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1. Lifespan tree of brain anatomy: diagnostic values for motor and cognitive neurodegenerative diseases

Author

Coupé, Pierrick, Mansencal, Boris, Manjón, José V., Péran, Patrice, Meissner, Wassilios G., Tourdias, Thomas, and Planche, Vincent

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Machine Learning
Abstract

The differential diagnosis of neurodegenerative diseases, characterized by overlapping symptoms, may be challenging. Brain imaging coupled with artificial intelligence has been previously proposed for diagnostic support, but most of these methods have been trained to discriminate only isolated diseases from controls. Here, we develop a novel machine learning framework, named lifespan tree of brain anatomy, dedicated to the differential diagnosis between multiple diseases simultaneously. It integrates the modeling of volume changes for 124 brain structures during the lifespan with non-linear dimensionality reduction and synthetic sampling techniques to create easily interpretable representations of brain anatomy over the course of disease progression. As clinically relevant proof-of-concept applications, we constructed a cognitive lifespan tree of brain anatomy for the differential diagnosis of six causes of neurodegenerative dementia and a motor lifespan tree of brain anatomy for the differential diagnosis of four causes of parkinsonism using 37594 MRI as a training dataset. This original approach enhanced significantly the efficiency of differential diagnosis in the external validation cohort of 1754 cases, outperforming existing state-of-the art machine learning techniques. Lifespan tree holds promise as a valuable tool for differential diagnostic in relevant clinical conditions, especially for diseases still lacking effective biological markers. more...

Published
2025

2. Structuring, Sequencing, Staging, Selecting: the 4S method for the longitudinal analysis of multidimensional measurement scales in chronic diseases

Author

Saulnier, Tiphaine, Meissner, Wassilios G., Fabbri, Margherita, Foubert-Samier, Alexandra, and Proust-Lima, Cécile

Subjects
Statistics - Methodology
Abstract

In clinical studies, measurement scales are often collected to report disease-related manifestations from clinician or patient perspectives. Their analysis can help identify relevant manifestations throughout the disease course, enhancing knowledge of disease progression and guiding clinicians in providing appropriate support. However, the analysis of measurement scales in health studies is not straightforward as made of repeated, ordinal, and potentially multidimensional item data. Their sum-score summaries may considerably reduce information and impend interpretation, their change over time occurs along clinical progression, and as many other longitudinal processes, their observation may be truncated by events. This work establishes a comprehensive strategy in four consecutive steps to leverage repeated data from multidimensional measurement scales. The 4S method successively (1) identifies the scale structure into subdimensions satisfying three calibration assumptions (unidimensionality, conditional independence, increasing monotonicity), (2) describes each subdimension progression using a joint latent process model which includes a continuous-time item response theory model for the longitudinal subpart, (3) aligns each subdimension's progression with disease stages through a projection approach, and (4) identifies the most informative items across disease stages using the Fisher's information. The method is comprehensively illustrated in multiple system atrophy (MSA), an alpha-synucleinopathy, with the analysis of daily activity and motor impairments over disease progression. The 4S method provides an effective and complete analytical strategy for any measurement scale repeatedly collected in health studies. more...

Published
2024

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4. Amantadine use in the French prospective NS-Park cohort

Author

Fabbri, Margherita, Rousseau, Vanessa, Corvol, Jean-Christophe, Sommet, Agnès, Tubach, Florence, De Rycke, Yann, Bertille, Nathalie, Selvarasa, Yajiththa, Carvalho, Stephanie, Chaigneau, Véronique, Brefel-Courbon, Christine, Ory-Magne, Fabienne, Tessier, Samuel, Tir, Melissa, Bereau, Matthieu, Meissner, Wassilios G., Thiriez, Claire, Marques, Ana, Remy, Philippe, Schneider, Vincent, Moro, Elena, Defebvre, Luc, Houeto, Jean Luc, Prange, Stephane, Eusebio, Alexandre, Geny, Christian, Frismand, Solène, Damier, Philippe, Reuther, Caroline Giordana, Castelnovo, Giovanni, Benatru, Isabelle, De Maindreville, Anne Doe, Drapier, Sophie, Maltête, David, Lagha-Boukbiza, Ouhaid, and Rascol, Olivier more...

Published
2024
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5. Patient-perceived progression in multiple system atrophy: natural history of quality of life

Author

Saulnier, Tiphaine, Fabbri, Margherita, Goff, Mélanie Le, Helmer, Catherine, Traon, Anne Pavy-Le, Meissner, Wassilios G., Rascol, Olivier, Proust-Lima, Cécile, and Foubert-Samier, Alexandra

Subjects
Quantitative Biology - Quantitative Methods, Statistics - Methodology
Abstract

Health-related quality of life (Hr-QoL) scales provide crucial information on neurodegenerative disease progression, help improving patient care, and constitute a meaningful endpoint for therapeutic research. However, Hr-QoL progression is usually poorly documented, as for multiple system atrophy (MSA), a rare and rapidly progressing alpha-synucleinopathy. This work aimed to describe Hr-QoL progression during the natural course of MSA, explore disparities between patients, and identify informative items using a four-step statistical strategy.We leveraged the data of the French MSA cohort comprising annual assessments with the MSA-QoL questionnaire for more than 500 patients over up to 11 years. The four-step strategy (1) determined the subdimensions of Hr-QoL in MSA; (2) modelled the subdimension trajectories over time, accounting for the risk of death; (3) mapped the sequence of item impairments with disease stages; and (4) identified the most informative items specific to each disease stage.Among the 536 patients included, 50% were women and they were aged on average 65.1 years old at entry. Among them, 63.1% died during the follow-up. Four dimensions were identified. In addition to the original motor, nonmotor, and emotional domains, an oropharyngeal component was highlighted. While the motor and oropharyngeal domains deteriorated rapidly, the nonmotor and emotional aspects were already slightly to moderately impaired at cohort entry and deteriorated slowly over the course of the disease. Impairments were associated with sex, diagnosis subtype, and delay since symptom onset. Except for the emotional domain, each dimension was driven by key identified items.Hr-QoL is a multidimensional concept that deteriorates progressively over the course of MSA and brings essential knowledge for improving patient care. As exemplified with MSA, the thorough description of Hr-QoL using the 4-step original analysis can provide new perspectives on neurodegenerative diseases' management to ultimately deliver better support focused on the patient's perspective. more...

Published
2023

8. Describing complex disease progression using joint latent class models for multivariate longitudinal markers and clinical endpoints

Author

Proust-Lima, Cécile, Saulnier, Tiphaine, Philipps, Viviane, Traon, Anne Pavy-Le, Péran, Patrice, Rascol, Olivier, Meissner, Wassilios G, and Foubert-Samier, Alexandra

Subjects
Statistics - Applications, Statistics - Methodology
Abstract

Neurodegenerative diseases are characterized by numerous markers of progression and clinical endpoints. For instance, Multiple System Atrophy (MSA), a rare neurodegenerative synucleinopathy, is characterized by various combinations of progressive autonomic failure and motor dysfunction, and a very poor prognosis. Describing the progression of such complex and multi-dimensional diseases is particularly difficult. One has to simultaneously account for the assessment of multivariate markers over time, the occurrence of clinical endpoints, and a highly suspected heterogeneity between patients. Yet, such description is crucial for understanding the natural history of the disease, staging patients diagnosed with the disease, unravelling subphenotypes, and predicting the prognosis. Through the example of MSA progression, we show how a latent class approach modeling multiple repeated markers and clinical endpoints can help describe complex disease progression and identify subphenotypes for exploring new pathological hypotheses. The proposed joint latent class model includes class-specific multivariate mixed models to handle multivariate repeated biomarkers possibly summarized into latent dimensions and class-and-cause-specific proportional hazard models to handle time-to-event data. Maximum likelihood estimation procedure, validated through simulations is available in the lcmm R package. In the French MSA cohort comprising data of 598 patients during up to 13 years, five subphenotypes of MSA were identified that differ by the sequence and shape of biomarkers degradation, and the associated risk of death. In posterior analyses, the five subphenotypes were used to explore the association between clinical progression and external imaging and fluid biomarkers, while properly accounting for the uncertainty in the subphenotypes membership. more...

Published
2022
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10. Joint models for the longitudinal analysis of measurement scales in the presence of informative dropout

Author

Saulnier, Tiphaine, Philipps, Viviane, Meissner, Wassilios G, Rascol, Olivier, Traon, Anne Pavy-Le, Foubert-Samier, Alexandra, and Proust-Lima, Cécile

Subjects
Statistics - Methodology
Abstract

In health cohort studies, repeated measures of markers are often used to describe the natural history of a disease. Joint models allow to study their evolution by taking into account the possible informative dropout usually due to clinical events. However, joint modeling developments mostly focused on continuous Gaussian markers while, in an increasing number of studies, the actual quantity of interest is non-directly measurable; it constitutes a latent variable evaluated by a set of observed indicators from questionnaires or measurement scales. Classical examples include anxiety, fatigue, cognition. In this work,we explain how joint models can be extended to the framework of a latent quantity measured over time by indicators of different nature (e.g. continuous, binary, ordinal). The longitudinal submodel describes the evolution over time of the quantity of interest defined as a latent process in a structural mixed model, and links the latent process to each observation of the indicators through appropriate measurement models. Simultaneously, the risk of multi-cause event is modelled via a proportional cause-specific hazard model that includes a function of the mixed model elements as linear predictor to take into account the association between the latent process and the risk of event. Estimation, carried out in the maximum likelihood framework and implemented in the R-package JLPM, has been validated by simulations. The methodology is illustrated in the French cohort on Multiple-System Atrophy (MSA), a rare and fatal neurodegenerative disease, with the study of dysphagia progression over time stopped by the occurrence of death. more...

Published
2021
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11. Volumetric changes and clinical trajectories in Parkinson’s disease: a prospective multicentric study

Author

Marques, Ana, Macias, Elise, Pereira, Bruno, Durand, Elodie, Chassain, Carine, Vidal, Tiphaine, 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 G., Frismand, Solène, Schmitt, Emmanuelle, Doé de Maindreville, Anne, Portefaix, Christophe, Remy, Philippe, Fénelon, Gilles, Houeto, Jean Luc, Colin, Olivier, Rascol, Olivier, Peran, Patrice, Bonny, Jean-Marie, Fantini, Maria Livia, and Durif, Franck more...

Published
2023
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12. Genome sequence analyses identify novel risk loci for multiple system atrophy

Author

Chia, Ruth, Ray, Anindita, Shah, Zalak, Ding, Jinhui, Ruffo, Paola, Fujita, Masashi, Menon, Vilas, Saez-Atienzar, Sara, Reho, Paolo, Kaivola, Karri, Walton, Ronald L., Reynolds, Regina H., Karra, Ramita, Sait, Shaimaa, Akcimen, Fulya, Diez-Fairen, Monica, Alvarez, Ignacio, Fanciulli, Alessandra, Stefanova, Nadia, Seppi, Klaus, Duerr, Susanne, Leys, Fabian, Krismer, Florian, Sidoroff, Victoria, Zimprich, Alexander, Pirker, Walter, Rascol, Olivier, Foubert-Samier, Alexandra, Meissner, Wassilios G., Tison, François, Pavy-Le Traon, Anne, Pellecchia, Maria Teresa, Barone, Paolo, Russillo, Maria Claudia, Marín-Lahoz, Juan, Kulisevsky, Jaime, Torres, Soraya, Mir, Pablo, Periñán, Maria Teresa, Proukakis, Christos, Chelban, Viorica, Wu, Lesley, Goh, Yee Y., Parkkinen, Laura, Hu, Michele T., Kobylecki, Christopher, Saxon, Jennifer A., Rollinson, Sara, Garland, Emily, Biaggioni, Italo, Litvan, Irene, Rubio, Ileana, Alcalay, Roy N., Kwei, Kimberly T., Lubbe, Steven J., Mao, Qinwen, Flanagan, Margaret E., Castellani, Rudolph J., Khurana, Vikram, Ndayisaba, Alain, Calvo, Andrea, Mora, Gabriele, Canosa, Antonio, Floris, Gianluca, Bohannan, Ryan C., Moore, Anni, Norcliffe-Kaufmann, Lucy, Palma, Jose-Alberto, Kaufmann, Horacio, Kim, Changyoun, Iba, Michiyo, Masliah, Eliezer, Dawson, Ted M., Rosenthal, Liana S., Pantelyat, Alexander, Albert, Marilyn S., Pletnikova, Olga, Troncoso, Juan C., Infante, Jon, Lage, Carmen, Sánchez-Juan, Pascual, Serrano, Geidy E., Beach, Thomas G., Pastor, Pau, Morris, Huw R., Albani, Diego, Clarimon, Jordi, Wenning, Gregor K., Hardy, John A., Ryten, Mina, Topol, Eric, Torkamani, Ali, Chiò, Adriano, Bennett, David A., De Jager, Philip L., Low, Philip A., Singer, Wolfgang, Cheshire, William P., Wszolek, Zbigniew K., Dickson, Dennis W., Traynor, Bryan J., Gibbs, J. Raphael, Dalgard, Clifton L., Ross, Owen A., Houlden, Henry, and Scholz, Sonja W. more...

Published
2024
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13. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy

Author

Wenning, Gregor K, Stankovic, Iva, Vignatelli, Luca, Fanciulli, Alessandra, Calandra‐Buonaura, Giovanna, Seppi, Klaus, Palma, Jose‐Alberto, Meissner, Wassilios G, Krismer, Florian, Berg, Daniela, Cortelli, Pietro, Freeman, Roy, Halliday, Glenda, Höglinger, Günter, Lang, Anthony, Ling, Helen, Litvan, Irene, Low, Phillip, Miki, Yasuo, Panicker, Jalesh, Pellecchia, Maria Teresa, Quinn, Niall, Sakakibara, Ryuji, Stamelou, Maria, Tolosa, Eduardo, Tsuji, Shoji, Warner, Tom, Poewe, Werner, and Kaufmann, Horacio more...

Subjects
Neurosciences, Rare Diseases, Prevention, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Brain, Consensus, Humans, Magnetic Resonance Imaging, Multiple System Atrophy, Prospective Studies, multiple system atrophy, diagnostic criteria, diagnosis, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

BackgroundThe second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages.ObjectiveTo develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence-based and consensus-based methodology.MethodsWe identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference.ResultsThe criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow.ConclusionsThis set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. more...

Published
2022

14. Laboratory-Supported Multiple System Atrophy beyond Autonomic Function Testing and Imaging: A Systematic Review by the MoDiMSA Study Group.

Author

Stankovic, Iva, Fanciulli, Alessandra, Kostic, Vladimir S, Krismer, Florian, Meissner, Wassilios G, Palma, Jose Alberto, Panicker, Jalesh N, Seppi, Klaus, Wenning, Gregor K, and MoDiMSA Study Group

Subjects
diagnostic tests, multiple system atrophy
Abstract

Background: Neuroimaging has been used to support a diagnosis of possible multiple system atrophy (MSA). Only blood pressure changes upon standing are included in the second consensus criteria but other autonomic function tests (AFT) are also useful to diagnose widespread and progressive autonomic failure typical of MSA. Additional diagnostic tools are of interest to improve accuracy of MSA diagnosis. Objectives: To assess the utility of diagnostic tools beyond brain imaging and AFT in enhancing a laboratory-supported diagnosis of MSA to support the upcoming revision of the consensus criteria. Methods: The International Parkinson and Movement Disorders Society MSA Study Group (MoDiMSA) performed a systematic review of original papers on biomarkers, sleep studies, genetic, neuroendocrine, neurophysiological, neuropsychological and other tests including olfactory testing and acute levodopa challenge test published before August 2019. Results: Evaluation of history of levodopa responsiveness and olfaction is useful in patients in whom MSA-parkinsonian subtype is suspected. Neuropsychological testing is useful to exclude dementia at time of diagnosis. Applicability of sphincter EMG is limited. When MSA-cerebellar subtype is suspected, a screening for the common causes of adult-onset progressive ataxia is useful, including spinocerebellar ataxias in selected patients. Diagnosing stridor and REM sleep behavior disorder is useful in both MSA subtypes. However, none of these tools are validated in large longitudinal cohorts of postmortem confirmed MSA cases. Conclusions: Despite limited evidence, additional laboratory work-up of patients with possible MSA beyond imaging and AFT should be considered to optimize the clinical diagnostic accuracy. more...

Published
2021

16. Can Autonomic Testing and Imaging Contribute to the Early Diagnosis of Multiple System Atrophy? A Systematic Review and Recommendations by the Movement Disorder Society Multiple System Atrophy Study Group.

Author

Pellecchia, Maria Teresa, Stankovic, Iva, Fanciulli, Alessandra, Krismer, Florian, Meissner, Wassilios G, Palma, Jose-Alberto, Panicker, Jalesh N, Seppi, Klaus, Wenning, Gregor K, and Members of the Movement Disorder Society Multiple System Atrophy Study Group more...

Subjects
Members of the Movement Disorder Society Multiple System Atrophy Study Group, diagnostic tests, multiple system atrophy, Neurodegenerative, Neurosciences, Parkinson's Disease, Brain Disorders, Rare Diseases, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Neurological
Abstract

BackgroundIn the current consensus diagnostic criteria, the diagnosis of probable multiple system atrophy (MSA) is based solely on clinical findings, whereas neuroimaging findings are listed as aid for the diagnosis of possible MSA. There are overlapping phenotypes between MSA-parkinsonian type and Parkinson's disease, progressive supranuclear palsy, and dementia with Lewy bodies, and between MSA-cerebellar type and sporadic adult-onset ataxia resulting in a significant diagnostic delay and misdiagnosis of MSA during life.ObjectivesIn light of an ongoing effort to revise the current consensus criteria for MSA, the Movement Disorders Society Multiple System Atrophy Study Group performed a systematic review of original articles published before August 2019.MethodsWe included articles that studied at least 10 patients with MSA as well as participants with another disorder or control group for comparison purposes. MSA was defined by neuropathological confirmation, or as clinically probable, or clinically probable plus possible according to consensus diagnostic criteria.ResultsWe discuss the pitfalls and benefits of each diagnostic test and provide specific recommendations on how to evaluate patients in whom MSA is suspected.ConclusionsThis systematic review of relevant studies indicates that imaging and autonomic function tests significantly contribute to increasing the accuracy of a diagnosis of MSA. more...

Published
2020

17. Validation of the movement disorder society criteria for the diagnosis of 4-repeat tauopathies.

Author

Respondek, Gesine, Grimm, Max-Joseph, Piot, Ines, Arzberger, Thomas, Compta, Yaroslau, Englund, Elisabet, Ferguson, Leslie W, Gelpi, Ellen, Roeber, Sigrun, Giese, Armin, Grossman, Murray, Irwin, David J, Meissner, Wassilios G, Nilsson, Christer, Pantelyat, Alexander, Rajput, Alex, van Swieten, John C, Troakes, Claire, Höglinger, Günter U, and Movement Disorder Society-Endorsed Progressive Supranuclear Palsy Study Group more...

Subjects
Movement Disorder Society-Endorsed Progressive Supranuclear Palsy Study Group, Brain, Humans, Multiple System Atrophy, Parkinsonian Disorders, Parkinson Disease, Supranuclear Palsy, Progressive, Tauopathies, Aged, Middle Aged, Female, Male, Four-repeat tauopathies, corticobasal degeneration, diagnostic criteria, progressive supranuclear palsy, Aging, Rare Diseases, Clinical Trials and Supportive Activities, Neurodegenerative, Neurosciences, Brain Disorders, Clinical Research, Pick's Disease, Acquired Cognitive Impairment, Dementia, Frontotemporal Dementia (FTD), 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Neurological, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

BackgroundThe Movement Disorder Society criteria for progressive supranuclear palsy introduced the category "probable 4-repeat (4R)-tauopathy" for joint clinical diagnosis of progressive supranuclear palsy and corticobasal degeneration.ObjectivesTo validate the accuracy of these clinical criteria for "probable 4R-tauopathy" to predict underlying 4R-tauopathy pathology.MethodsDiagnostic accuracy for 4R-tauopathies according to the established criteria was estimated retrospectively in autopsy-confirmed patients with progressive supranuclear palsy and corticobasal degeneration (grouped as 4R-tauopathies), and Parkinson's disease, multiple system atrophy, and frontotemporal lobar degeneration (grouped as non-4R-tauopathies).ResultsWe identified 250 cases with progressive supranuclear palsy (N = 195) and corticobasal degeneration (N = 55) and with and non-4R-tauopathies (N = 161). Sensitivity and specificity of "probable 4R-tauopathy" was 10% and 99% in the first year and 59% and 88% at final record.ConclusionsThe new diagnostic category "probable 4R-tauopathy" showed high specificity and may be suitable for the recruitment of patients with progressive supranuclear palsy and corticobasal degeneration into therapeutic trials targeting 4R-tauopathy. The low sensitivity underpins the need for diagnostic biomarkers. © 2019 International Parkinson and Movement Disorder Society. more...

Published
2020

18. How to apply the movement disorder society criteria for diagnosis of progressive supranuclear palsy.

Author

Grimm, Max-Joseph, Respondek, Gesine, Stamelou, Maria, Arzberger, Thomas, Ferguson, Leslie, Gelpi, Ellen, Giese, Armin, Grossman, Murray, Irwin, David J, Pantelyat, Alexander, Rajput, Alex, Roeber, Sigrun, van Swieten, John C, Troakes, Claire, Antonini, Angelo, Bhatia, Kailash P, Colosimo, Carlo, van Eimeren, Thilo, Kassubek, Jan, Levin, Johannes, Meissner, Wassilios G, Nilsson, Christer, Oertel, Wolfgang H, Piot, Ines, Poewe, Werner, Wenning, Gregor K, Boxer, Adam, Golbe, Lawrence I, Josephs, Keith A, Litvan, Irene, Morris, Huw R, Whitwell, Jennifer L, Compta, Yaroslau, Corvol, Jean-Christophe, Lang, Anthony E, Rowe, James B, Höglinger, Günter U, and Movement Disorder Society-endorsed PSP Study Group more...

Subjects
Movement Disorder Society-endorsed PSP Study Group, Brain, Humans, Parkinsonian Disorders, Supranuclear Palsy, Progressive, Ocular Motility Disorders, Sensation Disorders, Autopsy, Retrospective Studies, Cohort Studies, Adult, Aged, Aged, 80 and over, Middle Aged, Societies, Medical, Female, Male, Postural Balance, Cognitive Dysfunction, autopsy, diversity, phenotype, progressive supranuclear palsy, Brain Disorders, Pediatric, Neurosciences, Rare Diseases, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, 4.2 Evaluation of markers and technologies, Neurology & Neurosurgery, Clinical Sciences, Human Movement and Sports Sciences
Abstract

BackgroundThe Movement Disorder Society criteria for progressive supranuclear palsy define diagnostic allocations, stratified by certainty levels and clinical predominance types. We aimed to study the frequency of ambiguous multiple allocations and to develop rules to eliminate them.MethodsWe retrospectively collected standardized clinical data by chart review in a multicenter cohort of autopsy-confirmed patients with progressive supranuclear palsy, to classify them by diagnostic certainty level and predominance type and to identify multiple allocations.ResultsComprehensive data were available from 195 patients. More than one diagnostic allocation occurred in 157 patients (80.5%). On average, 5.4 allocations were possible per patient. We developed four rules for Multiple Allocations eXtinction (MAX). They reduced the number of patients with multiple allocations to 22 (11.3%), and the allocations per patient to 1.1.ConclusionsThe proposed MAX rules help to standardize the application of the Movement Disorder Society criteria for progressive supranuclear palsy. © 2019 International Parkinson and Movement Disorder Society. more...

Published
2019

20. Multiple system atrophy

Author

Poewe, Werner, Stankovic, Iva, Halliday, Glenda, Meissner, Wassilios G., Wenning, Gregor K., Pellecchia, Maria Teresa, Seppi, Klaus, Palma, Jose-Alberto, and Kaufmann, Horacio

Published
2022
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21. Which ante mortem clinical features predict progressive supranuclear palsy pathology?

Author

Respondek, Gesine, Kurz, Carolin, Arzberger, Thomas, Compta, Yaroslau, Englund, Elisabet, Ferguson, Leslie W, Gelpi, Ellen, Giese, Armin, Irwin, David J, Meissner, Wassilios G, Nilsson, Christer, Pantelyat, Alexander, Rajput, Alex, van Swieten, John C, Troakes, Claire, Josephs, Keith A, Lang, Anthony E, Mollenhauer, Brit, Müller, Ulrich, Whitwell, Jennifer L, Antonini, Angelo, Bhatia, Kailash P, Bordelon, Yvette, Corvol, Jean‐Christophe, Colosimo, Carlo, Dodel, Richard, Grossman, Murray, Kassubek, Jan, Krismer, Florian, Levin, Johannes, Lorenzl, Stefan, Morris, Huw, Nestor, Peter, Oertel, Wolfgang H, Rabinovici, Gil D, Rowe, James B, van Eimeren, Thilo, Wenning, Gregor K, Boxer, Adam, Golbe, Lawrence I, Litvan, Irene, Stamelou, Maria, Höglinger, Günter U, and Group, for the Movement Disorder Society‐Endorsed PSP Study more...

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Frontotemporal Dementia (FTD), Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Rare Diseases, Aging, Parkinson's Disease, Dementia, Brain Disorders, Neurosciences, Pick's Disease, Alzheimer's Disease Related Dementias (ADRD), Acquired Cognitive Impairment, 4.2 Evaluation of markers and technologies, 2.1 Biological and endogenous factors, Neurological, Humans, Supranuclear Palsy, Progressive, Progressive supranuclear palsy, clinical features, diagnosis, clinico-pathological series, systematic review, Movement Disorder Society-Endorsed PSP Study Group, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

BackgroundProgressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes.ObjectiveTo identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP.MethodsWe performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort.ResultsOf 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity.ConclusionsOur results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. more...

Published
2017

22. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.

Author

Höglinger, Günter U, Respondek, Gesine, Stamelou, Maria, Kurz, Carolin, Josephs, Keith A, Lang, Anthony E, Mollenhauer, Brit, Müller, Ulrich, Nilsson, Christer, Whitwell, Jennifer L, Arzberger, Thomas, Englund, Elisabet, Gelpi, Ellen, Giese, Armin, Irwin, David J, Meissner, Wassilios G, Pantelyat, Alexander, Rajput, Alex, van Swieten, John C, Troakes, Claire, Antonini, Angelo, Bhatia, Kailash P, Bordelon, Yvette, Compta, Yaroslau, Corvol, Jean-Christophe, Colosimo, Carlo, Dickson, Dennis W, Dodel, Richard, Ferguson, Leslie, Grossman, Murray, Kassubek, Jan, Krismer, Florian, Levin, Johannes, Lorenzl, Stefan, Morris, Huw R, Nestor, Peter, Oertel, Wolfgang H, Poewe, Werner, Rabinovici, Gil, Rowe, James B, Schellenberg, Gerard D, Seppi, Klaus, van Eimeren, Thilo, Wenning, Gregor K, Boxer, Adam L, Golbe, Lawrence I, Litvan, Irene, and Movement Disorder Society-endorsed PSP Study Group more...

Subjects
Movement Disorder Society-endorsed PSP Study Group, Humans, Supranuclear Palsy, Progressive, Societies, Medical, Practice Guidelines as Topic, clinical diagnostic criteria, consensus-based, evidence-based, progressive supranuclear palsy, Brain Disorders, Neurosciences, Neurological, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

BackgroundPSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome.ObjectiveWe aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP.MethodsWe searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds.ResultsDefined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features.ConclusionsHere, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence. © 2017 International Parkinson and Movement Disorder Society. more...

Published
2017

23. Dysphagia in multiple system atrophy consensus statement on diagnosis, prognosis and treatment

Author

Calandra-Buonaura, Giovanna, Alfonsi, Enrico, Vignatelli, Luca, Benarroch, Eduardo E., Giannini, Giulia, Iranzo, Alex, Low, Phillip A., Martinelli, Paolo, Provini, Federica, Quinn, Niall, Tolosa, Eduardo, Wenning, Gregor K., Abbruzzese, Giovanni, Bower, Pamela, Antonini, Angelo, Bhatia, Kailash P., Bonavita, Jacopo, Pellecchia, Maria Teresa, Pizzorni, Nicole, Tison, François, Ghorayeb, Imad, Meissner, Wassilios G., Ozawa, Tetsutaro, Pacchetti, Claudio, Pozzi, Nicolò Gabriele, Vicini, Claudio, Schindler, Antonio, Cortelli, Pietro, and Kaufmann, Horacio more...

Published
2021
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24. Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson's disease patients with GBA mutations

Author

Benchetrit, Eve, Delaby, Laure, Berthet, Deborah, Danjou, Fabrice, Vidaihlet, Marie, Krack, Paul, Pelissier, Pierre, Morand, Dominique, Delaigue, Christine, Barun, Nadia, Anheim, Mathieu, Pleuvret, Marie, Destée, Alain, Defebvre, Luc, Moreau, Caroline, Simonin, Clémence, Ryckewaert, Gilles, Kreisler, Alexandre, Mutez, Eugénie, Carrière, Nicolas, Hopes, Lucie, Tard, Céline, Grolez, Guillaume, Dujardin, Kathy, Pecheux, Nathalie, Delliaux, Marie, Rolland, Anne-Sophie, Broussolle, Emmanuel, Laurencin, Chloè, Tison, François, Burbaud, Pierre, Mangone, Graziella, Bekadar, Samir, Cormier-Dequaire, Florence, Tahiri, Khadija, Welaratne, Arlette, Czernecki, Virginie, Pineau, Fanny, Karachi, Carine, Castrioto, Anna, Durif, Frank, Tranchant, Christine, Devos, David, Thobois, Stéphane, Meissner, Wassilios G, Navarro, Maria Soledad, Cornu, Philippe, Lesage, Suzanne, Brice, Alexis, Welter, Marie Laure, and Corvol, Jean-Christophe more...

Published
2020
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26. A genome-wide association study in multiple system atrophy

Author

Sailer, Anna, Scholz, Sonja W, Nalls, Michael A, Schulte, Claudia, Federoff, Monica, Price, T Ryan, Lees, Andrew, Ross, Owen A, Dickson, Dennis W, Mok, Kin, Mencacci, Niccolo E, Schottlaender, Lucia, Chelban, Viorica, Ling, Helen, O'Sullivan, Sean S, Wood, Nicholas W, Traynor, Bryan J, Ferrucci, Luigi, Federoff, Howard J, Mhyre, Timothy R, Morris, Huw R, Deuschl, Günther, Quinn, Niall, Widner, Hakan, Albanese, Alberto, Infante, Jon, Bhatia, Kailash P, Poewe, Werner, Oertel, Wolfgang, Höglinger, Günter U, Wüllner, Ullrich, Goldwurm, Stefano, Pellecchia, Maria Teresa, Ferreira, Joaquim, Tolosa, Eduardo, Bloem, Bastiaan R, Rascol, Olivier, Meissner, Wassilios G, Hardy, John A, Revesz, Tamas, Holton, Janice L, Gasser, Thomas, Wenning, Gregor K, Singleton, Andrew B, Houlden, Henry, Calandra-Buonaura, Giovanna, Capellari, Sabina, and Cortelli, Pietro more...

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Alkyl and Aryl Transferases, Brain, Cohort Studies, Europe, Genetic Loci, Genome-Wide Association Study, Genotyping Techniques, Humans, Multiple System Atrophy, Polymorphism, Single Nucleotide, RNA, Messenger, United States, Whites, alpha-Synuclein, European Multiple System Atrophy Study Group and the UK Multiple System Atrophy Study Group, White People, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS).MethodsWe performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed.ResultsWe found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10-6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA.ConclusionsWe present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps. more...

Published
2016

27. Four-repeat tauopathies

Author

Rösler, Thomas W., Tayaranian Marvian, Amir, Brendel, Matthias, Nykänen, Niko-Petteri, Höllerhage, Matthias, Schwarz, Sigrid C., Hopfner, Franziska, Koeglsperger, Thomas, Respondek, Gesine, Schweyer, Kerstin, Levin, Johannes, Villemagne, Victor L., Barthel, Henryk, Sabri, Osama, Müller, Ulrich, Meissner, Wassilios G., Kovacs, Gabor G., and Höglinger, Günter U. more...

Published
2019
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28. Descriptive analysis of the French NS-Park registry: Towards a nation-wide Parkinson's disease cohort?

Author

Mariani, Louise-Laure, Doulazmi, Mohamed, Chaigneau, Véronique, Brefel-Courbon, Christine, Carrière, Nicolas, Danaila, Teodor, Defebvre, Luc, Defer, Gilles, Dellapina, Estelle, Doé de Maindreville, Anne, Geny, Christian, Maltête, David, Meissner, Wassilios G., Rascol, Olivier, Thobois, Stéphane, Torny, Frederic, Tranchant, Christine, Vidailhet, Marie, Corvol, Jean-Christophe, and Degos, Bertrand more...

Published
2019
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30. Care of Late‐Stage Parkinsonism: Resource Utilization of the Disease in Five European Countries

Author

Kruse, Christopher, primary, Lipinski, Anna, additional, Verheyen, Malte, additional, Balzer‐Geldsetzer, Monika, additional, Wittenberg, Michael, additional, Lorenzl, Stefan, additional, Richinger, Carmen, additional, Schmotz, Christian, additional, Tönges, Lars, additional, Woitalla, Dirk, additional, Klebe, Stephan, additional, Bloem, Bastiaan R., additional, Hommel, Adrianus, additional, Meissner, Wassilios G., additional, Laurens, Brice, additional, Boraud, Thomas, additional, Foubert‐Samier, Alexandra, additional, Vergnet, Sylvain, additional, Tison, François, additional, Costa, Nadège, additional, Odin, Per, additional, Rosqvist, Kristina, additional, Norlin, Jenny M., additional, Hjalte, Frida, additional, Schrag, Anette, additional, and Dodel, Richard, additional more...

Published
2024
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33. Naftazone in advanced Parkinson's disease: An acute L-DOPA challenge randomized controlled trial

Author

Corvol, Jean-Christophe, Durif, Franck, Meissner, Wassilios G., Azulay, Jean-Philippe, Haddad, Raphaël, Guimarães-Costa, Raquel, Mariani, Louise-Laure, Cormier-Dequaire, Florence, Thalamas, Claire, Galitzky, Monique, Boraud, Thomas, Debilly, Bérengère, Eusebio, Alexandre, Houot, Marion, Dellapina, Estelle, Chaigneau, Véronique, Salis, Alexandrine, Lacomblez, Lucette, Benel, Laurent, and Rascol, Olivier more...

Published
2019
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34. Deep brain stimulation does not enhance neuroinflammation in multiple system atrophy

Author

Lopez-Cuina, Miguel, Fernagut, Pierre-Olivier, Canron, Marie-Hélène, Vital, Anne, Lannes, Béatrice, De Paula, André Maues, Streichenberger, Nathalie, Guehl, Dominique, Damier, Philippe, Eusebio, Alexandre, Houeto, Jean-Luc, Tison, François, Tranchant, Christine, Viallet, François, Witjas, Tatiana, Thobois, Stéphane, and Meissner, Wassilios G. more...

Published
2018
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37. A Statement of the MDS on Biological Definition, Staging, and Classification of Parkinson's Disease

Author

Cardoso, Francisco, primary, Goetz, Christopher G., additional, Mestre, Tiago A., additional, Sampaio, Cristina, additional, Adler, Charles H., additional, Berg, Daniela, additional, Bloem, Bastiaan R., additional, Burn, David J., additional, Fitts, Michael S., additional, Gasser, Thomas, additional, Klein, Christine, additional, de Tijssen, Marina A.J., additional, Lang, Anthony E., additional, Lim, Shen‐Yang, additional, Litvan, Irene, additional, Meissner, Wassilios G., additional, Mollenhauer, Brit, additional, Okubadejo, Njideka, additional, Okun, Michael S., additional, Postuma, Ronald B., additional, Svenningsson, Per, additional, Tan, Louis C.S., additional, Tsunemi, Taiji, additional, Wahlstrom‐Helgren, Sarah, additional, Gershanik, Oscar S., additional, Fung, Victor S.C., additional, and Trenkwalder, Claudia, additional more...

Published
2023
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38. Meaning in Life in Late-Stage Parkinson’s Disease: Results from the Care of Late-Stage Parkinsonism Study (CLaSP) in Six European Countries

Author

Bublitz, Sarah K., primary, Brandstötter, Cornelia, additional, Fegg, Martin, additional, Ferreira, Joaquim J., additional, Odin, Per, additional, Bloem, Bastiaan R., additional, Meissner, Wassilios G., additional, Dodel, Richard, additional, Schrag, Anette, additional, and Lorenzl, Stefan, additional more...

Published
2023
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39. Progressive Brain Atrophy in Multiple System Atrophy: A Longitudinal, Multicenter, Magnetic Resonance Imaging Study

Author

Krismer, Florian, primary, Péran, Patrice, additional, Beliveau, Vincent, additional, Seppi, Klaus, additional, Arribarat, Germain, additional, Pavy‐Le Traon, Anne, additional, Meissner, Wassilios G., additional, Foubert‐Samier, Alexandra, additional, Fabbri, Margherita, additional, Schocke, Michael M., additional, Gordon, Mark Forrest, additional, Wenning, Gregor K., additional, Poewe, Werner, additional, Rascol, Olivier, additional, and Scherfler, Christoph, additional more...

Published
2023
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41. Early‐phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease.

Author

Aye, William W. T., Stark, Megan R., Horne, Kyla‐Louise, Livingston, Leslie, Grenfell, Sophie, Myall, Daniel J., Pitcher, Toni L., Almuqbel, Mustafa M., Keenan, Ross J., Meissner, Wassilios G., Dalrymple‐Alford, John C., Anderson, Tim J., Heron, Campbell Le, and Melzer, Tracy R. more...

Subjects
PARKINSON'S disease, COGNITION disorders, POSITRON emission tomography, MAGNETIC resonance imaging, AMYLOID, MILD cognitive impairment
Abstract

INTRODUCTION: Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid‐negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early‐phase 18F‐florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD. METHODS: One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual‐phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion. RESULTS: Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism‐associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions. DISCUSSION: EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual‐phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment. Highlights: Images taken at amyloid beta (Aβ) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid‐negative condition.Early‐phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism‐related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late‐phase Aβ burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion. [ABSTRACT FROM AUTHOR] more...

Published
2024
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42. Liver transplantation as a rescue therapy for severe neurologic forms of Wilson disease

Author

Poujois, Aurélia, Sobesky, Rodolphe, Meissner, Wassilios G., Brunet, Anne-Sophie, Broussolle, Emmanuel, Laurencin, Chloé, Lion-François, Laurence, Guillaud, Olivier, Lachaux, Alain, Maillot, François, Belin, Jérémie, Salamé, Ephrem, Vanlemmens, Claire, Heyd, Bruno, Bellesme, Céline, Habes, Dalila, Bureau, Christophe, Ory-Magne, Fabienne, Chaine, Pascal, Trocello, Jean-Marc, Cherqui, Daniel, Samuel, Didier, de Ledinghen, Victor, Duclos-Vallée, Jean-Charles, and Woimant, France more...

Published
2020
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44. Trial of Deferiprone in Parkinson’s Disease

Author

Devos, David, Labreuche, Julien, Dušek, Petr, Post, Bart, Bloem, Bastiaan R, Berg, Daniela, Maetzler, Walter, Otto, Markus, Habert, Marie-Odile, Lehericy, Stéphane, Ferreira, Joaquim, Dodel, Richard, Rascol, Olivier, Tranchant, Christine, Eusebio, Alexandre, Thobois, Stéphane, Marques, Ana-Raquel, Meissner, Wassilios G, Ory-Magne, Fabienne, Walter, Uwe, de Bie, Rob M A, Gago, Miguel, Vilas, Dolores, Corvol, Jean-Christophe, Kulisevsky, Jaime, Januario, Cristina, Coelho, Miguel V S, Behnke, Stefanie, Worth, Paul, Seppi, Klaus, Ouk, Thavarak, Potey, Camille, Leclercq, Céline, Viard, Romain, Duhamel, Alain, Kuchcinski, Gregory, Lopes, Renaud, Pruvo, Jean-Pierre, Pigny, Pascal, Garçon, Guillaume, Simonin, Ophélie, Carpentier, Jessica, Rolland, Anne-Sophie, Nyholm, Dag, Scherfler, Christoph, Guyon Delannoy, Pauline, Mangin, Jean-François, Chupin, Marie, Bordet, Régis, Dexter, David T, Fradette, Caroline, Spino, Michael, Tricta, Fernando, Ayton, Scott, Bush, Ashley I, Devedjian, Jean-Christophe, Poewe, Werner, Duce, James A, Cabantchik, Ioav, Defebvre, Luc, Deplanque, Dominique, Moreau, Caroline, Group, FAIRPARK-II Study, Compta, Yaroslau, Pavese, Nicola, Růžička, Evžen, Basenau, Sandra, Beliveau, Vincent, Benchetrit, Eve, Best, Laura, Bloem, Bas, Bonicel, Robin, Boraud, T., Bordet, Regis, Bouca, Raquel, Bourdain, Frédéric, Bouzas, Jimena, Brefel-Courbon, Christine, Bubenheim, Michael, Burn, David, Bush, Ashley I, Cabantchik, Ioav, Calvas, Fabienne, Cámara, Ana, Campolongo, Antonia, Carrière, Nicolas, Chaigneau, Véronique, Matthieu, Collin, Compta, Yaroslau, Connelly, John, Cormier-Dequaire, Florence, Cranston, Amy, Dean, Rory, De Marzi, Roberto, Degos, Bertrand, Demotes, Jacques, Dellapina, Estelle, Deplanque, Dominique, Devedjian, Jean-Christophe, Devos, David, Dexter, David, Dodel, Richard, Dongmo, Carole, Duce, James, Duhamel, Alain, Dupouy, Julia, Dusek, Petr, El Mountassir, Fouzia, Eyvrard, Frédéric, Fernández, Manel, Ferreira, Joaquim, Forni, Gian Luca, Foster, Victoria, Foubert-Samier, Alexandra, Fradette, Caroline, Fréville, Laëtitia, Galitzky, Monique, Gaudebout, Cecile, Gelé, Patrick, Giladi, Nir, Grabli, David, Gleixner, Franck, Grolez, Guillaume, Guyon, Pauline, Habert, Marie-Odile, Harroch, Estelle, Hartmann, Andreas, Hirsch, Denise, Hisbergues, Michael, Hobert, Markus A, Hopfner, Franziska, Jurado, Camille, Kaiser, Andreas, Keen, Gill, Klaus, Seppi, Kouassi, Nadège, Labreuch, Julien, Lacomblez, Lucette, Lagha Boukbiza, Ouhaid, Lanthaler, Barbara, Lechatellier, Gilles, Le Forestier, Nadine, Lehmann, Fred, Lloret, Teresa, Le Naour, J., Le Toullec, Benjamin, Locatelli, Maxime, Löhle, Matthias, Lomeña, F., Longato, Nadine, Lützen, Ulf, McNichol, Ann, Maetzler, Corina, Maetzler, Walter, Mahlknecht, Philipp, Mangone, Graziella, Marín-Lahoz, Juan, Mariani, Louise-Laure, Marques, Ana, Matei, Mihaela, Matthias, Löhle, Maucourt Bacchi, Emilie, Meissner, Wassilios, Michon, Amelie, Moreau, Caroline, Nardocci, Nardo, Nosal, Florence, Nyholm, Dag, Oeckl, Patrick, Oravska, Irena, Ory, Fabienne, Otto, Markus, Ouk, Thavarak, Pagonabarraga, Javier, Pascual-Sedano, Berta, Peball, Marina, Phillips, Clélie, Pineau, Fanny, Planellas, Lluís, Pop-Ilieva, Chiesi, Rabier, Aurélie, Olivier, D., Riedel, Christian, Rodrigues, Maura, Roullet-Solignac, Isabelle, Rose, Christian, Rozova, Anna, Růžička, Evžen, Salis, Alexandra, Schäffer, Eva, Scherfler, Christoph, Schiefermeier, Natalia, Seppi, Klaus, Smagghe, Delphine, Silva, Tânia, Silva, Pedro, Socha, Julie, Souyris, Corinne, Spampinato, Umberto, Spino, Michael, Steel, Alison, Sweta, Bajaj, Thalamas, Claire, Teodor, Danaila, Teresa, Anna, Tison, François, Tolosa, Eduardo, Tricta, Fernando, Trifirò Trifirò, Gianluca, Vidailhet, Marie, Wang, Yi, Werkmann, Mario, Yilmas, Rezzak, You, Hana, Zeuner, Kirsten, Defebvre, Luc, Rascol, Olivier, Tranchant, Christine, Eusebio, Alexandre, Thobois, Stéphane, Corvol, Jean-Christophe, Durif, Franck, Meissner, Wassilos, Yaroslau, Compta, Vilas, Dolores, Kulisevsky, Jaime, Poewe, Werner, Ruzicka, Evzen, Gago, Miguel, Januario, Cristina, Vilhena Soares Coelho, Miguel, Berg, Daniela, Behnke, Stefanie, Walter, Uwe, Worth, Paul, Pavese, Nicola, Post, Bart, de Bie, Rob M A, Abbruzzese, Giovanni, Accart, Bertrand, Allain, Marie-Anne, Anheim, Mathieu, Ardigo, Diego, Aracil-Bolaños, Ignacio, Baba, Paul, Bakker, Martijn, Balzer-Geldsetzer, Monika, Bargalló, Núria, Barone, Paolo, Neurology, ANS - Neurodegeneration, and APH - Aging & Later Life more...

Subjects
administration & dosage [Deferiprone], Dopamine, Dopamine Agents, Medizin, Administration, Oral, Levodopa, Antiparkinson Agents, therapeutic use [Dopamine Agents], therapeutic use [Deferiprone], Deferiprone, metabolism [Iron], adverse effects [Deferiprone], Geriatrics/Aging, Parkinson Disease, General Medicine, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Hematology/Oncology, chemistry [Substantia Nigra], adverse effects [Dopamine Agents], Disease Progression, administration & dosage [Dopamine Agents], physiopathology [Parkinson Disease], adverse effects [Iron Chelating Agents], Neutropenia, analysis [Iron], administration & dosage [Antiparkinson Agents], Iron, metabolism [Parkinson Disease], Neurology/Neurosurgery, therapeutic use [Levodopa], Iron Chelating Agents, pharmacology [Iron Chelating Agents], Double-Blind Method, adverse effects [Antiparkinson Agents], Genetics, diagnostic imaging [Substantia Nigra], metabolism [Substantia Nigra], Humans, ddc:610, diagnostic imaging [Brain], therapeutic use [Antiparkinson Agents], Brain Chemistry, pharmacology [Antiparkinson Agents], therapeutic use [Iron Chelating Agents], Hematology/Oncology General, chemically induced [Neutropenia], pharmacology [Deferiprone], drug therapy [Parkinson Disease], administration & dosage [Iron Chelating Agents], Geriatrics/Aging General, pharmacology [Dopamine Agents], drug effects [Substantia Nigra], Neuroscience
Abstract

Contains fulltext : 287484.pdf (Publisher’s version ) (Open Access) BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P more...

Published
2022
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45. Disease Progression in Multiple System Atrophy: The Value of Clinical Cohorts with Long Follow‐Up

Author

Saulnier, Tiphaine, primary, Fabbri, Margherita, additional, Pavy‐Le Traon, Anne, additional, Le Goff, Mélanie, additional, Helmer, Catherine, additional, Péran, Patrice, additional, Meissner, Wassilios G., additional, Rascol, Olivier, additional, Foubert‐Samier, Alexandra, additional, and Proust‐Lima, Cécile, additional more...

Published
2023
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48. Outcome of deep brain stimulation in slowly progressive multiple system atrophy: A clinico-pathological series and review of the literature

Author

Meissner, Wassilios G., Laurencin, Chloé, Tranchant, Christine, Witjas, Tatiana, Viallet, François, Guehl, Dominique, Damier, Philippe, Houeto, Jean-Luc, Tison, François, Eusebio, Alexandre, Vital, Anne, Streichenberger, Nathalie, Lannes, Béatrice, Maues de Paula, André, and Thobois, Stéphane more...

Published
2016
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49. Stridor in multiple system atrophy: Consensus statement on diagnosis, prognosis, and treatment

Author

Cortelli, Pietro, Calandra-Buonaura, Giovanna, Benarroch, Eduardo E., Giannini, Giulia, Iranzo, Alex, Low, Phillip A., Martinelli, Paolo, Provini, Federica, Quinn, Niall, Tolosa, Eduardo, Wenning, Gregor K., Abbruzzese, Giovanni, Bower, Pamela, Alfonsi, Enrico, Ghorayeb, Imad, Ozawa, Tetsutaro, Pacchetti, Claudio, Pozzi, Nicolò Gabriele, Vicini, Claudio, Antonini, Angelo, Bhatia, Kailash P., Bonavita, Jacopo, Kaufmann, Horacio, Pellecchia, Maria Teresa, Pizzorni, Nicole, Schindler, Antonio, Tison, François, Vignatelli, Luca, and Meissner, Wassilios G. more...

Published
2019
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50. A Statement of the MDS on Biological Definition, Staging, and Classification of Parkinson's Disease.

Author

Cardoso, Francisco, Goetz, Christopher G., Mestre, Tiago A., Sampaio, Cristina, Adler, Charles H., Berg, Daniela, Bloem, Bastiaan R., Burn, David J., Fitts, Michael S., Gasser, Thomas, Klein, Christine, de Tijssen, Marina A.J., Lang, Anthony E., Lim, Shen‐Yang, Litvan, Irene, Meissner, Wassilios G., Mollenhauer, Brit, Okubadejo, Njideka, Okun, Michael S., and Postuma, Ronald B. more...

Published
2024
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