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Parkinson Disease: HELP
Articles by Isabelle Arnulf
Based on 31 articles published since 2009
(Why 31 articles?)
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Between 2009 and 2019, I. Arnulf wrote the following 31 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Practice Parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology. 2010

Zesiewicz, T A / Sullivan, K L / Arnulf, I / Chaudhuri, K R / Morgan, J C / Gronseth, G S / Miyasaki, J / Iverson, D J / Weiner, W J / Anonymous2020653. ·University of South Florida, Tampa, USA. ·Neurology · Pubmed #20231670.

ABSTRACT: OBJECTIVE: Nonmotor symptoms (sleep dysfunction, sensory symptoms, autonomic dysfunction, mood disorders, and cognitive abnormalities) in Parkinson disease (PD) are a major cause of morbidity, yet are often underrecognized. This evidence-based practice parameter evaluates treatment options for the nonmotor symptoms of PD. Articles pertaining to cognitive and mood dysfunction in PD, as well as treatment of sialorrhea with botulinum toxin, were previously reviewed as part of American Academy of Neurology practice parameters and were not included here. METHODS: A literature search of MEDLINE, EMBASE, and Science Citation Index was performed to identify clinical trials in patients with nonmotor symptoms of PD published between 1966 and August 2008. Articles were classified according to a 4-tiered level of evidence scheme and recommendations were based on the level of evidence. RESULTS AND RECOMMENDATIONS: Sildenafil citrate (50 mg) may be considered to treat erectile dysfunction in patients with Parkinson disease (PD) (Level C). Macrogol (polyethylene glycol) may be considered to treat constipation in patients with PD (Level C). The use of levodopa/carbidopa probably decreases the frequency of spontaneous nighttime leg movements, and should be considered to treat periodic limb movements of sleep in patients with PD (Level B). There is insufficient evidence to support or refute specific treatments for urinary incontinence, orthostatic hypotension, and anxiety (Level U). Future research should include concerted and interdisciplinary efforts toward finding treatments for nonmotor symptoms of PD.

2 Editorial Not all that goes "bump in the night" is RLS: leg motor restlessness in PD. 2011

Arnulf, Isabelle / Morgan, John. · ·Neurology · Pubmed #22076545.

ABSTRACT: -- No abstract --

3 Review REM sleep behavior disorder: motor manifestations and pathophysiology. 2012

Arnulf, Isabelle. ·Sleep disorders unit, Pitié-Salpêtrière Hospital, Pierre and Marie Curie University, Inserm U975, CRICM, Paris, France. isabelle.arnulf@psl.aphp.fr ·Mov Disord · Pubmed #22447623.

ABSTRACT: Patients with REM sleep behavior disorder (RBD) enact violent dreams during REM sleep in the absence of normal muscle atonia. This disorder is highly frequent in patients with synucleinopathies (60%-100% of patients) and rare in patients with other neurodegenerative disorders. The disorder is detected by interview plus video and sleep monitoring. Abnormal movements expose the patients and bed partners to a high risk of injury and sleep disruption. The disorder is usually alleviated with melatonin and clonazepam. Limb movements are mainly minor, jerky, fast, pseudohallucinatory, and repeated, with a limp wrist during apparently grasping movements, although body jerks and complex violent (fights) and nonviolent culturally acquired behaviors are also observed. Notably, parkinsonism disappears during RBD-associated complex behaviors in patients with Parkinson's disease and with multiple system atrophy, suggesting that the upper motor stream bypasses the basal ganglia during REM sleep. Longitudinal studies show that idiopathic RBD predisposes patients to later develop Parkinson's disease, dementia with Lewy bodies, and, more rarely, multiple system atrophy, with a rate of conversion of 46% within 5 years. During this time window, patients concomitantly develop nonmotor signs (decreased olfaction and color vision, orthostatic hypotension, altered visuospatial abilities, increased harm avoidance) and have abnormal test results (decreased putamen dopamine uptake, slower EEG). Patients with idiopathic RBD have higher and faster risk for conversion to Parkinson's disease and dementia with Lewy bodies if abnormalities in dopamine transporter imaging, transcranial sonography, olfaction, and color vision are found at baseline. They constitute a highly specific target for testing neuroprotective agents.

4 Review Scales to assess sleep impairment in Parkinson's disease: critique and recommendations. 2010

Högl, Birgit / Arnulf, Isabelle / Comella, Cynthia / Ferreira, Joaquim / Iranzo, Alex / Tilley, Barbara / Trenkwalder, Claudia / Poewe, Werner / Rascol, Olivier / Sampaio, Cristina / Stebbins, Glenn T / Schrag, Anette / Goetz, Christopher G. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. birgit.ho@i-med.ac.at ·Mov Disord · Pubmed #20931631.

ABSTRACT: There is a broad spectrum of sleep disturbances observed in Parkinson's disease (PD). A variety of scales have been applied to the evaluation of PD sleep and wakefulness, but only a small number have been assessed specifically for clinimetric properties in the PD population. The movement disorder society has commissioned this task force to examine these scales and to assess their use in PD. A systematic literature review was conducted to explore the use of sleep scales in PD and to determine which scales qualified for a detailed critique. The task force members, all of whom have extensive experience in assessing sleep in PD reviewed each of the scales using a structured proforma. Scales were categorized into recommended, suggested and listed according to predefined criteria. A total of 48 potential scales were identified from the search and reviewed. Twenty-nine were excluded because they did not meet review criteria or were variations of scales already included, leaving 19 scales that were critiqued and rated by the task force based on the rating criteria. Only six were found to meet criteria for recommendation or suggestion by the task force: the PD sleep scale (PDSS) and the Pittsburgh sleep quality index (PSQI) are recommended for rating overall sleep problems to screen and to measure severity, the SCOPA-sleep (SCOPA) is recommended for rating overall sleep problems both to screen and to measure severity, and for rating daytime sleepiness; the Epworth sleepiness scale (ESS) is recommended for rating daytime sleepiness to screen and to measure severity; the inappropriate sleep composite score (ISCS) is suggested for rating severe daytime sleepiness or sleep attacks to screen and to measure severity; and the Stanford sleepiness scale (SSS) is suggested for rating sleepiness and to measure severity at a specific moment. The task force does not recommend the development of new scales, but emphasizes the need for educational efforts to train physicians in sleep interview techniques and polysomnography.

5 Review [REM sleep behavior disorder: an overt access to motor and cognitive control during sleep]. 2010

Arnulf, I. ·Unité des Pathologies du Sommeil, Hôpital Pitié-Salpêtrière, Groupe Hospitalier de la Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France. isabelle.arnulf@psl.aphp.fr ·Rev Neurol (Paris) · Pubmed #20801470.

ABSTRACT: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by violent, or potentially violent, movements during REM sleep, corresponding to enacted dreams. During sleep monitoring, there is a partial or total loss of the normal muscle atonia during REM sleep. REM sleep behavior disorder predominantly affects elderly subjects without any other disease (idiopathic RBD, a precursor of Parkinson disease and Lewy body dementia) or suffering from various neurological and neurodegenerative diseases, mainly synucleinopathies. In addition to being a treatable cause of nocturnal injury of the patients or their bed-partners, RBD is a fantastic window into motor and cognitive control during REM sleep. Notably, parkinsonism transiently disappears during RBD. The patient's voice is louder and better articulated than when awake, and movements are rapid (but jerky) suggesting that the deleterious message from the basal ganglia to the primary motor cortex is reduced or bypassed. As we observed culturally-acquired behaviors, retired patients practicing their former work with mastered gestures, as well as sentences pronounced with appropriate prosody, gesturing, fluency, and syntax during the RBD, we suggest that these behaviors are generated by the same cortical areas as during wakefulness. This model also enables the demonstration that REM during REM sleep are coded in the same direction as the arm and hand movements, as if the dreamer were scanning the dream images. This online access to the motor and verbal dream scenario (through the video and audio monitoring), and the physiological measures (via the EEG, eye movements, muscle tone, respiration, heart rate), together with the offline access to the mental content (dream report after the awakening) constitute a triangulation for validating new hypotheses about REM sleep and dreams.

6 Article Sleep and REM sleep behaviour disorder in Parkinson's disease with impulse control disorder. 2018

Fantini, Maria Livia / Figorilli, Michela / Arnulf, Isabelle / Zibetti, Maurizio / Pereira, Bruno / Beudin, Patricia / Puligheddu, Monica / Cormier-Dequaire, Florence / Lacomblez, Lucette / Benchetrit, Eve / Corvol, Jean Christophe / Cicolin, Alessandro / Lopiano, Leonardo / Marques, Ana / Durif, Franck. ·Sleep and EEG Unit, Centre Hospitalier Universitaire, Clermont-Ferrand, France. · EA7820 UFR Medecine, Universite Clermont Auvergne, Clermont-Ferrand, France. · Department of Neurology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France. · Neurophysiology Unit, Sleep Center, University of Cagliari, Monserrato, Italy. · Sleep Disorders Unit, AP-HP, Pitié-Salpêtrière Hospital and Pierre and Marie Curie University, Paris, France. · Department of Neuroscience, University of Turin, Turin, Italy. · Biostatistics DRCI, CHU Clermont-Ferrand, Clermont-Ferrand, France. · Department of Neurology, Hôpital Pitié-Salpêtrière, Sorbonne Universités, Paris, France. · Department of Neuroscience, Sleep Disorders Center, University of Turin, Turin, Italy. ·J Neurol Neurosurg Psychiatry · Pubmed #29066517.

ABSTRACT: INTRODUCTION: Because the association between rapid eye movement sleep behaviour disorder (RBD) and impulse control disorders (ICDs) in Parkinson's disease (PD) has been debated, we assessed the sleep characteristics and the frequency of RBD using video-polysomnography (v-PSG) in patients with PD with versus without ICDs. METHODS: Eighty non-demented patients with PD consecutively identified during routine evaluation at three movement disorders centres were enrolled in a case-control study. Forty patients (22 men; mean age: 62.6±9.7 years, Hoehn & Yahr: 2.1±0.6) with one or more current ICDs were age-matched and sex-matched with 40 patients with no history of ICDs (22 men, mean age: 64.9±7.8 years, Hoehn & Yahr: 2.2±0.6). They underwent a detailed sleep interview followed by a full-night in-lab v-PSG. Sleep was scored blindly to ICDs condition and RBD diagnosis included a clinical complaint of enacted dreams and/or documented behaviour during rapid eye movement (REM) sleep, with the presence of quantified REM sleep without atonia (RSWA). RESULTS: Patients with ICDs had a higher arousal index and higher RSWA than those without ICDs (51.9%±28.2%vs 32.2±27.1%, p=0.004). In addition, RBD was more frequent in the ICD group (85%vs53%, p=0.0001). RBD was still associated with ICDs in a multivariate regression analysis including age of onset, PD duration and severity, treatment duration, levodopa-equivalent and dopamine agonist-equivalent daily doses and antidepressant use (OR: 4.9 (95% CI 1.3 to 18.5), p=0.02). CONCLUSIONS: This large, controlled series of patients with PD with ICDs assessed by v-PSG confirms the association between ICDs and RBD. Increased surveillance of symptoms of ICDs should be recommended in patients with PD with RBD.

7 Article Magnetic Resonance Imaging Biomarkers to Assess Substantia Nigra Damage in Idiopathic Rapid Eye Movement Sleep Behavior Disorder. 2017

Pyatigorskaya, Nadya / Gaurav, Rahul / Arnaldi, Dario / Leu-Semenescu, Smaranda / Yahia-Cherif, Lydia / Valabregue, Romain / Vidailhet, Marie / Arnulf, Isabelle / Lehéricy, Stephane. ·Institut du Cerveau et de la Moelle épinière - ICM, Centre de NeuroImagerie de Recherche - CENIR, ICM, Paris, France. · Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, F-75013, Paris, France. · Assistance Publique Hôpitaux de Paris, Service de neuroradiologie, Hôpital Pitié-Salpêtrière, Paris, France. · Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, IRCCS AOU San Martino-IST, Genoa, Italy. · Assistance Publique Hôpitaux de Paris, Service des pathologies du Sommeil, Hôpital Pitié-Salpêtrière, Paris, France. · Assistance Publique Hôpitaux de Paris, Clinique des mouvements anormaux, Département des Maladies du Système Nerveux, Hôpital Pitié-Salpêtrière, Paris, France. · Assistance Publique Hôpitaux de Paris, INSERM, Centre d'Investigation Clinique (CIC9503), Département des Maladies du Système Nerveux, Hôpital Pitié-Salpêtrière, Paris, France. ·Sleep · Pubmed #28958075.

ABSTRACT: Objectives: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered to be a prodromal stage of Parkinson's disease (PD). At PD onset, 40 to 70% of the dopaminergic neurons in the substantia nigra (SN) are already lost. Thus, milder SN damage is expected in participants with iRBD. We aimed to quantify SN damage in participants with iRBD using multimodal magnetic resonance imaging (MRI) and to determine biomarker efficacy in preclinical Parkinsonism. Methods: Nineteen participants with iRBD and 18 controls underwent 3-Tesla MRI, including diffusion tensor imaging, neuromelanin (NM)-sensitive imaging, and T2* mapping. Regions of interest in the SN area were drawn in NM-sensitive and T2-weighted images. The volume and normalized signal intensity in NM-sensitive images, R2*, and diffusion tensor measures were quantified in the SN. Additionally, two raters performed visual analysis of the SN using the NM-sensitive images. Results: Participants with iRBD showed a reduction in the NM-sensitive volume and signal intensity and a decrease in fractional anisotropy (FA) versus controls, but showed no differences in axial, radial, or mean diffusivity or in R2*. For NM-sensitive volume and signal intensity, the receiver operating characteristic analysis discriminated between participants with iRBD and controls with a diagnostic accuracy of 0.86 and 0.79, respectively, whereas the accuracy was 0.77 for FA. The three biomarkers had a combined accuracy of 0.92. The fraction of participants correctly characterized by visual assessment was 0.81. Conclusions: NM-sensitive imaging and FA allowed for the detection of SN damage in participants with iRBD with good diagnostic accuracy. These measures may represent valuable biomarkers for prodromal Parkinsonism.

8 Article Is there a common motor dysregulation in sleepwalking and REM sleep behaviour disorder? 2017

Haridi, Mehdi / Weyn Banningh, Sebastian / Clé, Marion / Leu-Semenescu, Smaranda / Vidailhet, Marie / Arnulf, Isabelle. ·Sleep Disorders Unit, Pitié-Salpêtrière University Hospital, APHP, Paris, France. · Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière - UPMC-Paris 6, Inserm UMR_S 975, CNRS UMR 7225, Paris, France. · Pierre and Marie Curie University, Paris, France. · Clinical Investigation Centre Paris Est CIC-9304, Paris, France. ·J Sleep Res · Pubmed #28513054.

ABSTRACT: This study sought to determine if there is any overlap between the two major non-rapid eye movement and rapid eye movement parasomnias, i.e. sleepwalking/sleep terrors and rapid eye movement sleep behaviour disorder. We assessed adult patients with sleepwalking/sleep terrors using rapid eye movement sleep behaviour disorder screening questionnaires and determined if they had enhanced muscle tone during rapid eye movement sleep. Conversely, we assessed rapid eye movement sleep behaviour disorder patients using the Paris Arousal Disorders Severity Scale and determined if they had more N3 awakenings. The 251 participants included 64 patients with rapid eye movement sleep behaviour disorder (29 with idiopathic rapid eye movement sleep behaviour disorder and 35 with rapid eye movement sleep behaviour disorder associated with Parkinson's disease), 62 patients with sleepwalking/sleep terrors, 66 old healthy controls (age-matched with the rapid eye movement sleep behaviour disorder group) and 59 young healthy controls (age-matched with the sleepwalking/sleep terrors group). They completed the rapid eye movement sleep behaviour disorder screening questionnaire, rapid eye movement sleep behaviour disorder single question and Paris Arousal Disorders Severity Scale. In addition, all the participants underwent a video-polysomnography. The sleepwalking/sleep terrors patients scored positive on rapid eye movement sleep behaviour disorder scales and had a higher percentage of 'any' phasic rapid eye movement sleep without atonia when compared with controls; however, these patients did not have higher tonic rapid eye movement sleep without atonia or complex behaviours during rapid eye movement sleep. Patients with rapid eye movement sleep behaviour disorder had moderately elevated scores on the Paris Arousal Disorders Severity Scale but did not exhibit more N3 arousals (suggestive of non-rapid eye movement parasomnia) than the control group. These results indicate that dream-enacting behaviours (assessed by rapid eye movement sleep behaviour disorder screening questionnaires) are commonly reported by sleepwalking/sleep terrors patients, thus decreasing the questionnaire's specificity. Furthermore, sleepwalking/sleep terrors patients have excessive twitching during rapid eye movement sleep, which may result either from a higher dreaming activity in rapid eye movement sleep or from a more generalised non-rapid eye movement/rapid eye movement motor dyscontrol during sleep.

9 Article Pedunculopontine network dysfunction in Parkinson's disease with postural control and sleep disorders. 2017

Gallea, Cecile / Ewenczyk, Claire / Degos, Bertrand / Welter, Marie-Laure / Grabli, David / Leu-Semenescu, Smaranda / Valabregue, Romain / Berroir, Pierre / Yahia-Cherif, Lydia / Bertasi, Eric / Fernandez-Vidal, Sara / Bardinet, Eric / Roze, Emmanuel / Benali, Habib / Poupon, Cyril / François, Chantal / Arnulf, Isabelle / Lehéricy, Stéphane / Vidailhet, Marie. ·Centre de Neuroimagerie de Recherche (CENIR), Institut du Cerveau et de la Moelle, ICM, Paris, France. · Inserm, U 1127, Paris, France. · CNRS, UMR 7225, Paris, France. · Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Paris, France. · Institut du Cerveau et de la Moelle épinière, ICM, Paris, France. · Assistance Publique Hôpitaux de Paris (APHP), INSERM, ICM, Centre d'Investigation Clinique Pitié Neurosciences, CIC-1422, Département des Maladies du Système Nerveux, Hôpital Pitié-Salpêtrière, Paris, France. · AP-HP, Centre Inter-Régional de Coordination de la Maladie de Parkinson, Hôpital de la Pitié Salpêtrière, Département des Maladies du Système Nerveux, Paris, France. · Sleep Disorders Unit, Pitié-Salpêtrière Hospital, AP-HP, Paris, France. · CEA Saclay, Neurospin/LNAO, Gif sur Yvette, France. ·Mov Disord · Pubmed #28164375.

ABSTRACT: BACKGROUND: The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease. METHODS: We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs. RESULTS: Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers. CONCLUSIONS: These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society.

10 Article Phasic activity during non REM sleep. 2017

Miguel, Rita / Arnulf, Isabelle. ·Neurology Department, Egas Moniz Hospital - Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal; Directorate of Health, Portuguese Air Force, Lisbon, Portugal; Sleep Disorders Unit, APHP, Pitié-Salpêtrière Hospital, Paris, France. Electronic address: rita.miguel85@gmail.com. · Sleep Disorders Unit, APHP, Pitié-Salpêtrière Hospital, Paris, France; CRICM, Inserm U975-CNRS, Pierre and Marie Curie University (Sorbonne Universities, Univ Paris 6), Paris, France. ·Sleep Med · Pubmed #28153214.

ABSTRACT: -- No abstract --

11 Article The dementia-associated APOE ε4 allele is not associated with rapid eye movement sleep behavior disorder. 2017

Gan-Or, Ziv / Montplaisir, Jacques Y / Ross, Jay P / Poirier, Judes / Warby, Simon C / Arnulf, Isabelle / Strong, Stephanie / Dauvilliers, Yves / Leblond, Claire S / Hu, Michele T M / Högl, Birgit / Stefani, Ambra / Monaca, Christelle Charley / De Cock, Valérie Cochen / Boivin, Michel / Ferini-Strambi, Luigi / Plazzi, Giuseppe / Antelmi, Elena / Young, Peter / Heidbreder, Anna / Barber, Thomas R / Evetts, Samuel G / Rolinski, Michal / Dion, Patrick A / Desautels, Alex / Gagnon, Jean-François / Dupré, Nicolas / Postuma, Ronald B / Rouleau, Guy A. ·Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. Electronic address: ziv.gan-or@mail.mcgill.ca. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Psychiatry, Université de Montréal, Montréal, Quebec, Canada. · Department of Human Genetics, McGill University, Montréal, Quebec, Canada. · Department of Psychiatry, McGill University, Montréal, Quebec, Canada; Douglas Mental Health University Institute, Montréal, Quebec, Canada. · Sleep Disorders Unit, Pitié Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière and Sorbonne Universities, UPMC Paris 6 univ, Paris, France. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada. · Sleep Unit, National Reference Network for Narcolepsy, Department of Neurology Hôpital-Gui-de Chauliac, CHU Montpellier, INSERM U1061, Montpellier, France. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada. · Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. · Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. · Department of Clinical Neurophysiology and Sleep Center, University Lille North of France, CHU Lille, Lille, France. · Sleep and Neurology Unit, Beau Soleil Clinic, Montpellier, France; EuroMov, University of Montpellier, Montpellier, France. · GRIP, École de psychologie, Université Laval, Québec city, Quebec, Canada; Institute of Genetic, Neurobiological and Social Foundations of Child Development, Tomsk State University, Tomsk, Russia. · Department of Neurological Sciences, Università Vita-Salute San Raffaele, Milan, Italy. · Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy; IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy. · Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy. · Department of Sleep Medicine and Neuromuscular Disorders, University of Muenster, Germany. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Neurosciences, Université de Montréal, Montréal, Quebec, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Département de psychologie, Université du Québec à Montréal, Montréal, Quebec, Canada. · Faculté de Médecine, Université Laval, CHU de Québec (Enfant-Jésus), Québec, Quebec, Canada. · Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada; Department of Neurology, Montreal General Hospital, Montréal, Quebec, Canada. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. ·Neurobiol Aging · Pubmed #27814994.

ABSTRACT: The present study aimed to examine whether the APOE ε4 allele, associated with dementia with Lewy bodies (DLB), and possibly with dementia in Parkinson's disease (PD), is also associated with idiopathic rapid eye movement sleep behavior disorder (RBD). Two single nucleotide polymorphisms, rs429358 and rs7412, were genotyped in RBD patients (n = 480) and in controls (n = 823). APOE ε4 allele frequency was 0.14 among RBD patients and 0.13 among controls (OR = 1.11, 95% CI: 0.88-1.40, p = 0.41). APOE ε4 allele frequencies were similar in those who converted to DLB (0.14) and those who converted to Parkinson's disease (0.12) or multiple system atrophy (0.14, p = 1.0). The APOE ε4 allele is neither a risk factor for RBD nor it is associated with conversion from RBD to DLB or other synucleinopathies.

12 Article Medulla oblongata damage and cardiac autonomic dysfunction in Parkinson disease. 2016

Pyatigorskaya, Nadya / Mongin, Marie / Valabregue, Romain / Yahia-Cherif, Lydia / Ewenczyk, Claire / Poupon, Cyril / Debellemaniere, Eden / Vidailhet, Marie / Arnulf, Isabelle / Lehéricy, Stephane. ·From Centre de NeuroImagerie de Recherche-CENIR (N.P., M.M., R.V., L.Y-C., I.A., S.L.), Institut du Cerveau et de la Moelle Épinière (ICM), Paris · UPMC Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, F-75013 (N.P., M.M., R.V., L.Y-C., E.D., M.V., I.A., S.L.), Sorbonne Universités · Service de Neuroradiologie (N.P., S.L.), Clinique des Mouvements Anormaux, Département des Maladies du Système Nerveux (C.E., M.V.), INSERM, Centre d'Investigation Clinique (CIC9503), Département des Maladies du Système Nerveux (M.V.), and Service des Pathologies du Sommeil (E.D., I.A.), Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière · and NeuroSpin (C.P.), Commissariat à l'Energie Atomique (CEA), Gif-Sur-Yvette, France. ·Neurology · Pubmed #27837003.

ABSTRACT: OBJECTIVE: To characterize medulla oblongata damage using diffusion tensor imaging (DTI) in Parkinson disease (PD) and correlate it with dysfunction of the cardiac sympathetic/vagal balance. METHODS: Fifty-two patients with PD and 24 healthy controls were included in the study. All participants underwent clinical examination and 3T MRI using 3D T1-weighted imaging and DTI. DTI metrics were calculated within manually drawn regions of interest. Heart rate variability was evaluated using spectral analysis of the R-R cardiac interval during REM and slow-wave sleep based on continuous overnight electrocardiographic monitoring. Respiratory frequency was measured in 30-second contiguous epochs of REM and slow-wave sleep. The relationships between imaging and cardiac variables were calculated using partial correlations followed by the multiple comparisons permutation approach. RESULTS: The changes in heart rate and respiratory frequency variability from slow-wave sleep to REM sleep in healthy controls were no longer detectable in patients with PD. There were significant increases in the mean (p = 0.006), axial (p = 0.006), and radial diffusivities (p = 0.005) in the medulla oblongata of patients with PD. In PD, diffusion changes were specifically correlated with a lower heart rate and respiratory frequency variability during REM sleep. CONCLUSIONS: This study provides evidence that medulla oblongata damage underlies cardiac sympathetic/vagal balance and respiratory dysfunction in patients with PD.

13 Article The role of the melanoma gene MC1R in Parkinson disease and REM sleep behavior disorder. 2016

Gan-Or, Ziv / Mohsin, Noreen / Girard, Simon L / Montplaisir, Jacques Y / Ambalavanan, Amirthagowri / Strong, Stephanie / Mallett, Victoria / Laurent, Sandra B / Bourassa, Cynthia V / Boivin, Michel / Langlois, Melanie / Arnulf, Isabelle / Högl, Birgit / Frauscher, Birgit / Monaca, Christelle / Desautels, Alex / Gagnon, Jean-François / Postuma, Ronald B / Dion, Patrick A / Dauvilliers, Yves / Dupre, Nicolas / Alcalay, Roy N / Rouleau, Guy A. ·Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. Electronic address: ziv.gan-or@mail.mcgill.ca. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada. · Department of Human Genetics, McGill University, Montréal, Quebec, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Psychiatry, Université de Montréal, Montréal, Quebec, Canada. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada. · GRIP, École de Psychologie, Université Laval, Québec City, Quebec, Canada; Institute of Genetics, Neurobiological and Social Foundations of Child Development, Tomsk State University, Tomsk, Russia. · Faculté de Médecine, Université Laval, CHU de Québec (Enfant-Jésus), Québec, Quebec, Canada. · Sleep Disorders Unit, Pitié Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière and Sorbonne Universities, UPMC Paris 6 univ, Paris, France. · Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. · Department of Clinical Neurophysiology and Sleep Center, CHU Lille, University Lille North of France, Lille, France. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Neurosciences, Université de Montréal, Montréal, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Département de Psychologie, Université du Québec à Montréal, Montréal, Quebec, Canada. · Department of Neurology, Montreal General Hospital, Montréal, Quebec, Canada. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. · Sleep Unit, National Reference Network for Narcolepsy, Department of Neurology Hôpital-Gui-de Chauliac, CHU Montpellier, INSERM U1061, Montpellier, France. · Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. Electronic address: guy.rouleau@mcgill.ca. ·Neurobiol Aging · Pubmed #27131830.

ABSTRACT: The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n = 539) and controls (n = 265) from New York, and PD patients (n = 551), rapid eye movement sleep behavior disorder (RBD) patients (n = 351), and controls (n = 956) of European ancestry. Sixty-eight MC1R variants were identified, including 7 common variants with frequency > 0.01. None of the common variants was associated with PD or RBD in the different regression models. In a meta-analysis with fixed-effect model, the p.R160W variant was associated with an increased risk for PD (odds ratio = 1.22, 95% confidence interval = 1.02-1.47, p = 0.03) but with significant heterogeneity (p = 0.048). Removing one study that introduced the heterogeneity resulted in nonsignificant association (odds ratio = 1.11, 95% confidence interval, 0.92-1.35, p = 0.27, heterogeneity p = 0.57). Rare variants had similar frequencies in patients and controls (10.54% and 10.15%, respectively, p = 0.75), and no cumulative effect of carrying more than one MC1R variant was found. The present study does not support a role for the MC1R p.R160W and other variants in susceptibility for PD or RBD.

14 Article Does Postural Rigidity Decrease during REM Sleep without Atonia in Parkinson Disease? 2016

Arnaldi, Dario / Latimier, Alice / Leu-Semenescu, Smaranda / De Carli, Fabrizio / Vidailhet, Marie / Arnulf, Isabelle. ·APHP- Pitié-Salpêtrière Hospital, Sleep Disorders Unit, Paris, France. · Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Italy. · Brain Research Institute- UPMC Paris 6 Univ, Inserm U 1127; CNRS UMR 7225, IHU neuroscience, Paris, France. · Institute of Bioimaging and Molecular Physiology, National Research Council, Genoa, Italy. · APHP- Pitié-Salpêtrière Hospital, Neurology Department, Paris, France. ·J Clin Sleep Med · Pubmed #26857056.

ABSTRACT: STUDY OBJECTIVES: Rigidity is a muscle hypertonia typical of Parkinson disease (PD), whereas rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by abnormally increased muscle tone during REM sleep (REM sleep without atonia) and enacting dream behaviors. Because movements are not bradykinetic during RBD in patients with PD, we investigated whether the background, wake postural rigidity is attenuated during REM sleep without atonia, in absence of movement. METHODS: The amplitude of levator menti (postural muscle) electromyographic activity during relaxed evening wakefulness (considered as reference) and sleep (N2, N3, atonic REM sleep, and quiet REM sleep without atonia) was measured in 20 patients with PD (with and without RBD), 10 patients with idiopathic RBD patients and 10 healthy subjects. RESULTS: The chin tone amplitude progressively decreased from wake to N2, N3, and atonic REM sleep in the four groups, but the highest amplitude was observed in PD patients with RBD during atonic REM sleep. Furthermore, chin muscle tone amplitude did not attenuate from wake to REM sleep without atonia in patients with both PD and RBD but dramatically attenuated (by 40% on average) in patients with idiopathic RBD. CONCLUSIONS: The high amplitude of chin muscle tone in PD with RBD (but not in idiopathic RBD) during REM sleep with and without atonia suggests that both PD-related hypertonia and RBD-related enhanced muscle tone coexist during REM sleep, together affecting chin muscle tone. Consequently, some rapid RBD movements likely start against a rigid postural tone.

15 Article Loss of REM sleep features across nighttime in REM sleep behavior disorder. 2016

Arnaldi, Dario / Latimier, Alice / Leu-Semenescu, Smaranda / Vidailhet, Marie / Arnulf, Isabelle. ·Sleep Disorders Unit, APHP-Pitié-Salpêtrière Hospital, Paris, France; Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Genova, Italy. · Brain Research Institute-UPMC Paris 6 Univ, Inserm U 1127, CNRS UMR 7225, Paris, France. · Sleep Disorders Unit, APHP-Pitié-Salpêtrière Hospital, Paris, France; Brain Research Institute-UPMC Paris 6 Univ, Inserm U 1127, CNRS UMR 7225, Paris, France. · Brain Research Institute-UPMC Paris 6 Univ, Inserm U 1127, CNRS UMR 7225, Paris, France; Neurology Department, APHP- Pitié-Salpêtrière Hospital, Paris, France. · Sleep Disorders Unit, APHP-Pitié-Salpêtrière Hospital, Paris, France; Brain Research Institute-UPMC Paris 6 Univ, Inserm U 1127, CNRS UMR 7225, Paris, France. Electronic address: isabelle.arnulf@psl.aphp.fr. ·Sleep Med · Pubmed #26847988.

ABSTRACT: OBJECTIVES: Melatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects. METHODS: An overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD-), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity. RESULTS: From the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change. CONCLUSIONS: Patients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity.

16 Article Sleep aspects on video-polysomnography in LRRK2 mutation carriers. 2015

Ehrminger, Mickael / Leu-Semenescu, Smaranda / Cormier, Florence / Corvol, Jean-Christophe / Vidailhet, Marie / Debellemaniere, Eden / Brice, Alexis / Arnulf, Isabelle. ·Ecole Normale Supérieure, Paris, France. · AP-HP, Hôpital Pitié-Salpêtrière, Sleep Disorders unit and Neurology Department, F-75013, Paris, France. · Sorbonne Universitiés, UPMC Univ Paris 06, UMR_S1127, ICM, F-75013, Paris, France. · INSERM, UMR_S1127 and CIC-1422, ICM, F-75013, Paris, France. · CNRS, UMR_7225, ICM, F-75005, Paris, France. ·Mov Disord · Pubmed #26468079.

ABSTRACT: BACKGROUND: Rapid eye movement sleep behavior disorder and sleepiness precede or accompany idiopathic Parkinson's disease (PD), but their presence in subjects with leucine-rich repeat kinase 2 mutations is unknown. METHODS: Ten patients with leucine-rich repeat kinase 2-associated PD, four healthy leucine-rich repeat kinase 2 mutation carriers, 20 patients with idiopathic PD, and 12 healthy controls underwent clinical assessments and a nighttime video-polysomnography. RESULTS: No sleep changes, no rapid eye movement sleep behavior disorder, or rapid eye movement sleep without atonia was found in the 14 subjects with leucine-rich repeat kinase 2mutations compared with controls, whereas 41% of patients with idiopathic PD had rapid eye movement sleep behavior disorder. Eventually, 20% of patients with leucine-rich repeat kinase 2-associated PD had abnormal periodic leg movements, a frequency similar to the idiopathic PD group frequency. CONCLUSIONS: The sleep phenotype in leucine-rich repeat kinase 2 mutations parallels that of idiopathic PD, except for absent rapid eye movement sleep behavior disorder here in the presymptomatic and symptomatic stages.

17 Article Evidence that non-dreamers do dream: a REM sleep behaviour disorder model. 2015

Herlin, Bastien / Leu-Semenescu, Smaranda / Chaumereuil, Charlotte / Arnulf, Isabelle. ·Sleep Disorders Unit, Pitié-Salpêtrière University Hospital, APHP, Paris, France. · Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière - UPMC-Paris 6, Inserm UMR_S 975, CNRS UMR 7225, Paris, France. · Inserm U1127, Paris, France. · Pierre and Marie Curie University, Paris, France. ·J Sleep Res · Pubmed #26307463.

ABSTRACT: To determine whether non-dreamers do not produce dreams or do not recall them, subjects were identified with no dream recall with dreamlike behaviours during rapid eye movement sleep behaviour disorder, which is typically characterised by dream-enacting behaviours congruent with sleep mentation. All consecutive patients with idiopathic rapid eye movement sleep behaviour disorder or rapid eye movement sleep behaviour disorder associated with Parkinson's disease who underwent a video-polysomnography were interviewed regarding the presence or absence of dream recall, retrospectively or upon spontaneous arousals. The patients with no dream recall for at least 10 years, and never-ever recallers were compared with dream recallers with rapid eye movement sleep behaviour disorder regarding their clinical, cognitive and sleep features. Of the 289 patients with rapid eye movement sleep behaviour disorder, eight (2.8%) patients had no dream recall, including four (1.4%) patients who had never ever recalled dreams, and four patients who had no dream recall for 10-56 years. All non-recallers exhibited, daily or almost nightly, several complex, scenic and dreamlike behaviours and speeches, which were also observed during rapid eye movement sleep on video-polysomnography (arguing, fighting and speaking). They did not recall a dream following sudden awakenings from rapid eye movement sleep. These eight non-recallers with rapid eye movement sleep behaviour disorder did not differ in terms of cognition, clinical, treatment or sleep measures from the 17 dreamers with rapid eye movement sleep behaviour disorder matched for age, sex and disease. The scenic dreamlike behaviours reported and observed during rapid eye movement sleep in the rare non-recallers with rapid eye movement sleep behaviour disorder (even in the never-ever recallers) provide strong evidence that non-recallers produce dreams, but do not recall them. Rapid eye movement sleep behaviour disorder provides a new model to evaluate cognitive processing during dreaming and subsequent recall.

18 Article Sleepiness in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease. 2015

Arnulf, Isabelle / Neutel, Dulce / Herlin, Bastien / Golmard, Jean-Louis / Leu-Semenescu, Smaranda / Cochen de Cock, Valérie / Vidailhet, Marie. ·Sorbonne Universities, UPMC Univ Paris 06, Paris, France. · Brain Research Institute (CRICM - UPMC-Paris6), Paris, France. · Sleep Disorders Unit, Pitié-Salpêtrière University Hospital, Paris, France. · Department of Biostatistics, Salpêtrière Hospital, ER4, Sorbonne Universites, UPMC Univ Paris 06, Paris, France. ·Sleep · Pubmed #26085299.

ABSTRACT: OBJECTIVE: To determine whether patients with idiopathic and symptomatic RBD were sleepier than controls, and if sleepiness in idiopathic RBD predicted earlier conversion to Parkinson disease. METHODS: The Epworth Sleepiness Scale (ESS) and its determinants were compared at the time of a video-polysomnography for an RBD diagnosis in patients with idiopathic RBD, in patients with Parkinson disease, and in controls. Whether sleepiness at time of RBD diagnosis predicted an earlier conversion to neurodegenerative diseases was retrospectively analyzed in the followed-up patients. RESULTS: The 75 patients with idiopathic RBD were sleepier (ESS: 7.8 ± 4.6) at the time of RBD diagnosis than 74 age- and sex-matched controls (ESS: 5.0 ± 3.6, P < 0.0001). They reached the levels of 114 patients with Parkinson disease (ESS: 8.7 ± 4.8), whether they had (n = 78) or did not have (n = 36) concomitant RBD. The severity of sleepiness in idiopathic RBD correlated with younger age, but not with sleep measures. Among the 69 patients with idiopathic RBD who were followed up for a median 3 years (1-15 years), 16 (23.2%) developed parkinsonism (n = 6), dementia (n = 6), dementia plus parkinsonism (n = 2), and multiple system atrophy (n = 2). An ESS greater than 8 at time of RBD diagnosis predicted a shorter time to phenoconversion to parkinsonism and dementia, from RBD onset, and from RBD diagnosis (when adjusted for age and time between RBD onset and diagnosis). CONCLUSIONS: Sleepiness is associated with idiopathic REM sleep behavior disorder and predicts more rapid conversion to parkinsonism and dementia, suggesting it is an early marker of neuronal loss in brainstem arousal systems.

19 Article Parkinson's Disease Genetic Loci in Rapid Eye Movement Sleep Behavior Disorder. 2015

Gan-Or, Z / Girard, S L / Noreau, A / Leblond, C S / Gagnon, J F / Arnulf, I / Mirarchi, C / Dauvilliers, Y / Desautels, A / Mitterling, T / Cochen De Cock, V / Frauscher, B / Monaca, C / Hogl, B / Dion, P A / Postuma, R B / Montplaisir, J Y / Rouleau, G A. ·Montreal Neurological Institute and McGill University, Montréal, QC, Canada. ·J Mol Neurosci · Pubmed #25929833.

ABSTRACT: Rapid eye movement (REM) sleep behavior disorder (RBD) is a prodromal condition for Parkinson's disease (PD) and other synucleinopathies, which often occurs many years before the onset of PD. We analyzed 261 RBD patients and 379 controls for nine PD-associated SNPs and examined their effects, first upon on RBD risk and second, on eventual progression to synucleinopathies in a prospective follow-up in a subset of patients. The SCARB2 rs6812193 (OR = 0.67, 95 % CI = 0.51-0.88, p = 0.004) and the MAPT rs12185268 (OR-0.43, 95 % CI-0.26-0.72, p = 0.001) were associated with RBD in different models. Kaplan-Meier survival analysis in a subset of RBD patients (n = 56), demonstrated that homozygous carriers of the USP25 rs2823357 SNP had progressed to synucleinopathies faster than others (log-rank p = 0.003, Breslow p = 0.005, Tarone-Ware p = 0.004). As a proof-of-concept study, these results suggest that RBD may be associated with at least a subset of PD-associated genes, and demonstrate that combining genetic and prodromal clinical data may help identifying individuals that are either more or less susceptible to develop synucleinopathies. More studies are necessary to replicate these results, and identify more genetic factors affecting progression from RBD to synucleinopathies.

20 Article Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group. 2013

Schenck, C H / Montplaisir, J Y / Frauscher, B / Hogl, B / Gagnon, J-F / Postuma, R / Sonka, K / Jennum, P / Partinen, M / Arnulf, I / Cochen de Cock, V / Dauvilliers, Y / Luppi, P-H / Heidbreder, A / Mayer, G / Sixel-Döring, F / Trenkwalder, C / Unger, M / Young, P / Wing, Y K / Ferini-Strambi, L / Ferri, R / Plazzi, G / Zucconi, M / Inoue, Y / Iranzo, A / Santamaria, J / Bassetti, C / Möller, J C / Boeve, B F / Lai, Y Y / Pavlova, M / Saper, C / Schmidt, P / Siegel, J M / Singer, C / St Louis, E / Videnovic, A / Oertel, W. ·Minnesota Regional Sleep Disorders Center, Department of Psychiatry, Hennepin County Medical Center and University of Minnesota Medical School, Minneapolis, MN, USA. schen010@umn.edu ·Sleep Med · Pubmed #23886593.

ABSTRACT: OBJECTIVES: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. METHODS: The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). RESULTS: Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. CONCLUSIONS: The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

21 Article The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson's disease. 2013

García-Lorenzo, Daniel / Longo-Dos Santos, Clarisse / Ewenczyk, Claire / Leu-Semenescu, Smaranda / Gallea, Cecile / Quattrocchi, Graziella / Pita Lobo, Patricia / Poupon, Cyril / Benali, Habib / Arnulf, Isabelle / Vidailhet, Marie / Lehericy, Stéphane. ·Institut du Cerveau et de Moelle épinière, Centre de Neuroimagerie de Recherche, Paris, France. ·Brain · Pubmed #23801736.

ABSTRACT: In Parkinson's disease, rapid eye movement sleep behaviour disorder is an early non-dopaminergic syndrome with nocturnal violence and increased muscle tone during rapid eye movement sleep that can precede Parkinsonism by several years. The neuronal origin of rapid eye movement sleep behaviour disorder in Parkinson's disease is not precisely known; however, the locus subcoeruleus in the brainstem has been implicated as this structure blocks muscle tone during normal rapid eye movement sleep in animal models and can be damaged in Parkinson's disease. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex in patients with Parkinson's disease using combined neuromelanin-sensitive, structural and diffusion magnetic resonance imaging approaches. We compared 24 patients with Parkinson's disease and rapid eye movement sleep behaviour disorder, 12 patients without rapid eye movement sleep behaviour disorder and 19 age- and gender-matched healthy volunteers. All subjects underwent clinical examination and characterization of rapid eye movement sleep using video-polysomnography and multimodal imaging at 3 T. Using neuromelanin-sensitive imaging, reduced signal intensity was evident in the locus coeruleus/subcoeruleus area in patients with Parkinson's disease that was more marked in patients with than those without rapid eye movement sleep behaviour disorder. Reduced signal intensity correlated with the percentage of abnormally increased muscle tone during rapid eye movement sleep. The results confirmed that this complex is affected in Parkinson's disease and showed a gradual relationship between damage to this structure, presumably the locus subcoeruleus, and abnormal muscle tone during rapid eye movement sleep, which is the cardinal marker of rapid eye movement sleep behaviour disorder. In longitudinal studies, the technique may also provide early markers of non-dopaminergic Parkinson's disease pathology to predict the occurrence of Parkinson's disease.

22 Article Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. 2013

Boeve, B F / Silber, M H / Ferman, T J / Lin, S C / Benarroch, E E / Schmeichel, A M / Ahlskog, J E / Caselli, R J / Jacobson, S / Sabbagh, M / Adler, C / Woodruff, B / Beach, T G / Iranzo, A / Gelpi, E / Santamaria, J / Tolosa, E / Singer, C / Mash, D C / Luca, C / Arnulf, I / Duyckaerts, C / Schenck, C H / Mahowald, M W / Dauvilliers, Y / Graff-Radford, N R / Wszolek, Z K / Parisi, J E / Dugger, B / Murray, M E / Dickson, D W. ·Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. bboeve@mayo.edu ·Sleep Med · Pubmed #23474058.

ABSTRACT: OBJECTIVE: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. METHODS: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. RESULTS: 172 cases were identified, of whom 143 (83%) were men. The mean±SD age of onset in years for the core features were as follows - RBD, 62±14 (range, 20-93), cognitive impairment (n=147); 69±10 (range, 22-90), parkinsonism (n=151); 68±9 (range, 20-92), and autonomic dysfunction (n=42); 62±12 (range, 23-81). Death age was 75±9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10±12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n=97), Parkinson's disease with or without mild cognitive impairment or dementia (n=32), multiple system atrophy (MSA) (n=19), Alzheimer's disease (AD)(n=9) and other various disorders including secondary narcolepsy (n=2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n=1). The neuropathologic diagnoses were Lewy body disease (LBD)(n=77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n=59), MSA (n=19), AD (n=6), progressive supranulear palsy (PSP) (n=2), other mixed neurodegenerative pathologies (n=6), NBIA-1/LBD/tauopathy (n=1), and hypothalamic structural lesions (n=2). Among the neurodegenerative disorders associated with RBD (n=170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. CONCLUSIONS: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.

23 Article Hallucinations in narcolepsy with and without cataplexy: contrasts with Parkinson's disease. 2011

Leu-Semenescu, Smaranda / De Cock, Valerie Cochen / Le Masson, Valerie Dauriac / Debs, Rachel / Lavault, Sophie / Roze, Emmanuel / Vidailhet, Marie / Arnulf, Isabelle. ·Sleep Disorders Unit, Pitié-Salpêtrière Hospital, AP-HP, Paris 6 University, Paris, France. isabelle.arnulf@psl.aphp.fr ·Sleep Med · Pubmed #21486708.

ABSTRACT: BACKGROUND: Narcolepsy and Parkinson's disease (PD) are associated with hallucinations, excessive daytime sleepiness, REM sleep behavior disorder (RBD), as well as complete (narcolepsy with cataplexy) vs. partial (PD, narcolepsy without cataplexy) hypocretin-1 deficiency. OBJECTIVE: To compare the hallucinations associated with narcolepsy to those of PD. METHODS: One hundred patients with narcolepsy (with and without cataplexy) and 100 patients with PD were consecutively interviewed about their hallucinations (frequency, phenomenology, insight into unreality and association with sleep) as well as their risk factors. RESULTS: Hallucinations occurred more frequently and with more motor and multimodal aspects in narcolepsy with cataplexy (59%) than in narcolepsy without cataplexy (28%) and PD (26%). Compared to PD, the hallucinations in narcolepsy were less frequently of the passage/presence type (passage: brief visions of a person or animal passing sideways; presence: perception that a living character or an animal is behind or near the subject, without the subject actually seeing, hearing or touching it), more frequently auditory and more often associated with sleep. However, in 40% of the patients with narcolepsy and 54% of the patients with PD, the hallucinations occurred while the patients were wide awake. Patients with cataplexy had reduced immediate insight into the unreality of their hallucinations compared to patients with PD, but the delusions were exceptional (2%), transient and based on hallucinations in both groups. The risk factors for hallucinations were sleep paralysis and RBD in narcolepsy and motor disability and sleepiness in PD. CONCLUSIONS: The multimodal, dreamlike aspect of hallucinations in narcolepsy with cataplexy could transiently impair the patients' insight. The high frequency of these hallucinations (compared to those in narcolepsy without cataplexy or PD) suggests that complete (more than partial) hypocretin-1 deficiency promotes hallucinations.

24 Article The improvement of movement and speech during rapid eye movement sleep behaviour disorder in multiple system atrophy. 2011

De Cock, Valérie Cochen / Debs, Rachel / Oudiette, Delphine / Leu, Smaranda / Radji, Fatai / Tiberge, Michel / Yu, Huan / Bayard, Sophie / Roze, Emmanuel / Vidailhet, Marie / Dauvilliers, Yves / Rascol, Olivier / Arnulf, Isabelle. ·Unité des troubles du sommeil, Service de neurologie, Hôpital Gui de Chauliac, 2 av Emile Bertin Sans, 34000 Montpellier, France. valerie.decock@free.fr ·Brain · Pubmed #21310729.

ABSTRACT: Multiple system atrophy is an atypical parkinsonism characterized by severe motor disabilities that are poorly levodopa responsive. Most patients develop rapid eye movement sleep behaviour disorder. Because parkinsonism is absent during rapid eye movement sleep behaviour disorder in patients with Parkinson's disease, we studied the movements of patients with multiple system atrophy during rapid eye movement sleep. Forty-nine non-demented patients with multiple system atrophy and 49 patients with idiopathic Parkinson's disease were interviewed along with their 98 bed partners using a structured questionnaire. They rated the quality of movements, vocal and facial expressions during rapid eye movement sleep behaviour disorder as better than, equal to or worse than the same activities in an awake state. Sleep and movements were monitored using video-polysomnography in 22/49 patients with multiple system atrophy and in 19/49 patients with Parkinson's disease. These recordings were analysed for the presence of parkinsonism and cerebellar syndrome during rapid eye movement sleep movements. Clinical rapid eye movement sleep behaviour disorder was observed in 43/49 (88%) patients with multiple system atrophy. Reports from the 31/43 bed partners who were able to evaluate movements during sleep indicate that 81% of the patients showed some form of improvement during rapid eye movement sleep behaviour disorder. These included improved movement (73% of patients: faster, 67%; stronger, 52%; and smoother, 26%), improved speech (59% of patients: louder, 55%; more intelligible, 17%; and better articulated, 36%) and normalized facial expression (50% of patients). The rate of improvement was higher in Parkinson's disease than in multiple system atrophy, but no further difference was observed between the two forms of multiple system atrophy (predominant parkinsonism versus cerebellar syndrome). Video-monitored movements during rapid eye movement sleep in patients with multiple system atrophy revealed more expressive faces, and movements that were faster and more ample in comparison with facial expression and movements during wakefulness. These movements were still somewhat jerky but lacked any visible parkinsonism. Cerebellar signs were not assessable. We conclude that parkinsonism also disappears during rapid eye movement sleep behaviour disorder in patients with multiple system atrophy, but this improvement is not due to enhanced dopamine transmission because these patients are not levodopa-sensitive. These data suggest that these movements are not influenced by extrapyramidal regions; however, the influence of abnormal cerebellar control remains unclear. The transient disappearance of parkinsonism here is all the more surprising since no treatment (even dopaminergic) provides a real benefit in this disabling disease.

25 Article Sleep induced by stimulation in the human pedunculopontine nucleus area. 2010

Arnulf, Isabelle / Ferraye, Muriel / Fraix, Valérie / Benabid, Alim Louis / Chabardès, Stephan / Goetz, Laurent / Pollak, Pierre / Debû, Bettina. ·Sleep Disorders Unit, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_975 (Mixed Unity of Research), Pitié-Salpêtrière Hospital, Assistance Publique-Hopitaux de Paris, Paris 6 University, Paris, France. isabelle.arnulf@psl.aphp.fr ·Ann Neurol · Pubmed #20437591.

ABSTRACT: The pedunculopontine nucleus is part of the reticular ascending arousal system and is involved in locomotion and sleep. Two patients with Parkinson disease received electrodes that stimulated the pedunculopontine nucleus area to alleviate their severe gait impairment. Instead, we found that low-frequency stimulation of the pedunculopontine nucleus area increased alertness, whereas high-frequency stimulation induced non-rapid eye movement sleep. In addition, the sudden withdrawal of the low-frequency stimulation was consistently followed by rapid eye movement sleep episodes in 1 patient. These data have the potential to benefit patients who suffer from sleep disorders.

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