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.