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International audience; Background: The perception of diagnosis announcement, the social support and the coping strategies seem to be determining factors for the quality of life of multiple sclerosis (MS) patients, with possible transcultural variations. This study explores these psychosocial dimensions in Lebanese and French MS patients.Methods: For this cross-sectional multi-center study, 8 questionnaires were used to assess quality of life, family support, coping strategies, mood, fatigue, stress, and hopelessness in MS patients. 7 were translated into Arabic and then back translated into French. These were administered to a group of Lebanese MS patients and compared to an MS sample from France. The data was collected for both populations and analyzed.Results: A total of 107 patients were included, 46 Lebanese and 61 French. The majority of MS patients were young females with a high level of education, relapsing remitting form of MS and a low level of disability. Both populations exhibited comparable quality of life and answers on the questionnaires regarding mood disorders, hopelessness, and perceived stress. However, the French patients had significantly more fatigue. Perceived social support given by family was considered greater in the French group compared to the Lebanese one. Also, maladaptive coping strategies (such as self-distraction, denial, behavioral disengagement, substance use, self-blame, venting) were used more frequently by the French population compared to the Lebanese, and this correlated with higher anxiety scores. Diagnosis communication was overall brief, informative, and satisfying in both populations.Conclusion: This study highlighted transcultural differences between French and Lebanese MS patients mainly in social support and coping strategies.

La leucoencefalopatia multifocale progressiva (LEMP) e una grave malattia demielinizzante del sistema nervoso centrale legata a un’infezione attiva e osteolitica degli oligodendrociti da parte del poliomavirus JC. Essa compare con predilezione nei soggetti affetti da deficit dell’immunita cellulare, soprattutto in rapporto con un’infezione da virus dell’immunodeficienza umana (HIV), ma anche secondario a terapie immunosoppressive come alcuni anticorpi monoclonali. La presentazione clinica della malattia e variabile in funzione della sede delle lesioni di demielinizzazione e la sua evoluzione naturale e, di regola, letale. La diagnosi e posta con la risonanza magnetica, il riscontro del genoma virale nel liquor e, a volte, con l’esame istologico. Nessun trattamento specifico ha dimostrato un’efficacia clinica contro il poliomavirus JC. Tuttavia, un ripristino del sistema immunitario puo associarsi a un controllo della LEMP, ma si accompagna, a volte, a una reazione infiammatoria, in genere transitoria, all’interno delle lesioni. Le ricerche attuali si orientano anche verso l’identificazione di molecole in grado di limitare l’infezione virale e verso strategie di riparazione del sistema nervoso.

This article establishes the basics of a theoretical model for the constitutive law that describes the skin temperature and thermolysis heat losses undergone by a subject during a session of whole-body cryotherapy (WBC). This study focuses on the few minutes during which the human body is subjected to a thermal shock. The relationship between skin temperature and thermolysis heat losses during this period is still unknown and have not yet been studied in the context of the whole human body. The analytical approach here is based on the hypothesis that the skin thermal shock during a WBC session can be thermally modelled by the sum of both radiative and free convective heat transfer functions. The validation of this scientific approach and the derivation of temporal evolution thermal laws, both on skin temperature and dissipated thermal power during the thermal shock open many avenues of large scale studies with the aim of proposing individualized cryotherapy protocols as well as protocols intended for target populations. Furthermore, this study shows quantitatively the substantial imbalance between human metabolism and thermolysis during WBC, the explanation of which remains an open question.

Memantine, an uncompetitive antagonist of N-methyl- d -aspartate (NMDA)-type glutamate receptors that was approved for the treatment of moderate to severe Alzheimer's disease, has been negatively evaluated for the treatment of cognitive disorders of multiple sclerosis, but these studies were conducted only during short-term administration and on a heterogeneous group of patients with different forms of the disease. In addition, many adverse reactions were observed in these patients. Aims The purpose of the “EMERITE” (NCT01074619) study was to examine the efficacy and safety of the long-term administration of memantine as a symptomatic treatment for cognitive disorders in patients with relapsing-remitting multiple sclerosis (RR-MS). Methods The study was supported by the French Ministry of Health and received additional support from Lundbeck. In this double-blind, placebo-controlled, parallel group, randomized trial, the participants were assigned to receive memantine (20 mg/day) or a placebo for 52 weeks. The participants included males and females, 18–60 years of age, with a diagnosis of RR-MS and presenting with a cognitive complaint and/or demonstrating moderate cognitive impairment. The data were collected in the Department of Neurology in 19 French centers. The primary outcome was the Paced Auditory Serial Addition Test (PASAT) score at week 52. Secondary measurements included additional neuropsychological tests and the annualized relapse rate. The scores were adjusted according to the baseline scores in the analysis. The safety was assessed by the number of adverse events. The random sequence was generated using the Excel software. At each center, only the pharmacist had access to the allocation sequence and could be asked to unblind the trial. Results Fifty patients were allocated to the memantine group, and 43 to the placebo group. The intent-to-treat (ITT) population included 31 patients in each group. After adjusting for the PASAT scores at baseline, the PASAT scores at the end point did not differ between the memantine and the placebo groups (p = 0.88). Adjusted mean score difference (memantine minus placebo), was − 0.40 (95% confidence interval: -5.5; + 4.7). No significant differences were observed for the secondary outcomes (short term memory and attention scores, EDSS, and relapse rate). The findings remained unchanged after multiple imputation of the missing values. Neurological and psychiatric adverse events were significantly higher in the memantine group than in the placebo group, and these parameters were higher than those reported in the product literature of memantine. Conclusions No differences between the placebo and memantine groups were observed. Nevertheless, the tolerability of memantine was significantly worse than expected.

Introduction Des etudes ont demontre le benefice clinique de la mise sous fingolimod des patients atteints d’une SEP en echec de traitement de premiere ligne. Objectifs Evaluer la satisfaction du patient atteint de SEP-RR en France traite par le fingolimod apres l’echec d’un premier traitement de fond. Patients et methodes ESGILE est une etude observationnelle et prospective conduite en France chez des patients atteints de SEP-RR ayant initie un traitement par le fingolimod dans les 4 semaines precedant la visite d’inclusion (M0). L’appreciation du neurologue investigateur et du patient de l’evolution a 6 mois (M6) a ete evaluee respectivement par le Clinical Global Impression (CGI) et le Patient Global Impression (PGI). La satisfaction vis-a-vis du traitement a ete evaluee par l’auto-questionnaire ACCEPT (M0 et M6). Resultats Au total, 194 patients ont ete inclus (âge moyen : 40 ± 11 ans, femmes : 76 %). Selon l’investigateur, 36 % des patients s’etaient ameliores a M6 (CGI). 60 % des patients se consideraient ameliores (PGI). D’apres le questionnaire ACCEPT, la proportion de patients avec effets indesirables est passee de 47 % (M0) a 27 % (M6), la proportion considerant leur traitement efficace de 33 % a 62 % et celle jugeant les avantages du traitement superieurs a ses inconvenients de 56 % a 78 %. Discussion Suite a la mise sous fingolimod, la plupart des patients percoivent leur traitement comme efficace et bien tolere et considerent leur etat general comme ameliore. Les patients ont eu une perception plus positive de l’evolution de leur qualite de vie que leur neurologue. Les raisons de cette difference d’appreciation meriteraient etre explorees. Conclusion L’introduction du fingolimod apres echec d’un traitement de premiere ligne est percue de maniere tres positive, pour le patient et son prescripteur, sur l’impression globale d’amelioration et la satisfaction.

International audience; No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. Uncontrolled, non-blinded proof of concept study 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going.

Introduction Neuropsychiatric signs and MRI abnormalities can occur in patients with phenylketonuria in adulthood. We describe clinical and radiological features of phenylketonuric patients and we discuss the advantage of continuing diet in adulthood. Method We report late onset neuropsychiatric symptoms of four phenylketonuric patients (33–45 years) diagnosed in infancy and report the case of a patient (33 years) diagnosed with phenylketonuria because of late onset neurological signs. We describe clinical and radiological features of these 5 patients, and their evolution under diet and propose a review of the literature. Results The main neurological abnormalities in phenylketonuric patients diagnosed in infancy are: brisk reflexes, spastic paraparesis, psychiatric signs that appear 10.5 years after the diet arrest. A leukoencephalopathy was present in 93% of cases and 91.7% improve clinically after poor phenylalanine diet reintroduction. In 4 patients, neurological abnormalities (spastic paraparesis, dementia, Parkinsonism) led to the late diagnosis. Two of them had a leukoencephalopathy on brain MRI. Patients had high levels of phenylalanine (above 1500 μmol/L) when neuropsychiatric signs occurred. Improvement after diet suggests that hyperphenylalaninemia has a direct toxic effect on the brain. Discussion/Conclusion The long-term follow-up of phenylketonuric patients is mandatory to depict and treat neurological complications in time. Diet reintroduction is efficacious in most cases.

Introduction Le fingolimod FTY est utilises pour le traitement de la sclerose en plaques recurrente-remittente SEP-RR. Dans la plupart des pays europeens, le fingolimod est utilises habituellement comme un traitement de deuxieme ligne. Objectifs Evaluer l’efficacite du FTY en utilisant des parametres cliniques et radiologiques, chez les patients SEP-RR traites en deuxieme ligne suivant un schema d’escalade therapeutique apres echec d’un traitement de premiere ligne. Methodes Etude retrospective observationnelle inclut tous les patients SEP-RR traites pendant au moins 12 mois par immunomodulateurs et 24 mois par FTY apres echec du traitement de premiere ligne. Les donnees recueillies concernent le taux annualise de poussees (TAP), la progression du handicap mesure par le score EDSS et les nouvelles lesions en IRM (lesion Gd+/lesions nouvelles et etendues en T2). Nous avons inclus 52 patients traites par FTY. Resultats TAP a diminue de 1,31 avant le traitement a 0,3 apres 12 mois et 0,22 apres 24 mois p Discussion Devant un echec des traitements de premiere ligne, le passage a un traitement d’efficacite superieure est associe a un pronostic favorable. Dans cette etude nous avons montre que le passage a un traitement par le FTY etait associe a une amelioration des marqueurs de l’evolution de la maladie, reduction du TAP, diminution du handicap soutenu et diminution de l’activite radiologique. Conclusion L’escalade therapeutique par FTY est plus efficace pour controler l’activite clinique et radiologique de la maladie apres un echec du traitement de premiere ligne par un immunomodulateur.

Introduction MSCopilot est une solution smartphone (dispositif medical), concue pour l’auto-evaluation des patients atteints de SEP, et composee de 4 tests : marche, dexterite, cognition et vision a bas contraste. Objectifs Comparer la capacite de MSCopilot a discriminer des volontaires sains (VS) de patients atteints de SEP a celle du score MSFC (Multiple Sclerosis Functional Composite) et mesurer leur correlation globale et test a test. Patients et Methodes Etude multicentrique, ouverte, randomisee sur 141 patients et 76 volontaires sains apparies (âge, sexe, indice de masse corporelle et education.) qui ont successivement effectue les tests standard {Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Paced Auditory Serial Addition Task (PASAT) et Symbol Digit Modalities Test (SDMT) et acuite visuelle a bas contraste : Sloan Low-Contrast Letter Acuity Test (SLCLAT)}, puis les tests numeriques : {marche (MWT), dexterite (MCT), cognition (MAT), vision (MVT)}, et vice-versa. Resultats Sur 116 patients analysables (61 % femmes, 74 % SEP remittentes, 26 % SEP progressives) et 69 VS, MSCopilot etait non-inferieur a la MSFC (aire sous la courbe de 0,92 et 0,89 respectivement). La sensibilite de MSCopilot et MSFC etait respectivement de 81 % et 76 %, la specificite de 82 % et 88 %. Correlations (Pearson) : MSCopilot vs. MSFC, r = 0,81 ; MSCopilot vs MSFC (SDMT) : r = 0,83 ; MSCopilot vs MSFC4 (SDMT et SLCLAT) : r = 0,85. Discussion Independamment du score EDSS, les participants ont prefere MSCopilot aux tests standards et seraient prets a l’utiliser a la maison au moins une fois par mois. 46 patients ont passe 2 visites a un mois d’intervalle avec une reproductibilite satisfaisante des resultats. Conclusion MSCopilot est non-inferieur a la MSFC pour discriminer patients et VS avec de fortes correlations entre tests numeriques et standards. MSCopilot pourrait etre utile pour l’evaluation en vie reelle des patients SEP.

Objective The prevalence of multiple sclerosis (MS) in Lebanon is unknown, as there are no available or reliable epidemiological studies to date. The circumstances of Middle East countries are different from those of Europe and North America in terms of differential diagnoses and disease management. The aim of the conference is to establish guidelines for diagnosis, treatment, follow-up and management of patients with MS in Lebanon. Another objective is to discuss and participate in research projects based on epidemiology, clinical trials and more fundamental aspects of the disease in the future. Methods Under the authority of the Lebanese society of Neurology (LSN), a group of neurologists took the initiative to participate in this LSN MS committee with the purpose of establishing a consensus for the management of patients with MS, and under the supervision of a Coordinator (A.T.) designed by the LSN board. Results Diagnostic and therapeutic, follow-up and research recommendations were proposed with special emphasis on the specific needs and circumstances of Lebanon. The experts highlighted the importance of considering particular needs, the identification of patients at high risk of developing MS in order to maximize therapeutic opportunities, and cost-effective control of treatment efficacy, as well as global assessment of disability. Conclusions The experts established guidelines concerning diagnosis, treatment, and follow-up of patients with MS in Lebanon. Furthermore, they recommended some clinical and fundamental research projects.

Magnetic resonance imaging is the modality of choice to investigate patients with central nervous system diseases. In patients with optic neuritis, early MRI allows positive and differential diagnosis, and gives arguments for prognosis. The technique should be adapted for the exploration of visual pathways. Inflammatory optic neuritis is characterized by an early signal abnormality within the optic nerve, whereas optic nerve MRI is normal in the early phase of ischemic optic neuropathy. MRI also detects compressive and infiltrative lesions. Meningiomas are characterized by abnormalities within the peri-optical spaces, whereas a global increase in the size of the optic nerve is in favor of a glioma.

Resume Introduction La tomographie par coherence optique (OCT) represente un outil potentiel dans le diagnostic et le suivi des maladies du nerf optique et des voies visuelles anterieures pregeniculees. Elle permet une analyse quantitative, objective et reproductible de l’epaisseur moyenne de la couche des fibres ganglionnaires peripapillaires. L’utilite de l’OCT en pratique neuro-ophtalmologique a ete evaluee a travers une revue de la litterature. Materiels et methodes Une analyse des differentes applications cliniques de la mesure de l’epaisseur de la couche des fibres ganglionnaires (OCT par analyse temporelle) a ete realisee. La selection des publications est basee sur le moteur de recherche PubMed avec les mots cles : « neuropathie optique », « epaisseur des fibres ganglionnaires retiniennes », « OCT ». Les publications concernant la neuropathie glaucomateuse ont ete exclues de cette revue. Resultats Les atteintes des voies visuelles anterieures pregeniculees peuvent etre classees dans deux categories, selon l’evolution de l’epaisseur de la couche des fibres ganglionnaires peripapillaires : (I) une diminution progressive vers l’atrophie (ex. : nevrites optiques, compression chiasmatique) ou (II) une augmentation initiale suivie d’une diminution soit (IIa) vers une normalisation (ex. : œdeme papillaire de l’hypertension intracrânienne idiopathique) soit (IIb) vers l’atrophie (ex. : neuropathie optique ischemique anterieure, neuropathie optique hereditaire de Leber). Discussion Selon le type d’atteinte des voies visuelles anterieures, l’OCT apporte des donnees diagnostiques, evolutives et pronostiques. Comme en pathologie maculaire, l’OCT est devenu un outil de routine en neuro-ophtalmologie.

Resume Introduction La maladie de Behcet est une vascularite multisystemique pouvant atteindre le systeme nerveux central. L’atteinte du corps calleux en IRM est rarement rapportee dans cette affection. Observation Nous rapportons le cas d’une patiente caucasienne de 47 ans, hospitalisee pour un deficit neurologique d’allure vasculaire, associee a un syndrome confusionnel revelant une maladie de Behcet. L’IRM montrait, en outre, une atteinte pedonculo-thalamique et de la substance blanche suggestive de la maladie mais aussi du corps calleux, cette derniere etant tres inhabituelle. Conclusion Cette observation montre que la maladie de Behcet est a ajouter a la liste des affections dans lesquelles l’atteinte du corps calleux est possible.

Resume Introduction Les techniques conventionnelles de l’IRM permettent une approche diagnostique et pronostique des affections metaboliques de l’adulte. Etat des connaissances Des anomalies bilaterales et symetriques en sont suggestives. Les caracteristiques de signal (intensite, aspect sur les differentes sequences), l’extension et la topographie lesionnelle permettent alors d’orienter l’etiologie. L’imagerie non conventionnelle permet une approche essentiellement physiopathologique. Perspectives Les differentes modalites de l’IRM semblent prometteuses pour le suivi therapeutique. Conclusion La combinaison des differentes modalites de la RMN permettent une approche diagnostique, physiopathologique et semblent prometteuses pour le pronostic et le suivi therapeutique des patients atteints de maladies metaboliques de l’adulte.

Revue Neurologique - In Press.Proof corrected by the author Available online since mercredi 23 octobre 2013

Introduction Le Teriflunomide (TRF) et le Dimethyl-Fumarate (DMF) sont deux traitements approuves de 1re ligne pour la forme remittente de sclerose en plaques (SEP). Cependant, a ce jour, il n’existe aucun essai randomise ni aucune etude observationnelle comparant leur efficacite relative. Objectif Le but de cette etude est de comparer le TRF et le DMF sur des criteres d’efficacite clinique et IRM a partir des donnees observationnelles des 34 centres issus de la cohorte francaise OFSEP. Methodes Les patients SEP inclus dans l’etude avaient une forme remittente de la maladie, etaient âges de 18 a 65 ans, avaient un score EDSS entre 0 et 5,5 a l’inclusion et une IRM dans l’annee precedant l’initiation du traitement. Les donnees ont ete collectees prospectivement a partir de 585 patients traites par TRF et 890 par DMF. Le critere de jugement principal etait la proportion de patients ayant fait au moins une poussee dans l’annee suivant l’initiation du traitement par TRF ou DMF. Trois criteres de jugement secondaires ont aussi ete etudies : la proportion de patients avec au moins une nouvelle lesion T2, la proportion de patients avec au moins une lesion prenant le gadolinium (gado+) et la proportion de patients avec une augmentation du score EDSS apres un an de traitement. L’analyse statistique etait basee sur des scores de propension (IPTW) et une regression logistique. Resultats La comparaison des deux groupes (TRF et DMF) a l’initiation du traitement montre que les patients traites par DMF avaient une duree de maladie plus courte, une proportion augmentee de patients ayant fait une poussee ou plus dans l’annee ou les deux annees precedant la mise en route du traitement et une augmentation du pourcentage de patients avec au moins une lesion gado+. Cependant apres ajustement sur ces facteurs confondant, apres un an de traitement la proportion de patients ayant fait au moins une poussee etait similaire dans le groupe TRF et DMF (20,1 % versus 20,4 %). De la meme facon l’analyse des criteres secondaires IRM et EDSS revelait une efficacite similaire entre les deux groupes apres un an de traitement. Interpretation En France, les neurologues choisissent preferentiellement le DMF comme traitement en premiere intention pour les patients ayant une forme plus active de maladie. Cependant, apres un an de traitement et apres correction pour les facteurs confondants, l’efficacite du DMF et du TRF est similaire en termes de prevention des poussees et de survenue de nouvelle lesion T2 ou de lesion gado+.

Introduction Les resultats globaux de l’etude PROTEC demontrent la reduction du taux annualise de poussees (TAP) et l’impact du dimethyle fumarate (DMF) sur les criteres evalues par les patients (CEP) dans le traitement de la sclerose en plaques recurrente-remittente (SEP-RR). Objectifs L’objectif etait de determiner l’efficacite clinique et l’impact sur les CEP du DMF sur une duree de 12 mois, dans le sous-groupe de patients francais de l’etude. Methodes PROTEC etait une etude de phase 4, internationale, multicentrique en ouvert, incluant 1105 patients adultes (≥ 18 ans) presentant une SEP-RR et naifs de traitement par DMF ou de traitement de seconde ligne. Les patients etaient traites par DMF 240 mg × 2/jour. Les poussees et la tolerance au traitement etaient evaluees a chaque visite (planifiee ou non). Les CEP des patients etaient evalues a l’inclusion et apres 3, 6 et 12 mois. Resultats Au total, 198 patients ont ete inclus en France (âge moyen [± ecart-type] : 40,0 [± 11,0] ans, % femmes : 76,8 %). Le TAP non ajuste pour les 12 mois avant et apres initiation du DMF etait respectivement de 0,62 (intervalle de confiance [IC] a 95 % : 0,52–0,72) et 0,22 (IC95 % : 0,15–0,31), avec un ratio de 0,36 (IC95 % : 0,25–0,51 ; p Discussion Un an apres l’initiation du DMF, huit patients sur dix (82,8 %) n’avaient pas presente de poussees et une diminution de 64 % du TAP a ete mise en evidence. Par ailleurs, une amelioration du score MSIS-29 (dimensions physique et psychologique), et des scores de satisfaction vis-a-vis du traitement, fatigue et depression ont ete observes. Conclusion A l’instar des resultats de la population totale de l’etude, le traitement par DMF est associe, dans le sous-groupe de patients francais, a une diminution du TAP et une amelioration de certains CEP a 12 mois. Informations complementaires L’etude a ete financee par Biogen.

Natalizumab (Tysabri) is the first monoclonal antibody indicated for the treatment of active relapsing-remitting multiple sclerosis. Natalizumab is reserved for hospital use. Strict monitoring is necessary to detect side effects associated with the perfusion of the product, possible inefficacy of the treatment, and, more rarely, infectious complications, some of which (for example, progressive multifocal leukoencephalitis) are severe. Rigorous collection of efficacy and tolerance data will make it possible to assess the impact of this treatment on the natural history of multiple sclerosis.

MRI is one of the most important tools for the investigation of white matter diseases of the central nervous system. Other techniques based on the magnetic resonance phenomena (magnetization transfer imaging, diffusion imaging, magnetic resonance spectroscopy) have joined MRI to better caracterize certain diseases, understand their pathophysiology and follow their evolution.

Interferons (IFNs) were considered for the treatment of patients with multiple sclerosis (MS) after the demonstration, based on small studies, of the efficacy of type IFN beta in decreasing the frequency of exacerbations in relapsing-remitting multiple sclerosis when administered intrathecally, subcutaneously, or intramuscularly. Three preparations of IFN beta are now approved in Europe and North America: chronologically IFN beta-1b (Berlex/Schering), IFN beta-1a given intramuscularly (Biogen), and IFN beta-1a given subcutaneously (Ares Serono). These treatments have now been in use for more than 10 years, and are supposed to decrease relapse rates. However a lot of questions remain unanswered: it is difficult to compare the various preparations; there remain controversies about the effects of different routes of administration and of different dosage preparations; the role of neutralizing antibodies remains partially understood; and the long term effect on disability has not yet been demonstrated.