Desencadenantes migrañosos y habituación del potencial evocado visual. Definiendo subgrupos de pacientes / Migraine triggers and habituation of visual evoked potentials. Defining subset of patient

Identificar subgrupos específicos de pacientes dentro del espectro clínico de la migraña podría ayudar a personalizar el tratamiento de la misma. Definir perfiles de pacientes según su relación entre las características clínicas y los biomarcadores neurofisiológicos sería de suma importancia y es en gran medida un ámbito inexplorado. Los ataques de migraña pueden ser desencadenados por distintos factores, entre los cuales el estrés, los cambios hormonales, el ayuno y la falta de sueño son los mayormente asociados. Los desencadenantes de la migraña no forman parte de los criterios diagnósticos, pero pueden caracterizar subgrupos de pacientes. La deficiente habituación a los estímulos visuales repetidos es una característica neurofisiológica comúnmente encontrada en las cohortes de migraña, sin embargo, no se puede demostrar en todos los pacientes y no se ha reproducido en todos los estudios. Se puede suponer que los pacientes con diferentes perfiles de habituación pueden diferir por rasgos fenotípicos, como los desencadenantes de las crisis. Por ello nos propusimos estudiar qué asociación existe entre los desencadenantes del ataque de migraña y la habituación de los potenciales evocados visuales (PEV). (AU)

Identifying specific subsets of patients within the widespread clinical spectrum of migraine could help in developing a beneficial migraine treatment approach. The possibility of such categorization combining clinical features with accessible para-clinical tests remains quasi unexplored. Migraine attacks can be triggered by different factors, among which stress, hormonal changes, fasting, and lack of sleep are the most frequently referenced.1 Migraine triggers are not part of the diagnostic criteria for migraine, but they may characterize subgroups of patients. Also, deficient habituation to repeated stimulations is a neurophysiological feature commonly found in migraine cohorts, however it cannot be demonstrated in all patients and has not been reproduced in all studies. One may thus assume that patients with different habituation profiles might differ by phenotypic features, such as attack triggers. Therefore, we analyzed the visual evoked potentials habituation (VEP)4 profile in relation to the report of migraine triggers during a head-to-head, semi-structured interview, which preceded the neurophysiological recordings. (AU)

[Clinical pathway evaluation for left colectomy in abdominal surgery]. / Evaluation d'un itinéraire clinique pour colectomie gauche en chirurgie abdominale.

At the end of 2008, a left colectomy clinical pathway was implemented at Clinique Saint-Joseph (CHC) in Liège (Belgium). A sample of 213 patients with benign or malignant pathology requiring laparoscopic left colon resection was included in this clinical pathway during the years 2009 to 2015. We focused on the compliance with the protocol, on the complication rate and the incidence of re-hospitalization within 30 days after surgery. In comparison with a historical control group, we observed that the compliance was excellent (superior to 80 %) from 2009 to 2015. The re-hospitalization did not differ though the complication rate decreased. Although the hospital stay was not our primary objective, it decreased significantly from 8 to 4 days (average). This analysis leads to the conclusion that the introduction of a clinical pathway, when it is well prepared and brings together all the implicated persons with the same goal, is directly beneficial to the patient and the quality of its management.

Fin 2008, l'itinéraire clinique (IC) «colectomie gauche¼ a été mis en place au sein de la Clinique Saint-Joseph (CHC) de Liège. Une série de 213 patients présentant une pathologie bénigne ou maligne nécessitant une résection du côlon gauche par laparoscopie a été incluse dans cet IC entre 2009 et 2015. Nous nous sommes intéressés à l'observance du protocole de l'IC ainsi qu'aux taux de complications et de ré-hospitalisations dans les 30 jours post-opératoires. Nous avons constaté, après comparaison avec un groupe témoin historique, que l'adhésion au protocole IC a été d'emblée excellente (supérieur a 80 %) tout au long de la durée de l'étude. Il n'y a pas eu de modification du taux de ré-hospitalisations et le taux de lâchage de suture a été réduit. Bien que la diminution de la durée de séjour n'était pas l'objectif premier lors de la mise en place de cet IC, elle s'est significativement réduite passant, en moyenne, de 8 à 4 jours. En conclusion, l'introduction d'un IC, pour autant qu'il soit bien préparé et rassemble dans le même objectif l'ensemble des acteurs de soins, est directement bénéfique pour le patient et la qualité de sa prise en charge.

Analysis and clinical correlates of 20 Hz photic driving on routine EEG in migraine.

Enhanced photic driving (PD) during high-frequency flicker stimulation, the so-called H response, is a classical feature of migraine patients between attacks, but is thought to be of poor clinical utility. Visual inspection of the EEG for its detection may not be reliable, however, data on its possible correlations with clinical features and migraine pathophysiology are scarce. We have compared visual inspection and EEG spectral analysis to detect abnormal PD in 280 consecutive migraine patients of our headache clinic (episodic migraine without aura, n = 171; chronic migraine, n = 48; migraine with aura, n = 61) and in a group of 24 non-migrainous neurological controls. Spectral frequency analyses were performed blindly by one of us (YF). On visual inspection, 50.4 % of migraineurs were thought to have increased 20 Hz PD. After spectral analysis, only 62.4 % of them had PD power superior to the mean + 95 % CI of the control group. Sensitivity of visually identified PD was 82.24 %, specificity 69.36 %. Increased PD on spectral analysis was more prevalent in episodic migraine than in chronic migraine, in patients with low attack frequency, in those with ictal autonomic symptoms in addition to nausea and in those with a strong family history of migraine. We confirm therefore that 20 Hz photic driving is of little diagnostic utility and its prevalence in migraine overestimated on visual inspection. Its presence on spectral analysis of the EEG, however, might be of pathophysiological interest, as it identifies subgroups of migraineurs of whom the common denominator could be lack of habituation of cortical responses during repetitive stimulation.

[Migraine: from genetics to environment]. / Les migraines: des gènes à l'environnement.

Migraine is a frequent neurological syndrome with a heterogenous clinical presentation. Its pathophysiology remains poorly understood but a genetic aetiology has been suspected for a long time, as well as a significant influence of the environment. Familial hemiplegic migraine belongs to monogenic migraines, which are very rare entities with an autosomal dominant transmission. In that type of migraine, environment has a minor role, even if some attack triggering factors have been identified. The common forms of migraines, with and without aura, episodic or chronic, are polygenic and the results of genetic studies concerning these migraines are rather disappointing. The recent use of genome-wide approaches (linkage analyses and genome wide association studies) opened new perspectives and more convincing results are eagerly awaited in the next years. The environmental contribution (endogenous or exogenous) is much more pronounced in the common forms of migraine, with the identification of numerous predisposing or triggering factors, among which only some can be avoided. Finally, a recent behavioural hypothesis coming from adaptative darwinian theories has proposed a genetic-environment integrative model for common migraine. The latter would result of hereditary physiological adaptative defence mechanisms which would be progressively impaired by repeated brain homeostasis imbalances due to the environment.

[Neurostimulation: which place in the treatment of refractory headaches?]. / La neurostimulation: quelle place dans les céphalées réfractaires?

The management of refractory headaches (migraine or cluster headache) is often challenging in clinical practice. Most of the time, these patients are "desperate" and have already tried all existing medications. Many progresses have recently been made in the therapeutic approach of these diseases, especially with the advent of neurostimulation techniques. In this review of the literature, we describe various neurostimulation methods which have been studied in clinical trials or case reports of refractory headaches. The most effective and best studied methods are occipital nerve stimulation (ONS) and hypothalamic deep brain stimulation (DBS), the latter being however at higher surgical risk. Hence, there is a new hope for patients with refractory headaches. Various clinical trials are still underway.

Habituation of evoked responses is greater in patients with familial hemiplegic migraine than in controls: a contrast with the common forms of migraine.

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.

Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs.

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.

Evaluation and proposal for optimalization of neurophysiological tests in migraine: part 1--electrophysiological tests.

Neurophysiological testing has become a valuable tool for investigating brain excitability and nociceptive systems in headache disorders. Previous reviews have suggested that most neurophysiological tests have limited value for headache diagnosis, but a vast potential for exploring the pathophysiology of headaches, the central effects of certain pharmacological treatments and phenotype-genotype correlations. Many protocols, however, lack standardization. This meta-analytical review of neurophysiological methods in migraine was initiated by a task force within the EUROHEAD project (EU Strep LSHM-CT-2004-5044837-Workpackage 9). Most of the neurophysiological approaches that have been used in headache patients are reviewed, i.e. evoked potentials, nociception-specific blink reflex, single-fibre electromyography, neuroimaging methods (functional MRI, PET, and voxel-based morphometry) and the nitroglycerin attack-provoking test. For each of them, we summarize the results, analyse the methodological limitations and propose recommendations for improved methodology and standardization of research protocols. The first part is devoted to electrophysiological methods, the second to neuroimaging techniques and the NTG test.

Evaluation and proposal for optimization of neurophysiological tests in migraine: part 2--neuroimaging and the nitroglycerin test.

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.

Interictal abnormalities of gamma band activity in visual evoked responses in migraine: an indication of thalamocortical dysrhythmia?

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.

The vestibulo-collic reflex is abnormal in migraine.

Interictal evoked central nervous system responses are characterized in migraineurs by a deficit of habituation, at both cortical and subcortical levels. The click-evoked vestibulo-collic reflex (VCR) allows the assessment of otolith function and an oligosynaptic pathway linking receptors in the saccular macula to motoneurons of neck muscles. Three blocks of 75 averaged responses to monaural 95-dB normal hearing level 3-Hz clicks were recorded over the contracted ipsilateral sternocleidomastoid muscle in 25 migraineurs between attacks and 20 healthy subjects, without vestibular symptoms. Amplitudes, raw and corrected for baseline electromyography, were significantly smaller in migraine patients. Whereas in healthy volunteers the VCR habituated during stimulus repetition (-4.96% +/- 14.3), potentiation was found in migraineurs (4.34% +/- 15.3; P = 0.04). The combination with a reduced mean amplitude does not favour vestibular hyperexcitability as an explanation for the habituation deficit in migraine, but rather an abnormal processing of repeated stimuli in the reflex circuit.

[Therapeutic armamentarium in neurology: the birth of a new era]. / L'arsenal thérapeutique en neurologie: une nouvelle ère voit le jour.

The field of neurology was long infamous for a lack of therapeutic options. How many of you have once thought: "Neurologists don't cure the disease, they admire it". But those days have passed into history, and the field is now vibrant with new treatments and hope even for patients with the worst neurodegenerative diseases. We summarized in the present review the latest major advances in therapeutic principles and practice for some of the most frequent chronic neurological disorders such as headaches, epilepsy, multiple sclerosis, dementias, Parkinson's disease, sleep/wake disturbances and peripheral neuropathies. We cannot cure or prevent, but we can now halt or control symptoms and disease progression to provide physical and psychological relief, and a better quality of life for patients who suffer from these otherwise devastating neurological conditions.

Search for correlations between genotypes and electrophysiological patterns in migraine: the MTHFR C677T polymorphism and visual evoked potentials.

Interictally, migraineurs have on average a reduction in habituation of pattern-reversal visual evoked potentials (PR-VEP) and in mitochondrial energy reserve. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and its C677T polymorphism may be more prevalent in migraine. The aim of this study was to search in migraineurs for a correlation between the MTHFR C677T polymorphism and the PR-VEP profile. PR-VEP were recorded in 52 genotyped migraine patients: 40 female, 24 without (MoA), 28 with aura (MA). Among them 21 had a normal genotype (CC), 18 were heterozygous (CT) and 13 homozygous (TT) for the MTHFR C677T polymorphism. Mean PR-VEP N1-P1 amplitude was significantly lower in CT compared with CC, and tended to be lower in TT with increasing age. The habituation deficit was significantly greater in CC compared with TT subjects. The correlation between the cortical preactivation level, as reflected by the VEP amplitude in the first block of averages, and habituation was stronger in CC than in CT or TT. The MTHFR C677T polymorphism could thus have an ambiguous role in migraine. On one hand, the better VEP habituation which is associated with its homozygosity, and possibly mediated by homocysteine derivatives increasing serotoninergic transmission, may protect the brain against overstimulation. On the other hand, MTHFR C677T homozygosity is linked to a reduction of grand average VEP amplitude with illness duration, which has been attributed to brain damage.

Inhibition of the nociceptive R2 blink reflex after supraorbital or index finger stimulation is normal in migraine without aura between attacks.

In order to explore possible interictal brainstem dysfunctions in migraine, we have studied the R2 component of the nociceptive specific blink reflex (nBR) after conditioning by supraorbital or index finger stimuli in 14 untreated migraine without aura patients (MO) between attacks and in 15 healthy volunteers. We determined the R2 recovery curve at increasing inter-stimulus intervals between 50 and 600 ms. The nBR was conditioned by a paired supraorbital stimulus and, in another session, by an ipsilateral electrical shock delivered to the index finger. The R2 nBR recovery curves were normal in MO patients for both the supraorbital and peripheral conditioning. These results do not favour persistent interictal sensitization in the spinal trigeminal sensory system. They also suggest that the control exerted by descending brainstem pathways on medullary R2 interneurones is normal in migraine between attacks.

Interictal habituation deficit of the nociceptive blink reflex: an endophenotypic marker for presymptomatic migraine?

Habituation of the nociception-specific blink reflex (nBR) is reduced interictally in migraine patients. This could be related to the habituation deficit of evoked cortical responses, a reproducible abnormality in migraine which has a familial character, or to central trigeminal sensitization due to repeated attacks. We compared nBR habituation in healthy volunteers devoid of personal or family history of migraine (HV), in migraine without aura patients (MO) and in healthy volunteers with a family history of migraine in first degree relatives (HV-F). We elicited the nBR by stimulating the right supraorbital region with a custom-built electrode in 16 MO between attacks, 15 HV and 14 HV-F. Habituation was measured as the percentage area-under-the-curve decrease in 10 consecutive blocks of five averaged rectified responses. nBR habituation was clearly reduced in MO and HV-F compared to HV. Percentage area under the curve decreased between the 1st and the 10th block by 55.01% in HV, 25.71% in MO (P = 0.001) and 26.73% in HV-F (P = 0.043). HV-F had the most pronounced abnormality with potentiation instead of habituation in the second block. We found a positive intraindividual correlation between attack frequency and habituation in MO (r = 0.621; P = 0.010). Migraine patients have interictally a deficient habituation of the nBR which is inversely related to attack frequency, suggesting that it is not due to trigeminal sensitization. Surprisingly, the most pronounced habituation deficit is found in asymptomatic individuals with a family history of migraine. Deficient nBR habituation could thus be a trait marker for the genetic predisposition to migraine.

[Medication overuse headache]. / Les céphalées par abus d'antalgiques. et d'anti-migraineux.

Medication overuse headache (MOH) insidiously evolves from episodic migraine or tension-type headache because of overconsumption of analgesics, ergotamine or triptans. It affects 1-2% of the general population, but 15-20% of patients attending specialized headache centers. The precise neurobiologic mechanisms underlying this complication of episodic headaches are not well understood. Abnormalities of central monoaminergic systems have been suggested and substance dependence is more frequent in personal and family histories of affected subjects. In a recent FDG-PET study of 16 migraineurs with MOH before and after analgesics withdrawal we found a persistent hypometabolism of the medial orbitofrontal cortex, comparable to the one described after withdrawal in substance abuse. The orbitofrontal cortex plays a pivotal role in drive, decision-making and drug dependence. We postulate that its hypoactivity predisposes certain migraineurs to MOH and to relapse after withdrawal. There is no unique management strategy for these patients, but medication withdrawal is a prerequisite for the effectiveness of preventive treatments and headache improvement.

Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial.

Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10), is effective in migraine prophylaxis. We compared CoQ10 (3 x 100 mg/day) and placebo in 42 migraine patients in a double-blind, randomized, placebo-controlled trial. CoQ10 was superior to placebo for attack-frequency, headache-days and days-with-nausea in the third treatment month and well tolerated; 50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10 (number-needed-to-treat: 3). CoQ10 is efficacious and well tolerated.

[Alcohol, insulin sensitivity and diabetes]. / Alcool, sensibilité à l'insuline et diabète sucré.

The relationship between alcohol consumption and insulin resistance shows a U-shaped curve: insulin resistance is minimal in individuals with regular mild to moderate alcohol consumption and increases in both heavy drinkers and subjects without any alcohol consumption. These favourable metabolic effects on insulin sensitivity of moderate alcohol consumption may explain the significant reduction in the development of type 2 diabetes and the risk of cardiovascular complications reported in numerous epidemiological studies. This latter effect has also reported in patients with diabetes mellitus, although this observation remains controversial. However, alcohol consumption could increase the global risk of hypoglycaemia, both in the fasting state and after a meal (reactive hypoglycaemia) in both diabetic and nondiabetic subjects. These latter effects may result from a direct inhibition of gluconeogenesis, from a reduced secretion of counterregulatory hormones and/or from an alcohol-induced inappropriate behaviour.

[How I explore...glycemic kinetics by continuous glucose monitoring]. / Comment j'explore ... la cinétique glycémique des patients diabétiques par monitoring continu du glucose interstitiel.

The improvement of diabetic patients' glycaemic status requires an increase of fingerstick blood glucose measurements. Among the possibilities available to assess diabetes' control, we will consider new systems of continuous interstitial glucose monitoring. After a brief description of the devices presently commercialized, we will discuss their indications and their limitations, as well as their future prospects in a possible "closed loop" insulin delivery according to blood glucose level.

[Smoking, insulin resistance and type 2 diabetes]. / Tabagisme, insulinorésistance et diabète de type 2.

Smoking is a major risk factor for cardiovascular disease. It is associated with endothelial dysfunction and lipid disorders similar to those found in the insulin resistance syndrome. Studies have thus tried to demonstrate a relationship between smoking and insulin resistance, and between smoking and type 2 diabetes mellitus. Even if their results may sometimes differ, smoking does seem to be associated with an impaired insulin sensitivity that is proportional to tobacco consumption. Nicotine replacement therapies seem also to generate a certain, though lower, degree of insulin resistance. If there is no major weight gain after smoking cessation, the latter is accompanied by a progressive return to normal insulin sensitivity. Several large epidemiological studies recently demonstrated that smoking could increase the risk of type 2 diabetes mellitus, with a relative risk between 1.5 and 3.0. Finally, among type 2 diabetic patients, smoking has a harmful effect on metabolic control and long-term complications of the disease, at least partially by increasing the components of the insulin resistance syndrome. All these observations represent further argument to promote smoking cessation in the general population, and more particularly in individuals at risk to develop type 2 diabetes, as well as in the diabetic population.