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International audience; Objective: We aimed to identify timing distortions in production and perception of rhythmic events in patients with idiopathic REM sleep behavior disorder (iRBD) as early markers of Parkinson's disease (PD).Methods: Rhythmic skills, clinical characteristics, dysautonomia, depression, and olfaction were compared in 97 participants, including 21 participants with iRBD, 38 patients with PD, and 38 controls, matched for age, gender, and education level. Rhythmic disturbances can be easily detected with dedicated motor tasks via a tablet application. Rhythm production was tested in two conditions: to examine the ability to generate a spontaneous endogenous rhythm, tapping rate and variability in a finger tapping task without external stimulation was measured, while the ability to synchronize to an external rhythm was tested with finger tapping to external auditory cues. Rhythm perception was measured with a task, in which the participants had to detect a deviation from a regular rhythm. Participants with iRBD had dopamine transporter imaging.Results: Participants with iRBD and PD revealed impaired spontaneous rhythm production and poor rhythm perception compared to controls. Impaired rhythm production was correlated with olfaction deficits, dysautonomia, impaired non-motor aspects of daily living, and dopamine uptake measures.Conclusions: Participants with iRBD show impaired rhythm production and perception; this impairment is correlated with other early markers for PD. Testing rhythmic skills with short and inexpensive tests may be promising for screening for potential future PD in iRBD patients.

OBJECTIVE To determine whether brain amyloid burden in elderly patients with narcolepsy type 1 (NT1) is lower than in controls, and to assess in patients with NT1 the relationships between amyloid burden, cerebral spinal fluid (CSF) markers of Alzheimer disease (AD), CSF orexin-A, and cognitive profile. METHODS Cognitive and 18 F-florbetapir positron emission tomography (PET) data were compared in patients with NT1 aged ≥ 65 years (n = 23) and in age- and sex-matched controls free of clinical dementia selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 69) and the Multi-Domain Intervention Alzheimer's Prevention Trial (MAPT-18F AV45-PET; n = 23) cohorts. The standardized uptake values (SUVs) of the cortical retention index for 6 regions of interest were computed and averaged to create a mean SUV ratio normalized to 3 subcortical reference regions (cerebellum, pons, and a composite region). A cortical/cerebellum SUV ratio ≥ 1.17 defined positive PET amyloid. RESULTS Lower cortical amyloid burden was observed in the NT1 than in the ADNI and MAPT-AV45 groups (mean cortical/cerebellum SUV ratios = 0.95 ± 0.15, 1.11 ± 0.18 [p

International audience; Objective: The objective of this study was to assess the rotigotine effect on the nocturnal blood pressure (BP) dip by 24-hour ambulatory BP monitoring and on endothelial function in patients with restless legs syndrome (RLS) compared with placebo.Methods: In this double-blind, placebo-controlled trial, 76 adult patients with moderate to severe RLS and periodic legs movements in sleep index ≥10/hour were randomized to rotigotine at optimal dose of 3 mg per day or placebo for 6 weeks. A total of 6 patients had a major protocol deviation. Polysomnography, ambulatory BP monitoring, and endothelial function were assessed at baseline and end point. The primary outcome was the between-group difference in the percentage of BP nondipper profiles at end point. The main secondary outcomes were the mean BP dip, periodic legs movements in sleep index, and endothelial function.Results: Of the 70 patients (age, 59.4 ± 11.40; 43 women) randomized to rotigotine (n = 34) and placebo (n = 36), 66 (33 rotigotine, 33 placebo) completed the study. The percentage of BP nondippers at end point was higher in the placebo than in the rotigotine group (systolic BP, 72.22% vs 47.06%; diastolic BP, 47.22% vs 20.59%; P < 0.05). Mean BP dip at end point was higher in the rotigotine than in the placebo group (systolic BP, 11.24 ± 6.15 vs 6.12 ± 7.98; diastolic BP, 15.12 ± 7.09 vs 9.36 ± 10.23; P < 0.05). Endothelial function was comparable between the groups. No significant safety concerns were reported with similar incidences of adverse events between groups.Conclusion: Rotigotine increased the percentage of BP dipper profiles and the BP dip in patients with RLS. Future studies should assess whether this change is associated with a reduction in the long-term cardiovascular risk in RLS. © 2020 International Parkinson and Movement Disorder Society.

Background Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. Objectives To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. Methods Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11–25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barre syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008–2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. Results With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41–0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. Conclusion Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

To determine whether brain amyloid burden in elderly patients with narcolepsy type 1 (NT1) is lower than in controls, and to assess in patients with NT1 the relationships between amyloid burden, cerebral spinal fluid (CSF) markers of Alzheimer disease (AD), CSF orexin-A, and cognitive profile.Cognitive andLower cortical amyloid burden was observed in the NT1 than in the ADNI and MAPT-AV45 groups (mean cortical/cerebellum SUV ratios = 0.95 ± 0.15, 1.11 ± 0.18 [p 0.0001], and 1.14 ± 0.17 [p = 0.0005], respectively). Similar results were obtained with all subcortical reference regions and for all cortical regions of interest, except cingulum. Only 1 patient with NT1 (4.4%) had positive PET amyloid compared with 27.5% in the ADNI and 30.4% in the MAPT-AV45 group. In the NT1 group, cortical or regional amyloid load was not associated with CSF orexin-A, CSF AD biomarkers, or neuropsychological profile.Lower brain amyloid burden, assessed by

Next-generation sequencing (NGS) has an established diagnostic value for inherited ataxia. However, the need of a rigorous process of analysis and validation remains challenging. Moreover, copy number variations (CNV) or dynamic expansions of repeated sequence are classically considered not adequately detected by exome sequencing technique. We applied a strategy of mini-exome coupled to read-depth based CNV analysis to a series of 33 patients with probable inherited ataxia and onset

Objectif Rechercher les determinants cliniques et polysomnographiques du temps total de sommeil (TTS) sur l’enregistrement controle de 32 h chez une population de patients avec plainte d’hypersomnolence et de sujets temoins. Methodes Un enregistrement continu de 32 h en condition bed-rest precede d’une polysomnographie (PSG) et de tests iteratifs de latence d’endormissement (TILE) a ete realise chez 204 patients avec hypersomnie idiopathique (HI, 140 F, âge median 26), 20 patients avec narcolepsie de type 2 (NT2, 13 F, âge median 23), 63 sujets avec hypersomnolence non-specifiee, souvent comorbide (HNS, 43 F, âge median 30) et 24 temoins (14 F, âge median 25). Le TTS sur les 32 h a ete decoupe en tertiles de la population globale. Resultats Cent-cinq sujets (30 HI, 3 NT2, 52 HNS, 20 temoins) avaient un TTS Conclusion L’âge jeune, le sexe feminin, la plainte de somnolence diurne, un sommeil de nuit de bonne qualite et une possible dysregulation du SP s’associent a des durees du sommeil plus longues dans des conditions standardisees.

Objective To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD). Methods Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication use, family history, and autonomic/motor symptoms. After 4 years of follow-up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan–Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression. Results Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years and 41% after 5 years. Patients who converted were older (difference = 4.5 years, p

Objective:To validate the Narcolepsy Severity Scale (NSS), a brief clinical instrument to evaluate the severity and consequences of symptoms in patients with narcolepsy type 1 (NT1).Methods:A 15-item scale to assess the frequency and severity of excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nighttime sleep was developed and validated by sleep experts with patients' feedback. Seventy untreated and 146 treated adult patients with NT1 were evaluated and completed the NSS in a single reference sleep center. The NSS psychometric properties, score changes with treatment, and convergent validity with other clinical parameters were assessed.Results:The NSS showed good psychometric properties with significant item-total score correlations. The factor analysis indicated a 3-factor solution with good reliability, expressed by satisfactory Cronbach α values. The NSS total score temporal stability was good. Significant NSS score differences were observed between untreated and treated patients (dependent sample, 41 patients before and after sleep therapy; independent sample, 29 drug-free and 105 treated patients). Scores were lower in the treated populations (10-point difference between groups), without ceiling effect. Significant correlations were found among NSS total score and daytime sleepiness (Epworth Sleepiness Scale, Mean Sleep Latency Test), depressive symptoms, and health-related quality of life.Conclusions:The NSS can be considered a reliable and valid clinical tool for the quantification of narcolepsy symptoms to monitor and optimize narcolepsy management.

Objective:Polyglutamine (PolyQ) diseases are dominantly transmitted neurologic disorders, caused by coding and expanded CAG trinucleotide repeats. Cancer was reported retrospectively to be rare in patients with PolyQ diseases and we aimed to investigate its prevalence in France.Methods:Consecutive patients with Huntington disease (HD) and spinocerebellar ataxia (SCA) were questioned about cancer, cardiovascular diseases, and related risk factors in 4 university hospitals in Paris, Toulouse, Strasbourg, and Montpellier. Standardized incidence ratios (SIR), based on age- and sex-adjusted rate of the French population, were assessed for different types of cancer.Results:We questioned 372 patients with HD and 134 patients with SCA. SIR showed significantly reduced risk of cancer in HD: 23 observed cases vs 111.05 expected ones (SIR 0.21, 95% confidence interval [CI] 0.13–0.31), as well as in SCA: 7 observed cases vs 34.73 expected (SIR 0.23, 95% CI 0.08–0.42). This was surprising since risk behavior for cancer was increased in these patients, with significantly greater tobacco and alcohol consumption in patients with HD vs patients with SCA (p < 0.0056). There was no association between CAG repeat size and cancer or cardiovascular disease. However, in patients with HD, skin cancers were more frequent than expected (5 vs 0.98, SIR 5.11, 95% CI 1.65–11.95).Conclusions:There was a decreased cancer rate in PolyQ diseases despite high incidence of risk factors. Intriguingly, skin cancer incidence was higher, suggesting a crosstalk between neurodegeneration and skin tumorigenesis.

International audience; OBJECTIVES:Narcolepsy type 1 (NT1) is considered to be an immune-mediated disease in which environmental factors, such as vitamin D, might play a major role. The association between NT1 and vitamin D deficiency has previously been reported. The aim of this case-control study was to reassess vitamin D levels in a large clinic-based adult and paediatric population of patients with NT1 by considering several potential confounding factors.METHODS:The serum level of 25-hydroxyvitamin D (25OHD) was measured in 174 Caucasian patients with NT1 and 174 controls. Demographic and clinical features, body mass index (BMI), Pandemrix® vaccination, age, and season at the time of blood sampling were recorded. Between-group comparisons were made using univariate and multivariate logistic regression analyses. When appropriate, interaction terms were tested using the Wald Chi-squared test.RESULTS:Age, BMI, and season of blood sampling were different between groups. Conversely, the 25OHD level and fraction of subjects with vitamin D deficiency (serum level

Multiple sclerosis (MS) is the main nontraumatic cause of handicap in young adults. Immunomodulators and treatments limiting lymphocyte migration have been proven efficient to treat relapsing-remitting MS. Subcutaneous IFN-β1a improve relapse rate and MRI parameters in a series of double-blind, placebo-controlled trials in relapsing-remitting MS patients. Similar results, and with a greater extent, were obtained when treating patients with a first demyelinating event suggestive of MS. Except for the rare liver toxicity, the drug is well tolerated and has no severe adverse reaction. When compared with intramuscular IFN-β1a, both relapse rate and MRI parameters were modulated in favor of the subcutaneous administration. Although the effect of subcutaneous IFN-β1a on disability progression is limited, the good tolerance profile together with the efficiency of the drug explain why this treatment, as well as the other interferons and glatiramer acetate, is a first-line therapy for relapsing-remitting MS.

Objective Supine sleep is associated with increased obstructive sleep apnea. People with Parkinson's disease (PD) complain about difficulties turning around in bed. The relationship between supine sleep and sleep-disordered breathing has never been explored in people with Parkinson's disease. Methods Fifteen consecutive people with PD with severe Obstructive Sleep Apnea Syndrome (OSAS) were compared to: (1) 15 age-matched, gender-matched, body mass index-matched and Unified Parkinson's Disease Rating Scale-III score-matched people with PD without sleep-disordered breathing; (2) 11 age-matched and gender-matched people with severe obstructive sleep apnea syndrome (OSAS) alone; and (3) 11 age-matched and gender-matched healthy controls. Outcomes were: number of position changes during the night and per hour of sleep, and the percentage of sleep time spent in supine. Results People with PD and severe OSAS spent most of their sleep time in the supine position (93 ± 11%); while people with PD without OSAS (61 ± 24%, p 0.001), people with isolated, severe OSAS (50 ± 28%, p 0.001), and the controls (40 ± 21, p 0.001) spent significantly less time on their back. People with PD and severe OSAS changed their position in bed per hour of sleep (0.4 ± 0.5) less frequently than those with PD without OSAS (1.1 ± 0.8, p = 0.002), those with isolated OSAS (1.2 ± 1.0, p = 0.006) and the controls (1.5 ± 0.5, p 0.001). Conclusion PD and severe OSAS are associated with a major reduction in the number of position changes and an increased supine sleep position during the night. For people with PD, alleviating the difficulties of turning around in bed might reduce the supine sleep position and improve sleep-disordered breathing.

Objectif Valider un instrument de mesure afin d’evaluer la severite et les consequences des symptomes de la narcolepsie de type 1 (NT1). Methodes Au total, 146 adultes diagnostiques NT1 traites par psychostimulant et 70 NT1 non traites ont complete une echelle de 15 items evaluant la frequence, la severite et les consequences de la somnolence diurne excessive (SDE), de la perturbation du sommeil de nuit ainsi que des cataplexies, hallucinations et paralysies du sommeil. Les proprietes psychometriques de l’echelle et sa validite avec des parametres cliniques ont ete etudiees. Resultats L’echelle montre une consistance interne satisfaisante. L’analyse factorielle a permis de degager 3 domaines « SDE et sommeil de nuit », « cataplexies », et « paralysie du sommeil et hallucinations ». Elle est stable sur une periode de un an chez des sujets evalues dans des conditions similaires. Le score global a l’echelle est significativement plus bas chez les patients traites que chez ceux non traites que ce soit sur echantillon dependant (41 patients evalues avant et apres traitement) ou sur echantillon independant (29 patients non traites versus 105 traites), avec 10 points de difference entre les groupes. Le score est significativement correle a la SDE (evaluee subjectivement par l’echelle d’Epworth ou objectivement par tests de latence a l’endormissement), aux niveaux de depression et de qualite de vie. Conclusion Cette echelle se revele etre un outil clinique fiable pour quantifier les symptomes de la narcolepsie et pourrait ainsi permettre de controler et d’ameliorer sa prise en charge.

Resume Introduction L’association d’une atteinte demyelinisante peripherique et centrale a ete rarement rapportee. Observation Un homme de 30 ans, aux antecedents d’atteinte demyelinisante du SNC remplissant les criteres de SEP, presenta des troubles de l’equilibre et une areflexie diffuse en rapport avec une polyneuropathie remplissant les criteres de demyelinisation. Il fut ameliore transitoirement par des cures d’immunoglobulines intraveineuses puis se stabilisa apres introduction de methotrexate. Conclusion Malgre le tres faible nombre de cas rapportes, une nouvelle entite associant une demyelinisation du SNC et du SNP, avec une hyperproteinorachie majeure, sans bandes oligoclonales dans le LCR, semble se distinguer de la SEP et des PRNC.

OBJECTIVES To investigate decision-making and addictive behaviors in narcolepsy-cataplexy (NC). NC is caused by the loss of hypothalamic neurons that produce hypocretins. The hypocretin system plays a crucial role in sleep, wakefulness, and energy homeostasis, and is also involved in emotion regulation, reward processing, and addiction. SETTING Academic sleep center. PATIENTS 23 subject with NC and 23 matched healthy controls. DESIGN We used the Iowa Gambling Task (IGT) to assess decision making under ambiguity condition based on emotional feedback processing and the Game of Dice Task (GDT) to assess decision making under risk condition. All participants underwent a semi-structured psychiatric interview and completed the Beck Depression Inventory-II and the UPPS Impulsive Behavior Scale. Patients underwent one night of polysomnography followed by an MSLT, with neuropsychological evaluation performed between MSLT sessions. MEASUREMENTS AND RESULTS NC patients had higher depressive symptoms and showed a significant lack of perseverance. One NC patient had a past history of drug dependence. NC patients also exhibited selective reduced IGT performance and normal performance on the GDT. No clinical or polysomnographic characteristics were associated with increased sensitivity to reward and/or decreased sensitivity to punishment. However, lack of perseverance in NC patients was associated with disadvantageous decision making on the IGT. CONCLUSION We demonstrated a lack of perseverance and a selective reduced performance on decision making under ambiguity in NC in contrast to normal decision making under explicit conditions. Patients with narcolepsy-cataplexy may opt for choices with higher immediate emotional valence, regardless of higher future punishment, to compensate for their reduced reactivity to emotional stimuli.

Objectif Comparer la charge amyloide mesuree par TEP-florbetapir-AV45 des patients narcoleptiques orexine/hypocretine-deficient (NT1) âges versus des controles apparies en âge et sexe et evaluer chez les patients NT1 les correlations entre TEP-AV45, biomarqueurs du liquide cerebrospinal LCS d’Alzheimer, cognition et parametres sommeil. Methodes Les caracteristiques demographiques, neuropsychologiques et d’imagerie des 22 patients NT1 inclut sont comparees a celles des 66 controles apparies en âge et sexe issus de la cohorte ADNI. Le ratio de l’indice de retention cortical (SUVr) du florbetapir est defini par rapport au cervelet, au pont ou score composite et mesure dans le cortex et six regions d’interet. Le TEP-AV45 est considere positif visuellement ou lorsque SUVr-cortical/cervelet > 1,17. Le sommeil est evalue via des questionnaires valides. Les systemes mnesiques, executifs, instrumentaux sont etudies. Les concentrations LCS d’Aβ42, Tau, p-Tau sont mesurees par ELISA. Resultats L’âge median des 22 NT1 (14H/8F) est de 71 ans [65–86]. Un TEP-AV45 positif est objective dans 4,5 % des NT1 contre 28,8 % des controles. Le SUVr-cortical/cervelet median est plus faible pour le groupe NT1 compare aux controles (0,92 [0,64 ; 1,36] vs 1,06 [0,85 ; 1,90] p Conclusion Nos resultats sont en faveur d’un effet protecteur de l’absence d’orexine sur la genese des plaques amyloides en accord avec les donnees precliniques.

International audience; Objective To investigate brain changes in both basal and cataplectic conditions in awake patients with narcolepsy-cataplexy.;Background Recent insights in pathophysiology have demonstrated that narcolepsy-cataplexy is caused by early loss of hypothalamus hypocretin neurons. However, the neurophysiological mechanisms underlying sleepiness and the dramatic cataplexy reaction to positive emotion remain unclear.;Methods Twenty-one patients with narcolepsy-cataplexy and 21 age- and sex-matched controls were included. Diagnosis of narcolepsy was fully confirmed by polysomnography, HLA DQB1*0602 and CSF hypocretin levels (n=9). Seven patients were free of all drugs, and 14 were treated with psychostimulant and/or anticataplectic drugs. (18)-F-fluorodeoxy glucose positron emission tomography procedures were performed at baseline in all subjects and during cataplexy attacks (n=2).;Results The authors found significant hypermetabolism in narcolepsy-cataplexy in fully awake condition in the limbic cortex specifically in the anterior and mid cingulate cortex, in the right cuneus and lingual gyrus. In contrast, no hypometabolism was found. Hypermetabolism was detected in the cerebellum and pre-postcentral gyri in treated compared with untreated patients. During cataplectic attacks, cerebral metabolism significantly increased in the bilateral pre-postcentral gyri, primary somatosensory cortex, with a marked decrease in the hypothalamus.;Conclusion Hypermetabolism was found in the executive network in narcolepsy at baseline in fully awake condition. Wake state assessment during scanning appears critical to avoid results showing altered functional neurocircuitry secondary to sleepiness and not to the underlying neurological disorder per se. Finally, cataplexy attacks were characterised by a hypometabolism in the hypothalamus associated with wide bilateral brain area hypermetabolisms.

Resume Introduction La sclerose en plaques (SEP) est une maladie neurologique chronique et souvent invalidante. Elle evolue par poussees ou sur un mode progressif. La classique dissociation axonomyelinique n’est plus a l’heure actuelle retenue en raison de l’atteinte axonale frequente et precoce. Le nerf optique peut, lui aussi, etre le siege d’une atrophie par perte axonale. Objectif Cette etude a pour objectif de determiner la perte axonale par la mesure de la couche des fibres retiniennes peripapillaires en tomographie en coherence optique (OCT) chez des patients atteints de SEP. Materiels et methodes Quinze patients atteints de SEP suivant les criteres de MacDonald ont ete inclus dans cette etude. Ils ont tous eu un examen neurologique et ophtalmologique, une IRM cerebrale et un examen OCT mesurant la perte axonale optique (procedure fastRNFL et RNFL). Deux sous-groupes ont ete etudies : patients avec antecedents de neuropathie optique inflammatoire (NOI) aigue ( n = 8 ; 16 yeux) ou indemnes de NOI ( n = 7 ; 14 yeux). Les resultats sont compares a une population temoin appariee. Resultats Il existe une difference tres significative ( p Conclusion L’OCT (procedure RNFL ou fastRNFL) apparait etre un examen sensible, reproductible et indolore de mesure de la perte axonale optique chez les patients atteints de SEP.

Neuropathies optiques inflammatoires recidivantes Objectif : Evaluer les caracteristiques cliniques et paracliniques de patients presentant des neuropathies optiques isolees recidivantes. Patients et methode : Dans trois centres hospitaliers universitaires, Montpellier, Nimes et Strasbourg, entre octobre 2005 et septembre 2006, les dossiers de patients presentant des episodes de neuropathies optiques isolees corticosensibles evoluant par poussees, inclus prospectivement, ont ete analyses. Seuls les patients sans anomalie a l’imagerie par resonance magnetique de l’encephale ont ete inclus. Les parametres suivants ont ete releves : la date de la premiere poussee, l’âge, duree d’evolution, la corticodependance, l’atteinte uni- ou bilaterale, le nombre de poussees, l’acuite visuelle, l’epaisseur des fibres ganglionnaires, le bilan etiologique, l’existence et la nature d’un traitement de fond par immunosuppresseurs ou immunomodulateurs. Resultats : Sur la periode analysee, 13 patients (11 femmes, 2 hommes), âges de 17 a 54 ans ont ete inclus. Ils ont presente entre 2 et 6 poussees de neuropathies optiques sans signes d’evolution vers une sclerose en plaque. La duree mediane d’evolution a l’inclusion etait de 4 ans. Chez les patients non traites, l’acuite visuelle etait inversement correlee a la duree d’evolution (Spearman ; p = 0,0156), ce qui n’a pas ete observe chez les patients beneficiant d’un traitement de fond (Spearman ; p = 0,1032). Conclusion : La degradation de la fonction visuelle dans le temps observee dans cette etude retrospective de neuropathies optiques isolees recurrentes fait evoquer un mecanisme de perte axonale. Cette hypothese merite d’etre confirmee par une etude de cohorte multicentrique prospective avec evaluation de l’effet d’un traitement de fond sur la degradation fonctionnelle.

Resume Introduction Les syndromes neurologiques paraneoplasiques associes aux anticorps anti-Hu sont rares et de pronostic severe. La recherche et le traitement d’un cancer associe, un carcinome pulmonaire a petites cellules le plus souvent, demeure la meilleure approche therapeutique. Observation Les auteurs decrivent l’evolution clinique d’un patient atteint d’une neuronopathie sensitive subaigue associee aux anticorps anti-Hu chez un fumeur actif traite par une chimiotherapie precoce active contre un carcinome pulmonaire a petites cellules bien qu’aucune tumeur n’ait pu etre identifiee lors de bilans repetes. En depit de ce traitement, l’etat neurologique s’est aggrave avec l’apparition d’une degenerescence cerebelleuse et d’une encephalite limbique responsables d’une perte d’autonomie et definissant une encephalomyelite. Un carcinome pulmonaire a petites cellules fut identifie et traite 65 mois apres le debut des symptomes neurologiques. Le traitement du cancer associe, lorsqu’il est identifie, reste le traitement optimal des syndromes neurologiques paraneoplasiques. Malgre l’absence de cancer identifie initialement, nous avons traite notre patient par une chimiotherapie probabiliste, active contre le cancer le plus frequemment associe aux syndromes des anti-Hu chez un fumeur, sans obtenir de benefices. Conclusion La recherche active et repetee d’un cancer associe a un syndrome neurologique anti-Hu et son traitement sont indispensables. Le traitement probabiliste d’un cancer suppose n’ayant pas fait sa preuve n’a pas empeche l’aggravation neurologique chez ce patient. En l’absence de cancer identifie par les techniques d’imagerie de premiere intention, un FDG-PET scanner precoce puis regulier en cas de normalite initiale devrait donc etre propose.

Resume Donnees cliniques La narcolepsie est une maladie encore peu connue mais non exceptionnelle. Sa prevalence est de 25 a 35 pour 100 000 selon les enquetes. Elle debute de l’enfance a l’âge de 50 ans avec un pic dans la deuxieme decennie. Elle est caracterisee par deux signes cardinaux, les acces de sommeil irresistibles et les cataplexies ou pertes soudaines du tonus musculaire a declenchement emotionnel. Les autres signes, dits accessoires parce qu’inconstants, sont les hallucinations hypnagogiques, les paralysies du sommeil et le mauvais sommeil. Son diagnostic repose sur l’identification des signes cardinaux. Examens complementaires Necessaires pour confirmer le diagnostic avant la mise en œuvre d’un traitement destine a durer toute la vie, les examens complementaires comprennent l’enregistrement polysomnographique de nuit et de jour montrant les endormissements directs en sommeil paradoxal, le typage HLA remarquable par l’association a HLA DQB1*0602, et, dans les cas douteux seulement, le dosage de l’hypocretine-1 du liquide cephalo-rachidien (LCR) revelant des taux inferieurs a 110 pg/mL hautement specifiques de narcolepsie avec cataplexie. Physiopathologie La connaissance de la physiopathologie doit beaucoup a l’existence d’un modele animal naturel, le chien narcoleptique. Les acces de sommeil et les cataplexies ont un controle pharmacologique different, les systemes dopaminergiques agissant sur les premiers et les systemes noradrenergiques sur les seconds. Les acquisitions les plus remarquables de ces 20 dernieres annees sont l’association etroite a HLA DQB1*0602, la decouverte d’une mutation du recepteur-2 de l’hypocretine chez le chien narcoleptique et l’absence d’hypocretine-1 dans le LCR chez 90 % des malades. Un mecanisme auto-immunitaire est suppose mais non prouve a ce jour. Trois volets independants pour le traitement Les acces de sommeil sont traites en premiere intention par le modafinil, les cataplexies et les signes accessoires par les inhibiteurs specifiques de la recapture de la serotonine ou les antidepresseurs tricycliques ou l’oxybate de sodium et le mauvais sommeil par les hypnotiques ou l’oxybate de sodium. Les recherches therapeutiques actuelles s’orientent vers les agonistes de l’hypocretine et les immunosuppresseurs.

Hypocretin/orexin deficiency appears to be a consistent feature of narcolepsy with a putative autoimmune mechanism involved. We treated four hypocretin/orexin-deficient narcolepsy patients with intravenous immunoglobulins and assessed the efficacy by repeated polysomnographies and questionnaires. Three patients received the treatment within a few months after acute onset of narcolepsy. A clear improvement in the frequency and severity of cataplexy was obtained with a benefic effect up to 7 months without any anticataplectics drugs at follow-up. Our findings point to the importance of early diagnosis of narcolepsy, which once treated quickly may modify its long-term outlook.

Natalizumab dramatically reduces relapses in patients with active multiple sclerosis (MS), but it may induce progressive multifocal leukoencephalopathy (PML).1 A rebound of MS or an immune reconstitution inflammatory syndrome (IRIS) were described after natalizumab withdrawal, even in the absence of PML.2,3 Very few data concerning the potential severity and the neuropathology of this event are available. We report the case of a 50-year-old patient with MS who developed a fulminating relapse 3 months after stopping natalizumab, leading to death despite intensive care and immunosuppressive therapy. Radiologic and neuropathologic findings provide interesting data regarding the nature of the rebound.

Objectif Comparer le profil tensionnel des patients avec une narcolepsie de type 1 (NT1) traites vs non-traites. Methodes Un total de 68 patients NT1 non traites et 54 patients NT1 traites ont beneficie d’une polysomnographie et d’une mesure ambulatoire de la pression arterielle sur 24 heures. Parmi ces sujets, 38 ont ete evalue a deux reprises, en condition non-traitee et traitee avec une mediane de 1,7 ans. Le dipping etait caracterise par une baisse de moins de 10 % de la tension arterielle entre le jour et la nuit. Resultats Les patients NT1 traites etaient plus âges et prenaient plus d’antihypertenseurs que les patients non traites. Apres ajustement, les patients traites presentaient une augmentation de la tension arterielle (diastolique) le jour et la nuit en comparaison aux patients non traites, sans changement du profil du dipping. Lorsque les patients etaient compares a eux-memes, la condition traitee etait associee a une augmentation de la tension arterielle systolique le jour et sur les 24 heures. Conclusion Les patients narcoleptiques traites par psychostimulant ont une augmentation du profil tensionnel diurne suggerant un renforcement du suivi cardiovasculaire chez ces sujets potentiellement a risque de maladies cardiocerebrovasculaires.

Introduction: The relationship between ICD and RBD is still not yet understood and the results from the current literature are contradictory in PD. We aimed to explore the association between rapid eye movement (REM) sleep behavior disorder (RBD) and impulse control disorder in Parkinson's disease. Methods: Ninety-eight non-demented patients with Parkinson's disease underwent one night of videopolysomnography recording. The diagnosis of RBD was established according to clinical and polysomnographic criteria. Impulse control disorders were determined by a gold standard, semi-structured diagnostic interview. Results: Half of the patients (n ¼ 49) reported clinical history of RBD while polysomnographic diagnosis of RBD was confirmed in 31.6% of the patients (n ¼ 31). At least one impulse control disorder was identified in 21.4% of patients, 22.6% with RBD and 20.9% without. Logistic regression controlling for potential confounders indicated that both clinical RBD (OR ¼ 0.34, 95% CI ¼ 0.07e1.48, P ¼ 0.15) and polysomnographic confirmed RBD diagnoses (OR ¼ 0.1.28, 95% CI ¼ 0.31e5.33, P ¼ 0.34) were not associated with impulse control disorder. Conclusion: In Parkinson's disease, REM Sleep Behavior Disorder is not associated with impulse control disorder. The results of our study do not support the notion that PSG-confirmed RBD and ICD share a common pathophysiology.

International audience; Background: Excessive daytime sleepiness is a frequent complaint in Parkinson's disease (PD); however the frequency and risk factors for objective sleepiness remain mostly unknown. We investigated both the frequency and determinants of self-reported and objective daytime sleepiness in patients with Parkinson's disease (PD) using a wide range of potential predictors.Methods: One hundred and thirty four consecutive patients with PD, without selection bias for sleep complaint, underwent a semi-structured clinical interview and a one night polysomnography followed by a multiple sleep latency test (MSLT). Demographic characteristics, medical history, PD course and severity, daytime sleepiness, depressive and insomnia symptoms, treatment intake, pain, restless legs syndrome, REM sleep behaviour disorder, and nighttime sleep measures were collected. Self-reported daytime sleepiness was defined by an Epworth Sleepiness Scale (ESS) score above 10. A mean sleep latency on MSLT below 8 minutes defined objective daytime sleepiness.Results: Of 134 patients with PD, 46.3% had subjective and only 13.4% had objective sleepiness with a weak negative correlation between ESS and MSLT latency. A high body mass index (BMI) was associated with both ESS and MSLT, a pain complaint with ESS, and a higher apnea/hypopnea index with MSLT. However, no associations were found between both objective and subjective sleepiness, and measures of motor disability, disease onset, medication (type and dose), depression, insomnia, restless legs syndrome, REM sleep behaviour disorder and nighttime sleep evaluation.Conclusion: We found a high frequency of self-reported EDS in PD, a finding which is however not confirmed by the gold standard neurophysiological evaluation. Current treatment options for EDS in PD are very limited; it thus remains to be determined whether decreasing pain and BMI in association with the treatment of sleep apnea syndrome would decrease significantly daytime sleepiness in PD.

Background: Narcolepsy usually starts around adolescence; however, there is great variability in the clinical presentation of narcolepsy. Objective: To determine the age at onset in conjunction with severity of narcoleptic symptoms in two large populations of narcoleptic patients with a similar genetic background. Methods: Information on age at onset and severity of the condition was obtained in 317 patients with well-defined narcolepsy–cataplexy from Montpellier (France) and in 202 from Montreal (Canada). Results: The mean age at onset was 23.4 years in Montpellier and 24.4 in Montreal. The age at onset was bimodal in two independent patient populations: a first peak occurring at 14.7 years, and a second peak occurring at 35. Age at onset clearly differentiates patients with a positive family history of narcolepsy (early onset) from those without a family history. Other clinical and polygraphic findings may indicate that young age at onset is associated with increased severity of the condition (higher frequency of cataplexy and decreased mean sleep latency on the Multiple Sleep Latency Test). Conclusion: Bimodal distribution of age at onset of narcolepsy was found in two independent patient populations. Our data suggest that age at onset is genetically determined.

Objectif Le decubitus dorsal favorise les apnees obstructives du sommeil. Les patients parkinsoniens decrivent des difficultes a se retourner dans leur lit. L’objectif de notre etude est d’explorer le lien entre decubitus dorsal et troubles ventilatoires nocturnes au cours de la maladie de Parkinson (MP). Methodes Quinze patients consecutifs atteints de MP et d’un syndrome d’apnees obstructives du sommeil (SAOS) severe ont ete compares a : – 15 patients avec MP sans SAOS apparies en âge, sexe, index de masse corporel et severite de la MP (Unified Parkinson's Disease Rating Scale-III) ; – 11 patients apparies en âge et sexe, presentant un SAOS severe isole ; – 11 sujets sains apparies en âge et sexe. Nous avons compare le nombre de changements de positions pendant la nuit, par heure de sommeil et le pourcentage de temps de sommeil passe en decubitus dorsal dans ces quatre groupes. Resultats Les parkinsoniens avec SAOS severe ont passe presque tout leur temps de sommeil (93 ± 11 %) en decubitus dorsal alors que les parkinsoniens sans SAOS (61 ± 24 %, p Conclusion Le SAOS severe au cours de la MP est associe a une diminution majeure du nombre de changements de positions pendant le sommeil et a une augmentation du temps de sommeil passe en decubitus dorsal pendant la nuit. L’amelioration des difficultes a se retourner dans le lit au cours de la MP pourrait diminuer le temps passe en decubitus dorsal et ameliorer les troubles de la ventilation nocturne.

Idiopathic narcolepsy with cataplexy is thought to be an autoimmune disorder targeting hypothalamic hypocretin neurons. Symptomatic narcolepsy with low hypocretin level has been described in Ma antibody–associated encephalitis; however, the mechanisms underlying such an association remain unknown.We described a 63-year-old man with clinical criteria for diencephalic encephalitis with sleepiness, cataplexy, hypocretin deficiency, and central hypothyroidism, together with brainstem encephalitis reflected by supranuclear ophtalmoparesis and rapid eye movement sleep behavior disorder with underlying abnormalities on brain magnetic resonance imaging. An autoimmune process was demonstrated by the detection of antibodies against Ma protein. Death occurred 4 months after disease onset without any tumor detected. Neuropathology, immunohistochemistry, and immunoreactivity results were compared with those obtained in idiopathic narcolepsy-cataplexy and with normal control brains. The principal findings revealed almost exclusive inflammation and tissue injury in the hypothalamus. The type of inflammatory reaction suggests cytotoxic CD8+ T lymphocytes being responsible for the induction of tissue injury. Inflammation was associated with complete loss of hypocretinergic neurons. Autoantibodies of the patient predominantly stained neurons in the hypothalamus and could be absorbed with Ma2.The encephalitic process, responsible for narcolepsy-cataplexy and hypocretin deficiency, reflects a CD8+ inflammatory-mediated response against hypocretin neurons.

One hundred and forty patients (104 male and 36 female) aged 42.26 +/- 19.19 (range = 8 to 79.5 years) with narcolepsy-cataplexy were given modafinil (200 to 400 mg) at the Montpellier sleep disorders center from 1984 onwards. The follow-up focused on the reduction of excessive daytime somnolence (EDS), side effects and duration of treatment. In order to determine if any clinical aspect of narcolepsy could be involved in modafinil discontinuation, patients were divided into two groups according to continued or interrupted treatment. When modafinil effect on EDS was evaluated according to a scale varying from 0 (no effect) to 3 (excellent effect), 64.1% of the subjects, scored good or excellent. The mean duration of treatment was 22.05 months +/- 24.9, ranging from 1 to 114 months. Dependency signs were never observed.

The authors present clinical, sleep, and neuroendocrine features of a patient with genetically confirmed fatal familial insomnia (D178N mutation with heterozygosity at codon 129 of the prion protein gene). The patient exhibited pseudohypersomnia behavior instead of insomnia. There was profound alteration in the sleep-wake cycle with a clear dissociation in the disappearance of circadian and neuroendocrine rhythms, findings unrelated to abnormalities in the hypocretinergic system.

Study Objectives: A loss of hypocretin neurons has been observed in human narcolepsy; however, the cause of this disorder is still unknown. While family history and genetic factors are important individual risk factors for narcolepsy, environmental factors also contribute to the pathogenesis of the disease. The aim of the study was to find out whether there is a seasonality of month of birth in narcoleptic patients. Design: Diagnosis of narcolepsy with cataplexy was based on International Classification of Sleep Disorders criteria with clinical, standard polysomnographic, and Multiple Sleep Latency Test features Patients and Setting: The birth dates of 886 patients with a clear-cut diagnosis of narcolepsy with cataplexy from 3 large narcolepsy databases (352 from Montpellier-France, 157 from Montreal-Canada, and 377 from Stanford-United States of America) were compared with those of 35,160,522 subjects from the general population. Measurements and Results: Patients with narcolepsy had a significant ly different seasonality of month of birth compared to that of the genera population. The monthly distribution of birth yielded a peak in March will a maximal odds ratio at 1.45 and a trough in September with a minima odds ratio at 0.63. No gender or country of origin differences were observed. Conclusions: A birth seasonality in the development of narcolepsy sug gests the presence of environmental factors acting in combination will genetic factors during the fetal or perinatal period, in terms of an autoirr mune process targeting the hypocretin system.

Rhythmic movement disorder (RMD) is a stereotyped movement disorder of sleep characterized by rhythmic oscillations such as head banging, body rocking or head rolling [1]. RMD diagnosis relies on the clinical description of the movements, but also on video sleep recordings showing the rhythmic movements at the transition between wake and sleep. Common in childhood, RMD can persist quite long into adulthood [2,3]. The pathophysiology remains unknown. However, RMD has rarely been described in association with other sleep disorders such as sleep disordered breathing, periodic limb movements, narcolepsy and restless legs syndrome (RLS) [4,5]. RLS diagnosis is based on four clinical criteria: a desire to move the limbs, usually associated with dysaesthesias, the presence of motor restlessness, worsening of symptoms at rest with relief by activity and peaking of symptoms in the evening and/or during the night [6]. Polysomnography recordings (PSG) mostly reveal the

A multifactorial etiology for narcolepsy has been postulated, stressing the importance of environmental factors in the clinical onset of the condition. Our study evaluated the occurrence of stressful life events in the year preceding the onset of narcolepsy. Fifty narcoleptic and 50 control subjects completed a life event questionnaire (the Schedule of Recent Experiences). The proportion of narcoleptic subjects reporting the presence of life events in the year preceding the onset of narcolepsy was significantly greater than the proportion of control subjects reporting life events in the corresponding year. Moreover the weight of life events was increased in narcoleptic subjects in comparison with controls. In conclusion life events seem to be increased in narcoleptic subjects in the year preceding the onset of their condition. However a number of other factors could not be taken into consideration, which limits the full significance of these data.

OBJECTIVE. To assess objective and subjective evidence of sleep disturbances in patients with rheumatoid arthritis (RA) and to examine correlations between parameters of inflammatory activity and sleep pathology. METHODS. Nineteen RA patients and 19 age-matched healthy control subjects underwent all-night polysomnography on 2 consecutive nights. RA patients were also evaluated for daytime sleepiness by mean sleep latency test and responded to a self-report questionnaire on their first night. RESULTS. Whereas normal sleep architecture is conserved in RA, we confirmed former findings of severe sleep fragmentation and an enhanced presence of primary sleep disorders. No correlation exists between RA activity and the sleep disorders. Subjective assessment was not consistent with the objective evidence of sleep disruption, unlike the findings in patients with fibrositis. CONCLUSION. Sleep is severely disturbed in patients with RA, regardless of the inflammatory disease activity. The specificity of the sleep disorders assessed needs confirmation, as does specific sleep therapy for these patients.

Diagnosis of restless leg syndrome (RLS) in Parkinson's disease (PD) is difficult because of clinical confounds. The suggested immobilization test (SIT) is validated for diagnosis of primary RLS. This study evaluated the usefulness of the SIT for diagnosis of RLS in PD. We compared SIT scores, as well as polysomnography measures in 50 patients with PD (25 with RLS, 25 without), 25 patients with primary RLS, and 25 age/sex matched controls. Mean leg discomfort score was increased in patients with PD and RLS compared to PD without RLS, and also in patients with primary RLS compared to controls. Leg discomfort was significantly higher at the end of the test in patients with RLS compared to patients without RLS. Intensity of leg discomfort was similar between patients with RLS, with or without PD. Using a mean leg discomfort cutoff of 11, we showed sensitivity of 91% and specificity of 72% for RLS diagnosis in PD during symptomatic time intervals. Periodic leg movements index during the SIT did not differ between groups. Periodic leg movements index during sleep and wakefulness was increased in patients with primary RLS compared to controls, but did not differ between patients with PD, with and without RLS. The sensory SIT is a simple test that may help diagnose RLS in patients with PD.

NMO-IgG is a specific biomarker of neuromyelitis optica (NMO) that targets the aquaporin-4 (AQP4) water channel protein. The current gold standard for NMO-IgG identification is indirect immunofluorescence (IIF). Our aim in this study was to develop a new quantitative cell-based assay (CBA) and to propose a rational strategy for anti-AQP4 Ab identification and quantification. We observed an excellent correlation between the CBA and IIF for NMO-IgG/anti-AQP4 detection. The CBA appeared more sensitive than IIF but on the other hand, IIF allows the simultaneous detection of various auto-Abs, underlining the complementarity between both methods. In conclusion, we propose to use IIF for the screening of patients at diagnosis in order to identify auto-Abs targeting the central nervous system. A highly sensitive, AQP4 specific and quantitative assay such as our CBA could be used thereafter to specifically identify the target of the Ab and to monitor its serum concentration under treatment.

Since the discovery of an almost 100% association of HLA-DR2 with narcolepsy-cataplexy, many efforts have been made to demonstrate the intervention of immune factors in the pathogeny of the disease. Some epidemiological features could support this hypothesis: age of onset around 25, triggering factors, association with multiple sclerosis. Molecular studies at the DNA level have, up to now, failed to uncover an abnormal gene in the HLA system, which would imply that the DR2 antigen acts through its role in the immune response. However, results have been largely inconclusive as far as classical features of autoimmunity in blood and CSF are concerned. In canine narcolepsy, a linkage with a human immunoglobulin-related gene has recently been shown, and may constitute a counterpart of the HLA association in man. Thus, the hypothesis of a transient and discrete autoimmune aggression may be ruled out.

The dopamine system is implicated in reward-based decision making with explicit information (decision making under risk) and implicit probabilities (decision making under ambiguity). Although the pathophysiology of restless legs syndrome (RLS) is not yet fully understood, the genetic factors, iron status, and dopaminergic system are thought to play a role. RLS provides an opportunity to test the dopaminergic hypothesis in a drug-free population and to characterize reward processing using decision-making paradigms. We investigated impulsivity, impulse control disorders, and decision making in 50 untreated patients with primary RLS compared with 60 sex- and age-matched normal controls using one night of polysomnography recording, a structured psychiatric interview, and questionnaires (RLS Severity Scale, Beck Depression Inventory, and Urgency Premeditation Perseverance Impulsive Behavior Scale). Subjects performed the Iowa Gambling Task to assess decision making under ambiguity and the Game of Dice Task to assess decision making under risk. Patients with RLS showed selective changes in decision making on the Iowa Gambling Task and normal decision making on the Game of Dice Task compared with controls. Patients with RLS had greater depressive symptoms than controls, but no difference was found in impulsivity, impulse control disorders, or addictive behaviors. Clinical and polysomnographic variables were unrelated to decision-making performance. Results indicate reduced decision-making performance under ambiguity in drug-free patients with RLS. From a clinical perspective, when using dopaminergic medication to treat RLS, patients with abnormal baseline behaviors should be closely monitored.