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1. A simple EEG-based decision tool for neonatal therapeutic hypothermia in hypoxic-ischemic encephalopathy

Author

Fiammante, Marc, Vermersch, Anne-Isabelle, Vidailhet, Marie, and Chavez, Mario

Subjects
Quantitative Biology - Neurons and Cognition
Abstract

Indication of therapeutic hypothermia needs an accurate identification of brain injury in the early neonatal period. Here, we aim to provide a simple hypothermia decision-making tool for the term neonates with hypoxic-ischemic encephalopathy (HIE) based on features of conventional electroencephalogram (EEG) taken less than 6 hours from birth. EEG recordings from one hundred full-term babies with HIE were included in the study. Each EEG recording was graded by pediatric neurologists for HIE severity. Amplitude of each EEG segment was analyzed in the slow frequency bands. Temporal fluctuations of spectral power in delta (0.5 - 4 Hz) frequency band was used to characterize each HIE grade. For each grade of abnormality, we estimated level and duration (number of consecutive segments above a given level) probability densities for power of delta oscillations. These 2D representation of EEG dynamics can identify mild HIE group from those of requiring hypothermia. Our discrimination system yielded an accuracy, recall, positive predictive value (precision), negative predictive value, false alarm ratio and F1-score of 98%, 99%, 99%, 0.94%, 0.06 and 99%, respectively. These results provided an accurate discrimination of mild versus moderate or severe HIE, and only one mild case was erroneously detected as relevant for hypothermia. Quantized probability densities of slow spectral features (delta power) from early conventional EEG (withing 6 hours of birth) revealed significant differences in slow spectral dynamics between infants with mild HIE grades and those relevant for hypothermia., Comment: 20 pages, 1 table, 2 figures

Published
2024

2. Psychiatric phenotype in neurodevelopmental myoclonus-dystonia is underpinned by abnormality of cerebellar modulation on the cerebral cortex

Author

Tarrano, Clément, Galléa, Cécile, Delorme, Cécile, McGovern, Eavan M., Atkinson-Clement, Cyril, Brochard, Vanessa, Thobois, Stéphane, Tranchant, Christine, Grabli, David, Degos, Bertrand, Corvol, Jean Christophe, Pedespan, Jean-Michel, Krystkowiak, Pierre, Houeto, Jean-Luc, Degardin, Adrian, Defebvre, Luc, Beranger, Benoit, Martino, Davide, Apartis, Emmanuelle, Vidailhet, Marie, Roze, Emmanuel, and Worbe, Yulia

Published
2024
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4. Genotype–phenotype correlation in PRKN-associated Parkinson’s disease

Author

Menon, Poornima Jayadev, Sambin, Sara, Criniere-Boizet, Baptiste, Courtin, Thomas, Tesson, Christelle, Casse, Fanny, Ferrien, Melanie, Mariani, Louise-Laure, Carvalho, Stephanie, Lejeune, Francois-Xavier, Rebbah, Sana, Martet, Gaspard, Houot, Marion, Lanore, Aymeric, Mangone, Graziella, Roze, Emmanuel, Vidailhet, Marie, Aasly, Jan, Gan Or, Ziv, Yu, Eric, Dauvilliers, Yves, Zimprich, Alexander, Tomantschger, Volker, Pirker, Walter, Álvarez, Ignacio, Pastor, Pau, Di Fonzo, Alessio, Bhatia, Kailash P., Magrinelli, Francesca, Houlden, Henry, Real, Raquel, Quattrone, Andrea, Limousin, Patricia, Korlipara, Prasad, Foltynie, Thomas, Grosset, Donald, Williams, Nigel, Narendra, Derek, Lin, Hsin-Pin, Jovanovic, Carna, Svetel, Marina, Lynch, Timothy, Gallagher, Amy, Vandenberghe, Wim, Gasser, Thomas, Brockmann, Kathrin, Morris, Huw R., Borsche, Max, Klein, Christine, Corti, Olga, Brice, Alexis, Lesage, Suzanne, and Corvol, Jean Christophe

Published
2024
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6. Isolated parkinsonism is an atypical presentation of GRN and C9orf72 gene mutations

Author

Carneiro, Fábio, Saracino, Dario, Huin, Vincent, Clot, Fabienne, Delorme, Cécile, Méneret, Aurélie, Thobois, Stéphane, Cormier, Florence, Corvol, Jean Christophe, Lenglet, Timothée, Vidailhet, Marie, Habert, Marie-Odile, Gabelle, Audrey, Beaufils, Émilie, Mondon, Karl, Tir, Mélissa, Andriuta, Daniela, Brice, Alexis, Deramecourt, Vincent, and Ber, Isabelle Le

Subjects
Quantitative Biology - Neurons and Cognition
Abstract

Introduction: A phenotype of isolated parkinsonism mimicking Idiopathic Parkinson's Disease (IPD) is a rare clinical presentation of GRN and C9orf72 mutations, the major genetic causes of frontotemporal dementia (FTD). It still remains controversial if this association is fortuitous or not, and which clinical clues could reliably suggest a genetic FTD etiology in IPD patients. This study aims to describe the clinical characteristics of FTD mutation carriers presenting with IPD phenotype, provide neuropathological evidence of the mutation's causality, and specifically address their "red flags" according to current IPD criteria. Methods: Seven GRN and C9orf72 carriers with isolated parkinsonism at onset, and three patients from the literature were included in this study. To allow better delineation of their phenotype, the presence of supportive, exclusion and "red flag" features from MDS criteria were analyzed for each case. Results: Amongst the ten patients (5 GRN, 5 C9orf72), seven fulfilled probable IPD criteria during all the disease course, while behavioral/language or motoneuron dysfunctions occurred later in three. Disease duration was longer and dopa-responsiveness was more sustained in C9orf72 than in GRN carriers. Subtle motor features, cognitive/behavioral changes, family history of dementia/ALS were suggestive clues for a genetic diagnosis. Importantly, neuropathological examination in one patient revealed typical TDP-43-inclusions without alpha-synucleinopathy, thus demonstrating the causal link between FTD mutations, TDP-43-pathology and PD phenotype. Conclusion: We showed that, altogether, family history of early-onset dementia/ALS, the presence of cognitive/behavioral dysfunction and subtle motor characteristics are atypical features frequently present in the parkinsonian presentations of GRN and C9orf72 mutations .

Published
2022
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8. Sustained reduction of essential tremor with low-power non-thermal transcranial focused ultrasound stimulations in humans

Author

Bancel, Thomas, Béranger, Benoît, Daniel, Maxime, Didier, Mélanie, Santin, Mathieu, Rachmilevitch, Itay, Shapira, Yeruham, Tanter, Mickael, Bardinet, Eric, Fernandez Vidal, Sara, Attali, David, Galléa, Cécile, Dizeux, Alexandre, Vidailhet, Marie, Lehéricy, Stéphane, Grabli, David, Pyatigorskaya, Nadya, Karachi, Carine, Hainque, Elodie, and Aubry, Jean-François

Published
2024
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9. X-vectors: New Quantitative Biomarkers for Early Parkinson's Disease Detection from Speech

Author

Jeancolas, Laetitia, Petrovska-Delacrétaz, Dijana, Mangone, Graziella, Benkelfat, Badr-Eddine, Corvol, Jean-Christophe, Vidailhet, Marie, Lehéricy, Stéphane, and Benali, Habib

Subjects
Electrical Engineering and Systems Science - Audio and Speech Processing, Computer Science - Sound, Quantitative Biology - Quantitative Methods
Abstract

Many articles have used voice analysis to detect Parkinson's disease (PD), but few have focused on the early stages of the disease and the gender effect. In this article, we have adapted the latest speaker recognition system, called x-vectors, in order to detect an early stage of PD from voice analysis. X-vectors are embeddings extracted from a deep neural network, which provide robust speaker representations and improve speaker recognition when large amounts of training data are used. Our goal was to assess whether, in the context of early PD detection, this technique would outperform the more standard classifier MFCC-GMM (Mel-Frequency Cepstral Coefficients - Gaussian Mixture Model) and, if so, under which conditions. We recorded 221 French speakers (including recently diagnosed PD subjects and healthy controls) with a high-quality microphone and with their own telephone. Men and women were analyzed separately in order to have more precise models and to assess a possible gender effect. Several experimental and methodological aspects were tested in order to analyze their impacts on classification performance. We assessed the impact of audio segment duration, data augmentation, type of dataset used for the neural network training, kind of speech tasks, and back-end analyses. X-vectors technique provided better classification performances than MFCC-GMM for text-independent tasks, and seemed to be particularly suited for the early detection of PD in women (7 to 15% improvement). This result was observed for both recording types (high-quality microphone and telephone)., Comment: Submitted

Published
2020
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12. Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson's disease

Author

Khedher, Laila, Bonny, Jean-Marie, Marques, Ana, Durand, Elodie, Pereira, Bruno, Chupin, Marie, Vidal, Tiphaine, Chassain, Carine, Defebvre, Luc, Carriere, Nicolas, Fraix, Valerie, Moro, Elena, Thobois, Stéphane, Metereau, Elise, Mangone, Graziella, Vidailhet, Marie, Corvol, Jean-Christophe, Lehéricy, Stéphane, Menjot de Champfleur, Nicolas, Geny, Christian, Spampinato, Umberto, Meissner, Wassilios, Frismand, Solène, Schmitt, Emmanuelle, Doé de Maindreville, Anne, Portefaix, Christophe, Remy, Philippe, Fénelon, Gilles, Luc Houeto, Jean, Colin, Olivier, Rascol, Olivier, Peran, Patrice, and Durif, Franck

Published
2022
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13. Primary brain calcification: an international study reporting novel variants and associated phenotypes.

Author

Ramos, Eliana Marisa, Carecchio, Miryam, Lemos, Roberta, Ferreira, Joana, Legati, Andrea, Sears, Renee Louise, Hsu, Sandy Chan, Panteghini, Celeste, Magistrelli, Luca, Salsano, Ettore, Esposito, Silvia, Taroni, Franco, Richard, Anne-Claire, Tranchant, Christine, Anheim, Mathieu, Ayrignac, Xavier, Goizet, Cyril, Vidailhet, Marie, Maltete, David, Wallon, David, Frebourg, Thierry, Pimentel, Lylyan, Geschwind, Daniel H, Vanakker, Olivier, Galasko, Douglas, Fogel, Brent L, Innes, A Micheil, Ross, Alison, Dobyns, William B, Alcantara, Diana, O'Driscoll, Mark, Hannequin, Didier, Campion, Dominique, French PFBC study group, Oliveira, João R, Garavaglia, Barbara, Coppola, Giovanni, and Nicolas, Gaël

Subjects
French PFBC study group, Humans, Brain Diseases, Calcinosis, Receptor, Platelet-Derived Growth Factor beta, Proto-Oncogene Proteins c-sis, Receptors, G-Protein-Coupled, Receptors, Virus, Pedigree, Heterozygote, Phenotype, Mutation, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Female, Male, Sodium-Phosphate Cotransporter Proteins, Type III, Genetic Variation, Young Adult, Cognitive Dysfunction, Receptor, Platelet-Derived Growth Factor beta, Receptors, G-Protein-Coupled, Virus, and over, Sodium-Phosphate Cotransporter Proteins, Type III, Genetics, Genetics & Heredity, Clinical Sciences
Abstract

Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (n = 34, 19.2%) or VUS (n = 11, 6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic.

Published
2018

14. Association of abnormal explicit sense of agency with cerebellar impairment in myoclonus-dystonia

Author

Tarrano, Clément, primary, Galléa, Cécile, additional, Delorme, Cécile, additional, McGovern, Eavan M, additional, Atkinson-Clement, Cyril, additional, Jarratt Barnham, Isaac, additional, Brochard, Vanessa, additional, Thobois, Stéphane, additional, Tranchant, Christine, additional, Grabli, David, additional, Degos, Bertrand, additional, Corvol, Jean Christophe, additional, Pedespan, Jean-Michel, additional, Krystkowiak, Pierre, additional, Houeto, Jean-Luc, additional, Degardin, Adrian, additional, Defebvre, Luc, additional, Valabrègue, Romain, additional, Beranger, Benoit, additional, Apartis, Emmanuelle, additional, Vidailhet, Marie, additional, Roze, Emmanuel, additional, and Worbe, Yulia, additional

Published
2024
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15. Clinical and demographic characteristics related to onset site and spread of cervical dystonia.

Author

Norris, Scott A, Jinnah, HA, Espay, Alberto J, Klein, Christine, Brüggemann, Norbert, Barbano, Richard L, Malaty, Irene Andonia C, Rodriguez, Ramon L, Vidailhet, Marie, Roze, Emmanuel, Reich, Stephen G, Berman, Brian D, LeDoux, Mark S, Richardson, Sarah Pirio, Agarwal, Pinky, Mari, Zoltan, Ondo, William G, Shih, Ludy C, Fox, Susan H, Berardelli, Alfredo, Testa, Claudia M, Cheng, Florence Ching-Fen, Truong, Daniel, Nahab, Fatta B, Xie, Tao, Hallett, Mark, Rosen, Ami R, Wright, Laura J, and Perlmutter, Joel S

Subjects
Humans, Torticollis, Databases, Factual, Adult, Aged, Middle Aged, Female, Male, focal, geste antagoniste, neck, segmental, spasmodic torticollis, Databases, Factual, Neurology & Neurosurgery, Clinical Sciences, Human Movement and Sports Sciences, Cognitive Sciences, Neurosciences
Abstract

BackgroundClinical characteristics of isolated idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. The objectives of this study were to characterize the clinical characteristics and demographics of isolated idiopathic cervical dystonia in the largest standardized multicenter cohort.MethodsThe Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe, and Australia, recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread.ResultsSite of dystonia onset was: (1) focal neck only (78.5%), (2) focal onset elsewhere with later segmental spread to neck (13.3%), and (3) segmental onset with initial neck involvement (8.2%). Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than the 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, was associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age.ConclusionsSubgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. © 2016 International Parkinson and Movement Disorder Society.

Published
2016

17. Lessons from multitarget neurostimulation in isolated dystonia: Less is more?

Author

Cuartero, Marie-Charlotte, primary, Grabli, David, additional, Flamand-Roze, Emmanuel, additional, Karachi, Carine, additional, Rouaud, Tiphaine, additional, Derkinderen, Pascal, additional, Damier, Philippe, additional, Raoul, Sylvie, additional, Krack, Paul, additional, Moro, Elena, additional, Fraix, Valérie, additional, Chabardès, Stéphan, additional, Burbaud, Pierre, additional, Guehl, Dominique, additional, Cuny, Emmanuel, additional, Pinto, Serge, additional, and Vidailhet, Marie, additional

Published
2024
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18. Long-term effect of apomorphine infusion in advanced Parkinson’s disease: a real-life study

Author

Meira, Bruna, Degos, Bertrand, Corsetti, Elise, Doulazmi, Mohamed, Berthelot, Emeline, Virbel-Fleischman, Clara, Dodet, Pauline, Méneret, Aurélie, Mariani, Louise-Laure, Delorme, Cécile, Cormier-Dequaire, Florence, Bendetowicz, David, Villain, Nicolas, Tarrano, Clément, Mantisi, Lise, Letrillart, Hélène, Louapre, Céline, McGovern, Eavan, Worbe, Yulia, Grabli, David, Vidailhet, Marie, Hainque, Elodie, and Roze, Emmanuel

Published
2021
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19. A framework for quantifying the coupling between brain connectivity and heartbeat dynamics: Insights into the disrupted network physiology in Parkinson's disease.

Author

Candia‐Rivera, Diego, Vidailhet, Marie, Chavez, Mario, and De Vico Fallani, Fabrizio

Subjects
*PARKINSON'S disease, *COUPLINGS (Gearing), *DYSAUTONOMIA, *DOPAMINE agents, *PHYSIOLOGY, *MOVEMENT disorders
Abstract

Parkinson's disease (PD) often shows disrupted brain connectivity and autonomic dysfunctions, progressing alongside with motor and cognitive decline. Recently, PD has been linked to a reduced sensitivity to cardiac inputs, that is, cardiac interoception. Altogether, those signs suggest that PD causes an altered brain–heart connection whose mechanisms remain unclear. Our study aimed to explore the large‐scale network disruptions and the neurophysiology of disrupted interoceptive mechanisms in PD. We focused on examining the alterations in brain–heart coupling in PD and their potential connection to motor symptoms. We developed a proof‐of‐concept method to quantify relationships between the co‐fluctuations of brain connectivity and cardiac sympathetic and parasympathetic activities. We quantified the brain–heart couplings from electroencephalogram and electrocardiogram recordings from PD patients on and off dopaminergic medication, as well as in healthy individuals at rest. Our results show that the couplings of fluctuating alpha and gamma connectivity with cardiac sympathetic dynamics are reduced in PD patients, as compared to healthy individuals. Furthermore, we show that PD patients under dopamine medication recover part of the brain–heart coupling, in proportion with the reduced motor symptoms. Our proposal offers a promising approach to unveil the physiopathology of PD and promoting the development of new evaluation methods for the early stages of the disease. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Non-motor symptoms in dystonia: from diagnosis to treatment

Author

Peall, Kathryn J., primary, Berman, Brian D., additional, Bruggemann, Norbert, additional, Defazio, Giovanni, additional, Gimeno, Hortensia, additional, Jinnah, H. A., additional, Perlmutter, Joel S., additional, Richardson, Sarah E. Pirio, additional, Roze, Emmanuel, additional, Schrag, Anette, additional, Tinazzi, Michele, additional, Vidailhet, Marie, additional, Wagle Shukla, Aparna, additional, Worbe, Yulia, additional, Teller, Jan K., additional, and Martino, Davide, additional

Published
2023
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21. PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

Author

Fevga, Christina, Tesson, Christelle, Carreras Mascaro, Ana, Courtin, Thomas, Van Coller, Riaan, Sakka, Salma, Ferraro, Federico, Farhat, Nouha, Bardien, Soraya, Damak, Mariem, Carr, Jonathan, Ferrien, Melanie, Boumeester, Valerie, Hundscheid, Jasmijn, Grillenzoni, Nicola, Kessissoglou, Irini A., Kuipers, Demy J.S., Quadri, Marialuisa, Agid, Yves, Anheim, Mathieu, Borg, Michel, Brice, Alexis, Broussolle, Emmanuel, Corvol, Jean Christophe, Damier, Philippe, Defebvre, Luc, Dürr, Alexandra, Durif, Franck, Houeto, Jean Luc, Krack, Paul, Klebe, Stephan, Lesage, Suzanne, Lohmann, Ebba, Martinez, Maria, Mangone, Graziella, Mariani, Louise Laure, Pollak, Pierre, Rascol, Olivier, Tison, François, Tranchant, Christine, Verin, Marc, Viallet, François, Vidailhet, Marie, Emre, Murat, Hanagasi, Hasmet, Bilgic, Basar, Lu, Bedia Marangozog, Benmahdjoub, Mustapha, Arezki, Mohammed, Bouchetara, Sofiane A., Benhassine, Traki, Tazir, Meriem, Djebara, Mouna Ben, Gouider, Riadh, Romdhan, Sawssan Ben, Mhiri, Chokri, Bouhouche, Ahmed, Bonifati, Vincenzo, Mandemakers, Wim, Kievit, Anneke J.A., Boon, Agnita J.W., Ferreira, Joaquim J., Guedes, Leonor Correia, Hanagasi, Hasmet A., Tufekcioglu, Zeynep, Elibol, Bulent, Dog.u, Okan, Gultekin, Murat, Chien, Hsin F., Barbosa, Egberto, Jardim, Laura Bannach, Rieder, Carlos R.M., Chang, Hsiu Chen, Lu, Chin Song, Wu-Chou, Yah Huei, Yeh, Tu Hsueh, Lopiano, Leonardo, Tassorelli, Cristina, Pacchetti, Claudio, Comi, Cristoforo, Raudino, Francesco, Bertolasi, Laura, Tinazzi, Michele, Bonizzato, Alberto, Ferracci, Carlo, Marconi, Roberto, Guidi, Marco, Onofrj, Marco, Thomas, Astrid, Vanacore, Nicola, Meco, Giuseppe, Fabrizio, Edito, Fabbrini, Giovanni, Berardelli, Alfredo, Stocchi, Fabrizio, Vacca, Laura, Barone, Paolo, Picillo, Marina, De Michele, Giuseppe, Criscuolo, Chiara, De Mari, Michele, Dell'aquila, Claudia, Iliceto, Giovanni, Toni, Vincenzo, Trianni, Giorgio, Saddi, Valeria, Cossu, Gianni, Melis, Maurizio, Hassan, Bassem A., Breedveld, Guido J., Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Faculty of Health Sciences [Pretoria], University of Pretoria [South Africa], Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax], Stellenbosch University, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Motivation, cerveau et comportement = Motivation, Brain and Behavior [ICM Paris] (MBB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Tesson, Christelle, Clinical Genetics, and Neurology

Subjects
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, intellectual disability, PTPA, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], PPP2R4, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, parkinsonism, PP2A
Abstract

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T>G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C>A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.

Published
2023

22. Criteria for the diagnosis of corticobasal degeneration

Author

Armstrong, Melissa J, Litvan, Irene, Lang, Anthony E, Bak, Thomas H, Bhatia, Kailash P, Borroni, Barbara, Boxer, Adam L, Dickson, Dennis W, Grossman, Murray, Hallett, Mark, Josephs, Keith A, Kertesz, Andrew, Lee, Suzee E, Miller, Bruce L, Reich, Stephen G, Riley, David E, Tolosa, Eduardo, Tröster, Alexander I, Vidailhet, Marie, and Weiner, William J

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Aging, Frontotemporal Dementia (FTD), Dementia, Brain Disorders, Neurodegenerative, Rare Diseases, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Neurological, Age of Onset, Aged, Basal Ganglia, Cerebral Cortex, Cognition Disorders, Databases, Factual, Family Health, Female, Humans, Language Disorders, Male, Middle Aged, Neurodegenerative Diseases, Neurologic Examination, Phenotype, Retrospective Studies, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ≥ 50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed.

Published
2013

23. Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia

Author

Atkinson-Clement, Cyril, Tarrano, Clement, Porte, Camille-Albane, Wattiez, Nicolas, Delorme, Cécile, McGovern, Eavan M., Brochard, Vanessa, Thobois, Stéphane, Tranchant, Christine, Grabli, David, Degos, Bertrand, Corvol, Jean-Christophe, Pedespan, Jean-Michel, Krystkoviak, Pierre, Houeto, Jean-Luc, Degardin, Adrian, Defebvre, Luc, Valabregue, Romain, Rosso, Charlotte, Apartis, Emmanuelle, Vidailhet, Marie, Pouget, Pierre, Roze, Emmanuel, and Worbe, Yulia

Published
2020
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24. Hypersomnia in anti‐glutamic acid decarboxylase 65 (GAD65) associated neurological syndromes: A pilot study.

Author

Jeantin, Lina, Gales, Ana, Berzero, Giulia, Leu, Smaranda, Proust, Jérémy, Giry, Marine, Valyraki, Nefeli Eirini, Birzu, Cristina, Alentorn, Agusti, Vidailhet, Marie, Psimaras, Dimitri, and Arnulf, Isabelle

Subjects
HYPERSOMNIA, SLEEP duration, SLEEP latency, STIFF-person syndrome, SLEEP disorders, SYNDROMES
Abstract

Background and purpose: Despite their detrimental impact on the quality of life in autoimmune encephalitis, sleep disorders have not been investigated in anti‐glutamic acid decarboxylase (GAD65) associated neurological syndromes. Methods: Six consecutive adult patients diagnosed with anti‐GAD65‐associated neurological syndromes (four with limbic encephalitis and two with stiff‐person syndrome) and 12 healthy controls were enrolled. Participants underwent sleep interviews and sleep studies including night‐time video‐polysomnography, followed by five daytime multiple sleep latency tests (MSLTs, to assess propensity to fall asleep) and an 18 h bed rest polysomnography (to assess excessive sleep need). Results: Patients reported the need for daily naps and that their cognition and quality of life were altered by sleepiness, but they had normal scores on the Epworth sleepiness scale. Compared with controls, sleep latencies during the MSLT were shorter in the patient group (median 5.8 min, interquartile range [IQR] 4.5, 6.0 vs. 17.7 min, IQR 16.3, 19.7, p = 0.001), and the arousal index was reduced (2.5/h, IQR 2.3, 3.0 vs. 22.3/h, IQR 13.8, 30.0, p = 0.002), although total sleep time was similar between groups (621 min, IQR 464, 651 vs. 542.5 min, IQR 499, 582, p = 0.51). Remarkably, all six patients had MSLT latencies ≤8 min, indicating severe sleepiness. No parasomnia or sleep‐disordered breathing was detected. Conclusion: Central hypersomnia is a relevant characteristic of anti‐GAD65‐associated neurological syndromes. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Author

Vollstedt, Eva-Juliane, Schaake, Susen, Lohmann, Katja, Padmanabhan, Shalini, Brice, Alexis, Lesage, Suzanne, Tesson, Christelle, Vidailhet, Marie, Wurster, Isabel, Hentati, Faycel, Mirelman, Anat, Giladi, Nir, Marder, Karen, Waters, Cheryl, Fahn, Stanley, Kasten, Meike, Brüggemann, Norbert, Borsche, Max, Foroud, Tatiana, Tolosa, Eduardo, Garrido, Alicia, Annesi, Grazia, Gagliardi, Monica, Bozi, Maria, Stefanis, Leonidas, Ferreira, Joaquim J, Correia Guedes, Leonor, Avenali, Micol, Petrucci, Simona, Clark, Lorraine, Fedotova, Ekaterina Y, Abramycheva, Natalya Y, Alvarez, Victoria, Menéndez-González, Manuel, Jesús Maestre, Silvia, Gómez-Garre, Pilar, Mir, Pablo, Belin, Andrea Carmine, Ran, Caroline, Lin, Chin-Hsien, Kuo, Ming-Che, Crosiers, David, Wszolek, Zbigniew K, Ross, Owen A, Jankovic, Joseph, Nishioka, Kenya, Funayama, Manabu, Clarimon, Jordi, Williams-Gray, Caroline H, Camacho, Marta, Cornejo-Olivas, Mario, Torres-Ramirez, Luis, Wu, Yih-Ru, Lee-Chen, Guey-Jen, Morgadinho, Ana, Pulkes, Teeratorn, Termsarasab, Pichet, Berg, Daniela, Kuhlenbäumer, Gregor, Kühn, Andrea A, Borngräber, Friederike, De Michele, Giuseppe, De Rosa, Anna, Zimprich, Alexander, Puschmann, Andreas, Mellick, George D, Dorszewska, Jolanta, Carr, Jonathan, Ferese, Rosangela, Gambardella, Stefano, Chase, Bruce, Markopoulou, Katerina, Satake, Wataru, Toda, Tatsushi, Rossi, Malco, Merello, Marcelo, Lynch, Timothy, Olszewska, Diana A, Lim, Shen-Yang, Ahmad-Annuar, Azlina, Tan, Ai Huey, Al-Mubarak, Bashayer, Hanagasi, Hasmet, Koziorowski, Dariusz, Ertan, Sibel, Genç, Gençer, De Carvalho Aguiar, Patricia, Barkhuizen, Melinda, Pimentel, Marcia MG, Saunders-Pullman, Rachel, Van De Warrenburg, Bart, Bressman, Susan, Toft, Mathias, Appel-Cresswell, Silke, Lang, Anthony E, Skorvanek, Matej, Boon, Agnita JW, Krüger, Rejko, Sammler, Esther M, Tumas, Vitor, Zhang, Bao-Rong, Garraux, Gaetan, Chung, Sun Ju, Kim, Yun Joong, Winkelmann, Juliane, Sue, Carolyn M, Tan, Eng-King, Damásio, Joana, Klivényi, Péter, Kostic, Vladimir S, Arkadir, David, Martikainen, Mika, Borges, Vanderci, Hertz, Jens Michael, Brighina, Laura, Spitz, Mariana, Suchowersky, Oksana, Riess, Olaf, Das, Parimal, Mollenhauer, Brit, Gatto, Emilia M, Petersen, Maria Skaalum, Hattori, Nobutaka, Wu, Ruey-Meei, Illarioshkin, Sergey N, Valente, Enza Maria, Aasly, Jan O, Aasly, Anna, Alcalay, Roy N, Thaler, Avner, Farrer, Matthew J, Brockmann, Kathrin, Corvol, Jean-Christophe, Klein, Christine, MJFF Global Genetic Parkinson's Disease Study Group, Vollstedt, Ej, Schaake, S, Lohmann, K, Padmanabhan, S, Brice, A, Lesage, S, Tesson, C, Vidailhet, M, Wurster, I, Hentati, F, Mirelman, A, Giladi, N, Marder, K, Waters, C, Fahn, S, Kasten, M, Brüggemann, N, Borsche, M, Foroud, T, Tolosa, E, Garrido, A, Annesi, G, Gagliardi, M, Bozi, M, Stefanis, L, Ferreira, Jj, Correia Guedes, L, Avenali, M, Petrucci, S, Clark, L, Fedotova, Ey, Abramycheva, Ny, Alvarez, V, Menéndez-González, M, Jesús Maestre, S, Gómez-Garre, P, Mir, P, Belin, Ac, Ran, C, Lin, Ch, Kuo, Mc, Crosiers, D, Wszolek, Zk, Ross, Oa, Jankovic, J, Nishioka, K, Funayama, M, Clarimon, J, Williams-Gray, Ch, Camacho, M, Cornejo-Olivas, M, Torres-Ramirez, L, Wu, Yr, Lee-Chen, Gj, Morgadinho, A, Pulkes, T, Termsarasab, P, Berg, D, Kuhlenbäumer, G, Kühn, Aa, Borngräber, F, de Michele, G, De Rosa, A, Zimprich, A, Puschmann, A, Mellick, Gd, Dorszewska, J, Carr, J, Ferese, R, Gambardella, S, Chase, B, Markopoulou, K, Satake, W, Toda, T, Rossi, M, Merello, M, Lynch, T, Olszewska, Da, Lim, Sy, Ahmad-Annuar, A, Tan, Ah, Al-Mubarak, B, Hanagasi, H, Koziorowski, D, Ertan, S, Genç, G, de Carvalho Aguiar, P, Barkhuizen, M, Pimentel, Mmg, Saunders-Pullman, R, van de Warrenburg, B, Bressman, S, Toft, M, Appel-Cresswell, S, Lang, Ae, Skorvanek, M, Boon, Ajw, Krüger, R, Sammler, Em, Tu, Repositório da Universidade de Lisboa, Clinical Genetics, Neurology, Internal Medicine, Aasly, Anna, Aasly, Jan O, Abramycheva, Natalya Y, Ahmad-Annuar, Azlina, Albanese, Alberto, Alcalay, Roy N, Aldakheel, Amaal, Alkhairallah, Thamer, Al-Mubarak, Bashayer, Al-Tassan, Nada, Alvarez, Victoria, Amami, Paolo, Annesi, Grazia, Appel-Cresswell, Silke, Leite, Marco Antonio Araujo, Arkadir, David, Avenali, Micol, Ferraz, Henrique Ballalai, Bardien, Soraya, Barkhuizen, Melinda, Barrett, Matthew J, Başak, A Nazlı, Berg, Daniela, Bilgic, Basar, Bloem, Bastiaan R, Bonifati, Vincenzo, Boon, Agnita J W, Borges, Vanderci, Borngräber, Friederike, Borsche, Max, Bozi, Maria, Bressman, Susan, Brice, Alexis, Brighina, Laura, Brockmann, Kathrin, Brüggemann, Norbert, Camacho, Marta, Belin, Andrea Carmine, Carr, Jonathan, Cesarini, Martin Emiliano, Cornejo-Olivas, Mario, Chase, Bruce, Chung, Sun Ju, Guedes, Leonor Correia, Clarimon, Jordi, Clark, Lorraine, Corvol, Jean-Christophe, Crosiers, David, Das, Parimal, de Carvalho Aguiar, Patricia, Damásio, Joana, de Michele, Giuseppe, De Rosa, Anna, Dieguez, Elena, Dorszewska, Jolanta, Ertan, Sibel, Fahn, Stanley, Farrer, Matthew J, Fedotova, Ekaterina Y, Ferese, Rosangela, Ferreira, Joaquim J, Foroud, Tatiana, Funayama, Manabu, Fung, Victor S C, Gagliardi, Monica, Gambardella, Stefano, Garraux, Gaetan, Garrido, Alicia, Gatto, Emilia M, Genç, Gençer, Giladi, Nir, Gómez-Garre, Pilar, Hanagasi, Hasmet, Hattori, Nobutaka, Hentati, Faycel, Hertz, Jens Michael, Illarioshkin, Sergey N, Jankovic, Joseph, Januario, Cristina, Maestre, Silvia Jesús, Kaasinen, Valtteri, Kasten, Meike, Kataoka, Hiroshi, Kievit, Anneke A, Kim, Yun Joong, Klein, Christine, Klivényi, Péter, Kostic, Vladimir S, Koziorowski, Dariusz, Krüger, Rejko, Kühn, Andrea, Kuhlenbäumer, Gregor, Kuo, Ming-Che, Lang, Anthony E, Lee-Chen, Guey-Jen, Lesage, Suzanne, Lim, Jia Lun, Lim, Shen-Yang, Lin, Chin-Hsien, Lohmann, Katja, Lynch, Timothy, Marder, Karen, Markopoulou, Katerina, Martikainen, Mika, May, Patrick, McCarthy, Allan, Mellick, George D, Menéndez-González, Manuel, Merello, Marcelo, Mir, Pablo, Mirelman, Anat, Mollenhauer, Brit, Briceno, Hugo Morales, Morgadinho, Ana, Morris, Huw, Mosejova, Alexandra, Nishioka, Kenya, Çakmak, Özgür Öztop, Olszewska, Diana A, Orr-Urtreger, Avi, Pachchek, Sinthuja, Padmanabhan, Shalini, Periñán, Maria Teresa, Petrucci, Simona, Pimentel, Marcia M G, Procopio, Radha, Pulkes, Teeratorn, Puschmann, Andreas, Ran, Caroline, Riess, Olaf, Ross, Owen A, Rossi, Malco, Ruiz-Martinez, Javier, Sammler, Esther M, Pereira, João Santos, Satake, Wataru, Saunders-Pullman, Rachel, Schaake, Susen, Petersen, Maria Skaalum, Skorvanek, Matej, Stefanis, Leonidas, Soto-Beasley, Alexandra I, Sousa, Mário, Spitz, Mariana, Suchowersky, Oksana, Sue, Carolyn M, Tan, Ai Huey, Tan, Eng-King, Thaler, Avner, Tepgeç, Fatih, Termsarasab, Pichet, Tesson, Christelle, Toda, Tatsushi, Toft, Mathias, Tolosa, Eduardo, Torres-Ramirez, Luis, Tumas, Vitor, Uyguner, Oya, Valente, Enza Maria, van de Warrenburg, Bart, Vidailhet, Marie, Vollstedt, Eva-Juliane, Walton, Ronald L, Waters, Cheryl, Williams-Gray, Caroline H, Winkelmann, Juliane, Wu, Yih-Ru, Wurster, Isabel, Wszolek, Zbigniew K, Wu, Ruey-Meei, Zhang, Bao-Rong, Zimprich, Alexander, Vollstedt, Eva-Juliane [0000-0002-6898-9201], Lohmann, Katja [0000-0002-5121-1460], Mirelman, Anat [0000-0002-1520-2292], Brüggemann, Norbert [0000-0001-5969-6899], Borsche, Max [0000-0002-9651-5986], Tolosa, Eduardo [0000-0002-3781-0854], Ferreira, Joaquim J [0000-0003-3950-5113], Alvarez, Victoria [0000-0002-1916-2523], Mir, Pablo [0000-0003-1656-302X], Kuo, Ming-Che [0000-0003-3688-0225], Ross, Owen A [0000-0003-4813-756X], Nishioka, Kenya [0000-0001-8607-9757], Williams-Gray, Caroline H [0000-0002-2648-9743], Camacho, Marta [0000-0002-1490-5703], Cornejo-Olivas, Mario [0000-0001-6313-5680], Wu, Yih-Ru [0000-0003-1191-2542], Termsarasab, Pichet [0000-0002-3260-3119], Borngräber, Friederike [0000-0001-9650-6820], Zimprich, Alexander [0000-0002-1668-5177], Gambardella, Stefano [0000-0002-3727-4502], Chase, Bruce [0000-0001-5491-7242], Olszewska, Diana A [0000-0002-1814-8834], Tan, Ai Huey [0000-0002-2979-3839], Barkhuizen, Melinda [0000-0002-9952-7085], Appel-Cresswell, Silke [0000-0002-5986-1468], Skorvanek, Matej [0000-0001-5497-8715], Sammler, Esther M [0000-0003-3218-7116], Zhang, Bao-Rong [0000-0002-8099-7407], Chung, Sun Ju [0000-0003-4118-8233], Apollo - University of Cambridge Repository, and MJFF Global Genetic Parkinson's Disease Study Group

Subjects
parkinson's disease, monogenic pd, monogenic PD, Parkinson's disease, Monogenic PD, Parkinson Disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], ddc, Neurology, genetics [Parkinson Disease], Mutation, Humans, Human medicine, ddc:610, Neurology (clinical), Research Article, Research Articles
Abstract

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014

Published
2023

26. Non‐motor symptoms and quality of life in patients with PRRT2 ‐related paroxysmal kinesigenic dyskinesia

Author

Ekmen, Asya, primary, Doulazmi, Mohamed, additional, Méneret, Aurélie, additional, Jegatheesan, Prasanthi, additional, Hervé, Anais, additional, Damier, Philippe, additional, Gras, Domitille, additional, Roubertie, Agathe, additional, Piard, Juliette, additional, Mutez, Eugenie, additional, Tarrano, Clément, additional, Welniarz, Quentin, additional, Vidailhet, Marie, additional, Worbe, Yulia, additional, Gallea, Cécile, additional, and Roze, Emmanuel, additional

Published
2023
Full Text
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27. Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Fonds National de la Recherche - FnR [sponsor], MJFF [sponsor], H2020 (Orchestra) [sponsor], Vollstedt, Eva-Juliane, Schaake, Susen, Lohmann, Katja, Padmanabhan, Shalini, Brice, Alexis, Lesage, Suzanne, Tesson, Christelle, Vidailhet, Marie, Wurster, Isabel, Hentati, Faycel, Mirelman, Anat, Giladi, Nir, Karen, Marder, Waters, Cheryl, Fahn, Stanley, Kasten, Meike, Brüggemann, Norbert, Borsche, Max, Foroud, Tatiana, Tolosa, Eduardo, Garrido, Alicia, Annesi, Grazia, Gagliardi, Monica, Bozi, Maria, Stefanis, Leonidas, Ferreira, Joaquim J., Correia Guedes, Leonor, Avenali, Micol, Petrucci, Simona, Clark, Lorraine, Fedotova, Ekaterina Y., Abramycheva, Natalya Y., Alvarez, Victoria, Menéndez-González, Manuel, Jesús Maestre, Silvia, Gómez-Garre, Pilar, Mir, Pablo, Belin, Andrea Carmine, Ran, Caroline, Lin, Chin-Hsien, Kuo, Ming-Che, Crosiers, David, Wszolek, Zbigniew K., Ross, Owen A., Jankovic, Joseph, Nishioka, Kenya, Funayama, Manabu, Clarimon, Jordi, Williams-Gray, Caroline H., Camacho, Marta, Cornejo-Olivas, Mario, Torres-Ramirez, Luis, Wu, Yih-Ru, Lee-Chen, Guey-Jen, Morgadinho, Ana, Pulkes, Teeratorn, Termsarasab, Pichet, Berg, Daniela, Gregor, Kuhlenbäumer, Kühn, Andrea A., Borngräber, Friederike, de Michele, Giuseppe, De Rosa, Anna, Zimprich, Alexander, Puschmann, Andreas, Mellick, George D., Jolanta, Dorszewska, Carr, Jonathan, Ferese, Rosangela, Stefano, Gambardella, Chase, Bruce, Markopoulou, Katerina, Wataru, Satake, Toda, Tatsushi, Rossi, Malco, Merello, Marcelo, Lynch, Timothy, Olszewska, Diana A., Lim, Shen-Yang, Ahmad-Annuar, Azlina, Tan, Ai Huey, Al-Mubarak, Bashayer, Hanagasi, Hasmet, Koziorowski, Dariusz, Ertan, Sibel, Gen c, Gen Cer, de Carvalho Aguiar, Patricia, Barkhuizen, Melinda, Pimentel, Marcia M. G., Saunders-Pullman, Rachel, van de Warrenburg, Bart, Bressman, Susan, Toft, Mathias, Appel-Cresswell, Silke, Lang, Anthony E., Skorvanek, Matej, Boon, Agnita J. W., Krüger, Rejko, Sammler, Esther M., Tumas, Vitor, Zhang, Bao-Rong, Garraux, Gaetan, Chung, Sun Ju, Joong, Kim Yun, Winkelmann, Juliane, Sue, Carolyn M., Eng-King, Tan, Damásio, Joana, Klivényi, Péter, Kostic, Vladimir S., Arkadir, David, Martikainen, Mika, Borges, Vanderci, Hertz, Jens Michael, Brighina, Laura, Spitz, Mariana, Suchowersky, Oksana, Riess, Olaf, Parimal, Das, Mollenhauer, Brit, Gatto, Emilia M., Skaalum, Petersen Maria, Wu, Ruey-Meei, Illarioshkin, Sergey N., Valente, Enza Maria, Aasly, Jan O., Aasly, Anna, N, Alcalay Roy, Thaler, Avner, Farrer, Matthew J., Kathrin, Brockmann, Corvol, Jean-Christophe, Klein, Christine, Albanese, Alberto, Alcalay, Roy N., Aldakheel, Amaal, Alkhairallah, Thamer, Bashayer, Al-Mubarak, Al-Tassan, Nada, Paolo, Amami, Araujo, Leite Marco Antonio, Ferraz, Henrique Ballalai, Bardien, Soraya, Melinda, Barkhuizen, Barrett, Matthew J., Ba sak, A. Nazl I, Bilgic, Basar, Bloem, Bastiaan R., Bonifati, Vincenzo, Brockmann, Kathrin, Cesarini, Martin Emiliano, Ju, Chung Sun, Guedes, Leonor Correia, Lorraine, Clark, Dieguez, Elena, Dorszewska, Jolanta, Fung, Victor S. C., Pilar, Gómez-Garre, Hattori, Nobutaka, Faycel, Hentati, Januario, Cristina, Maestre, Silvia Jesús, Kaasinen, Valtteri, Hiroshi, Kataoka, Kievit, Anneke A., Kim, Yun Joong, Christine, Klein, Kuhlenbäumer, Gregor, Lim, Jia Lun, Timothy, Lynch, Marder, Karen, May, Patrick, McCarthy, Allan, Briceno, Hugo Morales, Morris, Huw, Mosejova, Alexandra, Cakmak, Özgür Öztop, Orr-Urtreger, Avi, Pachchek, Sinthuja, Periñ\'an, Maria Teresa, Procopio, Radha, Ruiz-Martinez, Javier, Pereira, João Santos, Satake, Wataru, Soto-Beasley, Alexandra I., Sousa, Mário, Tan, Eng-King, Tepge c, Fatih, Uyguner, Oya, Walton, Ronald L., H, Williams-Gray Caroline, Isabel, Wurster, Bao-Rong, Zhang, Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Fonds National de la Recherche - FnR [sponsor], MJFF [sponsor], H2020 (Orchestra) [sponsor], Vollstedt, Eva-Juliane, Schaake, Susen, Lohmann, Katja, Padmanabhan, Shalini, Brice, Alexis, Lesage, Suzanne, Tesson, Christelle, Vidailhet, Marie, Wurster, Isabel, Hentati, Faycel, Mirelman, Anat, Giladi, Nir, Karen, Marder, Waters, Cheryl, Fahn, Stanley, Kasten, Meike, Brüggemann, Norbert, Borsche, Max, Foroud, Tatiana, Tolosa, Eduardo, Garrido, Alicia, Annesi, Grazia, Gagliardi, Monica, Bozi, Maria, Stefanis, Leonidas, Ferreira, Joaquim J., Correia Guedes, Leonor, Avenali, Micol, Petrucci, Simona, Clark, Lorraine, Fedotova, Ekaterina Y., Abramycheva, Natalya Y., Alvarez, Victoria, Menéndez-González, Manuel, Jesús Maestre, Silvia, Gómez-Garre, Pilar, Mir, Pablo, Belin, Andrea Carmine, Ran, Caroline, Lin, Chin-Hsien, Kuo, Ming-Che, Crosiers, David, Wszolek, Zbigniew K., Ross, Owen A., Jankovic, Joseph, Nishioka, Kenya, Funayama, Manabu, Clarimon, Jordi, Williams-Gray, Caroline H., Camacho, Marta, Cornejo-Olivas, Mario, Torres-Ramirez, Luis, Wu, Yih-Ru, Lee-Chen, Guey-Jen, Morgadinho, Ana, Pulkes, Teeratorn, Termsarasab, Pichet, Berg, Daniela, Gregor, Kuhlenbäumer, Kühn, Andrea A., Borngräber, Friederike, de Michele, Giuseppe, De Rosa, Anna, Zimprich, Alexander, Puschmann, Andreas, Mellick, George D., Jolanta, Dorszewska, Carr, Jonathan, Ferese, Rosangela, Stefano, Gambardella, Chase, Bruce, Markopoulou, Katerina, Wataru, Satake, Toda, Tatsushi, Rossi, Malco, Merello, Marcelo, Lynch, Timothy, Olszewska, Diana A., Lim, Shen-Yang, Ahmad-Annuar, Azlina, Tan, Ai Huey, Al-Mubarak, Bashayer, Hanagasi, Hasmet, Koziorowski, Dariusz, Ertan, Sibel, Gen c, Gen Cer, de Carvalho Aguiar, Patricia, Barkhuizen, Melinda, Pimentel, Marcia M. G., Saunders-Pullman, Rachel, van de Warrenburg, Bart, Bressman, Susan, Toft, Mathias, Appel-Cresswell, Silke, Lang, Anthony E., Skorvanek, Matej, Boon, Agnita J. W., Krüger, Rejko, Sammler, Esther M., Tumas, Vitor, Zhang, Bao-Rong, Garraux, Gaetan, Chung, Sun Ju, Joong, Kim Yun, Winkelmann, Juliane, Sue, Carolyn M., Eng-King, Tan, Damásio, Joana, Klivényi, Péter, Kostic, Vladimir S., Arkadir, David, Martikainen, Mika, Borges, Vanderci, Hertz, Jens Michael, Brighina, Laura, Spitz, Mariana, Suchowersky, Oksana, Riess, Olaf, Parimal, Das, Mollenhauer, Brit, Gatto, Emilia M., Skaalum, Petersen Maria, Wu, Ruey-Meei, Illarioshkin, Sergey N., Valente, Enza Maria, Aasly, Jan O., Aasly, Anna, N, Alcalay Roy, Thaler, Avner, Farrer, Matthew J., Kathrin, Brockmann, Corvol, Jean-Christophe, Klein, Christine, Albanese, Alberto, Alcalay, Roy N., Aldakheel, Amaal, Alkhairallah, Thamer, Bashayer, Al-Mubarak, Al-Tassan, Nada, Paolo, Amami, Araujo, Leite Marco Antonio, Ferraz, Henrique Ballalai, Bardien, Soraya, Melinda, Barkhuizen, Barrett, Matthew J., Ba sak, A. Nazl I, Bilgic, Basar, Bloem, Bastiaan R., Bonifati, Vincenzo, Brockmann, Kathrin, Cesarini, Martin Emiliano, Ju, Chung Sun, Guedes, Leonor Correia, Lorraine, Clark, Dieguez, Elena, Dorszewska, Jolanta, Fung, Victor S. C., Pilar, Gómez-Garre, Hattori, Nobutaka, Faycel, Hentati, Januario, Cristina, Maestre, Silvia Jesús, Kaasinen, Valtteri, Hiroshi, Kataoka, Kievit, Anneke A., Kim, Yun Joong, Christine, Klein, Kuhlenbäumer, Gregor, Lim, Jia Lun, Timothy, Lynch, Marder, Karen, May, Patrick, McCarthy, Allan, Briceno, Hugo Morales, Morris, Huw, Mosejova, Alexandra, Cakmak, Özgür Öztop, Orr-Urtreger, Avi, Pachchek, Sinthuja, Periñ\'an, Maria Teresa, Procopio, Radha, Ruiz-Martinez, Javier, Pereira, João Santos, Satake, Wataru, Soto-Beasley, Alexandra I., Sousa, Mário, Tan, Eng-King, Tepge c, Fatih, Uyguner, Oya, Walton, Ronald L., H, Williams-Gray Caroline, Isabel, Wurster, and Bao-Rong, Zhang

Abstract

BACKGROUND: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. OBJECTIVE: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. METHODS: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2 VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. RESULTS: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34\%) were indicated as not previously published. CONCLUSIONS: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward cl

Published
2023

28. Embracing Monogenic Parkinson's Disease:The MJFF Global Genetic PD Cohort

Author

Vollstedt, Eva Juliane, Schaake, Susen, Lohmann, Katja, Padmanabhan, Shalini, Brice, Alexis, Lesage, Suzanne, Tesson, Christelle, Vidailhet, Marie, Wurster, Isabel, Hentati, Faycel, Mirelman, Anat, Giladi, Nir, Marder, Karen, Waters, Cheryl, Fahn, Stanley, Kasten, Meike, Brüggemann, Norbert, Borsche, Max, Foroud, Tatiana, Tolosa, Eduardo, Garrido, Alicia, Annesi, Grazia, Gagliardi, Monica, Bozi, Maria, Stefanis, Leonidas, Ferreira, Joaquim J., Correia Guedes, Leonor, Avenali, Micol, Petrucci, Simona, Clark, Lorraine, Fedotova, Ekaterina Y., Abramycheva, Natalya Y., Alvarez, Victoria, Menéndez-González, Manuel, Jesús Maestre, Silvia, Gómez-Garre, Pilar, Mir, Pablo, Belin, Andrea Carmine, Ran, Caroline, Lin, Chin Hsien, Kuo, Ming Che, Crosiers, David, Wszolek, Zbigniew K., Ross, Owen A., Boon, Agnita J.W., Riess, Olaf, Bonifati, Vincenzo, Kievit, Anneke A., Vollstedt, Eva Juliane, Schaake, Susen, Lohmann, Katja, Padmanabhan, Shalini, Brice, Alexis, Lesage, Suzanne, Tesson, Christelle, Vidailhet, Marie, Wurster, Isabel, Hentati, Faycel, Mirelman, Anat, Giladi, Nir, Marder, Karen, Waters, Cheryl, Fahn, Stanley, Kasten, Meike, Brüggemann, Norbert, Borsche, Max, Foroud, Tatiana, Tolosa, Eduardo, Garrido, Alicia, Annesi, Grazia, Gagliardi, Monica, Bozi, Maria, Stefanis, Leonidas, Ferreira, Joaquim J., Correia Guedes, Leonor, Avenali, Micol, Petrucci, Simona, Clark, Lorraine, Fedotova, Ekaterina Y., Abramycheva, Natalya Y., Alvarez, Victoria, Menéndez-González, Manuel, Jesús Maestre, Silvia, Gómez-Garre, Pilar, Mir, Pablo, Belin, Andrea Carmine, Ran, Caroline, Lin, Chin Hsien, Kuo, Ming Che, Crosiers, David, Wszolek, Zbigniew K., Ross, Owen A., Boon, Agnita J.W., Riess, Olaf, Bonifati, Vincenzo, and Kievit, Anneke A.

Abstract

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view towa

Published
2023

29. Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Author

Michael J. Fox Foundation for Parkinson's Research, Vollstedt, Eva-Juliane, Schaake, Susen, Lohmann, Katja, Padmanabhan, Shalini, Brice, Alexis, Lesage, Suzanne, Tesson, Christelle, Vidailhet, Marie, Wurster, Isabel, Hentati, Faycel, Mirelman, Anat, Giladi, Nir, Marder, Karen, Waters, Cheryl, Fahn, Stanley, Kasten, Meike, Brüggemann, Norbert, Borsche, Max, Foroud, Tatiana, Tolosa, Eduardo, Garrido, Alicia, Annesi, Grazia, Gagliardi, Monica, Bozi, Maria, Stefanis, Leonidas, Ferreira, Joaquim, Correia Guedes, Leonor, Avenali, Micol, Petrucci, Simona, Clark, Lorraine, Fedotova, Ekaterina Y., Abramycheva, Natalya Y., Alvarez, Victoria, Menéndez-González, Manuel, Jesús Maestre, Silvia, Gómez-Garre, Pilar, Mir, Pablo, Belin, Andrea Carmine, Ran, Caroline, Lin, Chin-Hsien, Kuo, Ming-Che, Crosiers, David, Wszolek, Zbigniew K., Ross, Owen A., Jankovic, Joseph, Nishioka, Kenya, Funayama, Manabu, Clarimon, Jordi, Williams-Gray, Caroline H., Camacho, Marta, Cornejo-Olivas, Mario, Torres-Ramírez, Luis, Wu, Yih-Ru, Lee-Chen, Guey-Jen, Morgadinho, Ana, Pulkes, Teeratorn, Termsarasab, Pichet, Berg, Daniela, Kuhlenbäumer, Gregor, Kühn, Andrea A., Borngräber, Friederike, Michele, Giuseppe de, Rosa, Anna De, Zimprich, Alexander, Puschmann, Andreas, Mellick, George D., Dorszewska, Jolanta, Carr, Jonathan, Ferese, Rosangela, Gambardella, Stefano, Chase, Bruce, Markopoulou, Katerina, Satake, Wataru, Toda, Tatsushi, Rossi, Malco, Merello, Marcelo, Lynch, Timothy, Olszewska, Diana A., Lim, Shen-Yang, Ahmad-Annuar, Azlina, Tan, Ai Huey, Al-Mubarak, Bashayer, Hanagasi, Hasmet, Koziorowski, Dariusz, Ertan, Sibel, Genç, Gençer, Aguiar, Patricia de Carvalho, Barkhuizen, Melinda, Pimentel, Marcia M. G., Saunders-Pullman, Rachel, Warrenburg, Bart van de, Bressman, Susan, Toft, Mathias, Appel-Cresswell, Silke, Lang, Anthony E., Skorvanek, Matej, Boon, Agnita J. W., Krüger, Rejko, Sammler, Esther M., Tumas, Vitor, Zhang, Bao-Rong, Garraux, Gaetan, Chung, Sun Ju, Kim, Yun Joong, Winkelmann, Juliane, Sue, Carolyn M., Tan, Eng-King, Damásio, Joana, Klivényi, Péter, Kostic, Vladimir S., Arkadir, David, Martikainen, Mika, Borges, Vanderci, Hertz, Jens Michael, Brighina, Laura, Spitz, Mariana, Suchowersky, Oksana, Riess, Olaf, Das, Parimal, Mollenhauer, Brit, Gatto, Emilia M., Petersen, Maria Skaalum, Hattori, Nobutaka, Wu, Ruey-Meei, Illarioshkin, Sergey N., Valente, Enza Maria, Aasly, Jan O., Aasly, Anna, Alcalay, Roy N., Thaler, Avner, Farrer, Matthew J., Brockmann, Kathrin, Corvol, Jean-Christophe, Klein, Christine, on behalf of the MJFF Global Genetic Parkinson's Disease Study Group, Michael J. Fox Foundation for Parkinson's Research, Vollstedt, Eva-Juliane, Schaake, Susen, Lohmann, Katja, Padmanabhan, Shalini, Brice, Alexis, Lesage, Suzanne, Tesson, Christelle, Vidailhet, Marie, Wurster, Isabel, Hentati, Faycel, Mirelman, Anat, Giladi, Nir, Marder, Karen, Waters, Cheryl, Fahn, Stanley, Kasten, Meike, Brüggemann, Norbert, Borsche, Max, Foroud, Tatiana, Tolosa, Eduardo, Garrido, Alicia, Annesi, Grazia, Gagliardi, Monica, Bozi, Maria, Stefanis, Leonidas, Ferreira, Joaquim, Correia Guedes, Leonor, Avenali, Micol, Petrucci, Simona, Clark, Lorraine, Fedotova, Ekaterina Y., Abramycheva, Natalya Y., Alvarez, Victoria, Menéndez-González, Manuel, Jesús Maestre, Silvia, Gómez-Garre, Pilar, Mir, Pablo, Belin, Andrea Carmine, Ran, Caroline, Lin, Chin-Hsien, Kuo, Ming-Che, Crosiers, David, Wszolek, Zbigniew K., Ross, Owen A., Jankovic, Joseph, Nishioka, Kenya, Funayama, Manabu, Clarimon, Jordi, Williams-Gray, Caroline H., Camacho, Marta, Cornejo-Olivas, Mario, Torres-Ramírez, Luis, Wu, Yih-Ru, Lee-Chen, Guey-Jen, Morgadinho, Ana, Pulkes, Teeratorn, Termsarasab, Pichet, Berg, Daniela, Kuhlenbäumer, Gregor, Kühn, Andrea A., Borngräber, Friederike, Michele, Giuseppe de, Rosa, Anna De, Zimprich, Alexander, Puschmann, Andreas, Mellick, George D., Dorszewska, Jolanta, Carr, Jonathan, Ferese, Rosangela, Gambardella, Stefano, Chase, Bruce, Markopoulou, Katerina, Satake, Wataru, Toda, Tatsushi, Rossi, Malco, Merello, Marcelo, Lynch, Timothy, Olszewska, Diana A., Lim, Shen-Yang, Ahmad-Annuar, Azlina, Tan, Ai Huey, Al-Mubarak, Bashayer, Hanagasi, Hasmet, Koziorowski, Dariusz, Ertan, Sibel, Genç, Gençer, Aguiar, Patricia de Carvalho, Barkhuizen, Melinda, Pimentel, Marcia M. G., Saunders-Pullman, Rachel, Warrenburg, Bart van de, Bressman, Susan, Toft, Mathias, Appel-Cresswell, Silke, Lang, Anthony E., Skorvanek, Matej, Boon, Agnita J. W., Krüger, Rejko, Sammler, Esther M., Tumas, Vitor, Zhang, Bao-Rong, Garraux, Gaetan, Chung, Sun Ju, Kim, Yun Joong, Winkelmann, Juliane, Sue, Carolyn M., Tan, Eng-King, Damásio, Joana, Klivényi, Péter, Kostic, Vladimir S., Arkadir, David, Martikainen, Mika, Borges, Vanderci, Hertz, Jens Michael, Brighina, Laura, Spitz, Mariana, Suchowersky, Oksana, Riess, Olaf, Das, Parimal, Mollenhauer, Brit, Gatto, Emilia M., Petersen, Maria Skaalum, Hattori, Nobutaka, Wu, Ruey-Meei, Illarioshkin, Sergey N., Valente, Enza Maria, Aasly, Jan O., Aasly, Anna, Alcalay, Roy N., Thaler, Avner, Farrer, Matthew J., Brockmann, Kathrin, Corvol, Jean-Christophe, Klein, Christine, and on behalf of the MJFF Global Genetic Parkinson's Disease Study Group

Abstract

[Background] As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited., [Objective] The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD., [Methods] We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed., [Results] We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published., [Conclusions] Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2023

32. Correction: Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome

Author

Depienne, Christel, primary, Ciura, Sorana, additional, Trouillard, Oriane, additional, Bouteiller, Delphine, additional, Leitão, Elsa, additional, Nava, Caroline, additional, Keren, Boris, additional, Marie, Yannick, additional, Guegan, Justine, additional, Forlani, Sylvie, additional, Brice, Alexis, additional, Anheim, Mathieu, additional, Agid, Yves, additional, Krack, Paul, additional, Damier, Philippe, additional, Viallet, François, additional, Houeto, Jean-Luc, additional, Durif, Franck, additional, Vidailhet, Marie, additional, Worbe, Yulia, additional, Roze, Emmanuel, additional, Kabashi, Edor, additional, and Hartmann, Andreas, additional

Published
2023
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33. High-frequency cerebellar tACS for managing essential tremor

Author

Lamy, Jean-Charles, primary, Olivier, Claire, additional, Kosutzka, Zuzana, additional, Van Hamme, Angèle, additional, Cherif, Saoussen, additional, Lau, Brian, additional, Vidailhet, Marie, additional, Karachi, Carine, additional, and Welter, Marie-Laure, additional

Published
2023
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34. Mutations in the netrin-1 gene cause congenital mirror movements

Author

Meneret, Aurelie, Franz, Elizabeth A., Trouillard, Oriane, Oliver, Thomas C., Zagar, Yvrick, Robertson, Stephen P., Welniarz, Quentin, MacKinlay Gardner, R.J., Gallea, Cecile, Srour, Myriam, Depienne, Christel, Jasoni, Christine L., Dubacq, Caroline, Riant, Florence, Lamy, Jean-Charles, Morel, Marie- Pierre, Guerois, Raphael, Andreani, Jessica, Fouquet, Coralie, Doulazmi, Mohamed, Vidailhet, Marie, Rouleau, Guy A., Brice, Alexis, Chedotal, Alain, Dusart, Isabelle, Roze, Emmanuel, and Markie, David

Subjects
Electromyography -- Usage, Movement disorders -- Diagnosis -- Care and treatment, Gene mutation -- Research, Cell migration -- Research, Health care industry
Abstract

Netrin-1 is a secreted protein that was first identified 20 years ago as an axon guidance molecule that regulates midline crossing in the CNS. It plays critical roles in various tissues throughout development and is implicated in tumorigenesis and inflammation in adulthood. Despite extensive studies, no inherited human disease has been directly associated with mutations in NTN1, the gene coding for netrin-1. Here, we have identified 3 mutations in exon 7 of NTN1 in 2 unrelated families and 1 sporadic case with isolated congenital mirror movements (CMM), a disorder characterized by involuntary movements of one hand that mirror intentional movements of the opposite hand. Given the diverse roles of netrin-1, the absence of manifestations other than CMM in NTN1 mutation carriers was unexpected. Using multimodal approaches, we discovered that the anatomy of the corticospinal tract (CST) is abnormal in patients with NTNI-mutant CMM. When expressed in HEK293 or stable HeLa cells, the 3 mutated netrin-1 proteins were almost exclusively detected in the intracellular compartment, contrary to WT netrin-1, which is detected in both intracellular and extracellular compartments. Since netrin-1 is a diffusible extracellular cue, the pathophysiology likely involves its loss of function and subsequent disruption of axon guidance, resulting in abnormal decussation of the CST., Introduction Netrins are a family of extracellular proteins that regulate cell migration and survival during development and adulthood. The first member, netrin-1, was identified as a secreted protein mediating axon [...]

Published
2017
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35. Correction: Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome

Author

Depienne, Christel, Ciura, Sorana, Trouillard, Oriane, Bouteiller, Delphine, Leitão, Elsa, Nava, Caroline, Keren, Boris, Marie, Yannick, Guegan, Justine, Forlani, Sylvie, Brice, Alexis, Anheim, Mathieu, Agid, Yves, Krack, Paul, Damier, Philippe, Viallet, François, Houeto, Jean-Luc, Durif, Franck, Vidailhet, Marie, Worbe, Yulia, Roze, Emmanuel, Kabashi, Edor, and Hartmann, Andreas

Subjects
610 Medicine & health
Abstract

[This corrects the article DOI: 10.5334/tohm.464.].

Published
2023

36. Night-Time Apomorphine Infusion: Who Are the Best Candidates?

Author

de Cock, Valérie Cochen, Dodet, Pauline, Leu-Semenescu, Smaranda, Aerts, Cécile, Abril, Beatriz, Castelnovo, Giovanni, Landragin, Nicolas, Drapier, Sophie, Olivet, Hélène, Corbillé, Anne Gaelle, Leclair-Visonneau, Laurène, Anheim, Mathieu, Vidailhet, Marie, Arnulf, Isabelle, Doulazmi, Mohamed, Roze, Emmanuel, Clinique Beau Soleil [Montpellier], EuroMov - Digital Health in Motion (Euromov DHM), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Montpellier (UM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Clinique du Millénaire - Oc Santé [Montpellier], Oc Santé [Montpellier], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Polyclinique Saint Laurent [Rennes], Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), CHU Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Orkyn Ltd Aguettant Pharma Société Française de Médecine Esthétique

Subjects
motor fluctuations, treatment, Parkinson's disease, insomnia, [SDV]Life Sciences [q-bio], [SCCO.NEUR]Cognitive science/Neuroscience, sleep, sleepiness, apomorphine
Abstract

International audience; Background: We recently demonstrated in a randomized controlled trial (APOMORPHEE, NCT02940912) that night-time only subcutaneous apomorphine infusion improves sleep disturbances and insomnia in patients with advanced Parkinson's disease and moderate to severe insomnia. Objectives: To identify the best candidates for receiving night-time only subcutaneous apomorphine infusion in routine care. Methods: In this post-hoc analysis of APOMORPHEE, we compared the characteristics of patients according to whether they chose to continue night-time only subcutaneous apomorphine infusion at the end of the study period or not. Results: Half of the patients (22/42) chose to continue the treatment. Off duration (day or night), painful Off dystonia, and insomnia severity at baseline were associated with night-time only apomorphine continuation. Multivariate analysis retained only Off duration as an independent predictor of continuation. Conclusions:The best candidates for night-time only apomorphine are patients with severe and prolonged Off periods (day or night) and severe insomnia.

Published
2023

37. Relationship between Substantia Nigra Neuromelanin Imaging and Dual Alpha-Synuclein Labeling of Labial Minor in Salivary Glands in Isolated Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Author

Mangone, Graziella, primary, Houot, Marion, additional, Gaurav, Rahul, additional, Boluda, Susana, additional, Pyatigorskaya, Nadya, additional, Chalancon, Alizé, additional, Seilhean, Danielle, additional, Prigent, Annick, additional, Lehéricy, Stéphane, additional, Arnulf, Isabelle, additional, Corvol, Jean-Christophe, additional, Vidailhet, Marie, additional, Duyckaerts, Charles, additional, and Degos, Bertrand, additional

Published
2022
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38. Excessive burden of lysosomal storage disorder gene variants in Parkinson’s disease

Author

Robak, Laurie A, Jansen, Iris E, van Rooij, Jeroen, Uitterlinden, André G, Kraaij, Robert, Jankovic, Joseph, Heutink, Peter, Shulman, Joshua M, Nalls, Mike A, Plagnol, Vincent, Hernandez, Dena G, Sharma, Manu, Sheerin, Una-Marie, Saad, Mohamad, Simón-Sánchez, Javier, Schulte, Claudia, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Barker, Roger, Ben-, Yoav, Berendse, Henk W, Berg, Daniela, Bhatia, Kailash, de Bie, Rob M A, Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Majounie, Elisa, Charlesworth, Gavin, Lungu, Codrin, Chen, Honglei, Chinnery, Patrick F, Chong, Sean, Clarke, Carl E, Cookson, Mark R, Mark Cooper, J, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean-François, Deloukas, Panos, Deuschl, Günther, Dexter, David T, van Dijk, Karin D, Dillman, Allissa, Durif, Frank, Dürr, Alexandra, Edkins, Sarah, Evans, Jonathan R, Foltynie, Thomas, Dong, Jing, Gardner, Michelle, Raphael Gibbs, J, Goate, Alison, Gray, Emma, Guerreiro, Rita, Harris, Clare, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Wurster, Isabel, Mätzler, Walter, Hudson, Gavin, Hunt, Sarah E, Huttenlocher, Johanna, Illig, Thomas, Jónsson, Pálmi V, Lambert, Jean-Charles, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, Lungu, Codrin, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw R, Morrison, Karen E, Escott-Price, Valentina, Mudanohwo, Ese, O’Sullivan, Sean S, Pearson, Justin, Perlmutter, Joel S, Pétursson, Hjörvar, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Shulman, Joshua, Sidransky, Ellen, Smith, Colin, Spencer, Chris C A, Stefánsson, Hreinn, Bettella, Francesco, Stockton, Joanna D, Strange, Amy, Talbot, Kevin, Tanner, Carlie M, Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J, Uitterlinden, André G, Velseboer, Daan, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H, Winder-Rhodes, Sophie, Stefánsson, Kári, Martinez, Maria, Wood, Nicholas W, Hardy, John, Heutink, Peter, Brice, Alexis, Gasser, Thomas, and Singleton, Andrew B

Published
2017
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39. Mitochondrial function-associated genes underlie cortical atrophy in prodromal synucleinopathies.

Author

Rahayel, Shady, Tremblay, Christina, Vo, Andrew, Misic, Bratislav, Lehéricy, Stéphane, Arnulf, Isabelle, Vidailhet, Marie, Corvol, Jean-Christophe, Group, the ICEBERG Study, Gagnon, Jean-François, Postuma, Ronald B, Montplaisir, Jacques, Lewis, Simon, Matar, Elie, Martens, Kaylena Ehgoetz, Borghammer, Per, Knudsen, Karoline, Hansen, Allan K, Monchi, Oury, and Gan-Or, Ziv

Subjects
GENE ontology, RAPID eye movement sleep, CEREBRAL atrophy, LEWY body dementia, PARTIAL least squares regression, ALZHEIMER'S disease
Abstract

Isolated rapid eye movement sleep behaviour disorder (iRBD) is a sleep disorder characterized by the loss of rapid eye movement sleep muscle atonia and the appearance of abnormal movements and vocalizations during rapid eye movement sleep. It is a strong marker of incipient synucleinopathy such as dementia with Lewy bodies and Parkinson's disease. Patients with iRBD already show brain changes that are reminiscent of manifest synucleinopathies including brain atrophy. However, the mechanisms underlying the development of this atrophy remain poorly understood. In this study, we performed cutting-edge imaging transcriptomics and comprehensive spatial mapping analyses in a multicentric cohort of 171 polysomnography-confirmed iRBD patients [67.7 ± 6.6 (49–87) years; 83% men] and 238 healthy controls [66.6 ± 7.9 (41–88) years; 77% men] with T1-weighted MRI to investigate the gene expression and connectivity patterns associated with changes in cortical thickness and surface area in iRBD. Partial least squares regression was performed to identify the gene expression patterns underlying cortical changes in iRBD. Gene set enrichment analysis and virtual histology were then done to assess the biological processes, cellular components, human disease gene terms, and cell types enriched in these gene expression patterns. We then used structural and functional neighbourhood analyses to assess whether the atrophy patterns in iRBD were constrained by the brain's structural and functional connectome. Moreover, we used comprehensive spatial mapping analyses to assess the specific neurotransmitter systems, functional networks, cytoarchitectonic classes, and cognitive brain systems associated with cortical changes in iRBD. All comparisons were tested against null models that preserved spatial autocorrelation between brain regions and compared to Alzheimer's disease to assess the specificity of findings to synucleinopathies. We found that genes involved in mitochondrial function and macroautophagy were the strongest contributors to the cortical thinning occurring in iRBD. Moreover, we demonstrated that cortical thinning was constrained by the brain's structural and functional connectome and that it mapped onto specific networks involved in motor and planning functions. In contrast with cortical thickness, changes in cortical surface area were related to distinct genes, namely genes involved in the inflammatory response, and to different spatial mapping patterns. The gene expression and connectivity patterns associated with iRBD were all distinct from those observed in Alzheimer's disease. In summary, this study demonstrates that the development of brain atrophy in synucleinopathies is constrained by specific genes and networks. [ABSTRACT FROM AUTHOR]

Published
2023
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40. Night‐Time Apomorphine Infusion: Who Are the Best Candidates?

Author

Cochen De Cock, Valérie, Dodet, Pauline, Leu‐Semenescu, Smaranda, Aerts, Cécile, Abril, Beatriz, Castelnovo, Giovanni, Landragin, Nicolas, Drapier, Sophie, Olivet, Hélène, Corbillé, Anne‐Gaëlle, Leclair‐Visonneau, Laurène, Anheim, Mathieu, Vidailhet, Marie, Arnulf, Isabelle, Doulazmi, Mohamed, and Roze, Emmanuel

Subjects
APOMORPHINE, SLEEP interruptions, SUBCUTANEOUS infusions, PARKINSON'S disease, RANDOMIZED controlled trials
Abstract

Background: We recently demonstrated in a randomized controlled trial (APOMORPHEE, NCT02940912) that night‐time only subcutaneous apomorphine infusion improves sleep disturbances and insomnia in patients with advanced Parkinson's disease and moderate to severe insomnia. Objectives: To identify the best candidates for receiving night‐time only subcutaneous apomorphine infusion in routine care. Methods: In this post‐hoc analysis of APOMORPHEE, we compared the characteristics of patients according to whether they chose to continue night‐time only subcutaneous apomorphine infusion at the end of the study period or not. Results: Half of the patients (22/42) chose to continue the treatment. Off duration (day or night), painful Off dystonia, and insomnia severity at baseline were associated with night‐time only apomorphine continuation. Multivariate analysis retained only Off duration as an independent predictor of continuation. Conclusions: The best candidates for night‐time only apomorphine are patients with severe and prolonged Off periods (day or night) and severe insomnia. [ABSTRACT FROM AUTHOR]

Published
2023
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42. European Academy of Neurology guidance for developing and reporting clinical practice guidelines on rare neurological diseases.

Author

UCL - (SLuc) Centre de référence neuromusculaire, Aleksovska, Katina, Kobulashvili, Teia, Costa, Joao, Zimmermann, Georg, Ritchie, Karen, Reinhard, Carola, Vignatelli, Luca, Fanciulli, Alessandra, Damian, Maxwel, Pavlakova, Lucia, Burgunder, Jean-Marc, Kopishinskaya, Svetlana, Rakusa, Martin, Kovacs, Norbert, Erdogan, Fusun Ferda, Linton, Lori Renna, Copetti, Massimiliano, Lamperti, Costanza, Servidei, Serenella, Evangelista, Theresina, Ayme, Segolene, Pareyson, Davide, Sellner, Johann, Krarup, Christian, de Visser, Marianne, van den Bergh, Peter, Toscano, Antonio, Graessner, Holm, Berger, Thomas, Bassetti, Claudio, Vidailhet, Marie, Trinka, Eugene, Deuschl, Guenther, Federico, Antonio, Leone, Maurizio A, UCL - (SLuc) Centre de référence neuromusculaire, Aleksovska, Katina, Kobulashvili, Teia, Costa, Joao, Zimmermann, Georg, Ritchie, Karen, Reinhard, Carola, Vignatelli, Luca, Fanciulli, Alessandra, Damian, Maxwel, Pavlakova, Lucia, Burgunder, Jean-Marc, Kopishinskaya, Svetlana, Rakusa, Martin, Kovacs, Norbert, Erdogan, Fusun Ferda, Linton, Lori Renna, Copetti, Massimiliano, Lamperti, Costanza, Servidei, Serenella, Evangelista, Theresina, Ayme, Segolene, Pareyson, Davide, Sellner, Johann, Krarup, Christian, de Visser, Marianne, van den Bergh, Peter, Toscano, Antonio, Graessner, Holm, Berger, Thomas, Bassetti, Claudio, Vidailhet, Marie, Trinka, Eugene, Deuschl, Guenther, Federico, Antonio, and Leone, Maurizio A

Abstract

Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.

Published
2022

43. Genetic stratification of motor and QoL outcomes in Parkinson's disease in the EARLYSTIM study

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Weiss, Daniel, Landoulsi, Zied, May, Patrick, Sharma, Manu, Schüpbach, Michael, You, Hana, Corvol, Jean Christophe, Paschen, Steffen, Helmers, Ann-Kristin, Barbe, Michael, Fink, Gereon, Kühn, Andrea A., Courbon, Christine Brefel, Wojtecki, Lars, Damier, Philippe, Fraix, Valerie, Houeto, Jean-Luc, Regis, Jean, Sixel-Döring, Friederike, Pinsker, Marcus O., Thobois, Stephane, Gharabaghi, Alireza, Stoker, Valerie, Timmermann, Lars, Schnitzler, Alfons, Krack, Paul, Vidailhet, Marie, Deuschl, Günther, Krüger, Rejko, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Weiss, Daniel, Landoulsi, Zied, May, Patrick, Sharma, Manu, Schüpbach, Michael, You, Hana, Corvol, Jean Christophe, Paschen, Steffen, Helmers, Ann-Kristin, Barbe, Michael, Fink, Gereon, Kühn, Andrea A., Courbon, Christine Brefel, Wojtecki, Lars, Damier, Philippe, Fraix, Valerie, Houeto, Jean-Luc, Regis, Jean, Sixel-Döring, Friederike, Pinsker, Marcus O., Thobois, Stephane, Gharabaghi, Alireza, Stoker, Valerie, Timmermann, Lars, Schnitzler, Alfons, Krack, Paul, Vidailhet, Marie, Deuschl, Günther, and Krüger, Rejko

Abstract

Purpose The decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation. Objective First, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-DBS motor response. In additional exploratory analyses, we studied if other PD risk and progression variants from the latest GWAS are associated with therapeutic outcome. Further, we evaluated the predictive value of polygenic risk scores. Methods We comprehensively genotyped patients from the EarlyStim cohort using NeuroChip, and assessed the clinico-genetic associations with longitudinal outcome parameters. Results The SNCA rs356220 variant did not predict UPDRS III outcomes. However, it was associated with quality of life improvement in secondary analyses. Several polymorphisms from previously identified GWAS hits predicted motor or quality of life outcomes in DBS patients. Polygenic risk scores did not predict any outcome parameter. Conclusions Our findings support the hypothesis that different common genetic markers are associated with favourable quality of life outcomes of STN-DBS in PD. These findings can be the basis for further validation in larger and independent cohorts.

Published
2022

44. Genetic stratification of motor and QoL outcomes in Parkinson's disease in the EARLYSTIM study

Author

Weiss, Daniel, Landoulsi, Zied, May, Patrick, Sharma, Manu, Schupbach, Michael, You, Hana, Corvol, Jean Christophe, Paschen, Steffen, Helmers, Ann-Kristin, Barbe, Michael, Fink, Gereon, Kuehn, Andrea A., Courbon, Christine Brefel, Wojtecki, Lars, Damier, Philippe, Fraix, Valerie, Houeto, Jean-Luc, Regis, Jean, Sixel-Doering, Friederike, Pinsker, Marcus O., Thobois, Stephane, Gharabaghi, Alireza, Stoker, Valerie, Timmermann, Lars, Schnitzler, Alfons, Krack, Paul, Vidailhet, Marie, Deuschl, Guenther, Kruger, Rejko, Weiss, Daniel, Landoulsi, Zied, May, Patrick, Sharma, Manu, Schupbach, Michael, You, Hana, Corvol, Jean Christophe, Paschen, Steffen, Helmers, Ann-Kristin, Barbe, Michael, Fink, Gereon, Kuehn, Andrea A., Courbon, Christine Brefel, Wojtecki, Lars, Damier, Philippe, Fraix, Valerie, Houeto, Jean-Luc, Regis, Jean, Sixel-Doering, Friederike, Pinsker, Marcus O., Thobois, Stephane, Gharabaghi, Alireza, Stoker, Valerie, Timmermann, Lars, Schnitzler, Alfons, Krack, Paul, Vidailhet, Marie, Deuschl, Guenther, and Kruger, Rejko

Abstract

Purpose: The decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation. Objective: First, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-DBS motor response. In additional exploratory analyses, we studied if other PD risk and pro-gression variants from the latest GWAS are associated with therapeutic outcome. Further, we evaluated the predictive value of polygenic risk scores. Methods: We comprehensively genotyped patients from the EarlyStim cohort using NeuroChip, and assessed the clinico-genetic associations with longitudinal outcome parameters. Results: The SNCA rs356220 variant did not predict UPDRS III outcomes. However, it was associated with quality of life improvement in secondary analyses. Several polymorphisms from previously identified GWAS hits pre-dicted motor or quality of life outcomes in DBS patients. Polygenic risk scores did not predict any outcome parameter. Conclusions: Our findings support the hypothesis that different common genetic markers are associated with favourable quality of life outcomes of STN-DBS in PD. These findings can be the basis for further validation in larger and independent cohorts.

Published
2022

45. The Contribution of Subthalamic Nucleus Deep Brain Stimulation to the Improvement in Motor Functions and Quality of Life

Author

Toedt, Inken, Al-Fatly, Bassam, Granert, Oliver, Kuehn, Andrea A., Krack, Paul, Rau, Joern, Timmermann, Lars, Schnitzler, Alfons, Paschen, Steffen, Helmers, Ann-Kristin, Hartmann, Andreas, Bardinet, Eric, Schuepbach, Michael, Barbe, Michael T., Dembek, Till A., Fraix, Valerie, Kuebler, Dorothee, Brefel-Courbon, Christine, Gharabaghi, Alireza, Wojtecki, Lars, Pinsker, Marcus O., Thobois, Stephane, Damier, Philippe, Witjas, Tatiana, Houeto, Jean-Luc, Schade-Brittinger, Carmen, Vidailhet, Marie, Horn, Andreas, Deuschl, Guenther, Toedt, Inken, Al-Fatly, Bassam, Granert, Oliver, Kuehn, Andrea A., Krack, Paul, Rau, Joern, Timmermann, Lars, Schnitzler, Alfons, Paschen, Steffen, Helmers, Ann-Kristin, Hartmann, Andreas, Bardinet, Eric, Schuepbach, Michael, Barbe, Michael T., Dembek, Till A., Fraix, Valerie, Kuebler, Dorothee, Brefel-Courbon, Christine, Gharabaghi, Alireza, Wojtecki, Lars, Pinsker, Marcus O., Thobois, Stephane, Damier, Philippe, Witjas, Tatiana, Houeto, Jean-Luc, Schade-Brittinger, Carmen, Vidailhet, Marie, Horn, Andreas, and Deuschl, Guenther

Abstract

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. Objectives: The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality-of-life questionnaire, was assessed in a subcohort of the EARLYSTIM study. Methods: Sixty-nine patients from the EARLYSTIM cohort who underwent DBS, with a comprehensive clinical characterization before and 24 months after surgery, were included. Intercorrelations of clinical outcome changes, correlation between the affected functional parts of the STN, and changes in clinical outcomes were investigated. We further calculated sweet spots for different clinical parameters. Results: Improvements in the UPDRS III and Parkinson's Disease Questionnaire (PDQ-39) correlated positively with the extent of the overlap with the sensorimotor STN. The sweet spots for the UPDRS III (x = 11.6, y = -13.1, z = -6.3) and the PDQ-39 differed (x = 14.8, y = -12.4, z = -4.3) similar to 3.8 mm. Conclusions: The main influence of DBS on QoL is likely mediated through the sensory-motor basal ganglia loop. The PDQ sweet spot is located in a posteroventral spatial location in the STN territory. For aspects of QoL, however, there was also evidence of improvement through stimulation of the other STN subnuclei. More research is necessary to customize the DBS target to individual symptoms of each patient. (C) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Published
2022

46. European Academy of Neurology guidance for developing and reporting clinical practice guidelines on rare neurological diseases

Author

Aleksovska, Katina, Kobulashvili, Teia, Costa, Joao, Zimmermann, Georg, Ritchie, Karen, Reinhard, Carola, Vignatelli, Luca, Fanciulli, Alessandra, Damian, Maxwel, Pavlakova, Lucia, Burgunder, Jean-Marc, Kopishinskaya, Svetlana, Rakusa, Martin, Kovacs, Norbert, Erdogan, Fusun Ferda, Linton, Lori Renna, Copetti, Massimiliano, Lamperti, Costanza, Servidei, Serenella, Evangelista, Theresina, Ayme, Segolene, Pareyson, Davide, Sellner, Johann, Krarup, Christian, de Visser, Marianne, van den Bergh, Peter, Toscano, Antonio, Graessner, Holm, Berger, Thomas, Bassetti, Claudio, Vidailhet, Marie, Trinka, Eugene, Deuschl, Guenther, Federico, Antonio, Leone, Maurizio A., Aleksovska, Katina, Kobulashvili, Teia, Costa, Joao, Zimmermann, Georg, Ritchie, Karen, Reinhard, Carola, Vignatelli, Luca, Fanciulli, Alessandra, Damian, Maxwel, Pavlakova, Lucia, Burgunder, Jean-Marc, Kopishinskaya, Svetlana, Rakusa, Martin, Kovacs, Norbert, Erdogan, Fusun Ferda, Linton, Lori Renna, Copetti, Massimiliano, Lamperti, Costanza, Servidei, Serenella, Evangelista, Theresina, Ayme, Segolene, Pareyson, Davide, Sellner, Johann, Krarup, Christian, de Visser, Marianne, van den Bergh, Peter, Toscano, Antonio, Graessner, Holm, Berger, Thomas, Bassetti, Claudio, Vidailhet, Marie, Trinka, Eugene, Deuschl, Guenther, Federico, Antonio, and Leone, Maurizio A.

Abstract

Background and purpose Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. Methods A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. Results The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. Conclusions This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.

Published
2022

48. Clinical Features and Evolution of Blepharospasm: A Multicenter International Cohort and Systematic Literature Review

Author

Scorr, Laura M., primary, Cho, Hyun Joo, additional, Kilic-Berkmen, Gamze, additional, McKay, J. Lucas, additional, Hallett, Mark, additional, Klein, Christine, additional, Baumer, Tobias, additional, Berman, Brian D., additional, Feuerstein, Jeanne S., additional, Perlmutter, Joel S., additional, Berardelli, Alfredo, additional, Ferrazzano, Gina, additional, Wagle-Shukla, Aparna, additional, Malaty, Irene A., additional, Jankovic, Joseph, additional, Bellows, Steven T., additional, Barbano, Richard L., additional, Vidailhet, Marie, additional, Roze, Emmanuel, additional, Bonnet, Cecilia, additional, Mahajan, Abhimanyu, additional, LeDoux, Mark S., additional, Fung, Victor S.C., additional, Chang, Florence C.F., additional, Defazio, Giovanni, additional, Ercoli, Tomaso, additional, Factor, Stewart, additional, Wojno, Ted, additional, and Jinnah, H. A., additional

Published
2022
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50. A Multimodal Omics Exploration of the Motor and Non-Motor Symptoms of Parkinson’s Disease

Author

Lejeune, François-Xavier, primary, Ichou, Farid, additional, Camenen, Etienne, additional, Colsch, Benoit, additional, Mauger, Florence, additional, Peltier, Caroline, additional, Moszer, Ivan, additional, Gilson, Emmanuel, additional, Pierre-Jean, Morgane, additional, Floch, Edith Le, additional, Sabarly, Victor, additional, Tenenhaus, Arthur, additional, Deleuze, Jean-François, additional, Ewenczyk, Claire, additional, Vidailhet, Marie, additional, and Mochel, Fanny, additional

Published
2022
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