Information processing in long delay memory-guided saccades: further insights from TMS

The performance of memory-guided saccades with two different delays (3s and 30s of memorisation) was studied in eight subjects. Single pulse transcranial magnetic stimulation (TMS) was applied simultaneously over the left and right dorsolateral prefrontal cortex (DLPFC) 1s after target presentation. In both delays, stimulation significantly increased the percentage of error in amplitude of memory-guided saccades. Furthermore, the interfering effect of TMS was significantly higher in the short delay compared to that of the long delay paradigm. The results are discussed in the context of a mixed model of spatial working memory control including two components: First, serial information processing with a predominant role of the DLPFC during the early period of memorisation and, second, parallel information processing, which is independent from the DLPFC, operating during longer delay

Clinical implications of a possible role of vitamin D in multiple sclerosis

Hypovitaminosis D is currently one of the most studied environmental risk factors for multiple sclerosis (MS) and is potentially the most promising in terms of new clinical implications. These practical consequences, which could be applied to MS patients without further delay, constitute the main purpose of this review. Vitamin D is involved in a number of important general actions, which were not even suspected until quite recently. In particular, this vitamin could play an immunomodulatory role in the central nervous system. Many and varied arguments support a significant role for vitamin D in MS. In animal studies, vitamin D prevents and improves experimental autoimmune encephalomyelitis. Epidemiologically, latitude, past exposure to sun and the serum level of vitamin D influence the risk of MS, with, furthermore, significant links existing between these different factors. Clinically, most MS patients have low serum levels of vitamin D and are in a state of insufficiency or even deficiency compared to the international norm, which has been established on a metabolic basis. Large therapeutic trials using vitamin D are still lacking but the first results of phase I/II studies are promising. In the meantime, while awaiting the results of future therapeutic trials, it can no longer be ignored that many MS patients have a lack of vitamin D, which could be detected by a serum titration and corrected using an appropriate vitamin D supplementation in order to restore their serum level to within the normal range. From a purely medical point of view, vitamin D supplementation appears in this light to be unavoidable in order to improve the general state of these patients. Furthermore, it cannot currently be ruled out that this supplementation could also be neurologically beneficial

Contrôle du mouvement du regard (3) : Déficits neurologiques

Les mouvements oculaires ont pour objectifs complémentaires mais antagonistes de changer rapidement l’image sur la rétine, au moyen des saccades, et de stabiliser cette nouvelle image, par différents mouvements oculaires lents. L’analyse sémiologique des principales paralysies oculomotrices permet de localiser le siège des lésions, en particulier dans le tronc cérébral. Les atteintes peuvent être infranucléaires (nerfs) ou nucléaires, touchant aussi bien les saccades que les mouvements oculaires lents (dont le réflexe vestibulo-oculaire), ou supranucléaires, touchant alors sélectivement les saccades ou les mouvements oculaires lents. Les mouvements latéraux sont organisés dans le pont et les mouvements oculaires verticaux dans les pédoncules cérébraux. Parmi les nombreux mouvements oculaires anormaux, les nystagmus sont les plus fréquents et sont en général dus à une atteinte vestibulaire périphérique ou centrale. Enfin, les mouvements oculaires peuvent servir de modèle moteur pour mieux connaître le fonctionnement cérébral. En effet, l’enregistrement de ces mouvements permet de détecter des anomalies légères et d’étudier les mécanismes neuropsychologiques qui préparent ces mouvements, tels que l’attention spatiale, l’inhibition motrice, la prédiction motrice, l’intégration visio-spatiale, la mémoire spatiale, l’apprentissage moteur, la programmation motrice et la motivation ou l’intention

Déficits neurologiques

Les mouvements oculaires ont pour objectifs complémentaires mais antagonistes de changer rapidement l’image sur la rétine, au moyen des saccades, et de stabiliser cette nouvelle image, par différents mouvements oculaires lents. L’analyse sémiologique des principales paralysies oculomotrices permet de localiser le siège des lésions, en particulier dans le tronc cérébral. Les atteintes peuvent être infranucléaires (nerfs) ou nucléaires, touchant aussi bien les saccades que les mouvements oculaires lents (dont le réflexe vestibulo-oculaire), ou supranucléaires, touchant alors sélectivement les saccades ou les mouvements oculaires lents. Les mouvements latéraux sont organisés dans le pont et les mouvements oculaires verticaux dans les pédoncules cérébraux. Parmi les nombreux mouvements oculaires anormaux, les nystagmus sont les plus fréquents et sont en général dus à une atteinte vestibulaire périphérique ou centrale. Enfin, les mouvements oculaires peuvent servir de modèle moteur pour mieux connaître le fonctionnement cérébral. En effet, l’enregistrement de ces mouvements permet de détecter des anomalies légères et d’étudier les mécanismes neuropsychologiques qui préparent ces mouvements, tels que l’attention spatiale, l’inhibition motrice, la prédiction motrice, l’intégration visio-spatiale, la mémoire spatiale, l’apprentissage moteur, la programmation motrice et la motivation ou l’intention.Eye movements serve vision, which has two different aims: changing images using saccades, i.e. rapid eye movements, and stabilizing new images on the retina using slow eye movements. Eye movements are performed by ocular motor nuclei in the brainstem, on which supranuclear pathways - originating in the cerebral cortex, cerebellum and vestibular structures - converge. It is useful for the neurologist to know the clinical abnormalities of eye movements visible at the bedside since such signs are helpful for localization. Eye movement paralysis may be nuclear or infranuclear (nerves), involving all types of eye movements, i.e. saccades as well as the vestibulo-ocular reflex (VOR), or supranuclear, in which case the VOR is usually preserved. Lateral eye movements are organized in the pons, with paralysis of adduction (and preservation of convergence) when the lesion affects the medial longitudinal fasciculus (internuclear ophthalmoplegia), paralysis of conjugate lateral eye movements when the lesion affects the abducens nucleus (VI) and the «one-and-a-half» syndrome when both these structures are involved. Vertical eye movements are organized in the midbrain, with ipsilateral oculomotor (III) paralysis and contralateral paralysis of the superior rectus muscle when the third nerve nucleus is unilaterally damaged, supranuclear upward gaze paralysis when the posterior commissure is unilaterally damaged and supranuclear downward gaze paralysis (often coupled with upward gaze paralysis) when the mesencephalic reticular formations are bilaterally damaged. Numerous types of abnormal eye movements exist, of which nystagmus is the most frequent and usually due to damage to peripheral or central vestibular pathways. Cerebral hemispheric or cerebellar damage results in subtle eye movement abnormalities at the bedside, in general only detected using eye movement recordings, because of the multiplicity of eye movement pathways at these levels and their reciprocal compensation in the case of a lesion. Lastly, eye movements can also help the neuroscientist to understand the organization of the brain. They are a good model of motricity allowing us, using eye movement recordings, to study the afferent pathways of the cortical areas that trigger them, and thus to analyze relatively complex neuropsychological processes such as visuo-spatial integration, spatial memory, motivation and the preparation of motor programs

Etude en imagerie par résonance magnétique fonctionnelle du rôle du cortex frontal et du cortex temporal dans les saccades mémorisées chez l'homme

ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

The contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis (MS) is reviewed. Among the multiple recently discovered actions of vitamin D, an immunomodulatory role has been documented in experimental autoimmune encephalomyelitis and in humans. This action in the peripheral immune system is currently the main known mechanism through which vitamin D might influence MS, but other types of actions could be involved within the central nervous system. Furthermore, vitamin D insufficiency is widespread in temperate countries and in patients with MS at the earliest stages of the disease, suggesting that the deleterious effects related to vitamin D insufficiency may be exerted in these patients. In fact, many genetic and environmental risk factors appear to interact and contribute to MS. In genetics, several human leukocyte antigen (HLA) alleles (more particularly HLA-DRB1*1501) could favour the disease whereas some others could be protective. Some of the genes involved in vitamin D metabolism (e.g. CYP27B1) also play a significant role. Furthermore, three environmental risk factors have been identified: past Epstein–Barr virus infection, vitamin D insufficiency and cigarette smoking. Interactions between genetic and environmental risk or protective factors may occur during the mother’s pregnancy and could continue during childhood and adolescence and until the disease is triggered in adulthood, therefore possibly modulating the MS risk throughout the first decades of life. Furthermore, some clinical findings already strongly suggest that vitamin D status influences the relapse rate and radiological lesions in patients with MS, although the results of adequately powered randomized clinical trials using vitamin D supplementation have not yet been reported. While awaiting these incontrovertible results, which might be long in coming, patients with MS who are currently in vitamin D insufficiency should be supplemented, at least for their general health status, using moderate doses of the vitamin

Vitamin D and multiple sclerosis: An update

International audienceThe most recent findings linking exposure to sun and vitamin D insufficiency to multiple sclerosis (MS) are reviewed. Due to insufficient sunshine and changing lifestyles, hypovitaminosis D is widespread in temperate countries. Numerous epidemiological studies have strongly suggested that sunshine and vitamin D insufficiency contributes to MS risk in these countries. Moreover, several large genetic studies in MS patients have recently stated unequivocally that diverse abnormalities involving vitamin D metabolism are related to the risk of the disease. The important implications of such results are discussed here. Then, the interactions of hypovitaminosis D with the other genetic and environmental protective and risk factors, such as the allele HLA DRB1*1501, Epstein-Barr virus infection, obesity, smoking and sexual hormones, are summarized. Vitamin D insufficiency and sufficiency could be a risk and a protective factor, respectively, among many other factors possibly continuously modulating the global MS risk from the mother's pregnancy to the triggering of MS in adulthood. However, many interactions between these different factors occur more particularly between conception and the end of adolescence, which corresponds to the period of maturation of the immune system and thymus and may be related to the dysimmune nature of the disease. The main mechanisms of action of vitamin D in MS appear to be immunomodulatory, involving the various categories of T and B lymphocytes in the general immune system, but neuroprotector and neurotrophic mechanisms could also be exerted at the central nervous system level. Furthermore, several controlled immunological studies performed in MS patients have recently confirmed that vitamin D supplementation has multiple beneficial immunomodulatory effects. However, there is still an enduring absence of major conclusive randomized clinical trials testing vitamin D supplementation in MS patients because of the quasi-insurmountable practical difficulties that exist nowadays in conducting and completing over several years such studies involving the use of a vitamin. Nevertheless, it should be noted that similar robust statistical models used in five different association studies have already predicted a favorable vitamin D effect reducing relapses by 50–70%. If there is now little doubt that vitamin D exerts a beneficial action on the inflammatory component of MS, the results are as yet much less clear for the progressive degenerative component. Lastly, until more information becomes available, vitamin D supplementation of MS patients, using a moderate physiological dose essentially correcting their vitamin insufficiency, is recommended

Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation

Background: Vitamin D could play a protective role in multiple sclerosis. Methods: In an observational, uncontrolled study, vitamin D3 supplementation (3010 IU/day on average) was given to 156 consecutive patients with relapsing–remitting multiple sclerosis, under first-line immunomodulatory therapy and with initial 25-OH-D serum level lower than 100 nmol/l (40 ng/ml). Relapses were determined for 29.1 ± 8.4 months during vitamin D and 29.8 ± 10.1 months before supplementation. The 25-OH-D level was measured before supplementation and several times during supplementation. The incidence rate of relapses before and during supplementation was estimated using negative binomial regression models with follow-up durations as offset terms. The incidence rate and incidence rate ratio of relapses at various 25-OH-D levels were also calculated using negative binomial regression models. Results: In 76 patients, immunomodulatory therapy preceded vitamin D supplementation (by 4.2 ± 2.7 years) and in 80 patients both treatments were started simultaneously. Under supplementation, the 25-OH-D level increased from 49 ± 22 nmol/l to 110 ± 26 nmol/l on average. Pooling data collected before and during supplementation, we found a significant strong inverse relationship between the relapse incidence rate and the 25-OH-D level ( p < 0.0001), suggesting that vitamin D did indeed influence the relapse rate. Results of univariate, bivariate and multivariate analyses were analogous: in the multivariate model adjusted for age, disease duration and previous use of immunomodulatory therapy, every 10 nmol increase in 25-OH-D level was associated with a reduction in the relapse incidence rate of 13.7%. Dividing iteratively the population made up of pooled periods into two subgroups according to the 25-OH-D levels, the relapse incidence rate ratio decreased as the 25-OH-D level increased up to 110 nmol/l, but a plateau effect was observed beyond this limit. Conclusion: Further studies are warranted for accurate quantification of the vitamin D effect