Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Parkinson Disease: HELP
Articles by Joan Santamaría
Based on 18 articles published since 2010
(Why 18 articles?)
||||

Between 2010 and 2020, Joan Santamaria wrote the following 18 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Review Precision Medicine in Rapid Eye Movement Sleep Behavior Disorder. 2019

Högl, Birgit / Santamaria, Joan / Iranzo, Alex / Stefani, Ambra. ·Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria. · Neurology Service, Multidisciplinary Sleep Unit, Hospital Clinic de Barcelona, Institut D'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas, Calle Villarroel, 170, Barcelona 08036, Spain. · Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria. Electronic address: ambra.stefani@i-med.ac.at. ·Sleep Med Clin · Pubmed #31375203.

ABSTRACT: In recent years, the diagnostic approach to rapid eye movement (REM) sleep behavior disorder (RBD) has become more objective and accurate. This was achieved mainly by introduction of methods to exactly quantify electromyographic (EMG) activity in various muscles during REM sleep. The most established muscle combination for RBD diagnosis is the mentalis and upper extremity EMG. Computer-assisted systems for this analysis have been described, and an increasing number of studies looked into analysis of video events. Recently, prodromal phases of isolated RBD have been recognized.

2 Clinical Trial Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. 2019

Postuma, Ronald B / Iranzo, Alex / Hu, Michele / Högl, Birgit / Boeve, Bradley F / Manni, Raffaele / Oertel, Wolfgang H / Arnulf, Isabelle / Ferini-Strambi, Luigi / Puligheddu, Monica / Antelmi, Elena / Cochen De Cock, Valerie / Arnaldi, Dario / Mollenhauer, Brit / Videnovic, Aleksandar / Sonka, Karel / Jung, Ki-Young / Kunz, Dieter / Dauvilliers, Yves / Provini, Federica / Lewis, Simon J / Buskova, Jitka / Pavlova, Milena / Heidbreder, Anna / Montplaisir, Jacques Y / Santamaria, Joan / Barber, Thomas R / Stefani, Ambra / St Louis, Erik K / Terzaghi, Michele / Janzen, Annette / Leu-Semenescu, Smandra / Plazzi, Guiseppe / Nobili, Flavio / Sixel-Doering, Friederike / Dusek, Petr / Bes, Frederik / Cortelli, Pietro / Ehgoetz Martens, Kaylena / Gagnon, Jean-Francois / Gaig, Carles / Zucconi, Marco / Trenkwalder, Claudia / Gan-Or, Ziv / Lo, Christine / Rolinski, Michal / Mahlknecht, Philip / Holzknecht, Evi / Boeve, Angel R / Teigen, Luke N / Toscano, Gianpaolo / Mayer, Geert / Morbelli, Silvia / Dawson, Benjamin / Pelletier, Amelie. ·Department of Neurology, McGill University, Montreal General Hospital, Montreal, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Canada. · Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Oxford Parkinson's Disease Centre (OPDC) and Oxford University, Oxford, UK. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Mayo Clinic, Rochester, MN, USA. · Unit of Sleep Medicine and Epilepsy, IRCCS, C.Mondino Foundation, Pavia, Italy. · Department of Neurology, Philipps-Universität, Marburg, Germany. · Sleep disorders unit, Pitie-Salpetriere Hospital, IHU@ICM and Sorbonne University, Paris, France. · Sleep Disorders Center, Department of Neurology, Scientific Institute Ospedale San Raffaele, Vita-Salute University, Milan, Italy. · Sleep Center, Department of Cardiovascular and Neurological Sciences, University of Cagliari, Italy. · Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. · IRCCS Institute of the Neurological Sciences, Ospedale Bellaria, ASL di Bologna, Bologna, Italy. · Sleep and Neurology Unit, Beau Soleil Clinic, Montpellier, France; EuroMov, University of Montpellier, Montpellier, France. · Clinical Neurology, Dept. of Neuroscience (DINOGMI), University of Genoa, and Polyclinic San Martino Hospital, Genoa, Italy. · Department of Neurosurgery (C.T.) University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M., C.T. F. S-D.), Kassel, Germany. · Movement Disorders Unit and Division of Sleep Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA. · Department of Neurology and Centre of Clinical Neurosciences of the First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. · Neuroscience Research Institute, Seoul National University College of Medicine, Department of Neurology, Seoul National University Hospital, Seoul, Korea. · Institute of Physiology Charité-Universitätsmedizin Berlin. Germany. · Sleep Unit, Department of Neurology, Hôpital Gui de Chauliac, Montpellier, INSERM U1061, Montpellier, F-34093 Cedex 5 France. · Department of Biomedical and Neuromotor Sciences, Bellaria Hospital, University of Bologna, Bologna, Italy. · IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy. · Brain and Mind Centre University of Sydney, Camperdown, Australia. · National Institute of Mental Health, Klecany, Third Faculty of Medicine, Charles Unviersity, Prague, Czech Republic. · Department of Neurology, Brigham and Women's Hospital, Boston; Harvard Medical School, Boston, USA. · Institute for Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. · Department of Psychology, Université du Québec à Montréal, Montreal, Quebec, Canada. · Department of Human Genetics, McGill University, Montreal, Canada. · Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada. · Department of Neurology, Hephata Klinik, Schwalmstadt-Treysa, Germany. · Nuclear Medicine, Department of Health Sciences (DISSAL), University of Genoa and Polyclinic San Martino Hospital, Genoa, Italy. ·Brain · Pubmed #30789229.

ABSTRACT: Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1-19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.

3 Article Lack of Asymmetry of Nigrostriatal Dopaminergic Function in Healthy Subjects. 2020

Garrido, Alicia / Iranzo, Alex / Stefani, Ambra / Serradell, Mònica / Muñoz-Lopetegi, Amaia / Marrero, Paula / Högl, Birgit / Gaig, Carles / Santamaria, Joan / Tolosa, Eduard / Poewe, Werner / Anonymous5011110. ·Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. · Center for Sleep Disorders, Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. ·Mov Disord · Pubmed #32141653.

ABSTRACT: OBJECTIVE: In right-handed patients with Parkinson's disease (PD) or isolated rapid eye movement sleep behavior disorder, dopamine transporter (DAT) [(123)I]β-carboxymethyoxy-3-β-(4-iodophenyl) tropane single photon emission computed tomography (SPECT) shows predominant nigrostriatal deficit in the left striatum. This suggests that in PD patients, the nigrostriatal system of the dominant hemisphere is more susceptible to disease-related dysfunction. To confirm this hypothesis, we investigated whether the nigrostriatal function is symmetric in healthy controls and in patients with PD. METHODS: In 113 right-handed healthy controls and 279 right-handed early-PD patients, we examined the striatal dopaminergic terminals function in each hemisphere using DAT-SPECT. RESULTS: In the controls, DAT-SPECT showed symmetric specific binding ratios in the putamen and caudate nucleus of each hemisphere. In patients with PD, the specific binding ratio was lower in the left than in the right putamen. CONCLUSIONS: Right-handed healthy controls have symmetric nigrostriatal dopaminergic function. The left hemispheric predominance of nigrostriatal deficit seen in right-handed premotor and manifest PD represents an early pathological feature of the disease. © 2020 International Parkinson and Movement Disorder Society.

4 Article Alpha-synuclein aggregates in the parotid gland of idiopathic REM sleep behavior disorder. 2018

Fernández-Arcos, Ana / Vilaseca, Isabel / Aldecoa, Iban / Serradell, Mónica / Tolosa, Eduard / Santamaría, Joan / Gelpi, Ellen / Iranzo, Alex. ·Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Otorhinolaryngology Service, Hospital Clínic de Barcelona, AGAUR Head Neck Clinic, CIBER Enfermedades Respiratorias, Bunyola, Spain; Faculty of Medicine, University of Barcelona, Barcelona, Spain. · Neurological Tissue Bank, Biobanc-Hospital Clinic, IDIBAPS, Barcelona, Spain; Pathology Service, Biomedical Diagnostic Center-CDB, Hospital Clinic, Barcelona, Spain. · Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain; Faculty of Medicine, University of Barcelona, Barcelona, Spain. · Neurological Tissue Bank, Biobanc-Hospital Clinic, IDIBAPS, Barcelona, Spain; Institute of Neurology, Medical University of Vienna, Vienna, Austria. Electronic address: ellen.gelpimantius@medunwien.ac.at. · Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain; Faculty of Medicine, University of Barcelona, Barcelona, Spain. Electronic address: airanzo@clinic.ub.es. ·Sleep Med · Pubmed #30195197.

ABSTRACT: BACKGROUND: The neuropathological hallmark of Parkinson's disease (PD) is the presence of aggregates of phosphorylated alpha-synuclein (pAS) in the nervous system. METHOD: We report a patient with video-polysomnography-confirmed idiopathic REM sleep behavior disorder that underwent parotidectomy because of parotid gland cancer. Immunohistochemistry of the gland tissue revealed abundant pAS deposits. One year after surgery the patient was diagnosed with PD. Prompted by this observation we examined the parotid gland in 10 consecutive individuals that underwent elective parotidectomy irrespective of their clinical condition. RESULTS: One had PD and another had mild parkinsonian signs plus reduced dopamine transporter uptake in the striatum. Both had pAS deposits in the parotid gland. The remaining eight subjects had no neurological signs and pAS was found in one of them. CONCLUSION: Our study shows that the parotid gland may contain pAS pathology in the prodromal stage of PD and in manifested PD.

5 Article α-Synuclein aggregates in labial salivary glands of idiopathic rapid eye movement sleep behavior disorder. 2018

Iranzo, Alex / Borrego, Sergi / Vilaseca, Isabel / Martí, Carles / Serradell, Mónica / Sánchez-Valle, Raquel / Kovacs, Gabor G / Valldeoriola, Francesc / Gaig, Carles / Santamaria, Joan / Tolosa, Eduard / Gelpi, Ellen. ·Neurology Service, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain. · Otorhinolaryngology Service, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Respiratorias, Bunyola, Spain. · Maxillofacial Surgery Service Hospital Clínic de Barcelona, Barcelona, Spain. · Institute of Neurology, Medical University of Vienna, Vienna, Austria. · Neurological Tissue Bank, Biobanc-Hospital Clinic, IDIBAPS, Barcelona, Spain. ·Sleep · Pubmed #29790977.

ABSTRACT: Study Objectives: To assess whether biopsy of the labial minor salivary glands safely detects phosphorylated α-synuclein (pAS) deposits in idiopathic rapid eye movement sleep behavior disorder (IRBD), a condition that precedes the cardinal manifestations of synuclein disorders associated with Lewy-type pathology, namely, Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Methods: In a prospective study, labial biopsy of the minor salivary glands was performed in 62 patients with IRBD, 13 patients with PD, and 10 patients with DLB who were initially diagnosed with IRBD, and in 33 controls. Aggregates of pAS were assessed by immunohistochemistry using antiserine 129-pAS antibody and the conformation-specific 5G4 antibody. Results: Sufficient biopsy material containing glandular parenchyma was obtained in all participants. Deposits of pAS were found in 31 of 62 (50%) participants with IRBD, 7 of 13 (54%) with PD, 5 of 10 (50%) with DLB, and in one of the 33 (3%) controls. Participants with IRBD, PD, and DLB with and without pAS immunoreactivity did not differ in demographic and clinical features. Adverse events were lip bruising (9.2%), swelling (6.6%), pain (2.4%), and numbness (1.7%) which were mild and transitory and did not require treatment. Conclusions: Labial minor salivary glands biopsy proved to be a safe and useful procedure to identify pAS in participants with IRBD, and in participants with PD and DLB initially diagnosed with IRBD. The biopsy provides direct histopathological evidence that IRBD represents a synucleinopathy and that could be useful for histological confirmation of synuclein pathology in PD and DLB.

6 Article Glucocerebrosidase gene variants are accumulated in idiopathic REM sleep behavior disorder. 2018

Gámez-Valero, Ana / Iranzo, Alex / Serradell, Monica / Vilas, Dolores / Santamaria, Joan / Gaig, Carles / Álvarez, Ramiro / Ariza, Aurelio / Tolosa, Eduardo / Beyer, Katrin. ·Department of Pathology, Hospital Universitari and Health Sciences Research Institute Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain. · Department of Neurology and Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Department of Neurology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. · Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, CIBERNED, IDIBAPS, Universitat de Barcelona, Spain. · Department of Pathology, Hospital Universitari and Health Sciences Research Institute Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: kbeyer@igtp.cat. ·Parkinsonism Relat Disord · Pubmed #29487000.

ABSTRACT: INTRODUCTION: Glucocerebrosidase (GBA) gene variants are associated with the development of the Lewy body disorders (LBD) Parkinson disease (PD) and dementia with Lewy bodies (DLB). Idiopathic REM sleep behavior disorder (IRBD) represents prodromal LBD in most instances. We investigated whether GBA variants are overrepresented in IRBD and if their presence shortens the time to conversion to clinically-defined LBD. METHODS: All GBA coding exons from 69 polysomnography-confirmed IRBD patients and 84 matched controls were sequenced by the Sanger method. RESULTS: Seven missense variants (E326K, L444P, A446T, A318G, R329C, T369M, N370S) were identified in eight (11.6%) IRBD patients and in one (1.2%) control (P = 0.026). After a mean follow-up of 8.9 ± 3.8 years from IRBD diagnosis, five subjects with GBA variants developed LBD (3 DLB and 2 PD) and three remained disease-free. The risk of developing a LBD was similar in IRBD subjects with GBA variants than in those without variants (log rank test, p = 0.935). CONCLUSIONS: In IRBD, GBA variants are 1) more frequent when compared to controls, 2) associated with impending PD and DLB but 3) not indicative of a short-term risk for LBD after IRBD diagnosis. IRBD patients carrying GBA variants could be studied with disease-modifying interventions aiming to restore the GBA metabolic pathway.

7 Article Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder. 2017

Iranzo, Alex / Santamaría, Joan / Valldeoriola, Francesc / Serradell, Monica / Salamero, Manel / Gaig, Carles / Niñerola-Baizán, Aida / Sánchez-Valle, Raquel / Lladó, Albert / De Marzi, Roberto / Stefani, Ambra / Seppi, Klaus / Pavia, Javier / Högl, Birgit / Poewe, Werner / Tolosa, Eduard / Lomeña, Francisco. ·Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Psychiatry Service, Hospital Clinic de Barcelona, Barcelona, Spain. · Biomedical Research Networking Center of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. · Department of Neurology, Medical University Innsbruck, Austria. · Nuclear Medicine Service, Hospital Clinic Barcelona, IDIBAPS, Barcelona, Spain. ·Ann Neurol · Pubmed #28833467.

ABSTRACT: OBJECTIVE: To determine the usefulness of dopamine transporter (DAT) imaging to identify idiopathic rapid eye movement sleep behavior disorder (IRBD) patients at risk for short-term development of clinically defined synucleinopathy. METHODS: Eighty-seven patients with polysomnography-confirmed IRBD underwent RESULTS: Baseline DAT deficit was found in 51 (58.6%) patients. During follow-up, 25 (28.7%) subjects developed clinically defined synucleinopathy (Parkinson's disease in 11, dementia with Lewy bodies in 13, and multiple system atrophy in 1) with mean latency of 3.2 ± 1.9 years from imaging. Kaplan-Meier survival analysis showed increased risk of incident synucleinopathy in patients with abnormal DAT-SPECT than with normal DAT-SPECT (20% vs 6% at 3 years, 33% vs 18% at 5 years; log rank test, p = 0.006). Receiver operating characteristics curve revealed that reduction of FP-CIT uptake in putamen greater than 25% discriminated patients with DAT deficit who developed synucleinopathy from patients with DAT deficit that remained disease free after 3 years of follow-up. At 5-year follow-up, DAT-SPECT had 75% sensitivity, 51% specificity, 44% positive predictive value, 80% negative predictive value, and likelihood ratio 1.54 to predict synucleinopathy. INTERPRETATION: DAT-SPECT identifies IRBD patients at short-term risk for synucleinopathy. Decreased FP-CIT putamen uptake greater than 25% predicts synucleinopathy after 3 years' follow-up. These observations may be useful to select candidates for disease modification trials in IRBD. Ann Neurol 2017;82:419-428.

8 Article Characterization of patients with longstanding idiopathic REM sleep behavior disorder. 2017

Iranzo, Alex / Stefani, Ambra / Serradell, Monica / Martí, Maria Jose / Lomeña, Francisco / Mahlknecht, Philipp / Stockner, Heike / Gaig, Carles / Fernández-Arcos, Ana / Poewe, Werner / Tolosa, Eduard / Högl, Birgit / Santamaria, Joan / Anonymous7380909. ·From the Neurology Service (A.I., M.S., M.J.M., C.G., A.F.-A., E.T., J.S.) and Nuclear Medicine Service (F.L.), Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Spain · and Department of Neurology (A.S., P.M., H.S., W.P., B.H.), Medical University Innsbruck, Austria. ·Neurology · Pubmed #28615430.

ABSTRACT: OBJECTIVE: To evaluate the presence of prodromal markers of Parkinson disease (PD) in patients with longstanding idiopathic REM sleep behavior disorder (IRBD), a small subgroup of individuals with IRBD with long-term follow-up thought not to be at risk of developing PD. METHODS: Demographic, clinical, and neuroimaging markers of PD were evaluated in 20 patients with polysomnographic-confirmed longstanding IRBD and in 32 matched controls. RESULTS: Patients were 16 men and 4 women with mean age of 72.9 ± 8.6 years and mean follow-up from IRBD diagnosis of 12.1 ± 2.6 years. Patients more often had objective smell loss (35% vs 3.4%, CONCLUSIONS: Prodromal PD markers are common in individuals with longstanding IRBD, suggesting that they are affected by an underlying neurodegenerative process. This observation may be useful for the design of disease-modifying trials to prevent PD onset in IRBD.

9 Article Assessment of α-synuclein in submandibular glands of patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. 2016

Vilas, Dolores / Iranzo, Alex / Tolosa, Eduardo / Aldecoa, Iban / Berenguer, Joan / Vilaseca, Isabel / Martí, Carles / Serradell, Mónica / Lomeña, Francisco / Alós, Llucia / Gaig, Carles / Santamaria, Joan / Gelpi, Ellen. ·Neurology Service, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain; Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. · Neurology Service, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain; Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. Electronic address: etolosa@clinic.ub.es. · Pathology Service, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain. · Radiology Service, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain. · Otorhinolaryngology Service, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain; CIBER Enfermedades Respiratorias, Bunyola, Spain. · Maxillofacial Surgery Service, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain. · Neurology Service, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain. · Nuclear Medicine Service, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Universidad de Barcelona, Barcelona, Spain. · Neurological Tissue Bank, Biobanc-Hospital Clinic, Instituto de Investigaciones Biomédicas August Pi i Sunyer, Barcelona, Spain. ·Lancet Neurol · Pubmed #27039162.

ABSTRACT: BACKGROUND: The histological feature of Parkinson's disease is the presence of intraneuronal aggregates of phosphorylated α-synuclein (αSyn). In patients with Parkinson's disease, deposits of αSyn are found in the autonomic nerve fibres of the submandibular gland. Since patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) can develop Parkinson's disease and other synucleinopathies, we investigated whether αSyn deposits could also be detected in their submandibular gland nerve fibres. METHODS: We did a case-control study at the Hospital Clinic de Barcelona (Barcelona, Spain) in patients with polysomnographic-confirmed IRBD, patients with clinically diagnosed Parkinson's disease, and controls matched by age with the IRBD group. The controls were either healthy, had had elective neck surgery in the clinic, or were patients who had died in the clinic and had an autopsy. We did a transcutaneous core needle biopsy of the submandibular gland with ultrasound guidance in patients with IRBD or Parkinson's disease, and healthy controls, and without ultrasound guidance in the other controls. We assessed the presence of αSyn with immunohistochemistry using 129-phosphorylated antiserine monoclonal antibody, and analysed quantitative variables with Kruskall-Wallis tests and qualitative variables with Fisher's exact tests. FINDINGS: We did our study between July 16, 2014, and May 16, 2015, and recruited 21 patients with IRBD, 24 patients with Parkinson's disease, and 26 controls (seven healthy, 11 patients undergoing neck surgery, and eight autopsies). We obtained submandibular biopsy material containing glandular parenchyma in nine (43%) of 21 patients with IRBD, 12 (50%) of 24 patients with Parkinson's disease, and all (100%) of the 26 controls. αSyn aggregates were detected in nerve fibres of the glandular parenchyma in eight (89%) of nine patients with IRBD and eight (67%) of 12 with Parkinson's disease, but none of the controls. Of the individuals whose biopsy samples did not contain glandular parenchyma, deposits of αSyn were found in extraglandular tissues in an additional three (25%) of 12 patients with IRBD and five (42%) of 12 patients with Parkinson's disease. None of the controls showed αSyn immunoreactivity in extraglandular tissues. Of the 52 participants who had ultrasonography-guided biopsy, 11 (21%) reported mild-to-moderate local pain, and nine (17%) developed a subcutaneous haematoma; however, these adverse events were transient and did not need treatment. INTERPRETATION: Our findings suggest that, in patients with IRBD, submandibular gland biopsy is a safe procedure for the detection of αSyn aggregates. αSyn detection could be useful for histological confirmation in individuals clinically diagnosed with Parkinson's disease. FUNDING: Centre for Networked Biomedical Research in Neurodegenerative Disorders (CIBERNED), Barcelona, Spain.

10 Article Loss of dorsolateral nigral hyperintensity on 3.0 tesla susceptibility-weighted imaging in idiopathic rapid eye movement sleep behavior disorder. 2016

De Marzi, Roberto / Seppi, Klaus / Högl, Birgit / Müller, Christoph / Scherfler, Christoph / Stefani, Ambra / Iranzo, Alex / Tolosa, Eduardo / Santamarìa, Joan / Gizewski, Elke / Schocke, Michael / Skalla, Elisabeth / Kremser, Christian / Poewe, Werner. ·Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria. · Neurology Service, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Department of Radiology, Medical University Innsbruck, Innsbruck, Austria. ·Ann Neurol · Pubmed #27016314.

ABSTRACT: We assessed loss of dorsolateral nigral hyperintensity (DNH) on high-field susceptibility-weighted imaging (SWI), a novel magnetic resonance imaging marker for Parkinson's disease (PD), in 15 subjects with idiopathic rapid eye movement sleep behavior disorder (iRBD) and compared findings to 42 healthy controls (HCs) and 104 PD patients. We found loss of DNH in at least two thirds of iRBD subjects, which approaches the rate observed in PD and is in contrast to findings in HCs. We propose that absence of DNH on high-field SWI could identify prodromal degenerative parkinsonism in iRBD. Ann Neurol 2016;79:1026-1030.

11 Article Sleep Disorders in Parkinsonian and Nonparkinsonian LRRK2 Mutation Carriers. 2015

Pont-Sunyer, Claustre / Iranzo, Alex / Gaig, Carles / Fernández-Arcos, Ana / Vilas, Dolores / Valldeoriola, Francesc / Compta, Yaroslau / Fernández-Santiago, Ruben / Fernández, Manel / Bayés, Angels / Calopa, Matilde / Casquero, Pilar / de Fàbregues, Oriol / Jaumà, Serge / Puente, Victor / Salamero, Manel / José Martí, Maria / Santamaría, Joan / Tolosa, Eduard. ·Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. · MultidisciplinarySleepDisordersUnit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. · Laboratory of Neurodegenerative Disorders, Department of Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Universitat de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. · Unidad de Parkinson Teknon, Barcelona, Spain. · NeurologyService, Hospital Universitari de Bellvitge, Barcelona, Spain. · Hospital Mateu Orfila, Maó, Menorca, Spain. · Neurology Service, Hospital Universitari Vall D'Hebron, Barcelona, Spain. · Neurology Service, Hospital Del Mar, Barcelona, Spain. · PsychologyService, Hospital Clinic,Barcelona, Spain. ·PLoS One · Pubmed #26177462.

ABSTRACT: OBJECTIVE: In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC). METHODS: A comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD. RESULTS: Sleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC. CONCLUSIONS: Sleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD.

12 Article Prevalence and timeline of nonmotor symptoms in idiopathic rapid eye movement sleep behavior disorder. 2015

Aguirre-Mardones, Carolina / Iranzo, Alex / Vilas, Dolores / Serradell, Mónica / Gaig, Carles / Santamaría, Joan / Tolosa, Eduardo. ·Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, C/Villarroel 170, 08036, Barcelona, Spain. ·J Neurol · Pubmed #25929658.

ABSTRACT: Parkinson disease (PD) patients may experience nonmotor symptoms (NMS) before Parkinsonism onset. Patients with idiopathic REM sleep behavior disorder (IRBD) eventually develop PD and may represent premotor PD. We aimed to evaluate the prevalence and perceived timeline of NMS in IRBD through validated scales and questionnaires used in PD research. In 44 IRBD patients and 40 matched controls, overall NMS evaluation was assessed by NMS questionnaire for Parkinson disease, olfaction by University of Pennsylvania Smell Identification Test, dysautonomia by scales for outcomes in Parkinson's disease-autonomic, constipation by Rome III criteria, depression by Hospital Anxiety and Depression Scale, cognitive impairment by Montreal cognitive assessment (MoCA) and hypersomnia by Epworth Sleepiness Scale. Patients were asked to report the perceived time of onset of hyposmia, constipation, and depression. Hyposmia (52.3 vs. 20.0 %, p = 0.002) and constipation (56.8 vs. 20.0 %, p = 0.001) were more frequent in patients than in controls. Patients reported more memory problems and showed a trend toward lower score in MoCA. Depression and hypersomnia were not more frequent in patients. The first symptom perceived was RBD in 38.6 % patients, hyposmia in 15.9 %, constipation in 11.4 %, and depression in 6.8 %. The temporal course of the NMS studied was heterogeneous. The three most common presentations were RBD followed by hyposmia; hyposmia followed by RBD; and hyposmia followed by RBD and constipation occurring at the same time span. IRBD patients frequently exhibit NMS that occur in premotor PD, particularly hyposmia and constipation. In IRBD, the perceived timeline of NMS is highly variable. This variability may suggest that pathological changes occurring in IRBD subjects are also heterogeneous and not restricted to the structures that regulate REM sleep.

13 Article Correlates of cerebrospinal fluid levels of oligomeric- and total-α-synuclein in premotor, motor and dementia stages of Parkinson's disease. 2015

Compta, Yaroslau / Valente, Tony / Saura, Josep / Segura, Bàrbara / Iranzo, Álex / Serradell, Mònica / Junqué, Carme / Tolosa, Eduard / Valldeoriola, Francesc / Muñoz, Esteban / Santamaria, Joan / Cámara, Ana / Fernández, Manel / Fortea, Juan / Buongiorno, Mariateresa / Molinuevo, José Luis / Bargalló, Núria / Martí, María José. ·Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, IDIBAPS, CIBERNED, Hospital Clínic, University of Barcelona, 170 Villarroel, 08036, Barcelona, Catalonia, Spain. ·J Neurol · Pubmed #25380583.

ABSTRACT: High-oligomeric and low-total-α-synuclein cerebrospinal fluid (CSF) levels have been found in Parkinson's disease (PD), but with inconsistent or limited data, particularly on their clinical and structural correlates in earliest (premotor) or latest (dementia) PD stages. We determined CSF oligomeric- and total-α-synuclein in 77 subjects: 23 with idiopathic REM-sleep behaviour disorder (iRBD, a condition likely to include a remarkable proportion of subjects in the premotor stage of PD) and 41 with PD [21 non-demented (PDND) + 20 demented (PDD)], intended to reflect the premotor-motor-dementia PD continuum, along with 13 healthy controls. The study protocol also included the Unified PD Rating Scale motor-section (UPDRS-III), mini mental state examination (MMSE), neuropsychological cognitive testing, 3T brain MRI for cortical-thickness analyses, CSF τ and CSF Aβ. CSF oligomeric-α-synuclein was higher in PDND than iRBD and in PDD than iRBD and controls, and correlated with UPDRS-III, MMSE, semantic fluency and visuo-perceptive scores across the proposed premotor-motor-dementia PD continuum (iRBD + PDND + PDD). CSF total-α-synuclein positively correlated with age, CSF Aβ, and, particularly, CSF τ, tending towards lower levels in PD (but not iRBD) vs. controls only when controlling for CSF τ. Low CSF total-α-synuclein was associated with dysfunction in phonetic-fluency (a frontal-lobe function) in PD and with frontal cortical thinning in iRBD and PDND independently of CSF τ. Conversely, the associations of high (instead of low) CSF total-α-synuclein with posterior-cortical neuropsychological deficits in PD and with posterior cortical thinning in PDD were driven by high CSF τ. These findings suggest that CSF oligomeric- and total-α-synuclein have different clinical, neuropsychological and MRI correlates across the proposed premotor-motor-dementia PD continuum. CSF total-α-synuclein correlations with CSF τ and Aβ support the hypothesis of an interaction among these proteins in PD, with CSF τ probably influencing the presence of high (instead of low) CSF total-α-synuclein and its correlates mostly in the setting of PD-related dementia.

14 Article Five-year follow-up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder. 2014

Iranzo, Alex / Stockner, Heike / Serradell, Mónica / Seppi, Klaus / Valldeoriola, Francesc / Frauscher, Birgit / Molinuevo, José Luis / Vilaseca, Isabel / Mitterling, Thomas / Gaig, Carles / Vilas, Dolores / Santamaria, Joan / Högl, Birgit / Tolosa, Eduard / Poewe, Werner. ·Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. ·Mov Disord · Pubmed #25384461.

ABSTRACT: Hyperechogenicity of the substantia nigra visualized by transcranial sonography occurs in most Parkinson's disease (PD) patients. Idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) subjects eventually develop PD and other synucleinopathies. This study was undertaken to evaluate whether in IRBD, transcranial sonography identifies subjects who convert to PD and other synucleinopathies, and whether substantia nigra echogenic size changes with time. It was a prospective study in which 55 IRBD patients underwent transcranial sonography at baseline and were invited to follow-up after 5 years. Patients were assessed by the same experienced sonographer who was blinded to clinical data and baseline transcranial sonography results, and used the same equipment and adjustments. Twenty-one (38.2%) subjects were diagnosed with a synucleinopathy (PD in 11, dementia with Lewy bodies in nine, and multiple system atrophy in one). Sensitivity of baseline substantia nigra hyperechogenicity for the development of a synucleinopathy was 42.1%, specificity 67.7%, positive predictive value 44.4%, negative predictive value 65.6%, and relative risk 1.29. No differences were detected between the first and second examination in mean size of the substantia nigra (0.20 ± 0.09 cm(2) vs. 0.19 ± 0.07 cm(2) ; P = 0.777) and in percentage of patients with substantia nigra hyperechogenicity (33.3% vs. 42.8%, P = 0.125). Transcranial sonography of the substantia nigra alone is not a useful tool to identify IRBD subjects at risk for the development of PD or a synucleinopathy after 5 years of follow-up. In IRBD, transcranial sonography cannot be used to monitor the degenerative process in the substantia nigra, because echogenicity size remains stable over time.

15 Article Neuropathology of prodromal Lewy body disease. 2014

Iranzo, Alex / Gelpi, Ellen / Tolosa, Eduard / Molinuevo, José Luis / Serradell, Mónica / Gaig, Carles / Santamaria, Joan. ·Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacións Biomédiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. ·Mov Disord · Pubmed #24488760.

ABSTRACT: BACKGROUND: Current evidence suggests that there is a prodromal stage in Parkinson disease characterized by a variety of nonmotor symptoms. METHODS AND RESULTS: A 69-year-old man presented to our sleep center with isolated rapid eye movement sleep behavior disorder. During a 10-year follow-up period, longitudinal clinical and laboratory assessments indicated the development of hyposmia, depression, mild cognitive impairment, and constipation. Parkinsonism was absent, but dopamine transporter imaging showed subclinical substantia nigra damage. Postmortem examination demonstrated neuronal loss and Lewy body pathology in the peripheral autonomic nervous system (eg, cardiac and myenteric plexus), olfactory bulb, medulla, pons, substantia nigra pars compacta (estimated cell loss, 20%-30%), nucleus basalis of Meynert, and amygdala, sparing the neocortex. CONCLUSIONS: Our observations indicate that nonmotor symptoms plus widespread peripheral and central nervous system pathological changes occur before parkinsonism and dementia onset in diseases associated with Lewy pathology. The current diagnostic criteria for Parkinson's disease miss these patients, who present only with nonmotor symptoms.

16 Article Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study). 2011

Moreno-López, Claudia / Santamaría, Joan / Salamero, Manuel / Del Sorbo, Francesca / Albanese, Alberto / Pellecchia, Maria Teresa / Barone, Paolo / Overeem, Sebastiaan / Bloem, Bastiaan / Aarden, Willemijn / Canesi, Margherita / Antonini, Angelo / Duerr, Susanne / Wenning, Gregor K / Poewe, Werner / Rubino, Alfonso / Meco, Giuseppe / Schneider, Susanne A / Bhatia, Kailash P / Djaldetti, Ruth / Coelho, Miguel / Sampaio, Cristina / Cochen, Valerie / Hellriegel, Helge / Deuschl, Günther / Colosimo, Carlo / Marsili, Luca / Gasser, Thomas / Tolosa, Eduardo. ·Movement Disorders Unit, Department of Neurology, Hospital Clinic of Barcelona, University of Barcelona Medical School and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, 08036 Barcelona, Spain. ·Arch Neurol · Pubmed #21320989.

ABSTRACT: BACKGROUND: Sleep disorders are common in multiple system atrophy (MSA), but the prevalence of excessive daytime sleepiness (EDS) is not well known. OBJECTIVE: To assess the frequency and associations of EDS in MSA. DESIGN: Survey of EDS in consecutive patients with MSA and comparison with patients with Parkinson disease (PD) and individuals without known neurologic disease. SETTING: Twelve tertiary referral centers. PARTICIPANTS: Eighty-six consecutive patients with MSA; 86 patients with PD matched for age, sex, and Hoehn and Yahr stage; and 86 healthy subject individuals matched for age and sex. MAIN OUTCOME MEASURES: Epworth Sleepiness Scale (ESS), modified ESS, Sudden Onset of Sleep Scale, Tandberg Sleepiness Scale, Pittsburgh Sleep Quality Index, disease severity, dopaminergic treatment amount, and presence of restless legs syndrome. RESULTS: Mean (SD) ESS scores were comparable in MSA (7.72 [5.05]) and PD (8.23 [4.62]) but were higher than in healthy subjects (4.52 [2.98]) (P < .001). Excessive daytime sleepiness (ESS score >10) was present in 28% of patients with MSA, 29% of patients with PD, and 2% of healthy subjects (P < .001). In MSA, in contrast to PD, the amount of dopaminergic treatment was not correlated with EDS. Disease severity was weakly correlated with EDS in MSA and PD. Restless legs syndrome occurred in 28% of patients with MSA, 14% of patients with PD, and 7% of healthy subjects (P < .001). Multiple regression analysis (with 95% confidence intervals obtained using nonparametric bootstrapping) showed that sleep-disordered breathing and sleep efficiency predicted EDS in MSA and amount of dopaminergic treatment and presence of restless legs syndrome in PD. CONCLUSIONS: More than one-quarter of patients with MSA experience EDS, a frequency similar to that encountered in PD. In these 2 conditions, EDS seems to be associated with different causes.

17 Minor Need for a consensus on definitions and on research methods in RBD and its prodromal phases. 2019

Stefani, Ambra / Iranzo, Alex / Sixel-Döring, Friederike / Videnovic, Aleksandar / Santamaria, Joan / Trenkwalder, Claudia / Högl, Birgit. ·Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. · Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Paracelsus-Elena Klinik, Kassel, Germany. · Department of Neurology, Philipps-University Marburg, Germany. · Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of Neurosurgery, University Medical Center, Göttingen, Germany. ·Sleep · Pubmed #31091537.

ABSTRACT: -- No abstract --

18 Minor Caveats of Neurodegenerative Risk Stratification in Idiopathic REM Sleep Behavior Disorder by Use of the MDS Research for Prodromal Parkinson's Disease. 2017

Mahlknecht, Philipp / Iranzo, Alex / Stefani, Ambra / Serradell, Monica / Santamaria, Joan / Tolosa, Eduardo / Högl, Birgit / Poewe, Werner. ·Department of Neurology, Medical University of Innsbruck, Austria. · Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. ·Sleep · Pubmed #28958020.

ABSTRACT: -- No abstract --