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Vagus nerve stimulation (VNS) is an old, yet new, option for treatment-resistant depression. Despite several clinical trials over the last 15 years showing a consistent benefit-risk balance of the technic, VNS still struggles to find its place in our therapeutic algorithms. This is especially true in France, where only a few surgeries have been performed nationwide, all in the last year. The reasons behind this lag are manifolds; (1) psychiatrists usually do not consider surgical treatments, even when they are minimally invasive and reversible, (2) early VNS trials stumbled on methodological difficulties that are common to all invasive neurostimulation technics, and initially failed to provide strong evidence for its efficacy, and (3) VNS requires multidisciplinary teams involving psychiatrists and neurosurgeons that did not exist then. Nevertheless, studies of the past twenty years support VNS as a treatment of depression endowed with a unique efficacy profile: a long runner best at maintaining remission in hard-to-stabilize depression, even in the context of ECT withdrawal, and irrespective of whether it is unipolar or bipolar. Thus, VNS potentially addresses the unmet medical needs of some of the most severe and chronic patients with depression. This review aims at introducing VNS as a treatment option for depression, summarizing available evidence for its efficacy and tolerance, and delineating patient profiles that might benefit the most of such treatment.

National audience; Introduction et but de l’étude : Les modèles murins d’obésité induite par l’alimentation comparent les effets de la consommation de régimes riches en lipides, composés d’ingrédients purifiés à ceux de la consommation de régimes normo-lipidiques formulés avec des ingrédients complexes. Des travaux récents suggèrent que les effets métaboliques de ces régimes ne seraient pas entièrement liés au taux de lipides de l’aliment mais également à la nature purifiée ou complexe des ingrédients qui les composent. Chez le rat, l’obésité s’accompagne d’une réduction de la sensibilité du nerf vague à la cholécystokinine (CCK), peptide satiétogène sécrété par l’intestin. Notre objectif était d’évaluer si cette perte de sensibilité à la CCK était liée à la consommation excessive de lipides ou à la nature purifiée/complexe des ingrédients composant les régimes et si la nature des fibres alimentaires (cellulose vs inuline) du régime obésogène pouvait moduler cette perte de sensibilité à la CCK. Matériel et méthodes : Des rats Wistar males ont été nourris avec un régime normo-lipidique composé d’ingrédients complexes (C), ou avec des régimes composés d’ingrédients purifiés, à teneur normale (10% de l’énergie) ou élevée en lipides (45%) et contenant une nature de fibres différente: 10% de cellulose (LFC et HFC) ou 10% d’inuline (LFI et HFI). Après 7 semaines de consommation, la sensibilité à la CCK des rats a été évaluée en comparant la prise alimentaire après injection i.p. de CCK8S (1 ou 3 μg/kg) ou de sérum physiologique. Les expériences ont été réalisées de façon randomisée à 3 jours d’intervalle. Après 8 semaines de consommation, le métabolome de leur contenu caecal a été évalué par 1H-RMN. Résultats et Analyse statistique : La consommation des régimes HFC et HFI a augmenté la prise de poids (+33%, P=0,01) et l’adiposité (+14%, P=0,01) des rats en comparaison des régimes C, LFC et LFI. La consommation des régimes synthétiques, quels que soient le taux de lipides ou la nature des fibres (cellulose ou inuline), a entrainé la perte de sensibilité à la CCK, i.e. une absence d’effet satiétogène de la CCK à la faible dose (diminution de la consommation par rapport à la condition sérum physiologique HFC: -24 HFI: -19, LFC:-18 et LFI:-19%, P>0,05) en comparaison du régime C (-42%, PConclusion : Les altérations de la communication intestin-cerveau régulant la satiété observées chez le rat obèse semblent liées à la nature purifiée des ingrédients des régimes consommés et non au taux de lipides ou à la nature des fibres alimentaires. Ainsi, ces régimes modifient profondément le métabolome intestinal et les interactions microbiote-hôte.

The past 20 years has witnessed tremendous progress in our understanding of Parkinson's disease. It is now well established that α-synuclein, a presynaptic neuronal protein, is not only a marker but also an actor of the disease. In this review, we discuss the advances that have been obtained in neuropathology using α-synuclein immunohistochemistry and the role of this protein in the spread of the disease.

The abdominal post surgical pain has two components : (1) a parietal component due toaggression of the abdominal wall muscles and the parietal peritoneum and (2) a visceralcomponent due to aggression of the visceral peritoneum and viscera. Parietal pain is welllocalized; it corresponds to identified dermatomes. Otherwhise, visceral pain is often badlylocalized. Local anesthetics injected through a parietal catheter of infiltration, an abdominal wall blockor by a systemic administration show clinical efficiency in post operative analgesia afterabdominal surgery. However, the action mechanisms of local anesthetics according to theiradministration route are not well clarified. The purpose of our studies is to explore localanesthetics effect on both components of the abdominal pain in an animal model according totheir administration route.In this purpose we realized three experimental studies :1- In the first study, we compared the effect of systemic administration or through a preperitoneal catheter of ropivacaïne on parietal and visceral pain in a model of surgicallaparotomy in the rat. 2- In the second study, we established a block of the abdominal wall in the rat. 3- In the third study, parietal and peritoneal inflammation were induced by carrageenaninjection in the abdominal wall or in the peritoneal cavity in the rat according to theexperimental group. Then, we compared the effect of a systemic administration of bupivacaïneto its administration by an abdominal wall block. Furthermore, the systemic effect of localanesthetics was compared to a preventive chemical vagotomy. These works showed that during laparotomy, local anesthetics are effective in thetreatment of the nociception as well as by systemic or locoregional administration. We showedthat an abdominal wall block as well as a pre peritoneal administration decreased thetransmission of the visceral nociception towards the central nervous system by direct action onthe parietal nerve endings. Furthermore, during a laparotomy, systemic administration of localanesthetics inhibited the transmission of visceral nociception towards the central nervoussystem associated with a local and systemic anti inflammatory effects. This anti inflammatoryeffect was higher than that what we showed by locoregional administration of bupivacaïne., La douleur abdominale post chirurgicale reste une douleur difficile à gérer. Cette douleur présente 2 composantes : (1) une composante pariétale liée à l’agression des muscles de la paroi abdominale et du péritoine pariétal et (2) une composante viscérale liée à l’agression du péritoine viscérale et des viscères. La douleur pariétale est bien systématisée, elle correspond à des métamères bien identifiés. Par contre la douleur viscérale est souvent mal localisée, irradiée ou transférée à un site cutané. Les AL administrés par l’intermédiaire d’un cathéter d’infiltration pariétal, d’un bloc de la paroi abdominale ou par voie systémique montrent une efficacité clinique dans l’analgésie post opératoire d’une chirurgie abdominale. Cependant le mécanisme d’action des AL en fonction de leurs voies d’administration n’est pas bien élucidé. Le but de nos études est d’explorer l’effet des AL sur les deux composantes de la douleur abdominale dans un modèle animal en fonction de leur voie d’administration. Nous avons réalisé 3 études expérimentales :1-Dans l’étude 1 nous avons comparé l’effet de la ropivacaïne administrée par voie systémique ou par un cathéter pré péritonéal sur la douleur pariétale et viscérale dans un modèle de laparotomie chirurgicale chez le rat.. 2-Dans l’étude 2 nous avons validé un bloc de la paroi abdominale chez le rat.. 3-Dans l’étude 3 nous avons comparé l’effet de la bupivacaïne par voie systémique à l’effet obtenu par l’administration de la bupivacaïne par un bloc de la paroi abdominale. Nous avons également comparé l’effet des Al par voie systémique à une vagotomie chimique préventive. L’ensemble de ces travaux montrent que lors d’une laparotomie, les AL sont efficaces dans le traitement de la nociception aussi bien par voie systémique que par voie locorégionale. Nous avons démontré qu’un bloc de la paroi abdominale, ainsi qu’une infiltration pré péritonéale diminuaient la transmission de la nociception viscérale vers le SNC par action directe sur les terminaisons nerveuses pariétales. De plus, lors d’une laparotomie, l’administration systémique d’AL montre une efficacité dans l’inhibition de la transmission de la nociception viscérale vers le SNC associée à un effet anti inflammatoire local et systémique supérieure à celui d’une administration locorégionale.

The abdominal post surgical pain has two components : (1) a parietal component due toaggression of the abdominal wall muscles and the parietal peritoneum and (2) a visceralcomponent due to aggression of the visceral peritoneum and viscera. Parietal pain is welllocalized; it corresponds to identified dermatomes. Otherwhise, visceral pain is often badlylocalized. Local anesthetics injected through a parietal catheter of infiltration, an abdominal wall blockor by a systemic administration show clinical efficiency in post operative analgesia afterabdominal surgery. However, the action mechanisms of local anesthetics according to theiradministration route are not well clarified. The purpose of our studies is to explore localanesthetics effect on both components of the abdominal pain in an animal model according totheir administration route.In this purpose we realized three experimental studies :1- In the first study, we compared the effect of systemic administration or through a preperitoneal catheter of ropivacaïne on parietal and visceral pain in a model of surgicallaparotomy in the rat. 2- In the second study, we established a block of the abdominal wall in the rat. 3- In the third study, parietal and peritoneal inflammation were induced by carrageenaninjection in the abdominal wall or in the peritoneal cavity in the rat according to theexperimental group. Then, we compared the effect of a systemic administration of bupivacaïneto its administration by an abdominal wall block. Furthermore, the systemic effect of localanesthetics was compared to a preventive chemical vagotomy. These works showed that during laparotomy, local anesthetics are effective in thetreatment of the nociception as well as by systemic or locoregional administration. We showedthat an abdominal wall block as well as a pre peritoneal administration decreased thetransmission of the visceral nociception towards the central nervous system by direct action onthe parietal nerve endings. Furthermore, during a laparotomy, systemic administration of localanesthetics inhibited the transmission of visceral nociception towards the central nervoussystem associated with a local and systemic anti inflammatory effects. This anti inflammatoryeffect was higher than that what we showed by locoregional administration of bupivacaïne.; La douleur abdominale post chirurgicale reste une douleur difficile à gérer. Cette douleur présente 2 composantes : (1) une composante pariétale liée à l’agression des muscles de la paroi abdominale et du péritoine pariétal et (2) une composante viscérale liée à l’agression du péritoine viscérale et des viscères. La douleur pariétale est bien systématisée, elle correspond à des métamères bien identifiés. Par contre la douleur viscérale est souvent mal localisée, irradiée ou transférée à un site cutané. Les AL administrés par l’intermédiaire d’un cathéter d’infiltration pariétal, d’un bloc de la paroi abdominale ou par voie systémique montrent une efficacité clinique dans l’analgésie post opératoire d’une chirurgie abdominale. Cependant le mécanisme d’action des AL en fonction de leurs voies d’administration n’est pas bien élucidé. Le but de nos études est d’explorer l’effet des AL sur les deux composantes de la douleur abdominale dans un modèle animal en fonction de leur voie d’administration. Nous avons réalisé 3 études expérimentales :1-Dans l’étude 1 nous avons comparé l’effet de la ropivacaïne administrée par voie systémique ou par un cathéter pré péritonéal sur la douleur pariétale et viscérale dans un modèle de laparotomie chirurgicale chez le rat.. 2-Dans l’étude 2 nous avons validé un bloc de la paroi abdominale chez le rat.. 3-Dans l’étude 3 nous avons comparé l’effet de la bupivacaïne par voie systémique à l’effet obtenu par l’administration de la bupivacaïne par un bloc de la paroi abdominale. Nous avons également comparé l’effet des Al par voie systémique à une vagotomie chimique préventive. L’ensemble de ces travaux montrent que lors d’une laparotomie, les AL sont efficaces dans le traitement de la nociception aussi bien par voie systémique que par voie locorégionale. Nous avons démontré qu’un bloc de la paroi abdominale, ainsi qu’une infiltration pré péritonéale diminuaient la transmission de la nociception viscérale vers le SNC par action directe sur les terminaisons nerveuses pariétales. De plus, lors d’une laparotomie, l’administration systémique d’AL montre une efficacité dans l’inhibition de la transmission de la nociception viscérale vers le SNC associée à un effet anti inflammatoire local et systémique supérieure à celui d’une administration locorégionale.

Plusieurs études ont montré que les maladies cardiovasculaires constituent un risque majeur de développement du trouble dépressif chez l’homme. Plus précisément, à la suite d’un infarctus du myocarde, 15 à 30 % des patients développent une dépression majeure dans les 6 à 8 mois suivant l’évènement cardiaque. Dans un modèle d’infarctus du myocarde chez le rat, développé dans notre laboratoire, nous avons noté la présence de comportements compatibles avec une dépression, deux semaines après l’infarctus. Nous avons également détecté des cellules apoptotiques dans le système limbique dès les premières minutes de reperfusion, nombre qui atteint son apogée à 3 jours de reperfusion. Nous avions émis l’hypothèse que l’apoptose que l’on observe dans le système limbique serait reliée à la réponse inflammatoire induite par l’infarctus du myocarde. Les comportements reliés à de la dépression ont été prévenus par l’administration d’un inhibiteur de la synthèse des cytokines pro-inflammatoires, la pentoxifylline, le célécoxib, un inhibiteur de la cyclooxygenase-2, par des probiotiques ainsi que par différents antidépresseurs. Les résultats des deux premières études de cette thèse montrent que la desvenlafaxine, un Inhibiteur de la recapture de la sérotonine et noradrénaline (IRSN) prévient les comportements dépressifs tout en diminuant l’apoptose à 3 jours post-infarctus dans le système limbique. Les comportements similaires à ceux d’une dépression que présentent les rats deux semaines après l’évènement cardiaque sont encore présents à 4 mois post-infarctus, si aucun traitement n’est entrepris. De plus, ces animaux développent des troubles d’apprentissage que la desvenlafaxine peut prévenir, et ceci même si le traitement n’est présent que pendant les 2 premières semaines post-infarctus. Dans la troisième étude de cette thèse, nous avons voulu savoir si le nerf vague était impliqué dans les effets bénéfiques de deux probiotiques sur l’apoptose dans le système limbique après un infarctus du myocarde. Nos résultats ont démontré que les probiotiques réduisent l’apoptose dans le système limbique après un infarctus du myocarde, mais que cet effet est perdu en présence d’une vagotomie. Les résultats obtenus démontrent que l’infarctus du myocarde induit une mort par apoptose dans le système limbique de même que des comportements dépressifs et des problèmes d’apprentissage à long terme. Ces problèmes peuvent être diminués par un traitement à la desvenlafaxine, et ceci même si le traitement n’est présent que pour les deux premières semaines post-infarctus. Finalement, nous avons observé que les probiotiques avaient des effets bénéfiques sur l’apoptose dans le système limbique par un mécanisme impliquant le nerf vague. En conclusion, plusieurs interventions différentes sont efficaces pour limiter les conséquences de l’infarctus du myocarde sur le système limbique et un traitement court est efficace pour prévenir les problèmes à plus long terme., Several studies have highlighted that disruption of the cardiovascular functions is a major risk of developing depressive disorder in humans. 15-30% of the general population develops major depression within 6 to 8 months after a myocardial infarction. To better understand the underlying mechanisms and identify therapeutic pathways, we use a rat model of post-myocardial infarction developed in our laboratory. We have observed in these animals an increased apoptosis in the limbic system, which starts in the first minutes following reperfusion and peaks 3 days post-reperfusion. As a result, a depression-like phenotype and learning impairments appear 2 weeks after the myocardial infarction, which will persist up to 4 months after the infarct. We hypothesize that the observed apoptosis and the resulting depressive-like behavior are mediated by the inflammatory response induced after myocardial infarction. Indeed, depression-like behavior is prevented by the administration of an inhibitor of the pro-inflammatory cytokines, (pentoxifillyne, celecoxib), as well as by probiotics. In this thesis, we show that desvenlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI) prevents death by apoptosis in the limbic system. Desvenlafaxine also helps to improve the depressive-like behavior in these rats as well as the learning impairments, even if the treatment is administered during the first 2 weeks post-reperfusion. Finally, we have discovered that vagotomy prevents the probiotics effect over the apoptosis appearing after myocardial infarction, highlighting the importance of the vagus nerve in the beneficial effects of probiotics. In conclusion, several interventions are effective in limiting the consequences of myocardial infarction on the limbic system and also key to prevent the apparition of secondary psychological disorders.

Schwannomas are a form of rare tumor, arising from neural tissue and representing 2 % of mediastinal tumors. They are usually located in the posterior mediastinum, most often in the paravertebral gutters and typically appended to intercostal nerves.We report two cases of unusual mediastinal schwannomas, appended to the vagus nerve. The schwannoma was located in the subcarinal region in the first case and in the right para-tracheal region in the second case. The lesions were thought to be bronchogenic cysts preoperatively in both cases because of a cystic appearance on preoperative CT scan and endobronchial ultrasonography. A surgical approach was adopted to remove the tumors. Video-assisted thoracoscopy was used in one case and robotic-assisted surgery in the second case, without any complication, allowing for complete resection and to establish a certain pathological diagnosis.Despite this location and cystic presentation being unusual, schwannoma should be considered as a possible cause of cystic lesions in the mediastinum. Minimally invasive surgery allows for complete resection and definitive pathological diagnosis.

National audience; The pig, which shares several similarities with humans, is increasingly used for biomedical research, particularly in nutrition and neurosciences. Recent studies in minipigs have shown that a deleterious nutritional environment (e.g. a high-fat and high-sugar diet) induces obesity which, as in humans, is associated with increased adiposity, insulin resistance, modified eating behaviour, and altered gastric function and intestinal sensitivity. These changes are accompanied by differences in the activation matrices and metabolic activity of several brain areas. Using this animal model, we have revisited the concept of dual hedonic and homeostatic control of food intake. We have thus developed a minimally invasive and potentially reversible surgical approach to the control of food intake, as an alternative to bariatric surgery, based on chronic vagal stimulation at the abdominal level.; Par sa proximité avec l’homme, le porc et plus particulièrement le porc miniature est devenu un modèle privilégié en nutrition et neurosciences. Chez ce dernier, un environnement nutritionnel délétère permet d’induire une obésité accompagnée, tout comme chez l’homme, d’une augmentation dramatique de l’adiposité, d’une résistance à l’insuline, d’un bouleversement des comportements alimentaires, de modifications de la fonction gastrique et d’une altération de la sensibilité intestinale. Ces phénomènes sont associés à des changements d’activation et de métabolisme de diverses zones cérébrales. Ce même modèle animal a permis de reconsidérer le concept d’une double valence hédonique et homéostatique contrôlant la prise alimentaire. Sur cette base, nous avons développé une stratégie minimalement invasive et réversible de contrôle de la prise alimentaire utilisant la stimulation chronique du nerf vague qui est susceptible d’offrir une alternative à la chirurgie bariatrique.

For most patients, sexual activity represents a low risk of triggering cardiac arrhythmias. However, particularly in patients with an underlying heart disease, sexual activity may cause cardiac arrhythmias which may be sometimes serious. From a physiological point of view, sexual activity produces increased sympathetic activity and thereby probably reduced vagal tone which at different degrees may induce cardiac arrythmias. Several presently available autopsy-studies have shown that this happens very rarely and that it mostly affects men. Finally, recently published recommendations allow us to better advise patients with cardiac arrhytmias to engage in sexual activity or to defer it until the condition is stabilized and optimally controlled.

International audience; Notre cerveau et notre tube digestif communiquent à travers l'axe cerveau-intestin ou brain-gut axis des Anglo-Saxons. Ces relations neuro-digestives assurent un fonctionnement coordonné et adapté du tractus gastro-intestinal à son environnement dans des conditions physiologiques. Cette communication se fait via le système nerveux autonome (SNA), représenté par le système nerveux parasympathique, en particulier le nerf vague, et le système nerveux sympathique qui tous deux ont une composante afférente prédominante et efférente. La balance sympatho-vagale est un reflet de cette communication. Une anomalie de cet axe cerveau-intestin est observée dans le syndrome de l'intestin irritable (SII) et les maladies inflammatoires chroniques de l'intestin (MICI), que l'on peut assimiler à des modèles bio-psycho-sociaux. Le stress et les émotions jouent un rôle dans l'initiation et l'aggravation du SII et des arguments plaident également en faveur de leur rôle dans les MICI. L'exploration et la caractérisation de l'état fonctionnel du SNA apparaissent comme un marqueur intéressant des relations neuro-digestives dans des conditions physiologiques et pathologiques. Les thérapies ciblant le SNA, qu'elles soient de type médicamenteuses, nutritionnelles, complémentaires ou par neurostimulation vagale, voire combinées, sont susceptibles de restaurer un fonctionnement adapté et coordonné du SNA. Elles ont leur place dans le traitement du SII et des MICI.

We describe the case of a 13-year-old boy who presented to the emergency department with an acute onset paresis of the left abducens, facial and vagus nerves. Bilateral papilledema was seen on fundoscopy. Blood tests and brain magnetic resonance imaging and angiography showed no abnormalities. A lumbar puncture revealed an elevated intracranial pressure (575mmH2O) and clear cerebrospinal fluid. The diagnosis of pseudotumor cerebri (PTC) associated with multiple cranial nerve palsies was made. Treatment with acetazolamide was initiated, resulting in progressive improvement with no sequelae and no clinical recurrence over an 8-month follow-up period. PTC in children can present with a wide spectrum of neurological signs, especially cranial nerve palsies which are most likely related to a pressure-dependent stretching mechanism. In 2007, distinctive diagnostic criteria for pediatric PTC were established, including the presence of any cranial nerve palsy in the absence of an identifiable etiology.

Introduction High frequency(30 Hz)vagus nerve stimulation(VNS)has been approved as a treatment for some types of epilepsy and depression in humans. Low-frequency (5 Hz)VNS has also been successful for the treatment of different animal inflammation models, notably digestive inflammation. Recent studies have shown that the anti-inflammatory effect is induced by the activation of the efferent vagal fibers, which secrete acetylcholine in periphery. It links itself to α-7-nicotinic receptors on the macrophages surface, inhibiting the release of pro-inflammatory cytokines. This pathway is known by the name of the cholinergic anti-inflammatory pathway. However, the mechanism of action of low-frequency VNS remains unclear and other pathways could be involved implicating the central nervous system (CNS) and the immune system. Aim The aim of this study was to evaluate the implication of the CNS and the immune system in the modulation of inflammation induced by low-frequency VNS in an anaesthetized rat model. Firstly, to study the implication of the CNS and the contribution of the afferent vagal fibers during 5Hz VNS, a study using functional magnetic resonance imaging (fMRI) on a «healthy» anaesthetized rat model was carried out. Secondly, an experiment on the effect of VNS on splenic immune cells as well as on the digestive tract was fulfilled on a «healthy» rat model followed by a study on a rat model of colitis induced by intracolonic injection of trinitrobenzene sulfonic acid (TNBS). Results fMRI data brought to light an important role of the afferent vagal fibers. They modulate some structures of the CNS which could contribute to the modulation of digestive inflammation by 5Hz VNS. The studies carried out by FACS on the sub-populations of splenic lymphocytes revealed that other immune cells than macrophages could be implicated by VNS. In the «healthy» rat model, with no digestive inflammation, FACS data show that 3h VNS decreases T CD4 lymphocytes activation and the percentage of NKT in relation to T lymphocytes. These data are in favor of an inhibiting role of VNS on lymphocytes activation and also has an impact on NKT cells which have immunoregulatory properties. 3h VNS does not have the same effect on the rat model of colitis. In fact, the quantification of secreted cytokines by cultured splenocytes show that VNS increases the potential of IL-10(anti-iflammatory)cytokine by splenocytes and particularly splenic T CD4 lymphocytes. In the same way, the anti-inflammatory effect of VNS is seen in the transverse colon (above the lesions): decrease of TNF-α and SOCS3 mRNA and of myeloperoxidase. These results show a role of VNS on the functionality of splenic T CD4 lymphocytes inducing an important secretion of IL-10. 3h low-frequency VNS turns the immune response towards an anti-inflammatory response during the early phase of digestive inflammation. Moreover, VNS anti-inflammatory effect is seen in the transverse colon, above the lesions. Conclusion These results reveal that other pathways implicating different cell types are potentially involved besides the classic cholinergic anti-inflammatory pathway by low-frequency VNS. It implicates CNS by the activation of vagal afferents and splenic immune cells such as T CD4 lymphocytes and NKT cells. An anti-inflammatory effect of VNS is found in the transverse colon (above the lesions) even during the initiation phase of digestive inflammation, but not in the distal colon (in the lesions). These date have therapeutic implications: low-frequency VNS is being clinically tested at the moment as a treatment for Crohn's disease., IntroductionLa neurostimulation vagale (NSV) à haute fréquence (30 Hz) est utilisée commethérapeutique de certaines formes d’épilepsie et de dépression réfractaires aux traitements chezl’Homme. De plus, la NSV à basse fréquence (5 Hz) a été expérimentée avec succès chez l’animalpour traiter différentes inflammations périphériques, notamment digestives. Des travaux récents ontmis en évidence que cet effet anti-inflammatoire est induit par l’activation des fibres efférentesvagales, libérant en périphérie de l’acétylcholine, inhibant la sécrétion des cytokines proinflammatoires.Cette voie est connue sous le nom de voie anti-inflammatoire cholinergique.Toutefois, le mécanisme d’action de la NSV 5 Hz reste mal connu et d’autres voies pourraient êtremises en jeu impliquant le système nerveux central (SNC) et le système immunitaire périphérique.ButLes travaux réalisés ont eu pour objectif d’étudier l’implication du SNC et du systèmeimmunitaire dans la modulation de l’inflammation induite par la NSV basse fréquence chez unmodèle de rat anesthésié. Tout d’abord, afin d’étudier l’implication du SNC lors de la NSV 5 Hz, uneétude d’imagerie par résonance magnétique fonctionnelle (IRMf) a été réalisée sur le rat «sain»anesthésié. Ensuite, une étude a été effectuée sur l’effet de la NSV sur les cellules immunitairesspléniques ainsi que sur le tube digestif chez un modèle de rat «sain» puis chez un modèle de ratatteint d’une colite expérimentale induite par une injection intra-colique d’acide trinitrobenzènesulfonique (TNBS).RésultatsLes données obtenues lors de l’étude d’IRMf ont mis en évidence un rôle important desfibres afférentes vagales; elles modulent certaines structures du SNC qui pourraient participer à larégulation de l’inflammation digestive induite par la NSV 5 Hz. Les études réalisées sur les souspopulationslymphocytaires spléniques ont révélé que d’autres cellules immunitaires que lesmacrophages étaient impliquées lors de la NSV. Chez le modèle de rat «sain», les résultats decytométrie en flux ont montré que la NSV 3h 5 Hz induisait une diminution de l’activation deslymphocytes T CD4 ainsi que du pourcentage de NKT par rapport aux lymphocytes T. Ces résultatssont en faveur d’un rôle de la NSV 3h inhibant l’activation lymphocytaire et jouant un rôle sur les NKTpossédant des propriétés immunorégulatrices. La NSV 3h n’a pas le même effet chez le modèle de ratprésentant une colite. En effet, le dosage de cytokines sécrétées par les splénocytes en culturemontre que la NSV augmente le potentiel de sécrétion d’IL-10 (cytokine anti-inflammatoire) dessplénocytes et plus particulièrement des lymphocytes T CD4 spléniques. Parallèlement, l’effet antiinflammatoirede la NSV a été mis en évidence au niveau du côlon transverse (au-dessus de la zonelésée) par une diminution des ARNm de SOCS3 et du TNF-α et de la myéloperoxidase. Ces donnéesont démontré un rôle de la NSV sur la fonctionnalité des lymphocytes T CD4 spléniques. La NSV 3h 5Hz orienterait la réponse immunitaire vers une réponse anti-inflammatoire en phase d’initiationd’inflammation digestive. De plus, l’effet anti-inflammatoire de la NSV est retrouvé au niveau du tubedigestif au-dessus de la zone lésée (côlon transverse).ConclusionCes données expérimentales montrent que d’autres voies impliquant différents typescellulaires sont susceptibles d’être mises en oeuvre par la NSV basse fréquence. Elle induitl’implication du SNC par l’activation des afférences vagales et des cellules immunitaires spléniquestelles que les lymphocytes T CD4 et les NKT. Un effet anti-inflammatoire de la NSV est retrouvé auniveau du côlon transverse, mais pas au niveau des lésions dans le côlon distal. Ces résultatsprésentent des implications thérapeutiques : la NSV basse fréquence est actuellement en essaiclinique pour être utilisée comme traitement dans la maladie de Crohn.

Scwhannomas are uncommon neurogenic tumors of the mediastinum. Most of them are located in the posterior mediastinum usually in the paralateral gutters. We report the case of an uncommon localisation of such a tumour appended to the right vagus nerve in the middle mediastinum.The patient was 50 years old and complained of thoracic pain, shortness of breath and dysphagia. CT scanning of thorax and abdomen revealed a heterogeneous mass in the middle mediastinum, which was not visible on plain radiography. Further investigation included transoesophageal ultrasound and PET scan. The diagnosis was confirmed by histopathology after mini video-assisted thoracotomy. The schwannoma was entirely removed without any post-surgical complications.We report a novel case of schwannoma arising from the vagus nerve and review the diagnostic strategies. PET scanning has poor sensitivity and specificity and does not therefore contribute to confirm the diagnosis which depends on exploring the mediastimun surgically.

International audience; Our digestive tract has an autonomous functioning but also has a bidirectional relation with our brain known as brain-gut interactions. This communication is mediated by the autonomous nervous system, i.e., the sympathetic and parasympathetic nervous systems, with a mixed afferent and efferent component, and the circumventricular organs located outside the blood-brain barrier. The vagus nerve, known as the principal component of the parasympathetic nervous system, is a mixed nerve composed of 90% afferent fibers, which has physiological roles due to its putative vegetative functions. The vagus nerve has also anti-inflammatory properties both through the hypothalamic pituitary adrenal axis (through its afferents) and the cholinergic anti-inflammatory pathway (through its efferents). The sympathetic nervous system has a classical antagonist effect on the parasympathetic nervous system at the origin of an equilibrated sympathovagal balance in normal conditions. The brain is able to integrate inputs coming from the digestive tract inside a central autonomic network organized around the hypothalamus, limbic system and cerebral cortex (insula, prefrontal, cingulate) and in return to modify the autonomic nervous system and the hypothalamic pituitary adrenal axis in the frame of physiological loops. A dysfunction of these brain-gut interactions, favoured by stress, is most likely involved in the pathophysiology of digestive diseases such as irritable bowel syndrome or even inflammatory bowel diseases. A better knowledge of these brain-gut interactions has therapeutic implications in the domain of pharmacology, neurophysiology, behavioural and cognitive management.

Electroconvulsivotherapy represents a key indication for severe Major Depressive Episode (MDE). However, an hospitalization with a general anaesthesia allowing a seizure induction followed by an almost systematic post-epileptic delirium justifies the development of other brain electrostimulation techniques. Trans-cranial Magnetic Stimulation (TMS) is a technique which offers to transform an electromagnetic field within the brain in an electric one. This therapeutic has been approved in 2008 in the MDE indication by the Food and Drug Administration. However a better knowledge of brain stimulation parameters such as the number of sequences, intensity, frequency, and the brain target, is necessary. Indeed it could enable to get some more homogeneous clinical results which will drive to the use of this technique in daily practice. Neurosurgical procedures represent also a stake for a better treatment of severe chronic and resistant depression. Whereas Vagus Nerve Stimulation (DBS) failed to be developed in France, Deep Brain Stimulation (DBS) is currently under development in this indication with some promising preliminary results.

The aim of our study has been to describe the cricopharyngeal muscle and its nerve supply from the recurrent laryngeal nerve and from the superior laryngeal nerve.Six normal adult human pharynges (12 sides) obtained from cadavers were studied. Micro-dissections were carried out thanks to a Leica microscope. Measures were obtained with a micro-digital caliber.The morphological feature of the cricopharyngeal muscle (CPM) showed three different muscular bundles: superior oblique muscle fibers are joining the inferior pharyngeal constrictor muscle, horizontal circular muscle fibers are 11 to 12mm high, and 3mm thick, inferior oblique muscle fibers are joining external layer of the superior oesophagus. The recurrent laryngeal nerve through its dorsal branch supplies the posterior part of the muscular bundles of the CPM. The superior laryngeal nerve by its lateral branch supplies the anterior part of the CPM. So this double vagal innervation of the CPM from superior and inferior laryngeal nerves participates in the laryngo-pharyngeal coordination specially for swallowing.

The glossopharyngeal nerve and the vagus nerve are mixed nerves containing sensory, gustatory, motor and autonomous fibers (parasympathetic). The glossopharyngeal nerve has mainly visceral afferent fibers from the tongue and pharynx, gustatory fibers from the posterior third of the tongue, parasympathetic afferent fibers from carotid sinus and carotid glomus, parasympathetic efferent fibers for the parotid gland and motor fibers for the muscles of the pharynx. The vagus nerve contains mostly visceral afferent fibers from laryngeal, intrathoracic and abdominal organs, parasympathetic efferent fibers for these intrathoracic and abdominal organs and motor fibers to the pharyngeal and laryngeal muscles. The accessory nerve is divided into two branches, different in their origins and their functions: the cranial portion joins the motor fibers of the vagus nerve, to form the recurrent laryngeal nerve, whereas the spinal portion innervates the sternocleidomastoid muscle and the trapezius muscle. Finally, the hypoglossal nerve is the main motor nerve of the tongue.

In various neurosurgical operations, there is a risk of cranial nerve lesion that can be avoided or minimized with intraoperative electrophysiological monitoring. Regarding motor function of the cranial nerves, stimulodetection techniques are used, including electrical stimulation of nerve trunks and electromyographic recording of evoked motor responses. These techniques can be used for monitoring the trigeminal nerve (Vth cranial nerve), facial nerve (VIIth), glossopharyngeal nerve (IXth), pneumogastric nerve (Xth), spinal accessory nerve (XIth), and hypoglossal nerve (XIIth), in particular during surgical removal of tumors of the cerebellopontine angle or skull base. When beginning an operation, electrical stimulation is only used to identify the nerve structures. As removal of the tumor progresses, the goal is to verify that a surgical injury to the nerve is avoided by looking for the absence of any change regarding amplitude, morphology, and latency of motor responses. Intraoperative electromyographic monitoring can also be applied during the surgical treatment of primary hemifacial spasm by microvascular decompression. An effective decompression is usually associated with the disappearance of "lateral spread" motor responses to facial nerve branch stimulation. Therefore, the intraoperative disappearance of the lateral spread responses can be considered a predictive factor of good postoperative clinical outcome, even if this assertion remains a matter of debate.

Background The vagus nerve is composed of 20% of efferents and 80% of afferents. Nowadays, vagus nerve stimulation (VNS) is used in the treatment of refractory epilepsy and depression in Human. Moreover, the vagus nerve has anti-inflammatory properties through its i) afferents by activating the hypothalamic pituitary adrenal axis, ii) its efferents by the cholinergic anti-inflammatory pathway has also been reported more recently. In fact, acetylcholine can binds alpha 7 nicotinic receptor of immune cells (like macrophages) to inhibit pro-inflammatory cytokines secretions (like TNFalpha). Inflammatory bowel diseases (IBD) are multifactorial pathologies that produce hyper-activations of the immune system and hence to intestinal lesion. Nowadays, IBD treatments not induce a total remission but have only suspensive effects. AimThe aim of this study was to evaluate the effect of chronic VNS on an experimental colitis in rats and characterize its anti-inflammatory mechanisms and its lateral effects on brain and on intestinal motility. MethodsColitis was induced in rats by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS). VNS was performed for 3 hours during five days in freely moving rats chronically implanted with an electrode on the left cervical vagus nerve with stimulation parameters known to activate vagal efferents (1mA, 5Hz, 500µs, 10s ON, 90s OFF). Body temperature and locomotor activity were recorded. At the end of stimulation, evaluation of colitis was assessed by physiological and local parameters both at the level of the damaged colon and immediately above. A global multiparametric index of colitis was generated. Western blot analysis and immunohistochemistry of STAT proteins were performed to best characterized mechanisms of action of VNS. A study of the lateral effects of VNS was performed by c-fos immunohistochemestry in the brain and by the recording of migrant motor complex at the peripheral level. ResultsVNS induced a significant improvement of physiological parameters such as body weight loss and a reduction of inflammatory markers notably in mild damaged tissues. This effect was associated with a reduction of the multivariate index of colitis. TNBS colitis induced significant increase of STAT levels in the lesion and above, these changes were improved by VNS. In addition, VNS induced slight effects on central neuronal activation, and on intestinal motility. ConclusionAll together, these data argue for a therapeutic effect of VNS on this model of colitis. This study opens a potential therapeutic avenue for the use of VNS in patients with IBD., IntroductionLe nerf vague est un nerf mixte composé de 20% de fibres efférentes et 80% de fibres afférentes. La stimulation électrique du nerf vague (VNS) est actuellement employée comme thérapie de certaines formes d'épilepsies et de dépressions chez l'Homme. Le nerf vague a également un double rôle anti-inflammatoire : i) d'une part via la voie classique faisant intervenir les fibres vagales afférentes centripètes qui peuvent activer l'axe corticotrope, ii) d'autre part via la voie cholinergique anti-inflammatoire, plus récemment décrite. L'effet anti-inflammatoire est dans ce cas lié à l'activation des efférences vagales centrifuges. En effet, les terminaisons de ces fibres libèrent, en périphérie, de l'acétylcholine qui, en se liant au récepteur alpha 7-nicotinique exprimé en particulier par les macrophages, inhibe la sécrétion de cytokines pro-inflammatoires (TNFalpha notamment). Bien que les maladies inflammatoires chroniques de l'intestin (MICI) aient une incidence en augmentation, leur origine exacte reste méconnue et semble liée à de nombreux facteurs. Les patients atteints de MICI présentent des troubles au niveau de l'activation du système immunitaire qui vont engendrer l'apparition de lésions au niveau intestinal. Les traitements des MICI disponibles actuellement ne permettent pas une guérison totale, mais ont uniquement un rôle suspensif. But Les travaux réalisés ont eu pour objectif d'utiliser la VNS afin de diminuer l'inflammation dans un modèle de colite expérimentale chez le rat. Des études complémentaires ont été réalisées pour étudier les mécanismes de cet effet anti-inflammatoire ainsi que les effets centraux et digestifs moteurs de la VNS. Matériels et Méthodes La colite a été induite par l'instillation intra-colique d'acide trinitrobenzène sulfonique (TNBS). La VNS a été réalisée grâce à une électrode bipolaire implantée de manière chronique au niveau du nerf vague gauche (paramètres de stimulation : 1mA, 5Hz, 500µs, 10s ON, 90s OFF) ; l'animal a été stimulé pendant 3 heures le jour de l'injection du TNBS et pendant les 4 jours suivants. Les paramètres physiologiques de température corporelle et d'activité locomotrice ont été suivis en continu par télémétrie pendant cette période. L'animal a été sacrifié 5 jours après l'instillation, le côlon a été prélevé et deux zones tissulaires ont été distinguées : la partie lésée et la partie adjacente. Ces prélèvements ont ensuite été utilisés pour une analyse histologique, une quantification de la myéloperoxydase et une quantification des ARNm des cytokines par la technique de RT-PCR. L'inflammation globale induite par la colite a été étudiée par l'intermédiaire d'un index multiparamétrique global comprenant des paramètres physiologiques intégrés (température corporelle, activité locomotrice), tissulaires (surface des lésions) et moléculaires (ARNm des marqueurs d'inflammation). L'approfondissement des connaissances mécanistiques de l'effet anti-inflammatoire obtenu a été réalisé par une étude par western blot et immunohistochimie de l'expression des protéines impliquées dans les voies intracellulaires d'activation des cellules immunitaires (protéines STAT). Enfin les effets latéraux de la VNS ont été étudiés au niveau central par la technique d'immunohistochimie du c-fos et par l'analyse des électromyogrammes du jéjunum au niveau périphérique.Les résultats mettent en évidence chez les animaux stimulés : une amélioration clinique significative avec une perte pondérale réduite, une tendance à la réduction des lésions intestinales, de l'expression de la myéloperoxidase et du taux d'ARNm de cytokines dans le tissu colique, ainsi qu'une diminution significative de l'index global d'inflammation. Au niveau mécanistique, la VNS induit des changements dans la signalisation intracellulaire, au niveau de la lésion et juste au-dessus de celle-ci. Enfin la VNS semble induire aussi des changements modérés au niveau de l'activation neuronale centrale et de la motricité digestive. Conclusion Ces données expérimentales montrent l'intérêt d'activer la voie cholinergique par la VNS pour obtenir un effet anti-inflammatoire ciblé au niveau du tube digestif. La VNS pourrait être envisagée dans le traitement des poussées ou le maintien en phase de rémission des patients atteints de MICI.

Vagus Nerve Stimulation (VNS) is recognized as an efficient procedure for controlling seizures in patients with drug-refractory epilepsies. It is used as a palliative procedure as a complement to conventional treatment by antiepileptic (AE) drugs and, according to literature, 40 to 50p.cent of patients report a decrease in seizures frequencyor=50p.cent, which is usually accepted to classify patients as responders in add on AE drug trials. The objectives of this study based on retrospective analysis of 50 consecutive patients with partial (39) or generalized (11) refractory epilepsy non eligible for surgery were; firstly to evaluate the global long term VNS efficacy and secondly to identify potential predictors of the VNS effects on seizure frequency. No patient has been seizure free at any moment of the follow up (2.8+/-1.8 years, max: 6 years) and the AE has been maintained in all. During follow up 44, 66, 61 and 58p.cent of patients were classified as responders at 6 months, 1, 2 and 3 years, respectively. Logistic regression analysis showed that: the percentage of responders at 6 months of follow up and later was significantly higher than that before 6 months (p=0.002); generalized epilepsy was predictive of a better outcome as compared to partial epilepsy (p=0.03); there was a trend for a better outcome in partial epilepsies symptomatic of a focal lesion than in those with normal brain MRI (p=0.06). These results are in line with previously published data in terms of global efficiency and confirm that seizures control does not reach its maximal level before at least one year of VNS. In severe generalized epilepsies (either secondary or cryptogenic) manifesting by frequent falls due to atonic or tonic-clonic generalized seizures VNS is a useful palliative procedure, which entails much les of surgical risk than callosotomy. The better VNS effects in patients with partial epilepsy possibly reflect the high incidence in our series of Malformations of Cortical Development, which have been identified as one the few variables possibly predictive of a response over 50p.cent of seizures frequency reduction.

Proposed as an additive symptomatic treatment of refractory epilepsy, vagus nerve stimulation (VNS) has proven to be effective and well-tolerated in patients presenting with refractory epilepsy for whom cortical resection is not indicated. After two years of treatment, the overall reduction of seizure frequency averaged 40%. In 50% of the patients, the frequency of seizures decreased by at least 50%. Moreover, even in absence of a significant reduction of seizures, patients who undergo this treatment reported an improvement in their quality of life. Economic surveys also demonstrate a favorable impact of VNS on the management of refractory epilepsy. Since 1988, 65,000 patients with refractory epilepsy throughout the world have been treated by VNS for this indication (1000 in France). The surgical implantation technique used in our department, the effects of vagus nerve stimulation reported in the literature, and our experience with a cohort of 70 patients with refractory epilepsy who received implants over the last 10 years are described.

We present the epilepsy surgery activity in infants and children at the Fondation Rothschild Hospital, the main center dedicated to this activity in France.A prospective study was conducted from 2003 to 2007 based on three populations: (1) children selected as candidates for surgery, (2) children undergoing presurgical evaluation and (3) children undergoing surgical procedures for epilepsy.Children selected as candidates for surgery: 304 children were referred and discussed by our multidisciplinary staff. They came from Paris and its suburbs (40%), the provinces (43%) or from other countries (14%). Sixty-one percent of them were included in our surgery program and 24% were excluded. Sixty-one percent of them were under 10 years of age. Children undergoing presurgical evaluation: 296 children were recorded: 140 EEG (47%), 46 with foramen ovale electrodes (16%) and 110 with invasive recording techniques (37%). Seventy percent of these children were under 10 years of age. Children undergoing surgical procedures: 316 children underwent surgery; 68% of them were under 10 years of age. The surgical procedures were focal resection (136 children), vertical parasagittal hemispherotomy (77 children), resection and or disconnection for hypothalamic hamartoma (69 children) and 34 had palliative surgery (callosotomy or vagal nerve stimulation).Eighty to 100 children undergo surgery each year in our department for drug-resistant partial epilepsy; 70% of them are less than 10 years of age. This activity is part of a network of pediatric neurologists who are deeply involved in treatment of severe epilepsy in children.

The autonomic nervous system sends messages through the sympathetic and parasympathetic nervous system. The sympathetic nervous system innervates the cardioaccelerating center of the heart, the lungs (increased ventilatory rhythm and dilatation of the bronchi) and the non-striated muscles (artery contraction). It releases adrenaline and noradrenaline. As opposed to the sympathetic nervous system, it innervates the cardiomoderator center of the heart, the lungs (slower ventilatory rhythm and contraction of the bronchi) and the non-striated muscles (artery dilatation). It uses acetylcholine (ACh) as its neurotransmitter. Sympathetic and parasympathetic divisions function antagonistically to preserve a dynamic modulation of vital functions. These systems act on the heart respectively through the stellar ganglion and the vagus nerve. The interaction of these messages towards the sinoauricular node is responsible for normal cardiac variability, which can be measured by monitoring heart rate variability (HRV). Heart rate is primarily controlled by vagal activity. Sensorial data coming from the heart are fed back to the central nervous system. HRV is an indicator of both how the central nervous system regulates the autonomic nervous system, and of how peripheral neurons feed information back to the central level. HRV measures are derived by estimating the variation among a set of temporally ordered interbeat intervals. The state of perfect symmetry, which, in medical parlance, is called respiratory sinus arrhythmia (RSA), can be described as a state of cardiac coherence. Obtaining a series of interbeat intervals requires a continuous measure of heart rate, typically electrocardiography (ECG). Commercially available software is then used to define the interbeat intervals within an ECG recording.The autonomic nervous system is highly adaptable and allows the organism to maintain its balance when experiencing strain or stress. Conversely, a lack of flexibility and a rigid system can lead to somatic and psychological pathologies. Several studies have shown a link between reduced HRV in postmyocardial infarction patients and increased risk for adverse cardiovascular events, including ventricular arrhythmias and sudden death. Recently, studies indicate that patients with depression and anxiety disorders exhibit abnormally low HRV compared with non-psychiatric controls. Reduced HRV seems indicate decreased cardiac vagal tone and elevated sympathetic activity in anxious and depressive patients and would reflect deficit in flexibility of emotional physiological mechanisms. A few studies have also revealed that biofeedback using respiratory control, relaxation and meditation techniques can increase HRV. For now, there is insufficient data to determine if paced respiration or subjective relaxation is necessary or sufficient for the efficacy of HRV biofeedback. Although the literature is modest, this review suggests that the use of biofeedback with relaxation and meditation approaches may result in increased HRV and parasympathetic activity. Limitations of the review literature have also been considered to identify areas for future research.

We present the case of a 10-year-old boy who presents with a severe epilepsy resistant to medical treatment in the context of a Miller-Dieker syndrome. This patient underwent the implantation of a pneumogastric nerve stimulator. We describe the patient's clinical history and the main characteristics of lissencephaly syndrome.

The Deep-Breathing (DB) test is of major importance in the evaluation of the vagal response (VR). We applied this test to assess the VR in a group of subjects with functional (neurological, cardiovascular or digestive) symptoms unexplained by standard cardiac examination and to compare it with the VR measured in a group of healthy controls.The following groups were considered: a C-Group of healthy controls (n=50), and three groups each consisting of 50 symptomatic patients (S1, S2, S3). Subjects in the S1-Group had a postural orthostatic tachycardia syndrome (POTS), while members of the S2-Group had arterial hypertension, and members of S3-Group had neither POTS nor arterial hypertension. The VR was expressed as a percentage variation of RR intervals 100x[(RR(max)-RR(min))/RR(min)], and was correlated with age and sex in the C-Group before any comparison.In controls the VR was 31.0%+/-8.2. It was negatively correlated with age (r=-0.42, p=0.003) and there was no significant difference between males (31.2%+/-5.7) and females (30.9%+/-9.0) (p=0.12). Compared to the C-Group, the VR was 51.6%+/-20.4 in the S1-Group (p0.001), 26.9%+/-11.3 in the S2-Group (p0.001), and 47.2%+/-22.7 in the S3-Group (p0.001).The VR was independent of sex but was negatively correlated with age. In comparison with healthy controls, it was significantly increased in the patients with POTS and significantly decreased in hypertensives.

Postural orthostatic tachycardia syndrome (POTS) is an inadequately understood pathology because its diagnosis is not based on the conventional methods of investigation. The orthostatic test allows to make the diagnosis easily. The objective of this study is to determine cardiovascular autonomic reflexes of 70 patients having POTS. The tests of exploration of the autonomic nervous system practised are: deep breathing, hand grip, mental stress and orthostatic test. The analysis of orthostatic test showed that the increase of the cardiac frequency, relative to the state of "beta" peripheral sympathetic hyperactivity occurred before the 2nd minute in 80% of patients. The POTS was considered "florid" in 43% of patients and had complicated of a rough and severe fall of systolic blood pressure inferior to 70 mmHg in four patients, after the fifth minute of the test. The analysis of the different tests had shown vagal hyperactivity in 63% of patients on deep breathing, in 93% of patients on hand grip and in 100% on orthostatic test. The "alpha" central sympathetic activity was increased in 76% of the cases and "beta" central sympathetic activity was high in 83% of cases. The "alpha" peripheral hyperactivity was observed in 63% of patients on hand grip, and in 44% on orthostatic test. The analysis of cardiovascular autonomic reflexes in patients affected by POTS allowing the determination of their autonomic profile, will contribute probably to a better understanding of this pathology and to a better orientation of its care.

Spasmodic laughter is a classical sign of pseudobulbar palsy, but it has never been reported, to our knowledge, to provoke syncope.A 63-year-old hypertensive and diabetic man with peripheral neuropathy and lacunar pseudobulbar palsy presented with three episodes of spasmodic laughter which had induced syncope. No new episode was observed after the beginning of low dose bisoprolol.Sustained or spasmodic laughter is accompanied by repetitive bursts of forced expiration, corresponding to short repetitive Valsalva maneuvers. Laughter-induced syncope is considered as one of the many Valsalva-type/vagally mediated syncopal attacks leading to rapid fall in blood pressure without compensatory tachycardia. The presence of autonomic diabetic neuropathy may also contribute to these attacks.

The epiglottis is known as a laryngeal structure. The authors studied the innervation of epiglottis using the Sihler method on six human epiglottises. Innervation of the epiglottis depended on the rami from the vagus, glossopharyngeal and hypoglossal nerves. By its innervation, epiglottis seems to be a glosso-laryngeal structure, as is confirmed by embryology, histology and clinical applications.

Recent advances have allowed the development of new physical techniques in neurology and psychiatry, such as Transcranial Magnetic Stimulation (TMS), Vagus Nerve Stimulation (VNS), and Deep Brain Stimulation (DBS). These techniques are already recognized as therapeutic approaches in several late stage refractory neurological disorders (Parkinson's disease, tremor, epilepsy), and currently investigated in psychiatric conditions, refractory to medical treatment (obsessive-compulsive disorder, resistant major depression). In Paralell, these new techniques offer a new window to understand the neurobiology of human behavior.

Vagus nerve stimulation (VNS) is a non-pharmacological treatment for drug resistant epilepsy.The good efficacy and tolerability of this device is now well established after several controlled studies, and more than 17000 people operated on in different countries. The physiology of VNS is not yet well known, and the potential mechanisms of action are reviewed. VNS seems to be as efficient as a new medication without some of the disadvantages (in case of pregnancy for example). SNV may have a beneficial effect for all kinds of drug-resistant epilepsy.Better knowledge of the underlying anti-epileptic mechanisms may help to select the better responders to this expensive anti-epileptic tool.

A sympathetic hyperactivity is a common feature in hypertension, type 2 diabetes (T2D), ageing and obesity-induced hypertension. This increase in sympathetic activity may lead to an elevation of arterial rigidity. By contrast, cardiac parasympathetic impairment is observed in these pathologies. Recently we showed in a model of rats with massive obesity (ventromedial hypothalamic lesions) that an enhanced vagal activity may be protective against hypertension. The aim of the present study was to evaluate the influence of an increase in sympathetic activity and a change in vagal activity on arterial rigidity and hypertension in T2D patients. Fourteen hypertensive T2D patients aged 54 +/- 2 years were compared to 22 elderly normotensive subjects (75 +/- 1 years: 11 controls and 11 T2D) and 34 middle aged normotensive subjects (43 +/- 1 years; 17 controls and 17 T2D). Cardiovascular vagosympathetic activity was investigated by spectral analysis of heart rate (HR) and blood pressure (BP) (Finapres) during 6 min at a controlled breathing rate (12 cycles/min). BP and the low frequencies of systolic BP (LF-SBP) were significantly (p0.01) higher in hypertensive T2D and elderly patients. Pulse pressure (PP) and the high frequencies of HR (HF-HR) were lower in hypertensive T2D patients. PP was positively correlated to LF-SBP (r=0.58; p=0.03) only in hypertensive T2D patients. Diastolic BP was negatively correlated to HF-HR in elderly control subjects (r=-0.63; p=0.03) but not in hypertensive T2D patients. The present results suggest that: sympathetic nervous system activity is enhanced in subjects over 70 years without any aggravating effect of T2D and in middle-aged hypertensive patients with type 2 diabetes; the increase in pulse pressure, an index of arterial rigidity, in elderly subjects may result from sympathetic override; the decrease in the cardiac sympathovagal balance, mainly due to a high vagal activity, may be protective against the occurrence of hypertension in patients with type 2 diabetes.