terms of symptomatology and most of the times to determine the etiology. If a doubt persists, further examinations should be performed following history taking and physical examination.
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Migraine is a common primary episodic headache disorder. The most common migraine form is migraine without aura, with an estimated prevalence of 10–12 % in most Western societies. It is more frequent in women and usually starts before the... more
Migraine is a common primary episodic headache disorder. The most common migraine form is migraine without aura, with an estimated prevalence of 10–12 % in most Western societies. It is more frequent in women and usually starts before the age of 20, peaking between 35 and 45. In women, migraine often develops post menarche, worsens during menses, and may vanish during the last two trimesters of pregnancy or after menopause, suggesting an endocrine component to be involved. Two forms of migraine without aura are recognized: episodic (0–14 days per month with headache) and chronic (15 or more days per month with headache; Table 1). Usually, headache is unilateral, in the frontotemporal region, reaches its peak intensity gradually, is moderate to severe, is usually throbbing, and is aggravated by movements. It lasts 4–72 h (untreated or unsuccessfully treated) and can be associated with other symptoms, such as phonophobia, photophobia, nausea, and vomiting. Premonitory symptoms occur in 20–60 % of patients with migraines, hours to days before headache onset. They can include depression, fatigue, irritability, sensory sensitivity, anorexia/hunger, diarrhea/constipation, sensations of heat or cold, and sweating. In migraine with aura, focal neurological symptoms, mainly in the visual field, precede the headache and last about 15–30 min.
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Regional cerebral blood flow (CBF) was studied in 51 young schizophrenics. A significant decrease of CBF was seen in frontal and prefrontal regions (hypofrontal pattern) in chronic patients whose disease had evolved for more than 2 years... more
Regional cerebral blood flow (CBF) was studied in 51 young schizophrenics. A significant decrease of CBF was seen in frontal and prefrontal regions (hypofrontal pattern) in chronic patients whose disease had evolved for more than 2 years and who were in remission. This hypofrontal pattern was reversible, as it disappeared during exacerbation of the disease. In 10 patients who had not been treated with neuroleptics for several weeks, we found a dopaminergic hypersensitivity in the frontal lobes, as a weak dose of piribedil restored near-normal frontality. This may reflect either the role of neuroleptic washout or a primitive dopaminergic depletion, as proposed by some authors in the chronic form of schizophrenia.
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Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence... more
Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence varies with the triptan used. In order to explore the pharmacological and physiological interaction of triptans and migraine headache recurrence further, some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class. These factors were 5-HT1B and 5-HT1D receptor activities, the pharmacokinetic elimination half-life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo. Clinical data were derived from 31 triptan, placebo-controlled, major efficacy studies used in a previous meta-analysis. The mean recurrence rate, mean headache response, and therapeutic gain were calculated using the results from the individual clinical studies. Mean headache response and therapeutic gain were calculated at the time point used to define recurrence in each study. Data for binding affinity and potency were taken from a direct-comparison in vitro pharmacology study, and the elimination half-life quoted in the data sheet for each triptan was used. Rank correlation with recurrence rate was performed for each of the test parameters. Mean headache recurrence rates ranged from 17% for frovatriptan 2.5 mg to 40% for rizatriptan. Elimination half-life and recurrence were inversely correlated (r = -1.0, P =.0016). There was also a significant inverse correlation between 5-HT1B receptor potency and recurrence (r = -0.68, P =.034), but 5-HT1D receptor potency was not correlated with recurrence (r = -0.20, P =.54). In addition, the binding affinities for the 5-HT1B and 5-HT1D receptors were not correlated to headache recurrence. Importantly, it also was demonstrated that initial clinical efficacy was not correlated to headache recurrence. The correlation coefficient for headache response was 0.18 (P =.53) and for therapeutic gain, -0.11 (P =.71). The incidence of migraine headache recurrence varies between drugs in the triptan class. Migraine recurrence does not appear to be related to initial clinical efficacy, but is influenced by the pharmacological and pharmacokinetic properties of the individual triptans. The triptans with longer half-lives and greater 5-HT1B receptor potency had the lowest rates of headache recurrence.
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311C90 is an orally active 5-HT1D agonist with both central and peripheral actions that is currently being developed as an acute antimigraine treatment. Several studies have demonstrated the safety and efficacy of 311C90 in the treatment... more
311C90 is an orally active 5-HT1D agonist with both central and peripheral actions that is currently being developed as an acute antimigraine treatment. Several studies have demonstrated the safety and efficacy of 311C90 in the treatment of a single migraine headache. The objectives of this open study are to assess the safety and efficacy of 311C90 when used for a period of up to one year. Patients can treat as many migraine headaches as desired with an oral treatment regimen of 311C90. An initial 5 mg dose for treatment of the migraine headache may be followed with a second 5 mg dose to treat recurrence should it develop. Safety assessments include electrocardiograms, the frequency, intensity and duration of adverse experiences, and routine haematology, urinalysis and clinical chemistry measures. Data presented here are an interim view of the database as of August 1995 and should be considered as preliminary observations. No clinically significant serious adverse experiences have been reported. The adverse experience and efficacy profile appears to be consistent with previous 311C90 studies and this dosing regimen of 311C90 was well tolerated during multiple exposures. Notably, response rates are as good after both initial and repeated exposure (up to 5 migraines).
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To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine. Frovatriptan is a new, selective serotonin agonist (triptan) developed for the acute treatment of migraine. Dose range-finding studies identified... more
To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine. Frovatriptan is a new, selective serotonin agonist (triptan) developed for the acute treatment of migraine. Dose range-finding studies identified 2.5 mg as the dose that conferred the optimal combination of efficacy and tolerability. The tolerability and safety of frovatriptan 2.5 mg were assessed during controlled, acute migraine treatment studies, including a study that compared frovatriptan 2.5 mg with sumatriptan 100 mg, as well as a 12-month open-label study during which patients could take up to three doses of frovatriptan 2.5 mg within a 24-hour period. Safety and tolerability were assessed through the collection of adverse events, monitoring of heart rate and blood pressure performance of 12-lead electrocardiogram, hematology screen, and blood chemistry studies. In the short-term studies, 1554 patients took frovatriptan 2.5 mg and 838 took placebo. In the 12-month study, 496 patients treated 13 878 migraine attacks. Frovatriptan was well tolerated in the short- and long-term studies with 1% of patients in the short-term studies and 5% of patients in the long-term study withdrawing due to lack of tolerability. The incidence of adverse events was higher in the frovatriptan-treated patients than in the patients who took placebo (47% versus 34%) and the spectrum of adverse events was similar. When compared to sumatriptan 100 mg, significantly fewer patients taking frovatriptan experienced adverse events (43% versus 36%; P=.03) and the number of adverse events was lower (0.62 versus 0.91), there were also fewer adverse events suggestive of cardiovascular symptoms in the frovatriptan group. Analysis of the entire clinical database (n=2392) demonstrated that frovatriptan was well tolerated by the patients regardless of their age, gender, race, concomitant medication, or the presence of cardiovascular risk factors. No effects of frovatriptan on heart rate, blood pressure, 12-lead electrocardiogram, hematology screen, or blood chemistry were observed. No patient suffered any treatment-related serious adverse event. Short- and long-term use of frovatriptan 2.5 mg was well tolerated by a wide variety of patients. Frovatriptan treatment produced an adverse events profile similar to that of placebo, and in a direct comparison study was better tolerated than sumatriptan 100 mg.
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The expression and distribution of two cell adhesion molecules, N-cadherin and N-CAM, at the surface of cultured leg muscle cells from 11-day-old chicken embryos were studied and compared. N-cadherin, which was expressed by fusing... more
The expression and distribution of two cell adhesion molecules, N-cadherin and N-CAM, at the surface of cultured leg muscle cells from 11-day-old chicken embryos were studied and compared. N-cadherin, which was expressed by fusing myoblasts, was down-regulated on old myotubes while N-CAM was still present. Both molecules, as viewed by confocal microscopy, appeared to have coaccumulated at the areas of contact between fusing myoblasts. However, immunogold electron microscopy did not reveal significant colocalization of N-cadherin and N-CAM, and their segregation after antibody-induced patching suggested the absence of direct interactions between N-cadherin and N-CAM. The role of the Ca2+ dependent cell adhesion molecule N-cadherin in myogenesis was investigated. Myoblast fusion was inhibited (1) with a synthetic peptide containing the H-A-V sequence and (2) with a monoclonal anti-N-cadherin antibody, demonstrating that N-cadherin-mediated cell adhesion is required for myoblast fusion...
Research Interests: Electron Microscopy, Calcium, Cell Adhesion, Membrane Proteins, Immunohistochemistry, and 13 moreConfocal Microscopy, Biological Sciences, Cell fusion, Animals, Muscles, Peptides, Skeletal Muscle, Amino Acid Sequence, Embryos, Gene Expression Regulation, Cell Cell Interaction, Molecular Sequence Data, and Cadherins
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To evaluate the proportion of migraineurs who are self-aware of their disease in France, to determine the factors (disability, quality of life, psychiatric comorbidities, and medical consultation) that may promote self-awareness of... more
To evaluate the proportion of migraineurs who are self-aware of their disease in France, to determine the factors (disability, quality of life, psychiatric comorbidities, and medical consultation) that may promote self-awareness of migraine, and to assess the influence of these factors on migraine attacks. New recommendations for migraine diagnosis and medical management were released in 2003 by the French medicoeconomic evaluation service (ANAES). In addition, the revised classification of headache disorders recently issued by the International Headache Society includes probable migraine as a form of migraine. However, strict and probable migraine now appear to be part of the same spectrum of disease. Subjects with migraine (strict or probable) according to the revised classification were identified by a postal questionnaire from a large representative sample of the French adult population. Migraine-related disability was assessed using the MIDAS questionnaire, anxiety and depression by the Hospital Anxiety and Depression scale (HADS), and health-related quality of life (HRQoL) by the 8 concepts of the Short-Form 12 (SF-12) questionnaire. Migraine management was assessed according to the use of recommended or nonrecommended treatments, and treatment efficacy according to the set of 4 questions designed by the ANAES. Of the 10,532 subjects interviewed, 1,179 subjects (21.3%) were identified as migraineurs. Sixty percent of all migraine subjects were not self-aware that they had migraine. Medical consultation, duration of migraine history, severe intensity of attacks, impact on daily living, and female gender promoted self-awareness of migraine. On the other hand, HRQoL and anxiety and depression scores were not different between subjects self-aware or not self-aware of migraine. Only 20% of all migraine subjects were medically followed-up. Quality of the first medical consultation appears determinant for continued consulting. Subjects self-aware of migraine more frequently used recommended acute treatments of migraine, which proved more effective than nonrecommended treatments as assessed according to the ANAES set of questions. Migraine medical diagnosis and follow-up remain low in France. Careful medical consultation is a prime factor for migraine subject self-awareness of migraine, continued consultation, and use of recommended medications for the treatment of migraine attacks.
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Research Interests: Early Intervention, Treatment Outcome, Adolescent, Activities of Daily Living, Humans, and 20 moreFemale, Male, Neck Pain, Statistical Significance, Placebos, Randomised Controlled Trial, Recurrence, SHOULDER PAIN, Clinical Sciences, Aged, Middle Aged, Adult, Time Factors, Adverse Event, Migraine With Aura, Neurosciences, Tryptamines, Migraine without Aura, Severity of Illness Index, and Acute Disease
In this international, multicentre, double-blind, placebo-controlled, single attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg,... more
In this international, multicentre, double-blind, placebo-controlled, single attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P=0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design.
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Research Interests: France, Prion Diseases, Brain, Humans, Female, and 7 moreMale, Pedigree, Clinical Sciences, Middle Aged, Prions, Adult, and Neurosciences
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Due to technical constraints and randomness of migraine attacks, studies using PET are scarce. Nevertheless, these studies have given new insights into migraine pathogenesis. One of the main facts revealed by PET studies is that posterior... more
Due to technical constraints and randomness of migraine attacks, studies using PET are scarce. Nevertheless, these studies have given new insights into migraine pathogenesis. One of the main facts revealed by PET studies is that posterior cerebral hypoperfusion accompanying migraine auras could also be present in migraine attacks without aura. This hypoperfusion is probably due to an increase of intrinsic vasoconstrictive tone in the cerebral circulation. Using PET within 6 hours after the onset of a spontaneous migraine attack, significant activations of brainstem (midbrain and pons) and of hypothalamus, persisting after headache relief by sumatriptan have been shown. These structures could play the role of migraine attack generators, modulating intrinsic vascular tone and central pain transmission.
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The first complete three dimensional ultrastructural reconstruction of pancreatic cell nucleoli, was done using EM and computer 3D-assisted reconstruction of serial sections with interactive 3D back-to-front and color display methods... more
The first complete three dimensional ultrastructural reconstruction of pancreatic cell nucleoli, was done using EM and computer 3D-assisted reconstruction of serial sections with interactive 3D back-to-front and color display methods based on voxel representation. The purpose of the study was to depict the architecture of the nucleolar components. We obtained information about the location of the nucleolus within the nuclear volume and about the shape and polarity of the 3 main nucleolar territories.
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Research Interests: Deep Brain Stimulation, Quality of life, Treatment Outcome, Humans, Hypothalamus, and 14 moreFemale, Male, Follow-up studies, The, Cluster Headache, Middle Aged, Adult, Time Factors, Adverse Event, Cross-Over Studies, Loss of Consciousness, Pain Measurement, Functional Laterality, and Outcome measure
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Research Interests: Quality of life, Self Care, France, Patient education, Humans, and 14 moreNeeds Assessment, Female, Male, Patient Compliance, Patient Satisfaction, Data Collection, Public Information, Middle Aged, Questionnaires, Adult, Health surveys, Pain Measurement, Severity of Illness Index, and Disability Evaluation
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ABSTRACT Introduction Les céphalées dites circonstancielles « à la toux, à l’effort et à l’activité sexuelle » sont incluses par l’International Headache Society dans le groupe 4 des « autres céphalées primaires ». Objectifs Notre travail... more
ABSTRACT Introduction Les céphalées dites circonstancielles « à la toux, à l’effort et à l’activité sexuelle » sont incluses par l’International Headache Society dans le groupe 4 des « autres céphalées primaires ». Objectifs Notre travail a pour but de réaliser une étude clinique et neuroradiologique chez les patients présentant ce type de céphalées circonstancielles afin d’essayer d’avancer dans la compréhension des mécanismes physiopathologiques de ces céphalées. Méthodes Il s’agit d’une étude nationale multicentrique menée au cours de laquelle les patients ont été évalués cliniquement par un même questionnaire et ont été explorés avec une IRM cérébrale et une véno IRM. Cette dernière a été réalisée selon des séquences préétablies et interprétées de manière consensuelle par deux neuroradiologues séniors, aveugle vis-à-vis du diagnostic clinique des sujets. Une VRM a été également réalisée au sein d’un groupe de patients « témoins » non céphalalgiques venant pour un dépistage ou un bilan d’extension. Résultats Quarante et un patients présentant une céphalée circonstancielle ont été recrutés au sein de six centres français : 20 patients avec une céphalée liée à l’activité sexuelle, 11 avec une céphalée à l’effort et 10 patients avec une céphalée à la toux. Les patients présentant une céphalée à la toux ont une moyenne d’âge plus élevée, une comorbidité avec la migraine moins fréquente que dans les céphalées liées à l’effort ou à l’activité sexuelle. Les céphalées d’effort et liées à l’activité sexuelle ont une présentation clinique semblable caractérisée par une céphalée de durée plus longue que celle observée lors de la céphalée à la toux. L’association avec la maladie migraineuse est plus fréquente. Sur le plan neuroradiologique, la VRM révèle des modifications du système veineux situées soit sur les sinus transverses, soit sur les jugulaires. Dans la population céphalée à la toux, un seul patient a un système veineux normal ou avec des modifications de calibre < 50%. Dans le groupe des céphalées à l’effort les patients ne semblent pas avoir de lésions jugulaires significatives, mais ce segment n’a pas été exploré de façon constante en fonction des centres. Enfin, les patients présentant des céphalées liées à l’activité sexuelle ont des sténoses veineuses à la fois sur les sinus transverses et les jugulaires. Conclusions Les patients présentant une céphalée circonstancielle semblent présenter un nombre plus important de modifications du système veineux cérébral. Cependant ce type de céphalée reste relativement rare et cette hypothèse nécessite d’être confirmée sur un échantillonnage plus important afin de voir la proportion précise de patients présentant des modifications du système veineux cérébral.
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The purposes of this study are to describe clinical features of primary cough headache, primary exertional headache, and primary headache associated with sexual activity and to evaluate potential association with abnormalities in the... more
The purposes of this study are to describe clinical features of primary cough headache, primary exertional headache, and primary headache associated with sexual activity and to evaluate potential association with abnormalities in the cerebral or cervical venous circulation. This multicentre, observational, non-interventional consecutive cohort study included patients fulfilling ICHD-II criteria for primary cough headache (N = 10), primary exertional headache (N = 11), or primary headache associated with sexual activity (N = 20), as well as 16 headache-free controls. Each patient was evaluated clinically and underwent craniocervical MRV of the cranial circulation. All scans were interpreted centrally by blinded raters, using the Farb criteria proposed for idiopathic intracranial hypertension. Stenosis was defined as a Farb score <3 in left or right transverse sinuses or jugular veins. In all primary headache groups, headaches were most frequently diffuse, severe, or very severe. Headache duration was significantly shorter in patients with cough headache (median 6.5 versus 20 and 60 min). An exploitable magnetic resonance venogram was obtained for 36 patients. Stenosis was detected in none of the control group, but in 5/7 patients with primary cough headache group, 2/10 patients with primary exertion headache, and 12/19 patients with primary headache associated with sexual activity. The frequency of stenosis was significantly different from the control group in the primary cough headache and primary headache associated with sexual activity groups. Headaches provoked by cough and sexual activity are possibly associated with venous abnormalities in a significant subgroup of affected patients. As the literature shows conflicting results, this venous stenosis can be considered as a promoting factor.
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Photophobia is an abnormal sensitivity to light experienced by migraineurs during attacks. The pathophysiology of photophobia is poorly understood. Nevertheless, 2 facts appear to have a link with photophobia: visual cortex... more
Photophobia is an abnormal sensitivity to light experienced by migraineurs during attacks. The pathophysiology of photophobia is poorly understood. Nevertheless, 2 facts appear to have a link with photophobia: visual cortex hyperexcitability on the one hand and interactions between visual pathway and trigeminal nociception on the other. We used H(2)(15)O PET to study photophobia induced by continuous luminous stimulation covering the whole visual field in 8 migraineurs during spontaneous migraine attacks, after headache relief by sumatriptan and during attack-free interval. The intensity of the luminous stimulation provoking photophobia with subsequent headache enhancement was specifically determined for each patient. We found that low luminous stimulation (median of 240 Cd/m(2)) activated the visual cortex during migraine attacks and after headache relief but not during the attack-free interval. The visual cortex activation was statistically stronger during migraine headache than after pain relief. These findings suggest that ictal photophobia is linked with a visual cortex hyperexcitability. The mechanism of this cortical hyperexcitability could not be explained only by trigeminal nociception because it persisted after headache relief. We hypothesize that modulation of cortical excitability during migraine attack could be under brainstem nuclei control.
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Research Interests: Ophthalmology, Pain, Positron Emission Tomography, Modulation, Visual Cortex, and 14 moreHumans, Multisensory Integration, Female, Functional Imaging, Posterior Parietal Cortex, Primary visual cortex, Adult, Parietal Lobe, Clinical Study, Photophobia, Trigeminal, Pain Measurement, photic stimulation, and Psychology and Cognitive Sciences
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To confirm the clinical efficacy of frovatriptan 2.5 mg. Frovatriptan is a new 5-hydroxytryptamine (5-HT)(1B/1D) receptor agonist being developed for the acute treatment of migraine with or without aura. Results from preclinical and... more
To confirm the clinical efficacy of frovatriptan 2.5 mg. Frovatriptan is a new 5-hydroxytryptamine (5-HT)(1B/1D) receptor agonist being developed for the acute treatment of migraine with or without aura. Results from preclinical and clinical pharmacology studies showed frovatriptan to be a potent 5-HT(1B) receptor agonist with a long terminal elimination half-life (26 hours) and a broad therapeutic index. Three randomized, placebo-controlled, double-blind, parallel-group trials, in a total of 2676 patients, were performed to confirm the clinical efficacy of frovatriptan 2.5 mg for the acute treatment of migraine. In all three studies, headache response 2 hours after frovatriptan dosing was significantly greater than that seen with placebo (P < or = .001) with approximately a two-fold measure of effect over placebo for headache response at 2 and 4 hours postdosing. Time to headache response occurred within 1.5 hours in a substantial proportion of patients. The incidence of 24-hour headache recurrence with frovatriptan was low (10% to 25%). Frovatriptan therapy also was associated with a high degree of patient satisfaction. Frovatriptan represents a consistently effective acute treatment for migraine and accompanying symptoms.
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To examine the efficacy of rizatriptan 10-mg orally disintegrating tablet (ODT) for treating migraines of mild intensity soon after onset, with or without patient-specific migraine education. Studies have shown rizatriptan tablet efficacy... more
To examine the efficacy of rizatriptan 10-mg orally disintegrating tablet (ODT) for treating migraines of mild intensity soon after onset, with or without patient-specific migraine education. Studies have shown rizatriptan tablet efficacy in early migraine treatment. In this randomized, placebo-controlled, double-blind, factorial design study, adults with a history of migraine were assigned to rizatriptan 10-mg ODT patient education (personalized summary of early migraine signs and symptoms) or placebo patient education in a 1 : 1 : 1 : 1 ratio. Patients were instructed to treat 1 attack at the earliest time they knew that their headache was a migraine, while pain was mild. During the next 24 hours, patients assessed pain severity, associated symptoms, functional disability, use of rescue medication, and treatment satisfaction. The primary endpoint was pain freedom at 2 hours; a key secondary endpoint was 24-hour sustained pain freedom. Of 207 patients randomized to treatment, 188 (91%) treated a study migraine. Significantly more patients taking rizatriptan reported pain freedom at 2 hours compared with placebo (66.3% vs 28.1%, P < .001). Similarly, significantly more patients taking rizatriptan reported 24-hour sustained pain freedom (52.2% vs 17.7%, P < .001). A greater proportion of patients in the rizatriptan + education group reported pain freedom at 2 hours compared with those in the rizatriptan + no education group (71.7% vs 60.9%, P = .430). Few adverse events were reported. Rizatriptan 10-mg ODT, when taken early, while headache pain is mild, was superior to placebo at providing pain freedom at 2 hours and 24-hour sustained pain freedom.
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Migraine sufferers experience premonitory symptoms which suggest that primary hypothalamic dysfunction is a likely trigger of the attacks. Neuroendocrine and laboratory data also support this hypothesis. To date, positron emission... more
Migraine sufferers experience premonitory symptoms which suggest that primary hypothalamic dysfunction is a likely trigger of the attacks. Neuroendocrine and laboratory data also support this hypothesis. To date, positron emission tomography (PET) scans of migraine sufferers have demonstrated activation of brainstem nuclei, but not of the hypothalamus. To record cerebral activations withH2 15OPET during spontaneous migraine without aura attacks. We scanned 7 patients with migraine without aura (6 females and 1 male) in each of 3 situations: within 4 hours of headache onset, after headache relief by sumatriptan injection (between the fourth and the sixth hour after headache onset), and during an attack-free period. During the headache we found not only significant activations in the midbrain and pons, but also in the hypothalamus, all persisting after headache relief by sumatriptan. Hypothalamic activity, long suspected by clinical and experimental arguments as a possible trigger for migraine, is demonstrated for the first time during spontaneous attacks.
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This randomized, double-blind, double-dummy, multicenter, parallel-group study aimed at comparing the efficacy and safety of calcium carbasalate (equivalent to 900 mg aspirin) plus metoclopramide 10 mg (CM) with ergotamine tartrate 1 mg... more
This randomized, double-blind, double-dummy, multicenter, parallel-group study aimed at comparing the efficacy and safety of calcium carbasalate (equivalent to 900 mg aspirin) plus metoclopramide 10 mg (CM) with ergotamine tartrate 1 mg plus caffeine 100 mg (EC) administered in the treatment of 2 acute migraine attacks. A total of 296 patients fulfilling the International Headache Society diagnostic criteria for migraine were enrolled. In total, one or two migraine attacks were treated in 268 and 235 patients, respectively. The primary endpoint for the first treated attack was headache relief, with intensity decreasing from moderate or severe to mild or absent 2 h after drug intake. Usual secondary efficacy endpoints were assessed. A superiority of CM over EC was observed for both treated attacks for the main endpoint: success in 54 versus 36%, p = 0.003 for the first attack and 60 versus 44%, p = 0.02 for the second attack. CM was also significantly superior to EC during the first attack for complete headache relief (20 vs. 8%, p = 0.006), nausea (42 vs. 63%, p = 0. 007) and willingness to take the drug again (90 vs. 80%, p = 0.043). The global efficacy evaluation, rated by the investigators, was significantly more favorable to CM for both attacks (p = 0.001 for the first attack and p = 0.02 for the second). The patients' evaluation was significant for the first attack (p = 0.002). The global incidence of adverse events was 45% higher with EC, though not significant (32 vs. 22%, p = 0.075). They were most often unspecific and mild to moderate in intensity. Gastrointestinal side effects were significantly less frequent with CM than EC (7 vs. 21%, p = 0.001). Thus, CM is more effective and has a better gastrointestinal safety than EC in the acute treatment of migraine attacks.
Research Interests: Treatment Outcome, Adolescent, Safety, Humans, Caffeine, and 20 moreFemale, Male, Urea, Aspirin, Nausea, Clinical Sciences, European, Aged, Middle Aged, Adult, Adverse Event, Combination drug therapy, Side Effect, Abdominal Pain, Neurosciences, Analgesics, Sleep Stages, Ergotamine, Diagnostic Criteria, and metoclopramide
This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666... more
This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.
Research Interests: Clinical Trial, Treatment Outcome, Adolescent, Humans, Female, and 16 moreMale, Aspirin, Clinical Sciences, Aged, Middle Aged, Adult, Adverse Event, Combination drug therapy, Acetylsalicylic Acid, Neurosciences, Oxazolidinones, Confidence Interval, Tryptamines, Acute Disease, Combination Therapy, and metoclopramide
Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to... more
Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.
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Migraine is a chronic disease that significantly reduces quality of life between, as well as during, attacks. Treatments that provide consistent relief may reduce the burden of the disease. In the open-label phase of a two-part study,... more
Migraine is a chronic disease that significantly reduces quality of life between, as well as during, attacks. Treatments that provide consistent relief may reduce the burden of the disease. In the open-label phase of a two-part study, patients could choose to treat initial, persistent or recurrent migraine headache of any intensity with 2.5 mg or 5 mg zolmitriptan. This novel study design allowed patients to manage and maximise their migraine relief. Headache response rates and pain-free response rates were assessed within two hours of dosing with zolmitriptan, and response rates were compared across migraines with and without a history of aura, and associated or not with menses. Consistency of response was also assessed in those patients treating at least 20 attacks. Of 49,784 attacks treated, 66% (32,737 attacks) were treated with a single dose of zolmitriptan. Two-hour headache response rates to an initial dose of 2.5 mg or 5 mg zolmitriptan were 85% (median 95%) and 79% (median 88%), respectively, across all attacks. Corresponding pain-free response rates were 69% and 59%. Responses were independent of gender and age and were similar in patients with and without aura and in attacks associated or not associated with menses. Consistent response rates were achieved within individual patients; during months 1 to 3, 64% of patients reported a headache response in > 75% of their migraine attacks. In patients treating at least 20 attacks, 2.5 mg and 5 mg zolmitriptan produced consistently high headache response rates (range 84-91% and 76-84%, respectively) and pain-free response rates (range 70-76% and 58-65%, respectively) across attacks. In the minority of attacks requiring a second dose of zolmitriptan for persistent or recurrent headache, response rates to a second dose were also consistent across attacks. In conclusion, zolmitriptan 2.5 mg and 5 mg show consistent effectiveness in the treatment of multiple migraine attacks in individual patients and are unaffected by gender, age and the presence of aura or the relationship to menses.
Research Interests: Economics, Adolescent, Humans, Child, Female, and 7 moreMale, Aged, Middle Aged, Adult, Time Factors, Oxazolidinones, and Tryptamines
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Research Interests: Primary Care, Primary Health Care, Coping Strategies, Depression, Treatment Outcome, and 17 moreAnxiety, Prospective studies, Humans, Female, Male, Cohort Study, Hospital Anxiety and Depression Scale, Clinical Sciences, Middle Aged, Adult, ANXIETY, Acetaminophen, Psychological Stress, Mood Disorder, Neurosciences, Tryptamines, and Cohort Studies
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Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. Thirteen CCH... more
Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. Thirteen CCH patients were operated and data were collected prospectively. All of them suffered from CCH according to the International Headache Society classification, lasting for more than 2 years, refractory to pharmacological prophylactic treatment with adequate trials, with at least one daily attack. Chronic ONS was delivered through a subcutaneous occipital electrode connected to an implanted generator, in order to induce paraesthesias perceived locally in the lower occipital region. After surgery (mean follow-up 14,6 months), the mean attack frequency and intensity decreased by 68% and 49%, respectively. At last follow-up, 10/13 patients were considered as responders (improvement >50%). Prophylactic treatment could be stopped or reduced in 8/13 cases. Local infection occurred in one patient, leading to hardware removal. Our data confirmed the results of the 36 similar cases reported in the literature, suggesting that ONS may act as a prophylactic treatment in chronic CH. Considering their respective risks, ONS should be proposed before deep brain stimulation in severe refractory CCH patients.
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Research Interests:
Deep brain stimulation of the posterior hypothalamus is a therapeutic approach to the treatment of refractory chronic cluster headache, but the precise anatomical location of the electrode contacts has not been clearly assessed. Our aim... more
Deep brain stimulation of the posterior hypothalamus is a therapeutic approach to the treatment of refractory chronic cluster headache, but the precise anatomical location of the electrode contacts has not been clearly assessed. Our aim was to study the location of the contacts used for chronic stimulation, projecting each contact centre on anatomic atlases. Electrodes were implanted in a series of 10 patients (prospective controlled trial) in the so-called 'posteroinferior hypothalamus' according to previously described coordinates, i.e. 2 mm lateral, 3 mm posterior and 5 mm below the mid-commissural point. The coordinates of the centre of each stimulating contact were measured on postoperative computed tomography or magnetic resonance imaging scans, taking into account the artefact of the electrode. Each contact centre (n=10; left and right hemispheres pooled) was displayed on the Schaltenbrand atlas and a stereotactic three dimensional magnetic resonance imaging atlas (4.7 tesla) of the diencephalon-mesencephalic junction for accurate anatomical location. Of the 10 patients with 1-year follow-up, 5 responded to deep brain stimulation (weekly frequency of attacks decrease >50%). In responders, the mean (standard deviation) coordinates of the contacts were 2.98 (1.16) mm lateral, 3.53 (1.97) mm posterior and 3.31 (1.97) mm below the mid-commissural point. All the effective contacts were located posterior to the hypothalamus. In responders, structures located <2 mm from the centres of effective contacts were: the mesencephalic grey substance (5/5), the red nucleus (4/5), the fascicle retroflexus (4/5), the fascicle longitudinal dorsal (3/5), the nucleus of ansa lenticularis (3/5), the fascicle longitudinal medial (1/5) and the thalamus superficialis medial (1/5). The contact coordinates (Wilcoxon test) and the structures (Fisher's exact test) were not significantly different between responders and non-responders. These findings suggest that failure of deep brain stimulation treatment in cluster headache may be due to factors unrelated to electrode misplacement. They also suggest that the therapeutic effect is probably not related to direct hypothalamic stimulation. Deep brain stimulation might modulate either a local cluster headache generator, located in the hypothalamus or in the mesencephalic grey substance, or non-specific anti-nocioceptive systems.
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SMILE was an observational study carried out in France among office-based general practitioners (GPs) and neurologists from November 2005 to July 2006 to assess the determinants of prescription of migraine preventive therapy in primary... more
SMILE was an observational study carried out in France among office-based general practitioners (GPs) and neurologists from November 2005 to July 2006 to assess the determinants of prescription of migraine preventive therapy in primary care medicine. A total of 1467 GPs and 83 neurologists were included, treating 5417 and 248 migraine sufferers, respectively. The main factors leading physicians to deem a patient eligible for preventive treatment were perceived medication overuse and frequency of headaches, and secondarily, severity of headaches and functional impact. On the other hand, patient satisfaction with the acute treatment of attacks and triptan use, and secondarily, a long migraine history were found to influence patient eligibility negatively. Noticeably, psychiatric disorders (anxiety, stress) did not appear, aside from somatic factors, among the determinants that significantly influence physicians' judgment about the option of establishing a preventive treatment. However, they are important features of migraine condition and should be listed among the factors guiding choices about migraine preventive therapy.